Conditions: Recurrent Pericarditis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 86
Healthy volunteers: no

Brief summary:
The primary objective of this study was to assess the efficacy of rilonacept treatment in participants with recurrent pericarditis.

Detailed description:
In the single-blind run-in (RI) period, rilonacept 320 mg (or 4.4 mg/kg in pediatric participants ≥12 and \<18 years old) subcutaneous (SC), followed by 160 mg (or 2.2 mg/kg in pediatric participants ≥12 and \<18 years old) injections once weekly.

During the Randomized-Withdrawal (RW) period, eligible participants are randomized 1:1 to double-blinded administration of study drug:

* Rilonacept 160 mg (or 2.2 mg/kg in pediatric participants ≥12 and \<18 years old) SC injections once weekly
* Matching placebo SC injections once weekly.

Participants with pericarditis recurrence who meet the protocol criteria for bailout rilonacept (report at least 1 day with pericarditis pain ≥4 on the 11-point numerical rating scale (NRS) and have 1 C-reactive protein (CRP) value ≥ 1 mg/dL \[either on the same day or separated by no more than 7 days\]) receive bailout rilonacept (2 open-label injections of 160 mg rilonacept \[or 4.4 mg/kg for pediatric subjects\]) irrespective of randomized treatment assignment and as soon as at least 5 days have passed since the last study drug injection.

Upon completion of the RW period (i.e., when the prespecified number of primary efficacy endpoints \[clinical events committee-confirmed pericarditis recurrence\] events have occurred), all participants who did not discontinue study drug have an option to continue treatment with open-label rilonacept in the Long-Term Extension (LTE) or to withdraw from the study. Participants still in the RI period at the time that the RW period has ended and the LTE is opened will have the option to enter the LTE directly when they have completed the RI period and have met the definition of clinical response or to withdraw from the study.

Arms:
arm 1: RI period: single-blind rilonacept 320 mg (or 4.4 mg/kg in pediatric participants) SC, followed by 160 mg (or 2.2 mg/kg in pediatric participants) injections once weekly.

RW period: eligible participants randomized to double-blinded administration of rilonacept 160 mg (or 2.2 mg/kg in pediatric participants) SC injections once weekly. Participants with pericarditis recurrence who meet the protocol criteria for bailout rilonacept (report at least 1 day with pericarditis pain ≥4 on the 11-point NRS and have 1 CRP value ≥ 1 mg/dL \[either on the same day or separated by no more than 7 days\]) receive bailout rilonacept (2 open-label injections of 160 mg rilonacept \[or 4.4 mg/kg for pediatric participants\]) irrespective of randomized treatment assignment and as soon as at least 5 days have passed since the last study drug injection.

LTE period: open-label administration of rilonacept 160 mg (or 2.2 mg/kg in pediatric participants) SC injections once weekly. arm 2: RI period: single-blind rilonacept 320 mg (or 4.4 mg/kg in pediatric participants) SC, followed by 160 mg (or 2.2 mg/kg in pediatric participants) injections once weekly.

RW period: eligible participants randomized to placebo SC injections once weekly. Participants with pericarditis recurrence who meet the protocol criteria for bailout rilonacept (report at least 1 day with pericarditis pain ≥4 on the 11-point NRS and have 1 CRP value ≥ 1 mg/dL \[either on the same day or separated by no more than 7 days\]) receive bailout rilonacept (2 open-label injections of 160 mg rilonacept \[or 4.4 mg/kg for pediatric participants\]) irrespective of randomized treatment assignment and as soon as at least 5 days have passed since the last study drug injection.

LTE period: open-label administration of rilonacept 160 mg (or 2.2 mg/kg in pediatric participants) SC injections once weekly.

Interventions: intervention 1: Rilonacept intervention 2: Placebo
Intervention descriptions: intervention 1: Rilonacept 320 mg (or 4.4 mg/kg in pediatric participants ≥12 and \<18 years old) SC , followed by 160 mg (or 2.2 mg/kg in pediatric participants ≥12 and \<18 years old) injections once weekly intervention 2: Placebo SC injections once weekly

Protocol document:
SAP_002.pdf: 
 
 
 
 
 
STATISTICAL ANALYSIS PLAN ADDENDUM 
 
 
PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED 
WITHDRAWAL STUDY WITH OPENLABEL EXTENSION, TO ASSESS THE 
EFFICACY AND SAFETY OF RILONACEPT TREATMENT IN SUBJECTS WITH 
RECURRENT PERICARDITIS – Rilonacept inHibition of interleukin-1 Alpha and beta 
for recurrent Pericarditis: a pivotal Symptomatology and Outcomes stuDY (RHAPSODY) 
 
 
Sponsor: 
 
Kiniksa Pharmaceuticals, Ltd. 
 
 
 
 
Study Drug: 
Rilonacept (KPL-914) 
Protocol Number:  
KPL-914-C002 
SAP Version: 
2.0 
Date of SAP Addendum: 
21JUL2022 
Author: 
 
 
 
CONFIDENTIALITY STATEMENT 
The information in this document is the property of Kiniksa Pharmaceuticals, Ltd. and contains proprietary and 
confidential information to be held in strict confidence and not disclosed to any third party, without prior written 
consent of Kiniksa Pharmaceuticals, Ltd. Persons within your organization to whom any information herein is 
disclosed is on a need-to-know basis solely to carry out the purpose of this document, and be informed that such 
information is confidential and shall not be further disclosed by them without prior written consent from Kiniksa 
Pharmaceuticals, Ltd.  Documentation, data, and all other information generated during the clinical study is 
proprietary and confidential information of Kiniksa Pharmaceuticals, Ltd. and shall not be disclosed to any third 
party, without prior written consent of Kiniksa Pharmaceuticals, Ltd. 


 
 
 
Contents 
1. 
INTRODUCTION ------------------------------------------------------------------------------------------------- 3 
2. 
ADDITIONAL ANALYSES ----------------------------------------------------------------------------------- 3 
2.1 
LTE 18-Month ------------------------------------------------------------------------------------------------------ 3 
2.2 
Adverse Events ----------------------------------------------------------------------------------------------------- 4 
3. 
CHANGES TO THE PLANNED ANALYSES ----------------------------------------------------------- 4 
3.1 
Efficacy Endpoints ------------------------------------------------------------------------------------------------ 4 
3.2 
Safety Endpoints --------------------------------------------------------------------------------------------------- 5 
 


Statistical Analysis Plan Addendum 
 
Kiniksa Pharmaceuticals, Ltd. 
 
 
Study KPL-914-C002 
 
 
Confidential 
        Page 3 of 5 
 
 
1. INTRODUCTION  
The final version (version 2.0) of Statistical Analysis Plan (SAP) for KPL-914-C002 study, based on 
the Protocol version 3.0 Amendment #2 dated 10MAR2020, was signed off on 16JUN2020. The 
statistical rules, efficacy and safety endpoints for long-term extension (LTE) period have been 
specified in SAP version 2.0. As a supplemental document, this addendum only summarizes key 
additional analyses, analyses planned but not conducted for LTE period in SAP V2.0 due to changes 
in business or scientific interests, or due to data availability.  
2. ADDITIONAL ANALYSES 
2.1 
LTE 18-Month  
LTE 18-month is the visit at 18 months after their most recent recurrence, (i.e., the qualifying 
episode for their original study enrollment prior to enrolling in the RI period or a recurrence in RW 
which was treated with bailout rilonacept, whichever is the later).  
If LTE 18-month visits are collected in CRF, those visits in CRF will be used for analyses. 
Otherwise, LTE 18-month visits will be mapped based on the visit date on LTE 18-month 
disposition with 60 days window. The closest assessments will be mapped. If two visits have the 
same distance, the later one will be used.  
 
In addition to treatment disposition and study disposition, disposition of LTE 18-month will be 
summarized as well: 
• Continue treatment with open-label KPL-914 
• Continue in study off-treatment for observation (with option to re-initiate open-label KPL-
914 on-study if there is a pericarditis recurrence) 
• Discontinue from the LTE 
o Patient decision 
o Investigator’s decision 
o No inflammation on MRI 
o Other  
For subjects who decided to continue in study off-treatment for observation, the following 
parameters will be summarized: 
• Time on observation: defined as minimum (first dose date after observation-1, EOS date) – 
disposition date of off-treatment for observation +1. 
• Days on treatment before entering observation, defined as: (disposition date of off-treatment 
for observation-1) - first dose date of LTE period +1.  
• Days on treatment after observation for subjects who entered observation and later resumed 
treatment: minimum (last dose date after observation +6, EOS date) - first dose date after 
observation + 1. 


Statistical Analysis Plan Addendum 
 
Kiniksa Pharmaceuticals, Ltd. 
 
 
Study KPL-914-C002 
 
 
Confidential 
        Page 4 of 5 
 
 
For the subgroups of subjects who decided to continue in study off-treatment for observation and 
subjects continue treatment with open-label KPL-914, additional analyses will be conducted. 
• Time to recurrence from LTE 18-month will be defined from LTE 18-month disposition date 
to recurrence or censored at last assessment before treatment resumed or end of study 
whichever is first.  
• Annualized incidence of recurrence after LTE 18-month visit will be defined as number of 
recurrences for all patients divided by sum of subject-years for all patients within each 
subgroup. Denominator will be calculated as below: 
For subjects who decided to continue in study off-treatment for observation 
o If subjects resumed treatment, first dose date after observation period – LTE 18-
month disposition date   
o If subjects never resumed treatment, EOS date – LTE 18-month disposition date +1   
For subjects who continued treatment with open-label KPL-914, 
o EOS date – LTE 18-month disposition date +1. 
The 95% CI will be calculated using an exact method with Poisson distribution. 
• Line plots of PGIPS, PGAPA, CRP over time will be provided as well. 
For all subjects treated in LTE period, annualized incidence of recurrence from LTE baseline to LTE 
18-month will be summarized. Denominator of subject years will be summarized from LTE first 
dose date to the minimum of End of study date, , LTE 18-month date-1. 
2.2 
Adverse Events  
Two additional summaries of adverse events will be conducted: 
• In addition to summarizing treatment-emergent adverse events, post-treatment adverse events 
will also be summarized. Post-treatment adverse events are defined as adverse events that 
started after the last dose of study drug in LTE period + 6 weeks. 
• Upper respiratory infection adverse events will be summarized. Upper respiratory infection 
will be identified by the following preferred terms: Nasopharyngitis, Pharyngitis, Pharyngitis 
streptococcal, Rhinitis, Sinusitis, Upper respiratory tract infection and Viral upper respiratory 
tract infection.  
3. CHANGES TO THE PLANNED ANALYSES  
3.1 
Efficacy Endpoints 
Changes to the analyses for the LTE Efficacy endpoints specified in SAP version 2.0 (section 
5.3.2.3) are listed below: 
Efficacy endpoints  
Changes  
Reason 


Statistical Analysis Plan Addendum 
 
Kiniksa Pharmaceuticals, Ltd. 
 
 
Study KPL-914-C002 
 
 
Confidential 
        Page 5 of 5 
 
 
2.Proportion of subjects with Clinical Response 
(rilonacept monotherapy + CRP≤0.5 mg/dL + 
NRS≤2) at each CRP assessment (weeks 12 and 
24). The pain NRS at the visit when CRP was 
assessed will be used.  
subjects randomized to KPL-914 utilizing pooled 
data in RW and LTE periods and there will be no 
hypothesis testing.  
Not done 
NRS scores were 
collected only upon 
pericarditis recurrence.  
4. Change over time in pericarditis pain NRS.  
Not done 
NRS were collected 
only upon pericarditis 
recurrence. 
14. Corticosteroid use over time. For subjects who 
are on corticosteroid at RI baseline, the proportion 
of subjects using corticosteroid at LTE will be 
summarized. The denominator will be the number 
of subjects using corticosteroid at RI and entering 
the LTE. The average daily dose of corticosteroid 
(mg/day) will be summarized.  
Not done  
Only limited data 
available as 
corticosteroid use is 
allowed only as rescue 
medication 
 
3.2 
Safety Endpoints 
Summaries of safety endpoints are  conducted by study period (RI, RW, and LTE period) only.  
 


16.1.9 Statistical Analysis Plan
KPL-914-C002 Statistical Analysis Plan (SAP) v1 02Apr2020 ...............................................................
KPL-914-C002 Statistical Analysis Plan (SAP) v2 16Jun2020 .............................................................
KPL-914-C002 SAP Summary of Changes 16Jun2020 .....................................................................
2
56
110
Clinical Study Report
KPL-914-C002
Page 1


 
 
 
STATISTICAL ANALYSIS PLAN 
 
 
 
 
PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED 
WITHDRAWAL STUDY WITH OPENLABEL EXTENSION, TO ASSESS THE 
EFFICACY AND SAFETY OF RILONACEPT TREATMENT IN SUBJECTS WITH 
RECURRENT PERICARDITIS – Rilonacept inHibition of interleukin-1 Alpha and 
beta for recurrent Pericarditis: a pivotal Symptomatology and Outcomes stuDY 
(RHAPSODY) 
 
 
 
 
Sponsor: 
 
Kiniksa Pharmaceuticals, Ltd. 
 
 
 
 
Study Drug: 
Rilonacept (KPL-914) 
Date of Issue: 
02 April 2020 
Version: 
1.0 
 
 
CONFIDENTIALITY STATEMENT 
The information in this document is the property of Kiniksa Pharmaceuticals, Ltd. and contains proprietary and 
confidential information to be held in strict confidence and not disclosed to any third party, without prior written 
consent of Kiniksa Pharmaceuticals, Ltd. Persons within your organization to whom any information herein is 
disclosed is on a need-to-know basis solely to carry out the purpose of this document, and be informed that such 
information is confidential and shall not be further disclosed by them without prior written consent from Kiniksa 
Pharmaceuticals, Ltd.  Documentation, data, and all other information generated during the clinical study is 
proprietary and confidential information of Kiniksa Pharmaceuticals, Ltd. and shall not be disclosed to any third 
party, without prior written consent of Kiniksa Pharmaceuticals, Ltd. 
Clinical Study Report
KPL-914-C002
Page 2


Statistical Analysis Plan 
 
Kiniksa Pharmaceuticals, Ltd. 
 
 
Study KPL-914-C002 
Version 1.0 
Confidential 
   Page 2 of 53 
History of Changes 
 
This document has undergone the following changes: 
 
Version 
Number 
Version Date Description of Changes 
1.0 
02 April 2020 Original document  
 
 
 
Clinical Study Report
KPL-914-C002
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Statistical Analysis Plan 
 
Kiniksa Pharmaceuticals, Ltd. 
 
 
Study KPL-914-C002 
Version 1.0 
Confidential 
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TABLE OF CONTENTS 
TABLE OF CONTENTS .................................................................................................................3 
LIST OF TABLES ...........................................................................................................................5 
LIST OF ABBREVIATIONS ..........................................................................................................5 
1. 
STUDY OBJECTIVES ................................................................................................8 
1.1. 
Study Objectives ...........................................................................................................8 
1.1.1. 
Primary Objective .........................................................................................................8 
1.1.2. 
Secondary Objectives ...................................................................................................8 
2. 
STUDY DESIGN .........................................................................................................8 
2.1. 
Design Overview ..........................................................................................................8 
2.2. 
Schedule of Assessments ............................................................................................10 
2.3. 
Sample Size Calculation and Randomization .............................................................10 
2.3.1. 
Sample Size Calculation .............................................................................................10 
2.3.2. 
Randomization ............................................................................................................10 
2.4. 
Timing of Analysis .....................................................................................................11 
2.5. 
Responsibilities ...........................................................................................................11 
3. 
GENERAL STATISTICAL CONSIDERATIONS ....................................................11 
3.1. 
General Methods .........................................................................................................11 
3.2. 
Stratified Analysis ......................................................................................................12 
3.3. 
Testing Hypotheses and Multiplicity Adjustment ......................................................12 
3.4. 
Subgroups to be Analyzed ..........................................................................................12 
3.5. 
Handling of Missing Data ...........................................................................................13 
4. 
ANALYSIS SETS ......................................................................................................13 
4.1. 
Intent-to-Treat (ITT) Analysis Set ..............................................................................13 
4.2. 
Safety Analysis Set (SS) .............................................................................................13 
4.3. 
Run-in Analysis Set (RIS) ..........................................................................................13 
4.4. 
Long Term Extension Analysis Set (LTES) ...............................................................14 
4.5. 
Per Protocol (PP) Analysis Set ...................................................................................14 
4.6. 
Pharmacokinetics Analysis Set ...................................................................................14 
4.7. 
Verification of Analysis Sets ......................................................................................14 
5. 
STATISTICAL METHODOLOGY ...........................................................................14 
5.1. 
Population Characteristics ..........................................................................................14 
5.1.1. 
Study Subjects Disposition .........................................................................................14 
5.1.2. 
Baseline Demographic ................................................................................................15 
5.1.3. 
Baseline Disease Characteristics ................................................................................15 
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5.1.4. 
Medical/Surgical History ............................................................................................16 
5.1.5. 
Prior and Concomitant Medications ...........................................................................17 
5.1.6. 
Study Drug Administration.........................................................................................17 
5.1.7. 
Protocol Deviations ....................................................................................................18 
5.2. 
Efficacy Analysis ........................................................................................................18 
5.2.1. 
Primary Efficacy Endpoint .........................................................................................18 
5.2.2. 
Secondary Efficacy Endpoint in the RW Period ........................................................21 
5.2.3. 
Secondary Endpoints in RI and LTE Period ...............................................................28 
5.3. 
Safety Analysis ...........................................................................................................31 
5.3.1. 
Adverse Events ...........................................................................................................32 
5.3.2. 
Clinical Laboratory Parameters ..................................................................................33 
5.3.3. 
Vital Signs ..................................................................................................................34 
5.3.4. 
Electrocardiogram .......................................................................................................34 
5.3.5. 
Physical Examination .................................................................................................35 
6. 
PHARMACOKINETIC ANALYSES ........................................................................35 
7. 
PHARMACOGENOMICS SUBSTUDY ...................................................................35 
8. 
ANTI-RILONACEPT ANTIBODIES........................................................................35 
9. 
BIOMARKER ............................................................................................................36 
10. 
INTERIM ANALYSIS ...............................................................................................36 
11. 
CHANGES FROM ANALYSES PLANNED IN THE PROTOCOL .......................36 
12. 
REFERENCES ...........................................................................................................38 
13. 
APPENDICES ............................................................................................................39 
13.1. 
Schedule of Assessments ............................................................................................39 
13.2. 
Missing Data Imputation Rules ..................................................................................50 
13.3. 
EQ-5D-5L Scoring ......................................................................................................51 
13.4. 
Calculation of 95% CI for Incidence Rate per 100 Subject-Years of 
Exposure/Observation .................................................................................................51 
 
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Statistical Analysis Plan 
 
Kiniksa Pharmaceuticals, Ltd. 
 
 
Study KPL-914-C002 
Version 1.0 
Confidential 
   Page 5 of 53 
LIST OF TABLES 
Table 1: 
Censoring Rules for Time to Pericarditis Recurrence in the RW Period ...................19 
Table 2: 
The 8 Domains in SF-36v2 .........................................................................................26 
Table 3: 
SF-36v2 Health Survey Items Scored for the SF-6D .................................................27 
Table 4: 
Study Schedule of Activities – Screening and Run-In Period ....................................39 
Table 5: 
Study Schedule of Activities – Randomized Withdrawal ..........................................43 
Table 6: 
Study Schedule of Activities – Long Term Extension ...............................................46 
Table 7: 
Study Schedule of Activities – Supplemental Visits ..................................................48 
Table 8: 
Imputation Rules for Partial Missing Dates ................................................................50 
 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
ADA 
anti-drug antibodies 
AE 
adverse event 
ALT 
alanine aminotransferase 
ANCOVA 
Analysis of covariance 
AST 
aspartate aminotransferase 
CEC 
Clinical Endpoint Committee 
CMH 
Cochran–Mantel–Haenszel 
CRO 
Contract Research Organization 
CRP 
C-reactive protein 
CS 
corticosteroids 
DMC 
Data Monitoring Committee 
ECG 
electrocardiogram 
ECHO 
echocardiography; echocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EORW 
End of Randomized Withdrawal (visit) 
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Statistical Analysis Plan 
 
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Study KPL-914-C002 
Version 1.0 
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Abbreviation 
Definition 
EOT 
End of Treatment (visit) 
EQ-5D-5L 
5-level EuroQoL-5D 
ESR 
erythrocyte sedimentation rate 
FDA 
US Food and Drug Administration 
GI 
gastrointestinal 
HDL 
High density lipoprotein 
HIV 
human immunodeficiency virus 
ICF 
informed consent form 
ISI 
Insomnia Severity Index 
ISR 
injection site reaction 
ITT 
intent to treat 
IV 
intravenous(ly) 
IWRS 
interactive web response system 
KM 
Kaplan-Meier 
KPL-914 
rilonacept 
LDL 
Low density lipoprotein 
LTE 
Long Term Extension Treatment Period 
MedDRA 
Medical Dictionary for Regulatory Activities 
cMRI 
cardiac magnetic resonance imaging 
MRI 
magnetic resonance imaging 
NMSC 
Non Melanoma Skin Cancer 
NSAID 
nonsteroidal anti-inflammatory drug 
NRS 
Numerical Rating Scale 
ORT 
Oral Rescue Therapy 
PGA-PA 
Physician Global Assessment of Pericarditis Activity 
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Abbreviation 
Definition 
PGIPS 
Patient Global Impression of Pericarditis Severity 
PK 
pharmacokinetic(s) 
POC 
point of care 
RE 
Role participation with emotional health problems in 
SF-6D 
RI 
Run-In (period) 
RP 
Role participation with physical health problems in 
SF-6D  
RW 
Randomized Withdrawal (period) 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis System 
SC 
subcutaneous(ly) 
SF-36 
36-Item Short Form Health Survey 
SFU 
safety follow up 
SOC 
standard of care 
TEAE 
Treatment emergent adverse event 
ULN 
upper limit of normal 
WBC 
white blood cell 
 
 
 
 
 
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Statistical Analysis Plan 
 
Kiniksa Pharmaceuticals, Ltd. 
 
 
Study KPL-914-C002 
Version 1.0 
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   Page 8 of 53 
1. 
STUDY OBJECTIVES 
1.1. 
Study Objectives 
1.1.1. 
Primary Objective 
The primary objective of this study is to assess the efficacy of rilonacept treatment in subjects 
with recurrent pericarditis. 
1.1.2. 
Secondary Objectives 
The secondary objective of this study is to assess the safety of rilonacept treatment in subjects 
with recurrent pericarditis. 
2. 
STUDY DESIGN 
2.1. 
Design Overview 
This study has the following periods: 
 Screening period, during which assessment of disease characteristics, baseline 
therapy, and the pretreatment workup is completed (up to 4 weeks).  
 Single-blind Run-In (RI) period (12 weeks), during which blinded rilonacept is 
administered subcutaneously (SC) once weekly in all subjects after the loading 
dose of double injections. The RI period includes the following: 
 1-week Stabilization period, during which blinded rilonacept is administered 
in addition to standard of care (SOC) pericarditis therapy and the ongoing 
pericarditis episode is treated. 
 9-week Weaning period, during which subjects are weaned off background 
SOC pericarditis therapy, as applicable, while treatment with blinded 
rilonacept continues. 
 2-week Monotherapy period during which subjects who have successfully 
weaned off background SOC pericarditis therapy will continue to receive 
blinded rilonacept.   
 
In the single blind RI period (subjects are blinded regarding the time of transition from the 
single- blind to the double- blind- period), adult subjects ≥18 years old will receive rilonacept 
as an initial loading dose of 320 mg (2 SC injections of 160 mg each) at the RI baseline visit 
(2 × 2 mL), followed by a 160 mg (2 ml) SC dose once weekly throughout the RI period. 
Pediatric subjects ((≥12 and <18 years old) will receive an initial loading dose of rilonacept 
4.4 mg/kg (2 SC injections of 2.2 mg/kg each) at the RI baseline visit (maximum 2 × 2 mL), 
and then 2.2 mg/kg (maximum 2 mL) SC once weekly throughout RI period. 
Subjects who achieve clinical response at RI Week 12 defined as stopping background 
pericarditis therapy no later than Week 10 and weekly average of daily pericarditis pain score 
≤2.0 on the 11-point Numerical Rating Scale (NRS) within the 7 days prior to and including 
the day of randomization on RI Week 12/Randomization Withdrawal (RW) baseline and a 
C-reactive protein (CRP) level ≤0.5 mg/dL at the RI Week 12/RW baseline visit, will proceed 
into the double-blind placebo-controlled RW period.  
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Subjects who do not achieve clinical response at RI Week 12/RW baseline on rilonacept 
monotherapy will be discontinued from study drug, transitioned to SOC pericarditis therapy 
at the Investigator’s discretion and followed through the end of the RW period. 
Additionally, after the randomized withdrawal period has been closed when at least 
22 confirmed recurrent pericarditis events have been accrued, subjects who have not yet 
completed the full 12 weeks of RI period at that time will be allowed to continue tapering of 
concomitant meds in the RI period; those subjects who achieved clinical response by Week 
12 will be given the option to receive open-label rilonacept in the Long-term Extension 
Treatment period (LTE) without having to proceed through the RW period.   
 Double-blind placebo-controlled RW period (pericarditis recurrence event-
driven duration), during which subjects who were able to stop background SOC 
pericarditis therapy and who achieve clinical response at RI Week 12/RW 
baseline are randomized in a double-blind manner at a 1:1 ratio to the following: 
 Rilonacept 160 mg (2.2 mg/kg in pediatric subjects) SC injections once 
weekly 
 Matching placebo SC injections once weekly 
Pericarditis Recurrence in the RW Period 
Pericarditis recurrence is defined as the recurrence of typical pericarditis pain associated with 
supportive objective evidence of pericarditis. Upon pericarditis recurrence, subjects who 
report at least 1 day with pericarditis pain measurement ≥4 on the 11point NRS and have 
1 CRP value ≥1 mg/dL (either on the same day or separated by no more than 7 days) will 
receive bailout rilonacept (2 open-label injections of 160 mg rilonacept [or 4.4 mg/kg for 
pediatric subjects] followed by once weekly open-label rilonacept SC injections of 160 mg 
[or 2.2 mg/kg for pediatric subjects]) irrespective of randomized treatment assignment and as 
soon as at least 5 days have passed since the last study drug injection. Sequential oral rescue 
therapy (ORT), i.e., analgesics first, then NSAIDs, and then colchicine, can be added if 
needed at the discretion of the Investigator, as outlined in the protocol and Pharmacy Manual. 
Subjects with pericarditis recurrence and who do not meet the protocol criteria for bailout 
rilonacept will continue blinded study drug until the protocol criteria for bailout rilonacept 
are met or through the end of the RW period. For those subjects, sequential ORT can be 
added to blinded study drug at the discretion of the Investigator, as outlined in the protocol 
and Pharmacy Manual. 
All suspected pericarditis recurrence events in the RW period will be formally adjudicated by 
the Clinical Endpoint Committee (CEC), and only events that are confirmed by the CEC as 
pericarditis recurrences will be used in the Primary Endpoint analysis. 
 
Long-term Extension Treatment period (LTE) (variable, up to 24 months), 
during which all subjects in the RW period (including subjects transitioned to open-
label rilonacept upon pericarditis recurrence) and subjects who are in the Run-In 
period after closure of the RW period, will have an option to receive up to 
24 months of open-label rilonacept 160 mg (or 2.2 mg/kg for pediatric subjects) SC 
injections once weekly based on their clinical status and at the discretion of the 
Investigator, after signing LTE informed consent.  
 
Subjects will be reviewed at 18 months after their most recent recurrence, (i.e., the 
qualifying episode for their original study enrollment prior to enrolling in the RI 
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Statistical Analysis Plan 
 
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Version 1.0 
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period or a recurrence in RW which was treated with bailout rilonacept, whichever 
is the later). During this month visit, the Investigator and subject will decide 
whether to continue treatment with open-label rilonacept, to continue in the study 
off-treatment for observation and rilonacept bailout upon subsequent recurrence, or 
discontinuation from the LTE. This review may be supplemented by:  
 cMRI and/or echocardiogram and/or additional diagnostic testing as 
determined by the Investigator.    
 subjects may be unblinded at that time (if available) at the request of the 
Investigator per procedures outlined in the Unblinding Plan to assist in clinical 
decision-making.   
Safety data will be reviewed throughout the LTE by the Data Monitoring Committee.  
2.2. 
Schedule of Assessments 
The schedule of assessments is in Section 13.1. 
2.3. 
Sample Size Calculation and Randomization 
2.3.1. 
Sample Size Calculation 
Sample size calculation is based on the primary endpoint, time to pericarditis recurrence 
defined as the time from randomization to the date of the first pericarditis recurrence for each 
subject.  Time to pericarditis recurrence is assumed to follow an exponential distribution. An 
event of interest is defined as a subject’s first adjudicated recurrence of pericarditis. The 
following assumptions are used in the sample size calculation using EAST 6.4.1: 
 1-sided significance level: 2.5% 
 Power: 90% 
 Median time to event (in weeks) in placebo: 8 
 Hazard ratio (rilonacept/placebo): 0.244 
 Percentage of subjects in the RI period that will not reach RW: 10%. 
Given these assumptions, a total of 22 adjudicated pericarditis recurrence events is required 
to achieve the power. About 25 subjects per arm (a total of 50 subjects) or more will be 
randomized. Considering 10% of subjects in the RI period that will not reach the RW period, 
approximately 56 subjects will be enrolled in this study.  
Subject enrollment and the pericarditis recurrence event accrual will be closely monitored 
during the study. The monitoring activities will be done in a blinded fashion during the RW 
period. If the number of subjects randomized is less than 50 and/or the time anticipated for 
the number of events required for the analysis of primary efficacy endpoint significantly 
exceeds the projected timeline, additional subjects may be enrolled and/or randomized at 
Kiniksa Pharmaceutical’s discretion. However, at this time it is anticipated that no more than 
100 subjects will be enrolled into this study.  
2.3.2. 
Randomization 
Subjects who achieve clinical response at RI Week 12 (Section 2.1) will proceed into the 
double-blind placebo controlled RW period. An interactive web response system (IWRS) will 
be used to administer the randomization schedule. CRO Biostatistics will generate the 
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randomization schedule using SAS® software Version 9.4 or later (SAS Institute Inc, Cary, 
North Carolina) for the IWRS, which will link sequential subject randomization numbers to 
treatment codes. The randomization schedule will be stratified by 2 factors: 
 Oral CS use at baseline (RI baseline, i.e., beginning of RI period): yes or no 
 Diagnosis of recurrent idiopathic pericarditis (RI baseline): yes or no 
2.4. 
Timing of Analysis 
The data cutoff for the primary analysis will be the end of RW period.  When at least 22 
adjudicated pericarditis recurrence events have occurred, end of RW period will be 
announced.  The sites will have their subjects return to the site for the end-of-RW assessment 
(EORW).  Data cutoff will occur after all subjects have completed this assessment.  All data 
for this cutoff will be used in the primary analysis for efficacy and safety.  
After the RW period, there will be a Long-term Extension Treatment period.  An analysis 
will also be conducted after the end of the study. Since the data cutoff for the primary 
analysis will be done by the end of RW period, summary for LTE period will not be included 
in the primary analysis.   
No interim analysis for claiming efficacy is planned. Interim safety review will be conducted 
by a Data Monitoring Committee (DMC).  The analysis will be performed by a designated 
CRO.  Details are in DMC charter and DMC Statistical Analysis Plan (SAP). 
2.5. 
Responsibilities 
The statistical analysis for the study will be performed by Kiniksa Biostatistics or its 
designated CROs. 
3. 
GENERAL STATISTICAL CONSIDERATIONS 
3.1. 
General Methods  
Statistical analysis will be performed using SAS® software Version 9.4 or later. Continuous 
variables will be summarized using the mean, the standard deviation, median, minimum 
value, and maximum value. Time-to-event variables will be summarized using percent 
censored, event rate, and 25th, 50th, and 75th percentiles with 95% CI, if estimable. 
Categorical variables will be summarized using frequency counts and percentages. Data will 
be listed in data listings. 
At RI, RW, and LTE periods, baseline will be the last value before the first dose of study 
drug within each individual period unless otherwise specified. For change-over-time 
endpoints in the RW period, by-visit analysis will be performed at each scheduled visit for at 
least 24 weeks. 
When weekly average of NRS is used, it will be calculated based on every 7 days starting on 
the day after the first injection in each period. If there are missing values during the 7- day 
period, the average will be calculated based on the non-missing values. If 50% or more 
values (≥4 days) are missing, the average value will be set to missing.  
By-visit analyses will be based on nominal visits and observed data, with unscheduled visits 
excluded. 
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3.2. 
Stratified Analysis 
There are two stratification variables for randomization: oral CS use at baseline (yes or no), 
and diagnosis of recurrent idiopathic pericarditis at RI baseline (yes or no).  When an analysis 
is to be stratified by these variables and a stratum has ≤5 events of interest in a log-rank test 
or the same response in all subjects in a CMH test, the strata for diagnosis of recurrent 
idiopathic pericarditis will be pooled. If the same situation still exists, the analysis will be 
done without stratification. 
3.3. 
Testing Hypotheses and Multiplicity Adjustment 
All statistical tests for the treatment comparison of efficacy endpoints in the RW period will 
be based on a 1-sided α=0.025. For each endpoint, the null hypothesis is that the effects of 
rilonacept and placebo are the same. The alternative hypothesis is that rilonacept is better 
than the placebo. 
In order to control the overall 1-sided type I error rate at the 0.025 level, a gatekeeping 
procedure in combination with Hochberg’s procedure will be applied to testing the primary 
and major secondary endpoints. If the 1-sided p-value for testing the primary endpoint is 
≤0.025, a significant treatment effect on the primary endpoint will be claimed. 
Section 5.2.2.1 provides the order of major secondary endpoints. If the primary endpoint is 
significant, the first major secondary endpoint, i.e., proportion of subjects who maintained 
clinical response at Week 16 of RW period will be tested at 1-sided α=0.025. A significant 
treatment effect on this major secondary endpoint will be claimed if the 1-sided p-value is 
≤0.025. If the treatment effect is not significant on the primary endpoint, significance on this 
major secondary endpoint cannot be claimed regardless of the result. 
If both primary and first major secondary endpoints are significant following the above 
procedure, the second and third major secondary endpoints defined in Section 5.2.2.1 will be 
tested with Hochberg’s procedure at overall 1-sided α=0.025. If both 1-sided unadjusted 
p-values are ≤0.025, claim significance of rilonacept for both endpoints. If the larger 1-sided 
p-value is >0.025, compare the smaller 1-sided p-value with 0.0125. If the smaller 1-sided 
p-value is ≤0.0125, claim significance of rilonacept on this endpoint. 
3.4. 
Subgroups to be Analyzed 
Subgroup analyses for the primary efficacy endpoint will be performed by the following 
variables for the RW period: 
 Oral CS use at baseline (RI baseline, i.e., beginning of RI period): yes or no 
 Diagnosis of recurrent idiopathic pericarditis (RI baseline): yes or no 
 Type of pericarditis: idiopathic, post pericardiotomy syndrome, Dressler’s 
syndrome, and Still’s disease. Other type will not be included in the subgroup 
analysis due to the small sample size. 
 Age group: 12 - <18, 18 - <65, and 65 – (maximum age in ITT analysis set) 
[Analysis for the pediatric group (12- <18) may not be performed if the sample 
size is too small.] 
 Gender: males vs. females 
 Race: Caucasian vs. non-Caucasian 
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 Region: USA vs. non-USA 
 Number of pericarditis episodes at enrollment (including index and qualifying 
episodes): <5 vs. ≥5 
 ADA status: ADA positive at any assessment, ADA positive with neutralizing 
antibody at any assessment, and ADA negative at every assessment. 
P-values and summary statistics will be generated following Section 5.2 , with the 
understanding that the sample size is likely too small to have an adequate power.  The forest 
plot with 95% CI will be provided for the primary efficacy endpoint. 
3.5. 
Handling of Missing Data 
To the extent possible, attempts will be made to minimize the amount of missing data through 
measures planned in the study. Unless otherwise specified, missing data will not be imputed 
and only the observed data will be used in the analyses. 
Additional rules for missing data imputation are provided in Section 13.2. 
4. 
ANALYSIS SETS 
4.1. 
Intent-to-Treat (ITT) Analysis Set  
All subjects who are randomized in the RW period will be included in the Intent-to-Treat 
(ITT) analysis set. The primary analysis for efficacy endpoints in the RW period will be 
based on the ITT analysis set unless otherwise specified. Treatment comparisons for all 
analyses will be based on each subject’s treatment assignment from randomization. 
The following analysis sets are defined for the analysis of secondary endpoints: 
 ITT Week 24 analysis set: All subjects randomized at least 24 weeks before data 
cutoff will be included. This analysis set will be used for secondary efficacy 
endpoints measured at week 24 in the RW period. 
 ITT Week 16 analysis set: All subjects randomized at least 16 weeks before data 
cutoff will be included. This analysis set will be used for secondary efficacy 
endpoints measured at week 16 in the RW period. 
 ITT Week 8 analysis set: All subjects randomized at least 8 weeks before data 
cutoff will be included. This analysis set will be used for secondary efficacy 
endpoints measured at week 8 in the RW period. 
4.2. 
Safety Analysis Set (SS) 
All subjects who take at least 1 dose of study drug in the RI period will be included in the 
Safety Analysis set (SS). Safety analyses will be based on the actual treatment a subject 
received. 
4.3. 
Run-in Analysis Set (RIS) 
All subjects who received at least 1 dose of study drug in the RI period will be included in the 
RI analysis set (RIS). 
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In addition, the following analysis set will be used for secondary efficacy endpoints measured 
at Week 12 in the RI period: 
 Run-in Week 12 Analysis Set: All subjects who received the first dose in the RI 
period at least 12 weeks before data cutoff.  
4.4. 
Long Term Extension Analysis Set (LTES) 
All subjects who received at least 1 dose of study drug in the LTE will be included in the 
Long-term Extension Analysis set (LTES). 
4.5. 
Per Protocol (PP) Analysis Set  
The Per Protocol Analysis set (PP) is a subset of the ITT analysis set with the exclusion of 
subjects with important protocol violations or violations that may potentially bias statistical 
analyses or the ethical conduct of the study. The criteria of these violations will be 
determined prior to unblinding. This analysis set may be used for sensitivity analyses for 
efficacy endpoints in the RW period. 
4.6. 
Pharmacokinetics Analysis Set  
The Pharmacokinetic (PK) Analysis set includes subjects who receive at least 1 dose of study 
drug and have at least 1 post-baseline PK sample. The PK analysis set will be used for all PK 
analyses. 
4.7. 
Verification of Analysis Sets 
A blinded review to verify all defined analysis sets excluding LTES will be conducted before 
database lock of primary analysis.  The results will be documented.  The document will list 
subjects excluded from each analysis set with reason(s). 
5. 
STATISTICAL METHODOLOGY 
5.1. 
Population Characteristics 
5.1.1. 
Study Subjects Disposition 
Subject disposition will be summarized as follows. 
 RI period  
 Screened Subjects (Signed Informed Consent) 
 Enrolled  
 Subjects treated in RI period 
 Subjects completed RI treatment 
 Subjects with early treatment discontinuation and reasons for treatment 
termination 
 Subjects with treatment ongoing at end of RI period 
 RW Period  
 Number of subjects randomized, by arm  
 Subjects treated in RW period 
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 Subjects who completed RW period 
 Subjects who discontinued study drug before end of RW period with 
reason of discontinuation 
 Subjects with treatment ongoing at end of RW period 
 Number of subjects who consented to the LTE period  
 LTE  
 Subjects who completed the Treatment Period 
 Subjects who discontinued study drug with reasons for treatment 
discontinuation 
 Study disposition   
 Subjects who completed 
 Subjects who terminated early and reasons for early termination 
 Subjects with study ongoing  at data cutoff 
5.1.2. 
Baseline Demographic  
Frequency counts (n) and percentages (%) will be presented for sex, race, ethnicity, and age 
group (i.e., 12-17 years, 18-64 years, and 65 years to the maximum age in the ITT analysis 
set). Descriptive statistics such as number of subjects (n), mean, standard deviation, median, 
minimum and maximum will be presented for age (years), weight (kg), Height (cm), and 
body mass index (BMI) kg/m2. 
5.1.3. 
Baseline Disease Characteristics   
Baseline disease characteristics include the following: 
 Oral corticosteroid use at RI Baseline (yes/no)  
 Diagnosis of recurrent idiopathic pericarditis at RI (yes/no) 
 Type of recurrent Pericarditis 
 Idiopathic 
 Pericardiotomy syndrome 
 Dressler’s syndrome 
 Still’s disease 
 Other  
 Duration of disease from first episode to the date of inform consent 
 Total number of pericarditis episodes, total number of episodes in the past year 
until first injection in the RI period, and annualized number of episodes per year,   
 Time since beginning of qualifying episode in days 
 Baseline central CRP value and weekly pain NRS score 
 Baseline pericardial rub, effusion, tamponade, electrocardiogram (ECG) findings 
(widespread ST-elevation and PR-Depression), ECG interpretation 
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 Pericarditis treatment at baseline 
 Non-opioid analgesics 
 Opioid analgesics 
 Aspirin 
 nonsteroidal anti-inflammatory drug (NSAIDs) 
 Colchicine  
 Oral corticosteroids 
 IM/IV corticosteroids 
 Other 
 
Disease characteristics for the qualifying episode, including the following: 
 Number and proportion of subjects with presence of pericarditis pain, pericardial 
rub, new widespread ST-segment elevation or PR-segment depression on ECG, 
new or worsening in pericardial effusion, and pericardial inflammation on 
magnetic resonance imaging (MRI). 
 Values of pain level, CRP (mg/dL), fever (Celsius), white blood cell (WBC; 
103/uL), and erythrocyte sedimentation rate (ESR) (mm/hr).  
 Treatment for the qualifying episode 
 Non-opioid analgesics 
 Opioid analgesics 
 Aspirin 
 NSAIDs 
 Colchicine  
 Oral corticosteroids 
 IM/IV corticosteroids 
The categorical (discrete) variables will be summarized using counts and percentages. The 
continuous variables will be summarized using n, mean, median, standard deviation, and 
range (minimum, maximum). Summaries will be presented for the RI, RW, and LTE periods. 
Baseline disease characteristics will also be summarized for subjects who are on 
corticosteroid at RI baseline. In addition to those specified above, the following baseline data 
will be summarized: 
 Duration (in weeks) of using oral prednisone prior to enrollment 
 Average dose (mg/day) of oral prednisone prior to enrollment 
 Cumulative dose (mg) of oral prednisone prior to enrollment 
5.1.4. 
Medical/Surgical History 
Medical/Surgical history will be summarized by Medical Dictionary for Regulatory Activities 
(MedDRA; v21.1) system organ class and preferred term. One subject will be counted only 
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once within one preferred term and one system organ class. The summary will be sorted in 
the alphabetic order of system organ classes and preferred terms.  
Medical history details as collected on the electronic case report form (eCRF) such as body 
system, description, the date of onset, stop date and the current status of the condition will be 
presented in a by-subject data listing. 
5.1.5. 
Prior and Concomitant Medications 
Prior medications are defined as those taken before the date of the first study drug 
administration, i.e. started before the start of the study drug.  
Concomitant medications are defined as any non-study medication taken during the treatment 
period which is from the date of first dose to the date of last dose plus 6 weeks.  
Additionally, the medications will be considered concomitant if the start date of the 
medication is missing.  
A medication that started prior to the first dose of the study drug and continued after that date 
will be considered as both prior and concomitant. 
Prior and concomitant medications will be coded using World Health Organization (WHO) 
Drug (version March 2018). Medications will be summarized by ATC level 2 code and 
preferred term.  Summary will be done by periods (i.e., RI, RW, and LTE) and by treatment 
(KPL-914 vs placebo) for RW period. One subject will be counted once within one preferred 
term and one ATC class.  The medication information will be presented in a by-subject listing 
with ATC class (level 2) and WHO Drug Dictionary preferred term, start and stop date, 
dosage, route, frequency and indication. 
Concomitant pericarditis treatment will be summarized by period and by treatment for RW 
period using the following categories:  
 non-opioids 
 opioid analgesics 
 aspirin, NSAIDs 
 colchicine 
 oral corticosteroids,  
 IM/IV corticosteroids or other medications 
In addition, concomitant pericarditis treatment received during the RW treatment period will 
also be summarized based on the status of receiving bailout treatment (i.e. concomitant 
medication received before start of bailout treatment vs after start bailout treatment) for each 
treatment group in the RW period.   
For RI period, use of concomitant pericarditis treatment (i.e., background treatment) will be 
summarized over time. 
5.1.6. 
Study Drug Administration 
The study medication administration details including the administration date and time, dose, 
site of injection and comments will be presented in a by-subject listing.  
The following parameters related to study drug administration will be summarized for each of 
the treatment periods: RI, RW, LTE, and Study Overall. 
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 Treatment duration in weeks: 
 For RI period, it is defined as [minimum of (date of last study drug +6, date of 
RI week 12 visit – 1, date of data cutoff) - date of first study drug + 1)/7].  
 For RW period it is defined as [minimum of (date of last study drug +6, date 
of end of RW visit) - date of first study drug + 1)/7]. 
 For LTE and study overall, it is defined as [minimum of (date of last study 
drug +6, end of study date, date of data cutoff) - date of first study drug + 1)/7. 
Number of administrations in each period regardless of full amount or partial amount of 
syringe injected. The loading dose includes two injections and will be counted as one 
administration.  
Compliance (%) in each period, calculated as (number of administrations) / (protocol planned 
number of administrations) ×100%.  The loading dose includes 2 injections and will be 
counted as one administration. 
Total rilonacept dose administered in each period, defined as the sum of all doses (mg) 
received in the corresponding period. The actual volume administered will be used to 
calculate the total dose. For subjects receiving weight-adjusted dose (e.g., 2.2 mg/kg) their 
weight collected at scheduled visits will be used to calculate the amount of the study drug 
received. 
Percentage of self-administrations by the subject, defined as [Number of self-
administrations] / [Total number of administrations received] × 100%.  The loading dose will 
be included in the denominator as one administration. If one of 2 injections in the loading 
dose is self-administered, it will be counted in the numerator.  
5.1.7. 
Protocol Deviations 
Protocol deviations will be derived programmatically as well as reported by sites.  
A blinded review before database lock will be conducted to determine important protocol 
deviations. Protocol deviations are considered important if based on Sponsor assessment they 
can impact study integrity or interpretability of study results.  
Important protocol deviations will also be evaluated if they have impact on efficacy data. 
Important protocol deviations with potential impact on efficacy will be used to exclude 
subjects from PP analysis set. 
All protocol deviations will be reviewed and categorized before database lock. All important 
protocol deviations will be summarized by deviation category (including Inclusion Criteria, 
Exclusion Criteria, ICF, Concomitant Medication, and other if applicable).  The protocol 
deviation data will also be presented as a by-subject data listing.  
5.2. 
Efficacy Analysis 
5.2.1. 
Primary Efficacy Endpoint 
5.2.1.1. 
Definition 
The primary efficacy endpoint is time to pericarditis recurrence, defined as the time from 
randomization to the date of the first pericarditis recurrence for each subject. Only 
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CEC-confirmed pericarditis recurrence will be considered as an event for the primary 
analysis.   
Time to pericarditis recurrence is calculated as: Data of Event/Censor – Date of 
randomization +1. 
Pericarditis recurrence is defined as the recurrence of typical pericarditis pain associated with 
supportive objective evidence of pericarditis. The assessments to be conducted by the 
investigator is described in protocol Section 6.1.4.  At any time during the RW period, 
subjects who experience a suspected recurrence of pericarditis symptoms will be requested to 
report to the study site/clinic for a scheduled or unscheduled visit, during which clinical 
assessments will be performed to gather all the necessary diagnostic data to confirm or rule 
out the presence of pericarditis recurrence.  
Pericarditis recurrence will also be evaluated by the investigators at the following time 
points: 
 Routine assessment (every 4 weeks until week 24 in RW, then every 8 weeks)  
 End of RW period 
 End of treatment 
 Post-treatment safety follow-up 
 LTE assessment (every 12 weeks up to 24 months and 18-month visit) 
Upon suspected pericarditis recurrence, the event is required to be captured in the electronic 
data capture (EDC) system within 24 hours of learning of the event, and a pericarditis 
recurrence event adjudication package must be prepared for adjudication by CEC. Details on 
endpoint package requirements will be described in the CEC charter. The CEC confirmed 
pericarditis recurrences will be used for the analysis of primary efficacy endpoint. 
The censoring rules in Table 1 will be used in the analysis of the primary efficacy endpoint, 
in which, the event/censor reason will be provided in a data listing. 
Table 1: 
Censoring Rules for Time to Pericarditis Recurrence in the RW Period 
 
Scenario* 
Event/ 
Censor 
Event/Censor 
Reason 
Date of Event/ 
Censor 
1 
Pericarditis recurrence occurred before 
or without receiving bailout rilonacept, 
including events after termination of 
study drug  
Event 
Recurrence 
Date of 
pericarditis 
recurrence 
2 
Pericarditis recurrence occurred after 
receiving ORT or prednisone  
Event 
Recurrence after 
receiving 
ORT/prednisone 
Date of 
pericarditis 
recurrence 
3 
Receiving bailout rilonacept before 
pericarditis recurrence  
Event 
Recurrence after 
receiving bailout  
Date of 
pericarditis 
recurrence 
4 
No pericarditis recurrence during RW 
period with or without receiving 
ORT/prednisone 
Censored 
No pericarditis 
recurrence  
Date of last 
assessment for 
pericarditis 
recurrence on or 
before data 
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Scenario* 
Event/ 
Censor 
Event/Censor 
Reason 
Date of Event/ 
Censor 
cutoff. 
 
5.2.1.2. 
Analysis Methods for the Primary Endpoint 
The log rank test will be the primary method for the analysis of time to recurrence based on 
CEC confirmed events, stratified by the stratification variables for randomization. Analysis 
based on the ITT analysis set will be used as the primary analysis. Analysis based on the PP 
analysis set will be considered as a sensitivity analysis.   
Time to recurrence will be summarized with the 25th, 50th (median), and 75th percentiles using 
the Kaplan-Meier (KM) method. The 95% confidence interval (CI) for the percentiles will be 
calculated using a log-log transformation.  The percentage of subjects with pericarditis 
recurrence and its 95% CI will be calculated at weeks 8, 16, 24, and 36 since randomization, 
using Greenwood’s formula with a log-log transformation. 
The hazard ratio for KPL-914 vs. placebo and the corresponding Wald 95% CI will be 
calculated based on a Cox proportional-hazards model with treatment as covariate, stratified 
by randomization strata. 
A sensitivity analysis will be performed based on the Investigator’s judgement of pericarditis 
recurrence. A 2×2 table for the concordance/discordance between Investigator’s judgement 
and CEC’s adjudication will be generated. 
Upon pericarditis recurrence as determined by the investigator, subjects who report at least 1 
day with pericarditis pain measurement ≥4 on the 11-point NRS and have 1 CRP value 
≥1 mg/dL (either on the same day or separated by no more than 7 days) will receive bailout 
rilonacept (2 open-label injections of 160 mg rilonacept [or 4.4 mg/kg for pediatric subjects]) 
irrespective of randomized treatment assignment and as soon as at least 5 days have passed 
since the last study drug injection. The subjects transitioning to bailout rilonacept will remain 
blinded to their randomized treatment assignment.  
For subjects who have pericarditis recurrence, the frequency table and listing will be 
generated for the following treatment prescribed by the Investigator: 
 Bailout rilonacept 
 Analgesics 
 NSAIDS 
 Colchicine 
 Other. 
The following criteria for pericarditis recurrence were provided to CEC to determine 
pericarditis recurrence: 
1. Re-appearance or worsening of typical pericarditis pain (with at least one pain NRS 
recording ≥4) AND elevated CRP (≥1.0 mg/dL) either on the same day or separated 
by no more than 7 days  
 
OR 
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2. Re-appearance or worsening of typical pericarditis pain (with at least one pain NRS 
recording ≥4), AND abnormal CRP (>0.5 mg/dL) either on the same day or separated 
by no more than 7 days AND at least 1 supportive evidence of pericarditis as below 
 
OR 
3. Re-appearance or worsening of typical pericarditis pain (but no NRS scores being 
≥4), AND elevated CRP (≥1.0 mg/dL) not attributable to other causes AND at least 1 
supportive manifestation of pericarditis as below. 
Supportive Evidence (Pericarditis manifestations): 
 increased WBC count >upper limit of normal (ULN)  
 fever >38C 
 presence of pericardial rub 
 ECG changes consistent with pericarditis, i.e., findings of new widespread 
ST-segment elevation and/ or PR-segment depression 
 new or worsened pericardial effusion on echocardiography (ECHO) 
 new or worsening pericardial inflammation on MRI or other imaging modality. 
The above information will be summarized and listed. 
5.2.2. 
Secondary Efficacy Endpoint in the RW Period 
This Section defines secondary efficacy endpoints for the RW period. Endpoints for the RI 
and LTE periods are defined in Section 5.2.3. 
5.2.2.1. 
Definition of Major Secondary Efficacy Endpoints in the RW Period 
This section defines 3 major secondary endpoints. These endpoints will be analyzed with the 
ITT Week 16 analysis set.  Handling of missing data due to end of RW period will be 
discussed in Section 5.2.2.2. 
1. Proportion of subjects who maintained clinical response at Week 16 of the RW 
period. clinical response is defined as a weekly average of daily pericarditis pain on 
the 11-point NRS ≤2.0 and CRP level ≤0.5 mg/dL, and on monotherapy of 
randomized study drug at Week 16.  
 
Subjects who complete 16-week of double-blinded treatment and meet the clinical 
response criteria at Week 16 will be considered as responders. Subjects who had 
recurrence, discontinued double-blinded treatment, lost to follow-up, and used bailout 
rilonacept or rescue medications (ORT or prednisone) before Week 16 will be 
considered as non-responders.     
 
If either weekly average of NRS or CRP is missing at week-16 assessment, the 
subject will be considered as a non-responder.  
2. Percentage of days with pain NRS ≤2 in the first 16 weeks of the RW period. No or 
minimal pain is defined as non-missing NRS ≤2. 
 
The denominator will be 168 (=16x7) for every subject.  NRS assessments after 
treatment termination will be included.  NRS assessments while on rescue 
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medications for pericarditis will considered not meeting this criterion.  Receiving each 
administration of bailout rilonacept will disqualify for meeting NRS ≤2 for 7 days.  
Missing values will be counted as 0 day meeting the criterion.  
3. Proportion of subjects with absent or minimal pericarditis symptoms (based on the 
7-point PGIPS) at Week 16 of the RW period. 
 
Subjects who do not have the assessment due to early termination or other reasons 
will be considered as not meeting the criterion.  Subjects who took rescue medications 
at the Week 16 assessment or used bailout rilonacept on or before Week 16 will also 
be considered not meeting the criteria. 
5.2.2.2. 
Analysis Methods for Major Secondary Efficacy Endpoints in the RW Period 
These endpoints will be analyzed with the ITT Week 16 analysis set. 
1. For the proportion of subjects who maintained Clinical Response at Week 16 of the 
RW period, the response rate and Clopper–Pearson 95% CI will be obtained for each 
arm. Difference of response rate (KPL-914 – Placebo) and 95% CI based on normal 
approximation will be provided. The Cochran–Mantel–Haenszel (CMH) test will be 
used to test the treatment effect, stratified by the stratification variables for 
randomization.  
2. For the percentage of days with pain NRS ≤2 in the first 16 weeks post 
randomization, an analysis of covariance will be used for treatment comparison.  In 
addition to treatment arm, the following covariates will be included in this analysis: 
the stratification variables for randomization, and RI baseline NRS in 2 categories: 
NRS ≤2 versus NRS >2. LS mean difference and the 95% CI will be provided. 
3. For proportion of subjects with absent or minimal pericarditis symptoms (based on the 
7-point PGIPS) at Week 16 of the RW period, the response rate and Clopper–Pearson 
95% CI will be obtained for each arm. Difference of response rate (KPL-914 – 
Placebo) and 95% CI based on normal approximation will be provided. The Cochran–
Mantel–Haenszel (CMH) test will be used to test the treatment effect, stratified by the 
stratification variables for randomization.  
5.2.2.3. 
Other Secondary Efficacy Endpoints in the RW Period and Statistical 
Method 
All time-to-event endpoints start from the day of randomization. The same censoring rules for 
the primary endpoint will be applied. Missing values will not be imputed unless otherwise 
specified. Analysis of secondary endpoints will be based on ITT analysis unless otherwise 
specified. 
1. Proportion of subjects who maintained Clinical Response at Week 24 of the RW 
period based on ITT Week 24 analysis set 
 
The same rules and method for the first major secondary endpoint will be applied, 
except that 16 weeks is replaced with 24 weeks.  
2. Proportion of subjects who maintained Clinical Response at Week 8 of the RW period 
based on based on ITT Week 8 analysis set 
 
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The same rules and method for the first major secondary endpoint will be applied, 
except that 16 weeks is replaced with 8 weeks. 
3. Percentage of days with minimal or no pain in the first 24 weeks post randomization 
based on ITT Week 24 analysis set 
 
The same rules and method for the second major secondary endpoint will be applied, 
except that 16 weeks is replaced with 24 weeks. 
4. Percentage of days with minimal or no pain in the first 8 weeks post randomization 
based on ITT Week 8 analysis set 
 
The same rules and method for the second major secondary endpoint will be applied, 
except that 16 weeks is replaced with 8 weeks. 
5. Proportion of subjects with absent or minimal pericarditis symptoms (based on the 
7‑point PGIPS) at Week 24 of the RW period based on subjects who were randomized 
at least 24 weeks before data cutoff 
 
The same rules and method for the third major secondary endpoint will be applied, 
except that 16 weeks is replaced with 24 weeks. 
6. Proportion of subjects with absent or minimal pericarditis symptoms (based on the 
7‑point PGIPS) at Week 8 of the RW period based on subjects who were randomized 
at least 8 weeks before data cutoff 
 
The same rules and method for the third major secondary endpoint will be applied, 
except that 16 weeks is replaced with 8 weeks. 
7. Proportion of subjects without pericarditis recurrence in the first 24 weeks of the RW 
period 
 
The proportion of subjects without pericarditis recurrence in the first 24 weeks of the 
RW period in each arm will be estimated using the KM method, as described in the 
analysis of the primary endpoint. The same censoring rules will apply. The variance 
of the difference in proportion between treatment arms will be the sum of the variance 
in each arm. The p-value and 95% CI will be calculated using a normal 
approximation. 
8. Time to pericarditis pain NRS ≥4 
 
Use the same method for the primary endpoint. 
9. Time to CRP level ≥1 mg/dL. This is for elevation of CRP for which no other cause 
other than pericarditis was identified.  
 
Use the same method for the primary endpoint. A manual review for any CRP ≥1 
mg/dL will be performed to make sure that the CRP increase was caused by 
pericarditis. 
10. Time to pericardial rub 
 
Use the same method for the primary endpoint. Subjects with pericardial rub at RW 
baseline will be excluded from the analysis. 
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11. Time to widespread ST-segment elevation or PR-segment depression on ECG 
 
Use the same method for the primary endpoint. Subjects with either condition at RW 
baseline will be excluded. 
12. Time to new or worsening pericardial effusion on ECHO 
 
Use the same method for the primary endpoint.  Proportion of subjects with new or 
worsening in pericardial effusion on ECHO and its 95% CI in each arm will be 
estimated using the K-M method. 
13. Change in category of ECHO pericardial effusion size at week 24 and end of RW 
based on central labs  
 The ITT Week 24 analysis set will be used for this endpoint.  Effusion size in 
ECHO has the following categories:  
 None or Trivial/Physiologic 
 Small 
 Moderate 
 Large 
 Very Large 
 NM/ND (Not Measurable/Not Recorded by Site) 
 
Change in ECHO pericardial effusion size will be summarized by before and 
including bailout rilonacept in each arm.  Shift tables for change from RW baseline to 
RW weeks 24 and to end of RW visit will be generated.  Due to potentially different 
number of subjects receiving bailout rilonacept between treatment arms, there will be 
no hypothesis testing for this endpoint.  
 
Endpoints 14-16 will be summarized for data before receiving bailout rilonacept and 
for data including bailout rilonacept in each arm.  P-values will not be provided due to 
potentially different number of subjects receiving bailout rilonacept.  
14. Change over time in central-lab CRP level 
 
A mixed model with repeated measures (MMRM) using TYPE=UN option in SAS 
Proc Mixed will be applied in the analysis of this endpoint. If the model does not 
converge, an analysis of covariance (ANCOVA) model will be used at each timepoint 
to calculate least-squares (LS) means. In the model, subjects will have repeated 
measures for the response variable change from baseline of the endpoint. The 
explanatory variables will include the baseline value, treatment arm, baseline value by 
treatment interaction, and the variables for randomization strata. Only observed values 
will be used in the analysis without imputation.     
15. Change over time in the subject’s assessments of pericarditis pain (weekly averages) 
 
The same method for change over time in CRP level will be applied. If bailout 
rilonacept is used in a week, the week will be considered as after bailout. 
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16. Number (percentage) of subjects with absent or minimal pericarditis activity over 
time after RW week 24 based on the PGIPS. The denominator in each arm will be the 
total number of subjects with the assessment at each visit. 
 
The CMH test stratified by the randomization strata will be applied. 
17. Number (percentage) of subjects with absent or minimal pericarditis activity over 
time based on the PGA-PA. The denominator in each arm will be the total number of 
subjects with the assessment at each visit. 
 
The same analysis method and analysis sets for PGPIS will be applied. 
 
The endpoints below (18 – 23) from patient reported outcomes will be summarized 
with descriptive statistics. There will be no hypothesis testing since they are measured 
at RW baseline and Week 24 only and receiving bailout rilonacept due to recurrence 
at Week 24 could be a confounding factor.   
18. Change from baseline to week 24 in the SF-36 Physical and Mental Component 
Scores (see below for definition)  
19. Change from baseline to week 24 in Physical Functioning, Role-Physical, Bodily 
Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental 
Health domains in SF-36. 
 
The SF-36v2® Health Survey (standard, four-week recall) is a 36-item generic (not 
indication specific) instrument used to evaluate subject reported health related quality 
of life (HRQoL) in adult subjects.  The questions are organized in eight health domain 
scales: physical functioning [PF] (10 items), role participation with physical health 
problems [RP] (four items), bodily pain [BP] (two items), general health status [GH] 
(one item), vitality [VT] (four items), social functioning [SF] (two items), role 
participation with emotional health problems [RE] (three items), and mental health 
(five items).  Scores from the eight domains are summarized into a physical 
component score (PCS) and mental component score (MCS).  
 
The SF-36v2 utilizes norm-based scoring involving a linear T-score transformation 
method so that scores for each of the health domain scales and component summary 
measures have a mean of 50 and a standard deviation of 10, based on the 2009 United 
States general population.  Scores above and below 50 are above and below the 
average, respectively, in the 2009 United States general population. Also, because the 
standard deviation is 10, each 1-point difference or change in scores has a direct 
interpretation; that is, 1 point is one-tenth of a standard deviation, or an effect size 
of 0.10. 
 
Subject responses will be scored, including the handling of missing data, consistent 
with the instructions in the SF-36v2 user manual using the Optum Smart 
Measurement System Scoring Solution software.  
 
The possible score for each item is from 1 to 6. Each item response is then assigned a 
numeric value according to one of 8 scales.  
 
Items 1, 2, 20, 22, 34, 36: 1=100, 2=75, 3=50, 4=25, 5=0  
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Items 3, 4, 5, 6, 7, 8, 9, 10, 11, 12: 1=0, 2=50, 3=100 
Items 13, 14, 15, 16, 17, 18, 19: 1=0, 2=100 
Items 21, 23, 26, 27, 30: 1=100, 2=80, 3=60, 4=40, 5=20, 6=0 
Items 24, 25, 28. 29, 31: 1=0, 2=20, 3=40, 4=60, 5=80, 6=100 
Items 32, 33, 35: 1=0, 2=25, 3=50, 4=25, 5=0. 
 
Final scores for each scale range from 0 to 100 with higher scores indicating better 
health. If a subject does not respond to a question, the average score for an item will 
use the number of non-missing scores for the denominator. 
 
Table 2 displays the items that are categorized.  Detailed information can be found in 
Mark, EM (2011). 
 
Table 2: 
The 8 Domains in SF-36v2 
Scale 
Number of items 
After recoding, average the following 
items 
Physical functioning 
10 
3 4 5 6 7 8 9 10 11 12 
Role-physical (RP) 
4 
13 14 15 16 
Bodily pain 
2 
21 22 
General health 
5 
1 33 34 35 36 
Vitality 
4 
23 27 29 31 
Social functioning 
2 
20 32 
Role-emotional (RE) 
3 
17 18 19 
Mental health 
5 
24 25 26 28 30 
 
20. Changes in SF-6D, 6 domain scores and the utility index 
 
The SF-6D is calculated based on responses to 11 items on the SF-36, that correspond 
to 6 domains: physical functioning, role participation (combined role-physical and 
role-emotional), social functioning, bodily pain, mental health, and vitality.  
 
RP and RE are combined, and general health is not included. The specific SF-36v2 
areas or activities contributing to the scoring of this index include: 
 ability to engage in both moderate and vigorous activities 
 ability to bathe and dress oneself 
 limitations in the kind of work or other activities as the result of physical health; 
accomplishing less due to emotional problems 
 bodily pain and its interference with normal work; nervousness, depression, and 
energy level 
 interference with social activities due to physical or emotional problems.  
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Individual respondents can be classified on any of four to six levels of functioning or 
limitations for each of six domains, thus allowing a respondent to be classified into 
any of 18,000 possible unique health states. Using a standard gamble technique, each 
of these health states were mapped onto the SF-6D index score, which ranges from 
0.00 (worst possible health state/death) to 1.00 (best possible health state/perfect 
health). 
The PRO Analytics software calculates and outputs the SF-6D for each subject at 
each assessment, just as it does for the 8 domain scores and 2 summary scores. 
In the 2009 QualityMetric US Normative survey (Maruish 2011), from which the 
scoring algorithms were derived, the SF-6D calculated for 3,856 participants who 
completed the standard (4-week recall) form of the SF-36v2 had a mean of 0.74 and a 
SD of 0.14. Based on a paper from Walters and Brazier (2003), a change of 0.05 in 
the SF-6D would indicate a minimally important difference. 
Table 3: 
SF-36v2 Health Survey Items Scored for the SF-6D 
SF-6D Domains 
SF-36v2TM Health Survey 
Items 
Physical Functioning 
3a, 3b, 3j 
Role Participation (RP & PE) 
4c, 5b 
Social Functioning  
10 
Bodily Pain 
7, 8 
Mental Health 
9b, 9f 
Vitality 
9e 
 
21. Change in EQ-5D-5L individual scores and index value 
 
The EQ-5D-5L is a subject reported health status utility index for adult subjects that is 
comprised of five questions plus a visual analog scale (VAS). The five questions ask 
the respondent to assess their health in terms of mobility, self-care, usual activities, 
pain/discomfort, and anxiety/depression. The VAS captures the respondent’s self-
reported level of the health on the day of completion, captured as a numeric input 
from 0 (‘the worst health you can imagine’) to 100 (‘the best health you can 
imagine’).  Subject responses will be scored, including the handline of missing values, 
as specified in the EuroQol Research Foundation, EQ-5D-5L User Guide, 2019, 
available from http://euroqol.org/publications/user-guides. 
 
Scores from the five questions will be reported individually and converted to a single 
index value using the value set for US.  Health state index scores generally range from 
less than 0 (where 0 is the value of a health state equivalent to dead; negative values 
representing values as worse than dead) to 1 (the value of full health), with higher 
scores indicating higher health utility. 
22. Change in subject’s sleep quality assessed with the Insomnia Severity Index (ISI).  
 
The ISI is a 7-item self-report questionnaire assessing the nature, severity, and impact 
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of insomnia. The usual recall period is the “last 2 weeks” and the dimensions 
evaluated are severity of sleep onset, sleep maintenance, early morning awakening 
problems, sleep dissatisfaction, interference of sleep difficulties with daytime 
functioning, noticeability of sleep problems by others, and distress caused by the sleep 
difficulties. A 5-point Likert scale is used to rate each item (e.g., 0=no problem; 
4=very severe problem), yielding a total score ranging from 0 to 28 (Morin et al 
2011).  
 
The ISI will be collected in subjects ≥18 years or older as described in the protocol. 
23.  Change in ISI categories. The ISI total scores are divided to 4 categories: 
 1)  0–7 = No clinically significant insomnia 
 2)  8–14 = Subthreshold insomnia 
 3)  15–21 = Clinical insomnia (moderate severity) 
 4)  22–28 = Clinical insomnia (severe) 
A shift table will also be used to summarize the changes over time.  
24. Cumulative number (percentage) of subjects who received sequential ORT, 
prednisone, or bailout rilonacept for pericarditis period every 4 weeks cumulatively in 
the RW period.  
 
The CMH test stratified by the randomization strata will be applied to this endpoint. 
25. Proportion of subjects using ORT (analgesics, NSAIDs, and/or colchicine) for 
pericarditis in the first 24 weeks.  ORT use while waiting for at least 5 days since 
previous administration of study medication before receiving bailout rilonacept or 
within 5 days prior to the assessment of pericarditis recurrence visit is excluded. The 
denominator of the percentages is the number of subjects in the ITT analysis set in 
each arm. There will be no hypothesis testing for this endpoint. 
26. The endpoints below for MRI assessments will be summarized at RW baseline and 
week 24.  P-values will not be calculated. 
 Proportion of subjects with pericardial delayed hyperenhancement 
 Proportion of subjects with myocardial delayed hyperenhancement  
 Proportion of subjects with pericardial effusion, and effusion size 
A subject will have pericardial effusion if the effusion size is rated “Small” or larger. 
5.2.3. 
Secondary Endpoints in RI and LTE Period 
These include efficacy endpoints in the RI period and the LTE. Since there is no control arm 
in these 2 periods, only descriptive statistics will be provided. Summary statistics will be 
generated following the methodologies stated in Section 3.1 using RIS or LTES analysis sets. 
All time-to-event endpoints start from the first day of receiving rilonacept in that period.  
Unless specified otherwise, the denominator of a response rate or percentage will be the total 
number of subjects treated in that period. 
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5.2.3.1. 
Secondary Endpoints in the RI Period  
The following efficacy endpoints will be included for the RI period. Unless specified 
otherwise, change means change from RI baseline to RI week 12, CRP level is from central 
lab, and the denominator for a proportion is the total number of subjects who were treated in 
the RI period. 
1. Time to pain response, defined as number of days from first dose to the first day a 
subject’s daily pain NRS is ≤ 2 of the 3 days over which, the rolling average daily 
pain NRS is ≤ 2. Subjects with baseline NRS ≤ 2 will be excluded from the analysis.  
2. Time to CRP normalization (≤0.5 mg/dL) 
 
Time to CRP normalization will be censored at treatment discontinuation, taking 
prohibited medication, or week 12, whichever occurs first. Subjects with baseline 
CRP ≤0.5 mg/dL will be excluded from the analysis.  
3. Time to rilonacept monotherapy 
 
Time to rilonacept monotherapy is defined as number of weeks from first dose to the 
first day of achieving monotherapy. Subjects without background therapies at RI 
baseline will be excluded from the analysis. 
4. Time to treatment response defined as time from first dose to the first day of pain 
response, and CRP ≤0.5 mg/dL within 7 days before or after pain response. Treatment 
response day will be the first day that the above criterion is met. If pain response 
occurs before CRP ≤0.5 mg/dL, each 3-day rolling average of NRS should be ≤2.0 
from the day of pain response to the day of CRP ≤0.5 mg/dL. The response day will 
be the day of pain response.  If CRP ≤0.5 mg/dL occurs before pain response, the 
response day will also be the day of pain response. 
5. Proportion of subjects achieving clinical response at RI week 12 based on RIS Week 
12 analysis set 
 
Subjects who stopped background SOC pericarditis therapy on or before week 10, as 
well as who achieve CRP ≤0.5 mg/dL  and weekly average of daily pericarditis pain 
score ≤2.0 on the 11-point NRS within the 7 days prior to and including the day of 
randomization on RI Week 12/Randomization are responders.   
6. Number (percentage) of subjects with normalization of CRP (≤0.5 mg/dL) at RI Week 
12.  Subjects with baseline CRP >0.5 mg/dL in the RI week 12 analysis set will be 
used in the analysis. 
7. Change from baseline in pericarditis weekly pain score at RI Week 12 and over time. 
8. Change from baseline in CRP level at RI Week 12 and over time. 
9. Proportion of subjects with resolution of echocardiographic and ECG abnormalities 
(yes/no) at RI Week 12. 
10. Percentage of days with no or minimal pain (NRS ≤2) while on treatment. The 
denominator is the number of days on treatment, calculated as [min(date of last dose 
of study drug in RI period + 6, last date on study, end of RI period) – date of first dose 
in RI period) +1].   
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11. Proportion of subjects with absent or minimal pericarditis symptoms based on PGIPS 
over time at baseline, week 6, and week 12. 
12. Proportion of subjects with absent or minimal pericarditis activity based on the PGA-
PA over time at baseline, week 6, and week 12. 
13. Change in the SF-36 8 domain scores, as well as the physical and mental scores. 
14. Change in the SF-6D 6 domain scores and the utility index. 
15. Change in the EQ-5D-5L individual scores and index value.  
16. Change in the subject’s sleep quality assessed with the ISI (see Section 5.2.2.3). 
17. Change in ISI categories. 
18. Number (percentage) of subjects who were off background pericarditis medication on 
or before weeks 4, 8, 10, and 12 
 
The RI Week 12 Analysis Set will be used for the summary.  At each timepoint, the 
numerator only includes subjects who have reached monotherapy on or before the 
timepoint and remain on monotherapy until the end of the RI period. 
5.2.3.2. 
Efficacy Endpoints in the LTE Period 
The efficacy endpoints below are included in this period. These endpoints will not be 
included in the primary analysis for the RW period since data will not be available at that 
time.  Each endpoint will be summarized through Week 24 in this period, by subjects who did 
and did not have an adjudicated pericarditis recurrence in the RW period and by subjects who 
enter LTE directly from the RI period, respectively, and overall.  The baseline for the LTE 
period will be the last assessment before the first dose in the LTE period. 
1. Number (percentage) of subjects with pericarditis recurrences based on investigators’ 
judgement. 
2. Proportion of subjects with Clinical Response (rilonacept monotherapy + CRP≤0.5 
mg/dL + NRS≤2) at each CRP assessment (weeks 12 and 24).  The pain NRS at the 
visit when CRP was assessed will be used. 
3. Change over time in CRP levels. 
4. Change over time in pericarditis pain NRS. 
5. Proportion of subjects with absent or minimal pericarditis symptoms over time based 
on PGIPS. 
6. Proportion of subjects with absent or minimal pericarditis activity over time based on 
the PGA-PA. 
7. Change from baseline in the SF-36 8 domain scores, as well as the physical and 
mental scores. 
8. Change in the SF-6D 6 domain scores and the utility index. 
9. Change from baseline in the EQ-5D-5L individual scores and index value. 
10. Change from baseline in the subject’s sleep quality assessed with the ISI.  
11. Change over time in ISI categories.   
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12. Number (percentage) of subjects requiring addition of SOC pericarditis therapy every 
4 weeks cumulatively. 
13. Change from baseline in pericardial signs in ECHO, ECG, and MRI. 
14. Prednisone use over time.  
 
For subjects who are on prednisone at RI baseline, the proportion of subjects using 
prednisone at LTE will be summarized.  The denominator will be the number of 
subjects using prednisone at RI and entering the LTE.  The average daily dose of 
prednisone (mg/day) will be summarized. 
15. In the MRI substudy, resolution in pericardial inflammation among subjects with 
pericardial inflammation at RI baseline as assessed by cardiac MRI.  The endpoints 
below will be summarized. 
a. Proportion of subjects with pericardial Delayed Hyperenhancement  
b. Proportion of subjects with Myocardial Delayed Hyperenhancement 
c. Proportion of subjects with pericardial effusion, and effusion size  
16. Annualized recurrent rate during treatment 
 
Annualized recurrent rate will be calculated for subjects randomized to KPL-914 
utilizing pooled data in RW and LTE periods and there will be no hypothesis testing.  
5.3. 
Safety Analysis  
The following safety endpoints will be analyzed: 
 Adverse events, 
 Clinical laboratory parameters, 
 Serology parameters, 
 Hematology parameters, 
 Non-fasting lipid panel, 
 Pregnancy test, 
 Vital signs, 
 Urinalysis, 
 Electrocardiogram, and  
 Physical examination. 
Descriptive statistics will be used to summarize safety endpoints for all subjects by the 
following periods:  
 RI period (KPL-914) 
 RW period  
 KPL-914 vs. Placebo Including Bailout Rilonacept 
 KPL-914 vs. Placebo before Bailout Rilonacept 
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 LTE period  
 Study overall (RI through LTE), KPL-914 or placebo, regardless of receiving 
bailout Rilonacept.  
Two-sided 95% CIs will be presented where meaningful. Data summaries will be displayed 
for clinical laboratory analyses, vital signs measurements, ECGs, and physical examination 
findings. 
5.3.1. 
Adverse Events 
Treatment-emergent AEs (TEAEs), defined as AEs that start or increase in severity after the 
first dose of study drug and before 6 weeks after the last dose of study drug, will be coded to 
system organ class and preferred term using MedDRA v21.1.   
TEAEs will be summarized by each period and study overall.  In the RW period, they will 
also be summarized by including and excluding bailout rilonacept, respectively. The average 
follow-up duration in weeks for TEAE will be provided in summary tables.  The duration of 
follow-up for each subject is defined as follows. 
 For the RI period, it is from first dose in RI period until the day before 
randomization, last dose day plus 6 weeks, last study day, or data cutoff, 
whichever occurs first. 
 For the RW period including bailout, it is from randomization to data cutoff, last 
dose day plus 6 weeks, or last study day, whichever occurs first. 
 For the RW period before bailout, it is from randomization to the start of using 
bailout rilonacept, data cutoff, last dose day plus 6 weeks, or last study day, 
whichever occurs first. 
 For the LTE period, it is from first dose day in LTE period to data cutoff, last dose 
day plus 6 weeks, or last study day, whichever occurs first. 
 For study overall, it is from first dose day in RI period to data cutoff, the last dose 
plus 6 weeks, or last study day, whichever occurs first. 
A summary of the frequency (number and percentage of subjects) of TEAEs will be 
presented by system organ class and preferred term. Adverse events will also be analyzed by 
their severity (mild, moderate or severe), relationship to study drug, serious AEs, AEs leading 
to death, AEs resulting in dose interruption, AEs leading to withdrawal of study treatment, 
and AEs of injection site reaction.  
Any AE of malignancy (excluding basal cell carcinoma of the skin) is of special interest.  AE 
of special interest will also be summarized.   
A subject experiencing the same AE multiple times will be counted only once for that 
preferred term. Similarly, if a subject experiences multiple AEs (preferred terms) within the 
same system organ class, then that subject will be counted only once for that system organ 
class. When summarizing by severity and relationship, only event with highest severity or 
relationship will be counted. All AEs will be presented by SOC and preferred terms. 
Incidence rate per 100 subject-years and its 95% CI will be calculated by the periods defined 
for follow-up duration above for the following groups of AEs: 
 All AEs (include any AE),  
 SAE (include any SAE), 
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 deaths,  
 all infections (including serious),  
 serious infections (serious only),  
 all ISR (injection site reaction, including serious and non-serious),    
 only serious ISR,  
 all malignancies excluding NMSC (Non-Melanoma Skin Cancer: ie. cutaneous 
basal cell carcinoma and cutaneous squamous cell carcinoma). 
Incidence rate per 100 subject-years = 100 × (number of different AE start days within the 
treatment period)/(Sum of treatment duration in years from all subjects in the cohort).  
Multiple events within a subject will be counted as multiple events. Treatment exposure 
duration and follow-up of AE’s in the Study Overall period will be 6 weeks after the last dose. 
There will be no formal hypothesis testing. 
5.3.2. 
Clinical Laboratory Parameters 
Hematology, chemistry, lipid panel, and urinalysis results will be summarized and listed.  
Pregnancy test will not be summarized but will be listed. Summaries will include descriptive 
statistics for actual values and change from baseline.  Shift tables from baseline condition to 
the condition at each visit will also be provided.  The shift table will include subjects without 
data so that all subjects in the safety population at the baseline of each period (RI, RW, and 
LTE) will be included.  
A summary of hepatic function abnormalities will be provided for the following criteria:  
 >2xULN 
 >3xULN 
 >5xULN  
 The number of percentage of subject’s meeting the criteria for Hy’s Law defined 
as elevations in ALT and/or AST of >= 3xULN with accompanying elevations in 
total bilirubin of >= 2xULN will also be summarized. 
The incidence rate per 100 subject-years and its 95% CI for the following lab abnormalities 
will be calculated: 
 Incidence of ALT >5xULN,   
 Incidence of AST >5x ULN,  
 Incidence of total bilirubin >2xULN 
 Incidence of absolute neutrophil count (ANC) <1.0 x 103 uL. 
Multiple lab abnormalities within a subject will be counted as multiple events within the 
follow-up period defined in Section 5.3.1 .  
Incidence rate per 100 subject years in a cohort = 100 × (# of different lab abnormalities from 
all subjects within the follow-up period)/(Sum of follow-up duration in years from all 
subjects in the cohort). 
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5.3.2.1. 
Hematology 
Hematology tests performed at central study laboratory include WBC count with differential, 
platelet count, red blood cell count, mean corpuscular volume, hemoglobin, mean corpuscular 
hemoglobin concentration. 
5.3.2.2. 
Chemistry 
Blood chemistry tests performed in the central study laboratory include albumin, total 
protein, alkaline phosphatase, alanine aminotransferase/serum glutamic pyruvic transminase 
(ALT/SGPT), aspartate aminotransferase/serum glutamic oxaloacetic transminase 
(AST/SGOT), direct bilirubin, total bilirubin, bicarbonate, chloride, potassium, sodium, 
creatinine, glucose. 
5.3.2.3. 
Non-fasting Lipid Panel 
Subjects treated with rilonacept may experience increases in their lipids, including total 
cholesterol, low-density lipoprotein (LDL), high-density lipoprotein HDL, and triglycerides. 
Non fasting measurements of total cholesterol, triglycerides, HDL, and direct LDL will be 
performed by central study laboratory as described in the Schedule of Assessments in 
Section 13.1. 
Investigators should monitor the lipid profiles in study subjects and consider ordering fasting 
lipid panel and/or lipid lowering therapies as needed based on cardiovascular risk factors and 
current guidelines. 
5.3.2.4. 
Urinalysis 
Urinalysis performed by the central study laboratory includes specific gravity, pH, protein, 
urobilinogen, ketones, glucose, blood, bilirubin, nitrites, leukocyte esterase will be 
summarized.  
5.3.2.5. 
Pregnancy Test 
For women of child-bearing potential, a urine pregnancy test using a licensed test (dipstick) 
should be performed prior to receiving the first administration of study drug, and as needed 
during the study, and also at the SFU visit. When needed, serum pregnancy test should be 
performed. Pregnancy test results will not be summarized but will be listed. 
5.3.3. 
Vital Signs 
Descriptive summaries of actual values and changes from baseline will be calculated for 
Temperature, Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Pulse Rate 
(PR), Respiratory Rate (RR), temperature, and weight (kg). A data listing of vital signs will 
also be provided. 
5.3.4. 
Electrocardiogram 
Frequency table for the following interpretations will be generated: 
 Widespread of ST elevation normal 
 PR-segment depression 
 ECG Interpretation 
 Normal 
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 abnormal not clinically significant, and abnormal clinically significant) 
 Abnormal not consistent with pericarditis but clinically significant 
 Abnormal consistent with pericarditis 
Shift table for shifts from baseline to the last post-baseline assessment in the treatment period 
and extension period in the overall interpretation based on local read will be created. All ECG 
data will be provided as a by-subject listing.  
5.3.5. 
Physical Examination 
There are full and abbreviated physical examinations.  Full physical examination includes at 
minimum evaluation of vital signs, head, eye, ear, nose, and throat as well as cardiovascular, 
dermatological, musculoskeletal, respiratory, gastrointestinal (GI), genitourinary, and 
neurological systems. The decision to perform examination of genitourinary system should be 
guided by clinical judgement.  Abbreviated physical examination includes at minimum 
evaluation of vital signs, lung and heart sounds, including evaluation for pericardial rub. 
Present or absent in pericardial rub will be recorded.  For each assessment of body system, 
the result will be recorded as normal, abnormal (not clinically significant), or abnormal 
(clinically significant).  The number and percentage of subjects in each result category will be 
summarized by body system and visit, as well as by arm in the RW period. 
All physical examination data will be provided in a listing. 
6. 
PHARMACOKINETIC ANALYSES 
For all subjects, serum samples will be collected at time points shown in Section 13.1 in order 
to quantify concentrations of rilonacept. Only individual listings of serum concentrations will 
be provided. The analysis plan for PK data will be described in a separate document. 
7. 
PHARMACOGENOMICS SUBSTUDY 
Samples for pharmacogenomics in the substudy will be collected according to the Study 
Schedule of Activities. More details of the analysis will be provided in a separate document. 
8. 
ANTI-RILONACEPT ANTIBODIES 
Blood sample for testing anti-rilonacept antibody (ADA) will be collected at RI baseline, RI 
weeks 2, 6, 12 (= RW baseline), RW week 24, end of RW/LTE baseline, and LTE week 24.  
ADA status will be categorized as follows. 
1. Treatment-emergent ADA, including treatment induced or boosted [increased by one 
quartile (with all titers collected) from the previous assessment]  
2. Prior existing ADA (without treatment boosted) 
3. ADA negative at every assessment. 
For subjects with treatment-emergent ADA, the maximum post-baseline titer level (low, 
medium, high) will be summarized.  The 3 levels (low, medium, high) will be divided based 
on 25th and 75th percentiles from all ADA titers pooled. 
The following endpoints will be summarized for each category of ADA status above: 
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 Number and percentage of subjects with injection site reactions within 24 hours of 
administration  
 Subjects with Neutralizing antibody in the first 2 categories above. 
A summary table will be provided for number and percent of subjects with positive or 
negative anti-rilonacept antibody by visit.  Individual’s ADA status and titer level (if 
positive) at each visit will be provided. 
The number and percent of subjects with anti-rilonacept-antibody positive at any visit vs. 
those with negative at every visit will also be provided.  The summary statistics of CRP and 
NRS level will be provided for these 2 subsets of subjects at each visit by study period, and 
by treatment arm in the RW period (before vs. after receiving bailout rilonacept and overall). 
The following 3 categories will be used in the subgroup analysis for the primary endpoint, 
Summary of NRS scores and CRP levels over time, summary of TEAEs (overall and drug 
related), and blood concentration over time: 
1. Subjects with ADA Positive at Any Assessment 
2. Subjects with ADA Positive and Neutralizing Antibody at Any Assessment 
3. Subjects with ADA Negative at Every Assessment 
9. 
BIOMARKER 
Serum and plasma will be collected according to the Study Schedule of Activities for 
biomarker analysis. More details of the biomarker analysis will be provided in a separate 
document. 
10. 
INTERIM ANALYSIS 
No interim analysis for claiming efficacy is planned. Interim safety review will be conducted 
by a Data Monitoring Committee (DMC).  The analysis will be performed by a designated 
CRO.  Details are in DMC charter and DMC SAP. 
11. 
CHANGES FROM ANALYSES PLANNED IN THE 
PROTOCOL 
Analysis in the SAP 
Analysis planed in the 
protocol  
Reason  
Section 5.2.3.1  
Time to pain response, defined as number of 
days from fist dose to the first day a subject’s 
daily pain NRS is ≤ 2 of the 3 days over which, 
the rolling average daily pain NRS is ≤ 2.  
Section 7.3.1 
Time to pain response 
defined as a rolling 
average of NRS score 
of 2 or less on three 
consecutive days. 
A score of 3 or 
higher on the first 
day of the rolling 
average should not 
qualify pain 
response. 
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Analysis in the SAP 
Analysis planed in the 
protocol  
Reason  
Section 5.2.3.1 
Time to treatment response defined as time 
from first dose to the first day of pain response, 
and CRP ≤0.5 within 7 days before or after 
pain response. Treatment response day will be 
the first day that the above criterion is met. If 
pain response occurs before CRP ≤0.5, each 3-
day rolling average of NRS should be ≤2.0 
from the day of pain response to the day of 
CRP ≤0.5. The response day will be the day of 
pain response.  If CRP ≤0.5 occurs before pain 
response, the response day will also be the day 
of pain response. 
Section 7.3.1 
Time to clinical 
response (monotherapy 
+ NRS ≤2 + CRP ≤0.5 
mg/dL) 
Subjects were 
enrolled with a 
qualifying episode 
and on background 
therapy.  The 
endpoint of interest 
is to evaluate how 
soon subjects will 
reach response in 
both pain and CRP 
after initiating 
rilonacept while on 
background therapy.  
 
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12. 
REFERENCES 
Brookmeyer R and Crowley J (1982), “A Confidence Interval for the Median Survival Time” 
Biometrics, 38, 29 - 41. 
Deng Q (2014), “Computing Confidence Interval for Poisson Mean” 
http://onbiostatistics.blogspot.com/2014/03/computing-confidence-interval-for.html. 
Lucis NC, Ron BSE, and Hays D (2015), “Scoring the SF-36 in Orthopaedics: A Brief 
Guide” J Bone Joint Surg Am 97(19): 1628-34. 
Maruish, M. E. (Ed., 2011), User’s manual for the SF-36v2 Health Survey (3rd ed.). Lincoln, 
RI: QualityMetric Incorporated. 
Maruish, ME (2011).  Manual for the SF-36v2 Health Survey (3rd Edition), QualityMetric, 
Inc., Lincoln, RI. 
Morin CM, Belleville G, Belanger L, et al (2011), “The insomnia severity index: 
psychometric indicators to detect insomnia cases and evaluate treatment response” Sleep. 
34(5):601-608. 
Poisson distribution, https://en.wikipedia.org/wiki/Poisson_distribution. 
Spritzer K (2014), “SAS Code for Scoring 36-Item Health Survey Version 2.0” 
http://sasstatistics.blogspot.com/2014/07/use-sas-to-score-sf-36.html. 
Sullivan KM and Soe MM (2006), “Confidence Intervals for a Rate” 
http://www.openepi.com/PDFDocs/PersonTime1Doc.pdf. 
Taft C, Karlsson J, Sullivan M (2001), “Do SF-36 summary component scores accurately 
summarize subscale scores?” Qual Life Res 10(5):395-404. 
Reenen MV, Janssen B. (2015) EQ-5D-5L User guide. Basic information on how to use the 
EQ-5D-5L instrument. Version 2.1. https://euroqol.org/docs/EQ-5D-5L-User-Guide.pdf.  
Walters, S.J. (2003), Brazier, J.E. What is the relationship between the minimally important 
difference and health state utility values? The case of the SF-6D. Health Qual Life Outcomes 
1, 4 doi:10.1186/1477-7525-1-4. 
 
 
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13. 
APPENDICES 
13.1. 
Schedule of Assessments 
Table 4: 
Study Schedule of Activities – Screening and Run-In Period  
Trial Period 
SCREENINGa 
RUN-IN (12 weeks)m 
  
ENROLLMENT 
  
RANDOMIZATION -q 
Visit Name 
Screening Visit 
RI  
Baseline 
RI  
Day 2 
RI  
Day 4 
RI  
Week 1 
RI  
Week 2 
RI  
Week 4 
RI  
Week 
6 
RI  
Week 
10 
RI Week 12/ 
RW Baseline 
Visit Windowb (days) 
(-28) 
NA 
NA 
+/- 1 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 3 
Visit Type 
Clinic 
Clinic 
Clinic 
TC/RN 
TC/RN 
TC/RN 
TC/RN 
Clinic 
TC 
Clinic 
Informed Consent Form 
X 
  
  
  
  
  
  
  
  
  
Inclusion and Exclusion criteria 
X 
X 
  
  
  
  
  
  
  
  
Demographics 
X 
  
  
  
  
  
  
  
  
  
Medical/Surgical History 
X 
  
  
  
  
  
  
  
  
  
Pericarditis Diagnosis & History 
X 
X 
  
  
  
  
  
  
  
  
Concomitant medications 
X 
X 
  
X 
X 
X 
X 
X 
X 
X 
Pericarditis Concomitant 
medications 
X 
X 
  
X 
X 
X 
X 
X 
X 
X 
Pericarditis Concomitant medication 
tapering 
  
  
  
  
X 
X 
X 
X 
X 
  
Full Physical Examinationc 
X 
  
  
  
  
  
  
  
  
  
Abbreviated Physical Examinationd 
  
X 
  
  
  
  
  
  
  
X 
Body weight and height 
  
X 
  
  
  
  
  
  
  
X 
12-Lead ECG 
  
X 
  
  
  
  
  
  
  
X 
Echoe 
  
Xe 
  
  
  
  
  
  
  
Xe 
MRI (substudy only) 
  
X 
  
  
  
  
  
  
  
  
Pericardial pain (11-point NRS) 
Xf 
DAILYg 
Xg 
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Trial Period 
SCREENINGa 
RUN-IN (12 weeks)m 
  
ENROLLMENT 
  
RANDOMIZATION -q 
Visit Name 
Screening Visit 
RI  
Baseline 
RI  
Day 2 
RI  
Day 4 
RI  
Week 1 
RI  
Week 2 
RI  
Week 4 
RI  
Week 
6 
RI  
Week 
10 
RI Week 12/ 
RW Baseline 
Visit Windowb (days) 
(-28) 
NA 
NA 
+/- 1 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 3 
Visit Type 
Clinic 
Clinic 
Clinic 
TC/RN 
TC/RN 
TC/RN 
TC/RN 
Clinic 
TC 
Clinic 
EQ-5D 
  
X 
  
  
  
  
  
  
  
X 
SF-36 
  
X 
  
  
  
  
  
  
  
X 
ISI 
  
X 
  
  
  
  
  
  
  
X 
PGIPS 
  
X 
  
  
  
  
  
X 
  
X 
PGA-PA 
  
X 
  
  
  
  
  
X 
  
X 
Hematology, Chemistry Labs 
(Central) 
  
X 
  
  
  
  
  
X 
  
X 
Lipid Panel (Central)h 
  
X 
  
  
  
  
  
  
  
X 
CRP (Local) 
Xf 
  
  
  
  
  
  
  
  
X 
CRP (Central) 
(X) 
X 
  
X 
X 
X 
X 
X 
  
X 
Hematology, Chemistry, IGRAr, 
hepatitis serology, HIV (Local) 
X 
  
  
  
  
  
  
  
  
  
Chest X-Ray 
X 
  
  
  
  
  
  
  
  
  
Urine Pregnancy (Local or Central)j 
X 
X 
  
  
  
  
  
  
  
  
Urinalysis (Central) 
  
X 
  
  
  
  
  
  
  
  
PK (Central)s 
  
  
Xi 
  
X 
X 
X 
  
  
  
ADA (Central)s 
  
X 
  
  
  
X 
  
X 
  
  
Biomarkers (Central)  
  
X 
  
  
X 
  
X 
  
  
  
Pharmacogenomics Informed 
Consentk 
  
X 
  
  
  
  
  
  
  
  
Pharmacogenomics Sampling 
(Central)k 
  
  
  
  
  
  
X 
  
  
  
IWRS Subject Status Update 
X 
X 
  
  
  
  
  
  
  
X 
IWRS Weight Input (pediatric only) 
  
X 
  
  
  
  
  
  
  
X 
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Trial Period 
SCREENINGa 
RUN-IN (12 weeks)m 
  
ENROLLMENT 
  
RANDOMIZATION -q 
Visit Name 
Screening Visit 
RI  
Baseline 
RI  
Day 2 
RI  
Day 4 
RI  
Week 1 
RI  
Week 2 
RI  
Week 4 
RI  
Week 
6 
RI  
Week 
10 
RI Week 12/ 
RW Baseline 
Visit Windowb (days) 
(-28) 
NA 
NA 
+/- 1 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 3 
Visit Type 
Clinic 
Clinic 
Clinic 
TC/RN 
TC/RN 
TC/RN 
TC/RN 
Clinic 
TC 
Clinic 
IWRS Drug Dispensing 
  
X 
  
X 
  
  
  
X 
  
X 
In Clinic Study Drug 
Administrationo 
  
Xn 
  
  
  
  
  
X 
  
X 
Outpatient Study Drug 
Administrationo 
  
  
  
  
WEEKLY 
Study Drug Compliance Review 
  
X 
  
  
X 
X 
X 
X 
X 
X 
Clinical Response Evaluation 
  
  
  
  
  
  
  
  
  
Xp 
Adverse Event Reportingl 
X 
X 
  
X 
X 
X 
X 
X 
X 
X 
a  
The screening and enrollment visit can be combined. 
b  
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
c  
Full physical examination includes at minimum evaluation of vital signs, head, eye, ear, nose, and throat as well as cardiovascular, dermatological, 
musculoskeletal, respiratory, GI, genitourinary, and neurological systems. The decision to perform examination of genitourinary system should be guided 
by clinical judgement. 
d  
Abbreviated physical examination includes at minimum evaluation of vital signs, lung and heart sounds, including evaluation for pericardial rub. 
e  
ECHO is required to be obtained according to the central core lab parameters and then read locally and submitted to the central core lab for separate 
review and analysis.  
f  
Both a documented CRP > 1.0 mg/dL AND a pericarditis pain level of > 4 is required 7 days prior to and including the Run-In Baseline visit. These are 
not required to occur on the same day. 
g  
Subjects missing ≥ 4 daily pain measurements during the 7 days prior to and including the Randomization Withdrawal baseline visit will be unable to 
proceed to randomization due to lack of data required for treatment response evaluation.  
h  
Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the randomization withdrawal and LTE periods, or more 
frequently as needed, with mandated evaluations as detailed in the schedule of events. 
i  
Applicable to 24-hour post dose PK sub-study participants only.  
j  
For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout the course of the study and serum pregnancy can be 
drawn as needed; urine pregnancy is required to be performed at enrollment and 6 weeks after the last dose of study drug.  
k  
Pharmacogenomics informed consent and subsequent sampling can be performed at any time in the study however, it is preferable to have this completed 
at the beginning of the study. 
l  
Adverse event reporting begins following the subject providing informed consent. 
m  
All procedures are to be completed prior to study drug administration. 
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n  
The first dose of study drug is a loading dose. Adult subjects receive 2 SC doses 160 mg (total 320 mg); pediatric subjects (subjects ≥12 and <18 years of 
age) receive 2 SC doses of 2 x 2.2 mg/kg. 
o  
Study drug administration is once weekly with a minimum of 5 days required between doses.  
p  
Randomization and subsequent study drug dispensing to occur after confirmation of Clinical Response (see definition of Clinical Response in Section 
6.2.2). 
q  
The Randomization visit serves as both the RI Week 12 visit and the RW baseline visit.  
s 
PK and ADA samples will be collected prior to study drug administration. PK at enrollment/baseline will be taken from ADA 
 
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Table 5: 
Study Schedule of Activities – Randomized Withdrawal  
Trial Period 
RANDOMIZED WITHDRAWAL (event-driven)m 
  
 
END OF 
RANDOMIZED 
 WITHDRAWAL  
(EORW)t 
Visit Name 
RW 
Week 4 
RW 
Week 8 
RW 
Week 12 
RW 
Week 16 
RW 
Week 20 
RW 
Week 24 
RW 
Every 8 
Weeks 
RW 
Every 
8 
Weeks 
Per Announced 
End Dateu/ 
LTE-Baseline 
Visit Windowb (days) 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 7 
Visit Type 
TC/RN 
Clinic 
TC/RN 
Clinic 
TC/RN 
Clinic 
TC/RN 
Clinic 
Clinic 
Informed Consent Form 
  
  
  
  
  
  
  
  
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pericarditis Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Full Physical Examinationc 
  
  
  
  
  
X 
  
  
X 
Abbreviated Physical Examinationd 
  
  
  
  
  
  
  
  
  
Body weight and height 
  
X 
  
X 
  
X 
  
X 
X 
12-Lead ECG 
  
  
  
  
  
X 
  
  
X 
Echoe 
  
  
  
  
  
Xe 
  
  
Xe 
MRI (substudy only) 
  
  
  
  
  
X 
  
  
  
Pericardial pain (11-point NRS) 
DAILY 
EQ-5D 
  
  
  
  
  
X 
  
  
X 
SF-36 
  
  
  
  
  
X 
  
  
X 
ISI 
  
  
  
  
  
X 
  
  
X 
PGIPS 
  
X 
  
X 
  
X 
  
X 
X 
PGA-PA 
  
X 
  
X 
  
X 
  
X 
X 
Hematology, Chemistry Labs (Central) 
  
X 
  
  
  
X 
  
X 
X 
Lipid Panel (Central)h 
  
  
  
  
  
X 
  
  
X 
CRP (Local) 
  
  
  
  
  
  
  
  
  
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Trial Period 
RANDOMIZED WITHDRAWAL (event-driven)m 
  
 
END OF 
RANDOMIZED 
 WITHDRAWAL  
(EORW)t 
Visit Name 
RW 
Week 4 
RW 
Week 8 
RW 
Week 12 
RW 
Week 16 
RW 
Week 20 
RW 
Week 24 
RW 
Every 8 
Weeks 
RW 
Every 
8 
Weeks 
Per Announced 
End Dateu/ 
LTE-Baseline 
Visit Windowb (days) 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 7 
Visit Type 
TC/RN 
Clinic 
TC/RN 
Clinic 
TC/RN 
Clinic 
TC/RN 
Clinic 
Clinic 
CRP(Central  
X 
X 
X 
X 
X 
X 
X 
X 
X 
PK (Central) 
  
X 
  
  
  
X 
  
  
X 
ADA (Central) 
  
  
  
  
  
X 
  
  
X 
Biomarkers (Central)  
  
X 
  
  
  
X 
  
  
  
Urine Pregnancyj (Local or Central) 
  
  
  
  
  
  
  
  
X 
Urinalysis 
  
  
  
  
  
  
  
  
X 
IWRS Subject Status Update 
  
  
  
  
  
  
  
  
X 
IWRS Weight Input (pediatric only) 
  
X 
  
X 
  
X 
  
X 
X 
IWRS Drug Dispensing 
  
X 
  
X 
  
X 
  
X 
Xv 
In Clinic Study Drug Administrationo 
  
X 
  
X 
  
X 
  
X 
Xv 
Outpatient Study Drug Administrationo 
X 
WEEKLY 
Study Drug Compliance Review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assessment of Pericarditis Recurrence 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Event Reportingl 
X 
X 
X 
X 
X 
X 
X 
X 
X 
b  Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug 
treatment. 
c  Full physical examination includes at minimum evaluation of vital signs, head, eye, ear, nose, and throat as well as cardiovascular, 
dermatological, musculoskeletal, respiratory, GI, genitourinary, and neurological systems. The decision to perform examination of 
genitourinary system should be guided by clinical judgement. 
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d  Abbreviated physical examination includes at minimum evaluation of vital signs, lung and heart sounds, including evaluation for pericardial 
rub. 
e  ECHO is required to be obtained according to the central core lab parameters and then read locally and submitted to the central core lab for 
separate review and analysis.  
h  Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the randomization withdrawal and LTE periods, or 
more frequently as needed, with mandated evaluations as detailed in the schedule of events. 
j   For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout the course of the study and serum 
pregnancy can be drawn as needed; urine pregnancy is required to be performed at enrollment and 6 weeks after the last dose of study drug.  
l   Adverse event reporting begins following the subject providing informed consent. 
m  All procedures are to be completed prior to study drug administration. 
o  Study drug administration is once weekly with a minimum of 5 days required between doses.  
s 
PK and ADA samples will be collected prior to study drug administration. PK at enrollment/baseline will be taken from ADA.  As required, 
ADA samples will be collected at EOS, ET, and Unscheduled visits. 
t  The EORW visit serves as both the last visit of the RW period and the baseline visit of the LTE period. 
u  For all subjects, the final clinic visit of the end of RW period is to be scheduled once the End of the Randomization Withdrawal end date is 
announced by Sponsor. This includes subjects that are taking blinded study drug, open-label rilonacept, or who have prematurely discontinued 
study drug. 
 v  Study drug administration to occur only after subject provides informed consent for the open-label extension period. 
 
 
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Table 6: 
Study Schedule of Activities – Long Term Extension 
Trial Period 
LONG TERM EXTENSION (up to 24 months) 
  
Long Term Extension Treatment (up to 24 
Months)m 
Visit Name 
LTE 
Week 
12 
LTE 
Week 24 
LTE 
Every 12 
Weeks 
LTE 18-
month 
Assessment 
Visit Windowb (days) 
+/- 2 
+/- 2 
+/- 2 
18 months 
from most 
recent 
recurrence 
Visit Type 
Clinic 
Clinic 
Clinic 
Clinic 
Concomitant medications 
X 
X 
X 
X 
Pericarditis Concomitant medications 
X 
X 
X 
X 
Full Physical Examinationc 
  
X 
  
X 
12-Lead ECG 
  
X 
  
X 
Echoe 
  
X 
  
X 
MRI  
  
Xz 
  
Xz 
EQ-5D 
  
X 
  
 
SF-36 
  
X 
  
 
ISI 
  
X 
  
 
PGIPS 
X 
X 
X 
 
PGA-PA 
X 
X 
X 
 
Hematology, Chemistry Labs (Central) 
X 
X 
X 
 
Lipid Panel (Central)h 
  
X 
  
 
CRP (Central)  
X 
X 
X 
X 
PK (Central) 
  
X 
  
X 
ADA (Central)  
 
X 
  
 
Biomarkers (Central)  
  
X 
  
 
Urine Pregnancyj (Local or Central) 
  
X 
  
X 
Urinalysis 
  
X 
  
 
IWRS Subject Status Update 
  
X 
  
X 
IWRS Weight Input (pediatric only) 
X 
  
X 
X 
IWRS Drug Dispensing 
X 
X 
X 
X 
In Clinic Study Drug Administrationo 
X 
X 
X 
 
Outpatient Study Drug Administrationo 
WEEKLY 
Study Drug Compliance Review 
X 
X 
X 
X 
Assessment of Pericarditis Recurrence 
X 
X 
X 
X 
Adverse Event Reportingl 
X 
X 
X 
X 
a  The screening and enrollment visit can be combined. 
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b  Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption 
to subject evaluation and study drug treatment. 
c  Full physical examination includes at minimum evaluation of vital signs, head, eye, ear, nose, and 
throat as well as cardiovascular, dermatological, musculoskeletal, respiratory, GI, genitourinary, and 
neurological systems. The decision to perform examination of genitourinary system should be guided 
by clinical judgement. 
e  ECHO is required to be obtained according to the central core lab parameters and then read locally 
and submitted to the central core lab for separate review and analysis.  
h  Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the 
randomization withdrawal and LTE periods, or more frequently as needed, with mandated evaluations 
as detailed in the schedule of events. 
j  For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout 
the course of the study and serum pregnancy can be drawn as needed; urine pregnancy is required to 
be performed at enrollment and 6 weeks after the last dose of study drug. 
l   Adverse event reporting begins following the subject providing informed consent. 
m  All procedures are to be completed prior to study drug administration. 
o  Study drug administration is once weekly with a minimum of 5 days required between doses.  
z  The MRI to occur only if the previous MRI was done longer than 6 months ago. 
 
 
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Table 7: 
Study Schedule of Activities – Supplemental Visits  
Visit Name 
PERICARDITIS 
RECURRENCE 
ASSESSMENT 
END of 
TREATMENT 
(EOT)x 
SAFETY 
FOLLOW UP 
(SFU)y  
(6 weeks post last 
dose) 
Visit Windowb (days) 
N/A 
N/A 
+/- 2 
Visit Type 
Clinic 
Clinic 
Clinic or TC/RN 
Concomitant medications 
X 
X 
X 
Pericarditis Concomitant medications 
X 
X 
X 
Full Physical Examinationc 
  
X 
  
Abbreviated Physical Examinationd 
X 
  
  
Body weight and height 
X 
  
  
12-Lead ECG 
X 
X 
  
Echoe 
Xe 
X 
  
MRI (substudy only) 
  
Xz 
  
Pericardial pain (11-point NRS) 
X 
X 
  
EQ-5D 
X 
X 
  
SF-36 
X 
X 
  
ISI 
X 
X 
  
PGIPS 
X 
X 
  
PGA-PA 
X 
X 
  
Hematology, Chemistry Labs (Central) 
  
X 
  
Lipid Panel (Central)h 
  
X 
  
CRP (Local) 
X 
  
  
CRP(Central  
X 
X 
  
PK (Central) 
X 
X 
X 
ADA (Central) 
X 
X 
X 
Biomarkers (Central)  
X 
X 
  
Urine Pregnancyj (Local or Central) 
 
  
X 
Urinalysis 
  
X 
  
IWRS Subject Status Update 
Xs 
X 
  
IWRS Weight Input (pediatric only) 
X 
  
  
IWRS Drug Dispensing 
X 
  
  
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Visit Name 
PERICARDITIS 
RECURRENCE 
ASSESSMENT 
END of 
TREATMENT 
(EOT)x 
SAFETY 
FOLLOW UP 
(SFU)y  
(6 weeks post last 
dose) 
Visit Windowb (days) 
N/A 
N/A 
+/- 2 
Visit Type 
Clinic 
Clinic 
Clinic or TC/RN 
Study Drug Compliance Review 
X 
X 
  
Assessment of Pericarditis Recurrence 
X 
X 
X 
Adverse Event Reportingl 
X 
X 
X 
b  
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to 
subject evaluation and study drug treatment. 
h  
Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the randomization 
withdrawal and LTE periods, or more frequently as needed, with mandated evaluations as detailed in the 
schedule of events. 
j  
 
For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout the 
course of the study and serum pregnancy can be drawn as needed; urine pregnancy is required to be performed 
at enrollment and 6 weeks after the last dose of study drug.  
l  
 
Adverse event reporting begins following the subject providing informed consent. 
s  
 
PK at enrollment/baseline will be taken from ADA.   
x 
 
An EOT visit is to be conducted throughout the course of the study when a subject permanently 
discontinues study drug. 
y  
An SFU is required to be conducted within 6 weeks of the last dose of rilonacept at any time throughout the 
course of the study including the RI period, the RW period, and the LTE period. 
z  
The MRI to occur only if the previous MRI was done longer than 6 months ago. 
 
 
 
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13.2. 
Missing Data Imputation Rules 
Partial missing dates will be imputed for start/stop dates of AE and prior/concomitant 
medications, as well as start date of each pericarditis episode according to the rules below.  
 
Table 8: 
Imputation Rules for Partial Missing Dates 
Category 
Scenario 
Rule for missing dates  
General rule 
All 
If year is missing, do not impute, unless otherwise 
specified 
AE and 
prior/concomitant 
medication start 
date 
Day is missing and (month, year) 
same as the first dose date 
The day will be imputed as the same day of the first 
dose day or stop date, whichever is earlier.   
Day is missing and (month, year) 
not the same as the first dose 
date 
The day will be imputed as the first day of the month 
or stop date, whichever is earlier. 
Month and day missing, year the 
same as the first dose date  
Date will be imputed with the first dose date or stop 
date, whichever is earlier. 
Month and day missing, year 
different from the first dose date 
Impute with the first day of the year. 
AE and 
prior/concomitant 
medication end 
date 
Day is missing  
Impute with min(last day of the month, data cutoff, 
end of study date)  
Day and month are missing 
Impute with min(last day of the year, data cutoff, 
end of study date) 
Entirely missing 
Impute with min(data cutoff, end of study date) 
First pericarditis 
episode start date 
Day missing  
Use first day of the month 
Month missing  
Use January 01 
Second or later 
pericarditis episode 
start date 
Day missing  
Use max(first day of the month, stop day of previous 
episode +1) 
Month missing  
January 01 
Other 
 
Non-specific 
For missing data handling rules not covered in this 
table, they will be defined in the ADaM Define file. 
 
 
 
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13.3. 
EQ-5D-5L Scoring 
The EQ-5D-5L consists of 2 pages – the EQ-5D-5L descriptive system and the EQ Visual 
Analogue scale (EQ VAS). The descriptive system comprises of 5 dimensions (mobility, self-
care, usual activities, pain/discomfort, anxiety/depression). Each dimension now has 5 levels: no 
problems, slight problems, moderate problems, severe problems, and extreme problems. The 
respondent is asked to indicate his/her health state by ticking (or placing a cross) in the box 
against the most appropriate statement in each of the 5 dimensions. This decision results in a 1-
digit number expressing the level selected for that dimension. The digits for 5 dimensions can be 
combined in a 5-digit number describing the respondent’s health state. It should be noted that the 
numerals 1-5 have no arithmetic properties and should not be used as a cardinal score.  
EQ-5D-5L health states, defined by the EQ-5D-5L descriptive system, may be converted into a 
single index value. The index values, presented in country specific value sets, are a major feature 
of the EQ-5D instrument, facilitating the calculation of quality-adjusted life years (QALYs) that 
are used to inform economic evaluations of health care interventions. 
The EQ VAS records the respondent’s self-rated health on a 20 cm vertical, visual analogue 
scale with endpoints labelled ‘the best health you can imagine’ and ‘the worst health you can 
imagine’. This information can be used as a quantitative measure of health as judged by the 
individual respondents. The EQ VAS asks respondents to simply ‘mark an X on the scale to 
indicate how your health is TODAY’ and then to ‘write the number you marked on the scale in 
the box below’.  
The EQ-5D-5L Crosswalk Index Value Calculator can be found using the following link: 
https://euroqol.org/eq-5d-instruments/eq-5d-5l-about/valuation-standard-value-sets/crosswalk-
index-value-calculator/ 
13.4. 
Calculation of 95% CI for Incidence Rate per 100 Subject-Years of 
Exposure/Observation 
We first construct a formula to calculate the exact 100(1-α)% 2-sided CI for the number of 
events in a time interval.  When this formula is applied to the number of events in a time interval 
of 100 subject-years in a study, we obtain the desired result to construct Fisher’s exact 2-sided 
100(1-α)% confidence interval for an incidence rate of interest per 100 subject-years.  When α = 
0.05, it provides a 95% CI.   
The number of events of interest in a time interval can be modelled using a Poisson distribution 
with parameter λ, where λ is the average number of events in this time interval.  The probability 
of observing k events in this time interval is:  
P(k events in interval) = 𝑒−λ λ𝑘
𝑘! 
If k events were observed in the interval, the lower bound 𝑙 and upper bound 𝑢 of the 100(1-α)% 
CI must satisfy the following conditions for Fisher’s exact CI: 
 
 
Lower bound: ∑
𝑒−𝑙𝑙𝑥
𝑥!
= 1 −𝛼
𝑘
𝑥=0
/2 
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Upper bound: ∑
𝑒−𝑢𝑢𝑥
𝑥!
= 1 −𝛼
𝑘
𝑥=0
/2 
The parameter λ can be estimated with k.  Using the relationship between the cumulative 
distribution functions of the Poisson and chi-squared distributions, the above lower and upper 
bounds can be expressed as follows:  
 
 
 
1
2 𝑥2(
𝛼
2 ; 2𝑘) ≤𝜆≤
1
2 𝑥2(1 −
𝛼
2 ; 2𝑘+ 2),           (1)  
 
      
 
 
 
where 𝑥2(𝑎; 𝑣) is the chi-square quantile for lower tail probability with v degrees of freedom. 
The inequalities in (1) are used in the SAS macro below to construct the confidence interval for 
the number of events. The lower bound, number of events, and upper bound are divided by the 
total treatment exposure expressed as subject-year to construct the incidence rate and its CI.  
Each number is then multiplied by 100 to obtain the incidence rate per 100 subject-years. 
 
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SAS Macro for the 95% CI of incidence rate per 100 subject-years 
 
%macro nppy(x=5, n=100, alpha=0.05); 
 ***  x=5 --# of events; 
 ***  n = # of subject-years.; 
 ***  alpha=2-sided type-I error rate, alpha=0.05 for 95% CI.; 
 
data temp; 
 x=&x; 
 n=&n; 
 alpha=&alpha; 
 length CI_coverage $12.; 
 CI_coverage=compress(round(100*(1-&alpha), 0.1))||'%'; 
 r=round((x/n)*100, 0.001); 
if x=0 then Lower_bound=0; 
 else Lower_bound = round((quantile('CHISQ',&alpha/2,2*&x)/2/n)*100, 0.001); 
  Upper_bound = round((quantile('CHISQ',1-&alpha/2,2*(x+1))/2/n)*100, 0.001); 
 
label x='# of events' 
 
 
 
 
n='# subject years' 
 
 
 
 
r='# of events per 100 subject-years' 
 
 
 
 
alpha='2-sided alpha'; 
call symput('ci', compress(ci_coverage)); 
proc print data=temp label noobs; 
  title1 "&CI confidence interval for # of events per 100 subject-years"; 
 
title2 '--Exact method using the relationship between Poisson and Chi Square 
distributions'; 
run; 
%mend; 
 
*%nppy(x=14, n=400, alpha=0.05); 
 
 
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Signature Page for RIM-CLIN-000261 v1.0
Signature Page for RIM-CLIN-000261 v1.0
Approval
01-Apr-2020 21:06:50 GMT+0000
Approval
01-Apr-2020 21:07:38 GMT+0000
Approval
01-Apr-2020 22:29:41 GMT+0000
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STATISTICAL ANALYSIS PLAN 
 
 
 
PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED 
WITHDRAWAL STUDY WITH OPENLABEL EXTENSION, TO ASSESS THE 
EFFICACY AND SAFETY OF RILONACEPT TREATMENT IN SUBJECTS WITH 
RECURRENT PERICARDITIS – Rilonacept inHibition of interleukin-1 Alpha and 
beta for recurrent Pericarditis: a pivotal Symptomatology and Outcomes stuDY 
(RHAPSODY) 
 
 
 
Sponsor: 
 
Kiniksa Pharmaceuticals, Ltd. 
 
 
 
 
Study Drug: 
Rilonacept (KPL-914) 
Protocol Number: 
KPL-914-C002 
Date of Issue: 
16 JUN 2020 
Version: 
2.0 
 
 
CONFIDENTIALITY STATEMENT 
The information in this document is the property of Kiniksa Pharmaceuticals, Ltd. and contains proprietary and 
confidential information to be held in strict confidence and not disclosed to any third party, without prior written 
consent of Kiniksa Pharmaceuticals, Ltd. Persons within your organization to whom any information herein is 
disclosed is on a need-to-know basis solely to carry out the purpose of this document, and be informed that such 
information is confidential and shall not be further disclosed by them without prior written consent from Kiniksa 
Pharmaceuticals, Ltd.  Documentation, data, and all other information generated during the clinical study is 
proprietary and confidential information of Kiniksa Pharmaceuticals, Ltd. and shall not be disclosed to any third 
party, without prior written consent of Kiniksa Pharmaceuticals, Ltd. 
 
 
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History of Changes 
 
This document is prepared based on the following protocol version: 
 
Version 
Number 
Version Date 
Description  
3.0 
10 MAR 2020 
Protocol Amendment #2 (Version 3.0) 
 
 
This document has undergone the following changes: 
 
Version 
Number 
Version Date Description of Changes 
1.0 
02 APR 2020 
Original draft SAP submitted to FDA 
2.0 
16 JUN 2020 
SAP Signed off version 
 
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TABLE OF CONTENTS 
TABLE OF CONTENTS .............................................................................................. 3 
LIST OF TABLES ........................................................................................................ 5 
LIST OF ABBREVIATIONS ....................................................................................... 5 
1. 
STUDY OBJECTIVES ............................................................................. 8 
1.1. 
Study Objectives ........................................................................................ 8 
1.1.1. 
Primary Objective ...................................................................................... 8 
1.1.2. 
Secondary Objectives ................................................................................ 8 
2. 
STUDY DESIGN ...................................................................................... 8 
2.1. 
Design Overview ....................................................................................... 8 
2.2. 
Schedule of Assessments ......................................................................... 10 
2.3. 
Sample Size Calculation and Randomization .......................................... 10 
2.3.1. 
Sample Size Calculation .......................................................................... 10 
2.3.2. 
Randomization ......................................................................................... 10 
2.4. 
Timing of Analysis .................................................................................. 11 
2.5. 
Responsibilities ........................................................................................ 11 
3. 
GENERAL STATISTICAL CONSIDERATIONS ................................. 11 
3.1. 
General Methods ...................................................................................... 11 
3.2. 
Stratified Analysis ................................................................................... 12 
3.3. 
Testing Hypotheses and Multiplicity Adjustment ................................... 12 
3.4. 
Subgroups to be Analyzed ....................................................................... 12 
3.5. 
Handling of Missing Data ........................................................................ 13 
4. 
ANALYSIS SETS ................................................................................... 13 
4.1. 
Intent-to-Treat (ITT) Analysis Set ........................................................... 13 
4.2. 
Safety Analysis Set (SS) .......................................................................... 13 
4.3. 
Run-in Analysis Set (RIS) ....................................................................... 13 
4.4. 
Long Term Extension Analysis Set (LTES) ............................................ 13 
4.5. 
Per Protocol (PP) Analysis Set ................................................................ 14 
4.6. 
Pharmacokinetics Analysis Set ................................................................ 14 
4.7. 
Verification of Analysis Sets ................................................................... 14 
5. 
STATISTICAL METHODOLOGY ........................................................ 14 
5.1. 
Population Characteristics ....................................................................... 14 
5.1.1. 
Study Subjects Disposition ...................................................................... 14 
5.1.2. 
Baseline Demographic ............................................................................. 15 
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5.1.3. 
Baseline Disease Characteristics ............................................................. 15 
5.1.4. 
Medical/Surgical History ......................................................................... 17 
5.1.5. 
Prior and Concomitant Medications ........................................................ 17 
5.1.6. 
Study Drug Administration...................................................................... 18 
5.1.7. 
Protocol Deviations ................................................................................. 18 
5.2. 
Efficacy Analysis ..................................................................................... 19 
5.2.1. 
Primary Efficacy Endpoint ...................................................................... 19 
5.2.2. 
Secondary Efficacy Endpoint in the RW Period ..................................... 21 
5.2.3. 
Secondary Endpoints in RI and LTE Period ............................................ 29 
5.3. 
Safety Analysis ........................................................................................ 31 
5.3.1. 
Adverse Events ........................................................................................ 32 
5.3.2. 
Clinical Laboratory Parameters ............................................................... 33 
5.3.3. 
Vital Signs ............................................................................................... 34 
5.3.4. 
Electrocardiogram .................................................................................... 35 
5.3.5. 
Physical Examination .............................................................................. 35 
6. 
PHARMACOKINETIC ANALYSES ..................................................... 35 
7. 
PHARMACOGENOMICS SUBSTUDY ................................................ 35 
8. 
ANTI-RILONACEPT ANTIBODIES..................................................... 36 
9. 
BIOMARKER ......................................................................................... 36 
10. 
INTERIM ANALYSIS ............................................................................ 36 
11. 
CHANGES FROM ANALYSES PLANNED IN THE PROTOCOL .... 37 
12. 
IMPACT OF COVID-19 PANDEMIC ................................................... 37 
13. 
REFERENCES ........................................................................................ 38 
14. 
APPENDICES ......................................................................................... 39 
14.1. 
Schedule of Assessments ......................................................................... 39 
14.2. 
Missing Data Imputation Rules ............................................................... 50 
14.3. 
EQ-5D-5L Scoring ................................................................................... 51 
14.4. 
Calculation of 95% CI for Incidence Rate per 100 Subject-Years of 
Exposure/Observation .............................................................................. 51 
 
 
 
 
 
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LIST OF TABLES 
Table 1: 
Censoring Rules for Time to Pericarditis Recurrence in the RW Period 20 
Table 2: 
The 8 Domains in SF-36v2 ...................................................................... 26 
Table 3: 
SF-36v2 Health Survey Items Scored for the SF-6D .............................. 27 
Table 4: 
Study Schedule of Activities – Screening and Run-In Period ................. 39 
Table 5: 
Study Schedule of Activities – Randomized Withdrawal ....................... 43 
Table 6: 
Study Schedule of Activities – Long Term Extension ............................ 46 
Table 7: 
Study Schedule of Activities – Supplemental Visits ............................... 48 
Table 8: 
Imputation Rules for Partial Missing Dates ............................................. 50 
 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
ADA 
anti-drug antibodies 
AE 
adverse event 
ALT 
alanine aminotransferase 
ANCOVA 
Analysis of covariance 
AST 
aspartate aminotransferase 
CEC 
Clinical Endpoint Committee 
CMH 
Cochran–Mantel–Haenszel 
CRO 
Contract Research Organization 
CRP 
C-reactive protein 
CS 
corticosteroids 
DMC 
Data Monitoring Committee 
ECG 
electrocardiogram 
ECHO 
echocardiography; echocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EORW 
End of Randomized Withdrawal (visit) 
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Abbreviation 
Definition 
EOT 
End of Treatment (visit) 
EQ-5D-5L 
5-level EuroQoL-5D 
ESR 
erythrocyte sedimentation rate 
FDA 
US Food and Drug Administration 
GI 
gastrointestinal 
HDL 
High density lipoprotein 
HIV 
human immunodeficiency virus 
ICF 
informed consent form 
ISI 
Insomnia Severity Index 
ISR 
injection site reaction 
ITT 
intent to treat 
IV 
intravenous(ly) 
IWRS 
interactive web response system 
KM 
Kaplan-Meier 
KPL-914 
rilonacept 
LDL 
Low density lipoprotein 
LTE 
Long Term Extension Treatment Period 
MedDRA 
Medical Dictionary for Regulatory Activities 
cMRI 
cardiac magnetic resonance imaging 
MRI 
magnetic resonance imaging 
NMSC 
Non Melanoma Skin Cancer 
NSAID 
nonsteroidal anti-inflammatory drug 
NRS 
Numerical Rating Scale 
ORT 
Oral Rescue Therapy 
PGA-PA 
Physician Global Assessment of Pericarditis Activity 
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Abbreviation 
Definition 
PGIPS 
Patient Global Impression of Pericarditis Severity 
PK 
pharmacokinetic(s) 
POC 
point of care 
RE 
Role participation with emotional health problems in 
SF-6D 
RI 
Run-In (period) 
RP 
Role participation with physical health problems in 
SF-6D  
RW 
Randomized Withdrawal (period) 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis System 
SC 
subcutaneous(ly) 
SF-36 
36-Item Short Form Health Survey 
SFU 
safety follow up 
SOC 
standard of care 
TEAE 
Treatment emergent adverse event 
ULN 
upper limit of normal 
WBC 
white blood cell 
 
 
 
 
 
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1. 
STUDY OBJECTIVES 
1.1. 
Study Objectives 
1.1.1. 
Primary Objective 
The primary objective of this study is to assess the efficacy of rilonacept treatment in subjects 
with recurrent pericarditis. 
1.1.2. 
Secondary Objectives 
The secondary objective of this study is to assess the safety of rilonacept treatment in subjects 
with recurrent pericarditis. 
2. 
STUDY DESIGN 
2.1. 
Design Overview 
This study has the following periods: 
• Screening period, during which assessment of disease characteristics, baseline 
therapy, and the pretreatment workup is completed (up to 4 weeks).  
• Single-blind Run-In (RI) period (12 weeks), during which blinded rilonacept is 
administered subcutaneously (SC) once weekly in all subjects after the loading 
dose of double injections. The RI period includes the following: 
− 1-week Stabilization period, during which blinded rilonacept is administered 
in addition to standard of care (SOC) pericarditis therapy and the ongoing 
pericarditis episode is treated. 
− 9-week Weaning period, during which subjects are weaned off background 
SOC pericarditis therapy, as applicable, while treatment with blinded 
rilonacept continues. 
− 2-week Monotherapy period during which subjects who have successfully 
weaned off background SOC pericarditis therapy will continue to receive 
blinded rilonacept.   
 
In the single blind RI period (subjects are blinded regarding the time of transition from the 
single- blind to the double- blind- period), adult subjects ≥18 years old will receive rilonacept 
as an initial loading dose of 320 mg (2 SC injections of 160 mg each) at the RI baseline visit 
(2 × 2 mL), followed by a 160 mg (2 ml) SC dose once weekly throughout the RI period. 
Pediatric subjects ((≥12 and <18 years old) will receive an initial loading dose of rilonacept 
4.4 mg/kg (2 SC injections of 2.2 mg/kg each) at the RI baseline visit (maximum 2 × 2 mL), 
and then 2.2 mg/kg (maximum 2 mL) SC once weekly throughout RI period. 
Subjects who achieve clinical response at RI Week 12 defined as stopping background 
pericarditis therapy no later than Week 10 and weekly average of daily pericarditis pain score 
≤2.0 on the 11-point Numerical Rating Scale (NRS) within the 7 days prior to and including 
the day of randomization on RI Week 12/Randomization Withdrawal (RW) baseline and a 
C-reactive protein (CRP) level ≤0.5 mg/dL at the RI Week 12/RW baseline visit, will proceed 
into the double-blind placebo-controlled RW period.  
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Subjects who do not achieve clinical response at RI Week 12/RW baseline on rilonacept 
monotherapy will be discontinued from study drug, transitioned to SOC pericarditis therapy 
at the Investigator’s discretion and followed through the end of the RW period. 
Additionally, after the randomized withdrawal period has been closed when at least 
22 confirmed recurrent pericarditis events have been accrued, subjects who have not yet 
completed the full 12 weeks of RI period at that time will be allowed to continue tapering of 
concomitant meds in the RI period; those subjects who achieved clinical response by Week 
12 will be given the option to receive open-label rilonacept in the Long-term Extension 
Treatment period (LTE) without having to proceed through the RW period.   
• Double-blind placebo-controlled RW period (pericarditis recurrence event-
driven duration), during which subjects who were able to stop background SOC 
pericarditis therapy and who achieve clinical response at RI Week 12/RW 
baseline are randomized in a double-blind manner at a 1:1 ratio to the following: 
− Rilonacept 160 mg (2.2 mg/kg in pediatric subjects) SC injections once 
weekly 
− Matching placebo SC injections once weekly 
Pericarditis Recurrence in the RW Period 
Pericarditis recurrence is defined as the recurrence of typical pericarditis pain associated with 
supportive objective evidence of pericarditis. Upon pericarditis recurrence, subjects who 
report at least 1 day with pericarditis pain measurement ≥4 on the 11point NRS and have 
1 CRP value ≥1 mg/dL (either on the same day or separated by no more than 7 days) will 
receive bailout rilonacept (2 open-label injections of 160 mg rilonacept [or 4.4 mg/kg for 
pediatric subjects] followed by once weekly open-label rilonacept SC injections of 160 mg 
[or 2.2 mg/kg for pediatric subjects]) irrespective of randomized treatment assignment and as 
soon as at least 5 days have passed since the last study drug injection. Sequential oral rescue 
therapy (ORT), i.e., analgesics first, then NSAIDs, and then colchicine, can be added if 
needed at the discretion of the Investigator, as outlined in the protocol and Pharmacy Manual. 
Subjects with pericarditis recurrence and who do not meet the protocol criteria for bailout 
rilonacept will continue blinded study drug until the protocol criteria for bailout rilonacept 
are met or through the end of the RW period. For those subjects, sequential ORT can be 
added to blinded study drug at the discretion of the Investigator, as outlined in the protocol 
and Pharmacy Manual. 
All suspected pericarditis recurrence events in the RW period will be formally adjudicated by 
the Clinical Endpoint Committee (CEC), and only events that are confirmed by the CEC as 
pericarditis recurrences will be used in the Primary Endpoint analysis. 
• 
Long-term Extension Treatment period (LTE) (variable, up to 24 months), 
during which all subjects in the RW period (including subjects transitioned to open-
label rilonacept upon pericarditis recurrence) and subjects who are in the Run-In 
period after closure of the RW period, will have an option to receive up to 
24 months of open-label rilonacept 160 mg (or 2.2 mg/kg for pediatric subjects) SC 
injections once weekly based on their clinical status and at the discretion of the 
Investigator, after signing LTE informed consent.  
 
Subjects will be reviewed at 18 months after their most recent recurrence, (i.e., the 
qualifying episode for their original study enrollment prior to enrolling in the RI 
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period or a recurrence in RW which was treated with bailout rilonacept, whichever 
is the later). During this month’s visit, the Investigator and subject will decide 
whether to continue treatment with open-label rilonacept, to continue in the study 
off-treatment for observation and rilonacept bailout upon subsequent recurrence, or 
discontinuation from the LTE. This review may be supplemented by:  
− cMRI and/or echocardiogram and/or additional diagnostic testing as 
determined by the Investigator.    
− subjects may be unblinded at that time (if available) at the request of the 
Investigator per procedures outlined in the Unblinding Plan to assist in clinical 
decision-making.   
Safety data will be reviewed throughout the LTE by the Data Monitoring Committee.  
2.2. 
Schedule of Assessments 
The schedule of assessments is in Section 13.1. 
2.3. 
Sample Size Calculation and Randomization 
2.3.1. 
Sample Size Calculation 
Sample size calculation is based on the primary endpoint, time to pericarditis recurrence 
defined as the time from randomization to the date of the first pericarditis recurrence for each 
subject.  Time to pericarditis recurrence is assumed to follow an exponential distribution. An 
event of interest is defined as a subject’s first adjudicated recurrence of pericarditis. The 
following assumptions are used in the sample size calculation using EAST 6.4.1: 
• 1-sided significance level: 2.5% 
• Power: 90% 
• Median time to event (in weeks) in placebo: 8 
• Hazard ratio (rilonacept/placebo): 0.244 
• Percentage of subjects in the RI period that will not reach RW: 10%. 
Given these assumptions, a total of 22 adjudicated pericarditis recurrence events is required 
to achieve the power. About 25 subjects per arm (a total of 50 subjects) or more will be 
randomized. Considering 10% of subjects in the RI period that will not reach the RW period, 
approximately 56 subjects will be enrolled in this study.  
Subject enrollment and the pericarditis recurrence event accrual will be closely monitored 
during the study. The monitoring activities will be done in a blinded fashion during the RW 
period. If the number of subjects randomized is less than 50 and/or the time anticipated for 
the number of events required for the analysis of primary efficacy endpoint significantly 
exceeds the projected timeline, additional subjects may be enrolled and/or randomized at 
Kiniksa Pharmaceutical’s discretion. However, at this time it is anticipated that no more than 
100 subjects will be enrolled into this study.  
2.3.2. 
Randomization 
Subjects who achieve clinical response at RI Week 12 (Section 2.1) will proceed into the 
double-blind placebo controlled RW period. An interactive web response system (IWRS) will 
be used to administer the randomization schedule. CRO Biostatistics will generate the 
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randomization schedule using SAS® software Version 9.4 or later (SAS Institute Inc, Cary, 
North Carolina) for the IWRS, which will link sequential subject randomization numbers to 
treatment codes. The randomization schedule will be stratified by 2 factors: 
• Oral CS use at baseline (RI baseline, i.e., beginning of RI period): yes or no 
• Diagnosis of recurrent idiopathic pericarditis (RI baseline): yes or no 
2.4. 
Timing of Analysis 
The data cutoff for the primary analysis will be the end of RW period.  When at least 22 
adjudicated pericarditis recurrence events have occurred, end of RW period will be 
announced.  The sites will have their subjects return to the site for the end-of-RW assessment 
(EORW).  Data cutoff will occur after all subjects have completed this assessment.  All data 
for this cutoff will be used in the primary analysis for efficacy and safety.  
After the RW period, there will be a Long-term Extension Treatment period.  An analysis 
will also be conducted after the end of the study. Since the data cutoff for the primary 
analysis will be done by the end of RW period, summary for LTE period will not be included 
in the primary analysis.   
No interim analysis for claiming efficacy is planned. Interim safety review will be conducted 
by a Data Monitoring Committee (DMC).  The analysis will be performed by a designated 
CRO.  Details are in DMC charter and DMC Statistical Analysis Plan (SAP). 
2.5. 
Responsibilities 
The statistical analysis for the study will be performed by Kiniksa Biostatistics or its 
designated CROs. 
3. 
GENERAL STATISTICAL CONSIDERATIONS 
3.1. 
General Methods  
Statistical analysis will be performed using SAS® software Version 9.4 or later. Continuous 
variables will be summarized using the mean, the standard deviation, median, minimum 
value, and maximum value. Time-to-event variables will be summarized using percent 
censored, event rate, and 25th, 50th, and 75th percentiles with 95% CI, if estimable. 
Categorical variables will be summarized using frequency counts and percentages. Data will 
be listed in data listings. 
At RI, RW, and LTE periods, baseline will be the last value before the first dose of study 
drug within each individual period unless otherwise specified. For change-over-time 
endpoints in the RW period, by-visit analysis will be performed at each scheduled visit for at 
least 24 weeks. 
When weekly average of NRS is used, it will be calculated based on every 7 days starting on 
the day after the first injection in each period. If there are missing values during the 7- day 
period, the average will be calculated based on the non-missing values. If 50% or more 
values (≥4 days) are missing, the average value will be set to missing.  
By-visit analyses will be based on nominal visits and observed data, with unscheduled visits 
excluded. 
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3.2. 
Stratified Analysis 
There are two stratification variables for randomization: oral CS use at baseline (yes or no), 
and diagnosis of recurrent idiopathic pericarditis at RI baseline (yes or no).  When an analysis 
is to be stratified by these variables and a stratum has ≤5 events of interest in a log-rank test 
or the same response in all subjects in a CMH test, the strata for diagnosis of recurrent 
idiopathic pericarditis will be pooled. If the same situation still exists, the analysis will be 
done without stratification. 
3.3. 
Testing Hypotheses and Multiplicity Adjustment 
All statistical tests for the treatment comparison of efficacy endpoints in the RW period will 
be based on a 1-sided α=0.025. For each endpoint, the null hypothesis is that the effects of 
rilonacept and placebo are the same. The alternative hypothesis is that rilonacept is better 
than the placebo. 
In order to control the overall 1-sided type I error rate at the 0.025 level, a gatekeeping 
procedure in combination with Hochberg’s procedure will be applied to testing the primary 
and major secondary endpoints. If the 1-sided p-value for testing the primary endpoint is 
≤0.025, a significant treatment effect on the primary endpoint will be claimed. 
Section 5.2.2.1 provides the order of major secondary endpoints. If the primary endpoint is 
significant, the first major secondary endpoint, i.e., proportion of subjects who maintained 
clinical response at Week 16 of RW period will be tested at 1-sided α=0.025. A significant 
treatment effect on this major secondary endpoint will be claimed if the 1-sided p-value is 
≤0.025. If the treatment effect is not significant on the primary endpoint, significance on this 
major secondary endpoint cannot be claimed regardless of the result. 
If both primary and first major secondary endpoints are significant following the above 
procedure, the second and third major secondary endpoints defined in Section 5.2.2.1 will be 
tested with Hochberg’s procedure at overall 1-sided α=0.025. If both 1-sided unadjusted 
p-values are ≤0.025, claim significance of rilonacept for both endpoints. If the larger 1-sided 
p-value is >0.025, compare the smaller 1-sided p-value with 0.0125. If the smaller 1-sided 
p-value is ≤0.0125, claim significance of rilonacept on this endpoint. 
3.4. 
Subgroups to be Analyzed 
Subgroup analyses for the primary efficacy endpoint will be performed by the following 
variables for the RW period: 
• Oral CS use at baseline (RI baseline, i.e., beginning of RI period): yes or no 
• Diagnosis of recurrent idiopathic pericarditis (RI baseline): yes or no 
• Age group: 12 - <18, 18 - <65, and 65 – (maximum age in ITT analysis set) 
[Analysis for the pediatric group (12- <18) may not be performed if the sample 
size is too small.] 
• Gender: males vs. females 
• Race: Caucasian vs. non-Caucasian 
• Region: USA vs. non-USA 
• Number of pericarditis episodes at enrollment (including index and qualifying 
episodes): <5 vs. ≥5 
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• ADA status: ADA positive at any assessment, ADA positive with neutralizing 
antibody at any assessment, and ADA negative at every assessment. 
P-values and summary statistics will be generated following Section 5.2, with the 
understanding that the sample size is likely too small to have an adequate power.  The forest 
plot with 95% CI will be provided for the primary efficacy endpoint. 
3.5. 
Handling of Missing Data 
To the extent possible, attempts will be made to minimize the amount of missing data through 
measures planned in the study. Unless otherwise specified, missing data will not be imputed 
and only the observed data will be used in the analyses. 
Additional rules for missing data imputation are provided in Section 13.2.  
4. 
ANALYSIS SETS 
4.1. 
Intent-to-Treat (ITT) Analysis Set  
All subjects who are randomized in the RW period will be included in the Intent-to-Treat 
(ITT) analysis set. The primary analysis for efficacy endpoints in the RW period will be 
based on the ITT analysis set unless otherwise specified. Treatment comparisons for all 
analyses will be based on each subject’s treatment assignment from randomization. 
The following analysis sets are defined for the analysis of secondary endpoints: 
• ITT Week 24 analysis set: All subjects randomized at least 24 weeks before data 
cutoff will be included. This analysis set will be used for secondary efficacy 
endpoints measured at week 24 in the RW period. 
• ITT Week 16 analysis set: All subjects randomized at least 16 weeks before data 
cutoff will be included. This analysis set will be used for secondary efficacy 
endpoints measured at week 16 in the RW period. 
• ITT Week 8 analysis set: All subjects randomized at least 8 weeks before data 
cutoff will be included. This analysis set will be used for secondary efficacy 
endpoints measured at week 8 in the RW period. 
4.2. 
Safety Analysis Set (SS) 
All subjects who take at least 1 dose of study drug in the RI period will be included in the 
Safety Analysis set (SS). Safety analyses will be based on the actual treatment a subject 
received. 
4.3. 
Run-in Analysis Set (RIS) 
All subjects who received at least 1 dose of study drug in the RI period will be included in the 
RI analysis set (RIS). 
4.4. 
Long Term Extension Analysis Set (LTES) 
All subjects who received at least 1 dose of study drug in the LTE will be included in the 
Long-term Extension Analysis set (LTES). 
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4.5. 
Per Protocol (PP) Analysis Set  
The Per Protocol Analysis set (PP) is a subset of the ITT analysis set with the exclusion of 
subjects with important protocol violations or violations that may potentially bias statistical 
analyses or the ethical conduct of the study. The criteria of these violations will be 
determined prior to unblinding. This analysis set may be used for sensitivity analyses for 
efficacy endpoints in the RW period. 
4.6. 
Pharmacokinetics Analysis Set  
The Pharmacokinetic (PK) Analysis set includes subjects who receive at least 1 dose of study 
drug and have at least 1 post-baseline PK sample. The PK analysis set will be used for all PK 
analyses. 
4.7. 
Verification of Analysis Sets 
A blinded review to verify all defined analysis sets excluding LTES will be conducted before 
database lock of primary analysis.  The results will be documented.  The document will list 
subjects excluded from each analysis set with reason(s). 
5. 
STATISTICAL METHODOLOGY 
5.1. 
Population Characteristics 
5.1.1. 
Study Subjects Disposition 
Subject disposition will be summarized as follows. 
• RI period  
− Screened Subjects (Signed Informed Consent) 
▪ Enrolled  
▪ Subjects treated in RI period 
▪ Subjects completed RI treatment 
▪ Subjects with early treatment discontinuation and reasons for treatment 
termination 
▪ Subjects with treatment ongoing at end of RI period 
• RW Period  
− Number of subjects randomized, by arm  
▪ Subjects treated in RW period 
▪ Subjects who completed RW period 
▪ Subjects who discontinued study drug before end of RW period with 
reason of discontinuation 
▪ Subjects with treatment ongoing at end of RW period 
• Number of subjects who consented to the LTE period  
• LTE  
− Subjects who completed the Treatment Period 
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− Subjects who discontinued study drug with reasons for treatment 
discontinuation 
• Study disposition   
− Subjects who completed 
− Subjects who terminated early and reasons for early termination 
− Subjects with study ongoing  at data cutoff 
5.1.2. 
Baseline Demographic  
Frequency counts (n) and percentages (%) will be presented for sex, race, ethnicity, and age 
group (i.e., 12-17 years, 18-64 years, and 65 years to the maximum age in the ITT analysis 
set). Descriptive statistics such as number of subjects (n), mean, standard deviation, median, 
minimum and maximum will be presented for age (years), weight (kg), Height (cm), and 
body mass index (BMI) kg/m2. 
5.1.3. 
Baseline Disease Characteristics   
Baseline disease characteristics include the following: 
• Oral corticosteroid use at RI Baseline (yes/no)  
• Diagnosis of recurrent idiopathic pericarditis at RI (yes/no) 
• Type of recurrent Pericarditis 
− Idiopathic 
− Pericardiotomy syndrome 
− Dressler’s syndrome 
− Still’s disease 
− Other  
• Duration of disease from first episode to the date of inform consent 
• Total number of pericarditis episodes, total number of episodes in the past year 
until first injection in the RI period, and annualized number of episodes per year,   
• Time since beginning of qualifying episode in days 
• Baseline central CRP value and weekly pain NRS score 
• Baseline pericardial rub, effusion, tamponade, electrocardiogram (ECG) findings 
(widespread ST-elevation and PR-Depression), ECG interpretation 
• Pericarditis treatment at baseline 
− Analgesics 
− Non-opioid analgesics 
− Opioid analgesics 
− Nonsteroidal anti-inflammatory drug (NSAIDs) 
− Aspirin 
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− Other NSAIDs 
− Colchicine  
− Corticosteroids 
− Oral corticosteroids 
− IM/IV corticosteroids 
− Other 
 
Disease characteristics for the qualifying episode, including the following: 
• Number and proportion of subjects with presence of pericarditis pain, pericardial 
rub, new widespread ST-segment elevation or PR-segment depression on ECG, 
new or worsening in pericardial effusion, and pericardial inflammation on 
magnetic resonance imaging (MRI). 
• Values of pain level, CRP (mg/dL), fever (Celsius), white blood cell (WBC; 
103/uL), and erythrocyte sedimentation rate (ESR) (mm/hr).  
• Treatment for the qualifying episode 
− Analgesics 
− Non-opioid analgesics 
− Opioid analgesics 
− Nonsteroidal anti-inflammatory drug (NSAIDs) 
− Aspirin 
− Other NSAIDs 
− Colchicine  
− Corticosteroids 
− Oral corticosteroids 
− IM/IV corticosteroids 
− Other 
The categorical (discrete) variables will be summarized using counts and percentages. The 
continuous variables will be summarized using n, mean, median, standard deviation, and 
range (minimum, maximum). Summaries will be presented for the RI, RW, and LTE periods. 
Baseline disease characteristics will also be summarized for subjects who are on 
corticosteroid at RI baseline. In addition to those specified above, the following baseline data 
will be summarized: 
• Duration (in weeks) of using oral corticosteroid prior to enrollment 
• Average dose (mg/day) of oral corticosteroid prior to enrollment 
• Cumulative dose (mg) of oral corticosteroid prior to enrollment 
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5.1.4. 
Medical/Surgical History 
Medical/Surgical history will be summarized by Medical Dictionary for Regulatory Activities 
(MedDRA; v21.1) system organ class and preferred term. One subject will be counted only 
once within one preferred term and one system organ class. The summary will be sorted in 
the alphabetic order of system organ classes and preferred terms.  
Medical history details as collected on the electronic case report form (eCRF) such as body 
system, description, the date of onset, stop date and the current status of the condition will be 
presented in a by-subject data listing. 
5.1.5. 
Prior and Concomitant Medications 
Prior medications are defined as those taken before the date of the first study drug 
administration, i.e. started before the start of the study drug.  
Concomitant medications are defined as any non-study medication taken during the treatment 
period which is from the date of first dose to the date of last dose plus 6 weeks.  
Additionally, the medications will be considered concomitant if the start date of the 
medication is missing.  
A medication that started prior to the first dose of the study drug and continued after that date 
will be considered as both prior and concomitant. 
Prior and concomitant medications will be coded using World Health Organization (WHO) 
Drug (version March 2018). Medications will be summarized by ATC level 2 code and 
preferred term.  Summary will be done by periods (i.e., RI, RW, and LTE) and by treatment 
(KPL-914 vs placebo) for RW period. One subject will be counted once within one preferred 
term and one ATC class.  The medication information will be presented in a by-subject listing 
with ATC class (level 2) and WHO Drug Dictionary preferred term, start and stop date, 
dosage, route, frequency and indication. 
Concomitant pericarditis treatment will be summarized by period and by treatment for RW 
period using the following categories:  
− Analgesics 
− Non-opioid analgesics 
− Opioid analgesics 
− Nonsteroidal anti-inflammatory drug (NSAIDs) 
− Aspirin 
− Other NSAIDs 
− Colchicine  
− Corticosteroids 
− Oral corticosteroids 
− IM/IV corticosteroids 
• Other 
In addition, concomitant pericarditis treatment received during the RW treatment period will 
also be summarized based on the status of receiving bailout treatment (i.e. concomitant 
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medication received before start of bailout treatment vs after start bailout treatment) for each 
treatment group in the RW period.   
For RI period, use of concomitant pericarditis treatment (i.e., background treatment) will be 
summarized over time. 
5.1.6. 
Study Drug Administration 
The study medication administration details including the administration date and time, dose, 
site of injection and comments will be presented in a by-subject listing.  
The following parameters related to study drug administration will be summarized for each of 
the treatment periods: RI, RW, LTE, and Study Overall. 
• Treatment duration in weeks: 
− For RI period, it is defined as [minimum of (date of last study drug +6, date of 
RI week 12 visit – 1, date of data cutoff) - date of first study drug + 1)/7].  
− For RW period it is defined as [minimum of (date of last study drug +6, date 
of end of RW visit) - date of first study drug + 1)/7]. 
− For LTE and study overall, it is defined as [minimum of (date of last study 
drug +6, end of study date, date of data cutoff) - date of first study drug + 1)/7. 
Number of administrations in each period regardless of full amount or partial amount of 
syringe injected. The loading dose includes two injections and will be counted as one 
administration.  
Compliance (%) in each period, calculated as (number of administrations) / (protocol planned 
number of administrations) ×100%.  The loading dose includes 2 injections and will be 
counted as one administration. 
Total rilonacept dose administered in each period, defined as the sum of all doses (mg) 
received in the corresponding period. The actual volume administered will be used to 
calculate the total dose. For subjects receiving weight-adjusted dose (e.g., 2.2 mg/kg) their 
weight collected at scheduled visits will be used to calculate the amount of the study drug 
received. 
Percentage of self-administrations by the subject, defined as [Number of self-
administrations] / [Total number of administrations received] × 100%.  The loading dose will 
be included in the denominator as one administration. If one of 2 injections in the loading 
dose is self-administered, it will be counted in the numerator.  
5.1.7. 
Protocol Deviations 
Protocol deviations will be derived programmatically as well as reported by sites.  
A blinded review before database lock will be conducted to determine important protocol 
deviations. Protocol deviations are considered important if based on Sponsor assessment they 
can impact study integrity or interpretability of study results.  
Important protocol deviations will also be evaluated if they have impact on efficacy data. 
Important protocol deviations with potential impact on efficacy will be used to exclude 
subjects from PP analysis set. 
All protocol deviations will be reviewed and categorized before database lock. All important 
protocol deviations will be summarized by deviation category (including Inclusion Criteria, 
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Exclusion Criteria, ICF, Concomitant Medication, and other if applicable).  The protocol 
deviation data will also be presented as a by-subject data listing.  
5.2. 
Efficacy Analysis 
5.2.1. 
Primary Efficacy Endpoint 
5.2.1.1. 
Definition 
The primary efficacy endpoint is time to pericarditis recurrence, defined as the time from 
randomization to the date of the first pericarditis recurrence for each subject. Only 
CEC-confirmed pericarditis recurrence will be considered as an event for the primary 
analysis.   
Time to pericarditis recurrence is calculated as: Data of Event/Censor – Date of 
randomization +1. 
Pericarditis recurrence is defined as the recurrence of typical pericarditis pain associated with 
supportive objective evidence of pericarditis. The assessments to be conducted by the 
investigator is described in protocol Section 6.1.4.  At any time during the RW period, 
subjects who experience a suspected recurrence of pericarditis symptoms will be requested to 
report to the study site/clinic for a scheduled or unscheduled visit, during which clinical 
assessments will be performed to gather all the necessary diagnostic data to confirm or rule 
out the presence of pericarditis recurrence.  
Pericarditis recurrence will also be evaluated by the investigators at the following time 
points: 
• Routine assessment (every 4 weeks until week 24 in RW, then every 8 weeks)  
• End of RW period 
• End of treatment 
• Post-treatment safety follow-up 
• LTE assessment (every 12 weeks up to 24 months and 18-month visit) 
Upon suspected pericarditis recurrence, the event is required to be captured in the electronic 
data capture (EDC) system within 24 hours of learning of the event, and a pericarditis 
recurrence event adjudication package must be prepared for adjudication by CEC. Details on 
endpoint package requirements will be described in the CEC charter. The CEC confirmed 
pericarditis recurrences will be used for the analysis of primary efficacy endpoint. 
The censoring rules in Table 1 will be used in the analysis of the primary efficacy endpoint, 
in which, the event/censor reason will be provided in a data listing. 
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Table 1: 
Censoring Rules for Time to Pericarditis Recurrence in the RW Period 
 
Scenario* 
Event/ 
Censor 
Event/Censor 
Reason 
Date of Event/ 
Censor 
1 
Pericarditis recurrence occurred before 
or without receiving bailout rilonacept, 
including events after termination of 
study drug  
Event 
Recurrence 
Date of 
pericarditis 
recurrence 
2 
Pericarditis recurrence occurred after 
receiving ORT* or corticosteroid  
Event 
Recurrence after 
receiving 
ORT/corticosteroi
d 
Date of 
pericarditis 
recurrence 
3 
Receiving bailout rilonacept before 
pericarditis recurrence  
Event 
Recurrence after 
receiving bailout  
Date of 
pericarditis 
recurrence 
4 
No pericarditis recurrence during RW 
period with or without receiving 
ORT/corticosteroid 
Censored 
No pericarditis 
recurrence  
Date of last 
assessment for 
pericarditis 
recurrence on or 
before data 
cutoff. 
*Excluding subjects receiving ORT/corticosteroid while waiting for at least 5 days since previous administration of study 
medication before receiving bailout rilonacept or within 5 days prior to recurrence visit. 
5.2.1.2. 
Analysis Methods for the Primary Endpoint 
The log rank test will be the primary method for the analysis of time to recurrence based on 
CEC confirmed events, stratified by the stratification variables for randomization. Analysis 
based on the ITT analysis set will be used as the primary analysis. Analysis based on the PP 
analysis set will be considered as a sensitivity analysis.   
Time to recurrence will be summarized with the 25th, 50th (median), and 75th percentiles using 
the Kaplan-Meier (KM) method. The 95% confidence interval (CI) for the percentiles will be 
calculated using a log-log transformation.  The percentage of subjects with pericarditis 
recurrence and its 95% CI will be calculated at weeks 8, 16, 24, and 36 since randomization, 
using Greenwood’s formula with a log-log transformation. 
The hazard ratio for KPL-914 vs. placebo and the corresponding Wald 95% CI will be 
calculated based on a Cox proportional-hazards model with treatment as covariate, stratified 
by randomization strata. 
A sensitivity analysis will be performed based on the Investigator’s judgement of pericarditis 
recurrence. A 2×2 table for the concordance/discordance between Investigator’s judgement 
and CEC’s adjudication will be generated. 
Upon pericarditis recurrence as determined by the investigator, subjects who report at least 1 
day with pericarditis pain measurement ≥4 on the 11-point NRS and have 1 CRP value 
≥1 mg/dL (either on the same day or separated by no more than 7 days) will receive bailout 
rilonacept (2 open-label injections of 160 mg rilonacept [or 4.4 mg/kg for pediatric subjects]) 
irrespective of randomized treatment assignment and as soon as at least 5 days have passed 
since the last study drug injection. The subjects transitioning to bailout rilonacept will remain 
blinded to their randomized treatment assignment.  
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For subjects who have pericarditis recurrence, the frequency table and listing will be 
generated for the following treatment prescribed by the Investigator: 
• Bailout rilonacept 
• Analgesics 
• NSAIDS 
• Colchicine 
• Other. 
The following criteria for pericarditis recurrence were provided to CEC to determine 
pericarditis recurrence: 
1. Re-appearance or worsening of typical pericarditis pain (with at least one pain NRS 
recording ≥4) AND elevated CRP (≥1.0 mg/dL) either on the same day or separated 
by no more than 7 days  
 
OR 
2. Re-appearance or worsening of typical pericarditis pain (with at least one pain NRS 
recording ≥4), AND abnormal CRP (>0.5 mg/dL) either on the same day or separated 
by no more than 7 days AND at least 1 supportive evidence of pericarditis as below 
 
OR 
3. Re-appearance or worsening of typical pericarditis pain (but no NRS scores being 
≥4), AND elevated CRP (≥1.0 mg/dL) not attributable to other causes AND at least 1 
supportive manifestation of pericarditis as below. 
Supportive Evidence (Pericarditis manifestations): 
• increased WBC count >upper limit of normal (ULN)  
• fever >38C 
• presence of pericardial rub 
• ECG changes consistent with pericarditis, i.e., findings of new widespread 
ST-segment elevation and/ or PR-segment depression 
• new or worsened pericardial effusion on echocardiography (ECHO) 
• new or worsening pericardial inflammation on MRI or other imaging modality. 
The above information will be summarized and/or listed. 
5.2.2. 
Secondary Efficacy Endpoint in the RW Period 
This Section defines secondary efficacy endpoints for the RW period. Endpoints for the RI 
and LTE periods are defined in Section 5.2.3. 
5.2.2.1. 
Definition of Major Secondary Efficacy Endpoints in the RW Period 
This section defines 3 major secondary endpoints. These endpoints will be analyzed with the 
ITT Week 16 analysis set.  Handling of missing data due to end of RW period will be 
discussed in Section 5.2.2.2. 
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1. Proportion of subjects who maintained clinical response at Week 16 of the RW 
period. clinical response is defined as a weekly average of daily pericarditis pain on 
the 11-point NRS ≤2.0 and CRP level ≤0.5 mg/dL, and on monotherapy of 
randomized study drug at Week 16.  
 
Subjects who complete 16-week of double-blinded treatment and meet the clinical 
response criteria at Week 16 will be considered as responders. Subjects who had 
recurrence, discontinued double-blinded treatment, lost to follow-up, and used bailout 
rilonacept or rescue medications (ORT or corticosteroid) before Week 16 will be 
considered as non-responders. 
 
If either weekly average of NRS or CRP is missing at week-16 assessment, the 
subject will be considered as a non-responder.  
2. Percentage of days with pain NRS ≤2 in the first 16 weeks of the RW period. No or 
minimal pain is defined as non-missing NRS ≤2. 
 
The denominator will be 112 (=16x7) for every subject.  NRS assessments after 
treatment termination will be included.  NRS assessments while on rescue 
medications for pericarditis will considered not meeting this criterion.  Receiving each 
administration of bailout rilonacept will disqualify for meeting NRS ≤2 for 7 days.  
Missing values will be counted as 0 day meeting the criterion.  
3. Proportion of subjects with absent or minimal pericarditis symptoms (based on the 
7-point PGIPS) at Week 16 of the RW period. 
 
Subjects who do not have the assessment due to early termination or other reasons 
will be considered as not meeting the criterion.  Subjects who took rescue medications 
at the Week 16 assessment or used bailout rilonacept on or before Week 16 will also 
be considered not meeting the criteria. 
5.2.2.2. 
Analysis Methods for Major Secondary Efficacy Endpoints in the RW Period 
These endpoints will be analyzed with the ITT Week 16 analysis set. 
1. For the proportion of subjects who maintained Clinical Response at Week 16 of the 
RW period, the response rate and Clopper–Pearson 95% CI will be obtained for each 
arm. Difference of response rate (KPL-914 – Placebo) and 95% CI based on normal 
approximation will be provided. The Cochran–Mantel–Haenszel (CMH) test will be 
used to test the treatment effect, stratified by the stratification variables for 
randomization.  
2. For the percentage of days with pain NRS ≤2 in the first 16 weeks post 
randomization, an analysis of covariance will be used for treatment comparison.  In 
addition to treatment arm, the following covariates will be included in this analysis: 
the stratification variables for randomization, and RI baseline NRS in 2 categories: 
NRS ≤2 versus NRS >2. LS mean difference and the 95% CI will be provided. 
3. For proportion of subjects with absent or minimal pericarditis symptoms (based on the 
7-point PGIPS) at Week 16 of the RW period, the response rate and Clopper–Pearson 
95% CI will be obtained for each arm. Difference of response rate (KPL-914 – 
Placebo) and 95% CI based on normal approximation will be provided. The Cochran–
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Mantel–Haenszel (CMH) test will be used to test the treatment effect, stratified by the 
stratification variables for randomization.  
5.2.2.3. 
Other Secondary Efficacy Endpoints in the RW Period and Statistical 
Method 
All time-to-event endpoints start from the day of randomization. The same censoring rules for 
the primary endpoint will be applied. Missing values will not be imputed unless otherwise 
specified. Analysis of secondary endpoints will be based on ITT analysis unless otherwise 
specified. 
1. Proportion of subjects who maintained Clinical Response at Week 24 of the RW 
period based on ITT Week 24 analysis set 
 
The same rules and method for the first major secondary endpoint will be applied, 
except that 16 weeks is replaced with 24 weeks.  
2. Proportion of subjects who maintained Clinical Response at Week 8 of the RW period 
based on based on ITT Week 8 analysis set 
 
The same rules and method for the first major secondary endpoint will be applied, 
except that 16 weeks is replaced with 8 weeks. 
3. Percentage of days with minimal or no pain in the first 24 weeks post randomization 
based on ITT Week 24 analysis set 
 
The same rules and method for the second major secondary endpoint will be applied, 
except that 16 weeks is replaced with 24 weeks. 
4. Percentage of days with minimal or no pain in the first 8 weeks post randomization 
based on ITT Week 8 analysis set 
 
The same rules and method for the second major secondary endpoint will be applied, 
except that 16 weeks is replaced with 8 weeks. 
5. Proportion of subjects with absent or minimal pericarditis symptoms (based on the 
7‑point PGIPS) at Week 24 of the RW period based on subjects who were randomized 
at least 24 weeks before data cutoff 
 
The same rules and method for the third major secondary endpoint will be applied, 
except that 16 weeks is replaced with 24 weeks. 
6. Proportion of subjects with absent or minimal pericarditis symptoms (based on the 
7‑point PGIPS) at Week 8 of the RW period based on subjects who were randomized 
at least 8 weeks before data cutoff 
 
The same rules and method for the third major secondary endpoint will be applied, 
except that 16 weeks is replaced with 8 weeks. 
7. Proportion of subjects without pericarditis recurrence in the first 24 weeks of the RW 
period 
 
The proportion of subjects without pericarditis recurrence in the first 24 weeks of the 
RW period in each arm will be estimated using the KM method, as described in the 
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analysis of the primary endpoint. The same censoring rules will apply. The variance 
of the difference in proportion between treatment arms will be the sum of the variance 
in each arm. The p-value and 95% CI will be calculated using a normal 
approximation. 
8. Time to pericarditis pain NRS ≥4 
 
Use the same method for the primary endpoint. 
9. Time to CRP level ≥1 mg/dL. This is for elevation of CRP for causes.  
 
Use the same method for the primary endpoint. A manual review for any CRP ≥1 
mg/dL will be performed to make sure that the CRP increase was caused by 
pericarditis. 
10. Time to pericardial rub 
 
Use the same method for the primary endpoint. Subjects with pericardial rub at RW 
baseline will be excluded from the analysis. 
11. Time to widespread ST-segment elevation or PR-segment depression on ECG 
 
Use the same method for the primary endpoint. Subjects with either condition at RW 
baseline will be excluded. 
12. Time to new or worsening pericardial effusion on ECHO 
 
Use the same method for the primary endpoint.  Proportion of subjects with new or 
worsening in pericardial effusion on ECHO and its 95% CI in each arm will be 
estimated using the K-M method. 
13. Change in category of ECHO pericardial effusion size at week 24 and end of RW 
based on central labs  
• The ITT Week 24 analysis set will be used for this endpoint.  Effusion size in 
ECHO has the following categories:  
• None or Trivial/Physiologic 
• Small 
• Moderate 
• Large 
• Very Large 
• NM/ND (Not Measurable/Not Recorded by Site) 
 
Shift tables for change from RW baseline to RW weeks 24 and to end of RW visit 
will be generated.  Due to potentially different number of subjects receiving bailout 
rilonacept between treatment arms, there will be no hypothesis testing for this 
endpoint.  
 
Endpoints 14-16 will be summarized for data before receiving bailout rilonacept and 
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for data including bailout rilonacept in each arm.  P-values will not be provided due to 
potentially different number of subjects receiving bailout rilonacept.  
14. Change over time in central-lab CRP level 
 
A mixed model with repeated measures (MMRM) using TYPE=UN option in SAS 
Proc Mixed will be applied in the analysis of this endpoint. If the model does not 
converge, an analysis of covariance (ANCOVA) model will be used at each timepoint 
to calculate least-squares (LS) means. In the model, subjects will have repeated 
measures for the response variable change from baseline of the endpoint. The 
explanatory variables will include the baseline value, treatment arm, baseline value by 
treatment interaction, and the variables for randomization strata. Only observed values 
will be used in the analysis without imputation.  
15. Change over time in the subject’s assessments of pericarditis pain (weekly averages) 
 
The same method for change over time in CRP level will be applied. If bailout 
rilonacept is used in a week, the week will be considered as after bailout. 
16. Number (percentage) of subjects with absent or minimal pericarditis activity over 
time after RW week 24 based on the PGIPS. The denominator in each arm will be the 
total number of subjects with the assessment at each visit. 
 
17. Number (percentage) of subjects with absent or minimal pericarditis activity over 
time based on the PGA-PA. The denominator in each arm will be the total number of 
subjects with the assessment at each visit. 
 
The same analysis method and analysis sets for PGPIS will be applied. 
 
The endpoints below (18 – 23) from patient reported outcomes will be summarized 
with descriptive statistics. There will be no hypothesis testing since they are measured 
at RW baseline and Week 24 only and receiving bailout rilonacept due to recurrence 
at Week 24 could be a confounding factor.   
18. Change from baseline to week 24 in the SF-36 Physical and Mental Component 
Scores (see below for definition)  
19. Change from baseline to week 24 in Physical Functioning, Role-Physical, Bodily 
Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental 
Health domains in SF-36. 
 
The SF-36v2® Health Survey (standard, four-week recall) is a 36-item generic (not 
indication specific) instrument used to evaluate subject reported health related quality 
of life (HRQoL) in adult subjects.  The questions are organized in eight health domain 
scales: physical functioning [PF] (10 items), role participation with physical health 
problems [RP] (four items), bodily pain [BP] (two items), general health status [GH] 
(one item), vitality [VT] (four items), social functioning [SF] (two items), role 
participation with emotional health problems [RE] (three items), and mental health 
(five items).  Scores from the eight domains are summarized into a physical 
component score (PCS) and mental component score (MCS).  
 
The SF-36v2 utilizes norm-based scoring involving a linear T-score transformation 
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method so that scores for each of the health domain scales and component summary 
measures have a mean of 50 and a standard deviation of 10, based on the 2009 United 
States general population.  Scores above and below 50 are above and below the 
average, respectively, in the 2009 United States general population. Also, because the 
standard deviation is 10, each 1-point difference or change in scores has a direct 
interpretation; that is, 1 point is one-tenth of a standard deviation, or an effect size 
of 0.10. 
 
Subject responses will be scored, including the handling of missing data, consistent 
with the instructions in the SF-36v2 user manual using the Optum Smart 
Measurement System Scoring Solution software.  
 
The possible score for each item is from 1 to 6. Each item response is then assigned a 
numeric value according to one of 8 scales.  
 
Items 1, 2, 20, 22, 34, 36: 1=100, 2=75, 3=50, 4=25, 5=0  
Items 3, 4, 5, 6, 7, 8, 9, 10, 11, 12: 1=0, 2=50, 3=100 
Items 13, 14, 15, 16, 17, 18, 19: 1=0, 2=100 
Items 21, 23, 26, 27, 30: 1=100, 2=80, 3=60, 4=40, 5=20, 6=0 
Items 24, 25, 28. 29, 31: 1=0, 2=20, 3=40, 4=60, 5=80, 6=100 
Items 32, 33, 35: 1=0, 2=25, 3=50, 4=25, 5=0. 
 
Final scores for each scale range from 0 to 100 with higher scores indicating better 
health. If a subject does not respond to a question, the average score for an item will 
use the number of non-missing scores for the denominator. 
 
Table 2 displays the items that are categorized.  Detailed information can be found in 
Mark, EM (2011). 
 
Table 2: 
The 8 Domains in SF-36v2 
Scale 
Number of items 
After recoding, average the following 
items 
Physical functioning 
10 
3 4 5 6 7 8 9 10 11 12 
Role-physical (RP) 
4 
13 14 15 16 
Bodily pain 
2 
21 22 
General health 
5 
1 33 34 35 36 
Vitality 
4 
23 27 29 31 
Social functioning 
2 
20 32 
Role-emotional (RE) 
3 
17 18 19 
Mental health 
5 
24 25 26 28 30 
 
20. Changes in SF-6D utility index score 
 
The SF-6D is calculated based on responses to 11 items on the SF-36, that correspond 
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to 6 domains: physical functioning, role participation (combined role-physical and 
role-emotional), social functioning, bodily pain, mental health, and vitality.  
 
RP and RE are combined, and general health is not included. The specific SF-36v2 
areas or activities contributing to the scoring of this index include: 
• ability to engage in both moderate and vigorous activities 
• ability to bathe and dress oneself 
• limitations in the kind of work or other activities as the result of physical health; 
accomplishing less due to emotional problems 
• bodily pain and its interference with normal work; nervousness, depression, and 
energy level 
• interference with social activities due to physical or emotional problems.  
Individual respondents can be classified on any of four to six levels of functioning or 
limitations for each of six domains, thus allowing a respondent to be classified into 
any of 18,000 possible unique health states. Using a standard gamble technique, each 
of these health states were mapped onto the SF-6D index score, which ranges from 
0.00 (worst possible health state/death) to 1.00 (best possible health state/perfect 
health). 
The PRO Analytics software calculates and outputs the SF-6D for each subject at 
each assessment, just as it does for the 8 domain scores and 2 summary scores. 
In the 2009 QualityMetric US Normative survey (Maruish 2011), from which the 
scoring algorithms were derived, the SF-6D calculated for 3,856 participants who 
completed the standard (4-week recall) form of the SF-36v2 had a mean of 0.74 and a 
SD of 0.14. Based on a paper from Walters and Brazier (2003), a change of 0.05 in 
the SF-6D would indicate a minimally important difference. 
 
Table 3: 
SF-36v2 Health Survey Items Scored for the SF-6D 
SF-6D Domains 
SF-36v2TM Health Survey 
Items 
Physical Functioning 
3a, 3b, 3j 
Role Participation (RP & PE) 
4c, 5b 
Social Functioning  
10 
Bodily Pain 
7, 8 
Mental Health 
9b, 9f 
Vitality 
9e 
 
21. Change in EQ-5D-5L individual scores and index value 
 
The EQ-5D-5L is a subject reported health status utility index for adult subjects that is 
comprised of five questions plus a visual analog scale (VAS). The five questions ask 
the respondent to assess their health in terms of mobility, self-care, usual activities, 
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pain/discomfort, and anxiety/depression. The VAS captures the respondent’s self-
reported level of the health on the day of completion, captured as a numeric input 
from 0 (‘the worst health you can imagine’) to 100 (‘the best health you can 
imagine’).  Subject responses will be scored, including the handline of missing values, 
as specified in the EuroQol Research Foundation, EQ-5D-5L User Guide, 2019, 
available from http://euroqol.org/publications/user-guides. 
 
Scores from the five questions will be reported individually and converted to a single 
index value using the value set for US.  Health state index scores generally range from 
less than 0 (where 0 is the value of a health state equivalent to dead; negative values 
representing values as worse than dead) to 1 (the value of full health), with higher 
scores indicating higher health utility. 
22. Change in subject’s sleep quality assessed with the Insomnia Severity Index (ISI).  
 
The ISI is a 7-item self-report questionnaire assessing the nature, severity, and impact 
of insomnia. The usual recall period is the “last 2 weeks” and the dimensions 
evaluated are severity of sleep onset, sleep maintenance, early morning awakening 
problems, sleep dissatisfaction, interference of sleep difficulties with daytime 
functioning, noticeability of sleep problems by others, and distress caused by the sleep 
difficulties. A 5-point Likert scale is used to rate each item (e.g., 0=no problem; 
4=very severe problem), yielding a total score ranging from 0 to 28 (Morin et al 
2011).  
 
The ISI will be collected in subjects ≥18 years or older as described in the protocol. 
23.  Change in ISI categories. The ISI total scores are divided to 4 categories: 
• 1)  0–7 = No clinically significant insomnia 
• 2)  8–14 = Subthreshold insomnia 
• 3)  15–21 = Clinical insomnia (moderate severity) 
• 4)  22–28 = Clinical insomnia (severe) 
A shift table will also be used to summarize the changes over time.  
24. Cumulative number (percentage) of subjects who received sequential ORT, 
corticosteroid, or bailout rilonacept for pericarditis period every 4 weeks cumulatively 
in the RW period.  
 
The CMH test stratified by the randomization strata will be applied to this endpoint. 
25. Proportion of subjects using ORT (analgesics, NSAIDs, and/or colchicine) for 
pericarditis in the first 24 weeks.  ORT use while waiting for at least 5 days since 
previous administration of study medication before receiving bailout rilonacept or 
within 5 days prior to the assessment of pericarditis recurrence visit is excluded. The 
denominator of the percentages is the number of subjects in the ITT analysis set in 
each arm. There will be no hypothesis testing for this endpoint. 
26. The endpoints below for MRI assessments will be summarized at RW baseline and 
week 24.  P-values will not be calculated. 
• Proportion of subjects with pericardial delayed hyperenhancement 
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• Proportion of subjects with myocardial delayed hyperenhancement  
• Proportion of subjects with pericardial effusion, and effusion size 
A subject will have pericardial effusion if the effusion size is rated “Small” or larger. 
5.2.3. 
Secondary Endpoints in RI and LTE Period 
These include efficacy endpoints in the RI period and the LTE. Since there is no control arm 
in these 2 periods, only descriptive statistics will be provided. Summary statistics will be 
generated following the methodologies stated in Section 3.1 using RIS or LTES analysis sets. 
All time-to-event endpoints start from the first day of receiving rilonacept in that period.  
Unless specified otherwise, the denominator of a response rate or percentage will be the total 
number of subjects treated in that period. 
5.2.3.1. 
Secondary Endpoints in the RI Period  
The following efficacy endpoints will be included for the RI period. Unless specified 
otherwise, change means change from RI baseline to RI week 12, and the denominator for a 
proportion is the total number of subjects who were treated in the RI period. 
1. Time to pain response, defined as number of days from first dose to the first day a 
subject’s daily pain NRS is ≤ 2 of the 3 days over which, the rolling average daily 
pain NRS is ≤ 2. Subjects with baseline NRS ≤ 2 will be excluded from the analysis. 
If one or more daily NRS score is missing, rolling average will be considered not 
meeting the response criteria.   
2. Time to CRP normalization (≤0.5 mg/dL) 
 
Time to CRP normalization will be censored at treatment discontinuation, taking 
prohibited medication, or week 12, whichever occurs first. Subjects with baseline 
CRP ≤0.5 mg/dL will be excluded from the analysis.  
3. Time to rilonacept monotherapy 
 
Time to rilonacept monotherapy is defined as number of weeks from first dose to the 
first day of achieving monotherapy. Subjects without background therapies at RI 
baseline will be excluded from the analysis. 
4. Time to treatment response defined as time from first dose to the first day of pain 
response (defined in endpoint 1 above), and CRP ≤0.5 mg/dL within 7 days before or 
after pain response. Treatment response day will be the day of pain response, whether 
pain response occurs before or after CRP ≤0.5 mg/dL.   
5. Proportion of subjects achieving clinical response at RI week 12 based on RIS 
analysis set 
 
Subjects who stopped background SOC pericarditis therapy on or before week 10, as 
well as who achieve CRP ≤0.5 mg/dL  and weekly average of daily pericarditis pain 
score ≤2.0 on the 11-point NRS within the 7 days prior to and including the day of 
randomization on RI Week 12/Randomization are responders. 
Additional analysis will be done base done the completers who finished the 12-weeks 
of RI treatment.  
 
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6. Number (percentage) of subjects with normalization of CRP (≤0.5 mg/dL) at RI Week 
12.  Subjects with baseline CRP >0.5 mg/dL in the RI analysis set will be used in the 
analysis. 
7. Change from baseline in pericarditis weekly pain score at RI Week 12 and over time. 
8. Change from baseline in CRP level at RI Week 12 and over time. 
9. Proportion of subjects with resolution of echocardiographic and ECG abnormalities 
(yes/no) at RI Week 12. 
10. Percentage of days with no or minimal pain (NRS ≤2) while on treatment. The 
denominator is the number of days on treatment, calculated as [min(date of last dose 
of study drug in RI period + 6, last date on study, end of RI period) – date of first dose 
in RI period) +1].   
11. Proportion of subjects with absent or minimal pericarditis symptoms based on PGIPS 
over time at baseline, week 6, and week 12. 
12. Proportion of subjects with absent or minimal pericarditis activity based on the PGA-
PA over time at baseline, week 6, and week 12. 
13. Change in the SF-36 8 domain scores, as well as the physical and mental scores. 
14. Change in the SF-6D 6 domain scores and the utility index. 
15. Change in the EQ-5D-5L individual scores and index value.  
16. Change in the subject’s sleep quality assessed with the ISI (see Section 5.2.2.3). 
17. Change in ISI categories. 
18. Number (percentage) of subjects who were off background pericarditis medication on 
or before weeks 4, 8, 10, and 12 
 
The RI Analysis Set will be used for the summary.  At each timepoint, the numerator 
only includes subjects who have reached monotherapy on or before the timepoint and 
remain on monotherapy until the end of the RI period. 
5.2.3.2. 
Efficacy Endpoints in the LTE Period 
The efficacy endpoints below are included in this period. These endpoints will not be 
included in the primary analysis for the RW period since data will not be available at that 
time.  Each endpoint will be summarized through Week 24 in this period, by subjects who did 
and did not have an adjudicated pericarditis recurrence in the RW period and by subjects who 
enter LTE directly from the RI period, respectively, and overall.  The baseline for the LTE 
period will be the last assessment before the first dose in the LTE period. 
1. Number (percentage) of subjects with pericarditis recurrences based on investigators’ 
judgement. 
2. Proportion of subjects with Clinical Response (rilonacept monotherapy + CRP≤0.5 
mg/dL + NRS≤2) at each CRP assessment (weeks 12 and 24).  The pain NRS at the 
visit when CRP was assessed will be used. 
3. Change over time in CRP levels. 
4. Change over time in pericarditis pain NRS. 
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5. Proportion of subjects with absent or minimal pericarditis symptoms over time based 
on PGIPS. 
6. Proportion of subjects with absent or minimal pericarditis activity over time based on 
the PGA-PA. 
7. Change from baseline in the SF-36 8 domain scores, as well as the physical and 
mental scores. 
8. Change in the SF-6D 6 domain scores and the utility index. 
9. Change from baseline in the EQ-5D-5L individual scores and index value. 
10. Change from baseline in the subject’s sleep quality assessed with the ISI.  
11. Change over time in ISI categories.   
12. Number (percentage) of subjects requiring addition of SOC pericarditis therapy every 
4 weeks cumulatively. 
13. Change from baseline in pericardial signs in ECHO, ECG, and MRI. 
14. Corticosteroid use over time.  
 
For subjects who are on corticosteroid at RI baseline, the proportion of subjects using 
corticosteroid at LTE will be summarized.  The denominator will be the number of 
subjects using corticosteroid at RI and entering the LTE.  The average daily dose of 
corticosteroid (mg/day) will be summarized. 
15. In the MRI substudy, resolution in pericardial inflammation among subjects with 
pericardial inflammation at RI baseline as assessed by cardiac MRI.  The endpoints 
below will be summarized. 
a. Proportion of subjects with pericardial Delayed Hyperenhancement  
b. Proportion of subjects with Myocardial Delayed Hyperenhancement 
c. Proportion of subjects with pericardial effusion, and effusion size  
16. Annualized recurrent rate during treatment 
 
Annualized recurrent rate will be calculated for subjects randomized to KPL-914 
utilizing pooled data in RW and LTE periods and there will be no hypothesis testing.  
5.3. 
Safety Analysis  
The following safety endpoints will be analyzed: 
• Adverse events, 
• Clinical laboratory parameters, 
• Serology parameters, 
• Hematology parameters, 
• Non-fasting lipid panel, 
• Pregnancy test, 
• Vital signs, 
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• Urinalysis, 
• Electrocardiogram, and  
• Physical examination. 
Descriptive statistics will be used to summarize safety endpoints for all subjects by the 
following periods:  
• RI period (KPL-914) 
• RW period  
− KPL-914 vs. Placebo Including Bailout Rilonacept 
− KPL-914 vs. Placebo before Bailout Rilonacept 
• LTE period  
• Study overall (RI through LTE), KPL-914 or placebo, regardless of receiving 
bailout Rilonacept.  
Two-sided 95% CIs will be presented where meaningful. Data summaries will be displayed 
for clinical laboratory analyses, vital signs measurements, ECGs, and physical examination 
findings. 
5.3.1. 
Adverse Events 
Treatment-emergent AEs (TEAEs), defined as AEs that start or increase in severity after the 
first dose of study drug and before 6 weeks after the last dose of study drug, will be coded to 
system organ class and preferred term using MedDRA v21.1.   
TEAEs will be summarized by each period and study overall.  In the RW period, they will 
also be summarized by including and excluding bailout rilonacept, respectively. The average 
follow-up duration in weeks for TEAE will be provided in summary tables.  The duration of 
follow-up for each subject is defined as follows. 
• For the RI period, it is from first dose in RI period until the day before 
randomization, last dose day plus 6 weeks, last study day, or data cutoff, 
whichever occurs first. 
• For the RW period including bailout, it is from randomization to data cutoff, last 
dose day plus 6 weeks, or last study day, whichever occurs first. 
• For the RW period before bailout, it is from randomization to the start of using 
bailout rilonacept, data cutoff, last dose day plus 6 weeks, or last study day, 
whichever occurs first. 
• For the LTE period, it is from first dose day in LTE period to data cutoff, last dose 
day plus 6 weeks, or last study day, whichever occurs first. 
• For study overall, it is from first dose day in RI period to data cutoff, the last dose 
plus 6 weeks, or last study day, whichever occurs first. 
A summary of the frequency (number and percentage of subjects) of TEAEs will be 
presented by system organ class and preferred term. Adverse events will also be analyzed by 
their severity (mild, moderate or severe), relationship to study drug, serious AEs, AEs leading 
to death, AEs resulting in dose interruption, AEs leading to withdrawal of study treatment, 
and AEs of injection site reaction.  
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Any AE of malignancy (excluding basal cell carcinoma of the skin) is of special interest.  AE 
of special interest will also be summarized.   
A subject experiencing the same AE multiple times will be counted only once for that 
preferred term. Similarly, if a subject experiences multiple AEs (preferred terms) within the 
same system organ class, then that subject will be counted only once for that system organ 
class. When summarizing by severity and relationship, only event with highest severity or 
relationship will be counted. All AEs will be presented by SOC and preferred terms. 
Incidence rate per 100 subject-years and its 95% CI will be calculated by the periods defined 
for follow-up duration above for the following groups of AEs: 
• All AEs (include any AE),  
• SAE (include any SAE), 
• deaths,  
• all infections (including serious),  
• serious infections (serious only),  
• all ISR (injection site reaction, including serious and non-serious),    
• only serious ISR,  
• all malignancies excluding NMSC (Non-Melanoma Skin Cancer: ie. cutaneous 
basal cell carcinoma and cutaneous squamous cell carcinoma). 
Incidence rate per 100 subject-years = 100 × (number of different AE start days within the 
treatment period)/(Sum of treatment duration in years from all subjects in the cohort).  
Multiple events within a subject will be counted as multiple events. Treatment exposure 
duration and follow-up of AE’s in the Study Overall period will be 6 weeks after the last 
dose. There will be no formal hypothesis testing. 
5.3.2. 
Clinical Laboratory Parameters 
Hematology, chemistry, lipid panel, and urinalysis results will be summarized and listed.  
Pregnancy test will not be summarized but will be listed. Summaries will include descriptive 
statistics for actual values and change from baseline.  Shift tables from baseline condition to 
the condition at each visit will also be provided.  The shift table will include subjects without 
data so that all subjects in the safety population at the baseline of each period (RI, RW, and 
LTE) will be included.  
A summary of hepatic function abnormalities will be provided for the following criteria:  
• >2xULN 
• >3xULN 
• >5xULN  
• The number of percentage of subject’s meeting the criteria for Hy’s Law defined 
as elevations in ALT and/or AST of >= 3xULN with accompanying elevations in 
total bilirubin of >= 2xULN will also be summarized. 
The incidence rate per 100 subject-years and its 95% CI for the following lab abnormalities 
will be calculated: 
• Incidence of ALT >5xULN,   
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• Incidence of AST >5x ULN,  
• Incidence of total bilirubin >2xULN 
• Incidence of absolute neutrophil count (ANC) <1.0 x 103 uL. 
Multiple lab abnormalities within a subject will be counted as multiple events within the 
follow-up period defined in Section 5.3.1 .  
Incidence rate per 100 subject years in a cohort = 100 × (# of different lab abnormalities from 
all subjects within the follow-up period)/(Sum of follow-up duration in years from all 
subjects in the cohort). 
5.3.2.1. 
Hematology 
Hematology tests performed at central study laboratory include WBC count with differential, 
platelet count, red blood cell count, mean corpuscular volume, hemoglobin, mean corpuscular 
hemoglobin concentration. 
5.3.2.2. 
Chemistry 
Blood chemistry tests performed in the central study laboratory include albumin, total 
protein, alkaline phosphatase, alanine aminotransferase/serum glutamic pyruvic transminase 
(ALT/SGPT), aspartate aminotransferase/serum glutamic oxaloacetic transminase 
(AST/SGOT), direct bilirubin, total bilirubin, bicarbonate, chloride, potassium, sodium, 
creatinine, glucose. 
5.3.2.3. 
Non-fasting Lipid Panel 
Subjects treated with rilonacept may experience increases in their lipids, including total 
cholesterol, low-density lipoprotein (LDL), high-density lipoprotein HDL, and triglycerides. 
Non fasting measurements of total cholesterol, triglycerides, HDL, and direct LDL will be 
performed by central study laboratory as described in the Schedule of Assessments in 
Section 13.1. 
Investigators should monitor the lipid profiles in study subjects and consider ordering fasting 
lipid panel and/or lipid lowering therapies as needed based on cardiovascular risk factors and 
current guidelines. 
5.3.2.4. 
Urinalysis 
Urinalysis performed by the central study laboratory includes specific gravity, pH, protein, 
urobilinogen, ketones, glucose, blood, bilirubin, nitrites, leukocyte esterase will be 
summarized.  
5.3.2.5. 
Pregnancy Test 
For women of child-bearing potential, a urine pregnancy test using a licensed test (dipstick) 
should be performed prior to receiving the first administration of study drug, and as needed 
during the study, and also at the SFU visit. When needed, serum pregnancy test should be 
performed. Pregnancy test results will not be summarized but will be listed. 
5.3.3. 
Vital Signs 
Descriptive summaries of actual values and changes from baseline will be calculated for 
Temperature, Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Pulse Rate 
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(PR), Respiratory Rate (RR), temperature, and weight (kg). A data listing of vital signs will 
also be provided. 
5.3.4. 
Electrocardiogram 
Frequency table for the following interpretations will be generated: 
• Widespread of ST elevation normal 
• PR-segment depression 
• ECG Interpretation 
− Normal 
− abnormal not clinically significant, and abnormal clinically significant) 
− Abnormal not consistent with pericarditis but clinically significant 
− Abnormal consistent with pericarditis 
Shift table for shifts from baseline to the last post-baseline assessment in the treatment period 
and extension period in the overall interpretation based on local read will be created. All ECG 
data will be provided as a by-subject listing.  
5.3.5. 
Physical Examination 
There are full and abbreviated physical examinations.  Full physical examination includes at 
minimum evaluation of vital signs, head, eye, ear, nose, and throat as well as cardiovascular, 
dermatological, musculoskeletal, respiratory, gastrointestinal (GI), genitourinary, and 
neurological systems. The decision to perform examination of genitourinary system should be 
guided by clinical judgement.  Abbreviated physical examination includes at minimum 
evaluation of vital signs, lung and heart sounds, including evaluation for pericardial rub. 
Present or absent in pericardial rub will be recorded.  For each assessment of body system, 
the result will be recorded as normal, abnormal (not clinically significant), or abnormal 
(clinically significant).  The number and percentage of subjects in each result category will be 
summarized by body system and visit, as well as by arm in the RW period. 
All physical examination data will be provided in a listing. 
6. 
PHARMACOKINETIC ANALYSES 
For all subjects, serum samples will be collected at time points shown in Section 13.1 in order 
to quantify concentrations of rilonacept. Only individual listings of serum concentrations will 
be provided. The analysis plan for PK data will be described in a separate document. 
7. 
PHARMACOGENOMICS SUBSTUDY 
Samples for pharmacogenomics in the substudy will be collected according to the Study 
Schedule of Activities. More details of the analysis will be provided in a separate document. 
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8. 
ANTI-RILONACEPT ANTIBODIES 
Blood sample for testing anti-rilonacept antibody (ADA) will be collected at RI baseline, RI 
weeks 2, 6, 12 (= RW baseline), RW week 24, end of RW/LTE baseline, and LTE week 24.  
ADA status will be categorized as follows. 
1. Treatment-emergent ADA, including treatment induced or boosted [increased by one 
quartile (with all titers collected) from the previous assessment]  
2. Prior existing ADA (without treatment boosted) 
3. ADA negative at every assessment. 
For subjects with treatment-emergent ADA, the maximum post-baseline titer level (low, 
medium, high) will be summarized.  The 3 levels (low, medium, high) will be divided based 
on 25th and 75th percentiles from all ADA titers pooled. 
The following endpoints will be summarized for each category of ADA status above: 
• Number and percentage of subjects with injection site reactions within 24 hours of 
administration  
• Subjects with Neutralizing antibody in the first 2 categories above. 
A summary table will be provided for number and percent of subjects with positive or 
negative anti-rilonacept antibody by visit.  Individual’s ADA status and titer level (if 
positive) at each visit will be provided. 
The number and percent of subjects with anti-rilonacept-antibody positive at any visit vs. 
those with negative at every visit will also be provided.  The summary statistics of CRP and 
NRS level will be provided for these 2 subsets of subjects at each visit by study period, and 
by treatment arm in the RW period (before vs. after receiving bailout rilonacept and overall). 
The following 3 categories will be used in the subgroup analysis for the primary endpoint, 
Summary of NRS scores and CRP levels over time, summary of TEAEs (overall and drug 
related), and blood concentration over time: 
1. Subjects with ADA Positive at Any Assessment 
2. Subjects with ADA Positive and Neutralizing Antibody at Any Assessment 
3. Subjects with ADA Negative at Every Assessment 
9. 
BIOMARKER 
Serum and plasma will be collected according to the Study Schedule of Activities for 
biomarker analysis. More details of the biomarker analysis will be provided in a separate 
document. 
10. 
INTERIM ANALYSIS 
No interim analysis for claiming efficacy is planned. Interim safety review will be conducted 
by a Data Monitoring Committee (DMC).  The analysis will be performed by a designated 
CRO.  Details are in DMC charter and DMC SAP. 
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11. 
CHANGES FROM ANALYSES PLANNED IN THE 
PROTOCOL 
11.1. 
Changes from Protocol 
 
Analysis in the SAP 
Analysis planed in the 
protocol  
Reason  
Section 5.2.2.3  
Changes in SF-6D utility index score. 
Section 7.2.2 
Change in the SF-6D 6 
domain scores and the 
utility index. 
The 6 domains were 
not generated for 
analysis by the Optum 
software. They were 
used to calculate the 
utility index score 
only. 
Section 5.2.3.1  
Time to pain response, defined as number of 
days from fist dose to the first day a subject’s 
daily pain NRS is ≤ 2 of the 3 days over which, 
the rolling average daily pain NRS is ≤ 2.  
Section 7.3.1 
Time to pain response 
defined as a rolling 
average of NRS score 
of 2 or less on three 
consecutive days. 
A score of 3 or 
higher on the first 
day of the rolling 
average should not 
qualify pain 
response. 
Section 5.2.3.1 
Time to treatment response defined as time 
from first dose to the first day of pain response, 
and CRP ≤0.5 within 7 days before or after 
pain response. Treatment response day will be 
the first day that the above criterion is met. If 
pain response occurs before CRP ≤0.5, each 3-
day rolling average of NRS should be ≤2.0 
from the day of pain response to the day of 
CRP ≤0.5. The response day will be the day of 
pain response.  If CRP ≤0.5 occurs before pain 
response, the response day will also be the day 
of pain response. 
Section 7.3.1 
Time to clinical 
response (monotherapy 
+ NRS ≤2 + CRP ≤0.5 
mg/dL) 
Subjects were 
enrolled with a 
qualifying episode 
and on background 
therapy.  The 
endpoint of interest 
is to evaluate how 
soon subjects will 
reach response in 
both pain and CRP 
after initiating 
rilonacept while on 
background therapy.  
 
11.2. 
Impact of COVID-19 Pandemic 
The KPL-914-C002 study was nearing the end of Randomized Withdrawal (RW) phase of 
the study when COVID-19 pandemic started. The impact of the pandemic to the study 
conduct is limited. A separate document will be prepared to summarize any protocol 
deviations which occurred as a result of the pandemic. 
There are no special data handling rules and analyses implemented for COVID-19 related 
protocol deviations.  
 
 
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12. 
REFERENCES 
Brookmeyer R and Crowley J (1982), “A Confidence Interval for the Median Survival Time” 
Biometrics, 38, 29 - 41. 
Deng Q (2014), “Computing Confidence Interval for Poisson Mean” 
http://onbiostatistics.blogspot.com/2014/03/computing-confidence-interval-for.html. 
Lucis NC, Ron BSE, and Hays D (2015), “Scoring the SF-36 in Orthopaedics: A Brief 
Guide” J Bone Joint Surg Am 97(19): 1628-34. 
Maruish, M. E. (Ed., 2011), User’s manual for the SF-36v2 Health Survey (3rd ed.). Lincoln, 
RI: QualityMetric Incorporated. 
Maruish, ME (2011).  Manual for the SF-36v2 Health Survey (3rd Edition), QualityMetric, 
Inc., Lincoln, RI. 
Morin CM, Belleville G, Belanger L, et al (2011), “The insomnia severity index: 
psychometric indicators to detect insomnia cases and evaluate treatment response” Sleep. 
34(5):601-608. 
Poisson distribution, https://en.wikipedia.org/wiki/Poisson_distribution. 
Spritzer K (2014), “SAS Code for Scoring 36-Item Health Survey Version 2.0” 
http://sasstatistics.blogspot.com/2014/07/use-sas-to-score-sf-36.html. 
Sullivan KM and Soe MM (2006), “Confidence Intervals for a Rate” 
http://www.openepi.com/PDFDocs/PersonTime1Doc.pdf. 
Taft C, Karlsson J, Sullivan M (2001), “Do SF-36 summary component scores accurately 
summarize subscale scores?” Qual Life Res 10(5):395-404. 
Reenen MV, Janssen B. (2015) EQ-5D-5L User guide. Basic information on how to use the 
EQ-5D-5L instrument. Version 2.1. https://euroqol.org/docs/EQ-5D-5L-User-Guide.pdf.  
Walters, S.J. (2003), Brazier, J.E. What is the relationship between the minimally important 
difference and health state utility values? The case of the SF-6D. Health Qual Life Outcomes 
1, 4 doi:10.1186/1477-7525-1-4. 
 
 
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13. 
APPENDICES 
13.1. 
Schedule of Assessments 
Table 4: 
Study Schedule of Activities – Screening and Run-In Period  
Trial Period 
SCREENINGa 
RUN-IN (12 weeks)m 
  
ENROLLMENT 
  
RANDOMIZATION -q 
Visit Name 
Screening Visit 
RI  
Baseline 
RI  
Day 2 
RI  
Day 4 
RI  
Week 1 
RI  
Week 2 
RI  
Week 4 
RI  
Week 
6 
RI  
Week 
10 
RI Week 12/ 
RW Baseline 
Visit Windowb (days) 
(-28) 
NA 
NA 
+/- 1 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 3 
Visit Type 
Clinic 
Clinic 
Clinic 
TC/RN 
TC/RN 
TC/RN 
TC/RN 
Clinic 
TC 
Clinic 
Informed Consent Form 
X 
  
  
  
  
  
  
  
  
  
Inclusion and Exclusion criteria 
X 
X 
  
  
  
  
  
  
  
  
Demographics 
X 
  
  
  
  
  
  
  
  
  
Medical/Surgical History 
X 
  
  
  
  
  
  
  
  
  
Pericarditis Diagnosis & History 
X 
X 
  
  
  
  
  
  
  
  
Concomitant medications 
X 
X 
  
X 
X 
X 
X 
X 
X 
X 
Pericarditis Concomitant 
medications 
X 
X 
  
X 
X 
X 
X 
X 
X 
X 
Pericarditis Concomitant medication 
tapering 
  
  
  
  
X 
X 
X 
X 
X 
  
Full Physical Examinationc 
X 
  
  
  
  
  
  
  
  
  
Abbreviated Physical Examinationd 
  
X 
  
  
  
  
  
  
  
X 
Body weight and height 
  
X 
  
  
  
  
  
  
  
X 
12-Lead ECG 
  
X 
  
  
  
  
  
  
  
X 
Echoe 
  
Xe 
  
  
  
  
  
  
  
Xe 
MRI (substudy only) 
  
X 
  
  
  
  
  
  
  
  
Pericardial pain (11-point NRS) 
Xf 
DAILYg 
Xg 
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Trial Period 
SCREENINGa 
RUN-IN (12 weeks)m 
  
ENROLLMENT 
  
RANDOMIZATION -q 
Visit Name 
Screening Visit 
RI  
Baseline 
RI  
Day 2 
RI  
Day 4 
RI  
Week 1 
RI  
Week 2 
RI  
Week 4 
RI  
Week 
6 
RI  
Week 
10 
RI Week 12/ 
RW Baseline 
Visit Windowb (days) 
(-28) 
NA 
NA 
+/- 1 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 3 
Visit Type 
Clinic 
Clinic 
Clinic 
TC/RN 
TC/RN 
TC/RN 
TC/RN 
Clinic 
TC 
Clinic 
EQ-5D 
  
X 
  
  
  
  
  
  
  
X 
SF-36 
  
X 
  
  
  
  
  
  
  
X 
ISI 
  
X 
  
  
  
  
  
  
  
X 
PGIPS 
  
X 
  
  
  
  
  
X 
  
X 
PGA-PA 
  
X 
  
  
  
  
  
X 
  
X 
Hematology, Chemistry Labs 
(Central) 
  
X 
  
  
  
  
  
X 
  
X 
Lipid Panel (Central)h 
  
X 
  
  
  
  
  
  
  
X 
CRP (Local) 
Xf 
  
  
  
  
  
  
  
  
X 
CRP (Central) 
(X) 
X 
  
X 
X 
X 
X 
X 
  
X 
Hematology, Chemistry, IGRAr, 
hepatitis serology, HIV (Local) 
X 
  
  
  
  
  
  
  
  
  
Chest X-Ray 
X 
  
  
  
  
  
  
  
  
  
Urine Pregnancy (Local or Central)j 
X 
X 
  
  
  
  
  
  
  
  
Urinalysis (Central) 
  
X 
  
  
  
  
  
  
  
  
PK (Central)s 
  
  
Xi 
  
X 
X 
X 
  
  
  
ADA (Central)s 
  
X 
  
  
  
X 
  
X 
  
  
Biomarkers (Central)  
  
X 
  
  
X 
  
X 
  
  
  
Pharmacogenomics Informed 
Consentk 
  
X 
  
  
  
  
  
  
  
  
Pharmacogenomics Sampling 
(Central)k 
  
  
  
  
  
  
X 
  
  
  
IWRS Subject Status Update 
X 
X 
  
  
  
  
  
  
  
X 
IWRS Weight Input (pediatric only) 
  
X 
  
  
  
  
  
  
  
X 
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Trial Period 
SCREENINGa 
RUN-IN (12 weeks)m 
  
ENROLLMENT 
  
RANDOMIZATION -q 
Visit Name 
Screening Visit 
RI  
Baseline 
RI  
Day 2 
RI  
Day 4 
RI  
Week 1 
RI  
Week 2 
RI  
Week 4 
RI  
Week 
6 
RI  
Week 
10 
RI Week 12/ 
RW Baseline 
Visit Windowb (days) 
(-28) 
NA 
NA 
+/- 1 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 3 
Visit Type 
Clinic 
Clinic 
Clinic 
TC/RN 
TC/RN 
TC/RN 
TC/RN 
Clinic 
TC 
Clinic 
IWRS Drug Dispensing 
  
X 
  
X 
  
  
  
X 
  
X 
In Clinic Study Drug 
Administrationo 
  
Xn 
  
  
  
  
  
X 
  
X 
Outpatient Study Drug 
Administrationo 
  
  
  
  
WEEKLY 
Study Drug Compliance Review 
  
X 
  
  
X 
X 
X 
X 
X 
X 
Clinical Response Evaluation 
  
  
  
  
  
  
  
  
  
Xp 
Adverse Event Reportingl 
X 
X 
  
X 
X 
X 
X 
X 
X 
X 
a  
The screening and enrollment visit can be combined. 
b  
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
c  
Full physical examination includes at minimum evaluation of vital signs, head, eye, ear, nose, and throat as well as cardiovascular, dermatological, 
musculoskeletal, respiratory, GI, genitourinary, and neurological systems. The decision to perform examination of genitourinary system should be guided 
by clinical judgement. 
d  
Abbreviated physical examination includes at minimum evaluation of vital signs, lung and heart sounds, including evaluation for pericardial rub. 
e  
ECHO is required to be obtained according to the central core lab parameters and then read locally and submitted to the central core lab for separate 
review and analysis.  
f  
Both a documented CRP > 1.0 mg/dL AND a pericarditis pain level of > 4 is required 7 days prior to and including the Run-In Baseline visit. These are 
not required to occur on the same day. 
g  
Subjects missing ≥ 4 daily pain measurements during the 7 days prior to and including the Randomization Withdrawal baseline visit will be unable to 
proceed to randomization due to lack of data required for treatment response evaluation.  
h  
Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the randomization withdrawal and LTE periods, or more 
frequently as needed, with mandated evaluations as detailed in the schedule of events. 
i  
Applicable to 24-hour post dose PK sub-study participants only.  
j  
For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout the course of the study and serum pregnancy can be 
drawn as needed; urine pregnancy is required to be performed at enrollment and 6 weeks after the last dose of study drug.  
k  
Pharmacogenomics informed consent and subsequent sampling can be performed at any time in the study however, it is preferable to have this completed 
at the beginning of the study. 
l  
Adverse event reporting begins following the subject providing informed consent. 
m  
All procedures are to be completed prior to study drug administration. 
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Statistical Analysis Plan 
 
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Study KPL-914-C002 
30 March 2020 
 
Confidentia 
 
 
 
Page 42 of 53 
n  
The first dose of study drug is a loading dose. Adult subjects receive 2 SC doses 160 mg (total 320 mg); pediatric subjects (subjects ≥12 and <18 years of 
age) receive 2 SC doses of 2 x 2.2 mg/kg. 
o  
Study drug administration is once weekly with a minimum of 5 days required between doses.  
p  
Randomization and subsequent study drug dispensing to occur after confirmation of Clinical Response (see definition of Clinical Response in Section 
6.2.2). 
q  
The Randomization visit serves as both the RI Week 12 visit and the RW baseline visit.  
s 
PK and ADA samples will be collected prior to study drug administration. PK at enrollment/baseline will be taken from ADA 
 
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Statistical Analysis Plan 
 
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Study KPL-914-C002 
30 March 2020 
 
Confidentia 
 
 
 
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Table 5: 
Study Schedule of Activities – Randomized Withdrawal  
Trial Period 
RANDOMIZED WITHDRAWAL (event-driven)m 
  
END OF 
RANDOMIZED 
 WITHDRAWAL  
(EORW)t 
Visit Name 
RW 
Week 4 
RW 
Week 8 
RW 
Week 12 
RW 
Week 16 
RW 
Week 20 
RW 
Week 24 
RW 
Every 8 
Weeks 
RW 
Every 
8 
Weeks 
Per Announced 
End Dateu/ 
LTE-Baseline 
Visit Windowb (days) 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 7 
Visit Type 
TC/RN 
Clinic 
TC/RN 
Clinic 
TC/RN 
Clinic 
TC/RN 
Clinic 
Clinic 
Informed Consent Form 
  
  
  
  
  
  
  
  
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pericarditis Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Full Physical Examinationc 
  
  
  
  
  
X 
  
  
X 
Abbreviated Physical Examinationd 
  
  
  
  
  
  
  
  
  
Body weight and height 
  
X 
  
X 
  
X 
  
X 
X 
12-Lead ECG 
  
  
  
  
  
X 
  
  
X 
Echoe 
  
  
  
  
  
Xe 
  
  
Xe 
MRI (substudy only) 
  
  
  
  
  
X 
  
  
  
Pericardial pain (11-point NRS) 
DAILY 
EQ-5D 
  
  
  
  
  
X 
  
  
X 
SF-36 
  
  
  
  
  
X 
  
  
X 
ISI 
  
  
  
  
  
X 
  
  
X 
PGIPS 
  
X 
  
X 
  
X 
  
X 
X 
PGA-PA 
  
X 
  
X 
  
X 
  
X 
X 
Hematology, Chemistry Labs (Central) 
  
X 
  
  
  
X 
  
X 
X 
Lipid Panel (Central)h 
  
  
  
  
  
X 
  
  
X 
CRP (Local) 
  
  
  
  
  
  
  
  
  
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Study KPL-914-C002 
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Confidentia 
 
 
 
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Trial Period 
RANDOMIZED WITHDRAWAL (event-driven)m 
  
 
END OF 
RANDOMIZED 
 WITHDRAWAL  
(EORW)t 
Visit Name 
RW 
Week 4 
RW 
Week 8 
RW 
Week 12 
RW 
Week 16 
RW 
Week 20 
RW 
Week 24 
RW 
Every 8 
Weeks 
RW 
Every 
8 
Weeks 
Per Announced 
End Dateu/ 
LTE-Baseline 
Visit Windowb (days) 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 7 
Visit Type 
TC/RN 
Clinic 
TC/RN 
Clinic 
TC/RN 
Clinic 
TC/RN 
Clinic 
Clinic 
CRP(Central  
X 
X 
X 
X 
X 
X 
X 
X 
X 
PK (Central) 
  
X 
  
  
  
X 
  
  
X 
ADA (Central) 
  
  
  
  
  
X 
  
  
X 
Biomarkers (Central)  
  
X 
  
  
  
X 
  
  
  
Urine Pregnancyj (Local or Central) 
  
  
  
  
  
  
  
  
X 
Urinalysis 
  
  
  
  
  
  
  
  
X 
IWRS Subject Status Update 
  
  
  
  
  
  
  
  
X 
IWRS Weight Input (pediatric only) 
  
X 
  
X 
  
X 
  
X 
X 
IWRS Drug Dispensing 
  
X 
  
X 
  
X 
  
X 
Xv 
In Clinic Study Drug Administrationo 
  
X 
  
X 
  
X 
  
X 
Xv 
Outpatient Study Drug Administrationo 
X 
WEEKLY 
Study Drug Compliance Review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assessment of Pericarditis Recurrence 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Event Reportingl 
X 
X 
X 
X 
X 
X 
X 
X 
X 
b  Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug 
treatment. 
c  Full physical examination includes at minimum evaluation of vital signs, head, eye, ear, nose, and throat as well as cardiovascular, 
dermatological, musculoskeletal, respiratory, GI, genitourinary, and neurological systems. The decision to perform examination of 
genitourinary system should be guided by clinical judgement. 
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d  Abbreviated physical examination includes at minimum evaluation of vital signs, lung and heart sounds, including evaluation for pericardial 
rub. 
e  ECHO is required to be obtained according to the central core lab parameters and then read locally and submitted to the central core lab for 
separate review and analysis.  
h  Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the randomization withdrawal and LTE periods, or 
more frequently as needed, with mandated evaluations as detailed in the schedule of events. 
j   For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout the course of the study and serum 
pregnancy can be drawn as needed; urine pregnancy is required to be performed at enrollment and 6 weeks after the last dose of study drug.  
l   Adverse event reporting begins following the subject providing informed consent. 
m  All procedures are to be completed prior to study drug administration. 
o  Study drug administration is once weekly with a minimum of 5 days required between doses.  
s 
PK and ADA samples will be collected prior to study drug administration. PK at enrollment/baseline will be taken from ADA.  As required, 
ADA samples will be collected at EOS, ET, and Unscheduled visits. 
t  The EORW visit serves as both the last visit of the RW period and the baseline visit of the LTE period. 
u  For all subjects, the final clinic visit of the end of RW period is to be scheduled once the End of the Randomization Withdrawal end date is 
announced by Sponsor. This includes subjects that are taking blinded study drug, open-label rilonacept, or who have prematurely discontinued 
study drug. 
 v  Study drug administration to occur only after subject provides informed consent for the open-label extension period. 
 
 
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Table 6: 
Study Schedule of Activities – Long Term Extension 
Trial Period 
LONG TERM EXTENSION (up to 24 months) 
  
Long Term Extension Treatment (up to 24 
Months)m 
Visit Name 
LTE 
Week 
12 
LTE 
Week 24 
LTE 
Every 12 
Weeks 
LTE 18-
month 
Assessment 
Visit Windowb (days) 
+/- 2 
+/- 2 
+/- 2 
18 months 
from most 
recent 
recurrence 
Visit Type 
Clinic 
Clinic 
Clinic 
Clinic 
Concomitant medications 
X 
X 
X 
X 
Pericarditis Concomitant medications 
X 
X 
X 
X 
Full Physical Examinationc 
  
X 
  
X 
12-Lead ECG 
  
X 
  
X 
Echoe 
  
X 
  
X 
MRI  
  
Xz 
  
Xz 
EQ-5D 
  
X 
  
 
SF-36 
  
X 
  
 
ISI 
  
X 
  
 
PGIPS 
X 
X 
X 
 
PGA-PA 
X 
X 
X 
 
Hematology, Chemistry Labs (Central) 
X 
X 
X 
 
Lipid Panel (Central)h 
  
X 
  
 
CRP (Central)  
X 
X 
X 
X 
PK (Central) 
  
X 
  
X 
ADA (Central)  
 
X 
  
 
Biomarkers (Central)  
  
X 
  
 
Urine Pregnancyj (Local or Central) 
  
X 
  
X 
Urinalysis 
  
X 
  
 
IWRS Subject Status Update 
  
X 
  
X 
IWRS Weight Input (pediatric only) 
X 
  
X 
X 
IWRS Drug Dispensing 
X 
X 
X 
X 
In Clinic Study Drug Administrationo 
X 
X 
X 
 
Outpatient Study Drug Administrationo 
WEEKLY 
Study Drug Compliance Review 
X 
X 
X 
X 
Assessment of Pericarditis Recurrence 
X 
X 
X 
X 
Adverse Event Reportingl 
X 
X 
X 
X 
a  The screening and enrollment visit can be combined. 
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Study KPL-914-C002 
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Page 47 of 53 
b  Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption 
to subject evaluation and study drug treatment. 
c  Full physical examination includes at minimum evaluation of vital signs, head, eye, ear, nose, and 
throat as well as cardiovascular, dermatological, musculoskeletal, respiratory, GI, genitourinary, and 
neurological systems. The decision to perform examination of genitourinary system should be guided 
by clinical judgement. 
e  ECHO is required to be obtained according to the central core lab parameters and then read locally 
and submitted to the central core lab for separate review and analysis.  
h  Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the 
randomization withdrawal and LTE periods, or more frequently as needed, with mandated evaluations 
as detailed in the schedule of events. 
j  For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout 
the course of the study and serum pregnancy can be drawn as needed; urine pregnancy is required to 
be performed at enrollment and 6 weeks after the last dose of study drug. 
l   Adverse event reporting begins following the subject providing informed consent. 
m  All procedures are to be completed prior to study drug administration. 
o  Study drug administration is once weekly with a minimum of 5 days required between doses.  
z  The MRI to occur only if the previous MRI was done longer than 6 months ago. 
 
 
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Study KPL-914-C002 
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Page 48 of 53 
Table 7: 
Study Schedule of Activities – Supplemental Visits  
Visit Name 
PERICARDITIS 
RECURRENCE 
ASSESSMENT 
END of 
TREATMENT 
(EOT)x 
SAFETY 
FOLLOW UP 
(SFU)y  
(6 weeks post last 
dose) 
Visit Windowb (days) 
N/A 
N/A 
+/- 2 
Visit Type 
Clinic 
Clinic 
Clinic or TC/RN 
Concomitant medications 
X 
X 
X 
Pericarditis Concomitant medications 
X 
X 
X 
Full Physical Examinationc 
  
X 
  
Abbreviated Physical Examinationd 
X 
  
  
Body weight and height 
X 
  
  
12-Lead ECG 
X 
X 
  
Echoe 
Xe 
X 
  
MRI (substudy only) 
  
Xz 
  
Pericardial pain (11-point NRS) 
X 
X 
  
EQ-5D 
X 
X 
  
SF-36 
X 
X 
  
ISI 
X 
X 
  
PGIPS 
X 
X 
  
PGA-PA 
X 
X 
  
Hematology, Chemistry Labs (Central) 
  
X 
  
Lipid Panel (Central)h 
  
X 
  
CRP (Local) 
X 
  
  
CRP(Central  
X 
X 
  
PK (Central) 
X 
X 
X 
ADA (Central) 
X 
X 
X 
Biomarkers (Central)  
X 
X 
  
Urine Pregnancyj (Local or Central) 
  
X 
Urinalysis 
  
X 
  
IWRS Subject Status Update 
Xs 
X 
  
IWRS Weight Input (pediatric only) 
X 
  
  
IWRS Drug Dispensing 
X 
  
  
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Study KPL-914-C002 
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Page 49 of 53 
Visit Name 
PERICARDITIS 
RECURRENCE 
ASSESSMENT 
END of 
TREATMENT 
(EOT)x 
SAFETY 
FOLLOW UP 
(SFU)y  
(6 weeks post last 
dose) 
Visit Windowb (days) 
N/A 
N/A 
+/- 2 
Visit Type 
Clinic 
Clinic 
Clinic or TC/RN 
Study Drug Compliance Review 
X 
X 
  
Assessment of Pericarditis Recurrence 
X 
X 
X 
Adverse Event Reportingl 
X 
X 
X 
b  
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to 
subject evaluation and study drug treatment. 
h  
Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the randomization 
withdrawal and LTE periods, or more frequently as needed, with mandated evaluations as detailed in the 
schedule of events. 
j  
 
For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout the 
course of the study and serum pregnancy can be drawn as needed; urine pregnancy is required to be performed 
at enrollment and 6 weeks after the last dose of study drug.  
l  
 
Adverse event reporting begins following the subject providing informed consent. 
s  
 
PK at enrollment/baseline will be taken from ADA.   
x 
 
An EOT visit is to be conducted throughout the course of the study when a subject permanently 
discontinues study drug. 
y  
An SFU is required to be conducted within 6 weeks of the last dose of rilonacept at any time throughout the 
course of the study including the RI period, the RW period, and the LTE period. 
z  
The MRI to occur only if the previous MRI was done longer than 6 months ago. 
 
 
 
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13.2. 
Missing Data Imputation Rules 
Partial missing dates will be imputed for start/stop dates of AE and prior/concomitant 
medications, as well as start date of each pericarditis episode according to the rules below.  
 
Table 8: 
Imputation Rules for Partial Missing Dates 
Category 
Scenario 
Rule for missing dates  
General rule 
All 
If year is missing, do not impute, unless otherwise 
specified 
AE and 
prior/concomitant 
medication start 
date 
Day is missing and (month, year) 
same as the first dose date 
The day will be imputed as the same day of the first 
dose day or stop date, whichever is earlier.   
Day is missing and (month, year) 
not the same as the first dose 
date 
The day will be imputed as the first day of the month 
or stop date, whichever is earlier. 
Month and day missing, year the 
same as the first dose date  
Date will be imputed with the first dose date or stop 
date, whichever is earlier. 
Month and day missing, year 
different from the first dose date 
Impute with the first day of the year. 
AE and 
prior/concomitant 
medication end 
date 
Day is missing  
Impute with min(last day of the month, data cutoff, 
end of study date)  
Day and month are missing 
Impute with min(last day of the year, data cutoff, 
end of study date) 
Entirely missing 
Impute with min(data cutoff, end of study date) 
First pericarditis 
episode start date 
Day missing  
Use first day of the month 
Month missing  
Use January 01 
Second or later 
pericarditis episode 
start date 
Day missing  
Use max(first day of the month, stop day of previous 
episode +1) 
Month missing  
January 01 
Other 
 
Non-specific 
For missing data handling rules not covered in this 
table, they will be defined in the ADaM Define file. 
 
 
 
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13.3. 
EQ-5D-5L Scoring 
The EQ-5D-5L consists of 2 pages – the EQ-5D-5L descriptive system and the EQ Visual 
Analogue scale (EQ VAS). The descriptive system comprises of 5 dimensions (mobility, self-
care, usual activities, pain/discomfort, anxiety/depression). Each dimension now has 5 levels: no 
problems, slight problems, moderate problems, severe problems, and extreme problems. The 
respondent is asked to indicate his/her health state by ticking (or placing a cross) in the box 
against the most appropriate statement in each of the 5 dimensions. This decision results in a 1-
digit number expressing the level selected for that dimension. The digits for 5 dimensions can be 
combined in a 5-digit number describing the respondent’s health state. It should be noted that the 
numerals 1-5 have no arithmetic properties and should not be used as a cardinal score.  
EQ-5D-5L health states, defined by the EQ-5D-5L descriptive system, may be converted into a 
single index value. The index values, presented in country specific value sets, are a major feature 
of the EQ-5D instrument, facilitating the calculation of quality-adjusted life years (QALYs) that 
are used to inform economic evaluations of health care interventions. 
The EQ VAS records the respondent’s self-rated health on a 20 cm vertical, visual analogue 
scale with endpoints labelled ‘the best health you can imagine’ and ‘the worst health you can 
imagine’. This information can be used as a quantitative measure of health as judged by the 
individual respondents. The EQ VAS asks respondents to simply ‘mark an X on the scale to 
indicate how your health is TODAY’ and then to ‘write the number you marked on the scale in 
the box below’.  
The EQ-5D-5L Crosswalk Index Value Calculator can be found using the following link: 
https://euroqol.org/eq-5d-instruments/eq-5d-5l-about/valuation-standard-value-sets/crosswalk-
index-value-calculator/ 
13.4. 
Calculation of 95% CI for Incidence Rate per 100 Subject-Years of 
Exposure/Observation 
We first construct a formula to calculate the exact 100(1-α)% 2-sided CI for the number of 
events in a time interval.  When this formula is applied to the number of events in a time interval 
of 100 subject-years in a study, we obtain the desired result to construct Fisher’s exact 2-sided 
100(1-α)% confidence interval for an incidence rate of interest per 100 subject-years.  When α = 
0.05, it provides a 95% CI.   
The number of events of interest in a time interval can be modelled using a Poisson distribution 
with parameter λ, where λ is the average number of events in this time interval.  The probability 
of observing k events in this time interval is:  
P(k events in interval) = 𝑒−λ λ𝑘
𝑘! 
If k events were observed in the interval, the lower bound 𝑙 and upper bound 𝑢 of the 100(1-α)% 
CI must satisfy the following conditions for Fisher’s exact CI: 
 
 
Lower bound: ∑
𝑒−𝑙𝑙𝑥
𝑥!
= 1 −𝛼
𝑘
𝑥=0
/2 
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Upper bound: ∑
𝑒−𝑢𝑢𝑥
𝑥!
= 1 −𝛼
𝑘
𝑥=0
/2 
The parameter λ can be estimated with k.  Using the relationship between the cumulative 
distribution functions of the Poisson and chi-squared distributions, the above lower and upper 
bounds can be expressed as follows:  
 
 
 
1
2 𝑥2(
𝛼
2 ; 2𝑘) ≤𝜆≤
1
2 𝑥2(1 −
𝛼
2 ; 2𝑘+ 2),           (1)  
 
      
 
 
 
where 𝑥2(𝑎; 𝑣) is the chi-square quantile for lower tail probability with v degrees of freedom. 
The inequalities in (1) are used in the SAS macro below to construct the confidence interval for 
the number of events. The lower bound, number of events, and upper bound are divided by the 
total treatment exposure expressed as subject-year to construct the incidence rate and its CI.  
Each number is then multiplied by 100 to obtain the incidence rate per 100 subject-years. 
 
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SAS Macro for the 95% CI of incidence rate per 100 subject-years 
 
%macro nppy(x=5, n=100, alpha=0.05); 
 ***  x=5 --# of events; 
 ***  n = # of subject-years.; 
 ***  alpha=2-sided type-I error rate, alpha=0.05 for 95% CI.; 
 
data temp; 
 x=&x; 
 n=&n; 
 alpha=&alpha; 
 length CI_coverage $12.; 
 CI_coverage=compress(round(100*(1-&alpha), 0.1))||'%'; 
 r=round((x/n)*100, 0.001); 
if x=0 then Lower_bound=0; 
 else Lower_bound = round((quantile('CHISQ',&alpha/2,2*&x)/2/n)*100, 0.001); 
  Upper_bound = round((quantile('CHISQ',1-&alpha/2,2*(x+1))/2/n)*100, 0.001); 
 
label x='# of events' 
 
 
 
 
n='# subject years' 
 
 
 
 
r='# of events per 100 subject-years' 
 
 
 
 
alpha='2-sided alpha'; 
call symput('ci', compress(ci_coverage)); 
proc print data=temp label noobs; 
  title1 "&CI confidence interval for # of events per 100 subject-years"; 
 
title2 '--Exact method using the relationship between Poisson and Chi Square 
distributions'; 
run; 
%mend; 
 
*%nppy(x=14, n=400, alpha=0.05); 
 
 
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6LJQDWXUH3DJHIRU5,0&/,1Y
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Clinical Study Report
KPL-914-C002
Page 109


 
 
 
 
 
CHANGES TO STATISTICAL ANALYSIS PLAN 
 
 
PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED 
WITHDRAWAL STUDY WITH OPENLABEL EXTENSION, TO ASSESS THE 
EFFICACY AND SAFETY OF RILONACEPT TREATMENT IN SUBJECTS WITH 
RECURRENT PERICARDITIS – Rilonacept inHibition of interleukin-1 Alpha and beta 
for recurrent Pericarditis: a pivotal Symptomatology and Outcomes stuDY (RHAPSODY) 
 
 
 
 
Sponsor: 
 
Kiniksa Pharmaceuticals, Ltd. 
 
 
 
 
Study Drug: 
Rilonacept (KPL-914) 
Protocol Number:  
KPL-914-C002 
Date of Issue: 
June 16, 2020 
 
 
CONFIDENTIALITY STATEMENT 
The information in this document is the property of Kiniksa Pharmaceuticals, Ltd. and contains proprietary and 
confidential information to be held in strict confidence and not disclosed to any third party, without prior written 
consent of Kiniksa Pharmaceuticals, Ltd. Persons within your organization to whom any information herein is 
disclosed is on a need-to-know basis solely to carry out the purpose of this document, and be informed that such 
information is confidential and shall not be further disclosed by them without prior written consent from Kiniksa 
Pharmaceuticals, Ltd.  Documentation, data, and all other information generated during the clinical study is 
proprietary and confidential information of Kiniksa Pharmaceuticals, Ltd. and shall not be disclosed to any third 
party, without prior written consent of Kiniksa Pharmaceuticals, Ltd.
Clinical Study Report
KPL-914-C002
Page 110


Change to Statistical Analysis Plan 
 
Kiniksa Pharmaceuticals, Ltd. 
 
 
Study KPL-914-C002 
 
 
Confidential 
        Page 2 of 4 
 
 
Draft Statistical Analysis Plan (Version 1.0) for KPL-914-C002 was submitted to FDA on 
03APR2020. Final SAP version 2.0 was signed off on 16JUN2020. This document summarized the 
changes made to the draft version submitted to FDA. 
Analysis in the draft SAP 
submitted to FDA on 03APR2020 
Analysis in the final singed off 
version 1.0 
Reason  
Section 3.4: Subgroups to be 
Analyze 
Type of pericarditis: idiopathic, post 
pericardiotomy syndrome, 
Dressler’s syndrome, and Still’s 
disease 
 
Deleted  
 
 
 
 
Categories are almost 
identical to categories for 
diagnosis of recurrent 
idiopathic pericarditis (RI 
baseline): yes or no 
Section 4: included Run-in Week 12 
Analysis Set 
Removed Run-in Week 12 
Analysis Set 
All subjects enrolled 12 
weeks before the cutoff. 
  
Section 5.1.3 and 5.1.5: Baseline 
and concomitant pericarditis 
medication categories: 
− Non-opioid analgesics 
− Opioid analgesics 
− Aspirin 
− NSAIDs 
− Colchicine  
− Oral corticosteroids 
− IM/IV corticosteroids 
− Other 
 
Baseline and concomitant 
pericarditis medication 
categories: 
− Analgesics 
− Non-opioid analgesics 
− Opioid analgesics 
− NSAIDs 
− Aspirin 
− Other NSAIDs 
− Colchicine  
− Corticosteroids 
− Oral corticosteroids 
− IM/IV corticosteroids 
− Other 
To reorganize categories 
Throughout the SAP: rescue 
medications (ORT or prednisone) 
rescue medications (ORT or 
corticosteroid) 
To change the wording 
from “prednisone” to 
“corticosteroid” to 
include all types of 
corticosteroid 
 
Section 5.2.1.1: Table 1 has no 
footnote 
 
 
 
 
 
 
Added footnote below to Table 1 
“*Excluding subjects receiving 
ORT/corticosteroid while 
waiting for at least 5 days since 
previous administration of study 
medication before receiving 
bailout rilonacept or within 5 
days prior to recurrence visit.” 
 
To clarify the definition 
of using 
ORT/Corticosteroid. 
 
 
 
 
 
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Change to Statistical Analysis Plan 
 
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Confidential 
        Page 3 of 4 
 
 
Analysis in the draft SAP 
submitted to FDA on 03APR2020 
Analysis in the final singed off 
version 1.0 
Reason  
Section 5.2.2.3 endpoint #9 time to 
CRP 
Removed condition of CRP 
increase caused of pericarditis 
recurrence from the definition. 
CRP increase is not 
specific to pericarditis 
recurrence. However, it 
is challenging to 
determine whether a CRP 
increase is caused by 
pericarditis recurrence or 
not. So, we decided to 
remove this condition. 
Section 5.2.2.3 endpoint #13: 
Change in ECHO pericardial 
effusion size will be summarized by 
before and including bailout 
rilonacept in each arm.   
Deleted  
Central ECHO data 
collected change from 
previous visit which is 
not change from baseline. 
Shift tables for effusion 
size were produced to 
summarize the change 
from baseline. 
 
Section 5.2.2.3 endpoint #16: The 
CMH test stratified by the 
randomization strata will be applied. 
Deleted  
SAP specified that for 
Endpoints 14-16, p-
values will not be 
provided.  This sentence 
was left in the SAP 
inadvertently. 
 
Section 5.2.3.1 endpoint #1 time to 
pain response 
Add “If one or more daily NRS 
score is missing, rolling average 
will be considered not meeting 
the response criteria.” 
 
To clarify pain response 
criteria. 
Clinical Study Report
KPL-914-C002
Page 112


Change to Statistical Analysis Plan 
 
Kiniksa Pharmaceuticals, Ltd. 
 
 
Study KPL-914-C002 
 
 
Confidential 
        Page 4 of 4 
 
 
Analysis in the draft SAP 
submitted to FDA on 03APR2020 
Analysis in the final singed off 
version 1.0 
Reason  
Section 5.2.3.1 endpoint #4 Time to 
treatment response defined as time 
from first dose to the first day of 
pain response, and CRP ≤0.5 within 
7 days before or after pain response. 
Treatment response day will be the 
first day that the above criterion is 
met. If pain response occurs before 
CRP ≤0.5, each 3-day rolling 
average of NRS should be ≤2.0 from 
the day of pain response to the day 
of CRP ≤0.5. The response day will 
be the day of pain response.  If CRP 
≤0.5 occurs before pain response, 
the response day will also be the day 
of pain response. 
 
Time to treatment response 
defined as time from first dose to 
the first day of pain response 
(defined in endpoint 1 above), 
and CRP ≤0.5 mg/dL within 7 
days before or after pain 
response. Treatment response day 
will be the day of pain response, 
whether pain response occurs 
before or after CRP ≤0.5 mg/dL.   
 
Simplify definition and 
not requiring all 3-day 
rolling averages ≤2 
before CRP≤0.5 
 
Add the following analysis to 
Section 5.2.3.1 endpoint #5 
proportion of subjects achieving 
clinical response at RI week 12: 
Additional analysis will be done 
base done the completers who 
finished the 12-weeks of RI 
treatment 
Add analysis for different 
analysis population 
 
Add a new Section 11.2 for 
impact of COVID-19 pandemic 
To evaluate the COVID-
19 pandemic impact on 
study 
 
 
 
 
Clinical Study Report
KPL-914-C002
Page 113

Prot_000.pdf: 
Clinical Study Report 
KPL-914-C002 
KPL-914-C002 Protocol 
Version 1.0,  25 Sep 2018 ................................................................................................................................................... 2 
Version 1.1,  05 Oct 2018 ................................................................................................................................................ 144 
Note to File (Administrative Changes Justification), Version 1.1 ....................................................................................... 286 
Version 2.0,  12 Apr 2019 ................................................................................................................................................ 288 
Summary of Changes, Version 2.0 .................................................................................................................................. 426 
Version 3.0, 10 Mar 2020 ............................................................................................................................................... 433 
Page 1 
 


Kiniksa Pharmaceuticals, Ltd. 
CLINICAL STUDY PROTOCOL 
PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
RANDOMIZED WITHDRAWAL STUDY WITH OPEN-LABEL 
EXTENSION, TO ASSESS THE EFFICACY AND SAFETY OF 
RILONACEPT TREATMENT IN SUBJECTS WITH 
RECURRENT PERICARDITIS – Rilonacept inHibition of 
interleukin-1 Alpha and beta for recurrent Pericarditis: a pivotal 
Symptomatology and Outcomes stuDY 
(RHAPSODY) 
VERSION 1.0, 26 September 2018 
IND: 
EudraCT: 
136,896 
2018-002719-87 
1 
Page 2 
CONFIDENTIALITY STATEMENT 
The information contained in this document, particularly unpublished data, is the property of Kiniksa Pharmaceuticals, 
Ltd., and is provided to you in confidence as an investigator, potential investigator, or consultant, for review by you, 
members of your staff who have a need to know the information, and an applicable Institutional Review Board or 
Independent Ethics Committee. You agree that the information contained herein shall be held in strict confidence and is 
only to be used by you and your staff as necessary to conduct the authorized clinical studies of the investigational drug 
described in the protocol. Documentation, data, and all other information generated during the study is the property of 
Kiniksa Pharmaceuticals, Ltd. and will be held in strict confidence by you and members of your staff. You further 
agree to not publish or otherwise disclose any of the information to others without written authorization from Kiniksa 
Pharmaceuticals, Ltd., except to the extent necessary to obtain informed consent from those persons to whom the drug 
may be administered. 
 


KPL-914-C002 
Sponsor: 
Sponsor Study Contact: 
Sponsor Medical Contact 
Medical Monitor: 
Version of Protocol: 
Date of Protocol: 
Version 1.0 
26 September 2018 
2 
Page 3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Kiniksa Plwnnaceuticals, Ltd. 
Rilonacept l KPL-914) 
Protocol KPL-914-CO()]. 
Version 1.0, 26 Sep 2018 
Protocol Approval - Sponsor Signatory 
Phase 3, double-blind, placebo-controlled, randomized \Vithdrmval study ,vith 
open-label extension. to assess the efficacy and safety of rilonacept treatment 
in subjects with recurrent pericarditis (RHAPSODY) 
Study Title 
KPL-914-C002 
Protocol Number 
26 September 2018 
Protocol Date 
Protocol accepted and approved by· 
Chief Medical Officer 
Page 4 
 
 
 
 


Protocol [(P[,-9 I 4-C002 
Version 1.0, 26 Sep 20 I 8 
Kiniksa Phannaceuticals, Ltd. 
Rilona1:ept (KPL-9141 
Protocol Approval - Lead Statistician 
Phase 3, double-blind, placebo-controlled, randomized withdrm'val study with 
open-label extension, to assess the efficacy and safety of rilonacept treatment 
in subjects v,·ith recurrent pericarditis (RHAPSODY) 
Study Title 
KPL-914-C002 
Protocol Number 
26 September 2018 
Protocol Date 
Protocol accepted and approved by· 
Lead Statistician 
4 
Page 5 
 
 
 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Declaration of Investigator 
I have read and understood all sections of the protocol entitled “Phase 3, double-blind, placebo-
controlled, randomized withdrawal study with open-label extension, to assess the efficacy and safety 
of rilonacept treatment in subjects with recurrent pericarditis (RHAPSODY)” and the accompanying 
Investigator’s Brochure. 
I agree to supervise all aspects of the protocol and to conduct the clinical investigation in accordance 
with the Final Protocol Version 1, dated 26 September 2018, the International Council for 
Harmonisation tripartite guideline E6(R2): Good Clinical Practice and all applicable government 
regulations. I will not make changes to the protocol before consulting with Kiniksa Pharmaceuticals 
or implement protocol changes without Institutional Review Board Independent Ethics Committee 
approval except to eliminate an immediate risk to subjects. I agree to administer study drug only to 
subjects under my personal supervision or the supervision of a sub-investigator. 
I will not supply the investigational drug to any person not authorized to receive it. Confidentiality 
will be protected. Subject identity will not be disclosed to third parties or appear in any study reports 
or publications. 
I will not disclose information regarding this clinical investigation 
investigation without authorization from Kiniksa Pharmaceuticals. 
or publish results of the 
Signature of Principal Investigator 
Date 
Printed Name of Principal Investigator 
5 
Page 6 
 
 
 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
TABLE OF CONTENTS 
TABLE OF CONTENTS ..................................................................................................... 6 
LIST OF TABLES..............................................................................................................11 
LIST OF FIGURES............................................................................................................11 
PROTOCOL SYNOPSIS ................................................................................................... 13 
STUDY SCHEDULE OF ACTIVITIES ............................................................................ 20 
LIST OF ABBREVIATIONS............................................................................................. 28 
1 
Introduction ................................................................................................................ 30 
1.1 
1.2 
1.3 
Current Therapeutic Management of Pericarditis ................................................. 31 
Pathogenesis of Recurrent Pericarditis: Role of IL-1 ............................................ 31 
Rilonacept (KPL-914) .......................................................................................... 33 
1.3.1 
1.3.2 
Safety of Rilonacept .............................................................................. 34 
KPL-914-C001 Study with Rilonacept (KPL-914) in Recurrent 
Pericarditis ............................................................................................ 36 
2 
Study Objectives and Endpoints ................................................................................ 36 
2.1 
2.2 
Primary Objective ................................................................................................ 36 
Secondary Objective ............................................................................................ 37 
3 
Investigational Plan .................................................................................................... 37 
3.1 
Study Design ....................................................................................................... 37 
3.1.1 
3.1.2 
3.1.3 
Screening Period (up to 4 weeks)........................................................... 37 
Single-blind Run-In (RI) Period (12 weeks). ......................................... 37 
Double-blind Placebo-controlled RW Period (pericarditis recurrence 
event-driven duration with a minimum of 24 weeks) ............................. 38 
Long Term Extension Treatment Period (LTE-TP) (24 weeks) .............. 39 
Long Term Extension Follow-Up Period (LTE-FUP) (24 weeks)........... 39 
Rationale of Study Design ..................................................................... 41 
Justification for Rilonacept Dose Selection ............................................ 42 
3.1.4 
3.1.5 
3.1.6 
3.1.7 
4 
Subject Selection and Withdrawal Criteria ............................................................... 43 
4.1 
Selection of Study Population .............................................................................. 43 
4.1.1 
4.1.2 
Inclusion Criteria ................................................................................... 44 
Exclusion Criteria.................................................................................. 45 
4.2 
Subject Completion, Withdrawal from Study, and Study Drug Discontinuation ... 49 
4.2.1 
4.2.2 
Completion ........................................................................................... 49 
Reasons for Discontinuation of Study Drug and Study Withdrawal ........ 49 
6 
Page 7 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
4.2.2.1 
4.2.2.2 
Discontinuation of Study Drug .............................................................. 49 
Withdrawal from the Study ................................................................... 50 
5 
Study Treatments ........................................................................................................ 51 
5.1 
5.2 
5.3 
5.4 
Method of Assigning Subjects to Treatment Groups ............................................. 51 
Treatments Administered ..................................................................................... 52 
Identity of Investigational Medicinal Product ....................................................... 53 
Management of Clinical Supplies......................................................................... 54 
5.4.1 
5.4.2 
5.4.3 
Study Drug Product Packaging and Storage ........................................... 54 
Study Drug Accountability .................................................................... 54 
Other Supplies ....................................................................................... 55 
5.5 
Study Drug Overdose ........................................................................................... 55 
5.5.1 
5.5.2 
Treatment of Study Drug Overdose ....................................................... 55 
Other Study Drug Errors ........................................................................ 56 
5.6 
5.7 
5.8 
Transmission of Infectious Agents ....................................................................... 56 
Misuse for Illegal Purposes .................................................................................. 56 
Prior and Concomitant Medications ..................................................................... 56 
5.8.1 
5.8.2 
5.8.3 
5.8.3.1 
5.8.4 
5.8.5 
5.8.6 
Screening .............................................................................................. 57 
Single-blind RI Period ........................................................................... 57 
Double-blind Placebo-controlled RW Period ......................................... 58 
Concomitant Medication Upon Pericarditis Recurrence ......................... 58 
Long Term Extension Treatment Period (LTE-TP) ................................ 59 
Long Term Extension Follow-Up Period (LTE-FUP) ............................ 59 
Prohibited Concomitant Medicines During the Study ............................ 59 
5.9 
Blinding. .............................................................................................................. 60 
5.9.1 
Breaking the Blind ................................................................................ 60 
5.10 Treatment Compliance ......................................................................................... 60 
6 
Study Assessments and Procedures ............................................................................ 61 
6.1 
Study Visits ......................................................................................................... 61 
6.1.1 
6.1.2 
6.1.2.1 
6.1.2.2 
6.1.2.3 
6.1.2.4 
6.1.2.5 
6.1.2.6 
Screening: Clinic and Remote as Needed ............................................... 61 
Single-blind Treatment: Run-In ............................................................. 63 
Enrollment (RI Baseline): Clinic Visit ................................................... 63 
RI Day 2: Clinic Visit (24-hour PK Substudy Participants Only) ............ 64 
RI Day 4: TC/RN Visit .......................................................................... 64 
RI Week 1: TC/RN Visit ....................................................................... 64 
RI Week 2: TC/RN Visit ....................................................................... 65 
RI Week 4: TC/RN Visit ....................................................................... 66 
7 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
6.1.2.7 
6.1.2.8 
6.1.2.9 
6.1.3 
6.1.3.1 
6.1.3.2 
6.1.4 
6.1.4.1 
6.1.4.2 
6.1.5 
6.1.5.1 
6.1.5.2 
6.1.6 
6.1.6.1 
6.1.6.2 
6.1.6.3 
RI Week 6: Clinic Visit ......................................................................... 67 
RI Week 10: TC Visit ............................................................................ 67 
Randomization (RI Week 12/RW Baseline): Clinic Visit ....................... 68 
Randomized-Withdrawal (RW) Period .................................................. 69 
RW WEEK 24: Clinic Visit ................................................................... 70 
EORW (End of RW Period/LTE Baseline): Clinic Visit ......................... 71 
Long Term Extension ............................................................................ 72 
LTE Weeks 8 and 16: Clinic Visit ......................................................... 72 
LTE Week 24 Clinic Visit ..................................................................... 73 
LTE Follow-Up Period .......................................................................... 74 
LTE Week 30 Visit: Clinic .................................................................... 74 
LTE Week 48 End of Study Visit: TC .................................................... 74 
Supplemental Visits ............................................................................... 75 
Pericarditis Recurrence Assessment: Clinic Visit ................................... 75 
End of Treatment Visit: Clinic ............................................................... 76 
Safety Follow-Up Visit: Clinic or TC/RN .............................................. 76 
6.2 
Efficacy Assessments ........................................................................................... 77 
6.2.1 
6.2.1.1 
6.2.1.2 
6.2.1.3 
6.2.1.4 
6.2.1.5 
6.2.1.6 
6.2.1.7 
6.2.1.8 
6.2.1.9 
6.2.1.10 
6.2.2 
Individual Efficacy Assessments ............................................................ 77 
C-Reactive Protein ................................................................................ 77 
11-Point Pericarditis Pain Numerical Rating Scale ................................. 78 
Electrocardiogram ................................................................................. 78 
Echocardiogram .................................................................................... 78 
Patient Global Impression of Pericarditis Severity ................................. 78 
Physician Global Assessment of Pericarditis Activity............................. 79 
36-Item Short Form Health Survey ........................................................ 79 
EQ-5D-5L ............................................................................................. 79 
Insomnia Severity Index ........................................................................ 80 
Cardiac MRI ......................................................................................... 80 
Assessment of Clinical Response at the End of the Run-In Period Week 
12/RW Baseline .................................................................................... 80 
Management of Suspected Pericarditis Recurrence in the RW Period..... 81 
6.2.3 
6.3 
Safety Assessments .............................................................................................. 82 
6.3.1 
6.3.2 
6.3.3 
6.3.4 
Physical Examination ............................................................................ 83 
Vital Signs ............................................................................................ 83 
Chest X-ray ........................................................................................... 83 
Tuberculosis Screening ......................................................................... 83 
6.4 
Adverse Events .................................................................................................... 83 
6.4.1 
Definitions ............................................................................................ 83 
8 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
6.4.1.1 
6.4.1.2 
6.4.1.3 
6.4.1.4 
6.4.1.5 
6.4.1.6 
6.4.2 
6.4.2.1 
6.4.2.2 
6.4.3 
6.4.3.1 
6.4.3.2 
6.4.3.3 
6.4.4 
6.4.5 
6.4.6 
6.4.6.1 
6.4.7 
6.4.8 
Adverse Event ....................................................................................... 83 
Treatment-emergent Adverse Event ....................................................... 84 
Serious Adverse Event ........................................................................... 84 
Adverse Event of Special Interest .......................................................... 85 
Adverse Reaction .................................................................................. 85 
Suspected Unexpected Serious Adverse Reaction .................................. 85 
Assessing Adverse Events ..................................................................... 85 
Relationship to Study Drug. ................................................................... 85 
Intensity ................................................................................................ 86 
Recording Adverse Events ..................................................................... 86 
Adverse Events Based on Signs and Symptoms ..................................... 87 
Adverse Events Based on Examinations and Tests ................................. 88 
Pericarditis Disease Related Events ....................................................... 88 
Time Period for Collection of Adverse Events ....................................... 88 
Follow-Up of Unresolved Adverse Events ............................................. 88 
Reporting Serious Adverse Events ......................................................... 88 
Other Reasons for Immediate Reporting ................................................ 89 
Pregnancy ............................................................................................. 89 
Evaluating and Reporting SUSARs ....................................................... 90 
6.5 
Other Assessments ............................................................................................... 90 
6.5.1 
6.5.2 
6.5.3 
6.5.4 
Pharmacokinetic Sample ....................................................................... 90 
Anti-Drug Antibodies (ADAs) against Rilonacept (KPL-914) ............... 91 
Biomarkers ............................................................................................ 91 
Pharmacogenomics................................................................................ 91 
6.6 
Laboratory Analyses ............................................................................................ 91 
6.6.1 
6.6.2 
6.6.3 
6.6.4 
6.6.5 
6.6.6 
6.6.7 
Serology ................................................................................................ 91 
Hematology ........................................................................................... 91 
Chemistry .............................................................................................. 92 
Non-fasting Lipid Panel ........................................................................ 92 
Urinalysis .............................................................................................. 92 
Pregnancy Test ...................................................................................... 92 
Sample Collection ................................................................................. 92 
6.7 
Committees.......................................................................................................... 93 
6.7.1 
6.7.2 
Independent Data Monitoring Committee (DMC) .................................. 93 
Clinical Endpoint Committee (CEC) ..................................................... 93 
7 
Statistical and Analytical Plan .................................................................................... 93 
7.1 
Primary Efficacy Endpoint ................................................................................... 93 
9 
Page 10 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
7.2 
Secondary Efficacy Endpoints for the RW Period................................................. 93 
7.2.1 
7.2.2 
Major Secondary Efficacy Endpoints ..................................................... 93 
Other Secondary Endpoints ................................................................... 94 
7.3 
Other Endpoints ................................................................................................... 95 
7.3.1 
7.3.2 
Efficacy Endpoints for the RI Period ..................................................... 95 
Efficacy Endpoints for the LTE-TP ....................................................... 96 
7.4 
7.5 
7.6 
7.7 
Sample Size Calculations ..................................................................................... 96 
Analysis Sets ....................................................................................................... 97 
Description of Subgroups to be Analyzed ............................................................. 98 
Statistical Analysis Methodology ......................................................................... 98 
7.7.1 
7.7.2 
7.7.3 
7.7.4 
7.7.5 
7.7.5.1 
7.7.5.2 
7.7.6 
7.7.7 
7.7.8 
7.7.9 
General Methods ................................................................................... 98 
Stratified Analysis ................................................................................. 98 
Testing Hypotheses and Multiplicity Adjustment ................................... 98 
Analysis of Primary Efficacy Endpoint .................................................. 99 
Analysis of Secondary Efficacy Endpoints............................................. 99 
Analysis of the Major Secondary Endpoints .......................................... 99 
Analyses of Other Secondary Endpoints in the RW Period .................. 100 
Analyses of Other Endpoints ............................................................... 101 
Pharmacokinetic Analyses ................................................................... 101 
Safety Analyses ................................................................................... 101 
Interim Analyses ................................................................................. 102 
8 
Data Quality Assurance ............................................................................................ 102 
8.1 
Data Management .............................................................................................. 102 
9 
Ethics ......................................................................................................................... 103 
9.1 
9.2 
9.3 
Independent Ethics Committee or Institutional Review Board ............................ 103 
Ethical Conduct of the Study ............................................................................. 103 
Subject Information and Consent ....................................................................... 103 
10 Investigator’s Obligations ......................................................................................... 104 
10.1 
10.2 
10.3 
10.4 
10.5 
10.6 
Confidentiality ................................................................................................... 104 
Financial Disclosure and Obligations ................................................................. 105 
Investigator Documentation ............................................................................... 105 
Study Conduct ................................................................................................... 105 
Adherence to Protocol........................................................................................ 106 
Adverse Events and Study Report Requirements ................................................ 106 
10 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
10.7 
10.8 
10.9 
Investigator’s Final Report ................................................................................. 106 
Records Retention .............................................................................................. 106 
Publications ....................................................................................................... 106 
11 Study Management ................................................................................................... 106 
11.1 Monitoring ......................................................................................................... 107 
11.1.1 
11.1.2 
Monitoring of the Study ...................................................................... 107 
Inspection of Records .......................................................................... 107 
11.2 Management of Protocol Amendments and Deviations ....................................... 107 
11.2.1 
11.2.2 
Modification of the Protocol ................................................................ 107 
Protocol Deviations ............................................................................. 107 
11.3 
11.4 
Study Termination ............................................................................................. 108 
Final Report ....................................................................................................... 108 
12 
13 
Reference List ........................................................................................................... 109 
Appendices ................................................................................................................ 111 
13.1 Appendix: ARCALYST® Prescribing Information .............................................. 111 
13.2 Appendix: 11-point Numerical Rating Scale (NRS) for Assessment of Pericarditis 
Pain ............................................................................................................ 142 
LIST OF TABLES 
Study Schedule of Activities – Screening and Run-In Period .............................. 20 
Table 1–1 
Table 1–2 
Study Schedule of Activities – Randomized Withdrawal .................................... 22 
Table 1–3 
Study Schedule of Activities – Long Term Extension ......................................... 24 
Table 1–4 
Study Schedule of Activities – Supplemental Visits ........................................... 26 
Table 5–1: 
Study Drug Dose Volume (After Reconstitution) by Body Weight in Kilograms 
for Pediatric Subjects Aged ≥12 and <18 Years .................................................. 53 
LIST OF FIGURES 
Schematic of Rilonacept (KPL-914) ................................................................... 34 
Figure 1: 
Figure 2: 
Overview of KPL-914-C002 Trial Design .......................................................... 40 
Figure 3: 
Management of Suspected Pericarditis Recurrence in the Randomized- 
Withdrawal Period ............................................................................................. 82 
11 
Page 12 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
12 
Page 13 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
PROTOCOL SYNOPSIS 
13 
Page 14 
Protocol Number: 
KPL-914-C002 
Title: 
Phase 3, double-blind, placebo-controlled, randomized withdrawal study with open-label extension, to 
assess the efficacy and safety of rilonacept treatment in subjects with recurrent pericarditis 
 
Study Acronym: 
Rilonacept inHibition of interleukin-1 Alpha and beta for recurrent Pericarditis: a pivotal 
Symptomatology and Outcomes stuDY 
RHAPSODY 
Sponsor: 
 
Study Phase: 
3 
Study Sites: 
Multicenter, global 
Indication: 
Recurrent pericarditis 
Study Rationale: 
Recurrent pericarditis is a rare autoinflammatory condition with no approved therapies. Current 
treatments, utilizing nonspecific inhibitors of inflammation (nonsteroidal anti-inflammatory drugs 
[NSAIDs], colchicine, corticosteroids [CS]), result in significant morbidity with chronic use. Some 
patients develop CS dependency or require surgical pericardiectomy to treat the symptoms of their 
disease. 
The interleukin-1 (IL-1) pathway plays a major role in the pathophysiology of recurrent pericarditis. 
Rilonacept (KPL-914) is a recombinant fusion protein that blocks IL-1 signaling. It is currently approved 
for treatment of another autoinflammatory condition, Cryopyrin-Associated Periodic Syndrome (CAPS). 
Based on its IL-1–antagonistic properties and pharmacokinetics (PK), which allow for once-weekly 
subcutaneous (SC) injections, it is reasonable to evaluate the efficacy and safety of rilonacept in subjects 
with recurrent pericarditis to address the unmet need in treatment of this disease. 
 
Study Objectives: 
Primary: 
To assess the efficacy of rilonacept treatment in subjects with recurrent 
pericarditis. 
Secondary: 
To assess the safety of rilonacept treatment in subjects with recurrent 
pericarditis. 
 
 
 
 
 
 
 
 
 
 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
14 
Page 15 
Study Population: 
Subjects eligible for the study are subjects with recurrent pericarditis who do not have pericarditis 
secondary to prohibited conditions. The study population includes both adult subjects ≥18 years old and 
pediatric subjects ≥12 and <18 years old with a history of at least 2 prior pericarditis episodes (including 
the first episode and 1 recurrence). Enrollment of pediatric subjects will be limited to up to 20% of the 
study population. To be eligible for the study, subjects must present at screening with at least a third 
pericarditis episode, defined as at least 1 day with pericarditis pain measurement ≥4 on the 11-point 
Numerical Rating Scale (NRS) and C-reactive protein (CRP) value ≥1 mg/dL (either on the same day or 
separated by no more than 7 days) within 7 days prior to first study drug administration. 
Subjects included in the study may be receiving concomitant NSAIDs and/or colchicine and/or oral CS 
treatment in any combination, provided that the dosages of these medications have been stable (or not 
increased) for at least 3 days prior to first administration of study drug, and that changes in medications 
made within this time period (for instance, 1-time use of NSAIDs) are not anticipated by the investigator 
to significantly alter assessments of baseline disease activity. 
 
Study Design: 
This study has 5 periods: 
(1) Screening period, during which assessment of disease characteristics, baseline therapy, and the 
pre-treatment workup is completed (up to 4 weeks) 
(2) Single-blind Run-In (RI) period (12 weeks), during which blinded rilonacept is administered SC 
once weekly in all subjects. The RI period includes the following: 
• 1-week Stabilization period, during which blinded rilonacept is administered in addition to standard 
of care (SOC) pericarditis therapy and the ongoing pericarditis episode is treated 
• 9-week Weaning period, during which subjects are weaned off background SOC pericarditis 
therapy, as applicable, while treatment with blinded rilonacept continues 
• 2-week Monotherapy period during which subjects who have successfully weaned off background 
SOC pericarditis therapy will continue to receive blinded rilonacept 
In the single-blind RI period (subjects are blinded regarding the time of transition from the 
single-blind to the double-blind period), adult subjects ≥18 years old will receive rilonacept as an 
initial loading dose of 320 mg (2 SC injections of 160 mg each) at the RI baseline visit (2 × 2 ml), 
followed by a 160 mg (2 ml) SC dose once weekly throughout the RI period. Pediatric subjects (≥12 and 
<18 years old) will receive an initial loading dose of rilonacept 4.4 mg/kg (2 SC injections of 2.2 mg/kg 
each) at the RI baseline visit (maximum 2 × 2 ml), and then 2.2 mg/kg (maximum 2 ml) SC once weekly 
throughout RI period. 
Subjects who stopped background SOC pericarditis therapy and who achieve Clinical Response at RI 
Week 12, defined as the weekly average of daily pericarditis pain score ≤2.0 on the 11-point NRS within 
the 7 days prior to and including the day of randomization on RI Week 12/Randomization Withdrawal 
(RW) baseline and a CRP level ≤0.5 mg/dL at the RI Week 12/RW baseline visit, will proceed into the 
double-blind placebo-controlled RW period. Subjects who do not achieve Clinical Response at 
 
 


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Study Design Continued 
RI Week 12/RW baseline on rilonacept monotherapy will be discontinued from study drug, transitioned 
to SOC 
pericarditis therapy at the investigator’s discretion and followed through the end of the RW period. 
(3) Double-blind placebo-controlled RW period (pericarditis recurrence event-driven duration, with a 
minimum of 24 weeks), during which subjects who were able to stop background SOC pericarditis 
therapy and who achieve Clinical Response at RI Week 12/RW baseline are randomized in a double-blind 
manner at a 1:1 ratio to the following: 
• Rilonacept 160 mg (2.2 mg/kg in pediatric subjects) SC injections once weekly 
• Matching placebo SC injections once weekly 
Pericarditis Recurrence in the RW Period 
Pericarditis recurrence is defined as the recurrence of typical pericarditis pain associated with supportive 
objective evidence of pericarditis. Upon pericarditis recurrence, subjects who report at least 1 day with 
pericarditis pain measurement ≥4 on the 11-point NRS and have 1 CRP value ≥1 mg/dL (either on the 
same day or separated by no more than 7 days) will receive bailout rilonacept (2 open-label injections of 
160 mg rilonacept [or 4.4 mg/kg for pediatric subjects] followed by once-weekly open-label rilonacept 
SC injections of 160 mg [or 2.2 mg/kg for pediatric subjects]). irrespective of randomized treatment 
assignment and as soon as at least 5 days have passed since the last study drug injection. Sequential Oral 
Rescue Therapy (ORT), i.e., analgesics first, then NSAIDs, and then colchicine, can be added if needed at 
the discretion of the investigator, as outlined in the protocol and Pharmacy Manual. 
Subjects with pericarditis recurrence and who do not meet the protocol criteria for bailout rilonacept will 
continue blinded study drug until the protocol criteria for bailout rilonacept are met or through the end of 
the RW period. For those subjects, sequential ORT can be added to blinded study drug at the discretion of 
the investigator, as outlined in the protocol and Pharmacy Manual. 
All suspected pericarditis recurrence events in the RW period will be formally adjudicated by the Clinical 
Endpoint Committee (CEC), and only events that are confirmed by the CEC as pericarditis recurrences 
will be used in the Primary Endpoint analysis. 
(4) Long Term Extension Treatment Period (LTE-TP) (24 weeks), during which all subjects 
completing the RW period (including subjects transitioned to open-label rilonacept upon pericarditis 
recurrence) will have an option to receive up to 24 weeks of open-label rilonacept 160 mg (or 2.2 mg/kg 
for pediatric subjects) SC injections once weekly based on their clinical status and at the discretion of the 
investigator, after signing LTE informed consent. Any subject who, in the opinion of investigator, should 
not continue open-label rilonacept will be offered participation in the LTE off study drug and after 
signing LTE informed consent. 
(5) Long Term Extension Follow-Up Period (LTE-FUP) (24 weeks), during which all subjects in the 
LTE-TP will be followed in the LTE-FUP for safety and potential pericarditis recurrences. 
 
 


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Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
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Estimated Study Duration: 
Subjects completing LTE-TP are projected to be dosed with rilonacept for a minimum of approximately 
1.2 years and up to 3 years based on enrollment assumptions and pericarditis recurrence events accrual 
time. 
 
Study Efficacy Assessments: 
• Daily pericarditis pain on the 11-point NRS in the subject’s electronic diary 
• CRP level 
• Electrocardiogram (ECG) 
• Echocardiography (ECHO) 
• Patient Global Impression of Pericarditis Severity (PGIPS) 
• Physician Global Assessment of Pericarditis Activity (PGA-PA) 
• 36-Item Short Form Health Survey (SF-36) 
• 5-Level EuroQoL-5D (EQ-5D-5L) 
• Insomnia Severity Index (ISI) 
• Cardiac magnetic resonance imaging (in a substudy in approximately 10 subjects) 
 
Study Pharmacokinetic or Pharmacodynamic Assessments: 
Pharmacokinetic or pharmacodynamic assessments will include: 
• PK analysis 
• Anti-rilonacept antibodies 
• Biomarkers 
• Peripheral blood mononuclear cell isolation (for subjects who sign the separate informed consent 
for pharmacogenomics assessments) 
 
Study Safety Assessments: 
Safety assessments during the study will include: 
• Physical examination 
• Vital signs measurements 
• Adverse event (AE) monitoring 
• Chest x-ray 
• Tuberculosis screening 
• Laboratory tests 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
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Investigational Medicinal Product, Dosage, and Route of Administration: 
Rilonacept (KPL-914) is a recombinant fusion protein consisting of the extracellular domains of human 
IL-1 cytokine receptor and the Fc portion of human immunoglobulin G1 (IgG1). It acts as a soluble decoy 
receptor binding IL-1α/IL-1β and prevents their interaction with the IL-1 cell-surface receptor. 
Study drug (rilonacept or placebo) is supplied in a single use, 20 ml glass vial containing a sterile, white 
to off-white, lyophilized powder. Each vial is to be reconstituted with 2.3 ml sterile Water for Injection 
(WFI). A volume up to 2 ml can be withdrawn, which is designated to deliver up to 160 mg of rilonacept 
or up to 2 ml of placebo for SC injection only. The resulting solution is clear, colorless to pale yellow, 
and essentially free of particulates. 
Each rilonacept vial contains 220 mg of rilonacept lyophilized powder. After reconstitution with 2.3 ml 
WFI, the rilonacept vial contains 80 mg/ml rilonacept, 40 mM histidine, 50 mM arginine, 3.0% (w/v) 
polyethylene glycol 3350, 2.0% (w/v) sucrose, and 1.0% (w/v) glycine at a pH of 6.5. No preservatives 
are present. 
The first injection of rilonacept loading dose at the RI baseline visit will be administered at the study site 
by study site staff. The second injection of rilonacept loading dose at the RI baseline visit will be prepared 
and administered by the subject or the subject’s caregiver after adequate training and under the 
supervision of study site personnel. Subsequent once-weekly study drug doses will be self-administered 
SC by the subject or administered to the subject by a trained caregiver as an outpatient SC administration. 
 
Sample Size: 
Approximately 56 subjects (not to exceed 75 subjects) with recurrent pericarditis will be enrolled, which 
will allow approximately 50 subjects to be randomly assigned to blinded treatment. 
 
Statistical Methods: 
The primary efficacy endpoint is time to pericarditis recurrence, defined as the time from randomization 
to the date of the first pericarditis recurrence for each subject. Only CEC-confirmed pericarditis 
recurrence will be considered as an event for the primary efficacy analysis. A sensitivity analysis will be 
done based on the investigator’s assessment of the pericarditis recurrence. 
In order to control the overall 1-sided type I error rate at the 0.025 level, a gatekeeping procedure in 
combination with Hochberg’s procedure will be applied to testing the primary and major secondary 
efficacy endpoints. 
Major secondary efficacy endpoints for the RW period include: 
• Proportion of subjects who maintained Clinical Response at Week 24 of the RW period 
• Percentage of days with no or minimal pain (pain ≤1 on the 11-point NRS) in the first 24 weeks of 
the RW period 
• Proportion of subjects with absent or minimal pericarditis symptoms (based on the 7-point rating 
scale of PGIPS) at Week 24 of the RW period 
Other secondary efficacy endpoints for the RW period include: 
• Proportion of subjects without pericarditis recurrence in the first 24 weeks of the RW period 
• Time to pericarditis pain NRS ≥4 
 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
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Statistical Methods Continued: 
• Time to CRP level ≥1 mg/dL 
• Time to pericardial rub 
• Time to widespread ST-segment elevation or PR-segment depression on ECG 
• Time to new or worsening pericardial effusion on ECHO 
• Change over time in CRP levels 
• Change over time in subject’s assessments of pericarditis pain (weekly average) 
• Proportion of subjects with absent or minimal pericarditis activity based on Physician Global 
Assessment of Pericarditis Activity (PGA-PA) 
• Change over time in SF-36 Physical Component Score 
• Change over time in SF-36 Mental Component Score 
• Change in EQ-5D-5L 
• Change over time in subject’s sleep quality assessed with the ISI 
• Change over time in ISI categories 
• Number (percentage) of subjects who receive sequential ORT therapy for pericarditis recurrence 
(analgesics, NSAIDs, and/or colchicine) in the RW period 
Efficacy endpoints for the RI period include: 
• Proportion of subjects who achieved Clinical Response at the RI Week 12 visit 
• Time to CRP normalization 
• Number (percentage) of subjects with normalization of CRP at RI Week 12 
• Change from baseline in pericarditis pain at RI Week 12 
• Change from baseline in CRP level at RI Week 12 
• Resolution of echocardiographic and ECG abnormalities (yes/no) at RI Week 12 
• Percentage of days with no or minimal pain 
• Proportion of subjects with absent or minimal pericarditis symptoms based on the PGIPS 
• Proportion of subjects with absent or minimal pericarditis activity based on the PGA-PA 
• Change over time in SF-36 Physical Component Score 
• Change over time in SF-36 Mental Component Score 
• Change in EQ-5D-5L 
• Change over time in subject’s sleep quality assessed with the ISI 
• Change over time in ISI categories 
• Number (percentage) of subjects who were off background SOC pericarditis therapy at RI Week 12 
Efficacy endpoints for the LTE-TP include: 
• Number (percentage) of subjects with pericarditis recurrences 
• Proportion of subjects with Clinical Response 
• Change over time in CRP levels 
• Change over time in subject’s assessments of pericarditis pain 
• Percentage of days with no or minimal pain 
• Proportion of subjects with absent or minimal pericarditis symptoms based on PGIPS 
• Proportion of subjects with absent or minimal pericarditis activity based on PGA-PA 
 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
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Statistical Methods Continued: 
• Change over time in SF-36 Physical Component Score 
• Change over time in SF-36 Mental Component Score 
• Change in EQ-5D-5L 
• Change over time in subject’s sleep quality assessed with the ISI 
• Change over time in ISI categories 
• Number (percentage) of subjects requiring addition of SOC pericarditis therapy 
Primary analysis of this study will be done after the 22nd CEC-confirmed pericarditis recurrence and after 
all subjects in the RW period have been treated for 24 weeks. Subjects who have not had an adjudicated 
pericarditis recurrence will be censored on the day of the last available assessment before data cutoff. 
Details of the analyses will be specified in the Statistical Analysis Plan. 
 
Protocol Version 
Version 1.0 
and Date: 
26 Sep 2018 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
STUDY SCHEDULE OF ACTIVITIES 
Table 1–1 
Study Schedule of Activities – Screening and Run-In Period (Part 1 of 2) 
a 
The screening and enrollment visit can be combined. 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Full physical examination includes at minimum evaluation of vital signs, head, eye, ear, nose, and throat as well as cardiovascular, dermatological, musculoskeletal, respiratory, GI, 
genitourinary, and neurological systems 
Abbreviated physical examination includes at minimum evaluation of vital signs, lung and heart sounds, including evaluation for pericardial rub 
ECHO is required to be obtained according to the central core lab parameters and then read locally and submitted to the central core lab for separate review and analysis. 
Both a documented CRP > 1.0 mg/dL AND a pericarditis pain level of > 4 is required 7 days prior to and including the Run-In Baseline visit. These are not required to occur on the same 
day. 
Subjects missing ≥ 4 daily pain measurements during the 7 days prior to and including the Randomization Withdrawal baseline visit will be unable to proceed to randomization due to lack 
of data required for treatment response evaluation. 
All procedures are to be completed prior to study drug administration. 
b 
c 
d 
e 
f 
g 
m 
20 
q 
The Randomization visit serves as both the RI Week 12 visit and the RW baseline visit. 
Page 21 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Table 1–1 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Study Schedule of Activities – Screening and Run-In Period (Part 2 of 2) 
a 
The screening and enrollment visit can be combined. 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Both a documented CRP > 1.0 mg/dL AND a pericarditis pain level of > 4 is required 7 days prior to and including the Run-In Baseline visit. These are not required to occur on the same day. 
Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the randomization withdrawal and LTE periods, or more frequently as needed, with mandated evaluations as detailed in the 
schedule of events. 
Applicable to 24-hour post dose PK sub-study participants only. 
For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout the course of the study and serum pregnancy can be drawn as needed; urine pregnancy is required to be performed 
at enrollment and 6 weeks after the last dose of study drug. 
Pharmacogenomics informed consent and subsequent sampling can be performed at any time in the study however, it is preferable to have this completed at the beginning of the study. 
Adverse event reporting begins following the subject providing informed consent. 
All procedures are to be completed prior to study drug administration. 
The first dose of study drug is a loading dose. Adult subjects receive 2 SC doses 160 mg (total 320 mg); pediatric subjects (subjects ≥12 and <18 years of age) receive 2 SC doses of 2 x 2.2 mg/kg. 
Study drug administration is once weekly with a minimum of 5 days required between doses. 
Randomization and subsequent study drug dispensing to occur after confirmation of Clinical Response (see definition of Clinical Response in Section 6.2.2). 
b 
f 
h 
i 
j 
k 
l 
m 
n 
o 
p 
q 
The Randomization visit serves as both the RI Week 12 visit and the RW baseline visit. 
21 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Table 1–2 
Study Schedule of Activities – Randomized Withdrawal (Part 1 of 2) 
b 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Full physical examination includes at minimum evaluation of vital signs, head, eye, ear, nose, and throat as well as cardiovascular, dermatological, musculoskeletal, respiratory, GI, 
genitourinary, and neurological systems 
Abbreviated physical examination includes at minimum evaluation of vital signs, lung and heart sounds, including evaluation for pericardial rub 
ECHO is required to be obtained according to the central core lab parameters and then read locally and submitted to the central core lab for separate review and analysis. 
All procedures are to be completed prior to study drug administration. 
The EORW visit serves as both the last visit of the RW period and the baseline visit of the LTE period. 
For all subjects, the final clinic visit of the end of RW period is to be scheduled once the End of the Randomization Withdrawal end date is announced by Sponsor. This includes subjects 
that are taking blinded study drug, open-label rilonacept, or who have prematurely discontinued study drug. 
c 
d 
e 
m 
t 
u 
22 
Page 23 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Table 1–2 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Study Schedule of Activities – Randomized Withdrawal (Part 2 of 2) 
b 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the randomization withdrawal and LTE periods, or more frequently as needed, with mandated evaluations as detailed in the 
schedule of events. 
For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout the course of the study and serum pregnancy can be drawn as needed; urine pregnancy is required to be 
performed at enrollment and 6 weeks after the last dose of study drug. 
Adverse event reporting begins following the subject providing informed consent. 
All procedures are to be completed prior to study drug administration. 
Study drug administration is once weekly with a minimum of 5 days required between doses. 
The EORW visit serves as both the last visit of the RW period and the baseline visit of the LTE period. 
For all subjects, the final clinic visit of the end of RW period is to be scheduled once the End of the Randomization Withdrawal end date is announced by Sponsor. This includes subjects that are taking blinded study 
drug, open-label rilonacept, or who have prematurely discontinued study drug. 
Study drug administration to occur only after subject provides informed consent for the open-label extension period. 
h 
j 
l 
m 
o 
t 
u 
v 
23 
Page 24 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Table 1–3 
Study Schedule of Activities – Long Term Extension (Part 1 of 2) 
b 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Full physical examination includes at minimum evaluation of vital signs, head, eye, ear, nose, and throat as well as cardiovascular, dermatological, musculoskeletal, respiratory, GI, 
genitourinary, and neurological systems 
ECHO is required to be obtained according to the central core lab parameters and then read locally and submitted to the central core lab for separate review and analysis. 
All procedures are to be completed prior to study drug administration. 
c 
e 
m 
24 
24 
Page 25 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Table 1–3 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Study Schedule of Activities – Long Term Extension (Part 2 of 2) 
b 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the randomization withdrawal and LTE periods, or more frequently as needed, with mandated 
evaluations as detailed in the schedule of events. 
For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout the course of the study and serum pregnancy can be drawn as needed; urine pregnancy 
is required to be performed at enrollment and 6 weeks after the last dose of study drug. 
Adverse event reporting begins following the subject providing informed consent. 
All procedures are to be completed prior to study drug administration. 
Study drug administration is once weekly with a minimum of 5 days required between doses. 
h 
j 
l 
m 
o 
25 
Page 26 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Table 1–4 
Study Schedule of Activities – Supplemental Visits (Part 1 of 2) 
b 
c 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Full physical examination includes at minimum evaluation of vital signs, head, eye, ear, nose, and throat as well as cardiovascular, dermatological, musculoskeletal, respiratory, GI, 
genitourinary, and neurological systems 
Abbreviated physical examination includes at minimum evaluation of vital signs, lung and heart sounds, including evaluation for pericardial rub 
ECHO is required to be obtained according to the central core lab parameters and then read locally and submitted to the central core lab for separate review and analysis. 
An EOT visit is to be conducted throughout the course of the study when a subject permanently discontinues study drug. 
An SFU is required to be conducted within 6 weeks of the last dose of rilonacept at any time throughout the course of the study including the RI period, the RW period, and the LTE period. 
The MRI to occur only if the previous MRI was done longer than 6 months ago. 
d 
e 
x 
y 
z 
26 
Page 27 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Table 1–4 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Study Schedule of Activities – Supplemental Visits (Part 2 of 2) 
b 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the randomization withdrawal and LTE periods, or more frequently as needed, with mandated 
evaluations as detailed in the schedule of events. 
For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout the course of the study and serum pregnancy can be drawn as needed; urine pregnancy is 
required to be performed at enrollment and 6 weeks after the last dose of study drug. 
Adverse event reporting begins following the subject providing informed consent. 
Upon investigator confirmation of pericarditis recurrence, the IWRS is to be updated. 
An EOT visit is to be conducted throughout the course of the study when a subject permanently discontinues study drug. 
An SFU is required to be conducted within 6 weeks of the last dose of rilonacept at any time throughout the course of the study including the RI period, the RW period, and the LTE period. 
h 
j 
l 
s 
x 
y 
27 
Page 28 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
LIST OF ABBREVIATIONS 
28 
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Abbreviation 
Definition 
ADA 
anti-drug antibodies 
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
CAPS 
Cryopyrin Associated Periodic Syndrome 
CEC 
Clinical Endpoint Committee 
CFR 
Code of Federal Regulations 
CMH 
Cochran–Mantel–Haenszel 
CRP 
C-reactive protein 
CS 
corticosteroids 
DMC 
Data Monitoring Committee 
ECG 
electrocardiogram 
ECHO 
echocardiography; echocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
eDiary 
electronic diary 
EORW 
End of Randomized-Withdrawal(visit) 
EOS 
End of Study 
EOT 
End of Treatment (visit) 
EQ-5D-5L 
5-level EuroQoL-5D 
ESC 
European Society of Cardiology 
ESR 
erythrocyte sedimentation rate 
FCAS 
Familial Cold Auto-Inflammatory Syndrome 
FDA 
US Food and Drug Administration 
GCP 
Good Clinical Practice 
GI 
gastrointestinal 
HDL 
high-density lipoprotein 
HIV 
human immunodeficiency virus 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
independent ethics committee 
IgG1 
human immunoglobulin G1 
IGRA 
Interferon Gamma Release Assay 
IL-1 
interleukin-1 
IRB 
Institutional Review Board 
ISI 
Insomnia Severity Index 
ISR 
injection site reaction 
ITT 
intent to treat 
IV 
intravenous(ly) 
IWRS 
interactive web response system 
KPL-914 
rilonacept 
 


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Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
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LDL 
low-density lipoprotein 
LTE-FUP 
Long Term Extension Follow-Up Period 
LTE-TP 
Long Term Extension Treatment Period 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
magnetic resonance imaging 
MWS 
Muckle-Wells Syndrome 
NSAID 
nonsteroidal anti-inflammatory drug 
NRS 
Numerical Rating Scale 
ORT 
Oral Rescue Therapy 
PHV 
Pharmacovigilance 
PGA-PA 
Physician Global Assessment of Pericarditis Activity 
PGIPS 
Patient Global Impression of Pericarditis Severity 
PK 
pharmacokinetic(s) 
POC 
point of care 
PRO 
patient-reported outcome 
RI 
Run-In (period) 
RN 
visiting registered nurse 
RW 
Randomized-Withdrawal (period) 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SC 
subcutaneous(ly) 
SF-36 
36-Item Short Form Health Survey 
SFU 
safety follow-up 
SOC 
standard of care 
SUSAR 
suspected unexpected serious adverse reaction 
TB 
tuberculosis 
TC 
site telephone visit (telephone contact) 
TEAE 
treatment-emergent adverse event 
TNF 
tumor necrosis factor 
ULN 
upper limit of normal 
WBC 
white blood cell 
WFI 
Water for Injection 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
1 
Introduction 
Pericarditis is inflammation of the pericardium, the double-walled sac surrounding the heart. 
Etiologies of pericarditis include infectious causes (viral, bacterial, fungal, and parasitic) and non-
infectious causes (idiopathic, autoimmune, neoplastic, metabolic, traumatic, post-surgical, and drug-
related) (Adler et al 2015). In 80% of cases in developed countries, the cause of pericarditis is either 
post-viral or “idiopathic” in that it cannot be attributed to a specific condition (Imazio et al 2010; 
Zayas et al 1995). 
The underlying pathogenesis of recurrent pericarditis remains unclear, although a growing body of 
evidence suggests that abnormal immune responses play a role in the pathogenic processes. While the 
adaptive immune system plays a role in autoimmune disorders that manifest with pericarditis as one 
of the many organ systems involved (such as in systemic lupus erythematosus or rheumatoid 
arthritis), the innate immune system, including interleukin 1 (IL-1) signaling, is often the major 
effector in autoinflammatory disorders, such as isolated pericarditis (Baskar et al 2016; Brucato et al 
2016; Imazio et al 2016, Dinarello et al 2012). 
Diagnosis of pericarditis is based on the presence of typical chest pain (improved by sitting up and 
leaning forward) along with fever, pericardial friction rub, electrocardiographic changes, pericardial 
effusion, or elevated levels of inflammation markers (white blood cell [WBC] count, C-reactive 
protein [CRP], or erythrocyte sedimentation rate [ESR]) (Adler et al 2015). The European Society of 
Cardiology (ESC) Guidelines for the Diagnosis and Management of Pericardial Diseases define an 
acute pericarditis episode as the presence of at least 2 of the 4 following criteria: pericarditic chest 
pain, pericardial rubs, new widespread ST-segment elevation or PR-segment depression based on 
electrocardiogram (ECG) findings, and pericardial effusion (new or worsening). Elevations of certain 
markers of inflammation (i.e., CRP, ESR, and WBC) or evidence of pericardial inflammation by an 
imaging technique (e.g., magnetic resonance imaging [MRI]) are used as supportive findings (Adler 
et al 2015). 
Recurrent pericarditis is characterized by the recurrence of pericarditis signs and symptoms after a 
symptom-free period of at least 4 to 6 weeks (Adler et al 2015). Recurrent pericarditis affects 20% to 
30% of patients with acute pericarditis (Imazio 2014) and can be debilitating for patients due to pain 
and limitations in physical function during pericarditis episodes. Pericarditis recurrences result in 
increased emergency room admissions and hospitalizations. In the United States, 5% of patients 
presenting to the emergency room with non-ischemic chest pain are diagnosed with pericarditis 
(Agarwal et al 2015). 
The estimated prevalence of recurrent pericarditis in the US and Europe is 70,000 to 160,000 patients 
including approximately 8,000 to 21,000 patients who are refractory or intolerant to current therapies 
or who require long-term administration of corticosteroids (CS) to control their disease (Brucato et al 
2016; Lazaros et al 2016; Imazio et al 2010; Khandaker et al 2010; Imazio et al 2008). 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
1.1 
Current Therapeutic Management of Pericarditis 
There are no approved therapies for the treatment of recurrent pericarditis. Current treatments include 
nonspecific inhibitors of inflammation, i.e., aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), 
colchicine, and CS (Lilly et al 2013). 
Aspirin and other NSAIDs are the first-line approach. Because high doses of aspirin and NSAIDs are 
often required, consideration must be given to gastric protection therapy, as potential risks of therapy 
include stomach ulcers and gastrointestinal (GI) bleeding, as well as renal and cardiovascular toxicity. 
Colchicine is another mainstay therapy for pericarditis and is commonly used with NSAIDs to hasten 
the response to NSAIDs and reduce the risk of subsequent recurrences. However, its use may be 
associated with the risk of fatal overdosing, significant drug interactions, and neuromuscular toxicity. 
In addition, approximately 10% to 15% of patients experience significant GI side effects with 
colchicine, including GI intolerance or severe diarrhea, requiring treatment discontinuation (Imazio et 
al 2016). 
Available ESC guidelines stipulate that CS should be prescribed for the management of pericarditis 
episodes only in cases of incomplete response, intolerance, or contraindications to NSAIDs and 
colchicine because of their unfavorable long-term benefit-risk profile. Corticosteroid use is associated 
with side effects, including weight gain, diabetes, osteoporosis, avascular bone necrosis, and 
increased risk for infections (Imazio et al 2008). For the management of pericarditis, CS are usually 
administered at low to moderate doses and can provide rapid control of symptoms. However, they 
often require many months of tapering after the normalization of CRP levels. In addition, there is a 
high rate of pericarditis relapse when CS use is tapered or stopped (Lotrionte et al 2010; Imazio et al 
2005; Maisch et al 2004), particularly in the absence of concurrent colchicine treatment. 
Patients with recurrent pericarditis who are refractory or intolerant to current therapeutic management 
options or who require long-term administration of CS to control their disease can be particularly 
challenging to manage. As a last resort, some refractory patients are being referred to the surgical 
procedure of pericardiectomy, with variable outcomes. Multiple immunosuppressive medications 
have been used without consistent benefit (Baskar et al 2016). 
1.2 
Pathogenesis of Recurrent Pericarditis: Role of IL-1 
Interleukin-1 is a key cytokine that drives the pathophysiology of many inflammatory processes, and 
it is implicated as a causative factor in various inflammatory diseases in humans. 
The two distinct IL-1 genes, IL1A and IL1B, encode IL-1α and IL-1β, respectively. IL-1α and IL-1β 
bind to the universally-expressed cell surface receptor, IL-1 receptor type-1, triggering a cascade of 
inflammatory mediators. The precursor form of IL-1α is expressed in keratinocytes, mucous 
membrane epithelial cells, and organs such as the liver and vascular endothelium in healthy 
individuals. During pathological states, IL-1α moves to the cell surface or is released after cell death 
to activate IL-1 receptors in adjacent cells, thus beginning the cascade of sterile inflammation. IL-1β, 
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Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
however, is not expressed in healthy individuals until a stimulus, such as microbial products or other 
chemokines, triggers its transcription in monocytes, tissue macrophages, and dendritic cells via the 
inflammasome. IL-1 drives the inflammatory cascade in classic autoinflammatory conditions, such as 
tumor necrosis factor (TNF)-associated periodic syndrome (TRAPS) and familial Mediterranean 
fever (FMF) and plays a significant role in systemic onset of juvenile idiopathic arthritis and in 
autoimmune diseases such as rheumatoid arthritis (Baskar et al 2016). 
IL-1–blocking therapies are effective at controlling end-organ disease and damage in patients with 
various autoinflammatory disorders, and different strategies to block IL-1 have been used in clinical 
trials and demonstrated substantial success in controlling episodes of fever and elevations in 
acute-phase reactants (Cantarini et al 2015). 
This mechanistic plausibility of IL-1 antagonism in addressing pathophysiology related to the 
inflammasome extends to other conditions characterized by sterile acute inflammation, such as 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
1.3 
Rilonacept (KPL-914) 
Rilonacept (designated in Kiniksa Pharmaceutical’s development program as KPL-914) was 
developed by Regeneron Pharmaceuticals, Inc. (Regeneron) of Tarrytown, NY, and is approved with 
the trade name ARCALYST® in the US for the treatment of CAPS, including Familial Cold Auto-
Inflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and children age 12 
and older. Rilonacept is currently manufactured and marketed as ARCALYST® by Regeneron. 
Rilonacept received marketing authorization in the European Union for the treatment of CAPS with 
severe symptoms, including FCAS and MWS in adults and children aged 12 years and older, but 
based on a request from Regeneron, the marketing authorization was withdrawn. The withdrawal was 
a business decision and was not related to any concern with the safety or efficacy of rilonacept. 
Rilonacept is a recombinant fusion protein consisting of human cytokine receptor extracellular 
domains and the Fc portion of human IgG1. Rilonacept is a dimeric glycoprotein with a total 
molecular weight of approximately 250 kDa. The dimer is covalently linked by disulfide bonds in the 
Fc region. Rilonacept incorporates in a single molecule the extracellular domains of both receptors 
required for IL-1 signaling: the IL-1 type I receptor (IL-1R1) and the IL-1 receptor accessory protein 
(IL-1R-AcP) (Figure 1). 
Rilonacept is expressed in recombinant Chinese hamster ovary (CHO) cells. Rilonacept blocks IL-1 
by acting as a soluble decoy receptor that binds IL-1 and prevents its interaction with cell surface 
receptors. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Figure 1: 
Schematic of Rilonacept (KPL-914) 
IL-1R Type 1 
IL-1R-AcP 
- 
IL-1R-AcP 
Extracellular 
Domains 
Extracellular 
Domains 
Cell Membrane 
IL-1R Type 1 
Cytoplasmic 
Domains 
s s 
s s 
hIgG Fc 
1.3.1 Safety of Rilonacept 
For a detailed review of the available rilonacept safety data, please refer to the current Investigator 
Brochure and the ARCALYST® package insert (Section 13.1: ARCALYST® Prescribing 
Information). The available rilonacept safety data is summarized below. 
Rilonacept has been evaluated in 23 studies, including 22 complete and 1 ongoing. In the completed 
studies, 2243 subjects (2152 patients and 91 healthy volunteers) were exposed to rilonacept. Thirty of 
these patients were pediatric (<18 years of age). 
Doses up to 320 mg subcutaneously (SC) once weekly and 2000 mg intravenously (IV) monthly have 
been studied for different indications, including CAPS, gout, and other inflammatory disorders. 
Injection Site Reactions 
In clinical studies with rilonacept, the most common and consistently reported AE associated with 
rilonacept was injection site reaction (ISR). The ISRs included erythema, swelling, pruritus, mass, 
bruising, inflammation, pain, edema, dermatitis, discomfort, urticaria, vesicles, warmth, and 
hemorrhage. Most ISRs were mild to moderate. In the gout clinical studies, approximately 1% of 
subjects treated with rilonacept discontinued due to ISRs. Similar results have been seen in other 
patient populations. 
Infections 
Interleukin-1 blockade may interfere with immune response to infections. Serious life-threatening 
infections have been reported in clinical trials in subjects treated with rilonacept. 
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CH3 
 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Changes in Laboratory Parameters 
Cholesterol and lipid levels may be reduced in patients with chronic inflammation. Subjects treated 
with rilonacept in clinical trials experienced increases in their mean total cholesterol, high-density 
lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides. 
Immunogenicity 
As with all therapeutic proteins, there is a potential for immunogenicity. Antibodies directed against 
the receptor domains of rilonacept were detected using an enzyme-linked immunosorbent assay 
(ELISA). In clinical trials with rilonacept, approximately 30% to 35% of subjects tested positive for 
treatment-emergent antibodies to rilonacept on at least 1 occasion. 
Systemic Hypersensitivity Reactions 
Hypersensitivity reactions are a potential risk with protein therapeutics in general. In clinical studies 
with rilonacept, systemic hypersensitivity reactions have been rare. 
Malignancies 
The impact of treatment with rilonacept on the development of malignancies is not known. However, 
treatment with immunosuppressants, including rilonacept, may result in an increase in the risk for 
malignancies. 
Fetal Defects 
There are no adequate and well-controlled studies of rilonacept in pregnant women. Based on animal 
data, rilonacept may cause fetal harm. An embryo-fetal developmental toxicity study was performed 
in cynomolgus monkeys treated with 0, 5, 15, or 30 mg/kg given twice a week (highest dose is 
approximately 3.7-fold higher than the human dose of 160 mg based on body surface area). The fetus 
of the only monkey with exposure to rilonacept during the later period of gestation showed multiple 
fusion and absence of the ribs and thoracic vertebral bodies and arches. Exposure to rilonacept during 
this time period was below that expected clinically. Likewise, in the cynomolgus monkey, all doses of 
rilonacept reduced serum levels of estradiol up to 64% compared to controls and increased the 
incidence of lumbar ribs compared to both control animals and historical control incidences. In 
perinatal and postnatal developmental toxicology studies in the mouse model using a murine analog 
of rilonacept (0, 20, 100, or 200 mg/kg), there was a 3-fold increase in the number of stillbirths in 
dams treated with 200 mg/kg 3 times per week (the highest dose is approximately 6-fold higher than 
the 160 mg maintenance dose based on body surface area). 
Nonteratogenic effects: A peri- and postnatal reproductive toxicology study was performed in which 
mice were administered a murine analog of rilonacept at doses of 20, 100, and 200 mg/kg SC 3 times 
per week (the highest dose is approximately 6-fold higher than the 160 mg maintenance dose based 
on body surface area). Results indicated an increased incidence in unscheduled deaths of the F1 
offspring during maturation at all doses tested. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
1.3.2 KPL-914-C001 
Pericarditis 
Study 
with 
Rilonacept 
(KPL-914) 
in 
Recurrent 
KPL-914-C001 is an open-label, single active-arm Phase 2 proof-of-concept study in subjects age ≥6 
to 75 years old with recurrent idiopathic or post-pericardiotomy syndrome (PPS) pericarditis. The 
study includes a 6-week Treatment Period in which all the subjects receive once-weekly rilonacept 
160 mg SC (2.2 mg/kg for subjects ≥6 and <18 years old) following a loading dose of 320 mg SC in 
subjects ≥18 years old (4.4 mg/kg in subjects ≥6 and <18 years old) in addition to background 
pericarditis therapies (NSAIDS, colchicine, CS). After completing the 6-week Treatment Period and 
based on response status, the subjects have the option to enter the 18-week Extension Period during 
which they continue to receive rilonacept at the same dose, but during which investigators are 
encouraged to wean and stop background pericarditis medications. 
The primary objectives of the study are to explore clinical and biochemical endpoints of recurrent 
pericarditis symptomatology, as well as to assess feasibility to wean from concomitant pericarditis 
medication in the Extension Period while continuing treatment with rilonacept. The study population 
includes the following 5 subject categories (Parts): 
• 
Part 1 enrolls symptomatic subjects with recurrent idiopathic pericarditis with an elevated marker 
of systemic inflammation (CRP level >1 mg/dL). 
Part 2 enrolls symptomatic subjects with recurrent idiopathic pericarditis with CRP level 
≤1 mg/dL that, in the opinion of the investigator, can be attributed to concomitant medications 
(e.g., CS) and with pericardial inflammation present on cardiac MRI confirmed by the imaging 
core lab. 
Part 3 enrolls subjects with CS-dependent recurrent idiopathic pericarditis not experiencing 
symptoms that would meet the diagnostic criteria for a recurrence of pericarditis. 
Part 4 enrolls symptomatic subjects with recurrent PPS with an elevated marker of systemic 
inflammation (CRP level >1 mg/dL). 
Part 5 enrolls subjects with CS-dependent recurrent PPS not experiencing symptoms that would 
meet the diagnostic criteria for a recurrence of pericarditis. 
• 
• 
• 
• 
Preliminary data in this ongoing study suggest that subjects enrolled in Part 1 experience 
improvements in pain, CRP levels, and other pericarditis parameters compared to baseline. 
Adverse events observed in the study are consistent with the overall rilonacept safety profile. 
2 
Study Objectives and Endpoints 
2.1 
Primary Objective 
The primary objective of this study is to assess the efficacy of rilonacept treatment in subjects with 
recurrent pericarditis. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
2.2 
Secondary Objective 
The secondary objective of this study is to assess the safety of rilonacept treatment in subjects with 
recurrent pericarditis. 
3 
Investigational Plan 
3.1 
Study Design 
This is a Phase 3, multi-center, double-blind, placebo-controlled, randomized withdrawal study with 
open-label extension, to assess the efficacy and safety of rilonacept treatment in subjects with 
recurrent pericarditis. This study has 5 periods (Figure 2). 
3.1.1 Screening Period (up to 4 weeks) 
During the screening period, assessment of disease characteristics, baseline therapy, and the pre-
treatment workup will be completed during a period of up to 4 weeks. 
3.1.2 Single-blind Run-In (RI) Period (12 weeks) 
During the single-blind RI period, treatment with blinded rilonacept is administered and subjects are 
weaned off background standard of care (SOC) therapy for their pericarditis disease. Subjects will be 
blinded regarding the time of transition from the single-blind to the double-blind period; i.e., they will 
not be aware of the duration of the RI period. 
In the single-blind RI period, subjects ≥18 years old will receive blinded rilonacept as an initial 
loading dose of 320 mg (2 SC injections of 160 mg each) at the RI baseline visit (2 × 2 ml), followed 
by a 160 mg (2 ml) SC dose once weekly throughout the RI period. Pediatric subjects (≥12 and <18 
years old) will receive an initial loading dose of blinded rilonacept 4.4 mg/kg (2 SC injections of 
2.2 mg/kg each) at the RI baseline visit (maximum 2 × 2 ml), and then 2.2 mg/kg (maximum 2 ml) 
SC once weekly throughout the RI period. 
The RI period includes: 
• 
1-week Stabilization period, during which blinded rilonacept is administered in addition to SOC 
pericarditis therapy, and the ongoing pericarditis episode is treated. 
9-week Weaning period, during which subjects are weaned off background SOC pericarditis 
therapy, as applicable, while treatment with blinded rilonacept continues. The dosages of CS, 
NSAIDs, and colchicine will be tapered according to the weaning protocol in the Pharmacy 
Manual (for the purpose of the protocol, aspirin is considered an NSAID). In general, CS doses 
will be tapered off starting at RI Week 1 and will be withdrawn by RI Week 10 (over a total of 
9 weeks). NSAID and colchicine doses will be tapered off starting at RI Week 4 and will be 
withdrawn by RI Week 10 (over a total of 6 weeks). 
2-week Monotherapy period: Subjects who have been successfully weaned off background SOC 
pericarditis therapy will continue to receive blinded rilonacept. 
• 
• 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Subjects who stopped background pericarditis medications and achieve Clinical Response on 
rilonacept monotherapy at RI Week 12/RW baseline will proceed into the double-blind placebo-
controlled Randomized-Withdrawal (RW) period of the study. For definition of Clinical Response, 
refer to Section 6.2.2. 
Subjects who are unable   to   achieve   Clinical   Response   on   rilonacept   monotherapy   at 
RI Week 12/RW baseline are to be discontinued from study drug, transitioned to SOC pericarditis 
therapy at the investigator’s discretion, and followed through the end of the RW period. 
3.1.3 Double-blind Placebo-controlled RW Period (pericarditis recurrence 
event-driven duration with a minimum of 24 weeks) 
During the RW period, subjects who were able to stop background pericarditis medications and who 
achieve Clinical Response on rilonacept monotherapy at RI Week 12/RW baseline will be 
randomized 1:1 to double-blinded administration of study drug: 
• 
Rilonacept 160 mg (or 2.2 mg/kg in pediatric subjects ≥12 and <18 years old) SC injections once 
weekly OR 
Matching placebo SC injections once weekly 
• 
Pericarditis Recurrence in the RW Period 
For the definition of pericarditis recurrence, refer to Section 6.2.3. 
Upon pericarditis recurrence, subjects who report at least 1 day with pericarditis pain measurement ≥4 
on the 11-point Numerical Rating Scale [NRS] and have 1 CRP value ≥1 mg/dL (either on the same 
day or separated by no more than 7 days) will receive bailout rilonacept (2 open-label injections of 
160 mg rilonacept [or 4.4 mg/kg for pediatric subjects]) irrespective of randomized treatment 
assignment and as soon as at least 5 days have passed since the last study drug injection. The subjects 
transitioning to bailout rilonacept will remain blinded to their prior RW period treatment assignment. 
Sequential Oral Rescue Therapy (ORT), i.e., analgesics first, then NSAIDs, and then colchicine, can 
be added, if needed, at the discretion of the investigator, as outlined in Section 5.8.3 and detailed in 
the Pharmacy Manual. 
Subjects with pericarditis recurrence who do not meet the protocol criteria for bailout rilonacept will 
continue blinded study drug until they meet the protocol criteria for bailout rilonacept or through the 
end of the RW period. For those subjects, sequential ORT can be added to blinded study drug at the 
discretion of the investigator, as outlined in Section 5.8.3 and detailed in the Pharmacy Manual. 
All suspected pericarditis recurrence events in the RW period will be formally adjudicated by the 
Clinical Endpoint Committee (CEC), and only events that are confirmed by the CEC as pericarditis 
recurrences will be used in the Primary Endpoint analysis. 
The RW period will continue until the prespecified number of primary endpoint (CEC-confirmed 
pericarditis recurrence) events have occurred and approximately 50 randomized subjects have 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
achieved a minimum of 24 weeks of treatment in the RW period. Based on projected event accrual 
and subject randomization, Kiniksa Pharmaceutical will determine the end of the RW period and 
announce to sites so that subject End of Randomized Withdrawal (EORW) visits can occur. All 
subjects, including those who have transitioned to open-label rilonacept or who prematurely 
discontinued study drug, should complete an EORW visit. 
3.1.4 Long Term Extension Treatment Period (LTE-TP) (24 weeks) 
Upon completion of the RW period and the EORW visit (site and subject unblinding), all subjects 
completing the RW period (including subjects transitioned to open-label rilonacept upon pericarditis 
recurrence) will have an option to receive up to 24 weeks of open-label rilonacept 160 mg (or 
2.2 mg/kg for pediatric subjects) SC injections once weekly based on their clinical status and at the 
discretion of the investigator, after signing LTE informed consent. Any subject who, in the opinion of 
investigator, should not continue open-label rilonacept will be offered participation in the LTE off 
study drug after signing LTE informed consent. 
3.1.5 Long Term Extension Follow-Up Period (LTE-FUP) (24 weeks) 
All subjects in the LTE-TP will be followed in the LTE-FUP for an additional 24 weeks for safety 
and for potential pericarditis recurrence assessments. 
The total duration of the study will be determined by the rate of enrollment, the rate of first recurrence 
of pericarditis events during the RW period, and the minimum duration of follow-up in the RW of 
24 weeks. It is anticipated that study completers (including LTE-TP) will be dosed with rilonacept for 
approximately 1.2 years and up 
recurrence events accrual time. 
to 3 years based on enrollment assumptions and pericarditis 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Figure 2: 
Overview of KPL-914-C002 Trial Design 
a 
Enrollment 
First Dose 
End of Study 
(EOS) 
Randomization 
1:1 
End of RW 
LTE Week 24 
(Last Dose) 
Screening 
Up to 
4 weeks 
Single-blind Run In 
(RI) 
12 Weeks 
Event Driven Double-blind Randomized- 
b 
Withdrawal Period (RW) 
(Until 22 confirmed recurrence events) 
Anticipated minimum of 24 Weeks 
LTE Follow-Up 
(LTE-FUP) 
24 Weeks 
Long Term Extension Treatment Period 
(LTE-TP) 
24 Weeks 
1 
Week 
9 
Weeks 
2 
Weeks 
c 
Blinded rilonacept 160 mg SC once weekly 
Blinded rilonacept 160 mg 
c 
SC once weekly 
c 
Open-label rilonacept 160 mg SC once weekly 
Blinded placebo SC once weekly 
Stabilization 
while on 
background 
medication 
Monotherapy 
with rilonacept 
Weaning 
of NSAID, 
Colchicine, 
CS 
Primary Endpoint 
Abbreviations: CS=corticosteroid; EOS=end of study, LTE=Long Term Extension; NSAID=nonsteroidal anti-inflammatory drug; RI=run in, RW=randomized withdrawal, SC=subcutaneously, TP=treatment period 
a. The first dose given is a loading dose of rilonacept. In adult subjects ≥18 years old, 320 mg is given as 2 SC doses of 160 mg. In pediatric subjects ≥12 and <18 years old, 4.4 mg/kg is given as 2 SC doses of 2.2 
mg/kg. After the loading dose, rilonacept will be administered as a 160 mg (adults) or 2.2 mg/kg (pediatric subjects) SC dose once weekly. 
b. Subject’s treatment duration will depend on when the subject is enrolled relative to the end of RW. 
c. The adult dose is 160 mg SC once weekly. The pediatric dose is 2.2 mg/kg SC once weekly. 
Note: This picture is not drawn to scale. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
3.1.6 Rationale of Study Design 
Subjects eligible for this KPL-914-C002 study will be subjects with recurrent pericarditis presenting 
with an acute pericarditis episode at screening. 
The KPL-914-C002 study design ensures that during the RI period all subjects will receive rilonacept, 
a drug with evidence supporting clinical activity based on the preliminary clinical data with rilonacept 
from Part 1 of the ongoing Phase 2 proof-of-concept study (KPL-914-C001) obtained to date. During 
the RI period, pericarditis will be stabilized with symptoms controlled and background pericarditis 
medications (NSAIDs, colchicine, CS) will be tapered and withdrawn, while rilonacept treatment 
continues. 
The design then allows half of the subjects to continue receiving active treatment after having 
achieved Clinical Response on that treatment, which maximizes subject exposure to a potentially 
beneficial therapy. The temporary withdrawal of rilonacept (by switching to placebo) in the half of 
the subjects who were randomly assigned to placebo is expected to result in an accelerated time to 
pericarditis recurrence and a higher recurrence rate compared to those who continue on active 
treatment, a finding that demonstrates that the underlying pericarditis etiology is still ongoing and will 
provide further support for the anticipated observation of the clinical effect of rilonacept during the RI 
period of the study. The period of exposure to an ineffective treatment is minimized in this design, as 
subjects will be removed from blinded treatment when the condition returns to a specified severity 
(i.e., for having met the criteria of pericarditis pain ≥4 on the 11-point NRS and CRP level ≥1 mg/dL) 
without unblinding them to prior treatment assignment, thus protecting the primary efficacy endpoint 
of the study. All subjects who meet the pain and CRP criteria described above will be treated with 
open-label bailout rilonacept using a loading dose, followed by once-weekly SC injections. In 
addition, sequential ORT such as NSAIDs and/or colchicine will be allowed upon recurrence at the 
investigator’s discretion based on the subject’s clinical status, as outlined in Section 5.8.3 and as 
stipulated in the Pharmacy Manual. Subjects with pericarditis recurrence not meeting criteria for 
bailout rilonacept, can be treated with sequential ORT based on investigator judgement and as 
described in protocol Section 5.8.3 and the Pharmacy Manual. If the subject requires the addition of 
CS treatment to control the pericarditis recurrence, the subject will be discontinued from study drug. 
All subjects will be followed for the duration of RW period. 
In summary, the proposed RW trial with rilonacept allows all enrolled subjects an opportunity to 
receive the active drug during the acute episode of pericarditis yet provides pivotal-quality data on the 
efficacy of rilonacept in this enriched cohort by subsequently randomly assigning subjects to placebo 
versus active treatment after they achieve a predefined clinical response. Subjects with pericarditis 
recurrences after randomization will receive bailout rilonacept treatment and/or sequential ORT 
according to the protocol. This approach minimizes the exposure to placebo, which is important for a 
study that requires active disease upon enrollment and includes a pediatric population. The available 
regulatory guidance supports the use of an RW study design in the setting of recurrent pericarditis as 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
a means  of establishing the long-term effectiveness of rilonacept, an approved product for the 
treatment of another rare autoinflammatory condition (CAPS). 
3.1.7 Justification for Rilonacept Dose Selection 
The rilonacept dosing regimen utilized in the current study 
i.e., 320 mg 
SC loading dose (4.4 mg/kg in subjects ≥12 and <18 years old), followed by once-weekly SC doses at 
160 mg (2.2 mg/kg in subjects ≥12 and <18 years old). 
In the rilonacept development program in CAPS, gout, rheumatoid arthritis, and other inflammatory 
conditions, over 2000 subjects were exposed to rilonacept, including 1650 subjects receiving a 
rilonacept dose of 160 mg or higher. A total of 103 and 169 subjects were exposed to any rilonacept 
dose for at least 1 year or 6 months, respectively. Most of the real-life experience with rilonacept 
comes from the CAPS population treated at this marketed dose. As of March 2018, approximately 
365 CAPS patients have been exposed to rilonacept in the post-marketing setting since 2008. The 
safety data accumulated so far support the benefit/risk ratio for the rilonacept dose intended to be 
evaluated in subjects with recurrent pericarditis. 
Based on the preliminary clinical data with rilonacept from Part 1 of the Phase 2 proof of concept 
study (KPL-914-C001) obtained to date, it is expected that rilonacept doses 
(320 mg followed by 160 mg SC once weekly and corresponding pediatric doses), and evaluated in 
the KPL-914-C001 study, will consistently provide adequate suppression of clinical inflammatory 
response, including CRP levels, in patients with recurrent pericarditis. 
Bailout Rilonacept Dose 
Subjects who meet the protocol criteria for bailout rilonacept upon pericarditis recurrence in the RW 
period of the study (Sections 3.1 and 6.2.3), irrespective of treatment assignment at randomization, 
will receive open-label rilonacept (loading dose of 320 mg SC followed by once-weekly SC 
injections of 160 mg, or the corresponding pediatric doses). 
The rationale for bailout rilonacept treatment upon pericarditis recurrence for subjects who were 
randomly assigned to placebo is that rilonacept had controlled their disease activity during the RI 
period; therefore, re-initiation of rilonacept is justified to regain control of pericarditis signs and 
symptoms upon recurrence. Subjects who were randomly assigned to rilonacept and qualify for 
bailout rilonacept upon pericarditis recurrence in the RW period were initial responders to rilonacept 
treatment during the RI period; thus it could be assumed that the loss of response during the RW 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
period could be due to development of resistance to rilonacept due to different mechanisms, e.g., 
higher IL-1 levels or a change in rilonacept pharmacokinetics (PK)/ pharmacodynamics. Therefore, 
re-administration of a loading dose of rilonacept may help to restore Clinical Response. 
4 
Subject Selection and Withdrawal Criteria 
4.1 
Selection of Study Population 
Approximately 56 subjects will be enrolled (and not more than 75 subjects), which will allow at least 
50 subjects to be randomized at approximately 50 sites globally. Subjects will be assigned to study 
drug only if they meet all of the inclusion criteria and none of the exclusion criteria. 
Deviations from the inclusion and exclusion criteria are not allowed because they can potentially 
jeopardize the scientific integrity of the study, regulatory acceptability, or subject safety. Therefore, 
adherence to the criteria as specified in the protocol is essential. 
Subjects eligible for the study are subjects with recurrent pericarditis who do not have pericarditis 
secondary to prohibited conditions. The study population includes both adult subjects ≥18 years old 
and pediatric subjects ≥12 and <18 years old with a history of at least 2 pericarditis episodes 
(including the first episode and 1 recurrence) prior to screening. Enrollment of pediatric subjects will 
be limited to up to 20% of the study population. To be eligible for the study, subjects must present 
with at least a third pericarditis episode, defined as at least 1 day with pericarditis pain measurement 
≥4 on the 11-point 
administration. 
NRS and CRP level ≥1 mg/dL within 7 days prior to the first study drug 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
4.1.1 Inclusion Criteria 
Each subject must meet all of the following criteria to be enrolled in this study: 
1. Is capable of understanding the written informed consent form (ICF) or assent form (for 
pediatric subjects ≥12 and <18 years old), has provided signed and witnessed written informed 
consent or assent (as applicable), and agrees to comply with protocol requirements. 
Is male or female 12 years of age or older with body weight of at least 23.6 kg (52 Lbs). 
Has a diagnosis of recurrent pericarditis. 
At least 1 of the pericarditis episodes experienced prior to screening has met at least 2 of the 
following 4 criteria, in the opinion of the investigator and based on the documented available 
data, according to the 2015 ESC Guidelines for the Diagnosis and Management of Pericardial 
Diseases (Adler et al 2015): 
2. 
3. 
4. 
a. 
b. 
c. 
Pericarditic chest pain 
Pericardial rub 
New widespread ST-segment elevation or PR-segment depression according to ECG 
findings 
Pericardial effusion (new or worsening) 
d. 
5. Presents with at least the third episode of pericarditis during screening (i.e., at least the second 
pericarditis recurrence following the first pericarditis episode), and within 7 days* prior to and 
including RI baseline (first administration of study drug) has: 
a. At least 1 day with pericarditis pain ≥4 on the 11-point NRS, AND 
b. CRP level ≥1.0 mg/dL (for details of CRP collection see Section 6.1.1) 
*Pericarditis pain ≥4 and CRP ≥1 mg/dL are not required to be present on the same day. 
6. Has received NSAIDs and/or colchicine and/or CS (in any combination), if used, at stable 
dose levels (or at least not increased) for at least 3 days prior to and including RI baseline 
(first administration of study drug), and changes in medications made within this time period 
(e.g., 1-time use of NSAIDs) are not anticipated, in the opinion of the investigator, to 
significantly alter assessments of baseline disease activity. 
If using NSAIDs and/or colchicine and/or CS at the time of RI baseline (first administration of 
study drug), is willing and able, in the opinion of the investigator, to taper and discontinue 
those medications within the 9-week weaning time in the RI period of the study while 
continuing rilonacept treatment. 
7. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
8.   Female subjects must be: 
a. Postmenopausal, defined as at least 12 months after the cessation of menses (without an 
alternative medical cause) OR 
Incapable of pregnancy OR 
Permanently sterile following documented hysterectomy, bilateral salpingectomy, 
bilateral oophorectomy, or bilateral tubal ligation or having a male partner with 
vasectomy as affirmed by the subject OR 
If of childbearing potential, must agree to use a highly effective method of contraception 
during the study and for 3 months after the last study drug administration (i.e., hormonal 
contraceptives associated with inhibition of ovulation, intrauterine device [IUD], 
intrauterine hormone-releasing system [IUS], or sexual abstinence) 
b. 
c. 
d. 
9. If male and sexually active, must have documented vasectomy or must practice birth control 
and not donate sperm during the study and for 3 months after the last study drug 
administration. 
10. Must be up-to-date with all immunizations, in agreement with current local immunization 
guidelines for immunosuppressed subjects, before RI baseline (first administration of study 
drug). 
11. Is able to adequately maintain a daily subject diary according to protocol. 
12. Must be able to adhere to the study visit schedule and understand and comply with the other 
protocol requirements. 
13. Agrees to refrain from making any new, major lifestyle changes that may affect pericarditis 
symptoms (e.g., changing exercise pattern) from the time of the ICF is signed through the end 
of the double-blind RW period. 
4.1.2 Exclusion Criteria 
Subjects meeting any of the following criteria will be excluded from the study: 
1. Has a diagnosis of pericarditis that is secondary to specific prohibited etiologies, including 
tuberculosis (TB); neoplastic, purulent, or radiation etiologies; post-thoracic blunt trauma 
(e.g., motor vehicle accident); myocarditis; or systemic autoimmune diseases with exception 
of Still’s disease. 
Is pregnant, breastfeeding, or planning a pregnancy or fathering a child during the study or 
within 3 months after the last study drug administration. 
Has a history of immunosuppression, including positive human immunodeficiency virus 
(HIV) test results. 
2. 
3. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
4. Is currently receiving CS at a dose of >60 mg/day prednisone (or equivalent) for adult 
subjects, or >0.5 mg/kg/day (or >60 mg/day, whichever is lower) prednisone (or equivalent) in 
pediatric subjects (≥12 and <18 years old). 
Has ever received cytotoxic drugs, including cyclophosphamide, chlorambucil, nitrogen 
mustard, or other alkylating agents. 
Has ever received agents that deplete B or T cells (e.g., rituximab, alemtuzumab). 
Has received systemic immunomodulatory agents (with exception of CS) within the following 
time frames prior to RI baseline (first administration of study drug): 
5. 
6. 
7. 
a. Azathioprine, 
mycophenolate 
mofetil, 
cyclosporine, 
tacrolimus, 
sirolimus, 
or 
mercaptopurine within 24 weeks. 
TNF inhibitors, IL-6 inhibitors, or janus-activating kinase inhibitors within 12 weeks. 
Canakinumab within 12 weeks. Canakinumab could not have been discontinued due to 
safety unless it was discontinued due to local injection site reactions. 
Rilonacept within 6 weeks. Rilonacept could not have been discontinued due to lack of 
efficacy or due to safety. 
Methotrexate within 2 weeks. 
Anakinra within 5 days. Anakinra could not have been discontinued due to lack of 
efficacy or due to safety unless it was discontinued due to local injection site reactions. 
b. 
c. 
d. 
e. 
f. 
8. 
9. 
Has a history of myeloproliferative disorder. 
Has a history of demyelinating disease or symptoms suggestive of multiple sclerosis. 
10. Meets the following TB criteria: 
a. 
b. 
c. 
History of active TB prior to screening OR 
History of latent TB that was not adequately treated prior to screening OR 
Signs or symptoms suggestive of active TB (e.g., new cough of >14 days in duration or a 
change in chronic cough, persistent fever, unintentional weight loss, or night sweats) 
upon review of medical history and/or physical examination at screening OR 
Recent close contact with a person with active TB OR 
Positive or indeterminate Interferon Gamma Release Assay (IGRA) test results or results 
from another positive TB test at screening based on acceptable clinical practice for the 
country in which the subject is enrolling. 
d. 
e. 
11. Has chest x-ray (posterior-anterior view) at screening (or history of results within 12 weeks 
before receiving first administration of study drug), with evidence of malignancy or 
abnormality consistent with prior or active TB infection. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
12. Has received immunization with a live (attenuated) vaccine within 12 weeks before screening 
or is expected to receive live (attenuated) vaccine during the study or within 12 weeks after 
the last study drug administration. 
13. Has a history of positive or intermediate results for hepatitis B surface antigen, hepatitis B 
core antibody, or hepatitis C virus antibody at screening. 
14. Has an estimated glomerular filtration rate (eGFR) <30 ml/min. 
15. Has a history of malignancy of any organ system within the past 5 years before screening 
(other than a successfully treated non-metastatic cutaneous squamous cell carcinoma or basal 
cell carcinoma and/or localized carcinoma in situ of the cervix). 
16. Has a known or suspected current active infection or a history of chronic or recurrent 
infectious disease, including, but not limited to, chronic renal infection, chronic chest 
infection, sinusitis, recurrent urinary tract infection, or an open, draining infected skin wound. 
17. Has had a serious infection, has been admitted to the hospital for an infection, has been treated 
with oral antibiotics within 2 weeks of RI baseline (first administration of study drug), or has 
been treated with IV antibiotics for an infection within 8 weeks of RI baseline. 
18. Has had an organ transplant. 
19. Has screening laboratory test results meeting any of the following criteria: 
a. 
b. 
c. 
d. 
e. 
Hemoglobin level <10.0 g/dL; 
WBC count <3.0 × 103/µL 
Neutrophil count <1.5 × 103/µL 
Platelet count <100 × 103/µL 
Total bilirubin level >1.5 × the upper limit of normal (ULN) unless the test results are 
consistent with those for Gilbert’s syndrome 
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values >2 × ULN 
f. 
20. In the investigator’s opinion, has a history of alcoholism or drug/chemical abuse within 
2 years before screening. 
21. Has a known hypersensitivity to ARCALYST® (rilonacept) or to any of its excipients. 
22. Has received an investigational drug during the 30 days (or 5 half-lives, whichever is longer) 
before screening or is planning to receive an investigational drug (other than that administered 
during this study) or use an investigational device at any time during the study. 
23. In the investigator’s opinion, has any other medical condition that could adversely affect the 
subject’s participation or interfere with study evaluations. This includes significant 
concomitant illnesses such as, but not limited to, cardiac, renal, 
neurological, 
endocrinological, metabolic, pulmonary, GI, or psychiatric diseases. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
24. In the opinion of the investigator, is not likely to be compliant with the study protocol. 
25. In the opinion of the investigator, should not participate in this study. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
4.2 
Subject Completion, Withdrawal from Study, and Study Drug 
Discontinuation 
Completion 
4.2.1 
A subject will be considered to have completed the study if she/he has completed the RW period and 
has completed assessments at the EORW visit. At the EORW visit, subjects who were randomly 
assigned to rilonacept or subjects who transitioned to open-label rilonacept upon protocol-defined 
pericarditis recurrence (Section 6.2.3) in the RW period will be offered an opportunity to receive an 
additional 24 weeks of open-label rilonacept treatment based on their clinical status and at the 
discretion of the investigator, and after signing the LTE informed consent. 
At the EORW visit, subjects who were randomly assigned to placebo and did not transition to bailout 
rilonacept will be offered an opportunity to receive an additional 24 weeks of open-label rilonacept 
treatment based on their clinical status and at the discretion of the investigator, after signing the LTE 
informed consent. 
Any subject who in the opinion of investigator should not continue open-label rilonacept in LTE will 
be offered the opportunity to continue follow-up off study drug treatment in LTE, after signing the 
LTE informed consent. 
Subjects who elect not to enter LTE will be followed for 6 weeks after receiving the last study drug 
administration. 
4.2.2 Reasons for Discontinuation of Study Drug and Study Withdrawal 
Subjects have the right to stop taking study drug before the end of the study or to withdraw their 
consent for further participation in the study (i.e., precluding continued data collection). A subject 
also may be asked to stop study drug at the investigator’s discretion. In the event that a subject 
permanently discontinues study drug but does not withdraw the informed consent, the investigator 
should continue to follow up with the subject by telephone contact (TC) visits, in the clinic, or by 
other means through the EORW visit if the subject discontinues in RI or RW, or through the end of 
LTE-FUP if the subject discontinues in LTE-TP, unless consent is withdrawn. 
The reasons for premature study drug discontinuation will be recorded in the electronic case report 
form (eCRF). 
4.2.2.1 
Discontinuation of Study Drug 
The study drug dosing will be permanently stopped if any of the following occurs: 
• 
The subject develops a serious or intolerable AE, TB, or malignancy, excluding non-metastatic 
cutaneous squamous cell carcinoma or basal cell carcinoma 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
• 
• 
• 
Initiation of protocol-prohibited medication (Section 5.8.6) 
Subject requires treatment with CS for pericarditis during RW or LTE-TP periods of the study 
Pregnancy or pregnancy planned during the study or within 3 months after the last study drug 
administration 
ALT or AST values ≥3 × ULN associated with total bilirubin ≥2 × ULN, with no underlying 
medical conditions to explain the elevated values 
Treatment with a live (attenuated) vaccine during the study 
• 
• 
• 
Investigator or Sponsor’s medical monitor or 
medical monitor decides that, for 
safety reasons, it is in the subject’s best interest 
Termination of the study by Kiniksa Pharmaceuticals 
• 
Permanent or temporary study drug discontinuation should be strongly considered at the time if any 
of the following occurs: 
• 
• 
• 
• 
• 
Subject develops an opportunistic infection. 
Subject develops moderate or severe infection 
Neutrophil count <1.0 × 103/µL 
Isolated ALT or AST values >5 × ULN 
Surgical procedure 
The Sponsor has the right to terminate the study at any time in case of safety concerns (e.g., suspected 
unexpected serious adverse reactions [SUSARs]) or if special circumstances concerning the study 
drug or the company itself occur. In this event, the investigator(s) will be informed of the reason for 
study termination. 
4.2.2.2 
Withdrawal from the Study 
Subjects may withdraw from the study at any time and for any reason, without prejudice to their 
future medical care by the investigator or at the study site. However, prior to withdrawal of consent, it 
should be confirmed that the subject will not allow any form of follow-up including options such as 
less frequent follow-up calls or visits, follow-up with a family member or friend, or follow-up 
through a local physician or medical records. Follow-up options will be summarized on a withdrawal 
of consent checklist source document that must be reviewed and signed by the investigator for any 
subject who withdraws consent for further participation in the study. The checklist must be completed 
for all enrolled subjects who have withdrawn consent. The reasons for a subject’s withdrawal from 
the study are also required to be recorded in the eCRF. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
A subject may be considered withdrawn from the study for any of the following reasons: 
• 
• 
• 
Lost to follow-up 
Documented withdrawal of informed consent 
Death 
If a subject is lost to follow-up, every reasonable effort must be made by the study site personnel to 
contact the subject and re-engage the subject in the study or determine the reason for withdrawal. The 
measures taken are to continue until study end and are required to be recorded in source 
documentation. 
In subjects who are documented as having withdrawn consent from all study activities, no further 
study visits or study-related TCs can be conducted. All data collected prior to the date of the subject’s 
confirmed withdrawal of consent will be included in the study, as specified in the subject’s signed 
ICF. 
5 
Study Treatments 
5.1 
Method of Assigning Subjects to Treatment Groups 
In the single-blind RI period, all subjects will receive blinded rilonacept at the same dose through 
Week 12; subjects will be blinded to the time of transitioning to RW. Subjects who stopped 
background SOC pericarditis therapy and who achieve Clinical Response on rilonacept at RI Week 
12/RW baseline will be randomly assigned in a double-blind manner to continue to receive blinded 
rilonacept or matching placebo using a 1:1 allocation ratio. The definition of Clinical Response is 
provided in Section 6.2.2. An interactive web response system (IWRS) will be used to administer the 
randomization schedule. Biostatistics will generate the randomization schedule using SAS® software 
Version 9.4 or later (SAS Institute Inc, Cary, North Carolina) for the IWRS, which will link 
sequential subject randomization numbers to treatment codes. The randomization schedule will be 
stratified by 2 factors: 
• 
• 
Oral CS use at baseline (RI baseline, i.e., beginning of RI period): yes or no 
Diagnosis of recurrent idiopathic pericarditis (RI baseline): yes or no 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
5.2 
Treatments Administered 
Throughout this protocol, “study drug” refers to the investigational medicinal products: rilonacept and 
matching placebo. Both will be administered as applicable by SC injection. 
Study drug administration will be performed once a week (every 7 ± 2 days). The interval between 
study drug administrations must be at least 5 days. 
Study drug will be dosed as follows: 
Adult Subjects (≥18 years old): 
Rilonacept: Loading dose 320 mg administered as 2 SC injections, 160 mg each (2 ml) at RI baseline, 
followed by once-weekly SC injections of 160 mg (2ml). 
Placebo: administered as once-weekly SC injections of 2 ml each in the RW period 
Upon meeting protocol criteria for bailout rilonacept (Sections 3.1 and 6.2.3) in the RW period, 
subjects will be transitioned to open-label rilonacept 320 mg administered as 2 SC injections, 160 mg 
each (2 ml) at the next scheduled study drug administration date, followed by once-weekly SC 
injections of 160 mg (2ml). 
Pediatric Subjects (≥12 and <18 years old): 
Rilonacept: Loading dose 4.4 mg/kg administered as 2 SC injections, 2.2 mg/kg each (maximum 
160 mg each) at RI baseline, followed by once-weekly SC injections of 2.2 mg/kg (maximum 
160 mg). The volume of injections will be based on the subject’s weight (Table 5–1). 
Placebo (in RW): once-weekly SC injections with volume based on the subject’s weight (Table 5–1, 
maximum 2 ml). 
Upon meeting protocol criteria for bailout rilonacept (Sections 3.1 and 6.2.3) in the RW period, 
subjects will be transitioned to open-label rilonacept 4.4 mg/kg administered as 1 (maximum 2 ml) or 
2 SC injections at the next scheduled study drug administration date, followed by once-weekly SC 
injections of 2.2 mg/kg (maximum 2 ml). The volume of injections will be based on the subject’s 
weight (Table 5–1). 
Study drug dose/volume will be calculated by the investigator or pharmacist during site clinic visits 
based on body weight (as specified in the Study Schedule of Activities) using a weight-based dosing 
chart in kilograms (Table 5–1). 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Table 5–1: 
Study Drug Dose  Volume (After  Reconstitution)  by Body Weight in 
Kilograms for Pediatric Subjects Aged ≥12 and <18 Years 
Study Drug Self-Administration 
The first study drug dose on RI baseline will be administered at the study site. During this visit, the 
subject will be trained on study drug preparation and injection. In case the subject is unwilling or 
unable to prepare and self-inject the study drug, the subject’s caregiver will be trained. 
The first study drug administration for adult and pediatric subjects on RI baseline will consist of 2 SC 
injections, constituting a loading dose. The first injection will be prepared and administered by study 
site staff. The second injection will be prepared and administered by the subject or the subject’s 
caregiver after adequate training and under the supervision of study site personnel. Subsequent once-
weekly study drug doses will be self-administered SC by the subject or administered to the subject by 
a trained caregiver as an outpatient SC administration. If the subject or subject’s caregiver is unable to 
prepare and inject the study dug, the subject may report for once-weekly injections to a study site, or 
injections can be administered by the visiting registered nurse (RN). 
5.3 
Identity of Investigational Medicinal Product 
Rilonacept (KPL-914) is the drug being evaluated in the current study. Refer to Section 1.3 for a 
detailed description of rilonacept’s mechanism of action. 
53 
Page 54 
Weight Range (kg) 
 
Loading Dose Volume (ml) 
 
Weekly Dose Volume (ml) 
 
23.6 to 27.2 
2 x 0.7 
0.7 
27.3 to 30.8 
2 x 0.8 
0.8 
30.9 to 34.4 
2 x 0.9 
0.9 
34.5 to 38.1 
2 x 1.0 
1.0 
38.2 to 41.7 
2 x 1.1 
1.1 
41.8 to 45.4 
2 x 1.2 
1.2 
45.5 to 49.0 
2 x 1.3 
1.3 
49.1 to 52.6 
2 x 1.4 
1.4 
52.7 to 56.3 
2 x 1.5 
1.5 
56.4 to 59.9 
2 x 1.6 
1.6 
60.0 to 63.5 
2 x 1.7 
1.7 
63.6 to 67.2 
2 x 1.8 
1.8 
67.3 to 70.8 
2 x 1.9 
1.9 
70.9 or greater 
2 x 2.0 
2.0 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Study drug (rilonacept or placebo) is supplied in a single-use, 20 ml glass vial containing a sterile, 
white to off-white, lyophilized powder. Each vial is to be reconstituted with 2.3 ml sterile Water for 
Injection (WFI). A volume up to 2 ml can be withdrawn, which is designated to deliver up to 160 mg 
of rilonacept or up to 2 ml placebo for SC injection only. The resulting solution is clear, colorless to 
pale yellow, and essentially free of particulates. 
Each rilonacept vial contains 220 mg of rilonacept lyophilized powder. After reconstitution with 
2.3 ml sterile WFI, the rilonacept vial contains 80 mg/ml rilonacept, 40 mM histidine, 50 mM 
arginine, 3.0% (w/v) polyethylene glycol 3350, 2.0% (w/v) sucrose, and 1.0% (w/v) glycine at a pH 
of 6.5. No preservatives are present. 
Each placebo vial contains lyophilized powder. After reconstitution with 2.3 ml sterile WFI, the 
placebo vial contains 40 mM histidine, 50 mM arginine, 3.0% (w/v) polyethylene glycol 3350, 
2.0% (w/v) sucrose, and 1.0% (w/v) glycine at a pH of 6.5. No preservatives are present. 
5.4 
Management of Clinical Supplies 
5.4.1 Study Drug Product Packaging and Storage 
Additional information regarding the preparation, dispensation, administration, and storage of 
rilonacept or placebo will be described in the Pharmacy Manual. 
Study drug will be provided by Kiniksa Pharmaceuticals to the study sites in the lyophilized 
formulation in glass vials as described in Section 5.3. Each single-use vial will have a clinical label 
adhered to the vial. One labeled vial will be placed into a carton. Each carton will have a clinical label 
adhered to the outside of the carton. One tamper-evident seal will be placed on the top of the carton to 
securely close the lid. 
Study drug is to be stored and shipped refrigerated at 2°C to 8°C (36°F to 46°F) inside the original 
carton to protect it from light. 
5.4.2 Study Drug Accountability 
The sites will receive study drug for on-site administration at study site visits. Upon receipt of study 
drug, the investigator (or delegate) will conduct an inventory of the supplies and verify that the 
supplies are received intact, at the appropriate temperature, and in the correct amounts prior to 
completing a supplies receipt. The investigator will confirm receipt of study drug in the IWRS and 
retain a copy of this receipt at the study site. The inventory of supplies at each study site will be 
reviewed by the study monitor. 
Study drug will be dispensed to the study subjects for outpatient self-administration according to the 
supply chain described in the Pharmacy Manual. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
The investigator will maintain accurate records of receipt of all test articles, including dates of receipt. 
In addition, accurate records will be kept regarding when and how much study drug is dispensed and 
used by each subject in the study. Reasons for deviating from the expected dispensing regimen must 
also be recorded. At the completion of the study, to satisfy regulatory requirements regarding drug 
accountability, all used and unused study drug containers must be retained by the study site/clinic and 
subject for cataloguing and documentation of compliance. The full process for drug dispensing, 
documentation, and destruction will be described in the Pharmacy Manual. 
A full drug accountability log will be maintained at the study site at all times. 
5.4.3 Other Supplies 
Rilonacept should be reconstituted with preservative-free WFI that will be provided by Kiniksa 
Pharmaceuticals or designee along with 27-gauge, ½-inch needles, 3-ml syringes, alcohol wipes, 
gauze pads, bandages, and a puncture resistant container for disposal of needles and syringes. Only 
the syringes and needles provided by the Sponsor or its designee should be used to prepare and inject 
the study drug. The Sponsor also will provide coolers and refrigerated gel packs to ensure that the 
subjects transport the study drug at the proper temperature. On occasion, sites may be asked to locally 
procure ancillary materials. 
5.5 
Study Drug Overdose 
An overdose is any dose of study drug given to a subject or taken by a subject that exceeds the dose 
described in the protocol. Any overdose must be promptly reported to the 
Pharmacovigilance 
(PVG) in the same way and using the same procedures as for a serious  adverse event (SAE) 
(Section 6.4.6), regardless of whether any AEs are associated with the overdose. 
If there are AEs associated with the overdose, these should be recorded on the relevant AE/SAE 
sections in the eCRF; however, overdoses without signs or symptoms do not need to be recorded as 
AEs in the eCRF. 
5.5.1 Treatment of Study Drug Overdose 
The maximum amount of rilonacept that can be safely administered has not been determined. 
Maximum once-weekly doses of rilonacept up to 320 mg have been administered SC for up to 
approximately 18 months in a small number of subjects with CAPS, and for up to 6 months in 
subjects in an unapproved indication in clinical trials without evidence of dose-limiting toxicities. In 
addition, rilonacept given IV at doses up to 2000 mg monthly for up to 6 months in another subject 
population was tolerated without dose-limiting toxicities (Rilonacept IB). In case of overdose, it is 
recommended that the subject be monitored for any signs or symptoms of AEs and appropriate 
symptomatic treatment instituted immediately (Section 13.1, ARCALYST® Prescribing Information). 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
5.5.2 Other Study Drug Errors 
To avoid study drug errors, it is important to note the following: 
• 
In this study, rilonacept is designated for SC injections only. It should be taken only by the 
subjects participating in the study and as instructed by study site personnel. 
Guidelines regarding the management of temperature excursions during storage will be detailed 
in the Pharmacy Manual. 
Pediatric dosing is calculated based on body weight in kilograms, not pounds. 
• 
• 
Any study drug error must be promptly reported to the 
same procedures as for an SAE (Section 6.4.6) 
PVG, in the same way and using the 
5.6 
Transmission of Infectious Agents 
The lyophilized study drug is to be stored refrigerated at 2°C to 8°C (36°F to 46°F) inside the original 
carton to protect it from light. Study drug should not be used beyond the date stamped on the label. 
After reconstitution, study drug may be kept at room temperature, should be protected from light, and 
should be used within 3 hours of reconstitution. Study drug does not contain preservatives; therefore, 
unused portions of study drug should be discarded. 
5.7 
Misuse for Illegal Purposes 
Rilonacept does not have addicting potential, and the risk of misuse for illegal purposes is minimal. 
5.8 
Prior and Concomitant Medications 
Use of all concomitant medications and any changes in concomitant medications will be recorded in 
the subject’s eCRF. The minimum requirement is that drug name and dates of administration are to be 
recorded. This will include all prescription drugs, herbal products, vitamins, minerals, and over-the-
counter medications. 
Any concomitant medication deemed necessary for the welfare of the subject during the study may be 
given at the discretion of the investigator. However, it is the responsibility of the investigator to 
ensure that details regarding the medication are recorded in full in the eCRF. The initiation of 
protocol prohibited medication (Section 5.8.6) requires discontinuation of study drug. 
Guidelines regarding the use of concomitant medication will be detailed in the Pharmacy Manual and 
are summarized in the following sections. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
5.8.1 Screening 
Subjects included in the study may be receiving concomitant NSAIDs and/or colchicine, and/or oral 
CS treatment in any combination, provided that the dosages of these medications have been stable (or 
not increased) for at least 3 days prior to and including RI baseline (first administration of study 
drug), and changes in medications made within this time period (e.g., 1-time use of NSAIDs), in the 
opinion of the investigator, are not anticipated to significantly alter assessments of baseline disease 
activity. 
Analgesics can be used at the discretion of the investigator during screening activities prior to the first 
study drug dose, but only after the subject has documented a pericarditis pain level ≥4 on the 11-point 
NRS within 7 days prior to and including RI baseline (first administration of study drug). 
Subjects can enter the study on prednisone (or equivalent dose) not exceeding 60 mg/day for adults 
and not exceeding 0.5 mg/kg/day (with a maximum dose of 60 mg/day) in pediatric subjects. 
5.8.2 Single-blind RI Period 
• 
1-week Stabilization period, during which rilonacept is administered in addition to SOC 
pericarditis therapy and ongoing pericarditis episode is treated. All concomitant pericarditis 
medications including NSAIDs, analgesics, colchicine and CS will remain stable, unless the 
dosing must be decreased or stopped in the judgement of the investigator due to an AE. 
9-week background medication Weaning period, during which subjects are weaned off 
background SOC pericarditis therapy, as applicable, while treatment with blinded rilonacept 
continues. The guidelines for background medication taper and discontinuation will be provided 
in the Pharmacy Manual. 
Corticosteroids 
Starting at Week 1 and through Week 10, CS will be tapered and discontinued at a rate dependent 
on the dose at study entry. 
Analgesics 
Starting at Week 1 and through Week 10, analgesics (non-opioid and opioid) will be tapered and 
discontinued. Opioid analgesics can continue beyond Week 10 at stable doses through the end of 
the RW period if it is not feasible to discontinue them without causing withdrawal symptoms. 
NSAIDs and Colchicine 
Starting at Week 4 and through Week 10, NSAIDs and colchicine will be tapered and 
discontinued. 
• 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
• 
2-week Monotherapy period during which rilonacept administration continues: Subjects are 
required to be off all background SOC pericarditis therapy, with the exception of opioid 
analgesics if their discontinuation is not feasible. 
5.8.3 Double-blind Placebo-controlled RW Period 
During the RW period, subjects should not be receiving any concomitant medications for pericarditis, 
with the exception of opioid analgesics in case their taper down and discontinuation was not feasible 
in the RI period. 
5.8.3.1 
Concomitant Medication Upon Pericarditis Recurrence 
Subjects meeting protocol criteria for bailout rilonacept 
Upon pericarditis recurrence and meeting protocol criteria for bailout rilonacept (Sections 3.1 and 
6.2.3) and completing the diagnostic workup as confirmed by the 
medical monitor, 
subjects will be transitioned to open-label rilonacept, as described in Section 3.1. Because open-label 
rilonacept can be administered only if at least 5 days have passed from the last blinded study drug 
administration, the investigators are allowed to use sequential ORT, i.e., analgesics, NSAIDs, and 
colchicine if necessary at their discretion. The use of those medications will be detailed in the 
Pharmacy Manual; it is briefly given as follows: 
• 
Analgesics (including non-opioid and opioid) can be used for pain control prior to completing the 
diagnostic workup for a recurrent pericarditis episode. The use of analgesics during pericarditis 
recurrence evaluation will provide pain relief for subjects without impacting their CRP levels or 
other objective components of the diagnostic workup. 
• 
After the diagnostic workup is completed based on the 
medical monitor’s 
assessment, NSAIDs followed by colchicine can be added to open-label rilonacept based on the 
subject’s clinical status and at the discretion of the investigator. 
If, after transition to open-label rilonacept, the investigator decides that the subject requires CS 
for pericarditis therapy, the subject will be discontinued from rilonacept and followed through the 
EORW visit. 
• 
Subjects not meeting protocol criteria for bailout rilonacept 
If, based on the investigator’s judgement, the subject is experiencing pericarditis recurrence that does 
not meet the protocol criteria for bailout rilonacept (Sections 3.1 and 6.2.3) but does require 
additional treatment, the subject will continue blinded study drug, and the investigator should manage 
the pericarditis recurrence using sequential ORT for pericarditis, i.e., analgesics, NSAIDs, colchicine 
as described in the Pharmacy Manual and outlined briefly below: 
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• 
Analgesics (including non-opioid and opioid) can be used for pain control prior to completing the 
diagnostic workup for a recurrent pericarditis episode. The use of analgesics during pericarditis 
recurrence evaluation will provide pain relief for subjects without impacting their CRP levels or 
other objective components of the diagnostic workup. 
• 
After the diagnostic workup is completed based on the 
medical monitor’s 
assessment, NSAIDs followed by colchicine can be added to blinded study drug based on the 
subject’s clinical status and at the discretion of the investigator. 
If, after the addition of NSAIDs and colchicine, the investigator decides that the subject requires 
CS for pericarditis therapy, the subject will be discontinued from blinded study drug and followed 
through the EORW visit. 
• 
5.8.4 Long Term Extension Treatment Period (LTE-TP) 
Subjects who opt to continue open-label rilonacept in the LTE-TP will have their concomitant 
pericarditis medications managed at the discretion of the investigator and based on the subject’s 
clinical status. If CS are required in addition to rilonacept to manage recurrent pericarditis, rilonacept 
should be discontinued. 
5.8.5 Long Term Extension Follow-Up Period (LTE-FUP) 
During LTE-FUP, pericarditis medication can be managed at the investigator’s discretion. 
5.8.6 Prohibited Concomitant Medicines During the Study 
Prohibited medications during the study and throughout the end of LTE-TP include the following: 
• 
• 
• 
• 
• 
Interleukin (IL) blockers other than rilonacept 
IL-6 blockers 
Janus-activating kinase inhibitors 
TNF inhibitors 
Potent immunosuppressants (azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, 
sirolimus, mercaptopurine, cyclophosphamide, chlorambucil, nitrogen mustard, or other 
alkylating agents, agents that deplete B or T cells [e.g., rituximab, alemtuzumab]) 
Live (attenuated) vaccines, which are prohibited during the study and within 12 weeks after the 
last study drug administration 
• 
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5.9 
Blinding 
In the single-blind RI period, all subjects will receive rilonacept but will be blinded to the duration of 
the RI period and the timing of randomization. 
The RW period is a double-blind period in which rilonacept and placebo are identical in appearance. 
Neither the subject nor any of the investigator/site staff, 
or Sponsor staff who are involved in 
the treatment or clinical evaluation of the subjects will be aware of the treatment received 
(International Council for Harmonisation [ICH] E9). 
In the event of a pericarditis recurrence that meets the criteria for bailout rilonacept (Sections 3.1 and 
6.2.3), the subject will be transitioned to open-label rilonacept but will remain blinded to their prior 
RW treatment assignment. 
At the end of the RW period, all sites and subjects will be unblinded. Subjects will be offered 
participation in the LTE-TP, in which once-weekly open-label rilonacept can be continued for an 
additional 24 weeks. 
5.9.1 Breaking the Blind 
A subject’s treatment assignment will not be broken until the end of the RW period. 
If the treatment allocation for a subject becomes known to the investigator or other study staff 
involved in the management of study subjects, the Sponsor must be notified immediately. If the 
investigator intends to unblind treatment allocation for a subject, then the Sponsor should be notified 
immediately. The investigator may unblind a subject’s treatment assignment only in the case of an 
emergency, when knowledge of the study drug is essential for the appropriate clinical management or 
welfare of the subject. In most cases, the management of a medical emergency would be the same, 
regardless of whether the subject received active drug. The treatment assignment will be unblinded 
through the IWRS. The investigator must notify Kiniksa Pharmaceuticals and 
medical monitors 
as soon as possible but without revealing the treatment assignment of the unblinded subject, unless 
that information is important for the safety of subjects currently in the study. The date and reason for 
the unblinding must be recorded in the eCRF. 
The 
PVG staff may unblind the treatment assignment for any subject with an SAE. If the SAE 
requires that an expedited regulatory report be sent to one or more regulatory agencies, a copy of the 
blinded report may be sent to clinical investigators in accordance with local regulations. 
5.10 Treatment Compliance 
Subjects will record the administration of all doses of study drug (whether as an outpatient or in the 
clinic) in a subject’s diary. In addition, throughout all study periods, adherence to study drug 
administration will be assessed by the study site in collaboration with the visiting RN (Section 6). 
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6 
Study Assessments and Procedures 
Before performing any study procedures, all potential subjects will provide informed consent or an 
assent, if applicable. Potential subjects will have the study risks and benefits explained to them, the 
associated ICF reviewed with them, and all questions answered for them. Subjects will undergo 
screening procedures specific to the study only after the ICF has been provided by the subject unless 
performed as part of SOC practice. The investigator or designee will also sign the ICF. 
6.1 
Study Visits 
The schedule of assessments for the study site visits is summarized in the Study Schedule of 
Activities. Following screening assessments, qualifying subjects will be enrolled and enter the 
RI period. Subjects who stop background pericarditis medications and achieve Clinical Response at 
RI Week 12 (Section 6.2.2), will be randomized and enter the RW period. During both the RI and 
RW period, a combination of clinic and outpatient visits will occur. Outpatient visits may consist of 
telephone or virtual contacts as well as home visits conducted by a visiting nurse. For each scheduled 
visit of the study (including outpatient and clinic), assessments should occur prior to scheduled 
injections of study drug. Subjects can be brought to the clinic in place of a scheduled outpatient visit 
or for an unscheduled visit at the discretion of the investigator. 
The visit schedule is derived from the day of the RI baseline visit. One week is equal to 7 calendar 
days. Although visits do not occur every week, subjects are required to record pericarditis pain NRS 
measurements on a daily basis in their study device and to administer study drug on a once-weekly 
basis and record it in their study electronic diary (eDiary). If a subject is unable to independently 
complete the daily eDiary, a caregiver may help enter the data. 
Upon completion of the RI and RW periods, all subjects will have the opportunity to continue 
participating in the LTE. This will require each subject again providing informed consent prior to 
LTE participation. The LTE period will have a treatment period (LTE-TP) and an off treatment 
follow-up period (LTE-FUP). 
Any subject who prematurely discontinues study drug will be followed for the duration of the trial as 
specified in Section 4.2.2. In addition, throughout all study periods, compliance with study drug 
administration will be assessed by the site in collaboration with the visiting RN. 
6.1.1 Screening: Clinic and Remote as Needed 
A study screening eCRF is required to be completed for every subject with a signed ICF. For each 
subject, the subject identification is obtained from the IWRS. 
It is anticipated that some subjects may have a portion of the study screening procedures done as part 
of routine care outside the auspices of this study. As long as these procedures were done within the 
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allotted screening period timeframe, the results of these procedures may be used to support study 
screening and completion of the study screening eCRF. Any protocol-specified study qualification 
procedures/tests not already done as part of routine care will need to be conducted after the subject 
provides informed consent and before enrollment. It is possible that the screening and enrollment visit 
will occur on the same day. 
The below procedures are required to be completed to screen a subject ≤28 days prior to enrollment. 
All assessments and procedures are not required to be completed on-site; however, the site is 
expected to obtain the medical records for subject source documentation. 
• 
• 
• 
Obtain the ICF. 
Enter the subject into the IWRS. 
Review inclusion/exclusion criteria; ensure that the subject has a diagnosis of recurrent 
pericarditis based and is presenting with at least the third pericarditis episode. 
Record: demographic information, medical/surgical history, concomitant medications, all prior 
and current concomitant pericarditis medications, a detailed pericarditis history including all 
recurrent pericarditis events. 
Perform a full physical examination (may be performed by an investigator or other healthcare 
provider designated by the investigator). 
Perform/obtain: 
• 
• 
• 
- 
11-point pericarditis pain NRS assessment – required to be >4 within 7 days prior to and 
including the day of RI baseline. The qualifying NRS assessment and CRP are not required to 
occur on the same day. 
CRP (mg/dL) – required within 7 days prior to and including the day of RI baseline. For 
study qualification purposes, the CRP may be assessed using 1 of 4 approaches: 
- 
▪ 
▪ 
▪ 
Point of care (POC) device provided by Sponsor (preferred method) 
Blood sample sent to the local laboratory 
CRP measurement taken as part of the subject’s routine care (e.g., not specifically 
obtained for this study) 
Blood sample sent to the central laboratory 
▪ 
- 
- 
- 
- 
Local laboratory hematology, chemistry, IGRA, hepatitis serology, HIV 
Chest x-ray (unless performed and available within the past 12 weeks) 
Local or central laboratory urine pregnancy test for women of childbearing potential 
AE collection 
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Protocol KPL-914-C002 
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6.1.2 
6.1.2.1 
Single-blind Treatment: Run-In 
Enrollment (RI Baseline): Clinic Visit 
For subjects who meet study entry criteria, enrollment commences at the RI baseline visit. The 
following procedures occur: 
• 
• 
• 
• 
Review inclusion and exclusion criteria to confirm subject qualification. 
Review and record updates to recurrent pericarditis history since the screening visit. 
Revise IWRS status change to enrollment. 
Assess and record all concomitant medications as well as all prior and concomitant pericarditis 
medication. 
Perform an abbreviated physical examination, height and body weight. 
Acquire a 12-lead ECG. 
Acquire and submit a cardiac ECHO to the core laboratory per the core laboratory imaging 
guidelines; the ECHO is to be read locally prior to sending to the core lab. 
Perform cardiac MRI (for substudy participants only). 
Provide the subject with their study device and complete the following: 
• 
• 
• 
• 
• 
- 
For subjects ≥18 years, have them complete the 36-Item Short Form Health Survey (SF-36), 
5-level EuroQoL-5D (EQ-5D-5L), Insomnia Severity Index (ISI) 
For all subjects, instruct how to complete the 11-point pericarditis pain NRS (as outlined in 
Section 6.2.1.2) and the medication diary. 
Have all subjects complete the Patient Global Impression of Pericarditis Severity (PGIPS) 
score. 
- 
- 
• 
The investigator is to complete the Physician Global Assessment of Pericarditis Activity (PGA-
PA). 
Obtain the Pharmacogenomics ICF. 
Obtain a local or central laboratory urine pregnancy test for women of childbearing potential. 
Obtain central laboratory chemistry, hematology, lipid panel, CRP, anti-drug antibodies (ADAs), 
biomarkers, and urinalysis (laboratory tests should be drawn prior to the first study drug 
administration, but results of those tests are not required before enrollment). 
AE reporting. 
Additional discussion/assessment as needed. 
• 
• 
• 
• 
• 
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Upon completion of the above study activities, study drug dispensing can commence. The following 
procedures occur: 
• 
Complete the IWRS to dispense assigned study drug; record the amount (number of vials) 
dispensed. 
Explain the study drug, proper once-weekly dosing, proper study drug administration technique, 
study drug administration documentation, and confirm that the subject (and subject’s caregiver as 
applicable) understands. 
For pediatric subjects, body weight (in kilograms) obtained at the RI baseline visit is to be used to 
determine appropriate study drug dosing in the RI period. Please refer to the pediatric study drug 
dosing Table 5–1 as well as the Study Schedule of Activities for subsequent visits with weight 
assessments for pediatric dosing. 
Prepare and administer the first injection of study drug and train the subject or caregiver to 
prepare and administer the second dose of study drug. 
Instruct the subject to bring to each clinic visit all medications the subject is taking, including 
used and unused study drug vials. 
Arrange upcoming study visits (as many visits as possible that can be arranged ahead of time is 
advised). 
• 
• 
• 
• 
• 
6.1.2.2 
RI Day 2: Clinic Visit (24-hour PK Sub-study Participants Only) 
The RI Day 2 visit includes a PK sample that is collected 24 hours after the loading dose of study 
drug and then sent to the central laboratory. 
6.1.2.3 
RI Day 4: TC/RN Visit 
The timing of the site TC visit on the RI Day 4 visit can occur independently of the RN visit. During 
the site TC visit, the subject is contacted to assess for AEs in follow-up to the initial injections 
received, to review the daily input of the pericarditis pain NRS score, as well as to review all 
concomitant medications, including concomitant pericarditis medication. The site then dispenses 
study drug (along with ancillary supplies) through the IWRS and coordinates shipment as outlined in 
the Pharmacy Manual. During the visiting RN visit, a CRP sample is drawn and sent to the central 
lab. 
6.1.2.4 
RI Week 1: TC/RN Visit 
It is preferred that the site TC occur prior to the RN visits. It is required that visit assessments occur 
prior to scheduled study drug dosing. The RI Week 1 visit is as follows: 
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Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Site TC visit: 
• 
• 
• 
Assess for AEs. 
Evaluate all concomitant medications as well as pericarditis concomitant medications. 
Provide instruction on the pericarditis concomitant medication oral corticosteroid tapering if 
applicable. 
Confirm and review upcoming visit arrangements. 
Additional discussion/assessment as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
• 
• 
RN home visit: 
• 
Obtain the central laboratory samples for CRP, PK, and biomarkers (these are collected prior to 
study drug administration). 
Provide review of self-administration of the study drug. 
Monitor administration of the study drug (whenever possible). 
Ensure the subject records study drug administration in the medication diary. 
Obtain used study drug vials and materials. 
Confirm upcoming visit arrangements. 
• 
• 
• 
• 
• 
6.1.2.5 
RI Week 2: TC/RN Visit 
It is required that visit assessments occur prior to scheduled study drug dosing. The RI Week 2 visit is 
as follows: 
Site TC visit: 
• 
• 
• 
• 
• 
• 
Assess for AEs. 
Evaluate all concomitant medications as well as pericarditis concomitant medications. 
Assess subject progress on the oral pericarditis corticosteroid tapering, if applicable. 
Review study drug administration and documentation compliance. 
Confirm and review upcoming visit arrangements. 
Additional discussion/assessment as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
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RN home visit: 
• 
• 
Record study drug dispensing to the subject. 
Obtain central laboratory samples for CRP, PK, and ADAs (these are drawn prior to study drug 
administration). 
Provide review of self-administration of the study drug. 
Monitor administration of the study drug (whenever possible). 
Obtain used study drug vials and materials. 
Confirm upcoming visit arrangements. 
• 
• 
• 
• 
6.1.2.6 
RI Week 4: TC/RN Visit 
It is required that visit assessments occur prior to scheduled study drug dosing. The RI Week 4 visit is 
as follows: 
Site TC visit: 
• 
• 
• 
Assess for AEs. 
Evaluate all concomitant medications as well as pericarditis concomitant medications. 
Assess subject progress on the oral corticosteroid tapering if applicable and provide instruction on 
NSAID and/or colchicine tapering if applicable. 
Additional discussion/assessment as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
Confirm and review upcoming visit arrangements. 
Instruct the subject to bring used and unused study drug vials (those not yet obtained by the 
visiting RN) to the next clinic visit. 
• 
• 
• 
RN home visit: 
• 
Obtain central laboratory samples for CRP, PK, and biomarkers (these are drawn prior to study 
drug administration). 
Obtain a pharmacogenomics sample for those subjects who have provided informed consent. 
Provide review of self-administration of the study drug. 
Monitor administration of the study drug (whenever possible). 
Obtain used study drug vials and materials. 
Confirm upcoming visit arrangements. 
• 
• 
• 
• 
• 
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6.1.2.7 
RI Week 6: Clinic Visit 
The RI Week 6 visit in the clinic includes the following assessments and procedures: 
• 
• 
• 
Assess for AEs. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Assess subject progress on the concomitant oral corticosteroid, NSAID and/or colchicine tapering 
if applicable. 
Obtain used and unused study drug vials for study drug compliance evaluation. 
Have all subjects complete the PGIPS score. 
The investigator is to complete the PGA-PA. 
Obtain central laboratory samples for hematology, chemistry, CRP, and ADAs. 
Additional discussion/assessment as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
• 
• 
• 
• 
• 
Upon completion  of the above study  activities, the study drug  dispensing  can commence. The 
following procedures occur: 
• 
Have the subject administer the next scheduled injection of study drug (if within the study drug 
window) and have the subject record in the medication diary. 
Dispense study drug through the IWRS and record the amount (number of vials) dispensed. 
Review the study drug dosing schedule, administration techniques, and documentation. 
Confirm upcoming visit arrangements. 
• 
• 
• 
6.1.2.8 
RI Week 10: TC Visit 
The following assessments and procedures are to be completed: 
• 
• 
• 
• 
• 
• 
Assess for AEs. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Assess concomitant oral corticosteroid, NSAID and/or colchicine tapering completion. 
Assess study drug administration documentation. 
Confirm the RI Week 12/RW baseline clinic visit arrangements. 
Additional discussion/assessments as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
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Version 1.0, 26 Sep 2018 
6.1.2.9 
Randomization (RI Week 12/RW Baseline): Clinic Visit 
The following assessments and procedures are conducted at the RI Week 12 visit, prior to 
randomization: 
• 
CRP assessment (local and central) (the POC device provided for the study is the preferred 
method for local laboratory CRP assessment). 
Obtain a pericarditis pain NRS average score for the prior 7 days, including the day of the visit 
(4 missing NRS values within this week may result in an inability to move forward with 
randomization). 
Acquire a 12-lead ECG. 
Acquire and submit a cardiac ECHO to the core laboratory per the core laboratory imaging 
guidelines; ECHO is read locally prior to submission to the core lab. 
Abbreviated physical examination, height and body weight. 
For subjects ≥18 years, complete on their device SF-36, EQ-5D-5L, ISI. 
For all subjects, complete the PGIPS score. 
The investigator is to complete the PGA-PA. 
Obtain central laboratory samples for chemistry, hematology, lipid panel, PK, and ADAs. 
Evaluate concomitant medications including pericarditis concomitant medication. 
Assess for AEs. 
Obtain used and unused study drug vials for study drug compliance evaluation. 
Additional discussion/assessments as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
Assess for Clinical Response (refer to Section 6.2.2). 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
For subjects who have successfully completed the RI period and are assessed as achieving Clinical 
Response at the RI Week 12 visit, the RW baseline visit commences. 
The following assessments and procedures are conducted at the RW baseline visit: 
• 
• 
Update the subject status in the IWRS by randomizing the subject in the IWRS. 
Obtain weight for pediatric drug dispensing and dosing (Table 5–1). Please refer to the pediatric 
study drug dosing Table 5–1 as well as the Study Schedule of Activities for subsequent visits with 
weight assessments for pediatric dosing during RW. 
Dispense study drug and record the amount (number of vials) dispensed. 
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• 
Have the subject administer the study drug and record in the diary (if within the study drug 
window). 
Instruct the subject to bring all medications including used and unused study drug to each clinic 
visit. 
Instruct the subjects on the process to follow for a pericarditis recurrence event. 
Arrange upcoming visits. 
• 
• 
• 
For subjects that do not qualify for randomization per the IWRS, the 
medical monitor is to be 
immediately contacted to evaluate the reasons for non-qualification. Following medical monitor 
consultation, if the subject is deemed to not be a treatment responder, the RI Week 12 visit will be 
completed, study drug will be discontinued, and the subject will not proceed to randomization. The 
subject will be requested to perform a 6-week safety follow-up (SFU) visit after his/her last dose of 
study drug as well as continue with follow-up as agreed upon until the EORW period. 
6.1.3 Randomized-Withdrawal (RW) Period 
During the RW period, subjects will continue with once-weekly study drug administration as well as 
daily 11-point pericarditis pain NRS scoring. Visits will occur every 4 weeks, alternating TC/RN 
visits and clinic visits, with the first visit during the RW period (RW Week 4) being a TC/RN visit. 
Additional unscheduled visits may occur at any time for evaluation of suspected pericarditis 
recurrence (Section 6.1.6.1) or for other reasons as deemed necessary by the study investigator. 
The following procedures are to occur during the TC/RN visits: 
Site TC visits: 
• 
• 
• 
• 
• 
• 
Assess for AEs. 
Assess for suspected pericarditis recurrence events. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Additional discussion/assessment as needed. 
Confirm and review upcoming visit arrangements. 
Instruct the subject to bring used and unused study drug vials (those not yet obtained by visiting 
RN) to the next clinic visit. 
RN home visits: 
• 
• 
Obtain central laboratory samples for CRP. 
Provide review of self-administration of the study drug as needed. 
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• 
• 
Monitor administration of the study drug (whenever possible). 
Obtain used study drug vials and materials. 
The following procedures are to occur during the clinic visits (except for Week 24; see below): 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
Assess for AEs. 
Assess for suspected pericarditis recurrence events. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Record height and body weight. 
Obtain central laboratory samples for chemistry, hematology, and CRP. 
Obtain central laboratory sample for PK and biomarkers (Weeks 8 and 24 only). 
Obtain central laboratory sample for ADAs (Week 24 only). 
Have all subjects complete the PGIPS score. 
The investigator is to complete the PGA-PA. 
Additional discussion/assessment as needed (i.e., remind the subject about daily pericarditis pain 
NRS entry). 
Obtain used and unused study drug vials for study drug compliance evaluation. 
• 
Upon completion of the above study activities, study drug dispensing can commence. The following 
procedures occur: 
• 
• 
Obtain weight for pediatric drug dispensing and dosing (Table 5–1). 
Monitor administration of the study drug dose (whenever possible) and have the subject record in 
the medication diary. 
Dispense study drug through the IWRS and record the amount (number of vials) dispensed. 
Review the study drug dosing schedule, administration techniques, and documentation. 
Confirm upcoming visit arrangements. 
• 
• 
• 
6.1.3.1 
RW WEEK 24: Clinic Visit 
The Week 24 visit in the clinic includes the following assessments and procedures: 
• 
• 
Assess for AEs. 
Assess for suspected pericarditis recurrences. 
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• 
• 
• 
• 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Perform a full physical examination, height and body weight. 
Acquire a 12-lead ECG. 
Acquire a cardiac ECHO for core laboratory central review; the ECHO is to be read locally 
before sending to the core lab. 
Obtain an MRI (for substudy participants only). 
For subjects >18 years, complete the SF-36, EQ-5D-5L, ISI. 
For all subjects, complete the PGIPS score. 
The investigator is to complete the PGA-PA. 
Obtain central laboratory samples for chemistry, hematology, lipid panel, CRP, PK, ADAs, and 
biomarkers. 
Obtain used and unused study drug vials for study drug compliance evaluation. 
Additional discussion/assessment as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
• 
• 
• 
• 
• 
• 
• 
Upon completion  of the above study  activities, the study drug  dispensing  can commence. The 
following procedures occur: 
• 
• 
Obtain weight for pediatric drug dispensing and dosing (Table 5–1). 
Have the subject administer the RW Week 24 study drug dose (if within the study drug window) 
and have the subject record it in the medication diary. 
Dispense study drug through the IWRS and record the amount (number of vials) dispensed. 
Review the study drug dosing schedule, administration techniques, and documentation. 
Confirm upcoming study visits. 
• 
• 
• 
6.1.3.2 
EORW (End of RW Period/LTE Baseline): Clinic Visit 
The EORW visit will be same day as LTE-TP baseline visit. 
All randomized subjects, including those that have had pericarditis recurrence or have permanently 
discontinued study drug will have an EORW visit at the end of the RW period. The EORW activities 
are listed below: 
• 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
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• 
• 
Acquire a 12-lead ECG. 
Acquire and submit a cardiac ECHO to the core laboratory per the core laboratory imaging 
guidelines; the EHCO is to be read locally prior to submission to the core lab. 
Perform a full physical examination, height and body weight. 
For subjects >18 years, complete the SF-36, EQ-5D-5L, ISI. 
For all subjects, complete the PGIPS score. 
The investigator is to complete the PGA-PA. 
Obtain central laboratory samples for chemistry, hematology, lipid panel, CRP, PK, ADAs, and 
urinalysis. 
Assess for AEs. 
Assess for pericarditis recurrences. 
Obtain informed consent for participation in the LTE period. 
Additional discussion/assessment as needed. 
• 
• 
• 
• 
• 
• 
• 
• 
• 
Upon completion of the EORW visit procedures and obtaining subject informed consent to participate 
in the LTE period, the LTE baseline visit procedures are as follows: 
• 
Change the subject’s status in the IWRS and obtain unblinding information; proceed with subject 
unblinding. 
Obtain weight for pediatric drug dispensing and dosing (Table 5–1). 
Dispense study drug and record the amount (number of vials) dispensed. 
Have the subject administer the LTE-TP Day 1 study drug dose as applicable (if within the study 
drug window) and have the subject record it in the medication diary. 
Instruct subjects on continuing the 11-point pericarditis pain NRS score daily entry. 
Review the study drug dosing schedule, administration techniques, and documentation. 
Additional discussion/assessments as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
Confirm the upcoming study visits. 
• 
• 
• 
• 
• 
• 
• 
6.1.4 
6.1.4.1 
Long Term Extension 
LTE Weeks 8 and 16: Clinic Visit 
The LTE Weeks 8 and 16 clinic visit procedures are as follows: 
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• 
• 
• 
• 
• 
• 
• 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Have all subjects complete the PGIPS score. 
The investigator is to complete the PGA-PA. 
Obtain central laboratory samples for chemistry, hematology, and CRP. 
Assess for AEs. 
Assess for pericarditis recurrence events. 
Additional discussion/assessment as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
Confirm upcoming visit arrangements. 
Obtain weight for pediatric drug dispensing and dosing (Table 5–1). 
Dispense study drug through the IWRS and record the amount (number of vials) dispensed. 
Review the study drug dosing schedule, administration techniques, and documentation. 
Have the subject administer the regularly scheduled study drug dose as applicable (if within the 
study drug window) and have the subject record it in the medication diary. 
Confirm the upcoming study visits. 
• 
• 
• 
• 
• 
• 
6.1.4.2 
LTE Week 24 Clinic Visit 
The LTE Week 24 visit is the final visit of the LTE-TP. However, if at any time throughout the 
course of the study a subject prematurely discontinues study drug, an End of Treatment (EOT) visit is 
to occur. The visit procedures are as follows: 
• 
• 
• 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Acquire a 12-lead ECG. 
Acquire a cardiac ECHO for core laboratory central review; the EHCO is to be read locally prior 
to submission to the core lab. 
Obtain cardiac MRI (substudy participants only). 
Perform a full physical examination. 
For subjects >18 years, complete the SF-36, EQ-5D-5L, ISI. 
For all subjects, complete the PGIPS score. 
The investigator is to complete the PGA-PA. 
• 
• 
• 
• 
• 
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• 
Obtain central laboratory 
biomarkers, and urinalysis. 
Assess for AEs. 
samples for chemistry, hematology, lipid  panel, CRP, PK, ADAs, 
• 
• 
• 
Assess for pericarditis recurrence events. 
Have the subject administer the regularly scheduled study drug as applicable (if within study drug 
window), and have the subject record it in the medication diary. 
Change the subject status in the IWRS. 
Arrange an LTE Week 30 visit. 
• 
• 
6.1.5 
LTE Follow-Up Period 
Upon completion of the LTE Week 24 EOT visit, subjects continue long term follow-up until the end 
of the study (EOS). The LTE-FUP includes 2 visits. 
6.1.5.1 
LTE Week 30 Visit: Clinic 
The LTE Week 30 visit is a clinic visit. Visit activities are as follows: 
• 
• 
• 
• 
• 
• 
Assess for AEs. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Assess for pericarditis recurrence events. 
Additional discussion/assessment as needed. 
Obtain central laboratory samples for CRP, ADAs, and urine pregnancy test. 
Any left-over ancillary supplies are to be returned to the site. 
6.1.5.2 
LTE Week 48 End of Study Visit: TC 
The LTE Week 48 EOS TC visit procedures are as follows: 
• 
• 
• 
Assess for AEs. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Assess pericarditis recurrence. 
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6.1.6 
6.1.6.1 
Supplemental Visits 
Pericarditis Recurrence Assessment: Clinic Visit 
If a subject experiences symptoms consistent with pericarditis recurrence, he/she should contact the 
study investigator immediately for evaluation. It is possible that a subject may have assessments 
performed remotely, however, assessments are also expected be performed at the study site as soon as 
possible. Required assessments include: 
• 
• 
• 
Evaluate pericarditis pain on the 11-point NRS. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Obtain laboratory samples for CRP (local and central) (the POC device provided by Kiniksa 
Pharmaceuticals is the preferred method for local laboratory CRP assessment). 
Acquire a 12 lead ECG. 
Acquire a cardiac ECHO per core laboratory imaging parameters; this ECHO is read locally for 
the purpose of pericarditis recurrence assessment and is then submitted to the ECHO core 
laboratory for central review. 
Perform an abbreviated physical examination, height and body weight. 
For subjects >18 years, complete the SF 36, EQ-5D 5L, ISI. 
For all subjects, complete the PGIPS score. 
The investigator is to complete the PGA PA. 
Obtain central laboratory samples for PK, ADAs, and biomarkers. 
Other procedures deemed necessary per the investigator or delegated site personnel. 
• 
• 
• 
• 
• 
• 
• 
• 
Upon having completed the evaluation, if the investigator makes a clinical diagnosis that the subject 
is having a pericarditis recurrence event, he/she should contact the 
medical monitor to review 
and confirm that all assessments have been performed and collected. Upon 
medical monitor 
confirmation of completion of the assessment, the investigator commences as described in Section 
6.2.3. 
Subjects treated for a pericarditis recurrence event will continue to follow the same visit schedule 
described for the RW period (Section 6.1.3). 
Source documentation including the assessments and evaluations used to confirm a pericarditis 
recurrence event, are required to be sent to CEC. 
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6.1.6.2 
End of Treatment Visit: Clinic 
The EOT visit is to be conducted when a subject permanently discontinues study drug. For subjects 
who complete the RW period but do not consent to participate in the LTE period, the EORW and 
EOT visit can be combined. For those subjects who do consent to participate in the LTE period, the 
EOT visit can be combined with the LTE Week 24 visit. In the event that a subject prematurely 
discontinues study drug, it is expected that the subject will have an EOT visit as soon as possible and 
continue to be followed as described in Section 4.2.2. 
The EOT visit procedures are as follows: 
• 
• 
• 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Acquire a 12 lead ECG. 
Acquire a cardiac ECHO for core laboratory central review; the ECHO is to be read locally prior 
to submission to the core lab. 
Perform a cardiac MRI (for sub-study participants only) only if the previous MRI was done 
longer than 6 months ago. 
Perform a full physical examination. 
For subjects >18 years, complete the SF-36, EQ-5D-5L, ISI. 
For all subjects, complete the PGIPS score. 
The investigator is to complete the PGA PA. 
Obtain central laboratory samples for chemistry, hematology, lipid panel, CRP, PK, ADAs, 
biomarkers, and urinalysis. 
Assess for AEs. 
Assess for pericarditis recurrence events. 
Arrange SFU visit. 
• 
• 
• 
• 
• 
• 
• 
• 
• 
6.1.6.3 
Safety Follow-Up Visit: Clinic or TC/RN 
The SFU visit is to be conducted 6 weeks after the last dose of study drug. For those subjects who 
discontinue study drug at the LTE Week 24 visit, the SFU visit is to occur as a clinic visit. However, 
for those subjects who prematurely discontinue study drug during the study, the visit may be 
conducted in the clinic or as an outpatient (TC/RN visit) based on investigator discretion. The visit 
activities are as follows: 
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Site TC visit: 
• 
• 
• 
• 
Assess for AEs. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Assess for pericarditis recurrence events. 
Remind the subject to continue daily pericarditis pain NRS input if the SFU is occurring prior to 
the LTE Week 24 visit. 
Additional discussion/assessment as needed. 
• 
RN home visit: 
• 
• 
Obtain central laboratory samples for CRP, ADAs, and urine pregnancy test. 
Collect any leftover ancillary supplies and return to the site. 
When the visit is conducted as a clinic visit, all of the RN visit activities are to be performed during 
the clinic visit. 
6.2 
Efficacy Assessments 
Efficacy assessments to be performed at study visits are summarized in the Study Schedule of 
Activities and include: CRP, daily pericarditis pain assessment (11-point NRS), ECG, ECHO, Patient 
Global Impression of Pericarditis Severity (PGIPS), Physician Global Assessment of Pericarditis 
Activity (PGA-PA), and subject’s quality of life assessments (SF-36, EQ-5D-5L) and insomnia 
questionnaire (ISI). In a substudy at selected sites in approximately 10 subjects, a cardiac MRI will be 
performed. 
Note that in case the electronic versions of the PROs and assessments/questionnaires (PGIPS, PGA-
PA, SF-36, EQ-5D-5L, and ISI) are not available, the paper forms must be completed until the 
electronic versions are available again. 
6.2.1 
6.2.1.1 
Individual Efficacy Assessments 
C-Reactive Protein 
Central and local laboratory assessments of CRP will be performed at study visits as described in the 
Study Schedule of Activities. Centrally assayed CRP values will be used for statistical evaluations of 
changes from baseline. Locally assayed CRP will be used for screening, evaluation of treatment 
response prior to randomization, and assessment of suspected pericarditis recurrence in the RW 
period. The POC device provided by Kiniksa Pharmaceuticals is the preferred method for local 
laboratory CRP assessment. 
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6.2.1.2 
11-Point Pericarditis Pain Numerical Rating Scale 
Subjects will be asked to provide a daily assessment of pericarditis pain starting at RI baseline. A 
validated 11-point pericarditis NRS (Section 13.2) will be used to measure the subject’s level of pain 
intensity on a daily basis throughout the study (Hawker et al 2011; Mannion et al 2007; Dworkin et al 
2005). 
It is recommended that daily pericarditis pain measurements using the 11-point NRS are performed 
by subjects at the same time of the day each day, and prior to study drug injection on days with study 
drug administration. 
6.2.1.3 
Electrocardiogram 
Twelve-lead ECGs will be performed at study visits as described in the Study Schedule of Activities. 
Pericarditis commonly involves changes in the electrophysiologic activity of the heart, resulting in 
typical ECG findings, namely widespread ST-segment elevation or PR-segment depression. 
6.2.1.4 
Echocardiogram 
Echocardiographic assessment of presence of pericardial effusion including new or worsening of 
pericardial effusion should be obtained at study visits as described in the Study Schedule of 
Activities. Pericardial effusion is characterized by accumulation of excess fluid in the pericardial 
space surrounding the heart, and pericarditis is one of the main causes of pericardial effusion. 
Echocardiography is a sensitive tool and the most widely used imaging technique for the detection of 
pericardial effusion and/or thickening. Echocardiograms are to be acquired per the ECHO core 
imaging parameters. Upon local assessment and interpretation, the ECHO is then to be submitted to 
the designated central imaging laboratory. 
6.2.1.5 
Patient Global Impression of Pericarditis Severity 
Patient Global Impression questionnaires have been developed for a variety of indications. The 
PGIPS is a single-item PRO measure that assesses the subject’s impression of overall severity of 
pericarditis symptoms at the time the questionnaire is administered, using a 7-point rating scale 
ranging from absent (no recurrent pericarditis symptoms) to very severe (recurrent pericarditis 
symptoms cannot be ignored) (Guy 1976). The PGIPS can be completed in less than 30 seconds. 
The subject will select the box that best describes the severity of pericarditis symptoms right now: 
 
 
 
 
 
Absent: no symptoms 
Minimal: can be easily ignored without effort 
Mild: can be ignored with effort 
Moderate: cannot be ignored but does not influence my daily activities 
Moderately severe: cannot be ignored and occasionally limits my daily activities 
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 
 
Severe: cannot be ignored and often limits my concentration on daily activities 
Very severe: cannot be ignored and markedly limits my daily activities 
The PGIPS will be collected as described in the Study Schedule of Activities. 
6.2.1.6 
Physician Global Assessment of Pericarditis Activity 
Physician Global Assessment questionnaires have been developed for a variety of indications. The 
PGA-PA is a single-item clinician-reported outcome measure that investigators use to rate their 
impression of the patient’s overall pericarditis disease activity at the time the assessment is 
completed, using a 7-point rating scale ranging from absent to very severe (Guy 1976). Like the 
PGIPS, the PGA-PA can be completed in less than 30 seconds. 
The investigator will select the box that best describes subject’s pericarditis activity right now. 
 
 
 
 
 
 
 
Absent 
Minimal 
Mild 
Moderate 
Moderately severe 
Severe 
Very severe 
The PGA-PA will be collected as described in the Study Schedule of Activities. 
6.2.1.7 
36-Item Short Form Health Survey 
The SF-36 is a set of generic, coherent, and easily administered quality-of-life measures. The SF-36 
was developed at RAND Corporation as part of its Medical Outcomes Study. The SF-36 assesses 
8 health domains: physical functioning, bodily pain, role limitations due to physical health problems, 
role limitations due to personal or emotional problems, general mental health, social functioning, 
energy/fatigue, and general health perceptions. It also includes a single item that provides an 
indication of perceived change in health. 
SF-36 will be collected in subjects ≥18 years or older as described in the Study Schedule of 
Activities. 
6.2.1.8 
EQ-5D-5L 
The EQ-5D-5L is a standardized instrument developed by the EuroQol Group as a measure of health-
related quality of life that can be used in a wide range of health conditions and treatments. The EQ-
5D-5L consists of a descriptive system and the EQ VAS. The descriptive system comprises 5 
dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The rating 
scale records the subject’s self-rated health on a vertical VAS. This can be used as a quantitative 
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measure of health outcome that reflects the subject’s own judgement. The scores on these 
5 dimensions can be presented as a health profile or can be converted to a single summary index 
number 
(utility) 
reflecting 
preferability 
compared 
to 
other 
health 
profiles 
(https://euroqol.org/eq-5d-instruments). 
The EQ-5D-5L will be collected in subjects ≥18 years or older as described in Study Schedule of 
Activities. 
6.2.1.9 
Insomnia Severity Index 
The ISI is a 7-item self-report questionnaire assessing the nature, severity, and impact of insomnia. 
The usual recall period is the “last 2 weeks” and the dimensions evaluated are severity of sleep onset, 
sleep maintenance, early morning awakening problems, sleep dissatisfaction, interference of sleep 
difficulties with daytime functioning, noticeability of sleep problems by others, and distress caused by 
the sleep difficulties. A 5-point Likert scale is used to rate each item (e.g., 0=no problem; 4=very 
severe problem), yielding a total score ranging from 0 to 28. The total score is interpreted as follows: 
no clinically significant insomnia (0–7); subthreshold insomnia (8–14); clinical (moderate) insomnia 
(15–21); and clinical (severe) insomnia (22–28) (Morin et al 2011). 
The ISI will be collected in subjects ≥18 years or older as described in Study Schedule of Activities. 
6.2.1.10 Cardiac MRI 
Cardiac MRI will be performed as described in the Study Schedule of Activities at selected sites in 
approximately 10 subjects in the cardiac MRI substudy. Cardiac MRI will be performed to assess any 
changes in pericardial inflammation. Cardiac MRI readings will be performed by a central imaging 
laboratory. The study site/clinic reading of the MRI at the time of the examination may be used by the 
investigator for clinical decision-making. 
6.2.2 Assessment of Clinical Response at the End of the Run-In Period Week 
12/RW Baseline 
At RI Week 12/RW baseline visit, all subjects receiving rilonacept who are able to discontinue 
background SOC pericarditis therapy during the RI period (Section 3.1) are assessed for Clinical 
Response. Only subjects who achieve Clinical Response at RI Week 12 and have discontinued 
background medications for pericarditis are eligible for randomization in the RW period. 
Clinical Response at RI Week 12 is defined as follows: 
• 
A weekly average of daily pericarditis pain of ≤2.0 on the 11-point NRS during the 7 days prior 
to and including the day of randomization, AND 
CRP level ≤0.5 mg/dL at the RI Week 12/RW baseline visit. 
• 
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6.2.3 Management of Suspected Pericarditis Recurrence in the RW Period 
Pericarditis Recurrence Definition: Pericarditis recurrence, for the purpose of the protocol, is 
defined as the recurrence of typical pericarditis pain associated with supportive objective evidence of 
pericarditis. 
At any time point during the RW period, subjects who experience suspected recurrence of their 
pericarditis will have been instructed to inform their site investigator as soon as possible. Subjects 
who experience a suspected recurrence of pericarditis symptoms will be requested to report to the 
study site/clinic for a scheduled or unscheduled visit, during which clinical assessments will be 
performed to gather all the necessary diagnostic data to confirm or rule out the presence of 
pericarditis recurrence (Section 6.1.6.1). The investigator will evaluate all assessments performed for 
a diagnostic workup, whether at the study site or at locations outside. 
Upon completion of pericarditis workup, the investigator is required to contact the 
medical monitor to confirm that the protocol required diagnostic workup is complete prior to 
implementing treatment for the event. 
Following communication with the 
medical monitor, if the event meets the criteria 
for bailout rilonacept (at least 1 day with pericarditis pain measurement ≥4 on the 11-point NRS and 
one CRP value ≥1 mg/dL either on the same day or separated by no more than 7 days), and after the 
medical monitor has confirmed with the investigator that the diagnostic workup is 
complete, the attainment of bailout criteria is confirmed in the IWRS, blinded study drug is 
discontinued, and open-label rilonacept treatment is dispensed. If needed, sequential ORT is allowed 
as outlined in Section 5.8.3. The subject will continue to be followed up according to the Study 
Schedule of Activities for the RW period. 
Following communication with the 
medical monitor, if the event does not meet the 
protocol criteria for bailout rilonacept but in the judgement of investigator requires treatment, after 
the 
medical monitor has confirmed with the investigator that the diagnostic workup 
is complete, the investigator is allowed to add sequential ORT to blinded study drug, and as outlined 
in Section 5.8.3. Blinded study drug treatment will continue until a pericarditis recurrence that meets 
criteria for bailout rilonacept, or until the end of the RW period. 
For a summary of management of suspected pericarditis recurrence, refer to Figure 3. 
Upon suspected pericarditis recurrence, the event is required to be captured in the electronic data 
capture (EDC) system within 24 hours of learning of the event, and a pericarditis recurrence event 
adjudication package must be prepared for adjudication by CEC. The event package will include, but 
may not be limited to, data on the subject’s pericarditis pain level, CRP value, ECG tracing, ECHO 
result, the presence or absence of pericardial rub, and any additional source documentation relevant to 
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the assessment of the suspected event. Details on endpoint package requirements will be described in 
the CEC charter. The CEC-confirmed pericarditis recurrences will be used for Primary Endpoint 
efficacy analysis. For more details on the CEC, refer to Section 6.7.2 
Figure 3: 
Management of Suspected Pericarditis Recurrence in the Randomized- 
Withdrawal Period 
Pericarditis 
Recurrence * 
*Per protocol: CRP, ECG, ECHO, and pericardial rub assessment 
to be completed prior to treatment intervention 
NRS ≥ 4 
NO 
Able to observe 
NO 
YES 
event without 
treatment 
CRP ≥ 1.0 mg/dL 
YES 
YES 
Symptom 
Progression 
YES 
ORT=Oral Rescue Therapy 
6.3 
Safety Assessments 
Safety assessments to be performed at study visits are summarized in Study Schedule of Activities 
and include: assessment of AEs (Section 6.4), physical examinations (full and abbreviated) including 
vital signs measurements, chest x-ray, TB screening, and clinical laboratory tests (serology, 
hematology, chemistry, urinalysis) (Section 6.6). A pregnancy test (Section 6.6.6) will be conducted 
at screening and as needed during the study and must be performed 6 weeks after the last study drug 
administration. 
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Bailout open-label 
rilonacept; and 
sequential ORT if 
needed 
(per Section 5.8.3) 
Continue 
observation and 
blinded study drug 
 
 
 
 
Continue blinded 
study drug; and 
sequential ORT if 
needed 
(per Section 5.8.3) 
 
 
 
 
 
 
 
 
 
 


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Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
6.3.1 Physical Examination 
A full physical examination should include at minimum an evaluation of vital signs, head, eyes, ears, 
nose, and throat as well as cardiovascular, dermatological, musculoskeletal, respiratory, GI, 
genitourinary, and neurological systems. Body weight and height will be measured as per the Study 
Schedule of Activities and will be recorded in the eCRF. Any abnormality identified at baseline 
should be recorded on the medical history and physical examination eCRFs. At selected visits as 
specified in the Study Schedule of Activities, an abbreviated physical examination will be performed 
to evaluate vital signs, lung and heart sounds, including evaluation for pericardial rub. 
At all visits at the study site, limited symptom-directed physical examinations may need to be 
performed in order to determine changes from baseline or abnormalities and should be recorded in the 
subject’s trial notes. New or worsened abnormalities should be recorded as AEs on the Adverse Event 
eCRF. 
6.3.2 Vital Signs 
Vital signs include measurements of respiratory rate, pulse rate, systolic and diastolic blood pressure, 
and temperature. Blood pressure measurements should be obtained after the subject has been seated 
for at least 5 minutes. 
6.3.3 Chest X-ray 
Chest x-rays in accordance with local requirements will be obtained at screening (or an existing chest 
x-ray within 12 weeks of first study drug administration can be used) according to the Study Schedule 
of Activities. Chest x-rays should be reviewed by a qualified radiologist for clinically significant 
abnormalities and evidence of pulmonary disease that would exclude the potential subject. 
6.3.4 Tuberculosis Screening 
An IGRA test or another TB test based on acceptable clinical practice in each country will be 
performed in order to evaluate for the presence of active or latent TB infection at screening. 
6.4 
Adverse Events 
The investigator is responsible for reporting all AEs that are observed or reported during the study, 
regardless of their relationship to study drug or their clinical significance. 
6.4.1 
6.4.1.1 
Definitions 
Adverse Event 
An AE is any untoward medical occurrence in a subject or clinical investigation subject administered 
a pharmaceutical product. An AE does not necessarily have a causal relationship with this treatment. 
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An AE can therefore be any unfavorable sign (including an abnormal laboratory finding), symptom or 
disease temporally associated with the use of a medicinal (investigational) product, whether or not 
related to the medicinal (investigational) product. AEs also include: any worsening (i.e., any clinically 
significant change in frequency and/or intensity) of a pre-existing condition that is temporally 
associated with the use of the study drug; abnormal laboratory findings considered by the reporting 
investigator to be clinically significant; and any untoward medical occurrence. 
6.4.1.2 
Treatment-emergent Adverse Event 
A treatment-emergent AE (TEAE) is defined as any event not present before exposure to the study 
drug or any event already present that worsens in either intensity or frequency after exposure to the 
study drug. 
6.4.1.3 
Serious Adverse Event 
A serious adverse event (SAE) is any untoward medical occurrence or effect that, at any dose: 
• 
Results in death. Includes all deaths, even those that appear to be completely unrelated to the 
study drug (e.g., car accident where the subject is a passenger). 
Is life-threatening. In the view of the investigator, the subject was at immediate risk of death from 
the event at the time of the event (i.e., it does not include an AE that might have caused death if it 
had occurred in a more serious form). 
Requires in-patient hospitalization or prolongs an existing hospitalization. (Complications 
occurring during hospitalization are AEs and are SAEs if they cause prolongation of the current 
hospitalization. Hospitalization for elective treatment of a pre-existing non-worsening condition 
is not, however, considered an AE. The details of such pre-existing condition must be recorded on 
the medical history or physical examination page of the eCRF. Hospitalization is defined as an 
admission to the hospital ward, a short-stay type unit, or Emergency Room for longer than 
24 hours. Prolongation of existing hospitalization is defined as a hospital stay longer than 
originally anticipated for the event or development of a new AE as determined by the Investigator 
or treating physician.) 
Results in persistent or significant disability/incapacity. (An AE is incapacitating or disabling if it 
results in a substantial and/or permanent disruption of the subject’s ability to carry out normal life 
functions.) 
Is a congenital anomaly/birth defect. 
Is an important medical event. Important medical events may not be immediately life-threatening 
or result in death or hospitalization but may jeopardize the subject or may require intervention to 
prevent one of the other serious outcomes listed above (e.g., intensive treatment in an emergency 
room or at home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in 
hospitalization; or development of drug dependency or drug abuse). 
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• 
• 
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In addition, medical and scientific judgment is required to decide if prompt notification is required in 
situations other than those defined for SAEs above, i.e., any event that the investigator regards as 
serious that did not strictly meet the criteria above but may have jeopardized the subject or required 
intervention to prevent one of the outcomes listed above, or that would suggest any significant hazard, 
contraindication, side effect, or precaution that may be associated with the use of the study drug. 
All SAEs that occur after signing of study-related informed consent, whether or not the SAEs are 
related to the study drug or study procedures, must be reported. 
6.4.1.4 
Adverse Event of Special Interest 
An adverse event of special interest (AESI) is defined as an AE of scientific and medical interest 
specific to the understanding of the study drug and requiring close monitoring and rapid 
communication by the investigator to the Sponsor. An AESI may be serious or non-serious. The rapid 
reporting of AESIs allows ongoing analysis of these events in order to characterize and understand 
them in association with the use of the study drug. 
Treatments with immunosuppressants, including rilonacept, may result in an increase in the risk of 
malignancies. Therefore, malignancy is an AESI for rilonacept. Any AE of malignancy (excluding 
basal cell carcinoma of the skin) requires reporting to the 
Pharmacovigilance (PHV) within 
24 hours after the time the site personnel first learn about the event, following the process as 
described in Section 6.4.6. 
6.4.1.5 
Adverse Reaction 
Any noxious and unintended response to the study drug (i.e., where a causal relationship between the 
study drug and an AE is at least a reasonable possibility) related to any dose should be considered 
adverse drug reaction. 
6.4.1.6 
Suspected Unexpected Serious Adverse Reaction 
Suspected Unexpected Serious Adverse Reaction (SUSAR) is an adverse reaction that is 
“unexpected”, i.e., it is not listed (or not listed at the severity that has been observed) in the 
designated Reference Safety Information of the Investigator’s Brochure. Evaluation and reporting 
requirements for SUSARs are detailed in Section 6.4.8. 
6.4.2 
6.4.2.1 
Assessing Adverse Events 
Relationship to Study Drug 
The investigator’s assessment of an AE’s relationship to the study drug is part of the documentation 
process, but it is not a factor in determining what is or is not reported in the study. If there is any 
doubt as to whether a clinical observation is an AE, the event should be reported. 
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The relationship or association of the study drug in causing or contributing to the AE will be 
characterized by investigator using the following classification and criteria: 
• 
Not Related: when the AE is definitely caused by the subject’s clinical state or the study 
procedure/conditions 
Unlikely Related: when the temporal association between the AE and the study drug is such that 
the drug is not likely to have any reasonable association with the AE 
Possibly Related: when the AE follows a reasonable temporal sequence from the time of study 
drug administration but could have been produced by the subject’s clinical state or the study 
procedures/conditions 
Related: when the AE follows a reasonable temporal sequence from administration of the study 
drug, abates upon discontinuation of the drug, follows a known or hypothesized cause-effect 
relationship, and (if appropriate) reappears when the drug is reintroduced 
• 
• 
• 
6.4.2.2 
Intensity 
The severity of an AE will be recorded as one of the following: 
• 
Mild: easily tolerated, does not interfere with normal daily activities, does not require 
intervention 
Moderate: causes some interference with daily activities; minimal, local, or noninvasive 
intervention indicated 
Severe: as a consequence of the event, daily activities are limited or completely halted; 
hospitalization or prolongation of hospitalization indicated 
• 
• 
Changes in the severity of an AE should be documented to allow an assessment of the duration of the 
event at each level of intensity to be performed. Adverse events characterized as intermittent do not 
require documentation of onset and duration of each episode. 
6.4.3 Recording Adverse Events 
Each subject should be monitored for the development of any AEs. This information should be 
collected by asking nonleading questions (such as “How are you feeling?”) and from observations of 
and conversations with patients. AEs may also be collected by direct physical exam, diagnostic 
procedures, or any other appropriate source. 
At every study visit (telephone or at the site), subjects will be asked a standard nonleading question to 
elicit any medically related changes in their well-being. They will also be asked if they have been 
admitted to the hospital, had any accidents, used any new medications, or changed concomitant 
medication regimens (both prescription and over-the-counter medications). 
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All AEs (serious and non-serious) will be documented in the subject’s source documents and 
recorded in the eCRF. Any clinically relevant (as determined by the investigator) deterioration in 
laboratory assessments or other clinical findings is considered an AE and must be recorded in the 
subject’s source documents and in the eCRF. 
The AE term should be reported in standard medical terminology when possible. Also, when 
possible, signs and symptoms indicating a common underlying pathology should be noted as 
one comprehensive event. Information to be collected includes the following: 
• 
• 
• 
• 
• 
• 
• 
• 
• 
Event term 
Date and time of onset 
Investigator-specified assessment of severity and relationship study drug 
Date of resolution of the event 
Seriousness 
Any required treatment or actions 
Outcome 
Whether or not it caused the subject to discontinue the study drug. 
Whether or not the AE is an Injection Site Reaction (ISR). ISR is defined as any AE that occurs at 
the study drug injection site. If an ISR is observed, the subject may be treated at the discretion of 
the investigator. 
Adverse events resulting from concurrent illnesses, reactions to concurrent illnesses, reactions to 
concurrent medications, or progression of disease states must also be reported. All AEs will be 
followed to adequate resolution. The Medical Dictionary for Regulatory Activities (MedDRA) will be 
used to code all AEs. 
Any medical condition that is present at the time that the subject is screened but does not deteriorate 
should not be reported as an AE. However, if the condition deteriorates at any time during the study, 
it should be recorded as an AE. 
6.4.3.1 
Adverse Events Based on Signs and Symptoms 
All AEs spontaneously reported by the subject or reported in response to the open question from the 
study personnel or revealed by observation will be collected and recorded in the eCRF. When 
collecting AEs, the recording of a diagnosis is preferred (when possible) to the recording of a list of 
signs and symptoms. However, if a diagnosis is known and there are other signs or symptoms that are 
not generally part of the diagnosis, the diagnosis and each sign or symptom will be recorded 
separately. 
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6.4.3.2 
Adverse Events Based on Examinations and Tests 
If an abnormal laboratory value/vital sign is associated with clinical signs and symptoms, the sign or 
symptom will be reported as an AE and the associated laboratory result/vital sign will be considered 
as additional information. Wherever possible the reporting investigator uses the clinical rather than 
the laboratory term (e.g., anemia vs low hemoglobin value). In the absence of clinical signs or 
symptoms, clinically significant findings on examinations and tests should be reported as AEs. 
Any new or aggravated clinically significant abnormal medical finding at a physical examination as 
compared with the baseline assessment will be reported as an AE. 
6.4.3.3 
Pericarditis Disease Related Events 
Signs, symptoms, and abnormal findings associated with pericarditis are to be captured as a 
pericarditis recurrence event rather than as an AE unless the event is more severe than expected for 
the subject. In any case, pericarditis recurrence is required to be captured in the eCRF (see Section 
6.2.3) within 24 hours of learning of the event. 
6.4.4 Time Period for Collection of Adverse Events 
Adverse events will be assessed from the time the subjects signs the ICF and through the duration of 
the study, or at least through the SFU period (6 weeks after the last dose of study drug). 
6.4.5 Follow-Up of Unresolved Adverse Events 
Every reasonable effort will be made to follow subjects who have AEs. 
Any AEs that are unresolved at the subject’s SFU visit are to be followed up by the investigator until 
resolution or for as long as medically indicated. Additional information for any subject with an 
ongoing AE at the end of the SFU period may be requested by the 
PHV, as needed. 
6.4.6 Reporting Serious Adverse Events 
Any AE that meets SAE criteria (Section 6.4.1.3) must be reported to the 
PHV using the EDC 
system, immediately (i.e., within 24 hours) after the time site personnel first learn about the event. 
In the event the EDC entry is not possible (e.g., system failure or access problems), the study site 
should complete the paper SAE report form and fax the form to the 
PHV within 24 hours of 
awareness. The EDC system should be updated as soon as it is available. 
A full description of every SAE will need to be provided to the 
PHV (this may be supported by 
source documentation such as discharge summary or laboratory report should these documents be 
requested by the 
PHV). Additional follow-up information, if required or available, should be 
sent to the 
PHV as soon as possible and placed with the original SAE information. 
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The following contact information is to be used for SAE reporting: 
Telephone: 
Telephone: 
Fax: 
Information on non-serious AEs that become serious must also be reported to the 
as it is available. 
PHV as soon 
Investigators must report SAEs and follow-up information to their responsible Institutional Review 
Board (IRB) or Independent Ethics Committee (IEC) as applicable per institutional policy. 
The Sponsor or designee will provide regulatory authorities, IRBs, IECs, and principal investigators 
with clinical safety updates/reports according to local requirements. 
6.4.6.1 
Other Reasons for Immediate Reporting 
The following events require reporting to the 
personnel first learn about the event: 
PHV within 24 hours after the time the site 
• 
• 
• 
• 
Pregnancy in subject or female partner of male subject 
Overdose of the study drug or concomitant medication, regardless of whether it is considered AE 
Other study drug errors 
Any AE of malignancy (excluding basal cell carcinoma of the skin) 
6.4.7 Pregnancy 
Pregnancy is regarded as an AE only if there is a suspicion that study drug may have interfered with 
the effectiveness of a contraceptive medication. Nonetheless, any pregnancy that occurs during study 
participation (including pregnancy in a female partner of a male subject) must be reported to the 
PHV in the same way and using the same procedures as for an SAE (Section 6.4.6). The subject with 
pregnancy must not receive (additional) study drug. The pregnancy must be followed up to determine 
outcome (including spontaneous miscarriage, elective termination, normal birth, or congenital 
abnormality) and status of mother and child, even if the subject was discontinued from the study. 
Pregnancy complications and elective terminations for medical reasons must be reported as an AE or 
SAE. Spontaneous miscarriage must be reported as an SAE. 
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Any SAE occurring in association with a pregnancy, brought to the investigator’s attention after the 
subject has completed the study, and considered by the investigator as possibly related to the study 
drug, must be promptly reported to the 
PHV. 
In the event that a subject is found to be pregnant after having received at least 1 study drug dose, the 
study drug must be discontinued, and the pregnancy will be followed to term and the status of mother 
and child will be reported to the 
PHV after delivery. Instances of perinatal death or congenital 
abnormality, if brought to the attention of the investigator at any time after cessation of study drug, 
will be reported to the 
PHV within 24 hours. 
6.4.8 Evaluating and Reporting SUSARs 
Pharmacovigilance will promptly evaluate all SUSARs and nonserious AEs of special interest 
against cumulative product experience to identify and expeditiously communicate possible new safety 
findings to investigators, IRBs/IECs, and applicable health authorities based on applicable legislation. 
To determine reporting requirements for single AE cases, 
PHV staff in collaboration with 
Kiniksa Pharmaceuticals will assess the expectedness of these events using the Reference Safety 
Information (Section 6.2) of the rilonacept Investigator’s Brochure. 
PHV will compare the severity of each SUSAR and the cumulative event frequency reported for 
the study with the severity and frequency reported in the applicable reference document. 
Reporting requirements will also be based on the investigator’s assessment of causality and 
seriousness, with allowance for upgrading by 
PHV and Kiniksa Pharmaceuticals as needed. 
All relevant information about suspected SUSARs that are fatal or life-threatening will be recorded 
and reported to the competent authorities in all the applicable countries, and IRBs/IECs in 
conjunction with Directive 2001/20/EC. 
6.5 
Other Assessments 
6.5.1 Pharmacokinetic Sample 
All subjects will have PK samples obtained according to the Study Schedule of Activities. For PK 
analyses, it is important that the exact time of the SC injection is recorded for each subject. When PK 
samples are to be collected on dosing days, serum will be collected pre-dose to measure rilonacept 
concentrations. Specific procedures for sample collection, processing, storage, and shipment can be 
found in a separate Laboratory Manual provided to sites. 
A PK substudy will be conducted in a subset of subjects agreeing to provide a PK sample 24 hours 
after the first dose of study drug in the RI period. Specific procedures for sample collection, 
processing, storage, and shipment can be found in a separate Laboratory Manual provided to sites. 
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6.5.2 Anti-Drug Antibodies (ADAs) against Rilonacept (KPL-914) 
Serum samples to measure the presence of ADAs against rilonacept will be collected according to the 
Study Schedule of Activities. Instructions for sample collection, processing, storage, and shipment 
can be found in a separate Laboratory Manual provided to the site. 
6.5.3 Biomarkers 
Serum and plasma will be collected according to the Study Schedule of Activities for biomarker 
analysis. 
6.5.4 Pharmacogenomics 
Whole blood for peripheral blood mononuclear cell (PBMC) isolation will be collected for 
pharmacogenomics assessments after signing the separate Pharmacogenomics ICF. 
6.6 
Laboratory Analyses 
Any abnormal laboratory test results (hematology, chemistry, or urinalysis) or other safety 
assessments (e.g., physical examination, vital signs measurements), including those that worsen from 
baseline, felt to be clinically significant in the medical and scientific judgement of the investigator are 
to be recorded as AEs or SAEs. 
Laboratory assessments will be performed at study visits as summarized in Study Schedule of 
Activities. Unscheduled laboratory assessments for safety issues are permitted as deemed necessary 
by the investigator. 
Whenever possible in pediatric subjects, local laboratory tests should be drawn using pediatric tubes. 
6.6.1 Serology 
Samples for local laboratory assessment of hepatitis B surface antigen, hepatitis B core antibody, 
hepatitis C virus antibody, and HIV levels will be collected at screening. If clinically indicated, those 
tests may be also collected during the study. 
6.6.2 Hematology 
Hematology tests performed at central study laboratory include WBC count with differential, platelet 
count, red blood cell count, mean corpuscular volume, hemoglobin, mean corpuscular hemoglobin 
concentration. 
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6.6.3 Chemistry 
Blood chemistry tests performed in the central study laboratory include albumin, total protein, 
alkaline phosphatase, ALT/SGPT, AST/SGOT, direct bilirubin, total bilirubin, bicarbonate, chloride, 
potassium, sodium, creatinine, glucose. 
In addition, the following chemistry tests may be performed together with local CRP measurement 
when using POC device: chloride, creatine kinase, creatinine, glucose, potassium, sodium, total 
carbon dioxide, blood urea nitrogen. 
6.6.4 Non-fasting Lipid Panel 
Subjects treated with rilonacept may experience increases in their lipids, including total cholesterol, 
LDL, HDL, and triglycerides. 
Non fasting measurements of total cholesterol, triglycerides, HDL, and direct LDL will be performed 
by central study laboratory as described in the Study Schedule of Activities. 
Investigators should monitor the lipid profiles in study subjects and consider ordering fasting lipid 
panel and/or lipid lowering therapies as needed based on cardiovascular risk factors and current 
guidelines. 
6.6.5 Urinalysis 
Urinalysis performed by the central study laboratory includes specific gravity, pH, protein, 
urobilinogen, ketones, glucose, blood, bilirubin, nitrites, leukocyte esterase. It will be performed as 
described in the Study Schedule of Activities. 
6.6.6 
Pregnancy Test 
For women of child-bearing potential, a urine pregnancy test using a licensed test (dipstick) should be 
performed prior to receiving the first administration of study drug, and as needed during the study, 
and also at the SFU visit. When needed, serum pregnancy test should be performed. The purpose of 
pregnancy test is to prevent embryo/fetal exposure to study drug. Subjects with positive or 
indeterminate pregnancy test during the screening are not eligible for the study. 
6.6.7 Sample Collection 
The procedures for the collection, handling, and shipment of laboratory samples are specified in the 
Laboratory Manual supplied to sites by the central laboratory. 
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6.7 
Committees 
6.7.1 Independent Data Monitoring Committee (DMC) 
A DMC will be utilized in this study to ensure external objective medical and/or statistical (if needed) 
review of safety data in order to protect the ethical and safety interests of subjects. The DMC will 
review unblinded aggregate (and, where necessary, individual) subject safety data at pre-defined 
intervals according to a DMC charter. The analysis plan for the DMC review will be described in the 
DMC charter, which will also contain details of the composition and the responsibilities of the DMC. 
6.7.2 Clinical Endpoint Committee (CEC) 
An independent CEC will review and adjudicate all suspected recurrent pericarditis events that occur 
during the RW period of the study. The procedures for adjudicating events will be described in the 
CEC Charter. This will be done independent of the investigators, and in a manner blinded to 
treatment assignment. The CEC will complete assessments on an ongoing basis. 
7 
7.1 
The 
Statistical and Analytical Plan 
Primary Efficacy Endpoint 
primary efficacy endpoint is time to pericarditis recurrence, defined as the time from 
randomization to the date of the first pericarditis recurrence for each subject. Only CEC-confirmed 
pericarditis recurrence will be considered as an event for the primary analysis. 
A sensitivity analysis will be done based on the investigator’s assessment of the event. 
Pericarditis recurrence is defined in Section 6.2.3. 
Subjects who do not have a pericarditis recurrence will be censored at the date of the last available 
assessment during the RW period before data cutoff. Detailed censoring rules will be specified in the 
Statistical Analysis Plan (SAP). 
7.2 
Secondary Efficacy Endpoints for the RW Period 
This section defines secondary efficacy endpoints for the RW period. Endpoints for the RI period and 
for the LTE-TP are defined in Section 7.3. 
7.2.1 Major Secondary Efficacy Endpoints 
1. Proportion of subjects who maintained Clinical Response at Week 24 of the RW period. 
Clinical Response is defined as a weekly average of daily pericarditis pain on the 11-point 
NRS ≤2.0 and CRP level ≤0.5 mg/dL. 
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2. Percentage of days with no or minimal pain in the first 24 weeks of the RW period. No or 
minimal pain is defined as non-missing NRS ≤1. 
Proportion of subjects with absent or minimal pericarditis symptoms (based on the 7-point 
PGIPS) at Week 24 of the RW period. 
3. 
7.2.2 Other Secondary Endpoints 
All time-to-event endpoints start from the day of randomization. The following variables will be 
analyzed: 
• 
• 
• 
• 
• 
• 
• 
• 
• 
Proportion of subjects without pericarditis recurrence in the first 24 weeks of the RW period 
Time to pericarditis pain NRS ≥4 
Time to CRP level ≥1 mg/dL 
Time to pericardial rub 
Time to widespread ST-segment elevation or PR-segment depression on ECG 
Time to new or worsening pericardial effusion on ECHO 
Change over time in CRP levels 
Change over time in the subject’s assessments of pericarditis pain (weekly average) 
Number (percentage) of subjects with absent or minimal pericarditis activity based on PGA-
PA 
Change over time in the SF-36 Physical Component Score 
Change over time in the SF-36 Mental Component Score 
the 
• 
• 
• 
Change in EQ-5D-5L. There are 6 questions in this instrument (Section 6.2.1.8). Each of the first 
5 questions has 5 levels, from level 1 (best) to level 5 (worst). They are mobility, self-care, usual 
activities, pain/discomfort, and anxiety/depression. The sixth question is the health on the day, 
from 0 (the worst) to 100 (the best) (van Reenen and Janssen 2015). The levels of the first 
5 questions (EQ-5D-5L profile) will be converted to an index value. Change from baseline in 
each one of these 7 values will be an endpoint. 
Change over time in subject’s sleep quality assessed with the ISI (Section 6.2.1.9). There are 
7 items in the ISI. Change in ISI total score, which is the sum of the 7 items over time, will be the 
endpoint. 
Change over time in ISI categories. The ISI total scores are divided to 4 categories: 
• 
• 
- 
- 
0–7 = No clinically significant insomnia 
8–14 = Subthreshold insomnia 
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- 
- 
15–21 = Clinical insomnia (moderate severity) 
22–28 = Clinical insomnia (severe) 
• 
Number (percentage) of subjects who receive sequential ORT for pericarditis (analgesics, 
NSAIDs, and/or colchicine) in the RW period 
7.3 
Other Endpoints 
These include efficacy endpoints in the RI period and the LTE-TP. Since there is no control arm in 
these 2 periods, only descriptive statistics will be provided. All time-to-event endpoints start from the 
day of receiving rilonacept in that period. 
7.3.1 Efficacy Endpoints for the RI Period 
The following efficacy endpoints are included in this period: 
• 
Proportion of subjects who achieved Clinical Response at the RI Week 12/RW baseline visit. 
Clinical Response is defined as a weekly average of daily pericarditis pain of ≤2.0 on the 11-point 
NRS and CRP level ≤0.5 mg/dL at the RI Week 12/RW baseline visit. 
Time to CRP normalization (≤0.5 mg/dL) 
Number (percentage) of subjects with normalization of CRP at RI Week 12 
Change from baseline in pericarditis pain at RI Week 12 
Change from baseline in CRP level at RI Week 12 
Resolution of ECHO and ECG abnormalities (yes/no) at RI Week 12 
Percentage of days with no or minimal pain 
Proportion of subjects with absent or minimal pericarditis symptoms based on PGIPS 
Proportion of subjects with absent or minimal pericarditis activity based on the PGA-PA 
Change over time in the SF-36 Physical Component Score 
Change over time in the SF-36 Mental Component Score 
Change in the EQ-5D-5L (Section 7.2.2 contains details about calculation) 
Change over time in the subject’s sleep quality assessed with the ISI (Section 7.2.2 contains 
details about calculation) 
Change over time in ISI categories 
Number (percentage) of subjects who were off background pericarditis medication at RI Week 12 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
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7.3.2 Efficacy Endpoints for the LTE-TP 
The efficacy endpoints below are included in this period. Each endpoint will be summarized through 
Week 24, by subjects who did and did not have an adjudicated pericarditis recurrence in the RW 
period, respectively, and overall: 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
Number (percentage) of subjects with pericarditis recurrences 
Proportion of subjects with Clinical Response 
Change over time in CRP levels 
Change over time in the subject’s assessments of pericarditis pain 
Percentage of days with no or minimal pain 
Proportion of subjects with absent or minimal pericarditis symptoms based on PGIPS 
Proportion of subjects with absent or minimal pericarditis activity based on the PGA-PA 
Change over time in the SF-36 Physical Component Score 
Change over time in the SF-36 Mental Component Score 
Change in the EQ-5D-5L (Section 7.2.2 contains details about calculation) 
Change over time in the subject’s sleep quality assessed with the ISI (Section 7.2.2 contains 
details about calculation) 
Change over time in ISI categories 
Number (percentage) of subjects requiring addition of SOC pericarditis therapy 
• 
• 
7.4 
Sample Size Calculations 
For the purpose of sample size estimation, time to pericarditis recurrence is assumed to follow an 
exponential distribution. An event of interest is defined as a subject’s first adjudicated recurrence of 
pericarditis. The following assumptions are used in the sample size calculation using EAST 6.4.1: 
• 
• 
• 
• 
• 
2.5% 
90% 
8 
0.244 
10% 
1-sided significance level 
Power 
Median time to event (in weeks) in placebo 
Hazard ratio (rilonacept/placebo) 
Percentage of subjects in the RI period that will not reach RW 
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Given these assumptions, a total of 22 adjudicated pericarditis recurrence events is required to 
achieve the power. About 25 subjects per arm (a total of 50 subjects) will be randomized. Considering 
10% of subjects in the RI period that will not reach the RW period, approximately 56 subjects will be 
enrolled in this study. 
Patient enrollment and the pericarditis recurrence event accrual will be closely monitored during the 
study. The monitoring activities will be done in a blinded fashion during the RW period. If the 
number of patients randomized is less than 50 and/or the time anticipated for the number of events 
required for the analysis of primary efficacy endpoint significantly exceeds the projected timeline, 
additional patients may be enrolled and/or randomized at Kiniksa Pharmaceutical’s discretion. 
However, at this time it is anticipated that no more than 75 subjects will be enrolled into this study. 
Since the data cutoff will be the event date of the 22nd adjudicated pericarditis recurrence AND all 
subjects still in the RW period have been treated for 24 weeks, the actual power could be higher if the 
assumed hazard ratio holds. 
7.5 
Analysis Sets 
The following analysis sets will be used in the statistical analyses. 
Intent-to-Treat (ITT) Analysis Set: All subjects who are randomized in the RW period will be 
included in the ITT analysis set. The primary analysis for efficacy endpoints in the RW period will be 
based on the ITT analysis set. Treatment comparisons for all ITT analyses will be based on each 
subject’s treatment assignment from randomization. 
Safety Analysis Set: All subjects who take at least 1 dose of study drug in the RI period will be 
included in the safety analysis set (SS). Safety analyses will be based on the actual treatment a subject 
received. 
Run-in Analysis Set: All subjects who received at least 1 dose of study drug in the RI period will be 
included in the RI analysis set (RIS). 
Per-protocol Analysis Set: The per protocol (PP) analysis set is a subset of the ITT analysis set with 
the exclusion of subjects with major protocol violations or violations that may potentially bias 
statistical analyses or the ethical conduct of the study. The criteria of these violations will be 
determined prior to unblinding. This analysis set may be used for sensitivity analyses for efficacy 
endpoints in the RW period. 
Pharmacokinetic Analysis Set: The PK analysis set includes subjects who receive at least 1 dose of 
study drug and have at least 1 PK sample. The PK analysis set will be used for all PK analyses. 
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7.6 
Description of Subgroups to be Analyzed 
Subgroup analyses for the primary endpoint will be performed by the stratification variable for 
randomization, as well as by important variables for baseline demographics and patient 
characteristics. These analyses are for the RW period only. Details will be provided in the SAP. 
7.7 
Statistical Analysis Methodology 
This section outlines the overall methodologies. Details of the statistical analyses, methods, and data 
conventions will be described in the SAP. 
7.7.1 General Methods 
Statistical analysis will be performed using SAS® software Version 9.4 or later. Continuous variables 
will be summarized using the mean, the standard deviation, median, minimum value, and maximum 
value. Time-to-event variables will be summarized using percent censored, event rate, and 25th, 50th, 
75th 
and 
percentiles with 95% CI, if estimable. Categorical variables will be summarized using 
frequency counts and percentages. Data will be listed in data listings. 
At each of RI and RW periods and in the LTE-TP, baseline will be the last value before the first dose 
of study drug within each individual period unless otherwise specified. For change-over-time 
endpoints in the RW period, by-visit analysis will be performed at each scheduled visit for at least 
24 weeks. 
7.7.2 Stratified Analysis 
There will be 2 stratification variables for randomization: 
• 
• 
Oral CS use at RI baseline: yes or no 
Diagnosis of recurrent idiopathic pericarditis at RI baseline: yes or no 
When a stratified analysis is used in the analysis and a stratum has no event of interest or no 
responder, the stratum will be pooled with the other stratum in the same stratification variable. 
7.7.3 Testing Hypotheses and Multiplicity Adjustment 
All statistical tests for the treatment comparison of efficacy endpoints in the RW period will be based 
on the ITT analysis set with 1-sided α=0.025. For each endpoint, the null hypothesis is that the effects 
of rilonacept and placebo are the same. The alternative hypothesis is that rilonacept is better than the 
placebo. 
In order to control the overall 1-sided type I error rate at the 0.025 level, a gatekeeping procedure in 
combination with Hochberg’s procedure will be applied to testing the primary and major secondary 
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endpoints. If the 1-sided p-value for testing the primary endpoint is ≤0.025, a significant treatment 
effect on the primary endpoint will be claimed. 
Section 7.2.1 provides the order of major secondary endpoints. If the primary endpoint is significant, 
the first major secondary endpoint, i.e., proportion of subjects who maintained Clinical Response at 
Week 24 of RW period will be tested at 1-sided α=0.025. A significant treatment effect on this major 
secondary endpoint will be claimed if the 1-sided p-value is ≤0.025. If the treatment effect is not 
significant on the primary endpoint, significance on this major secondary endpoint cannot be claimed 
regardless of the result. 
If both primary and first major secondary endpoints are significant following the above procedure, the 
second and third major secondary endpoints defined in Section 7.2.1 will be tested with Hochberg’s 
procedure at overall 1-sided α=0.025. If both 1-sided unadjusted p-values are ≤0.025, claim 
significance of rilonacept for both endpoints. If the larger 1-sided p-value is >0.025, compare the 
smaller 1-sided p-value with 0.0125. If the smaller 1-sided p-value is ≤0.0125, claim significance of 
rilonacept on this endpoint. 
7.7.4 Analysis of Primary Efficacy Endpoint 
22nd 
Primary analysis of this study will be done after 
CEC-confirmed pericarditis recurrence AND 
after all subjects in the RW period have been treated for 24 weeks. The log rank test will be the 
primary method for the analysis of time to recurrence, stratified by the stratification variables for 
randomization. 
A sensitivity analysis will be performed based on the investigator’s judgement of pericarditis 
recurrence. Additional sensitivity may be defined in the SAP. 
7.7.5 
7.7.5.1 
Analysis of Secondary Efficacy Endpoints 
Analysis of the Major Secondary Endpoints 
1. Proportion of subjects who maintained Clinical Response at Week 24 of the RW period 
(defined as a weekly average of daily pericarditis pain ≤2.0 on the 11-point NRS and CRP 
≤0.5 mg/dL at Week 24). The Cochran–Mantel–Haenszel (CMH) test will be used in this 
analysis, stratified by the stratification variables for randomization. 
2. Percentage of days with minimal or no pain in the first 24 weeks post randomization. Minimal 
or no pain is defined as non-missing daily NRS ≤1. This endpoint will be analyzed with an 
analysis of covariance. In addition to treatment arm, the following covariates will be included 
in this analysis: the stratification variables for randomization, and baseline NRS weekly 
average in 2 categories: NRS ≤1 versus NRS >1. 
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3.   Proportion of subjects with absent or minimal pericarditis symptoms (based on the 7-point 
PGIPS) at Week 24 of the RW period. The CMH test will be used in this analysis, stratified by 
the stratification variables for randomization. 
7.7.5.2 
Analyses of Other Secondary Endpoints in the RW Period 
The following endpoints will be analyzed using the same method for the primary endpoint: 
• 
• 
• 
• 
• 
Time to pericarditis pain NRS ≥4 
Time to CRP level ≥1 mg/dL 
Time to pericardial rub 
Time to widespread ST-segment elevation or PR-segment depression on ECG 
Time to new or worsening pericardial effusion on ECHO 
A mixed model with repeated measures (MMRM) will be used in the analysis of the endpoints below. 
In the model, subjects will have repeated measures for the response variable change from baseline of 
the endpoint. The explanatory variables will include the baseline value, treatment arm, and the 
variables for stratification at randomization. The p-value for treatment comparison will be calculated 
at each scheduled assessment for at least 24 weeks as part of the summary statistics. This is done with 
the understanding that the comparison could be biased due to dropouts or subjects with pericarditis 
recurrence. 
• 
• 
• 
• 
• 
• 
Change over time in CRP levels 
Change over time in the subject’s assessments of pericarditis pain (weekly average) 
Change over time in the SF-36 Physical Component Score 
Change over time in the SF-36 Mental Component Score 
Change in the EQ-5D-5L: Health score and Index value, respectively 
Change over time in the subject’s sleep quality: sum of the ISI scores. 
The CMH test will be used in the analysis of the endpoints below, stratified by the stratification 
variables for randomization. 
• 
• 
Proportion of patients without pericarditis recurrence in the first 24 weeks of the RW period 
Number (percent) of subjects with absent or minimal pericarditis activity based on the 
investigator’s assessment 
Number (percentage) of subjects who receive SOC pericarditis therapy in the RW period 
• 
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The following endpoints will be analyzed using the Mantel-Haenszel test with 1 degree of freedom: 
• 
Change in each 1 of the first 5 questions in the EQ-5D-5L, i.e., mobility, self-care, usual 
activities, pain/discomfort, and anxiety/depression 
Change over time in ISI categories 
• 
7.7.6 Analyses of Other Endpoints 
Endpoints listed in Section 7.3 for the RI period and the LTE-TP will be descriptive in nature since 
there is no control arm. Summary statistics will be generated following the methodologies stated in 
Section 7.7. 
Other analyses include anti-rilonacept antibodies and biomarker analyses. These analyses will be 
described in the SAP. 
7.7.7 Pharmacokinetic Analyses 
For all subjects, serum samples will be collected at time points shown in the Study Schedule of 
Activities in order to quantify concentrations of rilonacept. Descriptive statistics will be calculated for 
the serum concentrations of rilonacept by visit. Individual listings of serum concentrations will be 
provided. 
Pharmacokinetic data may be used in a subsequent population PK evaluation that will be conducted 
outside of this study and described in a separate report. 
7.7.8 Safety Analyses 
Treatment-emergent AEs (TEAEs), defined as AEs that start or increase in severity after the first dose 
of study drug and before 6 weeks after the last dose of study drug, will be coded to system organ class 
and preferred term using the most recent version of MedDRA. TEAEs will be analyzed for all 
subjects combined and by treatment group in the RW period. Further analyses by severity and 
relationship to study drug as well as analyses of serious TEAEs will be presented. 
Descriptive statistics will be used to summarize safety endpoints by visit for all subjects combined in 
the RI period and by treatment group in the RW period. Two-sided 95% CIs will be presented where 
meaningful. Data summaries will be displayed for clinical laboratory analyses (including safety 
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laboratory measurements, ADAs, etc.), vital signs measurements, ECGs, and physical examination 
findings. 
7.7.9 Interim Analyses 
No interim analyses are planned for this study. 
8 
Data Quality Assurance 
Assessment of subject compliance and adherence to study drug administration will be assessed by the 
site in collaboration with the visiting RN. 
This study will be conducted according to the ICH E6(R2) risk and quality processes described in the 
applicable procedural documents. The quality management approach to be implemented in this study 
will be documented and will comply with the current ICH guidance on quality and risk management 
(ICH Q9). 
8.1 
Data Management 
As part of the responsibilities assumed by participating in the study, the investigator agrees to 
maintain adequate case histories for the subjects treated as part of the research under this protocol. 
The investigator agrees to maintain accurate eCRFs and source documentation as part of the case 
histories. These source documents may include laboratory reports, ECG strips, etc. 
will be responsible for activities associated with the data management of this study. This will 
include setting up a relevant database and data transfer mechanisms, along with appropriate validation 
of data and resolution of queries. Data generated within this clinical study will be handled according 
to the relevant Standard Operating Procedures (SOPs) of 
. 
Investigative site personnel will enter subject data into an EDC system. The analysis data sets will be 
a combination of these data and data from other sources (e.g., laboratory data). 
Clinical data management will be performed in accordance with applicable 
standards and data 
cleaning procedures to ensure the integrity of the data, e.g., removing errors and inconsistencies in the 
data. Adverse event terms will be coded using MedDRA, an internal validated medical dictionary, 
and concomitant medications will be coded using the World Health Organization Drug Dictionary. 
After the last study database lock, each study site will receive a CD-ROM containing all of their site 
specific eCRF data as entered into Medidata Rave for the study, including full discrepancy and audit 
history. Additionally, a Master DVD/CD-ROM copy of all of the site data from the study will be 
created and sent to Kiniksa for storage. 
will maintain a duplicate Master DVD/CD-ROM copy 
for their records. In all cases, subject initials will not be collected or transmitted to Kiniksa 
Pharmaceuticals. 
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9 
Ethics 
9.1 
Independent Ethics Committee or Institutional Review Board 
Regulatory agencies and the ICH guidelines require that approval be obtained from an IRB/IEC 
before participation of human subjects in research studies. Before study onset, the protocol, informed 
consent, informed assent, advertisements to be used for the recruitment of study subjects, and any 
other written information regarding this study to be provided to the subject or the subject’s legal 
guardian must be approved by the IRB/IEC. Documentation of all IRB/IEC approvals and of the 
IRB/IEC compliance with ICH harmonised tripartite guideline E6(R2): Good Clinical Practice (GCP) 
will be maintained by the site and will be available for review by Kiniksa Pharmaceutical or its 
designee. 
All IRB/IEC approvals should be signed by the IRB/IEC chairman or designee and must identify the 
IRB/IEC name and address, the clinical protocol by title or protocol number or both, and the date 
approval or a favorable opinion was granted. 
The investigator is responsible for providing written summaries of the progress and status of the study 
at intervals not exceeding 1 year or otherwise specified by the IRB/IEC. The investigator must 
promptly supply Kiniksa Pharmaceutical or its designee, the IRB/IEC, and, where applicable, the 
institution, with written reports on any changes significantly affecting the conduct of the study or 
increasing the risk to subjects. 
9.2 
Ethical Conduct of the Study 
The study will be performed in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki, ICH GCP, the protocol, and all applicable regulations. 
9.3 
Subject Information and Consent 
A written informed consent in compliance approved by an IRB/IEC, as appropriate, at each 
center/country shall be obtained from each subject before entering the study or performing any 
unusual or nonroutine procedure that involves risk to the subject. An informed consent for (or assent 
form, as applicable) template may be provided by Kiniksa Pharmaceutical or its designee to 
investigative sites. If any institution-specific modifications to study-related procedures are proposed 
or made by the site, the consent should be reviewed by Kiniksa Pharmaceutical or its designee or both 
before IRB/IEC submission. Once reviewed, the consent will be submitted by the investigator to his 
or her IRB/IEC for review and approval before the start of the study. If the ICF is revised during the 
course of the study, all active participating subjects must sign the revised form. 
Before screening, each prospective subject or his or her legal guardian will be given a full explanation 
of the study and be allowed to read the approved ICF. Once the investigator is assured that the 
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subject/legal guardian understands the implications of participating in the study, the subject/legal 
guardian will be asked to give consent to participate in the study by signing the ICF. 
It should be emphasized to the subjects that they may withdraw from the study at any time and for 
any reason without prejudice to their future medical care by the investigator or at the study site. 
Subjects who refuse to give or who withdraw written informed consent should not be included or 
continue in the study. 
For potential subjects under the age of 18, a parent or legal guardian is required to sign and date the 
ICF and the potential subject is also required to sign and date an informed assent form. The informed 
assent form explains the trial, it’s purpose, procedures as well as risk and benefits in age-appropriate 
language. Both the ICF and informed assent form, as applicable, are required prior to participation in 
the trial. The investigator shall retain the signed original ICF(s)/assent form(s), as applicable, and give 
a copy of the signed original form to the subject or legal guardian. 
For this study subjects will be required to sign and date the ICF (or assent form, if applicable) prior to 
entry to the study and prior to entry to LTE. 
In addition, a separate ICF (assent, if applicable) will be needed for subjects participating in 
pharmacogenomic testing. 
10 Investigator’s Obligations 
The following administrative items are meant to guide the investigator in the conduct of the study but 
may be subject to change based on local or country-specific industry and government standard 
operating procedures, working practice documents, or guidelines. 
10.1 Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records will be identified in a manner 
designed to maintain subject confidentiality. All records will be kept in a secure storage area with 
limited access. Clinical information will not be released without the written permission of the subject 
(or the subject’s legal guardian), except as necessary for monitoring and auditing by Kiniksa 
Pharmaceuticals, its designee, the regulatory agencies/authorities, or the IRB/IEC. 
The Investigator and all employees and co-workers involved with this study may not disclose or use 
for any purpose other than performance of the study any data, record, or other unpublished, 
confidential information disclosed to those individuals for the purpose of the study. Prior written 
agreement from Kiniksa Pharmaceuticals or its designee must be obtained for the disclosure of any 
said confidential information to other parties. 
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10.2 Financial Disclosure and Obligations 
Investigators   are   required to   provide   financial disclosure   information   to allow   Kiniksa 
Pharmaceuticals or its designee to submit the complete and accurate certification or disclosure 
statements required under US Title 21 Code of Federal Regulations (CFR) Part 54. In addition, the 
investigator must provide to Kiniksa Pharmaceuticals a commitment to promptly update this 
information if any relevant changes occur during the course of the investigation and for 1 year 
following the completion of the study. 
Neither Kiniksa Pharmaceuticals nor 
is financially responsible for further testing or treatment of 
any medical condition that may be detected during the screening process. In addition, in the absence 
of specific arrangements, neither Kiniksa Pharmaceuticals nor 
further treatment of the subject’s disease. 
is financially responsible for 
10.3 Investigator Documentation 
Prior to beginning the study, the investigator will be asked to comply with ICH E6(R2) 8.2 and Title 
21 of the CFR by providing the following essential documents, including but not limited to: 
• 
• 
• 
IRB/IEC approval 
Original investigator-signed investigator agreement page of the protocol 
Form FDA 1572, fully executed, and all updates on a new fully executed Form FDA 1572 or 
local country-specific equivalent for outside the US 
Curriculum vitae for the investigator and each sub-investigator listed on Form FDA 1572 
Financial disclosure information 
IRB/IEC-approved ICFs/assent forms, as applicable, samples of site advertisements for 
recruitment for this study, and any other written information regarding this study that is to be 
provided to the subject or legal guardian 
Laboratory certifications and normal ranges for any local laboratories used by the site, in 
accordance with 42 CFR 493 
• 
• 
• 
• 
10.4 Study Conduct 
The investigator agrees that the study will be conducted according to the principles of ICH E6(R2). 
The investigator will conduct all aspects of this study in accordance with all national, state, and local 
laws or regulations. Study information from this protocol will be posted on publicly available clinical 
trial registers before enrollment of subjects begins. 
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10.5 Adherence to Protocol 
The investigator agrees to conduct the study as outlined in this protocol in accordance with ICH 
E6(R2) and all applicable guidelines and regulations. 
10.6 Adverse Events and Study Report Requirements 
By participating in this study, the investigator agrees to submit reports of SAEs to 
and/or 
IRB/IEC according to the time line and method outlined in the protocol. In addition, the investigator 
agrees to submit annual reports to the study site IRB/IEC as appropriate. 
10.7 Investigator’s Final Report 
Upon completion of the study, the investigator, where applicable, should inform the institution; the 
investigator/institution should provide the IRB/IEC with a summary of the study’s outcome and 
Kiniksa Pharmaceuticals and regulatory authority(ies) with any reports required. 
10.8 Records Retention 
It is the responsibility of the investigator to ensure all essential trial documentation and source records 
(e.g., signed ICFs, study site/clinic files, subjects’ hospital notes, copies of eCRFs) at their site are 
securely retained. The Sponsor will inform the investigator of the time periods for retaining study 
records to comply with all applicable regulatory requirements. The minimum retention time will meet 
the strictest standard applicable to that site for the study, as dictated by any institutional requirements 
or local laws or regulations; otherwise, the retention period by default will be 15 years. 
10.9 Publications 
Kiniksa shall have the sole and exclusive right to publish information obtained from the study, 
including any data, results, and conclusions. Investigators are encouraged to participate in the study 
execution such that they may be invited to participate in the authorship of a potential publication in a 
manner commensurate with their participation in the study execution in accordance with International 
Committee of Medicinal Journal Editors standards. Any publication of the results will be subject to 
the terms and conditions provided in the study agreement. 
11 Study Management 
The administrative structure will include a Data Monitoring Committee (DMC) and a Clinical 
Endpoint Committee (CEC). Please refer to Section 6.7 for further details. 
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11.1 Monitoring 
11.1.1 Monitoring of the Study 
Data for each subject will be recorded in source records and in the eCRF. Data collection must be 
completed for each subject who signs an ICF. 
For each subject enrolled, the investigator or designee will document in the source records of the 
subject that the subject is enrolled in this study along with all safety and efficacy information. The 
investigator is responsible for maintaining adequate case histories in the source records of each 
subject. Source data should be preserved for the maximum period of time permitted by the 
hospital/institution and made available by the investigator in the cases described above. 
In accordance with current GCP and ICH guidelines, the study monitor will carry out source 
document verification at regular intervals to ensure that the data collected in the eCRF are accurate 
and reliable. 
11.1.2 Inspection of Records 
Investigators and institutions involved in the study will permit study-related monitoring, audits, 
IRB/IEC review, and regulatory inspections by providing direct access to all study records. In the 
event of an audit, the investigator agrees to allow Kiniksa Pharmaceuticals, representatives of Kiniksa 
Pharmaceuticals, or a regulatory agency(ies) access to all study records. 
The investigator should promptly notify Kiniksa Pharmaceuticals and 
of any audits scheduled by 
any regulatory authorities and promptly forward copies of any audit reports received to Kiniksa 
Pharmaceuticals and 
. 
11.2 Management of Protocol Amendments and Deviations 
11.2.1 Modification of the Protocol 
Sponsor initiated amendments to the protocol must be submitted in writing to the investigator’s 
IRB/IEC for approval and to the regulatory authorities, if required, before subjects can be enrolled 
into an amended protocol. 
11.2.2 Protocol Deviations 
A deviation from the protocol is any change, divergence, or departure from the study design or 
procedures defined in the protocol. No waivers will be granted for exemptions to inclusion/exclusion 
criteria. The Investigator will conduct the study in compliance with the protocol agreed to with the 
Sponsor and, if required, the regulatory authorities, and which was given approval/favorable opinion 
by the IRB/IEC. In the event of a protocol deviation, the Sponsor or a designee must be notified. 
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The Investigator, or person designated by the Investigator, must document and explain any deviation 
from the approved protocol. The Investigator will notify the IRB/IEC of deviations from the protocol 
in accordance with local procedures. 
11.3 Study Termination 
Although Kiniksa Pharmaceuticals has every intention of completing the study, Kiniksa 
Pharmaceuticals reserves the right to discontinue the study at any time in case of safety concerns 
(e.g., SUSARs) or if special circumstances concerning the study drug or the company itself occur, 
making further treatment of subjects impossible. In this event, the investigator(s) will be informed of 
the reason for study termination. 
The end of the study is defined as the date on which the last subject completes the last visit (includes 
follow-up visit). 
11.4 Final Report 
Whether the study is completed or prematurely terminated, Kiniksa Pharmaceutical will ensure that 
the clinical study report(s) are prepared and provided to the regulatory agency(ies) as required by the 
applicable regulatory requirement(s). The Sponsor will also ensure that the clinical study reports in 
marketing applications meet the standards of the ICH harmonised tripartite guideline E3: Structure 
and content of clinical study reports. 
Where required by applicable regulatory requirements, an investigator signatory will be identified to 
approve the clinical study report. The investigator will be provided reasonable access to statistical 
tables, figures, and relevant reports and will have the opportunity to review the complete study 
results. 
Upon completion of the clinical study report, Kiniksa Pharmaceutical will provide the investigator(s) 
with the full summary of the study results. The investigator(s) are encouraged to share the summary 
results with the study subjects, as appropriate. The study results will be posted on publicly available 
clinical trial registers, as applicable. 
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12 Reference List 
Adler Y, Charron P, Imazio M, et al. 2015 ESC Guidelines for the diagnosis and management of 
pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the 
European Society of Cardiology (ESC) Endorsed by: The European Association for Cardio-Thoracic 
Surgery (EACTS). Eur Heart J. 2015;36(42):2921-2964. 
Agarwal SK, Vallurupalli S, Uretsky BF, et al. Effectiveness of colchicine for the prevention of 
recurrent pericarditis and post-pericardiotomy syndrome: an updated meta-analysis of randomized 
clinical data. Eur Heart J Cardiovasc Pharmacother. 2015;1(2):117-125. 
Baskar S, Klein AL, Zeft A. The use of IL-1 receptor antagonist (anakinra) in idiopathic recurrent 
pericarditis: A narrative review. Cardiol Res Pract. 2016;2016:7840724. 
Brucato A, Imazio M, Gattorno M, et al. Effect of anakinra on recurrent pericarditis among patients 
with colchicine resistance and corticosteroid dependence: The AIRTRIP randomized clinical trial. 
JAMA. 2016;316(18):1906-1912. 
Cantarini L, Lopalco G, Selmi C, et al. Autoimmunity and autoinflammation as the yin and yang of 
idiopathic recurrent acute pericarditis. Autoimmun Rev. 2015;14(2):90-97. 
Dinarello CA, Simon A, van der Meer JW. Treating inflammation by blocking interleukin-1 in a 
broad spectrum of diseases. Nat. Rev. Drug Discov. 2012; 11(8):633-652. 
Dworkin RH, Turk DC, Farrar JT, et al. Core outcome measures for chronic pain clinical trials: 
IMMPACT recommendations. Pain. 2005;113(1-2):9-19. 
Garg M, de Jesus AA, Chapelle D, et al. Rilonacept maintains long-term inflammatory remission in 
patients with deficiency of the IL-1 receptor antagonist. JCI Insight. 2017;2(16):e94838. 
Goldbach-Mansky R, Shroff S, Wilson M, et al. A pilot study to evaluate the safety and efficacy of 
the long-acting IL-1 inhibitor, rilonacept (IL-1 Trap) in patients with familial cold autoinflammatory 
syndrome (FCAS). Arthritis Rheum. 2008;58(8):2432-2442. 
Guy W. Clinical global impressions. In: U.S. Department of Health, Education, and Welfare, Public 
Health 
Service, 
Alcohol, 
Drug 
Abuse, 
and 
Mental 
Health 
Administration, 
NIMH 
Psychopharmacology Research Branch, Division of Extramural Research Programs, eds. ECDEU 
Assessment Manual for Psychopharmacology. Rockville, MD: National Institute for Mental Health; 
1976:218–22. Revised DHEW Pub No ADM 76–338. 
Hawker GA, Mian S, Kendzerska T, et al. Measures of adult pain: visual analog scale for pain (VAS 
Pain), numeric rating scale for pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form 
McGill Pain Questionnaire (SF-MPQ), chronic pain grade scale (CPGS), Short Form-36 Bodily Pain 
Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis 
Care Res. 2011;63(Suppl 11):S240-S252. 
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Imazio M, Brucato A, Pluymaekers N, et al. Recurrent pericarditis in children and adolescents:a 
multicenter cohort study. J Cardiovasc Med 2016; 17(9):707-712. 
Imazio M. Treatment of recurrent pericarditis. Rev Esp Cardiol. 2014;67(5):345-348. 
Imazio M, Spodick DH, Brucato A, et al. Controversial issues in the management of pericardial 
diseases. Circulation. 2010; 121(7):916-928. 
Imazio M, Brucato A, Cumetti D, et al. Corticosteroids for recurrent pericarditis: high versus low 
doses: a nonrandomized observation. Circulation. 2008; 118(6):667-671. 
Imazio M, Demichelis B, Parrini I,  et al.  Management, risk factors,  and outcomes in recurrent 
pericarditis. Am J Cardiol. 2005;96(5):736-739. 
Khandaker MH, Espinosa RE, Nishimura RA, et al. Pericardial disease: diagnosis and management. 
Mayo Clin Proc. 2010; 85(6):572-593. 
Lazaros G, Imazio M, Brucato A, et al. Anakinra: an emerging option for refractory idiopathic 
recurrent pericarditis: a systematic review of published evidence. J Cardiovasc Med. 2016;17(4):256- 
262. 
Lilly SL. Treatment of acute and recurrent idiopathic pericarditis. Circulation. 2013;127(16):1723- 
1726. 
Lotrionte M, Biondi-Zoccai G, Imazio M, et al. International collaborative systematic review of 
controlled clinical trials on pharmacologic treatments for acute pericarditis and its recurrences. Am 
Heart J. 2010; 160(4):662-670. 
Maisch B, Seferović PM, Ristić AD, et al. Guidelines on the diagnosis and management of pericardial 
diseases executive summary: The Task Force on the Diagnosis and Management of Pericardial 
Diseases of the European Society of Cardiology. Eur Heart J. 2004;25(7):587-610. 
Mannion AF, Balagué F, Pellisé F, et al. Pain measurement in patients with low back pain. Nat Clin 
Practice Rheumatol. 2007;3(11):610-618. 
Morin CM, Belleville G, Bélanger L, et al. The insomnia severity index: psychometric indicators to 
detect insomnia cases and evaluate treatment response. Sleep. 2011;34(5):601-608. 
Theodoropoulou K, von Scheven-Gête A, Bressieux-Degueldre S, et al. A case of corticosteroid- 
dependent recurrent pericarditis with different response to two IL-1 blocking agents. Pediatr 
Rheumatol Online J. 2015;13(Suppl 1):P155. 
van Reenen M, Janssen B. EQ-5D-5L User Guide. Version 2.1. April 2015. Available from: 
https://euroqol.org/wp-content/uploads/2016/09/EQ-5D-5L_UserGuide_2015.pdf. 
Zayas R, Anguita M, Torres F, et al. Incidence of specific etiology and role of methods for specific 
etiologic diagnosis of primary acute pericarditis. Am J Cardiol. 1995;75(5):378-382. 
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13 Appendices 
13.1 Appendix: ARCALYST® 
Information 
Prescribing 
CONTRAINDICATIONS 
HIGHLIGHTS OF PRESCRIBING INFORMATION 
These highlights do not include all the information needed 
to use ARCALYST safely and effectively. See full 
prescribing information for ARCALYST. 
None. (4) 
WARNINGS AND PRECAUTIONS 
• Interleukin-1 blockade may interfere with immune 
response to infections. Serious, life-threatening infections 
have been reported in patients taking ARCALYST. 
Discontinue treatment with ARCALYST if a patient 
develops a serious infection. Do not initiate treatment with 
ARCALYST in patients with active or chronic infections. 
(5.1) 
Hypersensitivity reactions associated with ARCALYST 
administration have been rare. If a hypersensitivity 
reaction occurs, discontinue administration of 
ARCALYST and initiate appropriate therapy. (5.5) 
Live vaccines should not be given concurrently with 
ARCALYST. Prior to initiation of therapy with 
ARCALYST, patients should receive all recommended 
vaccinations. (5.3) 
ARCALYST® (rilonacept) 
Injection for Subcutaneous Use 
Initial U.S. Approval: 2008 
INDICATIONS AND USAGE 
ARCALYST (rilonacept) is an interleukin-1 blocker indicated 
for the treatment of Cryopyrin-Associated Periodic Syndromes 
(CAPS), including Familial Cold Auto-inflammatory 
Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in 
adults and children 12 and older. (1) 
• 
• 
DOSAGE AND ADMINISTRATION 
• Adult patients 18 yrs and older: Initiate treatment with a 
loading dose of 320 mg delivered as two, 2-mL, 
subcutaneous injections of 160 mg on the same day at two 
different sites. Continue dosing with a once-weekly 
injection of 160 mg administered as a single, 2-mL, 
subcutaneous injection. Do not administer ARCALYST 
more often than once weekly. (2) 
Pediatric patients aged 12 to 17 years: Initiate treatment 
with a loading dose of 4.4 mg/kg, up to a maximum of 320 
mg, delivered as one or two subcutaneous injections with a 
maximum single-injection volume of 2 mL. Continue 
dosing with a once-weekly injection of 2.2 mg/kg, up to a 
maximum of 160 mg, administered as a single 
subcutaneous injection, up to 2 mL. If the initial dose is 
given as two injections, they should be given on the same 
day at two different sites. Do not administer ARCALYST 
more often than once weekly. (2) 
ADVERSE REACTIONS 
The most common adverse reactions reported by patients with 
CAPS treated with ARCALYST are injection-site reactions 
and upper respiratory tract infections. (6.2, 6.3) 
• 
To report SUSPECTED ADVERSE REACTIONS, contact 
Regeneron at 1-877-REGN-777 (1-877-734-6777) or FDA 
at 1-800-FDA-1088 or www.fda.gov/medwatch. 
DRUG INTERACTIONS 
No formal drug interaction studies have been conducted with 
ARCALYST. (7) 
USE IN SPECIFIC POPULATIONS 
Pregnancy – No human data. Based on animal data, may cause 
fetal harm. (8.1) 
DOSAGE FORMS AND STRENGTHS 
Sterile, single-use 20-mL, glass vial containing 220 mg of 
rilonacept as a lyophilized powder for reconstitution. (3) 
See 17 for PATIENT COUNSELING INFORMATION 
and FDA-approved patient labeling. 
Revised: 9/2016 
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FULL PRESCRIBING INFORMATION 
1 
INDICATIONS AND USAGE 
ARCALYST® (rilonacept) is an interleukin-1 blocker indicated for the treatment of Cryopyrin-Associated 
Periodic Syndromes (CAPS), including Familial Cold Auto-inflammatory Syndrome (FCAS) and 
Muckle-Wells Syndrome (MWS) in adults and children 12 and older. 
2 
2.1 
DOSAGE AND ADMINISTRATION 
General Dosing Information 
Injection for Subcutaneous Use Only. 
2.2 
Dosing 
Adult patients 18 years and older: Treatment should be initiated with a loading dose of 320 mg delivered 
as two, 2-mL, subcutaneous injections of 160 mg each given on the same day at two different sites. 
Dosing should be continued with a once-weekly injection of 160 mg administered as a single, 2-mL, 
subcutaneous injection. ARCALYST should not be given more often than once weekly. Dosage 
modification is not required based on advanced age or gender. 
Pediatric patients aged 12 to 17 years: Treatment should be initiated with a loading dose of 4.4 mg/kg, up 
to a maximum of 320 mg, delivered as one or two subcutaneous injections with a maximum single- 
injection volume of 2 mL. Dosing should be continued with a once-weekly injection of 2.2 mg/kg, up to a 
maximum of 160 mg, administered as a single subcutaneous injection, up to 2 mL. If the initial dose is 
given as two injections, they should be given on the same day at two different sites. ARCALYST should 
not be given more often than once weekly. 
2.3 
Preparation for Administration 
Each single-use vial of ARCALYST contains a sterile, white to off-white, preservative-free, lyophilized 
powder. Reconstitution with 2.3 mL of preservative-free Sterile Water for Injection (supplied separately) 
is required prior to subcutaneous administration of the drug. 
2.4 
Administration 
Using aseptic technique, withdraw 2.3 mL of preservative-free Sterile Water for Injection through a 27- 
gauge, ½-inch needle attached to a 3-mL syringe and inject the preservative-free Sterile Water for 
Injection into the drug product vial for reconstitution. The needle and syringe used for reconstitution with 
preservative-free Sterile Water for Injection should then be discarded and should not be used for 
subcutaneous injections. After the addition of preservative-free Sterile Water for Injection, the vial 
contents should be reconstituted by shaking the vial for approximately one minute and then allowing it to 
sit for one minute. The resulting 80-mg/mL solution is sufficient to allow a withdrawal volume of up to 2 
mL for subcutaneous administration. The reconstituted solution is viscous, clear, colorless to pale yellow, 
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and essentially free from particulates. Prior to injection, the reconstituted solution should be carefully 
inspected for any discoloration or particulate matter. If there is discoloration or particulate matter in the 
solution, the product in that vial should not be used. 
Using aseptic technique, withdraw the recommended dose volume, up to 2 mL (160 mg), of the solution 
with a new 27-gauge, ½-inch needle attached to a new 3-mL syringe for subcutaneous injection. EACH 
VIAL SHOULD BE USED FOR A SINGLE DOSE ONLY. Discard the vial after withdrawal of drug. 
Sites for subcutaneous injection, such as the abdomen, thigh, or upper arm, should be rotated. Injections 
should never be made at sites that are bruised, red, tender, or hard. 
2.5 
Stability and Storage 
The lyophilized ARCALYST product is to be stored refrigerated at 2° to 8°C (36° to 46°F) inside the 
original carton to protect it from light. Do not use beyond the date stamped on the label. After 
reconstitution, ARCALYST may be kept at room temperature, should be protected from light, and should 
be used within three hours of reconstitution. ARCALYST does not contain preservatives; therefore, 
unused portions of ARCALYST should be discarded. 
3 
DOSAGE FORMS AND STRENGTHS 
ARCALYST is supplied in sterile, single-use, 20-mL, glass vials. Each vial contains 220 mg of rilonacept 
as a white to off-white, preservative-free, lyophilized powder. Reconstitution with 2.3 mL of 
preservative-free Sterile Water for Injection is required prior to subcutaneous administration of the drug. 
The reconstituted ARCALYST is a viscous, clear, colorless to pale yellow, essentially free from 
particulates, 80-mg/mL solution. 
4 
None. 
CONTRAINDICATIONS 
5 
5.1 
WARNINGS AND PRECAUTIONS 
Infections 
Interleukin-1 (IL-1) blockade may interfere with the immune response to infections. Treatment with 
another medication that works through inhibition of IL-1 has been associated with an increased risk of 
serious infections, and serious infections have been reported in patients taking ARCALYST [see Clinical 
Studies (14)]. There was a greater incidence of infections in patients on ARCALYST compared with 
placebo. In the controlled portion of the study, one infection was reported as severe, which was bronchitis 
in a patient on ARCALYST. 
In an open-label extension study, one patient developed bacterial meningitis and died [see Adverse 
Reactions (6.3)]. ARCALYST should be discontinued if a patient develops a serious infection. Treatment 
with ARCALYST should not be initiated in patients with an active or chronic infection. 
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Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
In clinical studies, ARCALYST has not been administered concomitantly with tumor necrosis factor 
(TNF) inhibitors. An increased incidence of serious infections has been associated with administration of 
an IL-1 blocker in combination with TNF inhibitors. Taking ARCALYST with TNF inhibitors is not 
recommended because this may increase the risk of serious infections. 
Drugs that affect the immune system by blocking TNF have been associated with an increased risk of 
reactivation of latent tuberculosis (TB). It is possible that taking drugs such as ARCALYST that block IL- 
1 increases the risk of TB or other atypical or opportunistic infections. Healthcare providers should follow 
current CDC guidelines both to evaluate for and to treat possible latent tuberculosis infections before 
initiating therapy with ARCALYST. 
5.2 
Immunosuppression 
The impact of treatment with ARCALYST on active and/or chronic infections and the development of 
malignancies is not known [see Adverse Reactions (6.3)]. However, treatment with immunosuppressants, 
including ARCALYST, may result in an increase in the risk of malignancies. 
5.3 
Immunizations 
Since no data are available on either the efficacy of live vaccines or on the risks of secondary 
transmission of infection by live vaccines in patients receiving ARCALYST, live vaccines should not be 
given concurrently with ARCALYST. In addition, because ARCALYST may interfere with normal 
immune response to new antigens, vaccinations may not be effective in patients receiving ARCALYST. 
No data are available on the effectiveness of vaccination with inactivated (killed) antigens in patients 
receiving ARCALYST. 
Because IL-1 blockade may interfere with immune response to infections, it is recommended that prior to 
initiation of therapy with ARCALYST adult and pediatric patients receive all recommended vaccinations, 
as appropriate, including pneumococcal vaccine and inactivated influenza vaccine. (See current 
Recommended Immunizations schedules at the website of the Centers for Disease Control and 
Prevention. http://www.cdc.gov/vaccines/schedules/index.html). 
5.4 
Lipid Profile Changes 
Patients should be monitored for changes in their lipid profiles and provided with medical treatment if 
warranted [see Adverse Reactions (6.7)]. 
5.5 
Hypersensitivity 
Hypersensitivity reactions associated with ARCALYST administration in the clinical studies were rare. If 
a hypersensitivity reaction occurs, administration of ARCALYST should be discontinued and appropriate 
therapy initiated. 
6 
ADVERSE REACTIONS 
Six serious adverse reactions were reported by four patients during the clinical program. These serious 
adverse reactions were Mycobacterium intracellulare infection; gastrointestinal bleeding and colitis; 
sinusitis and bronchitis; and Streptococcus pneumoniae meningitis [see Adverse Reactions (6.3)]. 
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Protocol KPL-914-C002 
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The most commonly reported adverse reaction associated with ARCALYST was injection-site reaction 
(ISR) [see Adverse Reactions (6.2)]. The next most commonly reported adverse reaction was upper 
respiratory infection [see Adverse Reactions (6.3)]. 
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in 
the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and 
may not reflect the rates observed in practice. 
The data described herein reflect exposure to ARCALYST in 600 patients, including 85 exposed for at 
least 6 months and 65 exposed for at least one year. These included patients with CAPS, patients with 
other diseases, and healthy volunteers. Approximately 60 patients with CAPS have been treated weekly 
with 160 mg of ARCALYST. The pivotal trial population included 47 patients with CAPS. These patients 
were between the ages of 22 and 78 years (average 51 years). Thirty-one patients were female and 16 
were male. All of the patients were White/Caucasian. Six pediatric patients (12-17 years) were enrolled 
directly into the open-label extension phase. 
6.1 
Clinical Trial Experience 
Part A of the clinical trial was conducted in patients with CAPS who were naïve to treatment with 
ARCALYST. Part A of the study was a randomized, double-blind, placebo-controlled, six-week study 
comparing ARCALYST to placebo [see Clinical Studies (14)]. Table 1 reflects the frequency of adverse 
events reported by at least two patients during Part A. 
Table 1: 
Most Frequent Adverse Reactions (Part A, Reported by at Least Two Patients) 
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Adverse Event 
 
ARCALYST 
160 mg 
(n = 23) 
Placebo 
(n= 24) 
 
Any AE 
17 (74%) 
13 (54%) 
Injection-site reactions 
11 (48%) 
3 (13%) 
Upper respiratory tract infection 
6 (26%) 
1 (4%) 
Nausea 
1 (4%) 
3 (13%) 
Diarrhea 
1 (4%) 
3 (13%) 
Sinusitis 
2 (9%) 
1 (4%) 
Abdominal pain upper 
0 
2 (8%) 
Cough 
2 (9%) 
0 
Hypoesthesia 
2 (9%) 
0 
Stomach discomfort 
1 (4%) 
1 (4%) 
Urinary tract infection 
1 (4%) 
1 (4%) 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
6.2 
Injection-Site Reactions 
In patients with CAPS, the most common and consistently reported adverse event associated with 
ARCALYST was injection-site reaction (ISR). The ISRs included erythema, swelling, pruritus, mass, 
bruising, inflammation, pain, edema, dermatitis, discomfort, urticaria, vesicles, warmth and hemorrhage. 
Most injection-site reactions lasted for one to two days. No ISRs were assessed as severe, and no patient 
discontinued study participation due to an ISR. 
6.3 
Infections 
During Part A, the incidence of patients reporting infections was greater with ARCALYST (48%) than 
with placebo (17%). In Part B, randomized withdrawal, the incidence of infections were similar in the 
ARCALYST (18%) and the placebo patients (22%). Part A of the trial was initiated in the winter months, 
while Part B was predominantly performed in the summer months. 
In placebo-controlled studies across a variety of patient populations encompassing 360 patients treated 
with rilonacept and 179 treated with placebo, the incidence of infections was 34% and 27% (2.15 per 
patient-exposure year and 1.81 per patient-exposure year), respectively, for rilonacept and placebo. 
Serious Infections: One patient receiving ARCALYST for an unapproved indication in another study 
developed an infection in his olecranon bursa with Mycobacterium intracellulare. The patient was on 
chronic glucocorticoid treatment. The infection occurred after an intraarticular glucocorticoid injection 
into the bursa with subsequent local exposure to a suspected source of mycobacteria. The patient 
recovered after the administration of the appropriate antimicrobial therapy. One patient treated for another 
unapproved indication developed bronchitis/sinusitis, which resulted in hospitalization. One patient died 
in an open-label study of CAPS from Streptococcus pneumoniae meningitis. 
6.4 
Malignancies 
[see Warnings and Precautions (5.2)]. 
6.5 
Hematologic Events 
One patient in a study in an unapproved indication developed transient neutropenia (ANC < 1 x 109/L) 
after receiving a large dose (2000 mg intravenously) of ARCALYST. The patient did not experience any 
infection associated with the neutropenia. 
6.6 
Immunogenicity 
Antibodies directed against the receptor domains of rilonacept were detected by an ELISA assay in 
patients with CAPS after treatment with ARCALYST. Nineteen of 55 patients (35%) who had received 
ARCALYST for at least 6 weeks tested positive for treatment-emergent binding antibodies on at least one 
occasion. Of the 19, seven tested positive at the last assessment (Week 18 or 24 of the open-label 
extension period), and five patients tested positive for neutralizing antibodies on at least one occasion. 
There was no correlation of antibody activity and either clinical effectiveness or safety. 
The data reflect the percentage of patients whose test results were positive for antibodies to the rilonacept 
receptor domains in specific assays, and are highly dependent on the sensitivity and specificity of the 
assays. The observed incidence of antibody (including neutralizing antibody) positivity in an assay is 
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Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
highly dependent on several factors including assay sensitivity and specificity, assay methodology, 
sample handling, timing of sample collection, concomitant medications, and underlying disease. For these 
reasons, comparison of the incidence of antibodies to rilonacept with the incidence of antibodies to other 
products may be misleading. 
6.7 
Lipid Profiles 
Cholesterol and lipid levels may be reduced in patients with chronic inflammation. Patients with CAPS 
treated with ARCALYST experienced increases in their mean total cholesterol, HDL cholesterol, LDL 
cholesterol, and triglycerides. The mean increases from baseline for total cholesterol, HDL cholesterol, 
LDL cholesterol, and triglycerides were 19 mg/dL, 2 mg/dL, 10 mg/dL, and 57 mg/dL respectively after 6 
weeks of open-label therapy. Physicians should monitor the lipid profiles of their patients (for example 
after 2-3 months) and consider lipid-lowering therapies as needed based upon cardiovascular risk factors 
and current guidelines. 
7 
7.1 
DRUG INTERACTIONS 
TNF-Blocking Agent and IL-1 Blocking Agent 
Specific drug interaction studies have not been conducted with ARCALYST. Concomitant administration 
of another drug that blocks IL-1 with a TNF-blocking agent in another patient population has been 
associated with an increased risk of serious infections and an increased risk of neutropenia. The 
concomitant administration of ARCALYST with TNF-blocking agents may also result in similar 
toxicities and is not recommended [see Warnings and Precautions (5.1)]. The concomitant administration 
of ARCALYST with other drugs that block IL-1 has not been studied. Based upon the potential for 
pharmacologic interactions between rilonacept and a recombinant IL-1ra, concomitant administration of 
ARCALYST and other agents that block IL-1 or its receptors is not recommended. 
7.2 
Cytochrome P450 Substrates 
The formation of CYP450 enzymes is suppressed by increased levels of cytokines (e.g., IL-1) during 
chronic inflammation. Thus it is expected that for a molecule that binds to IL-1, such as rilonacept, the 
formation of CYP450 enzymes could be normalized. This is clinically relevant for CYP450 substrates 
with a narrow therapeutic index, where the dose is individually adjusted (e.g., warfarin). Upon initiation 
of ARCALYST, in patients being treated with these types of medicinal products, therapeutic monitoring 
of the effect or drug concentration should be performed and the individual dose of the medicinal product 
may need to be adjusted as needed. 
8 
8.1 
USE IN SPECIFIC POPULATIONS 
Pregnancy 
Pregnancy Category C. There are no adequate and well-controlled studies of ARCALYST in pregnant 
women. Based on animal data, ARCALYST may cause fetal harm. An embryo-fetal developmental 
toxicity study was performed in cynomolgus monkeys treated with 0, 5, 15 or 30 mg/kg given twice a 
week (highest dose is approximately 3.7-fold higher than the human doses of 160 mg based on body 
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surface area). The fetus of the only monkey with exposure to rilonacept during the later period of 
gestation showed multiple fusion and absence of the ribs and thoracic vertebral bodies and arches. 
Exposure to rilonacept during this time period was below that expected clinically. Likewise, in the 
cynomolgus monkey, all doses of rilonacept reduced serum levels of estradiol up to 64% compared to 
controls and increased the incidence of lumbar ribs compared to both control animals and historical 
control incidences. In perinatal and postnatal developmental toxicology studies in the mouse model using 
a murine analog of rilonacept (0, 20, 100 or 200 mg/kg), there was a 3-fold increase in the number of 
stillbirths in dams treated with 200 mg/kg three times per week (the highest dose is approximately 6-fold 
higher than the 160 mg maintenance dose based on body surface area). ARCALYST should be used 
during pregnancy only if the benefit justifies the potential risk to the fetus. 
Nonteratogenic effects. A peri- and post-natal reproductive toxicology study was performed in which 
mice were subcutaneously administered a murine analog of rilonacept at doses of 20, 100, 200 mg/kg 
three times per week (the highest dose is approximately 6-fold higher than the 160 mg maintenance dose 
based on body surface area). Results indicated an increased incidence in unscheduled deaths of the F1 
offspring during maturation at all doses tested. 
8.3 
Nursing Mothers 
It is not known whether rilonacept is excreted in human milk. Because many drugs are excreted in human 
milk, caution should be exercised when ARCALYST is administered to a nursing woman. 
8.4 
Pediatric Use 
Six pediatric patients with CAPS between the ages of 12 and 16 were treated with ARCALYST at a 
weekly, subcutaneous dose of 2.2 mg/kg (up to a maximum of 160 mg) for 24-weeks during the open- 
label extension phase. These patients showed improvement from baseline in their symptom scores and in 
objective markers of inflammation (e.g. Serum Amyloid A and C-Reactive Protein). The adverse events 
included injection site reactions and upper respiratory symptoms as were commonly seen in the adult 
patients. 
The trough drug levels for four pediatric patients measured at the end of the weekly dose interval (mean 
20 mcg/mL, range 3.6 to 33 mcg/mL) were similar to those observed in adult patients with CAPS (mean 
24 mcg/mL, range 7 to 56 mcg/mL). 
Safety and effectiveness in pediatric patients below the age of 12 have not been established. 
When administered to pregnant primates, rilonacept treatment may have contributed to alterations in bone 
ossification in the fetus. It is not known if ARCALYST will alter bone development in pediatric patients. 
Pediatric patients treated with ARCALYST should undergo appropriate monitoring for growth and 
development. [see Use in Specific Populations (8.1)] 
8.5 
Geriatric Use 
In the placebo-controlled clinical studies in patients with CAPS and other indications, 70 patients 
randomized to treatment with ARCALYST were  65 years of age, and 6 were  75 years of age. In the 
CAPS clinical trial, efficacy, safety and tolerability were generally similar in elderly patients as compared 
to younger adults; however, only ten patients  65 years old participated in the trial. In an open-label 
extension study of CAPS, a 71 year old woman developed bacterial meningitis and died [see Adverse 
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Version 1.0, 26 Sep 2018 
Reactions (6.3)]. Age did not appear to have a significant effect on steady-state trough concentrations in 
the clinical study. 
8.6 
Patients with Renal Impairment 
No formal studies have been conducted to examine the pharmacokinetics of rilonacept administered 
subcutaneously in patients with renal impairment. 
8.7 
Patients with Hepatic Impairment 
No formal studies have been conducted to examine the pharmacokinetics of rilonacept administered 
subcutaneously in patients with hepatic impairment. 
10 
OVERDOSAGE 
There have been no reports of overdose with ARCALYST. Maximum weekly doses of up to 320 mg have 
been administered subcutaneously for up to approximately 18 months in a small number of patients with 
CAPS and up to 6 months in patients with an unapproved indication in clinical trials without evidence of 
dose-limiting toxicities. In addition, ARCALYST given intravenously at doses up to 2000 mg monthly in 
another patient population for up to six months were tolerated without dose-limiting toxicities. The 
maximum amount of ARCALYST that can be safely administered has not been determined. 
In case of overdose, it is recommended that the patient be monitored for any signs or symptoms of 
adverse reactions or effects, and appropriate symptomatic treatment instituted immediately. 
11 
DESCRIPTION 
Rilonacept is a dimeric fusion protein consisting of the ligand-binding domains of the extracellular 
portions of the human interleukin-1 receptor component (IL-1RI) and IL-1 receptor accessory protein (IL- 
1RAcP) linked in-line to the Fc portion of human IgG1. Rilonacept has a molecular weight of 
approximately 251 kDa. Rilonacept is expressed in recombinant Chinese hamster ovary (CHO) cells. 
ARCALYST is supplied in single-use, 20-mL glass vials containing a sterile, white to off-white, 
lyophilized powder. Each vial of ARCALYST is to be reconstituted with 2.3 mL of Sterile Water for 
Injection. A volume of up to 2 mL can be withdrawn, which is designed to deliver 160 mg for 
subcutaneous administration only. The resulting solution is viscous, clear, colorless to pale yellow, and 
essentially free from particulates. Each vial contains 220 mg rilonacept. After reconstitution, each vial 
contains 80 mg/mL rilonacept, 46 mM histidine, 50 mM arginine, 3.0% (w/v) polyethylene glycol 3350, 
2.0% (w/v) sucrose, and 1.0% (w/v) glycine at a pH of 6.5 ± 0.3. No preservatives are present. 
12 
12.1 
CLINICAL PHARMACOLOGY 
Mechanism of Action 
CAPS refer to rare genetic syndromes generally caused by mutations in the NLRP-3 [Nucleotide-binding 
domain, leucine rich family (NLR), pyrin domain containing 3] gene (also known as Cold-Induced Auto- 
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Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
inflammatory Syndrome-1 [CIAS1]). CAPS disorders are inherited in an autosomal dominant pattern with 
male and female offspring equally affected. Features common to all disorders include fever, urticaria-like 
rash, arthralgia, myalgia, fatigue, and conjunctivitis. 
In most cases, inflammation in CAPS is associated with mutations in the NLRP-3 gene which encodes the 
protein cryopyrin, an important component of the inflammasome. Cryopyrin regulates the protease 
caspase-1 and controls the activation of interleukin-1 beta (IL-1β). Mutations in NLRP-3 result in an 
overactive inflammasome resulting in excessive release of activated IL-1β that drives inflammation. 
Rilonacept blocks IL-1β signaling by acting as a soluble decoy receptor that binds IL-1β and prevents its 
interaction with cell surface receptors. Rilonacept also binds IL-1α and IL-1 receptor antagonist (IL-1ra) 
with reduced affinity. The equilibrium dissociation constants for rilonacept binding to IL-1β, IL-1α and 
IL-1ra were 0.5 pM, 1.4 pM and 6.1 pM, respectively. 
12.2 
Pharmacodynamics 
C-Reactive Protein (CRP) and Serum Amyloid A (SAA) are indicators of inflammatory disease activity 
that are elevated in patients with CAPS. Elevated SAA has been associated with the development of 
systemic amyloidosis in patients with CAPS. Compared to placebo, treatment with ARCALYST resulted 
in sustained reductions from baseline in mean serum CRP and SAA to normal levels during the clinical 
trial. ARCALYST also normalized mean SAA from elevated levels. 
12.3 
Pharmacokinetics 
The average trough levels of rilonacept were approximately 24 mcg/mL at steady-state following weekly 
subcutaneous doses of 160 mg for up to 48 weeks in patients with CAPS. The steady-state appeared to be 
reached by 6 weeks. 
No pharmacokinetic data are available in patients with hepatic or renal impairment. 
No study was conducted to evaluate the effect of age, gender, or body weight on rilonacept exposure. 
Based on limited data obtained from the clinical study, steady state trough concentrations were similar 
between male and female patients. Age (26-78 years old) and body weight (50-120 kg) did not appear to 
have a significant effect on trough rilonacept concentrations. The effect of race could not be assessed 
because only Caucasian patients participated in the clinical study, reflecting the epidemiology of the 
disease. 
13 
13.1 
NONCLINICAL TOXICOLOGY 
Carcinogenesis, Mutagenesis, Impairment of Fertility 
Long-term animal studies have not been performed to evaluate the carcinogenic potential of rilonacept. 
The mutagenic potential of rilonacept was not evaluated. 
Male and female fertility was evaluated in a mouse surrogate model using a murine analog of rilonacept. 
Male mice were treated beginning 8 weeks prior to mating and continuing through female gestation day 
15. Female mice were treated for 2 weeks prior to mating and on gestation days 0, 3, and 6. The murine 
analog of rilonacept did not alter either male or female fertility parameters at doses up to 200 mg/kg (this 
dose is approximately 6-fold higher than the 160 mg maintenance dose based on body surface area). 
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14 
CLINICAL STUDIES 
The safety and efficacy of ARCALYST for the treatment of CAPS was demonstrated in a randomized, 
double-blind, placebo-controlled study with two parts (A and B) conducted sequentially in the same 
patients with FCAS and MWS. 
Part A was a 6-week, randomized, double-blind, parallel-group period comparing ARCALYST at a dose 
of 160 mg weekly after an initial loading dose of 320 mg to placebo. Part B followed immediately after 
Part A and consisted of a 9-week, patient-blind period during which all patients received ARCALYST 
160 mg weekly, followed by a 9-week, double-blind, randomized withdrawal period in which patients 
were randomly assigned to either remain on ARCALYST 160 mg weekly or to receive placebo. Patients 
were then given the option to enroll in a 24-week, open-label treatment extension phase in which all 
patients were treated with ARCALYST 160 mg weekly. 
Using a daily diary questionnaire, patients rated the following five signs and symptoms of CAPS: joint 
pain, rash, feeling of fever/chills, eye redness/pain, and fatigue, each on a scale of 0 (none, no severity) to 
10 (very severe). The study evaluated the mean symptom score using the change from baseline to the end 
of treatment. 
The changes in mean symptom scores for the randomized parallel-group period (Part A) and the 
randomized withdrawal period (Part B) of the study are shown in Table 2. ARCALYST-treated patients 
had a larger reduction in the mean symptom score in Part A compared to placebo-treated patients. In Part 
B, mean symptom scores increased more in patients withdrawn to placebo compared to patients who 
remained on ARCALYST. 
Table 2: Mean Symptom Scores 
*Differences are adjusted using an analysis of covariance model with terms for treatment and Part A baseline. 
**A confidence interval lying entirely below zero indicates a statistical difference favoring ARCALYST versus 
placebo. 
Daily mean symptom scores over time for Part A are shown in Figure 1. 
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Part A 
 
Placebo 
(n=24) 
ARCALYST 
(n=23) 
Part B 
 
Placebo 
(n=23) 
ARCALYST 
(n=22) 
Pre-treatment 
Baseline Period 
(Weeks -3 to 0) 
2.4 
 
3.1 
 
Active 
ARCALYST 
Baseline Period 
(Weeks 13 to 15) 
0.2 
 
0.3 
 
Endpoint Period 
(Weeks 4 to 6) 
2.1 
 
0.5 
 
Endpoint Period 
(Weeks 22 to 24) 
1.2 
 
0.4 
 
LS* Mean Change 
from Baseline to 
Endpoint 
-0.5 
 
-2.4 
 
LS* Mean Change 
from Baseline to 
Endpoint 
0.9 
 
0.1 
 
95% confidence 
interval for 
difference between 
treatment groups 
(-2.4, -1.3)** 
 
95% confidence 
interval for 
difference between 
treatment groups 
(-1.3, -0.4)** 
 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Figure 1: Group Mean Daily Symptom Scores by Treatment Group in Part A and 
Single-blind ARCALYST Treatment Phase from Week -3 to Week 15 
Improvement in symptom scores was noted within several days of initiation of ARCALYST therapy in 
most patients. 
In Part A, patients treated with ARCALYST experienced more improvement in each of the five 
components of the composite endpoint (joint pain, rash, feeling of fever/chills, eye redness/pain, and 
fatigue) than placebo-treated patients. 
In Part A, a higher proportion of patients in the ARCALYST group experienced improvement from 
baseline in the composite score by at least 30% (96% vs. 29% of patients), by at least 50% (87% vs. 8%) 
and by at least 75% (70% vs. 0%) compared to the placebo group. 
Serum Amyloid A (SAA) and C-Reactive Protein (CRP) levels are acute phase reactants that are typically 
elevated in patients with CAPS with active disease. During Part A, mean levels of CRP decreased versus 
baseline for the ARCALYST treated patients, while there was no change for those on placebo (Table 3). 
ARCALYST also led to a decrease in SAA versus baseline to levels within the normal range. 
Table 3. Mean Serum Amyloid A and C-Reactive Protein Levels Over Time in Part A 
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Part A 
ARCALYST 
Placebo 
SAA 
(normal range: 0.7 – 6.4 mg/L) 
(n=22) 
(n=24) 
Pre-treatment Baseline 
60 
110 
Week 6 
4 
110 
CRP 
(normal range: 0.0 – 8.4 mg/L) 
(n= 21) 
(n=24) 
Pre-treatment Baseline 
22 
30 
Week 6 
2 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
During the open-label extension, reductions in mean symptom scores, serum CRP, and serum SAA levels 
were maintained for up to one year. 
16 
HOW SUPPLIED/STORAGE AND HANDLING 
Each 20-mL glass vial of ARCALYST contains a sterile, white to off-white, preservative-free, lyophilized 
powder. ARCALYST is supplied in a carton containing four vials (NDC 61755-001-01). 
The lyophilized ARCALYST product is to be stored refrigerated at 2° to 8°C (36° to 46°F) inside the 
original carton to protect from light. Do not use beyond the date stamped on the label. After 
reconstitution, ARCALYST may be kept at room temperature, should be kept from light, and should be 
used within three hours of reconstitution. ARCALYST does not contain preservatives; therefore, unused 
portions of ARCALYST should be discarded. Discard the vial after a single withdrawal of drug. 
17 
PATIENT COUNSELING INFORMATION 
See FDA-approved patient labeling. 
The first injection of ARCALYST should be performed under the supervision of a qualified healthcare 
professional. If a patient or caregiver is to administer ARCALYST, he/she should be instructed on aseptic 
reconstitution of the lyophilized product and injection technique. The ability to inject subcutaneously 
should be assessed to ensure proper administration of ARCALYST, including rotation of injection sites. 
(See Patient Information Leaflet for ARCALYST®). ARCALYST should be reconstituted with 
preservative-free Sterile Water for Injection to be provided by the pharmacy. A puncture-resistant 
container for disposal of vials, needles and syringes should be used. Patients or caregivers should be 
instructed in proper vial, syringe, and needle disposal, and should be cautioned against reuse of these 
items. 
Injection-site Reactions: Physicians should explain to patients that almost half of the patients in the 
clinical trials experienced a reaction at the injection site. Injection-site reactions may include pain, 
erythema, swelling, pruritus, bruising, mass, inflammation, dermatitis, edema, urticaria, vesicles, warmth, 
and hemorrhage. Patients should be cautioned to avoid injecting into an area that is already swollen or 
red. Any persistent reaction should be brought to the attention of the prescribing physician. 
Infections: Patients should be cautioned that ARCALYST has been associated with serious, 
life-threatening infections, and not to initiate treatment with ARCALYST if they have a chronic or active 
infection. Patients should be counseled to contact their healthcare professional immediately if they 
develop an infection after starting ARCALYST. Treatment with ARCALYST should be discontinued if a 
patient develops a serious infection. Patients should be counseled not to take any IL-1 blocking drug, 
including ARCALYST, if they are also taking a drug that blocks TNF such as etanercept, infliximab, or 
adalimumab. Use of ARCALYST with other IL-1 blocking agents, such as anakinra, is not recommended. 
Vaccinations: Prior to initiation of therapy with ARCALYST physicians should review with adult and 
pediatric patients their vaccination history relative to current medical guidelines for vaccine use, including 
taking into account the potential of increased risk of infection during treatment with ARCALYST. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Manufactured and distributed by: 
Regeneron Pharmaceuticals, Inc. 
777 Old Saw Mill River Road, 
Tarrytown, NY 10591-6707, 1-877-REGN-777 (1-877-734-6777) 
U.S. License Number 1760 
NDC 61755-001-01 
© 2016, Regeneron Pharmaceuticals, Inc. 
All rights reserved. 
V 5.0 
Patient Information 
ARCALYST® (ARK-a-list) 
(rilonacept) 
Injection for Subcutaneous Use 
Read the patient information that comes with ARCALYST before you start taking it and each time 
you refill your prescription. There may be new information. The information in this leaflet does not 
take the place of talking with your healthcare provider about your medical condition and your 
treatment. 
What is the most important information I should know about ARCALYST? 
ARCALYST can affect your immune system. ARCALYST can lower the ability of your immune 
system to fight infections. Serious infections, including life-threatening infections and death have 
happened in patients taking ARCALYST. Taking ARCALYST can make you more likely to get 
infections, including life-threatening serious infections, or may make any infection that you 
have worse. 
You should not begin treatment with ARCALYST if you have an infection or have infections 
that keep coming back (chronic infection). 
After starting ARCALYST, if you get an infection, any sign of an infection including a fever, 
cough, flu-like symptoms, or have any open sores on your body, call your healthcare provider right 
away. Treatment with ARCALYST should be stopped if you develop a serious infection. 
You should not take medicines that block Tumor Necrosis Factor (TNF), such as Enbrel® 
(etanercept), Humira® (adalimumab), or Remicade® (infliximab), while you are taking 
ARCALYST. You should also not take other medicines that block Interleukin-1 (IL-1), such as 
Kineret  (anakinra), while taking ARCALYST. Taking ARCALYST with any of these 
medicines may increase your risk of getting a serious infection. 
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Protocol KPL-914-C002 
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Before starting treatment with ARCALYST, tell your healthcare provider if you: 
• 
• 
• 
• 
• 
• 
• 
think you have an infection 
are being treated for an infection 
have signs of an infection, such as fever, cough, or flu-like symptoms 
have any open sores on your body 
have a history of infections that keep coming back 
have asthma. Patients with asthma may have an increased risk of infection. 
have diabetes or an immune system problem. People with these conditions have a higher 
chance for infections. 
have tuberculosis (TB), or if you have been in close contact with someone who has had 
tuberculosis. 
have or have had HIV, Hepatitis B, or Hepatitis C 
take other medicines that affect your immune system 
• 
• 
• 
Before you begin treatment with ARCALYST, talk with your healthcare provider about your 
vaccination history. Ask your healthcare provider whether you should receive any vaccinations, 
including pneumonia vaccine and flu vaccine, before you begin treatment with ARCALYST. 
What is ARCALYST? 
ARCALYST is a prescription medicine called an interleukin-1 (IL-1) blocker. ARCALYST is used to 
treat adults and children 12 years and older with Cryopyrin-Associated Periodic Syndromes (CAPS), 
including Familial Cold Auto-inflammatory Syndrome (FCAS) and Muckle Wells Syndrome (MWS). 
ARCALYST can help lessen the signs and symptoms of CAPS, such as rash, joint pain, fever, and 
tiredness, but it can also lead to serious side effects because of the effects on your immune system. 
What should I tell my healthcare provider before taking ARCALYST? 
ARCALYST may not be right for you. Before taking ARCALYST, tell your healthcare provider 
about all of your medical conditions, including if you: 
• are scheduled to receive any vaccines. You should not receive live vaccines if you take 
ARCALYST. 
are pregnant or planning to become pregnant. It is not known if ARCALYST will harm 
your unborn child. Tell your healthcare provider right away if you become pregnant while 
taking ARCALYST. 
are breast-feeding or planning to breast-feed. It is not known if ARCALYST passes into 
your breast milk. 
• 
• 
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Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
See “What is the most important information I should know about ARCALYST?” 
Tell your healthcare provider about all the medicines you take, including prescription and 
non-prescription medicines, vitamins, and herbal supplements. Especially tell your healthcare 
provider if you take other medicines that affect your immune system, such as: 
• other medicines that block IL-1, such as Kineret  (anakinra). 
• medicines that block Tumor Necrosis Factor (TNF), such as Enbrel  (etanercept), Humira  
(adalimumab), or Remicade  (infliximab). 
• corticosteroids. 
See “What is the most important information I should know about ARCALYST?” 
Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider 
and pharmacist every time you get a new prescription. 
If you are not sure or have any questions about any of this information, ask your healthcare provider. 
How should I take ARCALYST? 
See the “Patient Instructions for Use” at the end of this leaflet. 
• 
• 
• 
Take ARCALYST exactly as prescribed by your healthcare provider. 
ARCALYST is given by injection under the skin (subcutaneous injection) one time each week. 
Your healthcare provider will tell and show you or your caregiver: 
▪ 
▪ 
▪ 
how much ARCALYST to inject 
how to prepare your dose 
how to give the injection 
• 
Do not try to give ARCALYST injections until you are sure that you or your caregiver 
understands how to prepare and inject your dose. Call your healthcare provider or pharmacist if 
you have any questions about preparing and injecting your dose, or if you or your caregiver 
would like more training. 
If you miss a dose of ARCALYST, inject it as soon as you remember, up to the day before your 
next scheduled dose. The next dose should be taken at the next regularly scheduled time. If you 
have any questions, contact your healthcare provider. 
If you accidentally take more ARCALYST than prescribed, call your healthcare provider. 
• 
• 
What are the possible side effects of ARCALYST? 
Serious side effects may occur while you are taking and after you finish taking ARCALYST 
including: 
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Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
• Serious Infections. See “What is the most important information I should know about 
taking ARCALYST?” Treatment with ARCALYST should be discontinued if you 
develop a serious infection. 
• Allergic Reaction. Call your healthcare provider or seek emergency care right away if you 
get any of the following symptoms of an allergic reaction while taking ARCALYST: 
• 
• 
• 
rash 
swollen face 
trouble breathing 
Common side effects with ARCALYST include: 
• Injection-site reaction. This includes: pain, redness, swelling, itching, bruising, lumps, 
inflammation, skin rash, blisters, warmth, and bleeding at the injection site. 
Upper respiratory infection. 
Changes in your blood cholesterol and triglycerides (lipids). Your healthcare provider 
will check you for this. 
• 
• 
These are not all the possible side effects of ARCALYST. Tell your healthcare provider about any 
side effects that bother you or that do not go away. For more information ask your healthcare provider 
or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to 
FDA at 1-800-FDA-1088. 
How should I store ARCALYST? 
• 
• 
Keep ARCALYST in the carton it comes in. 
Store ARCALYST in a refrigerator between 36°F to 46°F (2°C to 8°C). Call your pharmacy if 
you have any questions. 
Always keep ARCALYST away from light. 
Refrigerated ARCALYST can be used until the expiration date printed on the vial and carton. 
ARCALYST may be kept at room temperature after mixing. ARCALYST should be used within 
three hours of mixing. Keep ARCALYST away from light. 
If you need to take ARCALYST with you when traveling, store the carton in a cool carrier with a 
cold pack and protect it from light. 
• 
• 
• 
• 
Keep ARCALYST, injection supplies, and all other medicines out of reach of children. 
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Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
What are the ingredients in ARCALYST? 
Active ingredient: rilonacept. 
Inactive ingredients: histidine, arginine, polyethylene glycol 3350, sucrose, and glycine. 
General Information about ARCALYST 
Medicines are sometimes prescribed for conditions other than those listed in patient information 
leaflets. Do not use ARCALYST for a condition for which it was not prescribed. Do not give 
ARCALYST to other people even if they have the same condition. It may harm them. 
This leaflet summarizes the most important information about ARCALYST. If you would like more 
information, speak with your healthcare provider. You can ask your healthcare provider or pharmacist 
for information about ARCALYST that was written for healthcare professionals. For more 
information about ARCALYST, call 1-877-REGN-777 (1-877-734-6777), or visit 
www.ARCALYST.com. 
Patient Instructions for Use 
It is important for you to read, understand and follow the instructions below exactly. Following the 
instructions correctly will help to make sure that you use, prepare and inject the medicine the right 
way to prevent infection. 
How do I prepare and give an injection of ARCALYST? 
STEP 1: Setting up for an injection 
1. Choose a table or other flat surface area to set up the supplies for your injection. Be sure that 
the area is clean or clean it with an antiseptic or soap and water first. 
Wash your hands well with soap and water, and dry with a clean towel. 
Put the following items on a table, or other flat surface, for each injection (see Figure 1): 
2. 
3. 
Figure 1 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
• 
2 sterile, 3-milliliter (mL) disposable syringes with markings at each 0.1 mL (see Figure 
2): 
• 
• 
one needed for mixing (reconstitution) ARCALYST 
one needed for injection 
Figure 2 
2 sterile disposable needles (27-gauge, ½-inch) 
• 
• 
• 
one needed for mixing 
one needed for injection 
• 
• 
• 
• 
• 
Note: 
• 
4 alcohol wipes 
1 2x2 gauze pad 
1 vial of ARCALYST (powder in vial) 
1 vial of preservative-free Sterile Water for Injection 
1 puncture-resistant container for disposal of used needles, syringes, and vials 
Do not use Sterile Water for Injection, syringes or needles other than those provided by 
your pharmacy. Contact your pharmacy if you need replacement syringes or needles. 
Do not touch the needles or the rubber stoppers on the vials with your hands. If you do 
touch a stopper, clean it with a fresh alcohol wipe. 
If you touch a needle or the needle touches any surface, throw away the entire syringe 
into the puncture-resistant container and start over with a new syringe. 
Do not reuse needles or syringes. 
• 
• 
• 
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Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
• 
To protect yourself and others from possible needle sticks, it is very important to throw 
away every syringe, with the needle attached, in the puncture proof container right after 
use. Do not try to recap the needle. 
STEP 2: Preparing Vials 
1. Check the expiration date on the carton of ARCALYST. Do not use the vial if the expiration 
date has passed. Contact your pharmacy for assistance. 
Check the expiration date on the vial of Sterile Water for Injection. Do not use the vial if the 
expiration date has passed. Contact your pharmacy for assistance. 
Remove the protective plastic cap from both vials. 
Clean the top of each vial with an alcohol wipe. Use one wipe for each vial and wipe in one 
direction around the top of the vial (see Figure 3). 
2. 
3. 
4. 
Figure 3 
Open the wrapper that contains the 27-gauge needle by pulling apart the tabs and set it aside 
for later use. Do not remove the needle cover. This needle will be used to mix the water with 
powder. Open the wrapper that contains the syringe by pulling apart the tabs. Hold the barrel 
of the syringe with one hand and twist the 27-gauge needle onto the tip of the syringe until it 
fits snugly with the other hand (see Figure 4). 
5. 
Figure 4 
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Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
6. Hold the syringe at eye level. With the needle covered pull back the plunger to the 2.3 mL 
mark, filling the syringe with air (see Figure 5). 
Figure 5 
Hold the syringe in one hand, use the other hand to pull the needle cover straight off. Do not 
twist the needle as you pull off the cover. Place the needle cover aside. Hold the syringe in 
the hand that you will use to mix (reconstitute) your medicine. Hold the Sterile Water vial on 
a firm surface with your other hand. Slowly insert the needle straight through the rubber 
stopper. Do not bend the needle. Push the plunger in all the way to push the air into the vial 
(see Figure 6). 
7. 
Figure 6 
Hold the vial in one hand and the syringe in the other hand and carefully turn the vial upside 
down so that the needle is pointing straight up. 
Make sure the tip of the needle is covered by the liquid and slowly pull back on the plunger to 
the 2.3 mL mark to withdraw the Sterile Water from the vial (see Figure 7). 
8. 
9. 
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Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Figure 7 
10. Keep the vial upside down and tap or flick the syringe with your fingers until any air bubbles 
rise to the top of the syringe. 
11. To remove the air bubbles, gently push in the plunger so only the air is pushed out of the 
syringe and back into the bottle. 
12. After removing the bubbles, check the syringe to be sure that the right amount of Sterile 
Water has been drawn into the syringe (see Figure 8). 
Figure 8 
13. Carefully remove the syringe with needle from the Sterile Water vial. Do not touch the 
needle. 
STEP 3: Mixing (Reconstituting) ARCALYST 
1. With one hand, hold the ARCALYST vial on a firm surface. 
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Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
2. With the other hand, take the syringe with the Sterile Water and the same needle, and slowly 
insert the needle straight down through the rubber stopper of the ARCALYST vial. Push the 
plunger in all the way to inject the Sterile Water into the vial. 
Direct the water stream to gently go down the side of the vial into the powder (see Figure 9). 
3. 
Figure 9 
Remove the syringe and needle from the stopper and throw away the needle, syringe, and 
Sterile Water vial in the puncture-resistant container. Do not try to put the needle cover back 
on the needle. 
Hold the vial containing the ARCALYST and sterile water for injection sideways (not 
upright) with your thumb and a finger at the top and bottom of the vial, and quickly shake the 
vial back and forth (side-to-side) for about 1 minute (see Figure 10). 
4. 
5. 
Figure 10 
Put the vial back on the table and let the vial sit for about 1 minute. 
Look at the vial for any particles or clumps of powder which have not dissolved. 
6. 
7. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
8. If the powder has not completely dissolved, shake the vial quickly back and forth for 
30 seconds more. Let the vial sit for about 1 minute. 
9. Repeat Step 8 until the powder is completely dissolved and the solution is clear. 
10. The mixed ARCALYST should be thick, clear, and colorless to pale yellow. Do not use the 
mixed liquid if it is discolored or cloudy, or if small particles are in it (see Figure 11). 
NOTE: Contact your pharmacy to report any mixed ARCALYST that is discolored or 
contains particles. 
Figure 11 
11. ARCALYST may be kept at room temperature after mixing. ARCALYST should be used 
within three hours of mixing. Keep ARCALYST away from light. 
STEP 4: Preparing the injection 
1. Hold the ARCALYST vial on a firm surface and wipe the top of the ARCALYST vial with a 
new alcohol wipe (see Figure 12). 
Figure 12 
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Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
2. Take a new sterile, disposable needle and attach securely to a new syringe without removing 
the needle cover (see Figure 13). 
Figure 13 
The amount of air you draw into the syringe should equal the amount of mixed ARCALYST 
that your healthcare provider has prescribed for you to inject. 
To draw air into the syringe, hold the syringe at eye level. Do not remove the needle cover. 
Pull back the plunger on the syringe to the mark that is equal to the amount of mixed 
ARCALYST that your healthcare provider has prescribed for you to inject (see Figure 14). 
3. 
4. 
Figure 14 
Remove the needle cover and be careful not to touch the needle. Keep the ARCALYST vial 
on a flat surface and slowly insert the needle straight down through the stopper. Push the 
plunger down and inject all the air into the vial (see Figure 15). 
5. 
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Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Figure 15 
Hold the vial in one hand and the syringe in the other hand and carefully turn the vial upside 
down so that the needle is pointing straight up. Hold the vial at eye level. 
Keep the tip of the needle in the liquid and slowly pull back on the plunger to the mark on the 
syringe that matches the amount of medicine prescribed by your healthcare provider (see 
Figure 16). 
6. 
7. 
Figure 16 
NOTE: The maximum adult dose of ARCALYST is 2 mL. 
Keep the vial upside down with the needle straight up, and gently tap the syringe until any air 
bubbles rise to the top of the syringe (see Figure 17). 
It is important to remove air bubbles so that you withdraw up the right amount of medicine 
from the vial. 
8. 
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Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Figure 17 
9. To remove the air bubbles, slowly and gently push in the plunger so only the air is pushed 
through the needle. 
10. Check to make sure that you have the amount of medicine prescribed by your healthcare 
provider in the syringe. 
11. Throw away the ARCALYST vial in the puncture-resistant container even if there is any 
medicine left in the vial (see Figure 18). Do not use any vial of ARCALYST more than one 
time. 
Figure 18 
STEP 5: Giving the Injection 
1. ARCALYST is given by subcutaneous injection, an injection that is given into the tissue 
directly below the layers of skin. It is not meant to go into any muscle, vein, or artery. 
You should change (rotate) the sites and inject in a different place each time in order to 
keep your skin healthy. 
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Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Rotating injection sites helps to prevent irritation and allows the medicine to be completely 
absorbed. Ask your healthcare provider any questions that you have about rotating injection 
sites. 
• 
Do not inject into skin that is tender, red, or hard. If an area is tender or feels 
hardened, choose another site for injection until the tenderness or "hardening" 
goes away. 
Tell your healthcare provider about any skin reactions including redness, 
swelling, or hardening of the skin. 
Areas where you may inject ARCALYST include the left and right sides of the 
abdomen, and left and right thighs. If someone else is giving the injection, the 
upper left and right arms may also be used for injection (see Figure 19): 
(Do not inject within a 2-inch area around the navel) 
• 
• 
Figure 19 
Choose the area for the injection. Clean the area in a circular motion with a new alcohol wipe. 
Begin at the center of the site and move outward. Let the alcohol air dry completely. 
Take the cover off the needle and be careful not to touch the needle. 
Hold the syringe in one hand like you would hold a pencil. 
With the other hand gently pinch a fold of skin at the cleaned site for injection (see Figure 
20). 
2. 
3. 
4. 
5. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Figure 20 
Use a quick “dart like” motion to insert the needle straight into the skin (90 degree angle) (see 
Figure 21). Do not push down on the plunger while inserting the needle into the skin. 
For small children or persons with little fat under the skin, you may need to hold the syringe 
and needle at a 45 degree angle (see Figure 21). 
6. 
Figure 21 
After the needle is completely in the skin, let go of the skin that you are pinching. 
With your free hand hold the syringe near its base. Gently pull back the plunger. If blood 
comes into the syringe, the needle has entered a blood vessel. Remove the needle, discard the 
syringe and needle. Start over with “STEP 1: Setting up for an injection” using new supplies 
(syringes, needles, vials, alcohol swabs and gauze pad). 
If no blood appears, inject all the medicine in the syringe at a slow, steady rate, pushing the 
plunger all the way down. It may take up to 30 seconds to inject the entire dose. 
7. 
8. 
9. 
10. Pull the needle out of the skin, and hold a piece of sterile gauze over the injection site for 
several seconds (see Figure 22). 
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Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Figure 22 
11. Do not replace the needle cover. Throw away the vials, used syringes and needles in the 
puncture-resistant container (see Figure 23). Do not recycle the container. DO NOT throw 
away vials, needles, or syringes in the household trash or recycle. 
Figure 23 
12. Keep the puncture-resistant container out of reach of children. When the container is about 
two-thirds full, dispose of it as instructed by your healthcare provider. Follow any special 
state or local laws about the right way to throw away needles and syringes. 
13. Used alcohol wipes can be thrown away in the household trash. 
Contact your healthcare provider right away with any questions or concerns about ARCALYST. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
Notes: 1. Enbrel , Humira , Kineret , and Remicade , respectively, are trademarks of Immunex 
Corporation, AbbVie Biotechnology Ltd., Amgen Inc., and Janssen Biotech, Inc., respectively. 
Manufactured and distributed by: 
Regeneron Pharmaceuticals, Inc. 
777 Old Saw Mill River Road 
Tarrytown, NY 10591-6707 
U.S. License Number 1760 
NDC 61755-001-01 
© 2016, Regeneron Pharmaceuticals, Inc. 
All rights reserved. 
V 4.0 
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Protocol KPL-914-C002 
Version 1.0, 26 Sep 2018 
13.2 Appendix: 11-point 
Pericarditis Pain 
Numerical Rating Scale (NRS) for Assessment of 
Subjects will be asked to select the score that best describes their average level of pericarditis 
pain over the previous 24 hours using an 11-point NRS, where zero (0) indicates ‘no pain’ 
and ten (10) means indicates ‘pain as bad as it could be’. 
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Kiniksa Pharmaceuticals, Ltd. 
CLINICAL STUDY PROTOCOL 
PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
RANDOMIZED WITHDRAWAL STUDY WITH OPEN-LABEL 
EXTENSION, TO ASSESS THE EFFICACY AND SAFETY OF 
RILONACEPT TREATMENT IN SUBJECTS WITH 
RECURRENT PERICARDITIS – Rilonacept inHibition of 
interleukin-1 Alpha and beta for recurrent Pericarditis: a pivotal 
Symptomatology and Outcomes stuDY 
(RHAPSODY) 
VERSION 1.1, 05 October 2018 
IND: 
EudraCT: 
136,896 
2018-002719-87 
1 
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CONFIDENTIALITY STATEMENT 
The information contained in this document, particularly unpublished data, is the property of Kiniksa Pharmaceuticals, 
Ltd., and is provided to you in confidence as an investigator, potential investigator, or consultant, for review by you, 
members of your staff who have a need to know the information, and an applicable Institutional Review Board or 
Independent Ethics Committee. You agree that the information contained herein shall be held in strict confidence and is 
only to be used by you and your staff as necessary to conduct the authorized clinical studies of the investigational drug 
described in the protocol. Documentation, data, and all other information generated during the study is the property of 
Kiniksa Pharmaceuticals, Ltd. and will be held in strict confidence by you and members of your staff. You further 
agree to not publish or otherwise disclose any of the information to others without written authorization from Kiniksa 
Pharmaceuticals, Ltd., except to the extent necessary to obtain informed consent from those persons to whom the drug 
may be administered. 
 


KPL-914-C002 
Sponsor: 
Sponsor Study Contact: 
Sponsor Medical Contact 
Medical Monitor: 
Version of Protocol: 
Date of Protocol: 
Version 1.1 
05 October 2018 
2 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-9 l 4-C002 
Version 1.1, 05 Oct 2018 
Protocol Approval - Sponsor Signatory 
Phase 3, double-blind, placebo-controlled, randomized withdrawal study with 
open-label extension, to assess the efficacy and safety of rilonacept treatment 
in subjects \vith recurrent pericarditis (RHAPSODY) 
Study Title 
KPL-9 l 4-C002 
Protocol Number 
05 October 2018 
Protocol Date 
Protocol accepted and approved by: 
Chief Medical Officer 
._.,, 
Page 146 
 
 
 
 
 
 


Kiniks□ Plmrmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-9 l 4-C002 
Version 1.1, 05 Oct 2018 
Protocol Approval - Lead Statistician 
Phase 3, double-blind, placebo-controlled, randomized withdrawal study with 
open-label extension, to assess the efficacy and safety of rilonacept treatment 
in subjects with recurrent pericarditis (RHAPSODY) 
Study Title 
KPL-9 l 4-C002 
Protocol Number 
05 October 2018 
Protocol Date 
Protocol accepted and approved by: 
Lead Statistician 
4 
Page 147 
 
 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
Declaration of Investigator 
I have read and understood all sections of the protocol entitled “Phase 3, double-blind, placebo-
controlled, randomized withdrawal study with open-label extension, to assess the efficacy and safety 
of rilonacept treatment in subjects with recurrent pericarditis (RHAPSODY)” and the accompanying 
Investigator’s Brochure. 
I agree to supervise all aspects of the protocol and to conduct the clinical investigation in accordance 
with the Final Protocol Version 1.1, dated 05 October 2018, the International Council for 
Harmonisation tripartite guideline E6(R2): Good Clinical Practice and all applicable government 
regulations. I will not make changes to the protocol before consulting with Kiniksa Pharmaceuticals 
or implement protocol changes without Institutional Review Board Independent Ethics Committee 
approval except to eliminate an immediate risk to subjects. I agree to administer study drug only to 
subjects under my personal supervision or the supervision of a sub-investigator. 
I will not supply the investigational drug to any person not authorized to receive it. Confidentiality 
will be protected. Subject identity will not be disclosed to third parties or appear in any study reports 
or publications. 
I will not disclose information regarding this clinical investigation 
investigation without authorization from Kiniksa Pharmaceuticals. 
or publish results of the 
Signature of Principal Investigator 
Date 
Printed Name of Principal Investigator 
5 
Page 148 
 
 
 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
TABLE OF CONTENTS 
TABLE OF CONTENTS ..................................................................................................... 6 
LIST OF TABLES..............................................................................................................11 
LIST OF FIGURES............................................................................................................11 
PROTOCOL SYNOPSIS ................................................................................................... 13 
STUDY SCHEDULE OF ACTIVITIES ............................................................................ 20 
LIST OF ABBREVIATIONS............................................................................................. 28 
1 
Introduction ................................................................................................................ 30 
1.1 
1.2 
1.3 
Current Therapeutic Management of Pericarditis ................................................. 31 
Pathogenesis of Recurrent Pericarditis: Role of IL-1 ............................................ 31 
Rilonacept (KPL-914) .......................................................................................... 33 
1.3.1 
1.3.2 
Safety of Rilonacept .............................................................................. 34 
KPL-914-C001 Study with Rilonacept (KPL-914) in Recurrent 
Pericarditis ............................................................................................ 36 
2 
Study Objectives and Endpoints ................................................................................ 36 
2.1 
2.2 
Primary Objective ................................................................................................ 36 
Secondary Objective ............................................................................................ 37 
3 
Investigational Plan .................................................................................................... 37 
3.1 
Study Design ....................................................................................................... 37 
3.1.1 
3.1.2 
3.1.3 
Screening Period (up to 4 weeks)........................................................... 37 
Single-blind Run-In (RI) Period (12 weeks). ......................................... 37 
Double-blind Placebo-controlled RW Period (pericarditis recurrence 
event-driven duration with a minimum of 24 weeks) ............................. 38 
Long Term Extension Treatment Period (LTE-TP) (24 weeks) .............. 39 
Long Term Extension Follow-Up Period (LTE-FUP) (24 weeks)........... 39 
Rationale of Study Design ..................................................................... 41 
Justification for Rilonacept Dose Selection ............................................ 42 
3.1.4 
3.1.5 
3.1.6 
3.1.7 
4 
Subject Selection and Withdrawal Criteria ............................................................... 43 
4.1 
Selection of Study Population .............................................................................. 43 
4.1.1 
4.1.2 
Inclusion Criteria ................................................................................... 44 
Exclusion Criteria.................................................................................. 45 
4.2 
Subject Completion, Withdrawal from Study, and Study Drug Discontinuation ... 49 
4.2.1 
4.2.2 
Completion ........................................................................................... 49 
Reasons for Discontinuation of Study Drug and Study Withdrawal ........ 49 
6 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
4.2.2.1 
4.2.2.2 
Discontinuation of Study Drug .............................................................. 49 
Withdrawal from the Study ................................................................... 50 
5 
Study Treatments ........................................................................................................ 51 
5.1 
5.2 
5.3 
5.4 
Method of Assigning Subjects to Treatment Groups ............................................. 51 
Treatments Administered ..................................................................................... 52 
Identity of Investigational Medicinal Product ....................................................... 53 
Management of Clinical Supplies......................................................................... 54 
5.4.1 
5.4.2 
5.4.3 
Study Drug Product Packaging and Storage ........................................... 54 
Study Drug Accountability .................................................................... 54 
Other Supplies ....................................................................................... 55 
5.5 
Study Drug Overdose ........................................................................................... 55 
5.5.1 
5.5.2 
Treatment of Study Drug Overdose ....................................................... 55 
Other Study Drug Errors ........................................................................ 56 
5.6 
5.7 
5.8 
Transmission of Infectious Agents ....................................................................... 56 
Misuse for Illegal Purposes .................................................................................. 56 
Prior and Concomitant Medications ..................................................................... 56 
5.8.1 
5.8.2 
5.8.3 
5.8.3.1 
5.8.4 
5.8.5 
5.8.6 
Screening .............................................................................................. 57 
Single-blind RI Period ........................................................................... 57 
Double-blind Placebo-controlled RW Period ......................................... 58 
Concomitant Medication Upon Pericarditis Recurrence ......................... 58 
Long Term Extension Treatment Period (LTE-TP) ................................ 59 
Long Term Extension Follow-Up Period (LTE-FUP) ............................ 59 
Prohibited Concomitant Medicines During the Study ............................ 59 
5.9 
Blinding. .............................................................................................................. 60 
5.9.1 
Breaking the Blind ................................................................................ 60 
5.10 Treatment Compliance ......................................................................................... 60 
6 
Study Assessments and Procedures ............................................................................ 61 
6.1 
Study Visits ......................................................................................................... 61 
6.1.1 
6.1.2 
6.1.2.1 
6.1.2.2 
6.1.2.3 
6.1.2.4 
6.1.2.5 
6.1.2.6 
Screening: Clinic and Remote as Needed ............................................... 61 
Single-blind Treatment: Run-In ............................................................. 63 
Enrollment (RI Baseline): Clinic Visit ................................................... 63 
RI Day 2: Clinic Visit (24-hour PK Substudy Participants Only) ............ 64 
RI Day 4: TC/RN Visit .......................................................................... 64 
RI Week 1: TC/RN Visit ....................................................................... 64 
RI Week 2: TC/RN Visit ....................................................................... 65 
RI Week 4: TC/RN Visit ....................................................................... 66 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
6.1.2.7 
6.1.2.8 
6.1.2.9 
6.1.3 
6.1.3.1 
6.1.3.2 
6.1.4 
6.1.4.1 
6.1.4.2 
6.1.5 
6.1.5.1 
6.1.5.2 
6.1.6 
6.1.6.1 
6.1.6.2 
6.1.6.3 
RI Week 6: Clinic Visit ......................................................................... 67 
RI Week 10: TC Visit ............................................................................ 67 
Randomization (RI Week 12/RW Baseline): Clinic Visit ....................... 68 
Randomized-Withdrawal (RW) Period .................................................. 69 
RW WEEK 24: Clinic Visit ................................................................... 70 
EORW (End of RW Period/LTE Baseline): Clinic Visit ......................... 71 
Long Term Extension ............................................................................ 72 
LTE Weeks 8 and 16: Clinic Visit ......................................................... 72 
LTE Week 24 Clinic Visit ..................................................................... 73 
LTE Follow-Up Period .......................................................................... 74 
LTE Week 30 Visit: Clinic .................................................................... 74 
LTE Week 48 End of Study Visit: TC .................................................... 74 
Supplemental Visits ............................................................................... 75 
Pericarditis Recurrence Assessment: Clinic Visit ................................... 75 
End of Treatment Visit: Clinic ............................................................... 76 
Safety Follow-Up Visit: Clinic or TC/RN .............................................. 76 
6.2 
Efficacy Assessments ........................................................................................... 77 
6.2.1 
6.2.1.1 
6.2.1.2 
6.2.1.3 
6.2.1.4 
6.2.1.5 
6.2.1.6 
6.2.1.7 
6.2.1.8 
6.2.1.9 
6.2.1.10 
6.2.2 
Individual Efficacy Assessments ............................................................ 77 
C-Reactive Protein ................................................................................ 77 
11-Point Pericarditis Pain Numerical Rating Scale ................................. 78 
Electrocardiogram ................................................................................. 78 
Echocardiogram .................................................................................... 78 
Patient Global Impression of Pericarditis Severity ................................. 78 
Physician Global Assessment of Pericarditis Activity............................. 79 
36-Item Short Form Health Survey ........................................................ 79 
EQ-5D-5L ............................................................................................. 79 
Insomnia Severity Index ........................................................................ 80 
Cardiac MRI ......................................................................................... 80 
Assessment of Clinical Response at the End of the Run-In Period Week 
12/RW Baseline .................................................................................... 80 
Management of Suspected Pericarditis Recurrence in the RW Period..... 81 
6.2.3 
6.3 
Safety Assessments .............................................................................................. 82 
6.3.1 
6.3.2 
6.3.3 
6.3.4 
Physical Examination ............................................................................ 83 
Vital Signs ............................................................................................ 83 
Chest X-ray ........................................................................................... 83 
Tuberculosis Screening ......................................................................... 83 
6.4 
Adverse Events .................................................................................................... 83 
6.4.1 
Definitions ............................................................................................ 83 
8 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
6.4.1.1 
6.4.1.2 
6.4.1.3 
6.4.1.4 
6.4.1.5 
6.4.1.6 
6.4.2 
6.4.2.1 
6.4.2.2 
6.4.3 
6.4.3.1 
6.4.3.2 
6.4.3.3 
6.4.4 
6.4.5 
6.4.6 
6.4.6.1 
6.4.7 
6.4.8 
Adverse Event ....................................................................................... 83 
Treatment-emergent Adverse Event ....................................................... 84 
Serious Adverse Event ........................................................................... 84 
Adverse Event of Special Interest .......................................................... 85 
Adverse Reaction .................................................................................. 85 
Suspected Unexpected Serious Adverse Reaction .................................. 85 
Assessing Adverse Events ..................................................................... 85 
Relationship to Study Drug. ................................................................... 85 
Intensity ................................................................................................ 86 
Recording Adverse Events ..................................................................... 86 
Adverse Events Based on Signs and Symptoms ..................................... 87 
Adverse Events Based on Examinations and Tests ................................. 88 
Pericarditis Disease Related Events ....................................................... 88 
Time Period for Collection of Adverse Events ....................................... 88 
Follow-Up of Unresolved Adverse Events ............................................. 88 
Reporting Serious Adverse Events ......................................................... 88 
Other Reasons for Immediate Reporting ................................................ 89 
Pregnancy ............................................................................................. 89 
Evaluating and Reporting SUSARs ....................................................... 90 
6.5 
Other Assessments ............................................................................................... 90 
6.5.1 
6.5.2 
6.5.3 
6.5.4 
Pharmacokinetic Sample ....................................................................... 90 
Anti-Drug Antibodies (ADAs) against Rilonacept (KPL-914) ............... 91 
Biomarkers ............................................................................................ 91 
Pharmacogenomics................................................................................ 91 
6.6 
Laboratory Analyses ............................................................................................ 91 
6.6.1 
6.6.2 
6.6.3 
6.6.4 
6.6.5 
6.6.6 
6.6.7 
Serology ................................................................................................ 91 
Hematology ........................................................................................... 91 
Chemistry .............................................................................................. 92 
Non-fasting Lipid Panel ........................................................................ 92 
Urinalysis .............................................................................................. 92 
Pregnancy Test ...................................................................................... 92 
Sample Collection ................................................................................. 92 
6.7 
Committees.......................................................................................................... 93 
6.7.1 
6.7.2 
Independent Data Monitoring Committee (DMC) .................................. 93 
Clinical Endpoint Committee (CEC) ..................................................... 93 
7 
Statistical and Analytical Plan .................................................................................... 93 
7.1 
Primary Efficacy Endpoint ................................................................................... 93 
9 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
7.2 
Secondary Efficacy Endpoints for the RW Period................................................. 93 
7.2.1 
7.2.2 
Major Secondary Efficacy Endpoints ..................................................... 93 
Other Secondary Endpoints ................................................................... 94 
7.3 
Other Endpoints ................................................................................................... 95 
7.3.1 
7.3.2 
Efficacy Endpoints for the RI Period ..................................................... 95 
Efficacy Endpoints for the LTE-TP ....................................................... 96 
7.4 
7.5 
7.6 
7.7 
Sample Size Calculations ..................................................................................... 96 
Analysis Sets ....................................................................................................... 97 
Description of Subgroups to be Analyzed ............................................................. 98 
Statistical Analysis Methodology ......................................................................... 98 
7.7.1 
7.7.2 
7.7.3 
7.7.4 
7.7.5 
7.7.5.1 
7.7.5.2 
7.7.6 
7.7.7 
7.7.8 
7.7.9 
General Methods ................................................................................... 98 
Stratified Analysis ................................................................................. 98 
Testing Hypotheses and Multiplicity Adjustment ................................... 98 
Analysis of Primary Efficacy Endpoint .................................................. 99 
Analysis of Secondary Efficacy Endpoints............................................. 99 
Analysis of the Major Secondary Endpoints .......................................... 99 
Analyses of Other Secondary Endpoints in the RW Period .................. 100 
Analyses of Other Endpoints ............................................................... 101 
Pharmacokinetic Analyses ................................................................... 101 
Safety Analyses ................................................................................... 101 
Interim Analyses ................................................................................. 102 
8 
Data Quality Assurance ............................................................................................ 102 
8.1 
Data Management .............................................................................................. 102 
9 
Ethics ......................................................................................................................... 103 
9.1 
9.2 
9.3 
Independent Ethics Committee or Institutional Review Board ............................ 103 
Ethical Conduct of the Study ............................................................................. 103 
Subject Information and Consent ....................................................................... 103 
10 Investigator’s Obligations ......................................................................................... 104 
10.1 
10.2 
10.3 
10.4 
10.5 
10.6 
Confidentiality ................................................................................................... 104 
Financial Disclosure and Obligations ................................................................. 105 
Investigator Documentation ............................................................................... 105 
Study Conduct ................................................................................................... 105 
Adherence to Protocol........................................................................................ 106 
Adverse Events and Study Report Requirements ................................................ 106 
10 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
10.7 
10.8 
10.9 
Investigator’s Final Report ................................................................................. 106 
Records Retention .............................................................................................. 106 
Publications ....................................................................................................... 106 
11 Study Management ................................................................................................... 106 
11.1 Monitoring ......................................................................................................... 107 
11.1.1 
11.1.2 
Monitoring of the Study ...................................................................... 107 
Inspection of Records .......................................................................... 107 
11.2 Management of Protocol Amendments and Deviations ....................................... 107 
11.2.1 
11.2.2 
Modification of the Protocol ................................................................ 107 
Protocol Deviations ............................................................................. 107 
11.3 
11.4 
Study Termination ............................................................................................. 108 
Final Report ....................................................................................................... 108 
12 
13 
Reference List ........................................................................................................... 109 
Appendices ................................................................................................................ 111 
13.1 Appendix: ARCALYST® Prescribing Information .............................................. 111 
13.2 Appendix: 11-point Numerical Rating Scale (NRS) for Assessment of Pericarditis 
Pain ............................................................................................................ 142 
LIST OF TABLES 
Study Schedule of Activities – Screening and Run-In Period .............................. 20 
Table 1–1 
Table 1–2 
Study Schedule of Activities – Randomized Withdrawal .................................... 22 
Table 1–3 
Study Schedule of Activities – Long Term Extension ......................................... 24 
Table 1–4 
Study Schedule of Activities – Supplemental Visits ........................................... 26 
Table 5–1: 
Study Drug Dose Volume (After Reconstitution) by Body Weight in Kilograms 
for Pediatric Subjects Aged ≥12 and <18 Years .................................................. 53 
LIST OF FIGURES 
Schematic of Rilonacept (KPL-914) ................................................................... 34 
Figure 1: 
Figure 2: 
Overview of KPL-914-C002 Trial Design .......................................................... 40 
Figure 3: 
Management of Suspected Pericarditis Recurrence in the Randomized- 
Withdrawal Period ............................................................................................. 82 
11 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
This page was intentionally left blank. 
12 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
PROTOCOL SYNOPSIS 
13 
Page 156 
Protocol Number: 
KPL-914-C002 
Title: 
Phase 3, double-blind, placebo-controlled, randomized withdrawal study with open-label extension, to 
assess the efficacy and safety of rilonacept treatment in subjects with recurrent pericarditis 
 
Study Acronym: 
Rilonacept inHibition of interleukin-1 Alpha and beta for recurrent Pericarditis: a pivotal 
Symptomatology and Outcomes stuDY 
RHAPSODY 
Sponsor: 
 
Study Phase: 
3 
Study Sites: 
Multicenter, global 
Indication: 
Recurrent pericarditis 
Study Rationale: 
Recurrent pericarditis is a rare autoinflammatory condition with no approved therapies. Current 
treatments, utilizing nonspecific inhibitors of inflammation (nonsteroidal anti-inflammatory drugs 
[NSAIDs], colchicine, corticosteroids [CS]), result in significant morbidity with chronic use. Some 
patients develop CS dependency or require surgical pericardiectomy to treat the symptoms of their 
disease. 
The interleukin-1 (IL-1) pathway plays a major role in the pathophysiology of recurrent pericarditis. 
Rilonacept (KPL-914) is a recombinant fusion protein that blocks IL-1 signaling. It is currently approved 
for treatment of another autoinflammatory condition, Cryopyrin-Associated Periodic Syndrome (CAPS). 
Based on its IL-1–antagonistic properties and pharmacokinetics (PK), which allow for once-weekly 
subcutaneous (SC) injections, it is reasonable to evaluate the efficacy and safety of rilonacept in subjects 
with recurrent pericarditis to address the unmet need in treatment of this disease. 
 
Study Objectives: 
Primary: 
To assess the efficacy of rilonacept treatment in subjects with recurrent 
pericarditis. 
Secondary: 
To assess the safety of rilonacept treatment in subjects with recurrent 
pericarditis. 
 
 
 
 
 
 
 
 
 
 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
14 
Page 157 
Study Population: 
Subjects eligible for the study are subjects with recurrent pericarditis who do not have pericarditis 
secondary to prohibited conditions. The study population includes both adult subjects ≥18 years old and 
pediatric subjects ≥12 and <18 years old with a history of at least 2 prior pericarditis episodes (including 
the first episode and 1 recurrence). Enrollment of pediatric subjects will be limited to up to 20% of the 
study population. To be eligible for the study, subjects must present at screening with at least a third 
pericarditis episode, defined as at least 1 day with pericarditis pain measurement ≥4 on the 11-point 
Numerical Rating Scale (NRS) and C-reactive protein (CRP) value ≥1 mg/dL (either on the same day or 
separated by no more than 7 days) within 7 days prior to first study drug administration. 
Subjects included in the study may be receiving concomitant NSAIDs and/or colchicine and/or oral CS 
treatment in any combination, provided that the dosages of these medications have been stable (or not 
increased) for at least 3 days prior to first administration of study drug, and that changes in medications 
made within this time period (for instance, 1-time use of NSAIDs) are not anticipated by the investigator 
to significantly alter assessments of baseline disease activity. 
 
Study Design: 
This study has 5 periods: 
(1) Screening period, during which assessment of disease characteristics, baseline therapy, and the 
pre-treatment workup is completed (up to 4 weeks) 
(2) Single-blind Run-In (RI) period (12 weeks), during which blinded rilonacept is administered SC 
once weekly in all subjects. The RI period includes the following: 
• 1-week Stabilization period, during which blinded rilonacept is administered in addition to standard 
of care (SOC) pericarditis therapy and the ongoing pericarditis episode is treated 
• 9-week Weaning period, during which subjects are weaned off background SOC pericarditis 
therapy, as applicable, while treatment with blinded rilonacept continues 
• 2-week Monotherapy period during which subjects who have successfully weaned off background 
SOC pericarditis therapy will continue to receive blinded rilonacept 
In the single-blind RI period (subjects are blinded regarding the time of transition from the 
single-blind to the double-blind period), adult subjects ≥18 years old will receive rilonacept as an 
initial loading dose of 320 mg (2 SC injections of 160 mg each) at the RI baseline visit (2 × 2 ml), 
followed by a 160 mg (2 ml) SC dose once weekly throughout the RI period. Pediatric subjects (≥12 and 
<18 years old) will receive an initial loading dose of rilonacept 4.4 mg/kg (2 SC injections of 2.2 mg/kg 
each) at the RI baseline visit (maximum 2 × 2 ml), and then 2.2 mg/kg (maximum 2 ml) SC once weekly 
throughout RI period. 
Subjects who stopped background SOC pericarditis therapy and who achieve Clinical Response at RI 
Week 12, defined as the weekly average of daily pericarditis pain score ≤2.0 on the 11-point NRS within 
the 7 days prior to and including the day of randomization on RI Week 12/Randomization Withdrawal 
(RW) baseline and a CRP level ≤0.5 mg/dL at the RI Week 12/RW baseline visit, will proceed into the 
double-blind placebo-controlled RW period. Subjects who do not achieve Clinical Response at 
 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
15 
Page 158 
Study Design Continued 
RI Week 12/RW baseline on rilonacept monotherapy will be discontinued from study drug, transitioned 
to SOC 
pericarditis therapy at the investigator’s discretion and followed through the end of the RW period. 
(3) Double-blind placebo-controlled RW period (pericarditis recurrence event-driven duration, with a 
minimum of 24 weeks), during which subjects who were able to stop background SOC pericarditis 
therapy and who achieve Clinical Response at RI Week 12/RW baseline are randomized in a double-blind 
manner at a 1:1 ratio to the following: 
• Rilonacept 160 mg (2.2 mg/kg in pediatric subjects) SC injections once weekly 
• Matching placebo SC injections once weekly 
Pericarditis Recurrence in the RW Period 
Pericarditis recurrence is defined as the recurrence of typical pericarditis pain associated with supportive 
objective evidence of pericarditis. Upon pericarditis recurrence, subjects who report at least 1 day with 
pericarditis pain measurement ≥4 on the 11-point NRS and have 1 CRP value ≥1 mg/dL (either on the 
same day or separated by no more than 7 days) will receive bailout rilonacept (2 open-label injections of 
160 mg rilonacept [or 4.4 mg/kg for pediatric subjects] followed by once-weekly open-label rilonacept 
SC injections of 160 mg [or 2.2 mg/kg for pediatric subjects]). irrespective of randomized treatment 
assignment and as soon as at least 5 days have passed since the last study drug injection. Sequential Oral 
Rescue Therapy (ORT), i.e., analgesics first, then NSAIDs, and then colchicine, can be added if needed at 
the discretion of the investigator, as outlined in the protocol and Pharmacy Manual. 
Subjects with pericarditis recurrence and who do not meet the protocol criteria for bailout rilonacept will 
continue blinded study drug until the protocol criteria for bailout rilonacept are met or through the end of 
the RW period. For those subjects, sequential ORT can be added to blinded study drug at the discretion of 
the investigator, as outlined in the protocol and Pharmacy Manual. 
All suspected pericarditis recurrence events in the RW period will be formally adjudicated by the Clinical 
Endpoint Committee (CEC), and only events that are confirmed by the CEC as pericarditis recurrences 
will be used in the Primary Endpoint analysis. 
(4) Long Term Extension Treatment Period (LTE-TP) (24 weeks), during which all subjects 
completing the RW period (including subjects transitioned to open-label rilonacept upon pericarditis 
recurrence) will have an option to receive up to 24 weeks of open-label rilonacept 160 mg (or 2.2 mg/kg 
for pediatric subjects) SC injections once weekly based on their clinical status and at the discretion of the 
investigator, after signing LTE informed consent. Any subject who, in the opinion of investigator, should 
not continue open-label rilonacept will be offered participation in the LTE off study drug and after 
signing LTE informed consent. 
(5) Long Term Extension Follow-Up Period (LTE-FUP) (24 weeks), during which all subjects in the 
LTE-TP will be followed in the LTE-FUP for safety and potential pericarditis recurrences. 
 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
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Estimated Study Duration: 
Subjects completing LTE-TP are projected to be dosed with rilonacept for a minimum of approximately 
1.2 years and up to 3 years based on enrollment assumptions and pericarditis recurrence events accrual 
time. 
 
Study Efficacy Assessments: 
• Daily pericarditis pain on the 11-point NRS in the subject’s electronic diary 
• CRP level 
• Electrocardiogram (ECG) 
• Echocardiography (ECHO) 
• Patient Global Impression of Pericarditis Severity (PGIPS) 
• Physician Global Assessment of Pericarditis Activity (PGA-PA) 
• 36-Item Short Form Health Survey (SF-36) 
• 5-Level EuroQoL-5D (EQ-5D-5L) 
• Insomnia Severity Index (ISI) 
• Cardiac magnetic resonance imaging (in a substudy in approximately 10 subjects) 
 
Study Pharmacokinetic or Pharmacodynamic Assessments: 
Pharmacokinetic or pharmacodynamic assessments will include: 
• PK analysis 
• Anti-rilonacept antibodies 
• Biomarkers 
• Peripheral blood mononuclear cell isolation (for subjects who sign the separate informed consent 
for pharmacogenomics assessments) 
 
Study Safety Assessments: 
Safety assessments during the study will include: 
• Physical examination 
• Vital signs measurements 
• Adverse event (AE) monitoring 
• Chest x-ray 
• Tuberculosis screening 
• Laboratory tests 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
17 
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Investigational Medicinal Product, Dosage, and Route of Administration: 
Rilonacept (KPL-914) is a recombinant fusion protein consisting of the extracellular domains of human 
IL-1 cytokine receptor and the Fc portion of human immunoglobulin G1 (IgG1). It acts as a soluble decoy 
receptor binding IL-1α/IL-1β and prevents their interaction with the IL-1 cell-surface receptor. 
Study drug (rilonacept or placebo) is supplied in a single use, 20 ml glass vial containing a sterile, white 
to off-white, lyophilized powder. Each vial is to be reconstituted with 2.3 ml sterile Water for Injection 
(WFI). A volume up to 2 ml can be withdrawn, which is designated to deliver up to 160 mg of rilonacept 
or up to 2 ml of placebo for SC injection only. The resulting solution is clear, colorless to pale yellow, 
and essentially free of particulates. 
Each rilonacept vial contains 220 mg of rilonacept lyophilized powder. After reconstitution with 2.3 ml 
WFI, the rilonacept vial contains 80 mg/ml rilonacept, 40 mM histidine, 50 mM arginine, 3.0% (w/v) 
polyethylene glycol 3350, 2.0% (w/v) sucrose, and 1.0% (w/v) glycine at a pH of 6.5. No preservatives 
are present. 
The first injection of rilonacept loading dose at the RI baseline visit will be administered at the study site 
by study site staff. The second injection of rilonacept loading dose at the RI baseline visit will be prepared 
and administered by the subject or the subject’s caregiver after adequate training and under the 
supervision of study site personnel. Subsequent once-weekly study drug doses will be self-administered 
SC by the subject or administered to the subject by a trained caregiver as an outpatient SC administration. 
 
Sample Size: 
Approximately 56 subjects (not to exceed 75 subjects) with recurrent pericarditis will be enrolled, which 
will allow approximately 50 subjects to be randomly assigned to blinded treatment. 
 
Statistical Methods: 
The primary efficacy endpoint is time to pericarditis recurrence, defined as the time from randomization 
to the date of the first pericarditis recurrence for each subject. Only CEC-confirmed pericarditis 
recurrence will be considered as an event for the primary efficacy analysis. A sensitivity analysis will be 
done based on the investigator’s assessment of the pericarditis recurrence. 
In order to control the overall 1-sided type I error rate at the 0.025 level, a gatekeeping procedure in 
combination with Hochberg’s procedure will be applied to testing the primary and major secondary 
efficacy endpoints. 
Major secondary efficacy endpoints for the RW period include: 
• Proportion of subjects who maintained Clinical Response at Week 24 of the RW period 
• Percentage of days with no or minimal pain (pain ≤1 on the 11-point NRS) in the first 24 weeks of 
the RW period 
• Proportion of subjects with absent or minimal pericarditis symptoms (based on the 7-point rating 
scale of PGIPS) at Week 24 of the RW period 
Other secondary efficacy endpoints for the RW period include: 
• Proportion of subjects without pericarditis recurrence in the first 24 weeks of the RW period 
• Time to pericarditis pain NRS ≥4 
 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
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Statistical Methods Continued: 
• Time to CRP level ≥1 mg/dL 
• Time to pericardial rub 
• Time to widespread ST-segment elevation or PR-segment depression on ECG 
• Time to new or worsening pericardial effusion on ECHO 
• Change over time in CRP levels 
• Change over time in subject’s assessments of pericarditis pain (weekly average) 
• Proportion of subjects with absent or minimal pericarditis activity based on Physician Global 
Assessment of Pericarditis Activity (PGA-PA) 
• Change over time in SF-36 Physical Component Score 
• Change over time in SF-36 Mental Component Score 
• Change in EQ-5D-5L 
• Change over time in subject’s sleep quality assessed with the ISI 
• Change over time in ISI categories 
• Number (percentage) of subjects who receive sequential ORT therapy for pericarditis recurrence 
(analgesics, NSAIDs, and/or colchicine) in the RW period 
Efficacy endpoints for the RI period include: 
• Proportion of subjects who achieved Clinical Response at the RI Week 12 visit 
• Time to CRP normalization 
• Number (percentage) of subjects with normalization of CRP at RI Week 12 
• Change from baseline in pericarditis pain at RI Week 12 
• Change from baseline in CRP level at RI Week 12 
• Resolution of echocardiographic and ECG abnormalities (yes/no) at RI Week 12 
• Percentage of days with no or minimal pain 
• Proportion of subjects with absent or minimal pericarditis symptoms based on the PGIPS 
• Proportion of subjects with absent or minimal pericarditis activity based on the PGA-PA 
• Change over time in SF-36 Physical Component Score 
• Change over time in SF-36 Mental Component Score 
• Change in EQ-5D-5L 
• Change over time in subject’s sleep quality assessed with the ISI 
• Change over time in ISI categories 
• Number (percentage) of subjects who were off background SOC pericarditis therapy at RI Week 12 
Efficacy endpoints for the LTE-TP include: 
• Number (percentage) of subjects with pericarditis recurrences 
• Proportion of subjects with Clinical Response 
• Change over time in CRP levels 
• Change over time in subject’s assessments of pericarditis pain 
• Percentage of days with no or minimal pain 
• Proportion of subjects with absent or minimal pericarditis symptoms based on PGIPS 
• Proportion of subjects with absent or minimal pericarditis activity based on PGA-PA 
 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
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Statistical Methods Continued: 
• Change over time in SF-36 Physical Component Score 
• Change over time in SF-36 Mental Component Score 
• Change in EQ-5D-5L 
• Change over time in subject’s sleep quality assessed with the ISI 
• Change over time in ISI categories 
• Number (percentage) of subjects requiring addition of SOC pericarditis therapy 
Primary analysis of this study will be done after the 22nd CEC-confirmed pericarditis recurrence and after 
all subjects in the RW period have been treated for 24 weeks. Subjects who have not had an adjudicated 
pericarditis recurrence will be censored on the day of the last available assessment before data cutoff. 
Details of the analyses will be specified in the Statistical Analysis Plan. 
 
Protocol Version 
Version 1.1 
and Date: 
05 Oct 2018 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol 
Version 1.1, 
KPL-914-C002 
05 Oct 2018 
STUDY SCHEDULE OF ACTIVITIES 
Table 1–1 
Study Schedule of Activities – Screening and Run-In Period (Part 1 of 2) 
a 
The screening and enrollment visit can be combined. 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Full physical examination includes at minimum evaluation of vital signs, head, eye, ear, nose, and throat as well as cardiovascular, dermatological, musculoskeletal, respiratory, GI, 
genitourinary, and neurological systems 
Abbreviated physical examination includes at minimum evaluation of vital signs, lung and heart sounds, including evaluation for pericardial rub 
ECHO is required to be obtained according to the central core lab parameters and then read locally and submitted to the central core lab for separate review and analysis. 
Both a documented CRP > 1.0 mg/dL AND a pericarditis pain level of > 4 is required 7 days prior to and including the Run-In Baseline visit. These are not required to occur on the same 
day. 
Subjects missing ≥ 4 daily pain measurements during the 7 days prior to and including the Randomization Withdrawal baseline visit will be unable to proceed to randomization due to lack 
of data required for treatment response evaluation. 
All procedures are to be completed prior to study drug administration. 
b 
c 
d 
e 
f 
g 
m 
20 
q 
The Randomization visit serves as both the RI Week 12 visit and the RW baseline visit. 
Page 163 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Table 1–1 
Protocol   KPL-914-C002 
Version 1.1, 05 Oct 2018 
Study Schedule of Activities – Screening and Run-In Period (Part 2 of 2) 
a 
The screening and enrollment visit can be combined. 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Both a documented CRP > 1.0 mg/dL AND a pericarditis pain level of > 4 is required 7 days prior to and including the Run-In Baseline visit. These are not required to occur on the same day. 
Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the randomization withdrawal and LTE periods, or more frequently as needed, with mandated evaluations as detailed in the 
schedule of events. 
Applicable to 24-hour post dose PK sub-study participants only. 
For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout the course of the study and serum pregnancy can be drawn as needed; urine pregnancy is required to be performed 
at enrollment and 6 weeks after the last dose of study drug. 
Pharmacogenomics informed consent and subsequent sampling can be performed at any time in the study however, it is preferable to have this completed at the beginning of the study. 
Adverse event reporting begins following the subject providing informed consent. 
All procedures are to be completed prior to study drug administration. 
The first dose of study drug is a loading dose. Adult subjects receive 2 SC doses 160 mg (total 320 mg); pediatric subjects (subjects ≥12 and <18 years of age) receive 2 SC doses of 2 x 2.2 mg/kg. 
Study drug administration is once weekly with a minimum of 5 days required between doses. 
Randomization and subsequent study drug dispensing to occur after confirmation of Clinical Response (see definition of Clinical Response in Section 6.2.2). 
b 
f 
h 
i 
j 
k 
l 
m 
n 
o 
p 
q 
The Randomization visit serves as both the RI Week 12 visit and the RW baseline visit. 
21 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol 
KPL-914-C002 
Version 1.1, 05 Oct 2018 
Table 1–2 
Study Schedule of Activities – Randomized Withdrawal (Part 1 of 2) 
b 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Full physical examination includes at minimum evaluation of vital signs, head, eye, ear, nose, and throat as well as cardiovascular, dermatological, musculoskeletal, respiratory, GI, 
genitourinary, and neurological systems 
Abbreviated physical examination includes at minimum evaluation of vital signs, lung and heart sounds, including evaluation for pericardial rub 
ECHO is required to be obtained according to the central core lab parameters and then read locally and submitted to the central core lab for separate review and analysis. 
All procedures are to be completed prior to study drug administration. 
The EORW visit serves as both the last visit of the RW period and the baseline visit of the LTE period. 
For all subjects, the final clinic visit of the end of RW period is to be scheduled once the End of the Randomization Withdrawal end date is announced by Sponsor. This includes subjects 
that are taking blinded study drug, open-label rilonacept, or who have prematurely discontinued study drug. 
c 
d 
e 
m 
t 
u 
22 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Table 1–2 
Protocol 
KPL-914-C002 
Version 1.1, 05 Oct 2018 
Study Schedule of Activities – Randomized Withdrawal (Part 2 of 2) 
b 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the randomization withdrawal and LTE periods, or more frequently as needed, with mandated evaluations as detailed in the 
schedule of events. 
For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout the course of the study and serum pregnancy can be drawn as needed; urine pregnancy is required to be 
performed at enrollment and 6 weeks after the last dose of study drug. 
Adverse event reporting begins following the subject providing informed consent. 
All procedures are to be completed prior to study drug administration. 
Study drug administration is once weekly with a minimum of 5 days required between doses. 
The EORW visit serves as both the last visit of the RW period and the baseline visit of the LTE period. 
For all subjects, the final clinic visit of the end of RW period is to be scheduled once the End of the Randomization Withdrawal end date is announced by Sponsor. This includes subjects that are taking blinded study 
drug, open-label rilonacept, or who have prematurely discontinued study drug. 
Study drug administration to occur only after subject provides informed consent for the open-label extension period. 
h 
j 
l 
m 
o 
t 
u 
v 
23 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol 
KPL-914-C002 
Version 1.1, 05 Oct 2018 
Table 1–3 
Study Schedule of Activities – Long Term Extension (Part 1 of 2) 
b 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Full physical examination includes at minimum evaluation of vital signs, head, eye, ear, nose, and throat as well as cardiovascular, dermatological, musculoskeletal, respiratory, GI, 
genitourinary, and neurological systems 
ECHO is required to be obtained according to the central core lab parameters and then read locally and submitted to the central core lab for separate review and analysis. 
All procedures are to be completed prior to study drug administration. 
c 
e 
m 
24 
24 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Table 1–3 
Protocol   KPL-914-C002 
Version 1.1, 05 Oct 2018 
Study Schedule of Activities – Long Term Extension (Part 2 of 2) 
b 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the randomization withdrawal and LTE periods, or more frequently as needed, with mandated 
evaluations as detailed in the schedule of events. 
For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout the course of the study and serum pregnancy can be drawn as needed; urine pregnancy 
is required to be performed at enrollment and 6 weeks after the last dose of study drug. 
Adverse event reporting begins following the subject providing informed consent. 
All procedures are to be completed prior to study drug administration. 
Study drug administration is once weekly with a minimum of 5 days required between doses. 
h 
j 
l 
m 
o 
25 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
Table 1–4 
Study Schedule of Activities – Supplemental Visits (Part 1 of 2) 
b 
c 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Full physical examination includes at minimum evaluation of vital signs, head, eye, ear, nose, and throat as well as cardiovascular, dermatological, musculoskeletal, respiratory, GI, 
genitourinary, and neurological systems 
Abbreviated physical examination includes at minimum evaluation of vital signs, lung and heart sounds, including evaluation for pericardial rub 
ECHO is required to be obtained according to the central core lab parameters and then read locally and submitted to the central core lab for separate review and analysis. 
An EOT visit is to be conducted throughout the course of the study when a subject permanently discontinues study drug. 
An SFU is required to be conducted within 6 weeks of the last dose of rilonacept at any time throughout the course of the study including the RI period, the RW period, and the LTE period. 
The MRI to occur only if the previous MRI was done longer than 6 months ago. 
d 
e 
x 
y 
z 
26 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Table 1–4 
Protocol   KPL-914-C002 
Version 1.1, 05 Oct 2018 
Study Schedule of Activities – Supplemental Visits (Part 2 of 2) 
b 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the randomization withdrawal and LTE periods, or more frequently as needed, with mandated 
evaluations as detailed in the schedule of events. 
For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout the course of the study and serum pregnancy can be drawn as needed; urine pregnancy is 
required to be performed at enrollment and 6 weeks after the last dose of study drug. 
Adverse event reporting begins following the subject providing informed consent. 
Upon investigator confirmation of pericarditis recurrence, the IWRS is to be updated. 
An EOT visit is to be conducted throughout the course of the study when a subject permanently discontinues study drug. 
An SFU is required to be conducted within 6 weeks of the last dose of rilonacept at any time throughout the course of the study including the RI period, the RW period, and the LTE period. 
h 
j 
l 
s 
x 
y 
27 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
LIST OF ABBREVIATIONS 
28 
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Abbreviation 
Definition 
ADA 
anti-drug antibodies 
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
CAPS 
Cryopyrin Associated Periodic Syndrome 
CEC 
Clinical Endpoint Committee 
CFR 
Code of Federal Regulations 
CMH 
Cochran–Mantel–Haenszel 
CRP 
C-reactive protein 
CS 
corticosteroids 
DMC 
Data Monitoring Committee 
ECG 
electrocardiogram 
ECHO 
echocardiography; echocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
eDiary 
electronic diary 
EORW 
End of Randomized-Withdrawal(visit) 
EOS 
End of Study 
EOT 
End of Treatment (visit) 
EQ-5D-5L 
5-level EuroQoL-5D 
ESC 
European Society of Cardiology 
ESR 
erythrocyte sedimentation rate 
FCAS 
Familial Cold Auto-Inflammatory Syndrome 
FDA 
US Food and Drug Administration 
GCP 
Good Clinical Practice 
GI 
gastrointestinal 
HDL 
high-density lipoprotein 
HIV 
human immunodeficiency virus 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
independent ethics committee 
IgG1 
human immunoglobulin G1 
IGRA 
Interferon Gamma Release Assay 
IL-1 
interleukin-1 
IRB 
Institutional Review Board 
ISI 
Insomnia Severity Index 
ISR 
injection site reaction 
ITT 
intent to treat 
IV 
intravenous(ly) 
IWRS 
interactive web response system 
KPL-914 
rilonacept 
 


Kiniksa Pharmaceuticals, Ltd. 
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Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
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LDL 
low-density lipoprotein 
LTE-FUP 
Long Term Extension Follow-Up Period 
LTE-TP 
Long Term Extension Treatment Period 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
magnetic resonance imaging 
MWS 
Muckle-Wells Syndrome 
NSAID 
nonsteroidal anti-inflammatory drug 
NRS 
Numerical Rating Scale 
ORT 
Oral Rescue Therapy 
PHV 
Pharmacovigilance 
PGA-PA 
Physician Global Assessment of Pericarditis Activity 
PGIPS 
Patient Global Impression of Pericarditis Severity 
PK 
pharmacokinetic(s) 
POC 
point of care 
PRO 
patient-reported outcome 
RI 
Run-In (period) 
RN 
visiting registered nurse 
RW 
Randomized-Withdrawal (period) 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SC 
subcutaneous(ly) 
SF-36 
36-Item Short Form Health Survey 
SFU 
safety follow-up 
SOC 
standard of care 
SUSAR 
suspected unexpected serious adverse reaction 
TB 
tuberculosis 
TC 
site telephone visit (telephone contact) 
TEAE 
treatment-emergent adverse event 
TNF 
tumor necrosis factor 
ULN 
upper limit of normal 
WBC 
white blood cell 
WFI 
Water for Injection 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
1 
Introduction 
Pericarditis is inflammation of the pericardium, the double-walled sac surrounding the heart. 
Etiologies of pericarditis include infectious causes (viral, bacterial, fungal, and parasitic) and non-
infectious causes (idiopathic, autoimmune, neoplastic, metabolic, traumatic, post-surgical, and drug-
related) (Adler et al 2015). In 80% of cases in developed countries, the cause of pericarditis is either 
post-viral or “idiopathic” in that it cannot be attributed to a specific condition (Imazio et al 2010; 
Zayas et al 1995). 
The underlying pathogenesis of recurrent pericarditis remains unclear, although a growing body of 
evidence suggests that abnormal immune responses play a role in the pathogenic processes. While the 
adaptive immune system plays a role in autoimmune disorders that manifest with pericarditis as one 
of the many organ systems involved (such as in systemic lupus erythematosus or rheumatoid 
arthritis), the innate immune system, including interleukin 1 (IL-1) signaling, is often the major 
effector in autoinflammatory disorders, such as isolated pericarditis (Baskar et al 2016; Brucato et al 
2016; Imazio et al 2016, Dinarello et al 2012). 
Diagnosis of pericarditis is based on the presence of typical chest pain (improved by sitting up and 
leaning forward) along with fever, pericardial friction rub, electrocardiographic changes, pericardial 
effusion, or elevated levels of inflammation markers (white blood cell [WBC] count, C-reactive 
protein [CRP], or erythrocyte sedimentation rate [ESR]) (Adler et al 2015). The European Society of 
Cardiology (ESC) Guidelines for the Diagnosis and Management of Pericardial Diseases define an 
acute pericarditis episode as the presence of at least 2 of the 4 following criteria: pericarditic chest 
pain, pericardial rubs, new widespread ST-segment elevation or PR-segment depression based on 
electrocardiogram (ECG) findings, and pericardial effusion (new or worsening). Elevations of certain 
markers of inflammation (i.e., CRP, ESR, and WBC) or evidence of pericardial inflammation by an 
imaging technique (e.g., magnetic resonance imaging [MRI]) are used as supportive findings (Adler 
et al 2015). 
Recurrent pericarditis is characterized by the recurrence of pericarditis signs and symptoms after a 
symptom-free period of at least 4 to 6 weeks (Adler et al 2015). Recurrent pericarditis affects 20% to 
30% of patients with acute pericarditis (Imazio 2014) and can be debilitating for patients due to pain 
and limitations in physical function during pericarditis episodes. Pericarditis recurrences result in 
increased emergency room admissions and hospitalizations. In the United States, 5% of patients 
presenting to the emergency room with non-ischemic chest pain are diagnosed with pericarditis 
(Agarwal et al 2015). 
The estimated prevalence of recurrent pericarditis in the US and Europe is 70,000 to 160,000 patients 
including approximately 8,000 to 21,000 patients who are refractory or intolerant to current therapies 
or who require long-term administration of corticosteroids (CS) to control their disease (Brucato et al 
2016; Lazaros et al 2016; Imazio et al 2010; Khandaker et al 2010; Imazio et al 2008). 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
1.1 
Current Therapeutic Management of Pericarditis 
There are no approved therapies for the treatment of recurrent pericarditis. Current treatments include 
nonspecific inhibitors of inflammation, i.e., aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), 
colchicine, and CS (Lilly et al 2013). 
Aspirin and other NSAIDs are the first-line approach. Because high doses of aspirin and NSAIDs are 
often required, consideration must be given to gastric protection therapy, as potential risks of therapy 
include stomach ulcers and gastrointestinal (GI) bleeding, as well as renal and cardiovascular toxicity. 
Colchicine is another mainstay therapy for pericarditis and is commonly used with NSAIDs to hasten 
the response to NSAIDs and reduce the risk of subsequent recurrences. However, its use may be 
associated with the risk of fatal overdosing, significant drug interactions, and neuromuscular toxicity. 
In addition, approximately 10% to 15% of patients experience significant GI side effects with 
colchicine, including GI intolerance or severe diarrhea, requiring treatment discontinuation (Imazio et 
al 2016). 
Available ESC guidelines stipulate that CS should be prescribed for the management of pericarditis 
episodes only in cases of incomplete response, intolerance, or contraindications to NSAIDs and 
colchicine because of their unfavorable long-term benefit-risk profile. Corticosteroid use is associated 
with side effects, including weight gain, diabetes, osteoporosis, avascular bone necrosis, and 
increased risk for infections (Imazio et al 2008). For the management of pericarditis, CS are usually 
administered at low to moderate doses and can provide rapid control of symptoms. However, they 
often require many months of tapering after the normalization of CRP levels. In addition, there is a 
high rate of pericarditis relapse when CS use is tapered or stopped (Lotrionte et al 2010; Imazio et al 
2005; Maisch et al 2004), particularly in the absence of concurrent colchicine treatment. 
Patients with recurrent pericarditis who are refractory or intolerant to current therapeutic management 
options or who require long-term administration of CS to control their disease can be particularly 
challenging to manage. As a last resort, some refractory patients are being referred to the surgical 
procedure of pericardiectomy, with variable outcomes. Multiple immunosuppressive medications 
have been used without consistent benefit (Baskar et al 2016). 
1.2 
Pathogenesis of Recurrent Pericarditis: Role of IL-1 
Interleukin-1 is a key cytokine that drives the pathophysiology of many inflammatory processes, and 
it is implicated as a causative factor in various inflammatory diseases in humans. 
The two distinct IL-1 genes, IL1A and IL1B, encode IL-1α and IL-1β, respectively. IL-1α and IL-1β 
bind to the universally-expressed cell surface receptor, IL-1 receptor type-1, triggering a cascade of 
inflammatory mediators. The precursor form of IL-1α is expressed in keratinocytes, mucous 
membrane epithelial cells, and organs such as the liver and vascular endothelium in healthy 
individuals. During pathological states, IL-1α moves to the cell surface or is released after cell death 
to activate IL-1 receptors in adjacent cells, thus beginning the cascade of sterile inflammation. IL-1β, 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
however, is not expressed in healthy individuals until a stimulus, such as microbial products or other 
chemokines, triggers its transcription in monocytes, tissue macrophages, and dendritic cells via the 
inflammasome. IL-1 drives the inflammatory cascade in classic autoinflammatory conditions, such as 
tumor necrosis factor (TNF)-associated periodic syndrome (TRAPS) and familial Mediterranean 
fever (FMF) and plays a significant role in systemic onset of juvenile idiopathic arthritis and in 
autoimmune diseases such as rheumatoid arthritis (Baskar et al 2016). 
IL-1–blocking therapies are effective at controlling end-organ disease and damage in patients with 
various autoinflammatory disorders, and different strategies to block IL-1 have been used in clinical 
trials and demonstrated substantial success in controlling episodes of fever and elevations in 
acute-phase reactants (Cantarini et al 2015). 
This mechanistic plausibility of IL-1 antagonism in addressing pathophysiology related to the 
inflammasome extends to other conditions characterized by sterile acute inflammation, such as 
32 
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recurrent pericarditis. 
 
 
 
 
 
 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
1.3 
Rilonacept (KPL-914) 
Rilonacept (designated in Kiniksa Pharmaceutical’s development program as KPL-914) was 
developed by Regeneron Pharmaceuticals, Inc. (Regeneron) of Tarrytown, NY, and is approved with 
the trade name ARCALYST® in the US for the treatment of CAPS, including Familial Cold Auto-
Inflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and children age 12 
and older. Rilonacept is currently manufactured and marketed as ARCALYST® by Regeneron. 
Rilonacept received marketing authorization in the European Union for the treatment of CAPS with 
severe symptoms, including FCAS and MWS in adults and children aged 12 years and older, but 
based on a request from Regeneron, the marketing authorization was withdrawn. The withdrawal was 
a business decision and was not related to any concern with the safety or efficacy of rilonacept. 
Rilonacept is a recombinant fusion protein consisting of human cytokine receptor extracellular 
domains and the Fc portion of human IgG1. Rilonacept is a dimeric glycoprotein with a total 
molecular weight of approximately 250 kDa. The dimer is covalently linked by disulfide bonds in the 
Fc region. Rilonacept incorporates in a single molecule the extracellular domains of both receptors 
required for IL-1 signaling: the IL-1 type I receptor (IL-1R1) and the IL-1 receptor accessory protein 
(IL-1R-AcP) (Figure 1). 
Rilonacept is expressed in recombinant Chinese hamster ovary (CHO) cells. Rilonacept blocks IL-1 
by acting as a soluble decoy receptor that binds IL-1 and prevents its interaction with cell surface 
receptors. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
Figure 1: 
Schematic of Rilonacept (KPL-914) 
IL-1R Type 1 
IL-1R-AcP 
- 
IL-1R-AcP 
Extracellular 
Domains 
Extracellular 
Domains 
Cell Membrane 
IL-1R Type 1 
Cytoplasmic 
Domains 
s s 
s s 
hIgG Fc 
1.3.1 Safety of Rilonacept 
For a detailed review of the available rilonacept safety data, please refer to the current Investigator 
Brochure and the ARCALYST® package insert (Section 13.1: ARCALYST® Prescribing 
Information). The available rilonacept safety data is summarized below. 
Rilonacept has been evaluated in 23 studies, including 22 complete and 1 ongoing. In the completed 
studies, 2243 subjects (2152 patients and 91 healthy volunteers) were exposed to rilonacept. Thirty of 
these patients were pediatric (<18 years of age). 
Doses up to 320 mg subcutaneously (SC) once weekly and 2000 mg intravenously (IV) monthly have 
been studied for different indications, including CAPS, gout, and other inflammatory disorders. 
Injection Site Reactions 
In clinical studies with rilonacept, the most common and consistently reported AE associated with 
rilonacept was injection site reaction (ISR). The ISRs included erythema, swelling, pruritus, mass, 
bruising, inflammation, pain, edema, dermatitis, discomfort, urticaria, vesicles, warmth, and 
hemorrhage. Most ISRs were mild to moderate. In the gout clinical studies, approximately 1% of 
subjects treated with rilonacept discontinued due to ISRs. Similar results have been seen in other 
patient populations. 
Infections 
Interleukin-1 blockade may interfere with immune response to infections. Serious life-threatening 
infections have been reported in clinical trials in subjects treated with rilonacept. 
34 
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CH3 
 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
Changes in Laboratory Parameters 
Cholesterol and lipid levels may be reduced in patients with chronic inflammation. Subjects treated 
with rilonacept in clinical trials experienced increases in their mean total cholesterol, high-density 
lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides. 
Immunogenicity 
As with all therapeutic proteins, there is a potential for immunogenicity. Antibodies directed against 
the receptor domains of rilonacept were detected using an enzyme-linked immunosorbent assay 
(ELISA). In clinical trials with rilonacept, approximately 30% to 35% of subjects tested positive for 
treatment-emergent antibodies to rilonacept on at least 1 occasion. 
Systemic Hypersensitivity Reactions 
Hypersensitivity reactions are a potential risk with protein therapeutics in general. In clinical studies 
with rilonacept, systemic hypersensitivity reactions have been rare. 
Malignancies 
The impact of treatment with rilonacept on the development of malignancies is not known. However, 
treatment with immunosuppressants, including rilonacept, may result in an increase in the risk for 
malignancies. 
Fetal Defects 
There are no adequate and well-controlled studies of rilonacept in pregnant women. Based on animal 
data, rilonacept may cause fetal harm. An embryo-fetal developmental toxicity study was performed 
in cynomolgus monkeys treated with 0, 5, 15, or 30 mg/kg given twice a week (highest dose is 
approximately 3.7-fold higher than the human dose of 160 mg based on body surface area). The fetus 
of the only monkey with exposure to rilonacept during the later period of gestation showed multiple 
fusion and absence of the ribs and thoracic vertebral bodies and arches. Exposure to rilonacept during 
this time period was below that expected clinically. Likewise, in the cynomolgus monkey, all doses of 
rilonacept reduced serum levels of estradiol up to 64% compared to controls and increased the 
incidence of lumbar ribs compared to both control animals and historical control incidences. In 
perinatal and postnatal developmental toxicology studies in the mouse model using a murine analog 
of rilonacept (0, 20, 100, or 200 mg/kg), there was a 3-fold increase in the number of stillbirths in 
dams treated with 200 mg/kg 3 times per week (the highest dose is approximately 6-fold higher than 
the 160 mg maintenance dose based on body surface area). 
Nonteratogenic effects: A peri- and postnatal reproductive toxicology study was performed in which 
mice were administered a murine analog of rilonacept at doses of 20, 100, and 200 mg/kg SC 3 times 
per week (the highest dose is approximately 6-fold higher than the 160 mg maintenance dose based 
on body surface area). Results indicated an increased incidence in unscheduled deaths of the F1 
offspring during maturation at all doses tested. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
1.3.2 KPL-914-C001 
Pericarditis 
Study 
with 
Rilonacept 
(KPL-914) 
in 
Recurrent 
KPL-914-C001 is an open-label, single active-arm Phase 2 proof-of-concept study in subjects age ≥6 
to 75 years old with recurrent idiopathic or post-pericardiotomy syndrome (PPS) pericarditis. The 
study includes a 6-week Treatment Period in which all the subjects receive once-weekly rilonacept 
160 mg SC (2.2 mg/kg for subjects ≥6 and <18 years old) following a loading dose of 320 mg SC in 
subjects ≥18 years old (4.4 mg/kg in subjects ≥6 and <18 years old) in addition to background 
pericarditis therapies (NSAIDS, colchicine, CS). After completing the 6-week Treatment Period and 
based on response status, the subjects have the option to enter the 18-week Extension Period during 
which they continue to receive rilonacept at the same dose, but during which investigators are 
encouraged to wean and stop background pericarditis medications. 
The primary objectives of the study are to explore clinical and biochemical endpoints of recurrent 
pericarditis symptomatology, as well as to assess feasibility to wean from concomitant pericarditis 
medication in the Extension Period while continuing treatment with rilonacept. The study population 
includes the following 5 subject categories (Parts): 
• 
Part 1 enrolls symptomatic subjects with recurrent idiopathic pericarditis with an elevated marker 
of systemic inflammation (CRP level >1 mg/dL). 
Part 2 enrolls symptomatic subjects with recurrent idiopathic pericarditis with CRP level 
≤1 mg/dL that, in the opinion of the investigator, can be attributed to concomitant medications 
(e.g., CS) and with pericardial inflammation present on cardiac MRI confirmed by the imaging 
core lab. 
Part 3 enrolls subjects with CS-dependent recurrent idiopathic pericarditis not experiencing 
symptoms that would meet the diagnostic criteria for a recurrence of pericarditis. 
Part 4 enrolls symptomatic subjects with recurrent PPS with an elevated marker of systemic 
inflammation (CRP level >1 mg/dL). 
Part 5 enrolls subjects with CS-dependent recurrent PPS not experiencing symptoms that would 
meet the diagnostic criteria for a recurrence of pericarditis. 
• 
• 
• 
• 
Preliminary data in this ongoing study suggest that subjects enrolled in Part 1 experience 
improvements in pain, CRP levels, and other pericarditis parameters compared to baseline. 
Adverse events observed in the study are consistent with the overall rilonacept safety profile. 
2 
Study Objectives and Endpoints 
2.1 
Primary Objective 
The primary objective of this study is to assess the efficacy of rilonacept treatment in subjects with 
recurrent pericarditis. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
2.2 
Secondary Objective 
The secondary objective of this study is to assess the safety of rilonacept treatment in subjects with 
recurrent pericarditis. 
3 
Investigational Plan 
3.1 
Study Design 
This is a Phase 3, multi-center, double-blind, placebo-controlled, randomized withdrawal study with 
open-label extension, to assess the efficacy and safety of rilonacept treatment in subjects with 
recurrent pericarditis. This study has 5 periods (Figure 2). 
3.1.1 Screening Period (up to 4 weeks) 
During the screening period, assessment of disease characteristics, baseline therapy, and the pre-
treatment workup will be completed during a period of up to 4 weeks. 
3.1.2 Single-blind Run-In (RI) Period (12 weeks) 
During the single-blind RI period, treatment with blinded rilonacept is administered and subjects are 
weaned off background standard of care (SOC) therapy for their pericarditis disease. Subjects will be 
blinded regarding the time of transition from the single-blind to the double-blind period; i.e., they will 
not be aware of the duration of the RI period. 
In the single-blind RI period, subjects ≥18 years old will receive blinded rilonacept as an initial 
loading dose of 320 mg (2 SC injections of 160 mg each) at the RI baseline visit (2 × 2 ml), followed 
by a 160 mg (2 ml) SC dose once weekly throughout the RI period. Pediatric subjects (≥12 and <18 
years old) will receive an initial loading dose of blinded rilonacept 4.4 mg/kg (2 SC injections of 
2.2 mg/kg each) at the RI baseline visit (maximum 2 × 2 ml), and then 2.2 mg/kg (maximum 2 ml) 
SC once weekly throughout the RI period. 
The RI period includes: 
• 
1-week Stabilization period, during which blinded rilonacept is administered in addition to SOC 
pericarditis therapy, and the ongoing pericarditis episode is treated. 
9-week Weaning period, during which subjects are weaned off background SOC pericarditis 
therapy, as applicable, while treatment with blinded rilonacept continues. The dosages of CS, 
NSAIDs, and colchicine will be tapered according to the weaning protocol in the Pharmacy 
Manual (for the purpose of the protocol, aspirin is considered an NSAID). In general, CS doses 
will be tapered off starting at RI Week 1 and will be withdrawn by RI Week 10 (over a total of 
9 weeks). NSAID and colchicine doses will be tapered off starting at RI Week 4 and will be 
withdrawn by RI Week 10 (over a total of 6 weeks). 
2-week Monotherapy period: Subjects who have been successfully weaned off background SOC 
pericarditis therapy will continue to receive blinded rilonacept. 
• 
• 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
Subjects who stopped background pericarditis medications and achieve Clinical Response on 
rilonacept monotherapy at RI Week 12/RW baseline will proceed into the double-blind placebo-
controlled Randomized-Withdrawal (RW) period of the study. For definition of Clinical Response, 
refer to Section 6.2.2. 
Subjects who are unable   to   achieve   Clinical   Response   on   rilonacept   m,onotherapy   at 
RI Week 12/RW baseline are to be discontinued from study drug, transitioned to SOC pericarditis 
therapy at the investigator’s discretion, and followed through the end of the RW period. 
3.1.3 Double-blind Placebo-controlled RW Period (pericarditis recurrence 
event-driven duration with a minimum of 24 weeks) 
During the RW period, subjects who were able to stop background pericarditis medications and who 
achieve Clinical Response on rilonacept monotherapy at RI Week 12/RW baseline will be 
randomized 1:1 to double-blinded administration of study drug: 
• 
Rilonacept 160 mg (or 2.2 mg/kg in pediatric subjects ≥12 and <18 years old) SC injections once 
weekly OR 
Matching placebo SC injections once weekly 
• 
Pericarditis Recurrence in the RW Period 
For the definition of pericarditis recurrence, refer to Section 6.2.3. 
Upon pericarditis recurrence, subjects who report at least 1 day with pericarditis pain measurement ≥4 
on the 11-point Numerical Rating Scale [NRS] and have 1 CRP value ≥1 mg/dL (either on the same 
day or separated by no more than 7 days) will receive bailout rilonacept (2 open-label injections of 
160 mg rilonacept [or 4.4 mg/kg for pediatric subjects]) irrespective of randomized treatment 
assignment and as soon as at least 5 days have passed since the last study drug injection. The subjects 
transitioning to bailout rilonacept will remain blinded to their prior RW period treatment assignment. 
Sequential Oral Rescue Therapy (ORT), i.e., analgesics first, then NSAIDs, and then colchicine, can 
be added, if needed, at the discretion of the investigator, as outlined in Section 5.8.3 and detailed in 
the Pharmacy Manual. 
Subjects with pericarditis recurrence who do not meet the protocol criteria for bailout rilonacept will 
continue blinded study drug until they meet the protocol criteria for bailout rilonacept or through the 
end of the RW period. For those subjects, sequential ORT can be added to blinded study drug at the 
discretion of the investigator, as outlined in Section 5.8.3 and detailed in the Pharmacy Manual. 
All suspected pericarditis recurrence events in the RW period will be formally adjudicated by the 
Clinical Endpoint Committee (CEC), and only events that are confirmed by the CEC as pericarditis 
recurrences will be used in the Primary Endpoint analysis. 
The RW period will continue until the prespecified number of primary endpoint (CEC-confirmed 
pericarditis recurrence) events have occurred and approximately 50 randomized subjects have 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
achieved a minimum of 24 weeks of treatment in the RW period. Based on projected event accrual 
and subject randomization, Kiniksa Pharmaceutical will determine the end of the RW period and 
announce to sites so that subject End of Randomized Withdrawal (EORW) visits can occur. All 
subjects, including those who have transitioned to open-label rilonacept or who prematurely 
discontinued study drug, should complete an EORW visit. 
3.1.4 Long Term Extension Treatment Period (LTE-TP) (24 weeks) 
Upon completion of the RW period and the EORW visit (site and subject unblinding), all subjects 
completing the RW period (including subjects transitioned to open-label rilonacept upon pericarditis 
recurrence) will have an option to receive up to 24 weeks of open-label rilonacept 160 mg (or 
2.2 mg/kg for pediatric subjects) SC injections once weekly based on their clinical status and at the 
discretion of the investigator, after signing LTE informed consent. Any subject who, in the opinion of 
investigator, should not continue open-label rilonacept will be offered participation in the LTE off 
study drug after signing LTE informed consent. 
3.1.5 Long Term Extension Follow-Up Period (LTE-FUP) (24 weeks) 
All subjects in the LTE-TP will be followed in the LTE-FUP for an additional 24 weeks for safety 
and for potential pericarditis recurrence assessments. 
The total duration of the study will be determined by the rate of enrollment, the rate of first recurrence 
of pericarditis events during the RW period, and the minimum duration of follow-up in the RW of 
24 weeks. It is anticipated that study completers (including LTE-TP) will be dosed with rilonacept for 
approximately 1.2 years and up 
recurrence events accrual time. 
to 3 years based on enrollment assumptions and pericarditis 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
Figure 2: 
Overview of KPL-914-C002 Trial Design 
a 
Enrollment 
First Dose 
End of Study 
(EOS) 
Randomization 
1:1 
End of RW 
LTE Week 24 
(Last Dose) 
Screening 
Up to 
4 weeks 
Single-blind Run In 
(RI) 
12 Weeks 
Event Driven Double-blind Randomized- 
b 
Withdrawal Period (RW) 
(Until 22 confirmed recurrence events) 
Anticipated minimum of 24 Weeks 
LTE Follow-Up 
(LTE-FUP) 
24 Weeks 
Long Term Extension Treatment Period 
(LTE-TP) 
24 Weeks 
1 
Week 
9 
Weeks 
2 
Weeks 
c 
Blinded rilonacept 160 mg SC once weekly 
Blinded rilonacept 160 mg 
c 
SC once weekly 
c 
Open-label rilonacept 160 mg SC once weekly 
Blinded placebo SC once weekly 
Stabilization 
while on 
background 
medication 
Monotherapy 
with rilonacept 
Weaning 
of NSAID, 
Colchicine, 
CS 
Primary Endpoint 
Abbreviations: CS=corticosteroid; EOS=end of study, LTE=Long Term Extension; NSAID=nonsteroidal anti-inflammatory drug; RI=run in, RW=randomized withdrawal, SC=subcutaneously, TP=treatment period 
a. The first dose given is a loading dose of rilonacept. In adult subjects ≥18 years old, 320 mg is given as 2 SC doses of 160 mg. In pediatric subjects ≥12 and <18 years old, 4.4 mg/kg is given as 2 SC doses of 2.2 
mg/kg. After the loading dose, rilonacept will be administered as a 160 mg (adults) or 2.2 mg/kg (pediatric subjects) SC dose once weekly. 
b. Subject’s treatment duration will depend on when the subject is enrolled relative to the end of RW. 
c. The adult dose is 160 mg SC once weekly. The pediatric dose is 2.2 mg/kg SC once weekly. 
Note: This picture is not drawn to scale. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
3.1.6 Rationale of Study Design 
Subjects eligible for this KPL-914-C002 study will be subjects with recurrent pericarditis presenting 
with an acute pericarditis episode at screening. 
The KPL-914-C002 study design ensures that during the RI period all subjects will receive rilonacept, 
a drug with evidence supporting clinical activity based on the preliminary clinical data with rilonacept 
from Part 1 of the ongoing Phase 2 proof-of-concept study (KPL-914-C001) obtained to date. During 
the RI period, pericarditis will be stabilized with symptoms controlled and background pericarditis 
medications (NSAIDs, colchicine, CS) will be tapered and withdrawn, while rilonacept treatment 
continues. 
The design then allows half of the subjects to continue receiving active treatment after having 
achieved Clinical Response on that treatment, which maximizes subject exposure to a potentially 
beneficial therapy. The temporary withdrawal of rilonacept (by switching to placebo) in the half of 
the subjects who were randomly assigned to placebo is expected to result in an accelerated time to 
pericarditis recurrence and a higher recurrence rate compared to those who continue on active 
treatment, a finding that demonstrates that the underlying pericarditis etiology is still ongoing and will 
provide further support for the anticipated observation of the clinical effect of rilonacept during the RI 
period of the study. The period of exposure to an ineffective treatment is minimized in this design, as 
subjects will be removed from blinded treatment when the condition returns to a specified severity 
(i.e., for having met the criteria of pericarditis pain ≥4 on the 11-point NRS and CRP level ≥1 mg/dL) 
without unblinding them to prior treatment assignment, thus protecting the primary efficacy endpoint 
of the study. All subjects who meet the pain and CRP criteria described above will be treated with 
open-label bailout rilonacept using a loading dose, followed by once-weekly SC injections. In 
addition, sequential ORT such as NSAIDs and/or colchicine will be allowed upon recurrence at the 
investigator’s discretion based on the subject’s clinical status, as outlined in Section 5.8.3 and as 
stipulated in the Pharmacy Manual. Subjects with pericarditis recurrence not meeting criteria for 
bailout rilonacept, can be treated with sequential ORT based on investigator judgement and as 
described in protocol Section 5.8.3 and the Pharmacy Manual. If the subject requires the addition of 
CS treatment to control the pericarditis recurrence, the subject will be discontinued from study drug. 
All subjects will be followed for the duration of RW period. 
In summary, the proposed RW trial with rilonacept allows all enrolled subjects an opportunity to 
receive the active drug during the acute episode of pericarditis yet provides pivotal-quality data on the 
efficacy of rilonacept in this enriched cohort by subsequently randomly assigning subjects to placebo 
versus active treatment after they achieve a predefined clinical response. Subjects with pericarditis 
recurrences after randomization will receive bailout rilonacept treatment and/or sequential ORT 
according to the protocol. This approach minimizes the exposure to placebo, which is important for a 
study that requires active disease upon enrollment and includes a pediatric population. The available 
regulatory guidance supports the use of an RW study design in the setting of recurrent pericarditis as 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
a means  of establishing the long-term effectiveness of rilonacept, an approved product for the 
treatment of another rare autoinflammatory condition (CAPS). 
3.1.7 Justification for Rilonacept Dose Selection 
, i.e., 320 mg 
SC loading dose (4.4 mg/kg in subjects ≥12 and <18 years old), followed by once-weekly SC doses at 
160 mg (2.2 mg/kg in subjects ≥12 and <18 years old). 
In the rilonacept development program in CAPS, gout, rheumatoid arthritis, and other inflammatory 
conditions, over 2000 subjects were exposed to rilonacept, including 1650 subjects receiving a 
rilonacept dose of 160 mg or higher. A total of 103 and 169 subjects were exposed to any rilonacept 
dose for at least 1 year or 6 months, respectively. Most of the real-life experience with rilonacept 
comes from the CAPS population treated at this marketed dose. As of March 2018, approximately 
365 CAPS patients have been exposed to rilonacept in the post-marketing setting since 2008. The 
safety data accumulated so far support the benefit/risk ratio for the rilonacept dose intended to be 
evaluated in subjects with recurrent pericarditis. 
Based on the preliminary clinical data with rilonacept from Part 1 of the Phase 2 proof of concept 
study (KPL-914-C001) obtained to date, it is expected that rilonacept doses 
(320 mg followed by 160 mg SC once weekly and corresponding pediatric doses), and evaluated in 
the KPL-914-C001 study, will consistently provide adequate suppression of clinical inflammatory 
response, including CRP levels, in patients with recurrent pericarditis. 
Bailout Rilonacept Dose 
Subjects who meet the protocol criteria for bailout rilonacept upon pericarditis recurrence in the RW 
period of the study (Sections 3.1 and 6.2.3), irrespective of treatment assignment at randomization, 
will receive open-label rilonacept (loading dose of 320 mg SC followed by once-weekly SC 
injections of 160 mg, or the corresponding pediatric doses). 
The rationale for bailout rilonacept treatment upon pericarditis recurrence for subjects who were 
randomly assigned to placebo is that rilonacept had controlled their disease activity during the RI 
period; therefore, re-initiation of rilonacept is justified to regain control of pericarditis signs and 
symptoms upon recurrence. Subjects who were randomly assigned to rilonacept and qualify for 
bailout rilonacept upon pericarditis recurrence in the RW period were initial responders to rilonacept 
treatment during the RI period; thus it could be assumed that the loss of response during the RW 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
period could be due to development of resistance to rilonacept due to different mechanisms, e.g., 
higher IL-1 levels or a change in rilonacept pharmacokinetics (PK)/ pharmacodynamics. Therefore, 
re-administration of a loading dose of rilonacept may help to restore Clinical Response. 
4 
Subject Selection and Withdrawal Criteria 
4.1 
Selection of Study Population 
Approximately 56 subjects will be enrolled (and not more than 75 subjects), which will allow at least 
50 subjects to be randomized at approximately 50 sites globally. Subjects will be assigned to study 
drug only if they meet all of the inclusion criteria and none of the exclusion criteria. 
Deviations from the inclusion and exclusion criteria are not allowed because they can potentially 
jeopardize the scientific integrity of the study, regulatory acceptability, or subject safety. Therefore, 
adherence to the criteria as specified in the protocol is essential. 
Subjects eligible for the study are subjects with recurrent pericarditis who do not have pericarditis 
secondary to prohibited conditions. The study population includes both adult subjects ≥18 years old 
and pediatric subjects ≥12 and <18 years old with a history of at least 2 pericarditis episodes 
(including the first episode and 1 recurrence) prior to screening. Enrollment of pediatric subjects will 
be limited to up to 20% of the study population. To be eligible for the study, subjects must present 
with at least a third pericarditis episode, defined as at least 1 day with pericarditis pain measurement 
≥4 on the 11-point 
administration. 
NRS and CRP level ≥1 mg/dL within 7 days prior to the first study drug 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
4.1.1 Inclusion Criteria 
Each subject must meet all of the following criteria to be enrolled in this study: 
1. Is capable of understanding the written informed consent form (ICF) or assent form (for 
pediatric subjects ≥12 and <18 years old), has provided signed and witnessed written informed 
consent or assent (as applicable), and agrees to comply with protocol requirements. 
Is male or female 12 years of age or older with body weight of at least 23.6 kg (52 Lbs). 
Has a diagnosis of recurrent pericarditis. 
At least 1 of the pericarditis episodes experienced prior to screening has met at least 2 of the 
following 4 criteria, in the opinion of the investigator and based on the documented available 
data, according to the 2015 ESC Guidelines for the Diagnosis and Management of Pericardial 
Diseases (Adler et al 2015): 
2. 
3. 
4. 
a. 
b. 
c. 
Pericarditic chest pain 
Pericardial rub 
New widespread ST-segment elevation or PR-segment depression according to ECG 
findings 
Pericardial effusion (new or worsening) 
d. 
5. Presents with at least the third episode of pericarditis during screening (i.e., at least the second 
pericarditis recurrence following the first pericarditis episode), and within 7 days* prior to and 
including RI baseline (first administration of study drug) has: 
a. At least 1 day with pericarditis pain ≥4 on the 11-point NRS, AND 
b. CRP level ≥1.0 mg/dL (for details of CRP collection see Section 6.1.1) 
*Pericarditis pain ≥4 and CRP ≥1 mg/dL are not required to be present on the same day. 
6. Has received NSAIDs and/or colchicine and/or CS (in any combination), if used, at stable 
dose levels (or at least not increased) for at least 3 days prior to and including RI baseline 
(first administration of study drug), and changes in medications made within this time period 
(e.g., 1-time use of NSAIDs) are not anticipated, in the opinion of the investigator, to 
significantly alter assessments of baseline disease activity. 
If using NSAIDs and/or colchicine and/or CS at the time of RI baseline (first administration of 
study drug), is willing and able, in the opinion of the investigator, to taper and discontinue 
those medications within the 9-week weaning time in the RI period of the study while 
continuing rilonacept treatment. 
7. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
8.   Female subjects must be: 
a. Postmenopausal, defined as at least 12 months after the cessation of menses (without an 
alternative medical cause) OR 
Incapable of pregnancy OR 
Permanently sterile following documented hysterectomy, bilateral salpingectomy, 
bilateral oophorectomy, or bilateral tubal ligation or having a male partner with 
vasectomy as affirmed by the subject OR 
If of childbearing potential, must agree to use a highly effective method of contraception 
during the study and for 3 months after the last study drug administration (i.e., hormonal 
contraceptives associated with inhibition of ovulation, intrauterine device [IUD], 
intrauterine hormone-releasing system [IUS], or sexual abstinence) 
b. 
c. 
d. 
9. If male and sexually active, must have documented vasectomy or must practice birth control 
and not donate sperm during the study and for 3 months after the last study drug 
administration. 
10. Must be up-to-date with all immunizations, in agreement with current local immunization 
guidelines for immunosuppressed subjects, before RI baseline (first administration of study 
drug). 
11. Is able to adequately maintain a daily subject diary according to protocol. 
12. Must be able to adhere to the study visit schedule and understand and comply with the other 
protocol requirements. 
13. Agrees to refrain from making any new, major lifestyle changes that may affect pericarditis 
symptoms (e.g., changing exercise pattern) from the time of the ICF is signed through the end 
of the double-blind RW period. 
4.1.2 Exclusion Criteria 
Subjects meeting any of the following criteria will be excluded from the study: 
1. Has a diagnosis of pericarditis that is secondary to specific prohibited etiologies, including 
tuberculosis (TB); neoplastic, purulent, or radiation etiologies; post-thoracic blunt trauma 
(e.g., motor vehicle accident); myocarditis; or systemic autoimmune diseases with exception 
of Still’s disease. 
Is pregnant, breastfeeding, or planning a pregnancy or fathering a child during the study or 
within 3 months after the last study drug administration. 
Has a history of immunosuppression, including positive human immunodeficiency virus 
(HIV) test results. 
2. 
3. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
4. Is currently receiving CS at a dose of >60 mg/day prednisone (or equivalent) for adult 
subjects, or >0.5 mg/kg/day (or >60 mg/day, whichever is lower) prednisone (or equivalent) in 
pediatric subjects (≥12 and <18 years old). 
Has ever received cytotoxic drugs, including cyclophosphamide, chlorambucil, nitrogen 
mustard, or other alkylating agents. 
Has ever received agents that deplete B or T cells (e.g., rituximab, alemtuzumab). 
Has received systemic immunomodulatory agents (with exception of CS) within the following 
time frames prior to RI baseline (first administration of study drug): 
5. 
6. 
7. 
a. Azathioprine, 
mycophenolate 
mofetil, 
cyclosporine, 
tacrolimus, 
sirolimus, 
or 
mercaptopurine within 24 weeks. 
TNF inhibitors, IL-6 inhibitors, or janus-activating kinase inhibitors within 12 weeks. 
Canakinumab within 12 weeks. Canakinumab could not have been discontinued due to 
safety unless it was discontinued due to local injection site reactions. 
Rilonacept within 6 weeks. Rilonacept could not have been discontinued due to lack of 
efficacy or due to safety. 
Methotrexate within 2 weeks. 
Anakinra within 5 days. Anakinra could not have been discontinued due to lack of 
efficacy or due to safety unless it was discontinued due to local injection site reactions. 
b. 
c. 
d. 
e. 
f. 
8. 
9. 
Has a history of myeloproliferative disorder. 
Has a history of demyelinating disease or symptoms suggestive of multiple sclerosis. 
10. Meets the following TB criteria: 
a. 
b. 
c. 
History of active TB prior to screening OR 
History of latent TB that was not adequately treated prior to screening OR 
Signs or symptoms suggestive of active TB (e.g., new cough of >14 days in duration or a 
change in chronic cough, persistent fever, unintentional weight loss, or night sweats) 
upon review of medical history and/or physical examination at screening OR 
Recent close contact with a person with active TB OR 
Positive or indeterminate Interferon Gamma Release Assay (IGRA) test results or results 
from another positive TB test at screening based on acceptable clinical practice for the 
country in which the subject is enrolling. 
d. 
e. 
11. Has chest x-ray (posterior-anterior view) at screening (or history of results within 12 weeks 
before receiving first administration of study drug), with evidence of malignancy or 
abnormality consistent with prior or active TB infection. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
12. Has received immunization with a live (attenuated) vaccine within 12 weeks before screening 
or is expected to receive live (attenuated) vaccine during the study or within 12 weeks after 
the last study drug administration. 
13. Has a history of positive or intermediate results for hepatitis B surface antigen, hepatitis B 
core antibody, or hepatitis C virus antibody at screening. 
14. Has an estimated glomerular filtration rate (eGFR) <30 ml/min. 
15. Has a history of malignancy of any organ system within the past 5 years before screening 
(other than a successfully treated non-metastatic cutaneous squamous cell carcinoma or basal 
cell carcinoma and/or localized carcinoma in situ of the cervix). 
16. Has a known or suspected current active infection or a history of chronic or recurrent 
infectious disease, including, but not limited to, chronic renal infection, chronic chest 
infection, sinusitis, recurrent urinary tract infection, or an open, draining infected skin wound. 
17. Has had a serious infection, has been admitted to the hospital for an infection, has been treated 
with oral antibiotics within 2 weeks of RI baseline (first administration of study drug), or has 
been treated with IV antibiotics for an infection within 8 weeks of RI baseline. 
18. Has had an organ transplant. 
19. Has screening laboratory test results meeting any of the following criteria: 
a. 
b. 
c. 
d. 
e. 
Hemoglobin level <10.0 g/dL; 
WBC count <3.0 × 103/µL 
Neutrophil count <1.5 × 103/µL 
Platelet count <100 × 103/µL 
Total bilirubin level >1.5 × the upper limit of normal (ULN) unless the test results are 
consistent with those for Gilbert’s syndrome 
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values >2 × ULN 
f. 
20. In the investigator’s opinion, has a history of alcoholism or drug/chemical abuse within 
2 years before screening. 
21. Has a known hypersensitivity to ARCALYST® (rilonacept) or to any of its excipients. 
22. Has received an investigational drug during the 30 days (or 5 half-lives, whichever is longer) 
before screening or is planning to receive an investigational drug (other than that administered 
during this study) or use an investigational device at any time during the study. 
23. In the investigator’s opinion, has any other medical condition that could adversely affect the 
subject’s participation or interfere with study evaluations. This includes significant 
concomitant illnesses such as, but not limited to, cardiac, renal, 
neurological, 
endocrinological, metabolic, pulmonary, GI, or psychiatric diseases. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
24. In the opinion of the investigator, is not likely to be compliant with the study protocol. 
25. In the opinion of the investigator, should not participate in this study. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
4.2 
Subject Completion, Withdrawal from Study, and Study Drug 
Discontinuation 
Completion 
4.2.1 
A subject will be considered to have completed the study if she/he has completed the RW period and 
has completed assessments at the EORW visit. At the EORW visit, subjects who were randomly 
assigned to rilonacept or subjects who transitioned to open-label rilonacept upon protocol-defined 
pericarditis recurrence (Section 6.2.3) in the RW period will be offered an opportunity to receive an 
additional 24 weeks of open-label rilonacept treatment based on their clinical status and at the 
discretion of the investigator, and after signing the LTE informed consent. 
At the EORW visit, subjects who were randomly assigned to placebo and did not transition to bailout 
rilonacept will be offered an opportunity to receive an additional 24 weeks of open-label rilonacept 
treatment based on their clinical status and at the discretion of the investigator, after signing the LTE 
informed consent. 
Any subject who in the opinion of investigator should not continue open-label rilonacept in LTE will 
be offered the opportunity to continue follow-up off study drug treatment in LTE, after signing the 
LTE informed consent. 
Subjects who elect not to enter LTE will be followed for 6 weeks after receiving the last study drug 
administration. 
4.2.2 Reasons for Discontinuation of Study Drug and Study Withdrawal 
Subjects have the right to stop taking study drug before the end of the study or to withdraw their 
consent for further participation in the study (i.e., precluding continued data collection). A subject 
also may be asked to stop study drug at the investigator’s discretion. In the event that a subject 
permanently discontinues study drug but does not withdraw the informed consent, the investigator 
should continue to follow up with the subject by telephone contact (TC) visits, in the clinic, or by 
other means through the EORW visit if the subject discontinues in RI or RW, or through the end of 
LTE-FUP if the subject discontinues in LTE-TP, unless consent is withdrawn. 
The reasons for premature study drug discontinuation will be recorded in the electronic case report 
form (eCRF). 
4.2.2.1 
Discontinuation of Study Drug 
The study drug dosing will be permanently stopped if any of the following occurs: 
• 
The subject develops a serious or intolerable AE, TB, or malignancy, excluding non-metastatic 
cutaneous squamous cell carcinoma or basal cell carcinoma 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
• 
• 
• 
Initiation of protocol-prohibited medication (Section 5.8.6) 
Subject requires treatment with CS for pericarditis during RW or LTE-TP periods of the study 
Pregnancy or pregnancy planned during the study or within 3 months after the last study drug 
administration 
ALT or AST values ≥3 × ULN associated with total bilirubin ≥2 × ULN, with no underlying 
medical conditions to explain the elevated values 
Treatment with a live (attenuated) vaccine during the study 
• 
• 
• 
Investigator or Sponsor’s medical monitor or 
-designated medical monitor decides that, for 
safety reasons, it is in the subject’s best interest 
Termination of the study by Kiniksa Pharmaceuticals 
• 
Permanent or temporary study drug discontinuation should be strongly considered at the time if any 
of the following occurs: 
• 
• 
• 
• 
• 
Subject develops an opportunistic infection. 
Subject develops moderate or severe infection 
Neutrophil count <1.0 × 103/µL 
Isolated ALT or AST values >5 × ULN 
Surgical procedure 
The Sponsor has the right to terminate the study at any time in case of safety concerns (e.g., suspected 
unexpected serious adverse reactions [SUSARs]) or if special circumstances concerning the study 
drug or the company itself occur. In this event, the investigator(s) will be informed of the reason for 
study termination. 
4.2.2.2 
Withdrawal from the Study 
Subjects may withdraw from the study at any time and for any reason, without prejudice to their 
future medical care by the investigator or at the study site. However, prior to withdrawal of consent, it 
should be confirmed that the subject will not allow any form of follow-up including options such as 
less frequent follow-up calls or visits, follow-up with a family member or friend, or follow-up 
through a local physician or medical records. Follow-up options will be summarized on a withdrawal 
of consent checklist source document that must be reviewed and signed by the investigator for any 
subject who withdraws consent for further participation in the study. The checklist must be completed 
for all enrolled subjects who have withdrawn consent. The reasons for a subject’s withdrawal from 
the study are also required to be recorded in the eCRF. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
A subject may be considered withdrawn from the study for any of the following reasons: 
• 
• 
• 
Lost to follow-up 
Documented withdrawal of informed consent 
Death 
If a subject is lost to follow-up, every reasonable effort must be made by the study site personnel to 
contact the subject and re-engage the subject in the study or determine the reason for withdrawal. The 
measures taken are to continue until study end and are required to be recorded in source 
documentation. 
In subjects who are documented as having withdrawn consent from all study activities, no further 
study visits or study-related TCs can be conducted. All data collected prior to the date of the subject’s 
confirmed withdrawal of consent will be included in the study, as specified in the subject’s signed 
ICF. 
5 
Study Treatments 
5.1 
Method of Assigning Subjects to Treatment Groups 
In the single-blind RI period, all subjects will receive blinded rilonacept at the same dose through 
Week 12; subjects will be blinded to the time of transitioning to RW. Subjects who stopped 
background SOC pericarditis therapy and who achieve Clinical Response on rilonacept at RI Week 
12/RW baseline will be randomly assigned in a double-blind manner to continue to receive blinded 
rilonacept or matching placebo using a 1:1 allocation ratio. The definition of Clinical Response is 
provided in Section 6.2.2. An interactive web response system (IWRS) will be used to administer the 
randomization schedule. Biostatistics will generate the randomization schedule using SAS® software 
Version 9.4 or later (SAS Institute Inc, Cary, North Carolina) for the IWRS, which will link 
sequential subject randomization numbers to treatment codes. The randomization schedule will be 
stratified by 2 factors: 
• 
• 
Oral CS use at baseline (RI baseline, i.e., beginning of RI period): yes or no 
Diagnosis of recurrent idiopathic pericarditis (RI baseline): yes or no 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
5.2 
Treatments Administered 
Throughout this protocol, “study drug” refers to the investigational medicinal products: rilonacept and 
matching placebo. Both will be administered as applicable by SC injection. 
Study drug administration will be performed once a week (every 7 ± 2 days). The interval between 
study drug administrations must be at least 5 days. 
Study drug will be dosed as follows: 
Adult Subjects (≥18 years old): 
Rilonacept: Loading dose 320 mg administered as 2 SC injections, 160 mg each (2 ml) at RI baseline, 
followed by once-weekly SC injections of 160 mg (2ml). 
Placebo: administered as once-weekly SC injections of 2 ml each in the RW period 
Upon meeting protocol criteria for bailout rilonacept (Sections 3.1 and 6.2.3) in the RW period, 
subjects will be transitioned to open-label rilonacept 320 mg administered as 2 SC injections, 160 mg 
each (2 ml) at the next scheduled study drug administration date, followed by once-weekly SC 
injections of 160 mg (2ml). 
Pediatric Subjects (≥12 and <18 years old): 
Rilonacept: Loading dose 4.4 mg/kg administered as 2 SC injections, 2.2 mg/kg each (maximum 
160 mg each) at RI baseline, followed by once-weekly SC injections of 2.2 mg/kg (maximum 
160 mg). The volume of injections will be based on the subject’s weight (Table 5–1). 
Placebo (in RW): once-weekly SC injections with volume based on the subject’s weight (Table 5–1, 
maximum 2 ml). 
Upon meeting protocol criteria for bailout rilonacept (Sections 3.1 and 6.2.3) in the RW period, 
subjects will be transitioned to open-label rilonacept 4.4 mg/kg administered as 1 (maximum 2 ml) or 
2 SC injections at the next scheduled study drug administration date, followed by once-weekly SC 
injections of 2.2 mg/kg (maximum 2 ml). The volume of injections will be based on the subject’s 
weight (Table 5–1). 
Study drug dose/volume will be calculated by the investigator or pharmacist during site clinic visits 
based on body weight (as specified in the Study Schedule of Activities) using a weight-based dosing 
chart in kilograms (Table 5–1). 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
Table 5–1: 
Study Drug Dose  Volume (After  Reconstitution)  by Body Weight in 
Kilograms for Pediatric Subjects Aged ≥12 and <18 Years 
Study Drug Self-Administration 
The first study drug dose on RI baseline will be administered at the study site. During this visit, the 
subject will be trained on study drug preparation and injection. In case the subject is unwilling or 
unable to prepare and self-inject the study drug, the subject’s caregiver will be trained. 
The first study drug administration for adult and pediatric subjects on RI baseline will consist of 2 SC 
injections, constituting a loading dose. The first injection will be prepared and administered by study 
site staff. The second injection will be prepared and administered by the subject or the subject’s 
caregiver after adequate training and under the supervision of study site personnel. Subsequent once-
weekly study drug doses will be self-administered SC by the subject or administered to the subject by 
a trained caregiver as an outpatient SC administration. If the subject or subject’s caregiver is unable to 
prepare and inject the study dug, the subject may report for once-weekly injections to a study site, or 
injections can be administered by the visiting registered nurse (RN). 
5.3 
Identity of Investigational Medicinal Product 
Rilonacept (KPL-914) is the drug being evaluated in the current study. Refer to Section 1.3 for a 
detailed description of rilonacept’s mechanism of action. 
53 
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Weight Range (kg) 
 
Loading Dose Volume (ml) 
 
Weekly Dose Volume (ml) 
 
23.6 to 27.2 
2 x 0.7 
0.7 
27.3 to 30.8 
2 x 0.8 
0.8 
30.9 to 34.4 
2 x 0.9 
0.9 
34.5 to 38.1 
2 x 1.0 
1.0 
38.2 to 41.7 
2 x 1.1 
1.1 
41.8 to 45.4 
2 x 1.2 
1.2 
45.5 to 49.0 
2 x 1.3 
1.3 
49.1 to 52.6 
2 x 1.4 
1.4 
52.7 to 56.3 
2 x 1.5 
1.5 
56.4 to 59.9 
2 x 1.6 
1.6 
60.0 to 63.5 
2 x 1.7 
1.7 
63.6 to 67.2 
2 x 1.8 
1.8 
67.3 to 70.8 
2 x 1.9 
1.9 
70.9 or greater 
2 x 2.0 
2.0 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
Study drug (rilonacept or placebo) is supplied in a single-use, 20 ml glass vial containing a sterile, 
white to off-white, lyophilized powder. Each vial is to be reconstituted with 2.3 ml sterile Water for 
Injection (WFI). A volume up to 2 ml can be withdrawn, which is designated to deliver up to 160 mg 
of rilonacept or up to 2 ml placebo for SC injection only. The resulting solution is clear, colorless to 
pale yellow, and essentially free of particulates. 
Each rilonacept vial contains 220 mg of rilonacept lyophilized powder. After reconstitution with 
2.3 ml sterile WFI, the rilonacept vial contains 80 mg/ml rilonacept, 40 mM histidine, 50 mM 
arginine, 3.0% (w/v) polyethylene glycol 3350, 2.0% (w/v) sucrose, and 1.0% (w/v) glycine at a pH 
of 6.5. No preservatives are present. 
Each placebo vial contains lyophilized powder. After reconstitution with 2.3 ml sterile WFI, the 
placebo vial contains 40 mM histidine, 50 mM arginine, 3.0% (w/v) polyethylene glycol 3350, 
2.0% (w/v) sucrose, and 1.0% (w/v) glycine at a pH of 6.5. No preservatives are present. 
5.4 
Management of Clinical Supplies 
5.4.1 Study Drug Product Packaging and Storage 
Additional information regarding the preparation, dispensation, administration, and storage of 
rilonacept or placebo will be described in the Pharmacy Manual. 
Study drug will be provided by Kiniksa Pharmaceuticals to the study sites in the lyophilized 
formulation in glass vials as described in Section 5.3. Each single-use vial will have a clinical label 
adhered to the vial. One labeled vial will be placed into a carton. Each carton will have a clinical label 
adhered to the outside of the carton. One tamper-evident seal will be placed on the top of the carton to 
securely close the lid. 
Study drug is to be stored and shipped refrigerated at 2°C to 8°C (36°F to 46°F) inside the original 
carton to protect it from light. 
5.4.2 Study Drug Accountability 
The sites will receive study drug for on-site administration at study site visits. Upon receipt of study 
drug, the investigator (or delegate) will conduct an inventory of the supplies and verify that the 
supplies are received intact, at the appropriate temperature, and in the correct amounts prior to 
completing a supplies receipt. The investigator will confirm receipt of study drug in the IWRS and 
retain a copy of this receipt at the study site. The inventory of supplies at each study site will be 
reviewed by the study monitor. 
Study drug will be dispensed to the study subjects for outpatient self-administration according to the 
supply chain described in the Pharmacy Manual. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
The investigator will maintain accurate records of receipt of all test articles, including dates of receipt. 
In addition, accurate records will be kept regarding when and how much study drug is dispensed and 
used by each subject in the study. Reasons for deviating from the expected dispensing regimen must 
also be recorded. At the completion of the study, to satisfy regulatory requirements regarding drug 
accountability, all used and unused study drug containers must be retained by the study site/clinic and 
subject for cataloguing and documentation of compliance. The full process for drug dispensing, 
documentation, and destruction will be described in the Pharmacy Manual. 
A full drug accountability log will be maintained at the study site at all times. 
5.4.3 Other Supplies 
Rilonacept should be reconstituted with preservative-free WFI that will be provided by Kiniksa 
Pharmaceuticals or designee along with 27-gauge, ½-inch needles, 3-ml syringes, alcohol wipes, 
gauze pads, bandages, and a puncture resistant container for disposal of needles and syringes. Only 
the syringes and needles provided by the Sponsor or its designee should be used to prepare and inject 
the study drug. The Sponsor also will provide coolers and refrigerated gel packs to ensure that the 
subjects transport the study drug at the proper temperature. On occasion, sites may be asked to locally 
procure ancillary materials. 
5.5 
Study Drug Overdose 
An overdose is any dose of study drug given to a subject or taken by a subject that exceeds the dose 
described in the protocol. Any overdose must be promptly reported to the 
Pharmacovigilance 
(PVG) in the same way and using the same procedures as for a serious  adverse event (SAE) 
(Section 6.4.6), regardless of whether any AEs are associated with the overdose. 
If there are AEs associated with the overdose, these should be recorded on the relevant AE/SAE 
sections in the eCRF; however, overdoses without signs or symptoms do not need to be recorded as 
AEs in the eCRF. 
5.5.1 Treatment of Study Drug Overdose 
The maximum amount of rilonacept that can be safely administered has not been determined. 
Maximum once-weekly doses of rilonacept up to 320 mg have been administered SC for up to 
approximately 18 months in a small number of subjects with CAPS, and for up to 6 months in 
subjects in an unapproved indication in clinical trials without evidence of dose-limiting toxicities. In 
addition, rilonacept given IV at doses up to 2000 mg monthly for up to 6 months in another subject 
population was tolerated without dose-limiting toxicities (Rilonacept IB). In case of overdose, it is 
recommended that the subject be monitored for any signs or symptoms of AEs and appropriate 
symptomatic treatment instituted immediately (Section 13.1, ARCALYST® Prescribing Information). 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
5.5.2 Other Study Drug Errors 
To avoid study drug errors, it is important to note the following: 
• 
In this study, rilonacept is designated for SC injections only. It should be taken only by the 
subjects participating in the study and as instructed by study site personnel. 
Guidelines regarding the management of temperature excursions during storage will be detailed 
in the Pharmacy Manual. 
Pediatric dosing is calculated based on body weight in kilograms, not pounds. 
• 
• 
Any study drug error must be promptly reported to the 
same procedures as for an SAE (Section 6.4.6) 
PVG, in the same way and using the 
5.6 
Transmission of Infectious Agents 
The lyophilized study drug is to be stored refrigerated at 2°C to 8°C (36°F to 46°F) inside the original 
carton to protect it from light. Study drug should not be used beyond the date stamped on the label. 
After reconstitution, study drug may be kept at room temperature, should be protected from light, and 
should be used within 3 hours of reconstitution. Study drug does not contain preservatives; therefore, 
unused portions of study drug should be discarded. 
5.7 
Misuse for Illegal Purposes 
Rilonacept does not have addicting potential, and the risk of misuse for illegal purposes is minimal. 
5.8 
Prior and Concomitant Medications 
Use of all concomitant medications and any changes in concomitant medications will be recorded in 
the subject’s eCRF. The minimum requirement is that drug name and dates of administration are to be 
recorded. This will include all prescription drugs, herbal products, vitamins, minerals, and over-the-
counter medications. 
Any concomitant medication deemed necessary for the welfare of the subject during the study may be 
given at the discretion of the investigator. However, it is the responsibility of the investigator to 
ensure that details regarding the medication are recorded in full in the eCRF. The initiation of 
protocol prohibited medication (Section 5.8.6) requires discontinuation of study drug. 
Guidelines regarding the use of concomitant medication will be detailed in the Pharmacy Manual and 
are summarized in the following sections. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
5.8.1 Screening 
Subjects included in the study may be receiving concomitant NSAIDs and/or colchicine, and/or oral 
CS treatment in any combination, provided that the dosages of these medications have been stable (or 
not increased) for at least 3 days prior to and including RI baseline (first administration of study 
drug), and changes in medications made within this time period (e.g., 1-time use of NSAIDs), in the 
opinion of the investigator, are not anticipated to significantly alter assessments of baseline disease 
activity. 
Analgesics can be used at the discretion of the investigator during screening activities prior to the first 
study drug dose, but only after the subject has documented a pericarditis pain level ≥4 on the 11-point 
NRS within 7 days prior to and including RI baseline (first administration of study drug). 
Subjects can enter the study on prednisone (or equivalent dose) not exceeding 60 mg/day for adults 
and not exceeding 0.5 mg/kg/day (with a maximum dose of 60 mg/day) in pediatric subjects. 
5.8.2 Single-blind RI Period 
• 
1-week Stabilization period, during which rilonacept is administered in addition to SOC 
pericarditis therapy and ongoing pericarditis episode is treated. All concomitant pericarditis 
medications including NSAIDs, analgesics, colchicine and CS will remain stable, unless the 
dosing must be decreased or stopped in the judgement of the investigator due to an AE. 
9-week background medication Weaning period, during which subjects are weaned off 
background SOC pericarditis therapy, as applicable, while treatment with blinded rilonacept 
continues. The guidelines for background medication taper and discontinuation will be provided 
in the Pharmacy Manual. 
Corticosteroids 
Starting at Week 1 and through Week 10, CS will be tapered and discontinued at a rate dependent 
on the dose at study entry. 
Analgesics 
Starting at Week 1 and through Week 10, analgesics (non-opioid and opioid) will be tapered and 
discontinued. Opioid analgesics can continue beyond Week 10 at stable doses through the end of 
the RW period if it is not feasible to discontinue them without causing withdrawal symptoms. 
NSAIDs and Colchicine 
Starting at Week 4 and through Week 10, NSAIDs and colchicine will be tapered and 
discontinued. 
• 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
• 
2-week Monotherapy period during which rilonacept administration continues: Subjects are 
required to be off all background SOC pericarditis therapy, with the exception of opioid 
analgesics if their discontinuation is not feasible. 
5.8.3 Double-blind Placebo-controlled RW Period 
During the RW period, subjects should not be receiving any concomitant medications for pericarditis, 
with the exception of opioid analgesics in case their taper down and discontinuation was not feasible 
in the RI period. 
5.8.3.1 
Concomitant Medication Upon Pericarditis Recurrence 
Subjects meeting protocol criteria for bailout rilonacept 
Upon pericarditis recurrence and meeting protocol criteria for bailout rilonacept (Sections 3.1 and 
6.2.3) and completing the diagnostic workup as confirmed by the 
medical monitor, 
subjects will be transitioned to open-label rilonacept, as described in Section 3.1. Because open-label 
rilonacept can be administered only if at least 5 days have passed from the last blinded study drug 
administration, the investigators are allowed to use sequential ORT, i.e., analgesics, NSAIDs, and 
colchicine if necessary at their discretion. The use of those medications will be detailed in the 
Pharmacy Manual; it is briefly given as follows: 
• 
Analgesics (including non-opioid and opioid) can be used for pain control prior to completing the 
diagnostic workup for a recurrent pericarditis episode. The use of analgesics during pericarditis 
recurrence evaluation will provide pain relief for subjects without impacting their CRP levels or 
other objective components of the diagnostic workup. 
• 
After the diagnostic workup is completed based on the 
medical monitor’s 
assessment, NSAIDs followed by colchicine can be added to open-label rilonacept based on the 
subject’s clinical status and at the discretion of the investigator. 
If, after transition to open-label rilonacept, the investigator decides that the subject requires CS 
for pericarditis therapy, the subject will be discontinued from rilonacept and followed through the 
EORW visit. 
• 
Subjects not meeting protocol criteria for bailout rilonacept 
If, based on the investigator’s judgement, the subject is experiencing pericarditis recurrence that does 
not meet the protocol criteria for bailout rilonacept (Sections 3.1 and 6.2.3) but does require 
additional treatment, the subject will continue blinded study drug, and the investigator should manage 
the pericarditis recurrence using sequential ORT for pericarditis, i.e., analgesics, NSAIDs, colchicine 
as described in the Pharmacy Manual and outlined briefly below: 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
• 
Analgesics (including non-opioid and opioid) can be used for pain control prior to completing the 
diagnostic workup for a recurrent pericarditis episode. The use of analgesics during pericarditis 
recurrence evaluation will provide pain relief for subjects without impacting their CRP levels or 
other objective components of the diagnostic workup. 
• 
After the diagnostic workup is completed based on the 
medical monitor’s 
assessment, NSAIDs followed by colchicine can be added to blinded study drug based on the 
subject’s clinical status and at the discretion of the investigator. 
If, after the addition of NSAIDs and colchicine, the investigator decides that the subject requires 
CS for pericarditis therapy, the subject will be discontinued from blinded study drug and followed 
through the EORW visit. 
• 
5.8.4 Long Term Extension Treatment Period (LTE-TP) 
Subjects who opt to continue open-label rilonacept in the LTE-TP will have their concomitant 
pericarditis medications managed at the discretion of the investigator and based on the subject’s 
clinical status. If CS are required in addition to rilonacept to manage recurrent pericarditis, rilonacept 
should be discontinued. 
5.8.5 Long Term Extension Follow-Up Period (LTE-FUP) 
During LTE-FUP, pericarditis medication can be managed at the investigator’s discretion. 
5.8.6 Prohibited Concomitant Medicines During the Study 
Prohibited medications during the study and throughout the end of LTE-TP include the following: 
• 
• 
• 
• 
• 
Interleukin (IL) blockers other than rilonacept 
IL-6 blockers 
Janus-activating kinase inhibitors 
TNF inhibitors 
Potent immunosuppressants (azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, 
sirolimus, mercaptopurine, cyclophosphamide, chlorambucil, nitrogen mustard, or other 
alkylating agents, agents that deplete B or T cells [e.g., rituximab, alemtuzumab]) 
Live (attenuated) vaccines, which are prohibited during the study and within 12 weeks after the 
last study drug administration 
• 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
5.9 
Blinding 
In the single-blind RI period, all subjects will receive rilonacept but will be blinded to the duration of 
the RI period and the timing of randomization. 
The RW period is a double-blind period in which rilonacept and placebo are identical in appearance. 
Neither the subject nor any of the investigator/site staff, 
, or Sponsor staff who are involved in 
the treatment or clinical evaluation of the subjects will be aware of the treatment received 
(International Council for Harmonisation [ICH] E9). 
In the event of a pericarditis recurrence that meets the criteria for bailout rilonacept (Sections 3.1 and 
6.2.3), the subject will be transitioned to open-label rilonacept but will remain blinded to their prior 
RW treatment assignment. 
At the end of the RW period, all sites and subjects will be unblinded. Subjects will be offered 
participation in the LTE-TP, in which once-weekly open-label rilonacept can be continued for an 
additional 24 weeks. 
5.9.1 Breaking the Blind 
A subject’s treatment assignment will not be broken until the end of the RW period. 
If the treatment allocation for a subject becomes known to the investigator or other study staff 
involved in the management of study subjects, the Sponsor must be notified immediately. If the 
investigator intends to unblind treatment allocation for a subject, then the Sponsor should be notified 
immediately. The investigator may unblind a subject’s treatment assignment only in the case of an 
emergency, when knowledge of the study drug is essential for the appropriate clinical management or 
welfare of the subject. In most cases, the management of a medical emergency would be the same, 
regardless of whether the subject received active drug. The treatment assignment will be unblinded 
through the IWRS. The investigator must notify Kiniksa Pharmaceuticals and 
medical monitors 
as soon as possible but without revealing the treatment assignment of the unblinded subject, unless 
that information is important for the safety of subjects currently in the study. The date and reason for 
the unblinding must be recorded in the eCRF. 
The 
PVG staff may unblind the treatment assignment for any subject with an SAE. If the SAE 
requires that an expedited regulatory report be sent to one or more regulatory agencies, a copy of the 
blinded report may be sent to clinical investigators in accordance with local regulations. 
5.10 Treatment Compliance 
Subjects will record the administration of all doses of study drug (whether as an outpatient or in the 
clinic) in a subject’s diary. In addition, throughout all study periods, adherence to study drug 
administration will be assessed by the study site in collaboration with the visiting RN (Section 6). 
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6 
Study Assessments and Procedures 
Before performing any study procedures, all potential subjects will provide informed consent or an 
assent, if applicable. Potential subjects will have the study risks and benefits explained to them, the 
associated ICF reviewed with them, and all questions answered for them. Subjects will undergo 
screening procedures specific to the study only after the ICF has been provided by the subject unless 
performed as part of SOC practice. The investigator or designee will also sign the ICF. 
6.1 
Study Visits 
The schedule of assessments for the study site visits is summarized in the Study Schedule of 
Activities. Following screening assessments, qualifying subjects will be enrolled and enter the 
RI period. Subjects who stop background pericarditis medications and achieve Clinical Response at 
RI Week 12 (Section 6.2.2), will be randomized and enter the RW period. During both the RI and 
RW period, a combination of clinic and outpatient visits will occur. Outpatient visits may consist of 
telephone or virtual contacts as well as home visits conducted by a visiting nurse. For each scheduled 
visit of the study (including outpatient and clinic), assessments should occur prior to scheduled 
injections of study drug. Subjects can be brought to the clinic in place of a scheduled outpatient visit 
or for an unscheduled visit at the discretion of the investigator. 
The visit schedule is derived from the day of the RI baseline visit. One week is equal to 7 calendar 
days. Although visits do not occur every week, subjects are required to record pericarditis pain NRS 
measurements on a daily basis in their study device and to administer study drug on a once-weekly 
basis and record it in their study electronic diary (eDiary). If a subject is unable to independently 
complete the daily eDiary, a caregiver may help enter the data. 
Upon completion of the RI and RW periods, all subjects will have the opportunity to continue 
participating in the LTE. This will require each subject again providing informed consent prior to 
LTE participation. The LTE period will have a treatment period (LTE-TP) and an off treatment 
follow-up period (LTE-FUP). 
Any subject who prematurely discontinues study drug will be followed for the duration of the trial as 
specified in Section 4.2.2. In addition, throughout all study periods, compliance with study drug 
administration will be assessed by the site in collaboration with the visiting RN. 
6.1.1 Screening: Clinic and Remote as Needed 
A study screening eCRF is required to be completed for every subject with a signed ICF. For each 
subject, the subject identification is obtained from the IWRS. 
It is anticipated that some subjects may have a portion of the study screening procedures done as part 
of routine care outside the auspices of this study. As long as these procedures were done within the 
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allotted screening period timeframe, the results of these procedures may be used to support study 
screening and completion of the study screening eCRF. Any protocol-specified study qualification 
procedures/tests not already done as part of routine care will need to be conducted after the subject 
provides informed consent and before enrollment. It is possible that the screening and enrollment visit 
will occur on the same day. 
The below procedures are required to be completed to screen a subject ≤28 days prior to enrollment. 
All assessments and procedures are not required to be completed on-site; however, the site is 
expected to obtain the medical records for subject source documentation. 
• 
• 
• 
Obtain the ICF. 
Enter the subject into the IWRS. 
Review inclusion/exclusion criteria; ensure that the subject has a diagnosis of recurrent 
pericarditis based and is presenting with at least the third pericarditis episode. 
Record: demographic information, medical/surgical history, concomitant medications, all prior 
and current concomitant pericarditis medications, a detailed pericarditis history including all 
recurrent pericarditis events. 
Perform a full physical examination (may be performed by an investigator or other healthcare 
provider designated by the investigator). 
Perform/obtain: 
• 
• 
• 
- 
11-point pericarditis pain NRS assessment – required to be >4 within 7 days prior to and 
including the day of RI baseline. The qualifying NRS assessment and CRP are not required to 
occur on the same day. 
CRP (mg/dL) – required within 7 days prior to and including the day of RI baseline. For 
study qualification purposes, the CRP may be assessed using 1 of 4 approaches: 
- 
▪ 
▪ 
▪ 
Point of care (POC) device provided by Sponsor (preferred method) 
Blood sample sent to the local laboratory 
CRP measurement taken as part of the subject’s routine care (e.g., not specifically 
obtained for this study) 
Blood sample sent to the central laboratory 
▪ 
- 
- 
- 
- 
Local laboratory hematology, chemistry, IGRA, hepatitis serology, HIV 
Chest x-ray (unless performed and available within the past 12 weeks) 
Local or central laboratory urine pregnancy test for women of childbearing potential 
AE collection 
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6.1.2 
6.1.2.1 
Single-blind Treatment: Run-In 
Enrollment (RI Baseline): Clinic Visit 
For subjects who meet study entry criteria, enrollment commences at the RI baseline visit. The 
following procedures occur: 
• 
• 
• 
• 
Review inclusion and exclusion criteria to confirm subject qualification. 
Review and record updates to recurrent pericarditis history since the screening visit. 
Revise IWRS status change to enrollment. 
Assess and record all concomitant medications as well as all prior and concomitant pericarditis 
medication. 
Perform an abbreviated physical examination, height and body weight. 
Acquire a 12-lead ECG. 
Acquire and submit a cardiac ECHO to the core laboratory per the core laboratory imaging 
guidelines; the ECHO is to be read locally prior to sending to the core lab. 
Perform cardiac MRI (for substudy participants only). 
Provide the subject with their study device and complete the following: 
• 
• 
• 
• 
• 
- 
For subjects ≥18 years, have them complete the 36-Item Short Form Health Survey (SF-36), 
5-level EuroQoL-5D (EQ-5D-5L), Insomnia Severity Index (ISI) 
For all subjects, instruct how to complete the 11-point pericarditis pain NRS (as outlined in 
Section 6.2.1.2) and the medication diary. 
Have all subjects complete the Patient Global Impression of Pericarditis Severity (PGIPS) 
score. 
- 
- 
• 
The investigator is to complete the Physician Global Assessment of Pericarditis Activity (PGA-
PA). 
Obtain the Pharmacogenomics ICF. 
Obtain a local or central laboratory urine pregnancy test for women of childbearing potential. 
Obtain central laboratory chemistry, hematology, lipid panel, CRP, anti-drug antibodies (ADAs), 
biomarkers, and urinalysis (laboratory tests should be drawn prior to the first study drug 
administration, but results of those tests are not required before enrollment). 
AE reporting. 
Additional discussion/assessment as needed. 
• 
• 
• 
• 
• 
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Upon completion of the above study activities, study drug dispensing can commence. The following 
procedures occur: 
• 
Complete the IWRS to dispense assigned study drug; record the amount (number of vials) 
dispensed. 
Explain the study drug, proper once-weekly dosing, proper study drug administration technique, 
study drug administration documentation, and confirm that the subject (and subject’s caregiver as 
applicable) understands. 
For pediatric subjects, body weight (in kilograms) obtained at the RI baseline visit is to be used to 
determine appropriate study drug dosing in the RI period. Please refer to the pediatric study drug 
dosing Table 5–1 as well as the Study Schedule of Activities for subsequent visits with weight 
assessments for pediatric dosing. 
Prepare and administer the first injection of study drug and train the subject or caregiver to 
prepare and administer the second dose of study drug. 
Instruct the subject to bring to each clinic visit all medications the subject is taking, including 
used and unused study drug vials. 
Arrange upcoming study visits (as many visits as possible that can be arranged ahead of time is 
advised). 
• 
• 
• 
• 
• 
6.1.2.2 
RI Day 2: Clinic Visit (24-hour PK Sub-study Participants Only) 
The RI Day 2 visit includes a PK sample that is collected 24 hours after the loading dose of study 
drug and then sent to the central laboratory. 
6.1.2.3 
RI Day 4: TC/RN Visit 
The timing of the site TC visit on the RI Day 4 visit can occur independently of the RN visit. During 
the site TC visit, the subject is contacted to assess for AEs in follow-up to the initial injections 
received, to review the daily input of the pericarditis pain NRS score, as well as to review all 
concomitant medications, including concomitant pericarditis medication. The site then dispenses 
study drug (along with ancillary supplies) through the IWRS and coordinates shipment as outlined in 
the Pharmacy Manual. During the visiting RN visit, a CRP sample is drawn and sent to the central 
lab. 
6.1.2.4 
RI Week 1: TC/RN Visit 
It is preferred that the site TC occur prior to the RN visits. It is required that visit assessments occur 
prior to scheduled study drug dosing. The RI Week 1 visit is as follows: 
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Site TC visit: 
• 
• 
• 
Assess for AEs. 
Evaluate all concomitant medications as well as pericarditis concomitant medications. 
Provide instruction on the pericarditis concomitant medication oral corticosteroid tapering if 
applicable. 
Confirm and review upcoming visit arrangements. 
Additional discussion/assessment as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
• 
• 
RN home visit: 
• 
Obtain the central laboratory samples for CRP, PK, and biomarkers (these are collected prior to 
study drug administration). 
Provide review of self-administration of the study drug. 
Monitor administration of the study drug (whenever possible). 
Ensure the subject records study drug administration in the medication diary. 
Obtain used study drug vials and materials. 
Confirm upcoming visit arrangements. 
• 
• 
• 
• 
• 
6.1.2.5 
RI Week 2: TC/RN Visit 
It is required that visit assessments occur prior to scheduled study drug dosing. The RI Week 2 visit is 
as follows: 
Site TC visit: 
• 
• 
• 
• 
• 
• 
Assess for AEs. 
Evaluate all concomitant medications as well as pericarditis concomitant medications. 
Assess subject progress on the oral pericarditis corticosteroid tapering, if applicable. 
Review study drug administration and documentation compliance. 
Confirm and review upcoming visit arrangements. 
Additional discussion/assessment as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
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RN home visit: 
• 
• 
Record study drug dispensing to the subject. 
Obtain central laboratory samples for CRP, PK, and ADAs (these are drawn prior to study drug 
administration). 
Provide review of self-administration of the study drug. 
Monitor administration of the study drug (whenever possible). 
Obtain used study drug vials and materials. 
Confirm upcoming visit arrangements. 
• 
• 
• 
• 
6.1.2.6 
RI Week 4: TC/RN Visit 
It is required that visit assessments occur prior to scheduled study drug dosing. The RI Week 4 visit is 
as follows: 
Site TC visit: 
• 
• 
• 
Assess for AEs. 
Evaluate all concomitant medications as well as pericarditis concomitant medications. 
Assess subject progress on the oral corticosteroid tapering if applicable and provide instruction on 
NSAID and/or colchicine tapering if applicable. 
Additional discussion/assessment as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
Confirm and review upcoming visit arrangements. 
Instruct the subject to bring used and unused study drug vials (those not yet obtained by the 
visiting RN) to the next clinic visit. 
• 
• 
• 
RN home visit: 
• 
Obtain central laboratory samples for CRP, PK, and biomarkers (these are drawn prior to study 
drug administration). 
Obtain a pharmacogenomics sample for those subjects who have provided informed consent. 
Provide review of self-administration of the study drug. 
Monitor administration of the study drug (whenever possible). 
Obtain used study drug vials and materials. 
Confirm upcoming visit arrangements. 
• 
• 
• 
• 
• 
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6.1.2.7 
RI Week 6: Clinic Visit 
The RI Week 6 visit in the clinic includes the following assessments and procedures: 
• 
• 
• 
Assess for AEs. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Assess subject progress on the concomitant oral corticosteroid, NSAID and/or colchicine tapering 
if applicable. 
Obtain used and unused study drug vials for study drug compliance evaluation. 
Have all subjects complete the PGIPS score. 
The investigator is to complete the PGA-PA. 
Obtain central laboratory samples for hematology, chemistry, CRP, and ADAs. 
Additional discussion/assessment as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
• 
• 
• 
• 
• 
Upon completion  of the above study  activities, the study drug  dispensing  can commence. The 
following procedures occur: 
• 
Have the subject administer the next scheduled injection of study drug (if within the study drug 
window) and have the subject record in the medication diary. 
Dispense study drug through the IWRS and record the amount (number of vials) dispensed. 
Review the study drug dosing schedule, administration techniques, and documentation. 
Confirm upcoming visit arrangements. 
• 
• 
• 
6.1.2.8 
RI Week 10: TC Visit 
The following assessments and procedures are to be completed: 
• 
• 
• 
• 
• 
• 
Assess for AEs. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Assess concomitant oral corticosteroid, NSAID and/or colchicine tapering completion. 
Assess study drug administration documentation. 
Confirm the RI Week 12/RW baseline clinic visit arrangements. 
Additional discussion/assessments as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
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Version 1.1, 05 Oct 2018 
6.1.2.9 
Randomization (RI Week 12/RW Baseline): Clinic Visit 
The following assessments and procedures are conducted at the RI Week 12 visit, prior to 
randomization: 
• 
CRP assessment (local and central) (the POC device provided for the study is the preferred 
method for local laboratory CRP assessment). 
Obtain a pericarditis pain NRS average score for the prior 7 days, including the day of the visit 
(4 missing NRS values within this week may result in an inability to move forward with 
randomization). 
Acquire a 12-lead ECG. 
Acquire and submit a cardiac ECHO to the core laboratory per the core laboratory imaging 
guidelines; ECHO is read locally prior to submission to the core lab. 
Abbreviated physical examination, height and body weight. 
For subjects ≥18 years, complete on their device SF-36, EQ-5D-5L, ISI. 
For all subjects, complete the PGIPS score. 
The investigator is to complete the PGA-PA. 
Obtain central laboratory samples for chemistry, hematology, lipid panel, PK, and ADAs. 
Evaluate concomitant medications including pericarditis concomitant medication. 
Assess for AEs. 
Obtain used and unused study drug vials for study drug compliance evaluation. 
Additional discussion/assessments as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
Assess for Clinical Response (refer to Section 6.2.2). 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
For subjects who have successfully completed the RI period and are assessed as achieving Clinical 
Response at the RI Week 12 visit, the RW baseline visit commences. 
The following assessments and procedures are conducted at the RW baseline visit: 
• 
• 
Update the subject status in the IWRS by randomizing the subject in the IWRS. 
Obtain weight for pediatric drug dispensing and dosing (Table 5–1). Please refer to the pediatric 
study drug dosing Table 5–1 as well as the Study Schedule of Activities for subsequent visits with 
weight assessments for pediatric dosing during RW. 
Dispense study drug and record the amount (number of vials) dispensed. 
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• 
Have the subject administer the study drug and record in the diary (if within the study drug 
window). 
Instruct the subject to bring all medications including used and unused study drug to each clinic 
visit. 
Instruct the subjects on the process to follow for a pericarditis recurrence event. 
Arrange upcoming visits. 
• 
• 
• 
For subjects that do not qualify for randomization per the IWRS, the 
medical monitor is to be 
immediately contacted to evaluate the reasons for non-qualification. Following medical monitor 
consultation, if the subject is deemed to not be a treatment responder, the RI Week 12 visit will be 
completed, study drug will be discontinued, and the subject will not proceed to randomization. The 
subject will be requested to perform a 6-week safety follow-up (SFU) visit after his/her last dose of 
study drug as well as continue with follow-up as agreed upon until the EORW period. 
6.1.3 Randomized-Withdrawal (RW) Period 
During the RW period, subjects will continue with once-weekly study drug administration as well as 
daily 11-point pericarditis pain NRS scoring. Visits will occur every 4 weeks, alternating TC/RN 
visits and clinic visits, with the first visit during the RW period (RW Week 4) being a TC/RN visit. 
Additional unscheduled visits may occur at any time for evaluation of suspected pericarditis 
recurrence (Section 6.1.6.1) or for other reasons as deemed necessary by the study investigator. 
The following procedures are to occur during the TC/RN visits: 
Site TC visits: 
• 
• 
• 
• 
• 
• 
Assess for AEs. 
Assess for suspected pericarditis recurrence events. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Additional discussion/assessment as needed. 
Confirm and review upcoming visit arrangements. 
Instruct the subject to bring used and unused study drug vials (those not yet obtained by visiting 
RN) to the next clinic visit. 
RN home visits: 
• 
• 
Obtain central laboratory samples for CRP. 
Provide review of self-administration of the study drug as needed. 
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• 
• 
Monitor administration of the study drug (whenever possible). 
Obtain used study drug vials and materials. 
The following procedures are to occur during the clinic visits (except for Week 24; see below): 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
Assess for AEs. 
Assess for suspected pericarditis recurrence events. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Record height and body weight. 
Obtain central laboratory samples for chemistry, hematology, and CRP. 
Obtain central laboratory sample for PK and biomarkers (Weeks 8 and 24 only). 
Obtain central laboratory sample for ADAs (Week 24 only). 
Have all subjects complete the PGIPS score. 
The investigator is to complete the PGA-PA. 
Additional discussion/assessment as needed (i.e., remind the subject about daily pericarditis pain 
NRS entry). 
Obtain used and unused study drug vials for study drug compliance evaluation. 
• 
Upon completion of the above study activities, study drug dispensing can commence. The following 
procedures occur: 
• 
• 
Obtain weight for pediatric drug dispensing and dosing (Table 5–1). 
Monitor administration of the study drug dose (whenever possible) and have the subject record in 
the medication diary. 
Dispense study drug through the IWRS and record the amount (number of vials) dispensed. 
Review the study drug dosing schedule, administration techniques, and documentation. 
Confirm upcoming visit arrangements. 
• 
• 
• 
6.1.3.1 
RW WEEK 24: Clinic Visit 
The Week 24 visit in the clinic includes the following assessments and procedures: 
• 
• 
Assess for AEs. 
Assess for suspected pericarditis recurrences. 
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• 
• 
• 
• 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Perform a full physical examination, height and body weight. 
Acquire a 12-lead ECG. 
Acquire a cardiac ECHO for core laboratory central review; the ECHO is to be read locally 
before sending to the core lab. 
Obtain an MRI (for substudy participants only). 
For subjects >18 years, complete the SF-36, EQ-5D-5L, ISI. 
For all subjects, complete the PGIPS score. 
The investigator is to complete the PGA-PA. 
Obtain central laboratory samples for chemistry, hematology, lipid panel, CRP, PK, ADAs, and 
biomarkers. 
Obtain used and unused study drug vials for study drug compliance evaluation. 
Additional discussion/assessment as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
• 
• 
• 
• 
• 
• 
• 
Upon completion  of the above study  activities, the study drug  dispensing  can commence. The 
following procedures occur: 
• 
• 
Obtain weight for pediatric drug dispensing and dosing (Table 5–1). 
Have the subject administer the RW Week 24 study drug dose (if within the study drug window) 
and have the subject record it in the medication diary. 
Dispense study drug through the IWRS and record the amount (number of vials) dispensed. 
Review the study drug dosing schedule, administration techniques, and documentation. 
Confirm upcoming study visits. 
• 
• 
• 
6.1.3.2 
EORW (End of RW Period/LTE Baseline): Clinic Visit 
The EORW visit will be same day as LTE-TP baseline visit. 
All randomized subjects, including those that have had pericarditis recurrence or have permanently 
discontinued study drug will have an EORW visit at the end of the RW period. The EORW activities 
are listed below: 
• 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
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• 
• 
Acquire a 12-lead ECG. 
Acquire and submit a cardiac ECHO to the core laboratory per the core laboratory imaging 
guidelines; the EHCO is to be read locally prior to submission to the core lab. 
Perform a full physical examination, height and body weight. 
For subjects >18 years, complete the SF-36, EQ-5D-5L, ISI. 
For all subjects, complete the PGIPS score. 
The investigator is to complete the PGA-PA. 
Obtain central laboratory samples for chemistry, hematology, lipid panel, CRP, PK, ADAs, and 
urinalysis. 
Assess for AEs. 
Assess for pericarditis recurrences. 
Obtain informed consent for participation in the LTE period. 
Additional discussion/assessment as needed. 
• 
• 
• 
• 
• 
• 
• 
• 
• 
Upon completion of the EORW visit procedures and obtaining subject informed consent to participate 
in the LTE period, the LTE baseline visit procedures are as follows: 
• 
Change the subject’s status in the IWRS and obtain unblinding information; proceed with subject 
unblinding. 
Obtain weight for pediatric drug dispensing and dosing (Table 5–1). 
Dispense study drug and record the amount (number of vials) dispensed. 
Have the subject administer the LTE-TP Day 1 study drug dose as applicable (if within the study 
drug window) and have the subject record it in the medication diary. 
Instruct subjects on continuing the 11-point pericarditis pain NRS score daily entry. 
Review the study drug dosing schedule, administration techniques, and documentation. 
Additional discussion/assessments as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
Confirm the upcoming study visits. 
• 
• 
• 
• 
• 
• 
• 
6.1.4 
6.1.4.1 
Long Term Extension 
LTE Weeks 8 and 16: Clinic Visit 
The LTE Weeks 8 and 16 clinic visit procedures are as follows: 
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• 
• 
• 
• 
• 
• 
• 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Have all subjects complete the PGIPS score. 
The investigator is to complete the PGA-PA. 
Obtain central laboratory samples for chemistry, hematology, and CRP. 
Assess for AEs. 
Assess for pericarditis recurrence events. 
Additional discussion/assessment as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
Confirm upcoming visit arrangements. 
Obtain weight for pediatric drug dispensing and dosing (Table 5–1). 
Dispense study drug through the IWRS and record the amount (number of vials) dispensed. 
Review the study drug dosing schedule, administration techniques, and documentation. 
Have the subject administer the regularly scheduled study drug dose as applicable (if within the 
study drug window) and have the subject record it in the medication diary. 
Confirm the upcoming study visits. 
• 
• 
• 
• 
• 
• 
6.1.4.2 
LTE Week 24 Clinic Visit 
The LTE Week 24 visit is the final visit of the LTE-TP. However, if at any time throughout the 
course of the study a subject prematurely discontinues study drug, an End of Treatment (EOT) visit is 
to occur. The visit procedures are as follows: 
• 
• 
• 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Acquire a 12-lead ECG. 
Acquire a cardiac ECHO for core laboratory central review; the EHCO is to be read locally prior 
to submission to the core lab. 
Obtain cardiac MRI (substudy participants only). 
Perform a full physical examination. 
For subjects >18 years, complete the SF-36, EQ-5D-5L, ISI. 
For all subjects, complete the PGIPS score. 
The investigator is to complete the PGA-PA. 
• 
• 
• 
• 
• 
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• 
Obtain central laboratory 
biomarkers, and urinalysis. 
Assess for AEs. 
samples for chemistry, hematology, lipid  panel, CRP, PK, ADAs, 
• 
• 
• 
Assess for pericarditis recurrence events. 
Have the subject administer the regularly scheduled study drug as applicable (if within study drug 
window), and have the subject record it in the medication diary. 
Change the subject status in the IWRS. 
Arrange an LTE Week 30 visit. 
• 
• 
6.1.5 
LTE Follow-Up Period 
Upon completion of the LTE Week 24 EOT visit, subjects continue long term follow-up until the end 
of the study (EOS). The LTE-FUP includes 2 visits. 
6.1.5.1 
LTE Week 30 Visit: Clinic 
The LTE Week 30 visit is a clinic visit. Visit activities are as follows: 
• 
• 
• 
• 
• 
• 
Assess for AEs. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Assess for pericarditis recurrence events. 
Additional discussion/assessment as needed. 
Obtain central laboratory samples for CRP, ADAs, and urine pregnancy test. 
Any left-over ancillary supplies are to be returned to the site. 
6.1.5.2 
LTE Week 48 End of Study Visit: TC 
The LTE Week 48 EOS TC visit procedures are as follows: 
• 
• 
• 
Assess for AEs. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Assess pericarditis recurrence. 
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6.1.6 
6.1.6.1 
Supplemental Visits 
Pericarditis Recurrence Assessment: Clinic Visit 
If a subject experiences symptoms consistent with pericarditis recurrence, he/she should contact the 
study investigator immediately for evaluation. It is possible that a subject may have assessments 
performed remotely, however, assessments are also expected be performed at the study site as soon as 
possible. Required assessments include: 
• 
• 
• 
Evaluate pericarditis pain on the 11-point NRS. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Obtain laboratory samples for CRP (local and central) (the POC device provided by Kiniksa 
Pharmaceuticals is the preferred method for local laboratory CRP assessment). 
Acquire a 12 lead ECG. 
Acquire a cardiac ECHO per core laboratory imaging parameters; this ECHO is read locally for 
the purpose of pericarditis recurrence assessment and is then submitted to the ECHO core 
laboratory for central review. 
Perform an abbreviated physical examination, height and body weight. 
For subjects >18 years, complete the SF 36, EQ-5D 5L, ISI. 
For all subjects, complete the PGIPS score. 
The investigator is to complete the PGA PA. 
Obtain central laboratory samples for PK, ADAs, and biomarkers. 
Other procedures deemed necessary per the investigator or delegated site personnel. 
• 
• 
• 
• 
• 
• 
• 
• 
Upon having completed the evaluation, if the investigator makes a clinical diagnosis that the subject 
is having a pericarditis recurrence event, he/she should contact the 
medical monitor to review 
and confirm that all assessments have been performed and collected. Upon 
medical monitor 
confirmation of completion of the assessment, the investigator commences as described in Section 
6.2.3. 
Subjects treated for a pericarditis recurrence event will continue to follow the same visit schedule 
described for the RW period (Section 6.1.3). 
Source documentation including the assessments and evaluations used to confirm a pericarditis 
recurrence event, are required to be sent to CEC. 
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6.1.6.2 
End of Treatment Visit: Clinic 
The EOT visit is to be conducted when a subject permanently discontinues study drug. For subjects 
who complete the RW period but do not consent to participate in the LTE period, the EORW and 
EOT visit can be combined. For those subjects who do consent to participate in the LTE period, the 
EOT visit can be combined with the LTE Week 24 visit. In the event that a subject prematurely 
discontinues study drug, it is expected that the subject will have an EOT visit as soon as possible and 
continue to be followed as described in Section 4.2.2. 
The EOT visit procedures are as follows: 
• 
• 
• 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Acquire a 12 lead ECG. 
Acquire a cardiac ECHO for core laboratory central review; the ECHO is to be read locally prior 
to submission to the core lab. 
Perform a cardiac MRI (for sub-study participants only) only if the previous MRI was done 
longer than 6 months ago. 
Perform a full physical examination. 
For subjects >18 years, complete the SF-36, EQ-5D-5L, ISI. 
For all subjects, complete the PGIPS score. 
The investigator is to complete the PGA PA. 
Obtain central laboratory samples for chemistry, hematology, lipid panel, CRP, PK, ADAs, 
biomarkers, and urinalysis. 
Assess for AEs. 
Assess for pericarditis recurrence events. 
Arrange SFU visit. 
• 
• 
• 
• 
• 
• 
• 
• 
• 
6.1.6.3 
Safety Follow-Up Visit: Clinic or TC/RN 
The SFU visit is to be conducted 6 weeks after the last dose of study drug. For those subjects who 
discontinue study drug at the LTE Week 24 visit, the SFU visit is to occur as a clinic visit. However, 
for those subjects who prematurely discontinue study drug during the study, the visit may be 
conducted in the clinic or as an outpatient (TC/RN visit) based on investigator discretion. The visit 
activities are as follows: 
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Site TC visit: 
• 
• 
• 
• 
Assess for AEs. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Assess for pericarditis recurrence events. 
Remind the subject to continue daily pericarditis pain NRS input if the SFU is occurring prior to 
the LTE Week 24 visit. 
Additional discussion/assessment as needed. 
• 
RN home visit: 
• 
• 
Obtain central laboratory samples for CRP, ADAs, and urine pregnancy test. 
Collect any leftover ancillary supplies and return to the site. 
When the visit is conducted as a clinic visit, all of the RN visit activities are to be performed during 
the clinic visit. 
6.2 
Efficacy Assessments 
Efficacy assessments to be performed at study visits are summarized in the Study Schedule of 
Activities and include: CRP, daily pericarditis pain assessment (11-point NRS), ECG, ECHO, Patient 
Global Impression of Pericarditis Severity (PGIPS), Physician Global Assessment of Pericarditis 
Activity (PGA-PA), and subject’s quality of life assessments (SF-36, EQ-5D-5L) and insomnia 
questionnaire (ISI). In a substudy at selected sites in approximately 10 subjects, a cardiac MRI will be 
performed. 
Note that in case the electronic versions of the PROs and assessments/questionnaires (PGIPS, PGA-
PA, SF-36, EQ-5D-5L, and ISI) are not available, the paper forms must be completed until the 
electronic versions are available again. 
6.2.1 
6.2.1.1 
Individual Efficacy Assessments 
C-Reactive Protein 
Central and local laboratory assessments of CRP will be performed at study visits as described in the 
Study Schedule of Activities. Centrally assayed CRP values will be used for statistical evaluations of 
changes from baseline. Locally assayed CRP will be used for screening, evaluation of treatment 
response prior to randomization, and assessment of suspected pericarditis recurrence in the RW 
period. The POC device provided by Kiniksa Pharmaceuticals is the preferred method for local 
laboratory CRP assessment. 
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6.2.1.2 
11-Point Pericarditis Pain Numerical Rating Scale 
Subjects will be asked to provide a daily assessment of pericarditis pain starting at RI baseline. A 
validated 11-point pericarditis NRS (Section 13.2) will be used to measure the subject’s level of pain 
intensity on a daily basis throughout the study (Hawker et al 2011; Mannion et al 2007; Dworkin et al 
2005). 
It is recommended that daily pericarditis pain measurements using the 11-point NRS are performed 
by subjects at the same time of the day each day, and prior to study drug injection on days with study 
drug administration. 
6.2.1.3 
Electrocardiogram 
Twelve-lead ECGs will be performed at study visits as described in the Study Schedule of Activities. 
Pericarditis commonly involves changes in the electrophysiologic activity of the heart, resulting in 
typical ECG findings, namely widespread ST-segment elevation or PR-segment depression. 
6.2.1.4 
Echocardiogram 
Echocardiographic assessment of presence of pericardial effusion including new or worsening of 
pericardial effusion should be obtained at study visits as described in the Study Schedule of 
Activities. Pericardial effusion is characterized by accumulation of excess fluid in the pericardial 
space surrounding the heart, and pericarditis is one of the main causes of pericardial effusion. 
Echocardiography is a sensitive tool and the most widely used imaging technique for the detection of 
pericardial effusion and/or thickening. Echocardiograms are to be acquired per the ECHO core 
imaging parameters. Upon local assessment and interpretation, the ECHO is then to be submitted to 
the designated central imaging laboratory. 
6.2.1.5 
Patient Global Impression of Pericarditis Severity 
Patient Global Impression questionnaires have been developed for a variety of indications. The 
PGIPS is a single-item PRO measure that assesses the subject’s impression of overall severity of 
pericarditis symptoms at the time the questionnaire is administered, using a 7-point rating scale 
ranging from absent (no recurrent pericarditis symptoms) to very severe (recurrent pericarditis 
symptoms cannot be ignored) (Guy 1976). The PGIPS can be completed in less than 30 seconds. 
The subject will select the box that best describes the severity of pericarditis symptoms right now: 
 
 
 
 
 
Absent: no symptoms 
Minimal: can be easily ignored without effort 
Mild: can be ignored with effort 
Moderate: cannot be ignored but does not influence my daily activities 
Moderately severe: cannot be ignored and occasionally limits my daily activities 
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 
 
Severe: cannot be ignored and often limits my concentration on daily activities 
Very severe: cannot be ignored and markedly limits my daily activities 
The PGIPS will be collected as described in the Study Schedule of Activities. 
6.2.1.6 
Physician Global Assessment of Pericarditis Activity 
Physician Global Assessment questionnaires have been developed for a variety of indications. The 
PGA-PA is a single-item clinician-reported outcome measure that investigators use to rate their 
impression of the patient’s overall pericarditis disease activity at the time the assessment is 
completed, using a 7-point rating scale ranging from absent to very severe (Guy 1976). Like the 
PGIPS, the PGA-PA can be completed in less than 30 seconds. 
The investigator will select the box that best describes subject’s pericarditis activity right now. 
 
 
 
 
 
 
 
Absent 
Minimal 
Mild 
Moderate 
Moderately severe 
Severe 
Very severe 
The PGA-PA will be collected as described in the Study Schedule of Activities. 
6.2.1.7 
36-Item Short Form Health Survey 
The SF-36 is a set of generic, coherent, and easily administered quality-of-life measures. The SF-36 
was developed at RAND Corporation as part of its Medical Outcomes Study. The SF-36 assesses 
8 health domains: physical functioning, bodily pain, role limitations due to physical health problems, 
role limitations due to personal or emotional problems, general mental health, social functioning, 
energy/fatigue, and general health perceptions. It also includes a single item that provides an 
indication of perceived change in health. 
SF-36 will be collected in subjects ≥18 years or older as described in the Study Schedule of Activities. 
6.2.1.8 
EQ-5D-5L 
The EQ-5D-5L is a standardized instrument developed by the EuroQol Group as a measure of health-
related quality of life that can be used in a wide range of health conditions and treatments. The EQ-
5D-5L consists of a descriptive system and the EQ VAS. The descriptive system comprises 5 
dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The rating 
scale records the subject’s self-rated health on a vertical VAS. This can be used as a quantitative 
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measure of health outcome that reflects the subject’s own judgement. The scores on these 
5 dimensions can be presented as a health profile or can be converted to a single summary index 
number 
(utility) 
reflecting 
preferability 
compared 
to 
other 
health 
profiles 
(https://euroqol.org/eq-5d-instruments). 
The EQ-5D-5L will be collected in subjects ≥18 years or older as described in Study Schedule of 
Activities. 
6.2.1.9 
Insomnia Severity Index 
The ISI is a 7-item self-report questionnaire assessing the nature, severity, and impact of insomnia. 
The usual recall period is the “last 2 weeks” and the dimensions evaluated are severity of sleep onset, 
sleep maintenance, early morning awakening problems, sleep dissatisfaction, interference of sleep 
difficulties with daytime functioning, noticeability of sleep problems by others, and distress caused by 
the sleep difficulties. A 5-point Likert scale is used to rate each item (e.g., 0=no problem; 4=very 
severe problem), yielding a total score ranging from 0 to 28. The total score is interpreted as follows: 
no clinically significant insomnia (0–7); subthreshold insomnia (8–14); clinical (moderate) insomnia 
(15–21); and clinical (severe) insomnia (22–28) (Morin et al 2011). 
The ISI will be collected in subjects ≥18 years or older as described in Study Schedule of Activities. 
6.2.1.10 Cardiac MRI 
Cardiac MRI will be performed as described in the Study Schedule of Activities at selected sites in 
approximately 10 subjects in the cardiac MRI substudy. Cardiac MRI will be performed to assess any 
changes in pericardial inflammation. Cardiac MRI readings will be performed by a central imaging 
laboratory. The study site/clinic reading of the MRI at the time of the examination may be used by the 
investigator for clinical decision-making. 
6.2.2 Assessment of Clinical Response at the End of the Run-In Period Week 
12/RW Baseline 
At RI Week 12/RW baseline visit, all subjects receiving rilonacept who are able to discontinue 
background SOC pericarditis therapy during the RI period (Section 3.1) are assessed for Clinical 
Response. Only subjects who achieve Clinical Response at RI Week 12 and have discontinued 
background medications for pericarditis are eligible for randomization in the RW period. 
Clinical Response at RI Week 12 is defined as follows: 
• 
A weekly average of daily pericarditis pain of ≤2.0 on the 11-point NRS during the 7 days prior 
to and including the day of randomization, AND 
CRP level ≤0.5 mg/dL at the RI Week 12/RW baseline visit. 
• 
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6.2.3 Management of Suspected Pericarditis Recurrence in the RW Period 
Pericarditis Recurrence Definition: Pericarditis recurrence, for the purpose of the protocol, is 
defined as the recurrence of typical pericarditis pain associated with supportive objective evidence of 
pericarditis. 
At any time point during the RW period, subjects who experience suspected recurrence of their 
pericarditis will have been instructed to inform their site investigator as soon as possible. Subjects 
who experience a suspected recurrence of pericarditis symptoms will be requested to report to the 
study site/clinic for a scheduled or unscheduled visit, during which clinical assessments will be 
performed to gather all the necessary diagnostic data to confirm or rule out the presence of 
pericarditis recurrence (Section 6.1.6.1). The investigator will evaluate all assessments performed for 
a diagnostic workup, whether at the study site or at locations outside. 
Upon completion of pericarditis workup, the investigator is required to contact the 
medical monitor to confirm that the protocol required diagnostic workup is complete prior to 
implementing treatment for the event. 
Following communication with the 
medical monitor, if the event meets the criteria 
for bailout rilonacept (at least 1 day with pericarditis pain measurement ≥4 on the 11-point NRS and 
one CRP value ≥1 mg/dL either on the same day or separated by no more than 7 days), and after the 
medical monitor has confirmed with the investigator that the diagnostic workup is 
complete, the attainment of bailout criteria is confirmed in the IWRS, blinded study drug is 
discontinued, and open-label rilonacept treatment is dispensed. If needed, sequential ORT is allowed 
as outlined in Section 5.8.3. The subject will continue to be followed up according to the Study 
Schedule of Activities for the RW period. 
Following communication with the 
medical monitor, if the event does not meet the 
protocol criteria for bailout rilonacept but in the judgement of investigator requires treatment, after 
the 
medical monitor has confirmed with the investigator that the diagnostic workup 
is complete, the investigator is allowed to add sequential ORT to blinded study drug, and as outlined 
in Section 5.8.3. Blinded study drug treatment will continue until a pericarditis recurrence that meets 
criteria for bailout rilonacept, or until the end of the RW period. 
For a summary of management of suspected pericarditis recurrence, refer to Figure 3. 
Upon suspected pericarditis recurrence, the event is required to be captured in the electronic data 
capture (EDC) system within 24 hours of learning of the event, and a pericarditis recurrence event 
adjudication package must be prepared for adjudication by CEC. The event package will include, but 
may not be limited to, data on the subject’s pericarditis pain level, CRP value, ECG tracing, ECHO 
result, the presence or absence of pericardial rub, and any additional source documentation relevant to 
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the assessment of the suspected event. Details on endpoint package requirements will be described in 
the CEC charter. The CEC-confirmed pericarditis recurrences will be used for Primary Endpoint 
efficacy analysis. For more details on the CEC, refer to Section 6.7.2 
Figure 3: 
Management of Suspected Pericarditis Recurrence in the Randomized- 
Withdrawal Period 
Pericarditis 
Recurrence * 
*Per protocol: CRP, ECG, ECHO, and pericardial rub assessment 
to be completed prior to treatment intervention 
NRS ≥ 4 
NO 
Able to observe 
NO 
YES 
event without 
treatment 
CRP ≥ 1.0 mg/dL 
YES 
YES 
Symptom 
Progression 
YES 
ORT=Oral Rescue Therapy 
6.3 
Safety Assessments 
Safety assessments to be performed at study visits are summarized in Study Schedule of Activities 
and include: assessment of AEs (Section 6.4), physical examinations (full and abbreviated) including 
vital signs measurements, chest x-ray, TB screening, and clinical laboratory tests (serology, 
hematology, chemistry, urinalysis) (Section 6.6). A pregnancy test (Section 6.6.6) will be conducted 
at screening and as needed during the study and must be performed 6 weeks after the last study drug 
administration. 
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Bailout open-label 
rilonacept; and 
sequential ORT if 
needed 
(per Section 5.8.3) 
Continue 
observation and 
blinded study drug 
 
 
 
 
Continue blinded 
study drug; and 
sequential ORT if 
needed 
(per Section 5.8.3) 
 
 
 
 
 
 
 
 
 
 


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Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
6.3.1 Physical Examination 
A full physical examination should include at minimum an evaluation of vital signs, head, eyes, ears, 
nose, and throat as well as cardiovascular, dermatological, musculoskeletal, respiratory, GI, 
genitourinary, and neurological systems. Body weight and height will be measured as per the Study 
Schedule of Activities and will be recorded in the eCRF. Any abnormality identified at baseline 
should be recorded on the medical history and physical examination eCRFs. At selected visits as 
specified in the Study Schedule of Activities, an abbreviated physical examination will be 
performed to evaluate vital signs, lung and heart sounds, including evaluation for pericardial rub. 
At all visits at the study site, limited symptom-directed physical examinations may need to be 
performed in order to determine changes from baseline or abnormalities and should be recorded in the 
subject’s trial notes. New or worsened abnormalities should be recorded as AEs on the Adverse Event 
eCRF. 
6.3.2 Vital Signs 
Vital signs include measurements of respiratory rate, pulse rate, systolic and diastolic blood pressure, 
and temperature. Blood pressure measurements should be obtained after the subject has been seated 
for at least 5 minutes. 
6.3.3 Chest X-ray 
Chest x-rays in accordance with local requirements will be obtained at screening (or an existing chest 
x-ray within 12 weeks of first study drug administration can be used) according to the Study Schedule 
of Activities. Chest x-rays should be reviewed by a qualified radiologist for clinically significant 
abnormalities and evidence of pulmonary disease that would exclude the potential subject. 
6.3.4 Tuberculosis Screening 
An IGRA test or another TB test based on acceptable clinical practice in each country will be 
performed in order to evaluate for the presence of active or latent TB infection at screening. 
6.4 
Adverse Events 
The investigator is responsible for reporting all AEs that are observed or reported during the study, 
regardless of their relationship to study drug or their clinical significance. 
6.4.1 
6.4.1.1 
Definitions 
Adverse Event 
An AE is any untoward medical occurrence in a subject or clinical investigation subject administered 
a pharmaceutical product. An AE does not necessarily have a causal relationship with this treatment. 
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An AE can therefore be any unfavorable sign (including an abnormal laboratory finding), symptom or 
disease temporally associated with the use of a medicinal (investigational) product, whether or not 
related to the medicinal (investigational) product. AEs also include: any worsening (i.e., any clinically 
significant change in frequency and/or intensity) of a pre-existing condition that is temporally 
associated with the use of the study drug; abnormal laboratory findings considered by the reporting 
investigator to be clinically significant; and any untoward medical occurrence. 
6.4.1.2 
Treatment-emergent Adverse Event 
A treatment-emergent AE (TEAE) is defined as any event not present before exposure to the study 
drug or any event already present that worsens in either intensity or frequency after exposure to the 
study drug. 
6.4.1.3 
Serious Adverse Event 
A serious adverse event (SAE) is any untoward medical occurrence or effect that, at any dose: 
• 
Results in death. Includes all deaths, even those that appear to be completely unrelated to the 
study drug (e.g., car accident where the subject is a passenger). 
Is life-threatening. In the view of the investigator, the subject was at immediate risk of death from 
the event at the time of the event (i.e., it does not include an AE that might have caused death if it 
had occurred in a more serious form). 
Requires in-patient hospitalization or prolongs an existing hospitalization. (Complications 
occurring during hospitalization are AEs and are SAEs if they cause prolongation of the current 
hospitalization. Hospitalization for elective treatment of a pre-existing non-worsening condition 
is not, however, considered an AE. The details of such pre-existing condition must be recorded on 
the medical history or physical examination page of the eCRF. Hospitalization is defined as an 
admission to the hospital ward, a short-stay type unit, or Emergency Room for longer than 
24 hours. Prolongation of existing hospitalization is defined as a hospital stay longer than 
originally anticipated for the event or development of a new AE as determined by the Investigator 
or treating physician.) 
Results in persistent or significant disability/incapacity. (An AE is incapacitating or disabling if it 
results in a substantial and/or permanent disruption of the subject’s ability to carry out normal life 
functions.) 
Is a congenital anomaly/birth defect. 
Is an important medical event. Important medical events may not be immediately life-threatening 
or result in death or hospitalization but may jeopardize the subject or may require intervention to 
prevent one of the other serious outcomes listed above (e.g., intensive treatment in an emergency 
room or at home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in 
hospitalization; or development of drug dependency or drug abuse). 
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• 
• 
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In addition, medical and scientific judgment is required to decide if prompt notification is required in 
situations other than those defined for SAEs above, i.e., any event that the investigator regards as 
serious that did not strictly meet the criteria above but may have jeopardized the subject or required 
intervention to prevent one of the outcomes listed above, or that would suggest any significant hazard, 
contraindication, side effect, or precaution that may be associated with the use of the study drug. 
All SAEs that occur after signing of study-related informed consent, whether or not the SAEs are 
related to the study drug or study procedures, must be reported. 
6.4.1.4 
Adverse Event of Special Interest 
An adverse event of special interest (AESI) is defined as an AE of scientific and medical interest 
specific to the understanding of the study drug and requiring close monitoring and rapid 
communication by the investigator to the Sponsor. An AESI may be serious or non-serious. The rapid 
reporting of AESIs allows ongoing analysis of these events in order to characterize and understand 
them in association with the use of the study drug. 
Treatments with immunosuppressants, including rilonacept, may result in an increase in the risk of 
malignancies. Therefore, malignancy is an AESI for rilonacept. Any AE of malignancy (excluding 
basal cell carcinoma of the skin) requires reporting to the 
Pharmacovigilance (PHV) within 
24 hours after the time the site personnel first learn about the event, following the process as 
described in Section 6.4.6. 
6.4.1.5 
Adverse Reaction 
Any noxious and unintended response to the study drug (i.e., where a causal relationship between the 
study drug and an AE is at least a reasonable possibility) related to any dose should be considered 
adverse drug reaction. 
6.4.1.6 
Suspected Unexpected Serious Adverse Reaction 
Suspected Unexpected Serious Adverse Reaction (SUSAR) is an adverse reaction that is 
“unexpected”, i.e., it is not listed (or not listed at the severity that has been observed) in the 
designated Reference Safety Information of the Investigator’s Brochure. Evaluation and reporting 
requirements for SUSARs are detailed in Section 6.4.8. 
6.4.2 
6.4.2.1 
Assessing Adverse Events 
Relationship to Study Drug 
The investigator’s assessment of an AE’s relationship to the study drug is part of the documentation 
process, but it is not a factor in determining what is or is not reported in the study. If there is any 
doubt as to whether a clinical observation is an AE, the event should be reported. 
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The relationship or association of the study drug in causing or contributing to the AE will be 
characterized by investigator using the following classification and criteria: 
• 
Not Related: when the AE is definitely caused by the subject’s clinical state or the study 
procedure/conditions 
Unlikely Related: when the temporal association between the AE and the study drug is such that 
the drug is not likely to have any reasonable association with the AE 
Possibly Related: when the AE follows a reasonable temporal sequence from the time of study 
drug administration but could have been produced by the subject’s clinical state or the study 
procedures/conditions 
Related: when the AE follows a reasonable temporal sequence from administration of the study 
drug, abates upon discontinuation of the drug, follows a known or hypothesized cause-effect 
relationship, and (if appropriate) reappears when the drug is reintroduced 
• 
• 
• 
6.4.2.2 
Intensity 
The severity of an AE will be recorded as one of the following: 
• 
Mild: easily tolerated, does not interfere with normal daily activities, does not require 
intervention 
Moderate: causes some interference with daily activities; minimal, local, or noninvasive 
intervention indicated 
Severe: as a consequence of the event, daily activities are limited or completely halted; 
hospitalization or prolongation of hospitalization indicated 
• 
• 
Changes in the severity of an AE should be documented to allow an assessment of the duration of the 
event at each level of intensity to be performed. Adverse events characterized as intermittent do not 
require documentation of onset and duration of each episode. 
6.4.3 Recording Adverse Events 
Each subject should be monitored for the development of any AEs. This information should be 
collected by asking nonleading questions (such as “How are you feeling?”) and from observations of 
and conversations with patients. AEs may also be collected by direct physical exam, diagnostic 
procedures, or any other appropriate source. 
At every study visit (telephone or at the site), subjects will be asked a standard nonleading question to 
elicit any medically related changes in their well-being. They will also be asked if they have been 
admitted to the hospital, had any accidents, used any new medications, or changed concomitant 
medication regimens (both prescription and over-the-counter medications). 
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All AEs (serious and non-serious) will be documented in the subject’s source documents and 
recorded in the eCRF. Any clinically relevant (as determined by the investigator) deterioration in 
laboratory assessments or other clinical findings is considered an AE and must be recorded in the 
subject’s source documents and in the eCRF. 
The AE term should be reported in standard medical terminology when possible. Also, when 
possible, signs and symptoms indicating a common underlying pathology should be noted as 
one comprehensive event. Information to be collected includes the following: 
• 
• 
• 
• 
• 
• 
• 
• 
• 
Event term 
Date and time of onset 
Investigator-specified assessment of severity and relationship study drug 
Date of resolution of the event 
Seriousness 
Any required treatment or actions 
Outcome 
Whether or not it caused the subject to discontinue the study drug. 
Whether or not the AE is an Injection Site Reaction (ISR). ISR is defined as any AE that occurs at 
the study drug injection site. If an ISR is observed, the subject may be treated at the discretion of 
the investigator. 
Adverse events resulting from concurrent illnesses, reactions to concurrent illnesses, reactions to 
concurrent medications, or progression of disease states must also be reported. All AEs will be 
followed to adequate resolution. The Medical Dictionary for Regulatory Activities (MedDRA) will be 
used to code all AEs. 
Any medical condition that is present at the time that the subject is screened but does not deteriorate 
should not be reported as an AE. However, if the condition deteriorates at any time during the study, 
it should be recorded as an AE. 
6.4.3.1 
Adverse Events Based on Signs and Symptoms 
All AEs spontaneously reported by the subject or reported in response to the open question from the 
study personnel or revealed by observation will be collected and recorded in the eCRF. When 
collecting AEs, the recording of a diagnosis is preferred (when possible) to the recording of a list of 
signs and symptoms. However, if a diagnosis is known and there are other signs or symptoms that are 
not generally part of the diagnosis, the diagnosis and each sign or symptom will be recorded 
separately. 
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6.4.3.2 
Adverse Events Based on Examinations and Tests 
If an abnormal laboratory value/vital sign is associated with clinical signs and symptoms, the sign or 
symptom will be reported as an AE and the associated laboratory result/vital sign will be considered 
as additional information. Wherever possible the reporting investigator uses the clinical rather than 
the laboratory term (e.g., anemia vs low hemoglobin value). In the absence of clinical signs or 
symptoms, clinically significant findings on examinations and tests should be reported as AEs. 
Any new or aggravated clinically significant abnormal medical finding at a physical examination as 
compared with the baseline assessment will be reported as an AE. 
6.4.3.3 
Pericarditis Disease Related Events 
Signs, symptoms, and abnormal findings associated with pericarditis are to be captured as a 
pericarditis recurrence event rather than as an AE unless the event is more severe than expected for 
the subject. In any case, pericarditis recurrence is required to be captured in the eCRF (see Section 
6.2.3) within 24 hours of learning of the event. 
6.4.4 Time Period for Collection of Adverse Events 
Adverse events will be assessed from the time the subjects signs the ICF and through the duration of 
the study, or at least through the SFU period (6 weeks after the last dose of study drug). 
6.4.5 Follow-Up of Unresolved Adverse Events 
Every reasonable effort will be made to follow subjects who have AEs. 
Any AEs that are unresolved at the subject’s SFU visit are to be followed up by the investigator until 
resolution or for as long as medically indicated. Additional information for any subject with an 
ongoing AE at the end of the SFU period may be requested by the 
PHV, as needed. 
6.4.6 Reporting Serious Adverse Events 
Any AE that meets SAE criteria (Section 6.4.1.3) must be reported to the 
PHV using the EDC 
system, immediately (i.e., within 24 hours) after the time site personnel first learn about the event. 
In the event the EDC entry is not possible (e.g., system failure or access problems), the study site 
should complete the paper SAE report form and fax the form to the 
PHV within 24 hours of 
awareness. The EDC system should be updated as soon as it is available. 
A full description of every SAE will need to be provided to the 
PHV (this may be supported by 
source documentation such as discharge summary or laboratory report should these documents be 
requested by the 
PHV). Additional follow-up information, if required or available, should be 
sent to the 
PHV as soon as possible and placed with the original SAE information. 
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The following contact information is to be used for SAE reporting: 
Information on non-serious AEs that become serious must also be reported to the 
as it is available. 
PHV as soon 
Investigators must report SAEs and follow-up information to their responsible Institutional Review 
Board (IRB) or Independent Ethics Committee (IEC) as applicable per institutional policy. 
The Sponsor or designee will provide regulatory authorities, IRBs, IECs, and principal investigators 
with clinical safety updates/reports according to local requirements. 
6.4.6.1 
Other Reasons for Immediate Reporting 
The following events require reporting to the 
personnel first learn about the event: 
PHV within 24 hours after the time the site 
• 
• 
• 
• 
Pregnancy in subject or female partner of male subject 
Overdose of the study drug or concomitant medication, regardless of whether it is considered AE 
Other study drug errors 
Any AE of malignancy (excluding basal cell carcinoma of the skin) 
6.4.7 Pregnancy 
Pregnancy is regarded as an AE only if there is a suspicion that study drug may have interfered with 
the effectiveness of a contraceptive medication. Nonetheless, any pregnancy that occurs during study 
participation (including pregnancy in a female partner of a male subject) must be reported to the 
PHV in the same way and using the same procedures as for an SAE (Section 6.4.6). The subject with 
pregnancy must not receive (additional) study drug. The pregnancy must be followed up to determine 
outcome (including spontaneous miscarriage, elective termination, normal birth, or congenital 
abnormality) and status of mother and child, even if the subject was discontinued from the study. 
Pregnancy complications and elective terminations for medical reasons must be reported as an AE or 
SAE. Spontaneous miscarriage must be reported as an SAE. 
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Any SAE occurring in association with a pregnancy, brought to the investigator’s attention after the 
subject has completed the study, and considered by the investigator as possibly related to the study 
drug, must be promptly reported to the 
PHV. 
In the event that a subject is found to be pregnant after having received at least 1 study drug dose, the 
study drug must be discontinued, and the pregnancy will be followed to term and the status of mother 
and child will be reported to the 
PHV after delivery. Instances of perinatal death or congenital 
abnormality, if brought to the attention of the investigator at any time after cessation of study drug, 
will be reported to the 
PHV within 24 hours. 
6.4.8 Evaluating and Reporting SUSARs 
Pharmacovigilance will promptly evaluate all SUSARs and nonserious AEs of special interest 
against cumulative product experience to identify and expeditiously communicate possible new safety 
findings to investigators, IRBs/IECs, and applicable health authorities based on applicable legislation. 
To determine reporting requirements for single AE cases, 
PHV staff in collaboration with 
Kiniksa Pharmaceuticals will assess the expectedness of these events using the Reference Safety 
Information (Section 6.2) of the rilonacept Investigator’s Brochure. 
PHV will compare the severity of each SUSAR and the cumulative event frequency reported for 
the study with the severity and frequency reported in the applicable reference document. 
Reporting requirements will also be based on the investigator’s assessment of causality and 
seriousness, with allowance for upgrading by 
PHV and Kiniksa Pharmaceuticals as needed. 
All relevant information about suspected SUSARs that are fatal or life-threatening will be recorded 
and reported to the competent authorities in all the applicable countries, and IRBs/IECs in 
conjunction with Directive 2001/20/EC. 
6.5 
Other Assessments 
6.5.1 Pharmacokinetic Sample 
All subjects will have PK samples obtained according to the Study Schedule of Activities. For PK 
analyses, it is important that the exact time of the SC injection is recorded for each subject. When PK 
samples are to be collected on dosing days, serum will be collected pre-dose to measure rilonacept 
concentrations. Specific procedures for sample collection, processing, storage, and shipment can be 
found in a separate Laboratory Manual provided to sites. 
A PK substudy will be conducted in a subset of subjects agreeing to provide a PK sample 24 hours 
after the first dose of study drug in the RI period. Specific procedures for sample collection, 
processing, storage, and shipment can be found in a separate Laboratory Manual provided to sites. 
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6.5.2 Anti-Drug Antibodies (ADAs) against Rilonacept (KPL-914) 
Serum samples to measure the presence of ADAs against rilonacept will be collected according to the 
Study Schedule of Activities. Instructions for sample collection, processing, storage, and shipment 
can be found in a separate Laboratory Manual provided to the site. 
6.5.3 Biomarkers 
Serum and plasma will be collected according to the Study Schedule of Activities for biomarker 
analysis. 
6.5.4 Pharmacogenomics 
Whole blood will be collected for pharmacogenomics assessments after signing the separate 
Pharmacogenomics ICF. 
6.6 
Laboratory Analyses 
Any abnormal laboratory test results (hematology, chemistry, or urinalysis) or other safety 
assessments (e.g., physical examination, vital signs measurements), including those that worsen from 
baseline, felt to be clinically significant in the medical and scientific judgement of the investigator are 
to be recorded as AEs or SAEs. 
Laboratory assessments will be performed at study visits as summarized in Study Schedule of 
Activities. Unscheduled laboratory assessments for safety issues are permitted as deemed necessary 
by the investigator. 
Whenever possible in pediatric subjects, local laboratory tests should be drawn using pediatric tubes. 
6.6.1 Serology 
Samples for local laboratory assessment of hepatitis B surface antigen, hepatitis B core antibody, 
hepatitis C virus antibody, and HIV levels will be collected at screening. If clinically indicated, those 
tests may be also collected during the study. 
6.6.2 Hematology 
Hematology tests performed at central study laboratory include WBC count with differential, platelet 
count, red blood cell count, mean corpuscular volume, hemoglobin, mean corpuscular hemoglobin 
concentration. 
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6.6.3 Chemistry 
Blood chemistry tests performed in the central study laboratory include albumin, total protein, 
alkaline phosphatase, ALT/SGPT, AST/SGOT, direct bilirubin, total bilirubin, bicarbonate, chloride, 
potassium, sodium, creatinine, glucose. 
In addition, the following chemistry tests may be performed together with local CRP measurement 
when using POC device: chloride, creatine kinase, creatinine, glucose, potassium, sodium, total 
carbon dioxide, blood urea nitrogen. 
6.6.4 Non-fasting Lipid Panel 
Subjects treated with rilonacept may experience increases in their lipids, including total cholesterol, 
LDL, HDL, and triglycerides. 
Non fasting measurements of total cholesterol, triglycerides, HDL, and direct LDL will be performed 
by central study laboratory as described in the Study Schedule of Activities. 
Investigators should monitor the lipid profiles in study subjects and consider ordering fasting lipid 
panel and/or lipid lowering therapies as needed based on cardiovascular risk factors and current 
guidelines. 
6.6.5 Urinalysis 
Urinalysis performed by the central study laboratory includes specific gravity, pH, protein, 
urobilinogen, ketones, glucose, blood, bilirubin, nitrites, leukocyte esterase. It will be performed as 
described in the Study Schedule of Activities. 
6.6.6 
Pregnancy Test 
For women of child-bearing potential, a urine pregnancy test using a licensed test (dipstick) should be 
performed prior to receiving the first administration of study drug, and as needed during the study, 
and also at the SFU visit. When needed, serum pregnancy test should be performed. The purpose of 
pregnancy test is to prevent embryo/fetal exposure to study drug. Subjects with positive or 
indeterminate pregnancy test during the screening are not eligible for the study. 
6.6.7 Sample Collection 
The procedures for the collection, handling, and shipment of laboratory samples are specified in the 
Laboratory Manual supplied to sites by the central laboratory. 
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6.7 
Committees 
6.7.1 Independent Data Monitoring Committee (DMC) 
A DMC will be utilized in this study to ensure external objective medical and/or statistical (if needed) 
review of safety data in order to protect the ethical and safety interests of subjects. The DMC will 
review unblinded aggregate (and, where necessary, individual) subject safety data at pre-defined 
intervals according to a DMC charter. The analysis plan for the DMC review will be described in the 
DMC charter, which will also contain details of the composition and the responsibilities of the DMC. 
6.7.2 Clinical Endpoint Committee (CEC) 
An independent CEC will review and adjudicate all suspected recurrent pericarditis events that occur 
during the RW period of the study. The procedures for adjudicating events will be described in the 
CEC Charter. This will be done independent of the investigators, and in a manner blinded to 
treatment assignment. The CEC will complete assessments on an ongoing basis. 
7 
7.1 
The 
Statistical and Analytical Plan 
Primary Efficacy Endpoint 
primary efficacy endpoint is time to pericarditis recurrence, defined as the time from 
randomization to the date of the first pericarditis recurrence for each subject. Only CEC-confirmed 
pericarditis recurrence will be considered as an event for the primary analysis. 
A sensitivity analysis will be done based on the investigator’s assessment of the event. 
Pericarditis recurrence is defined in Section 6.2.3. 
Subjects who do not have a pericarditis recurrence will be censored at the date of the last available 
assessment during the RW period before data cutoff. Detailed censoring rules will be specified in the 
Statistical Analysis Plan (SAP). 
7.2 
Secondary Efficacy Endpoints for the RW Period 
This section defines secondary efficacy endpoints for the RW period. Endpoints for the RI period and 
for the LTE-TP are defined in Section 7.3. 
7.2.1 Major Secondary Efficacy Endpoints 
1. Proportion of subjects who maintained Clinical Response at Week 24 of the RW period. 
Clinical Response is defined as a weekly average of daily pericarditis pain on the 11-point 
NRS ≤2.0 and CRP level ≤0.5 mg/dL. 
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2. Percentage of days with no or minimal pain in the first 24 weeks of the RW period. No or 
minimal pain is defined as non-missing NRS ≤1. 
Proportion of subjects with absent or minimal pericarditis symptoms (based on the 7-point 
PGIPS) at Week 24 of the RW period. 
3. 
7.2.2 Other Secondary Endpoints 
All time-to-event endpoints start from the day of randomization. The following variables will be 
analyzed: 
• 
• 
• 
• 
• 
• 
• 
• 
• 
Proportion of subjects without pericarditis recurrence in the first 24 weeks of the RW period 
Time to pericarditis pain NRS ≥4 
Time to CRP level ≥1 mg/dL 
Time to pericardial rub 
Time to widespread ST-segment elevation or PR-segment depression on ECG 
Time to new or worsening pericardial effusion on ECHO 
Change over time in CRP levels 
Change over time in the subject’s assessments of pericarditis pain (weekly average) 
Number (percentage) of subjects with absent or minimal pericarditis activity based on PGA-
PA 
Change over time in the SF-36 Physical Component Score 
Change over time in the SF-36 Mental Component Score 
the 
• 
• 
• 
Change in EQ-5D-5L. There are 6 questions in this instrument (Section 6.2.1.8). Each of the first 
5 questions has 5 levels, from level 1 (best) to level 5 (worst). They are mobility, self-care, usual 
activities, pain/discomfort, and anxiety/depression. The sixth question is the health on the day, 
from 0 (the worst) to 100 (the best) (van Reenen and Janssen 2015). The levels of the first 
5 questions (EQ-5D-5L profile) will be converted to an index value. Change from baseline in 
each one of these 7 values will be an endpoint. 
Change over time in subject’s sleep quality assessed with the ISI (Section 6.2.1.9). There are 
7 items in the ISI. Change in ISI total score, which is the sum of the 7 items over time, will be the 
endpoint. 
Change over time in ISI categories. The ISI total scores are divided to 4 categories: 
• 
• 
- 
- 
0–7 = No clinically significant insomnia 
8–14 = Subthreshold insomnia 
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- 
- 
15–21 = Clinical insomnia (moderate severity) 
22–28 = Clinical insomnia (severe) 
• 
Number (percentage) of subjects who receive sequential ORT for pericarditis (analgesics, 
NSAIDs, and/or colchicine) in the RW period 
7.3 
Other Endpoints 
These include efficacy endpoints in the RI period and the LTE-TP. Since there is no control arm in 
these 2 periods, only descriptive statistics will be provided. All time-to-event endpoints start from the 
day of receiving rilonacept in that period. 
7.3.1 Efficacy Endpoints for the RI Period 
The following efficacy endpoints are included in this period: 
• 
Proportion of subjects who achieved Clinical Response at the RI Week 12/RW baseline visit. 
Clinical Response is defined as a weekly average of daily pericarditis pain of ≤2.0 on the 11-point 
NRS and CRP level ≤0.5 mg/dL at the RI Week 12/RW baseline visit. 
Time to CRP normalization (≤0.5 mg/dL) 
Number (percentage) of subjects with normalization of CRP at RI Week 12 
Change from baseline in pericarditis pain at RI Week 12 
Change from baseline in CRP level at RI Week 12 
Resolution of ECHO and ECG abnormalities (yes/no) at RI Week 12 
Percentage of days with no or minimal pain 
Proportion of subjects with absent or minimal pericarditis symptoms based on PGIPS 
Proportion of subjects with absent or minimal pericarditis activity based on the PGA-PA 
Change over time in the SF-36 Physical Component Score 
Change over time in the SF-36 Mental Component Score 
Change in the EQ-5D-5L (Section 7.2.2 contains details about calculation) 
Change over time in the subject’s sleep quality assessed with the ISI (Section 7.2.2 contains 
details about calculation) 
Change over time in ISI categories 
Number (percentage) of subjects who were off background pericarditis medication at RI Week 12 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
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7.3.2 Efficacy Endpoints for the LTE-TP 
The efficacy endpoints below are included in this period. Each endpoint will be summarized through 
Week 24, by subjects who did and did not have an adjudicated pericarditis recurrence in the RW 
period, respectively, and overall: 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
Number (percentage) of subjects with pericarditis recurrences 
Proportion of subjects with Clinical Response 
Change over time in CRP levels 
Change over time in the subject’s assessments of pericarditis pain 
Percentage of days with no or minimal pain 
Proportion of subjects with absent or minimal pericarditis symptoms based on PGIPS 
Proportion of subjects with absent or minimal pericarditis activity based on the PGA-PA 
Change over time in the SF-36 Physical Component Score 
Change over time in the SF-36 Mental Component Score 
Change in the EQ-5D-5L (Section 7.2.2 contains details about calculation) 
Change over time in the subject’s sleep quality assessed with the ISI (Section 7.2.2 contains 
details about calculation) 
Change over time in ISI categories 
Number (percentage) of subjects requiring addition of SOC pericarditis therapy 
• 
• 
7.4 
Sample Size Calculations 
For the purpose of sample size estimation, time to pericarditis recurrence is assumed to follow an 
exponential distribution. An event of interest is defined as a subject’s first adjudicated recurrence of 
pericarditis. The following assumptions are used in the sample size calculation using EAST 6.4.1: 
• 
• 
• 
• 
• 
2.5% 
90% 
8 
0.244 
10% 
1-sided significance level 
Power 
Median time to event (in weeks) in placebo 
Hazard ratio (rilonacept/placebo) 
Percentage of subjects in the RI period that will not reach RW 
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Given these assumptions, a total of 22 adjudicated pericarditis recurrence events is required to 
achieve the power. About 25 subjects per arm (a total of 50 subjects) will be randomized. Considering 
10% of subjects in the RI period that will not reach the RW period, approximately 56 subjects will be 
enrolled in this study. 
Patient enrollment and the pericarditis recurrence event accrual will be closely monitored during the 
study. The monitoring activities will be done in a blinded fashion during the RW period. If the 
number of patients randomized is less than 50 and/or the time anticipated for the number of events 
required for the analysis of primary efficacy endpoint significantly exceeds the projected timeline, 
additional patients may be enrolled and/or randomized at Kiniksa Pharmaceutical’s discretion. 
However, at this time it is anticipated that no more than 75 subjects will be enrolled into this study. 
Since the data cutoff will be the event date of the 22nd adjudicated pericarditis recurrence AND all 
subjects still in the RW period have been treated for 24 weeks, the actual power could be higher if the 
assumed hazard ratio holds. 
7.5 
Analysis Sets 
The following analysis sets will be used in the statistical analyses. 
Intent-to-Treat (ITT) Analysis Set: All subjects who are randomized in the RW period will be 
included in the ITT analysis set. The primary analysis for efficacy endpoints in the RW period will be 
based on the ITT analysis set. Treatment comparisons for all ITT analyses will be based on each 
subject’s treatment assignment from randomization. 
Safety Analysis Set: All subjects who take at least 1 dose of study drug in the RI period will be 
included in the safety analysis set (SS). Safety analyses will be based on the actual treatment a subject 
received. 
Run-in Analysis Set: All subjects who received at least 1 dose of study drug in the RI period will be 
included in the RI analysis set (RIS). 
Per-protocol Analysis Set: The per protocol (PP) analysis set is a subset of the ITT analysis set with 
the exclusion of subjects with major protocol violations or violations that may potentially bias 
statistical analyses or the ethical conduct of the study. The criteria of these violations will be 
determined prior to unblinding. This analysis set may be used for sensitivity analyses for efficacy 
endpoints in the RW period. 
Pharmacokinetic Analysis Set: The PK analysis set includes subjects who receive at least 1 dose of 
study drug and have at least 1 PK sample. The PK analysis set will be used for all PK analyses. 
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7.6 
Description of Subgroups to be Analyzed 
Subgroup analyses for the primary endpoint will be performed by the stratification variable for 
randomization, as well as by important variables for baseline demographics and patient 
characteristics. These analyses are for the RW period only. Details will be provided in the SAP. 
7.7 
Statistical Analysis Methodology 
This section outlines the overall methodologies. Details of the statistical analyses, methods, and data 
conventions will be described in the SAP. 
7.7.1 General Methods 
Statistical analysis will be performed using SAS® software Version 9.4 or later. Continuous variables 
will be summarized using the mean, the standard deviation, median, minimum value, and maximum 
value. Time-to-event variables will be summarized using percent censored, event rate, and 25th, 50th, 
75th 
and 
percentiles with 95% CI, if estimable. Categorical variables will be summarized using 
frequency counts and percentages. Data will be listed in data listings. 
At each of RI and RW periods and in the LTE-TP, baseline will be the last value before the first dose 
of study drug within each individual period unless otherwise specified. For change-over-time 
endpoints in the RW period, by-visit analysis will be performed at each scheduled visit for at least 
24 weeks. 
7.7.2 Stratified Analysis 
There will be 2 stratification variables for randomization: 
• 
• 
Oral CS use at RI baseline: yes or no 
Diagnosis of recurrent idiopathic pericarditis at RI baseline: yes or no 
When a stratified analysis is used in the analysis and a stratum has no event of interest or no 
responder, the stratum will be pooled with the other stratum in the same stratification variable. 
7.7.3 Testing Hypotheses and Multiplicity Adjustment 
All statistical tests for the treatment comparison of efficacy endpoints in the RW period will be based 
on the ITT analysis set with 1-sided α=0.025. For each endpoint, the null hypothesis is that the effects 
of rilonacept and placebo are the same. The alternative hypothesis is that rilonacept is better than the 
placebo. 
In order to control the overall 1-sided type I error rate at the 0.025 level, a gatekeeping procedure in 
combination with Hochberg’s procedure will be applied to testing the primary and major secondary 
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endpoints. If the 1-sided p-value for testing the primary endpoint is ≤0.025, a significant treatment 
effect on the primary endpoint will be claimed. 
Section 7.2.1 provides the order of major secondary endpoints. If the primary endpoint is significant, 
the first major secondary endpoint, i.e., proportion of subjects who maintained Clinical Response at 
Week 24 of RW period will be tested at 1-sided α=0.025. A significant treatment effect on this major 
secondary endpoint will be claimed if the 1-sided p-value is ≤0.025. If the treatment effect is not 
significant on the primary endpoint, significance on this major secondary endpoint cannot be claimed 
regardless of the result. 
If both primary and first major secondary endpoints are significant following the above procedure, 
the second and third major secondary endpoints defined in Section 7.2.1 will be tested with Hochberg’s 
procedure at overall 1-sided α=00.52. If both 1-sided unadjusted p-values are ≤0.025, claim 
significance of rilonacept for both endpoints. If the larger 1-sided p-value is >0.025, compare the 
smaller 1-sided p-value with 0.0125. If the smaller 1-sided p-value is ≤0.0125, claim significance of 
rilonacept on this endpoint. 
7.7.4 Analysis of Primary Efficacy Endpoint 
22nd 
Primary analysis of this study will be done after 
CEC-confirmed pericarditis recurrence AND 
after all subjects in the RW period have been treated for 24 weeks. The log rank test will be the 
primary method for the analysis of time to recurrence, stratified by the stratification variables for 
randomization. 
A sensitivity analysis will be performed based on the investigator’s judgement of pericarditis 
recurrence. Additional sensitivity may be defined in the SAP. 
7.7.5 
7.7.5.1 
Analysis of Secondary Efficacy Endpoints 
Analysis of the Major Secondary Endpoints 
1. Proportion of subjects who maintained Clinical Response at Week 24 of the RW period 
(defined as a weekly average of daily pericarditis pain ≤2.0 on the 11-point NRS and CRP 
≤0.5 mg/dL at Week 24). The Cochran–Mantel–Haenszel (CMH) test will be used in this 
analysis, stratified by the stratification variables for randomization. 
2. Percentage of days with minimal or no pain in the first 24 weeks post randomization. Minimal 
or no pain is defined as non-missing daily NRS ≤1. This endpoint will be analyzed with an 
analysis of covariance. In addition to treatment arm, the following covariates will be included 
in this analysis: the stratification variables for randomization, and baseline NRS weekly 
average in 2 categories: NRS ≤1 versus NRS >1. 
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3.   Proportion of subjects with absent or minimal pericarditis symptoms (based on the 7-point 
PGIPS) at Week 24 of the RW period. The CMH test will be used in this analysis, stratified by 
the stratification variables for randomization. 
7.7.5.2 
Analyses of Other Secondary Endpoints in the RW Period 
The following endpoints will be analyzed using the same method for the primary endpoint: 
• 
• 
• 
• 
• 
Time to pericarditis pain NRS ≥4 
Time to CRP level ≥1 mg/dL 
Time to pericardial rub 
Time to widespread ST-segment elevation or PR-segment depression on ECG 
Time to new or worsening pericardial effusion on ECHO 
A mixed model with repeated measures (MMRM) will be used in the analysis of the endpoints below. 
In the model, subjects will have repeated measures for the response variable change from baseline of 
the endpoint. The explanatory variables will include the baseline value, treatment arm, and the 
variables for stratification at randomization. The p-value for treatment comparison will be calculated 
at each scheduled assessment for at least 24 weeks as part of the summary statistics. This is done with 
the understanding that the comparison could be biased due to dropouts or subjects with pericarditis 
recurrence. 
• 
• 
• 
• 
• 
• 
Change over time in CRP levels 
Change over time in the subject’s assessments of pericarditis pain (weekly average) 
Change over time in the SF-36 Physical Component Score 
Change over time in the SF-36 Mental Component Score 
Change in the EQ-5D-5L: Health score and Index value, respectively 
Change over time in the subject’s sleep quality: sum of the ISI scores. 
The CMH test will be used in the analysis of the endpoints below, stratified by the stratification 
variables for randomization. 
• 
• 
Proportion of patients without pericarditis recurrence in the first 24 weeks of the RW period 
Number (percent) of subjects with absent or minimal pericarditis activity based on the 
investigator’s assessment 
Number (percentage) of subjects who receive SOC pericarditis therapy in the RW period 
• 
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The following endpoints will be analyzed using the Mantel-Haenszel test with 1 degree of freedom: 
• 
Change in each 1 of the first 5 questions in the EQ-5D-5L, i.e., mobility, self-care, usual 
activities, pain/discomfort, and anxiety/depression 
Change over time in ISI categories 
• 
7.7.6 Analyses of Other Endpoints 
Endpoints listed in Section 7.3 for the RI period and the LTE-TP will be descriptive in nature since 
there is no control arm. Summary statistics will be generated following the methodologies stated in 
Section 7.7. 
Other analyses include anti-rilonacept antibodies and biomarker analyses. These analyses will be 
described in the SAP. 
7.7.7 Pharmacokinetic Analyses 
For all subjects, serum samples will be collected at time points shown in the Study Schedule of 
Activities in order to quantify concentrations of rilonacept. Descriptive statistics will be calculated for 
the serum concentrations of rilonacept by visit. Individual listings of serum concentrations will be 
provided. 
Pharmacokinetic data may be used in a subsequent population PK evaluation that will be conducted 
outside of this study and described in a separate report. 
7.7.8 Safety Analyses 
Treatment-emergent AEs (TEAEs), defined as AEs that start or increase in severity after the first dose 
of study drug and before 6 weeks after the last dose of study drug, will be coded to system organ class 
and preferred term using the most recent version of MedDRA. TEAEs will be analyzed for all 
subjects combined and by treatment group in the RW period. Further analyses by severity and 
relationship to study drug as well as analyses of serious TEAEs will be presented. 
Descriptive statistics will be used to summarize safety endpoints by visit for all subjects combined in 
the RI period and by treatment group in the RW period. Two-sided 95% CIs will be presented where 
meaningful. Data summaries will be displayed for clinical laboratory analyses (including safety 
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laboratory measurements, ADAs, etc.), vital signs measurements, ECGs, and physical examination 
findings. 
7.7.9 Interim Analyses 
No interim analyses are planned for this study. 
8 
Data Quality Assurance 
Assessment of subject compliance and adherence to study drug administration will be assessed by the 
site in collaboration with the visiting RN. 
This study will be conducted according to the ICH E6(R2) risk and quality processes described in the 
applicable procedural documents. The quality management approach to be implemented in this study 
will be documented and will comply with the current ICH guidance on quality and risk management 
(ICH Q9). 
8.1 
Data Management 
As part of the responsibilities assumed by participating in the study, the investigator agrees to 
maintain adequate case histories for the subjects treated as part of the research under this protocol. 
The investigator agrees to maintain accurate eCRFs and source documentation as part of the case 
histories. These source documents may include laboratory reports, ECG strips, etc. 
will be responsible for activities associated with the data management of this study. This will 
include setting up a relevant database and data transfer mechanisms, along with appropriate validation 
of data and resolution of queries. Data generated within this clinical study will be handled according 
to the relevant Standard Operating Procedures (SOPs) of 
Investigative site personnel will enter subject data into an EDC system. The analysis data sets will be 
a combination of these data and data from other sources (e.g., laboratory data). 
Clinical data management will be performed in accordance with applicable 
standards and data 
cleaning procedures to ensure the integrity of the data, e.g., removing errors and inconsistencies in the 
data. Adverse event terms will be coded using MedDRA, an internal validated medical dictionary, 
and concomitant medications will be coded using the World Health Organization Drug Dictionary. 
After the last study database lock, each study site will receive a CD-ROM containing all of their site 
specific eCRF data as entered into Medidata Rave for the study, including full discrepancy and audit 
history. Additionally, a Master DVD/CD-ROM copy of all of the site data from the study will be 
created and sent to Kiniksa for storage. 
will maintain a duplicate Master DVD/CD-ROM copy 
for their records. In all cases, subject initials will not be collected or transmitted to Kiniksa 
Pharmaceuticals. 
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9 
Ethics 
9.1 
Independent Ethics Committee or Institutional Review Board 
Regulatory agencies and the ICH guidelines require that approval be obtained from an IRB/IEC 
before participation of human subjects in research studies. Before study onset, the protocol, informed 
consent, informed assent, advertisements to be used for the recruitment of study subjects, and any 
other written information regarding this study to be provided to the subject or the subject’s legal 
guardian must be approved by the IRB/IEC. Documentation of all IRB/IEC approvals and of the 
IRB/IEC compliance with ICH harmonised tripartite guideline E6(R2): Good Clinical Practice (GCP) 
will be maintained by the site and will be available for review by Kiniksa Pharmaceutical or its 
designee. 
All IRB/IEC approvals should be signed by the IRB/IEC chairman or designee and must identify the 
IRB/IEC name and address, the clinical protocol by title or protocol number or both, and the date 
approval or a favorable opinion was granted. 
The investigator is responsible for providing written summaries of the progress and status of the study 
at intervals not exceeding 1 year or otherwise specified by the IRB/IEC. The investigator must 
promptly supply Kiniksa Pharmaceutical or its designee, the IRB/IEC, and, where applicable, the 
institution, with written reports on any changes significantly affecting the conduct of the study or 
increasing the risk to subjects. 
9.2 
Ethical Conduct of the Study 
The study will be performed in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki, ICH GCP, the protocol, and all applicable regulations. 
9.3 
Subject Information and Consent 
A written informed consent in compliance approved by an IRB/IEC, as appropriate, at each 
center/country shall be obtained from each subject before entering the study or performing any 
unusual or nonroutine procedure that involves risk to the subject. An informed consent for (or assent 
form, as applicable) template may be provided by Kiniksa Pharmaceutical or its designee to 
investigative sites. If any institution-specific modifications to study-related procedures are proposed 
or made by the site, the consent should be reviewed by Kiniksa Pharmaceutical or its designee or both 
before IRB/IEC submission. Once reviewed, the consent will be submitted by the investigator to his 
or her IRB/IEC for review and approval before the start of the study. If the ICF is revised during the 
course of the study, all active participating subjects must sign the revised form. 
Before screening, each prospective subject or his or her legal guardian will be given a full explanation 
of the study and be allowed to read the approved ICF. Once the investigator is assured that the 
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subject/legal guardian understands the implications of participating in the study, the subject/legal 
guardian will be asked to give consent to participate in the study by signing the ICF. 
It should be emphasized to the subjects that they may withdraw from the study at any time and for 
any reason without prejudice to their future medical care by the investigator or at the study site. 
Subjects who refuse to give or who withdraw written informed consent should not be included or 
continue in the study. 
For potential subjects under the age of 18, a parent or legal guardian is required to sign and date the 
ICF and the potential subject is also required to sign and date an informed assent form. The informed 
assent form explains the trial, it’s purpose, procedures as well as risk and benefits in age-appropriate 
language. Both the ICF and informed assent form, as applicable, are required prior to participation in 
the trial. The investigator shall retain the signed original ICF(s)/assent form(s), as applicable, and give 
a copy of the signed original form to the subject or legal guardian. 
For this study subjects will be required to sign and date the ICF (or assent form, if applicable) prior to 
entry to the study and prior to entry to LTE. 
In addition, a separate ICF (assent, if applicable) will be needed for subjects participating in 
pharmacogenomic testing. 
10 Investigator’s Obligations 
The following administrative items are meant to guide the investigator in the conduct of the study but 
may be subject to change based on local or country-specific industry and government standard 
operating procedures, working practice documents, or guidelines. 
10.1 Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records will be identified in a manner 
designed to maintain subject confidentiality. All records will be kept in a secure storage area with 
limited access. Clinical information will not be released without the written permission of the subject 
(or the subject’s legal guardian), except as necessary for monitoring and auditing by Kiniksa 
Pharmaceuticals, its designee, the regulatory agencies/authorities, or the IRB/IEC. 
The Investigator and all employees and co-workers involved with this study may not disclose or use 
for any purpose other than performance of the study any data, record, or other unpublished, 
confidential information disclosed to those individuals for the purpose of the study. Prior written 
agreement from Kiniksa Pharmaceuticals or its designee must be obtained for the disclosure of any 
said confidential information to other parties. 
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10.2 Financial Disclosure and Obligations 
Investigators   are   required to   provide   financial disclosure   information   to allow   Kiniksa 
Pharmaceuticals or its designee to submit the complete and accurate certification or disclosure 
statements required under US Title 21 Code of Federal Regulations (CFR) Part 54. In addition, the 
investigator must provide to Kiniksa Pharmaceuticals a commitment to promptly update this 
information if any relevant changes occur during the course of the investigation and for 1 year 
following the completion of the study. 
Neither Kiniksa Pharmaceuticals nor 
is financially responsible for further testing or treatment of 
any medical condition that may be detected during the screening process. In addition, in the absence 
of specific arrangements, neither Kiniksa Pharmaceuticals nor 
further treatment of the subject’s disease. 
is financially responsible for 
10.3 Investigator Documentation 
Prior to beginning the study, the investigator will be asked to comply with ICH E6(R2) 8.2 and Title 
21 of the CFR by providing the following essential documents, including but not limited to: 
• 
• 
• 
IRB/IEC approval 
Original investigator-signed investigator agreement page of the protocol 
Form FDA 1572, fully executed, and all updates on a new fully executed Form FDA 1572 or 
local country-specific equivalent for outside the US 
Curriculum vitae for the investigator and each sub-investigator listed on Form FDA 1572 
Financial disclosure information 
IRB/IEC-approved ICFs/assent forms, as applicable, samples of site advertisements for 
recruitment for this study, and any other written information regarding this study that is to be 
provided to the subject or legal guardian 
Laboratory certifications and normal ranges for any local laboratories used by the site, in 
accordance with 42 CFR 493 
• 
• 
• 
• 
10.4 Study Conduct 
The investigator agrees that the study will be conducted according to the principles of ICH E6(R2). 
The investigator will conduct all aspects of this study in accordance with all national, state, and local 
laws or regulations. Study information from this protocol will be posted on publicly available clinical 
trial registers before enrollment of subjects begins. 
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10.5 Adherence to Protocol 
The investigator agrees to conduct the study as outlined in this protocol in accordance with ICH 
E6(R2) and all applicable guidelines and regulations. 
10.6 Adverse Events and Study Report Requirements 
By participating in this study, the investigator agrees to submit reports of SAEs to 
and/or 
IRB/IEC according to the time line and method outlined in the protocol. In addition, the investigator 
agrees to submit annual reports to the study site IRB/IEC as appropriate. 
10.7 Investigator’s Final Report 
Upon completion of the study, the investigator, where applicable, should inform the institution; the 
investigator/institution should provide the IRB/IEC with a summary of the study’s outcome and 
Kiniksa Pharmaceuticals and regulatory authority(ies) with any reports required. 
10.8 Records Retention 
It is the responsibility of the investigator to ensure all essential trial documentation and source records 
(e.g., signed ICFs, study site/clinic files, subjects’ hospital notes, copies of eCRFs) at their site are 
securely retained. The Sponsor will inform the investigator of the time periods for retaining study 
records to comply with all applicable regulatory requirements. The minimum retention time will meet 
the strictest standard applicable to that site for the study, as dictated by any institutional requirements 
or local laws or regulations; otherwise, the retention period by default will be 15 years. 
10.9 Publications 
Kiniksa shall have the sole and exclusive right to publish information obtained from the study, 
including any data, results, and conclusions. Investigators are encouraged to participate in the study 
execution such that they may be invited to participate in the authorship of a potential publication in a 
manner commensurate with their participation in the study execution in accordance with International 
Committee of Medicinal Journal Editors standards. Any publication of the results will be subject to 
the terms and conditions provided in the study agreement. 
11 Study Management 
The administrative structure will include a Data Monitoring Committee (DMC) and a Clinical 
Endpoint Committee (CEC). Please refer to Section 6.7 for further details. 
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11.1 Monitoring 
11.1.1 Monitoring of the Study 
Data for each subject will be recorded in source records and in the eCRF. Data collection must be 
completed for each subject who signs an ICF. 
For each subject enrolled, the investigator or designee will document in the source records of the 
subject that the subject is enrolled in this study along with all safety and efficacy information. The 
investigator is responsible for maintaining adequate case histories in the source records of each 
subject. Source data should be preserved for the maximum period of time permitted by the 
hospital/institution and made available by the investigator in the cases described above. 
In accordance with current GCP and ICH guidelines, the study monitor will carry out source 
document verification at regular intervals to ensure that the data collected in the eCRF are accurate 
and reliable. 
11.1.2 Inspection of Records 
Investigators and institutions involved in the study will permit study-related monitoring, audits, 
IRB/IEC review, and regulatory inspections by providing direct access to all study records. In the 
event of an audit, the investigator agrees to allow Kiniksa Pharmaceuticals, representatives of Kiniksa 
Pharmaceuticals, or a regulatory agency(ies) access to all study records. 
The investigator should promptly notify Kiniksa Pharmaceuticals and 
of any audits scheduled by 
any regulatory authorities and promptly forward copies of any audit reports received to Kiniksa 
Pharmaceuticals and 
11.2 Management of Protocol Amendments and Deviations 
11.2.1 Modification of the Protocol 
Sponsor initiated amendments to the protocol must be submitted in writing to the investigator’s 
IRB/IEC for approval and to the regulatory authorities, if required, before subjects can be enrolled 
into an amended protocol. 
11.2.2 Protocol Deviations 
A deviation from the protocol is any change, divergence, or departure from the study design or 
procedures defined in the protocol. No waivers will be granted for exemptions to inclusion/exclusion 
criteria. The Investigator will conduct the study in compliance with the protocol agreed to with the 
Sponsor and, if required, the regulatory authorities, and which was given approval/favorable opinion 
by the IRB/IEC. In the event of a protocol deviation, the Sponsor or a designee must be notified. 
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The Investigator, or person designated by the Investigator, must document and explain any deviation 
from the approved protocol. The Investigator will notify the IRB/IEC of deviations from the protocol 
in accordance with local procedures. 
11.3 Study Termination 
Although Kiniksa Pharmaceuticals has every intention of completing the study, Kiniksa 
Pharmaceuticals reserves the right to discontinue the study at any time in case of safety concerns 
(e.g., SUSARs) or if special circumstances concerning the study drug or the company itself occur, 
making further treatment of subjects impossible. In this event, the investigator(s) will be informed of 
the reason for study termination. 
The end of the study is defined as the date on which the last subject completes the last visit (includes 
follow-up visit). 
11.4 Final Report 
Whether the study is completed or prematurely terminated, Kiniksa Pharmaceutical will ensure that 
the clinical study report(s) are prepared and provided to the regulatory agency(ies) as required by the 
applicable regulatory requirement(s). The Sponsor will also ensure that the clinical study reports in 
marketing applications meet the standards of the ICH harmonised tripartite guideline E3: Structure 
and content of clinical study reports. 
Where required by applicable regulatory requirements, an investigator signatory will be identified to 
approve the clinical study report. The investigator will be provided reasonable access to statistical 
tables, figures, and relevant reports and will have the opportunity to review the complete study 
results. 
Upon completion of the clinical study report, Kiniksa Pharmaceutical will provide the investigator(s) 
with the full summary of the study results. The investigator(s) are encouraged to share the summary 
results with the study subjects, as appropriate. The study results will be posted on publicly available 
clinical trial registers, as applicable. 
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12 Reference List 
Adler Y, Charron P, Imazio M, et al. 2015 ESC Guidelines for the diagnosis and management of 
pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the 
European Society of Cardiology (ESC) Endorsed by: The European Association for Cardio-Thoracic 
Surgery (EACTS). Eur Heart J. 2015;36(42):2921-2964. 
Agarwal SK, Vallurupalli S, Uretsky BF, et al. Effectiveness of colchicine for the prevention of 
recurrent pericarditis and post-pericardiotomy syndrome: an updated meta-analysis of randomized 
clinical data. Eur Heart J Cardiovasc Pharmacother. 2015;1(2):117-125. 
Baskar S, Klein AL, Zeft A. The use of IL-1 receptor antagonist (anakinra) in idiopathic recurrent 
pericarditis: A narrative review. Cardiol Res Pract. 2016;2016:7840724. 
Brucato A, Imazio M, Gattorno M, et al. Effect of anakinra on recurrent pericarditis among patients 
with colchicine resistance and corticosteroid dependence: The AIRTRIP randomized clinical trial. 
JAMA. 2016;316(18):1906-1912. 
Cantarini L, Lopalco G, Selmi C, et al. Autoimmunity and autoinflammation as the yin and yang of 
idiopathic recurrent acute pericarditis. Autoimmun Rev. 2015;14(2):90-97. 
Dinarello CA, Simon A, van der Meer JW. Treating inflammation by blocking interleukin-1 in a 
broad spectrum of diseases. Nat. Rev. Drug Discov. 2012; 11(8):633-652. 
Dworkin RH, Turk DC, Farrar JT, et al. Core outcome measures for chronic pain clinical trials: 
IMMPACT recommendations. Pain. 2005;113(1-2):9-19. 
Garg M, de Jesus AA, Chapelle D, et al. Rilonacept maintains long-term inflammatory remission in 
patients with deficiency of the IL-1 receptor antagonist. JCI Insight. 2017;2(16):e94838. 
Goldbach-Mansky R, Shroff S, Wilson M, et al. A pilot study to evaluate the safety and efficacy of 
the long-acting IL-1 inhibitor, rilonacept (IL-1 Trap) in patients with familial cold autoinflammatory 
syndrome (FCAS). Arthritis Rheum. 2008;58(8):2432-2442. 
Guy W. Clinical global impressions. In: U.S. Department of Health, Education, and Welfare, Public 
Health 
Service, 
Alcohol, 
Drug 
Abuse, 
and 
Mental 
Health 
Administration, 
NIMH 
Psychopharmacology Research Branch, Division of Extramural Research Programs, eds. ECDEU 
Assessment Manual for Psychopharmacology. Rockville, MD: National Institute for Mental Health; 
1976:218–22. Revised DHEW Pub No ADM 76–338. 
Hawker GA, Mian S, Kendzerska T, et al. Measures of adult pain: visual analog scale for pain (VAS 
Pain), numeric rating scale for pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form 
McGill Pain Questionnaire (SF-MPQ), chronic pain grade scale (CPGS), Short Form-36 Bodily Pain 
Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis 
Care Res. 2011;63(Suppl 11):S240-S252. 
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Imazio M, Brucato A, Pluymaekers N, et al. Recurrent pericarditis in children and adolescents:a 
multicenter cohort study. J Cardiovasc Med 2016; 17(9):707-712. 
Imazio M. Treatment of recurrent pericarditis. Rev Esp Cardiol. 2014;67(5):345-348. 
Imazio M, Spodick DH, Brucato A, et al. Controversial issues in the management of pericardial 
diseases. Circulation. 2010; 121(7):916-928. 
Imazio M, Brucato A, Trinchero R, et al. Corticosteroid therapy for pericarditis: a double-edged 
sword. Nature Clinical Practice Cardiovascular Medicine. 2008;5(3):188-119. 
Imazio M, Cecchi E, Demichelis B, et al. Myopericarditis versus viral or idiopathic acute 
pericarditis. Heart. 2008;94:498-501. 
Imazio M, Demichelis B, Parrini I, et al. Management, risk factors, and outcomes in recurrent 
pericarditis. Am J Cardiol. 2005;96(5):736-739. 
Khandaker MH, Espinosa RE, Nishimura RA, et al. Pericardial disease: diagnosis and management. 
Mayo Clin Proc. 2010; 85(6):572-593. 
Lazaros G, Imazio M, Brucato A, et al. Anakinra: an emerging option for refractory idiopathic 
recurrent pericarditis: a systematic review of published evidence. J Cardiovasc Med. 2016;17(4):256-
262. 
Lilly SL. Treatment of acute and recurrent idiopathic pericarditis. Circulation. 
2013;127(16):1723-1726. 
Lotrionte M, Biondi-Zoccai G, Imazio M, et al. International collaborative systematic review of 
controlled clinical trials on pharmacologic treatments for acute pericarditis and its recurrences. Am 
Heart J. 2010; 160(4):662-670. 
Maisch B, Seferović PM, Ristić AD, et al. Guidelines on the diagnosis and management of 
pericardial diseases executive summary: The Task Force on the Diagnosis and Management of 
Pericardial Diseases of the European Society of Cardiology. Eur Heart J. 2004;25(7):587-610. 
Mannion AF, Balagué F, Pellisé F, et al. Pain measurement in patients with low back pain. Nat Clin 
Practice Rheumatol. 2007;3(11):610-618. 
Morin CM, Belleville G, Bélanger L, et al. The insomnia severity index: psychometric indicators to 
detect insomnia cases and evaluate treatment response. Sleep. 2011;34(5):601-608. 
Theodoropoulou K, von Scheven-Gête A, Bressieux-Degueldre S, et al. A case of corticosteroid- 
dependent recurrent pericarditis with different response to two IL-1 blocking agents. Pediatr 
Rheumatol Online J. 2015;13(Suppl 1):P155. 
van Reenen M, Janssen B. EQ-5D-5L User Guide. Version 2.1. April 2015. Available 
from: https://euroqol.org/wp-content/uploads/2016/09/EQ-5D-5L_UserGuide_2015.pdf. 
Zayas R, Anguita M, Torres F, et al. Incidence of specific etiology and role of methods for specific 
etiologic diagnosis of primary acute pericarditis. Am J Cardiol. 1995;75(5):378-382. 
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13 Appendices 
13.1 Appendix: ARCALYST® 
Information 
Prescribing 
CONTRAINDICATIONS 
HIGHLIGHTS OF PRESCRIBING INFORMATION 
These highlights do not include all the information needed 
to use ARCALYST safely and effectively. See full 
prescribing information for ARCALYST. 
None. (4) 
WARNINGS AND PRECAUTIONS 
• Interleukin-1 blockade may interfere with immune 
response to infections. Serious, life-threatening infections 
have been reported in patients taking ARCALYST. 
Discontinue treatment with ARCALYST if a patient 
develops a serious infection. Do not initiate treatment with 
ARCALYST in patients with active or chronic infections. 
(5.1) 
Hypersensitivity reactions associated with ARCALYST 
administration have been rare. If a hypersensitivity 
reaction occurs, discontinue administration of 
ARCALYST and initiate appropriate therapy. (5.5) 
Live vaccines should not be given concurrently with 
ARCALYST. Prior to initiation of therapy with 
ARCALYST, patients should receive all recommended 
vaccinations. (5.3) 
ARCALYST® (rilonacept) 
Injection for Subcutaneous Use 
Initial U.S. Approval: 2008 
INDICATIONS AND USAGE 
ARCALYST (rilonacept) is an interleukin-1 blocker indicated 
for the treatment of Cryopyrin-Associated Periodic Syndromes 
(CAPS), including Familial Cold Auto-inflammatory 
Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in 
adults and children 12 and older. (1) 
• 
• 
DOSAGE AND ADMINISTRATION 
• Adult patients 18 yrs and older: Initiate treatment with a 
loading dose of 320 mg delivered as two, 2-mL, 
subcutaneous injections of 160 mg on the same day at two 
different sites. Continue dosing with a once-weekly 
injection of 160 mg administered as a single, 2-mL, 
subcutaneous injection. Do not administer ARCALYST 
more often than once weekly. (2) 
Pediatric patients aged 12 to 17 years: Initiate treatment 
with a loading dose of 4.4 mg/kg, up to a maximum of 320 
mg, delivered as one or two subcutaneous injections with a 
maximum single-injection volume of 2 mL. Continue 
dosing with a once-weekly injection of 2.2 mg/kg, up to a 
maximum of 160 mg, administered as a single 
subcutaneous injection, up to 2 mL. If the initial dose is 
given as two injections, they should be given on the same 
day at two different sites. Do not administer ARCALYST 
more often than once weekly. (2) 
ADVERSE REACTIONS 
The most common adverse reactions reported by patients with 
CAPS treated with ARCALYST are injection-site reactions 
and upper respiratory tract infections. (6.2, 6.3) 
• 
To report SUSPECTED ADVERSE REACTIONS, contact 
Regeneron at 1-877-REGN-777 (1-877-734-6777) or FDA 
at 1-800-FDA-1088 or www.fda.gov/medwatch. 
DRUG INTERACTIONS 
No formal drug interaction studies have been conducted with 
ARCALYST. (7) 
USE IN SPECIFIC POPULATIONS 
Pregnancy – No human data. Based on animal data, may cause 
fetal harm. (8.1) 
DOSAGE FORMS AND STRENGTHS 
Sterile, single-use 20-mL, glass vial containing 220 mg of 
rilonacept as a lyophilized powder for reconstitution. (3) 
See 17 for PATIENT COUNSELING INFORMATION 
and FDA-approved patient labeling. 
Revised: 9/2016 
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FULL PRESCRIBING INFORMATION 
1 
INDICATIONS AND USAGE 
ARCALYST® (rilonacept) is an interleukin-1 blocker indicated for the treatment of Cryopyrin-Associated 
Periodic Syndromes (CAPS), including Familial Cold Auto-inflammatory Syndrome (FCAS) and 
Muckle-Wells Syndrome (MWS) in adults and children 12 and older. 
2 
2.1 
DOSAGE AND ADMINISTRATION 
General Dosing Information 
Injection for Subcutaneous Use Only. 
2.2 
Dosing 
Adult patients 18 years and older: Treatment should be initiated with a loading dose of 320 mg delivered 
as two, 2-mL, subcutaneous injections of 160 mg each given on the same day at two different sites. 
Dosing should be continued with a once-weekly injection of 160 mg administered as a single, 2-mL, 
subcutaneous injection. ARCALYST should not be given more often than once weekly. Dosage 
modification is not required based on advanced age or gender. 
Pediatric patients aged 12 to 17 years: Treatment should be initiated with a loading dose of 4.4 mg/kg, up 
to a maximum of 320 mg, delivered as one or two subcutaneous injections with a maximum single- 
injection volume of 2 mL. Dosing should be continued with a once-weekly injection of 2.2 mg/kg, up to a 
maximum of 160 mg, administered as a single subcutaneous injection, up to 2 mL. If the initial dose is 
given as two injections, they should be given on the same day at two different sites. ARCALYST should 
not be given more often than once weekly. 
2.3 
Preparation for Administration 
Each single-use vial of ARCALYST contains a sterile, white to off-white, preservative-free, lyophilized 
powder. Reconstitution with 2.3 mL of preservative-free Sterile Water for Injection (supplied separately) 
is required prior to subcutaneous administration of the drug. 
2.4 
Administration 
Using aseptic technique, withdraw 2.3 mL of preservative-free Sterile Water for Injection through a 27- 
gauge, ½-inch needle attached to a 3-mL syringe and inject the preservative-free Sterile Water for 
Injection into the drug product vial for reconstitution. The needle and syringe used for reconstitution with 
preservative-free Sterile Water for Injection should then be discarded and should not be used for 
subcutaneous injections. After the addition of preservative-free Sterile Water for Injection, the vial 
contents should be reconstituted by shaking the vial for approximately one minute and then allowing it to 
sit for one minute. The resulting 80-mg/mL solution is sufficient to allow a withdrawal volume of up to 2 
mL for subcutaneous administration. The reconstituted solution is viscous, clear, colorless to pale yellow, 
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and essentially free from particulates. Prior to injection, the reconstituted solution should be carefully 
inspected for any discoloration or particulate matter. If there is discoloration or particulate matter in the 
solution, the product in that vial should not be used. 
Using aseptic technique, withdraw the recommended dose volume, up to 2 mL (160 mg), of the solution 
with a new 27-gauge, ½-inch needle attached to a new 3-mL syringe for subcutaneous injection. EACH 
VIAL SHOULD BE USED FOR A SINGLE DOSE ONLY. Discard the vial after withdrawal of drug. 
Sites for subcutaneous injection, such as the abdomen, thigh, or upper arm, should be rotated. Injections 
should never be made at sites that are bruised, red, tender, or hard. 
2.5 
Stability and Storage 
The lyophilized ARCALYST product is to be stored refrigerated at 2° to 8°C (36° to 46°F) inside the 
original carton to protect it from light. Do not use beyond the date stamped on the label. After 
reconstitution, ARCALYST may be kept at room temperature, should be protected from light, and should 
be used within three hours of reconstitution. ARCALYST does not contain preservatives; therefore, 
unused portions of ARCALYST should be discarded. 
3 
DOSAGE FORMS AND STRENGTHS 
ARCALYST is supplied in sterile, single-use, 20-mL, glass vials. Each vial contains 220 mg of rilonacept 
as a white to off-white, preservative-free, lyophilized powder. Reconstitution with 2.3 mL of 
preservative-free Sterile Water for Injection is required prior to subcutaneous administration of the drug. 
The reconstituted ARCALYST is a viscous, clear, colorless to pale yellow, essentially free from 
particulates, 80-mg/mL solution. 
4 
None. 
CONTRAINDICATIONS 
5 
5.1 
WARNINGS AND PRECAUTIONS 
Infections 
Interleukin-1 (IL-1) blockade may interfere with the immune response to infections. Treatment with 
another medication that works through inhibition of IL-1 has been associated with an increased risk of 
serious infections, and serious infections have been reported in patients taking ARCALYST [see Clinical 
Studies (14)]. There was a greater incidence of infections in patients on ARCALYST compared with 
placebo. In the controlled portion of the study, one infection was reported as severe, which was bronchitis 
in a patient on ARCALYST. 
In an open-label extension study, one patient developed bacterial meningitis and died [see Adverse 
Reactions (6.3)]. ARCALYST should be discontinued if a patient develops a serious infection. Treatment 
with ARCALYST should not be initiated in patients with an active or chronic infection. 
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In clinical studies, ARCALYST has not been administered concomitantly with tumor necrosis factor 
(TNF) inhibitors. An increased incidence of serious infections has been associated with administration of 
an IL-1 blocker in combination with TNF inhibitors. Taking ARCALYST with TNF inhibitors is not 
recommended because this may increase the risk of serious infections. 
Drugs that affect the immune system by blocking TNF have been associated with an increased risk of 
reactivation of latent tuberculosis (TB). It is possible that taking drugs such as ARCALYST that block IL- 
1 increases the risk of TB or other atypical or opportunistic infections. Healthcare providers should follow 
current CDC guidelines both to evaluate for and to treat possible latent tuberculosis infections before 
initiating therapy with ARCALYST. 
5.2 
Immunosuppression 
The impact of treatment with ARCALYST on active and/or chronic infections and the development of 
malignancies is not known [see Adverse Reactions (6.3)]. However, treatment with immunosuppressants, 
including ARCALYST, may result in an increase in the risk of malignancies. 
5.3 
Immunizations 
Since no data are available on either the efficacy of live vaccines or on the risks of secondary 
transmission of infection by live vaccines in patients receiving ARCALYST, live vaccines should not be 
given concurrently with ARCALYST. In addition, because ARCALYST may interfere with normal 
immune response to new antigens, vaccinations may not be effective in patients receiving ARCALYST. 
No data are available on the effectiveness of vaccination with inactivated (killed) antigens in patients 
receiving ARCALYST. 
Because IL-1 blockade may interfere with immune response to infections, it is recommended that prior to 
initiation of therapy with ARCALYST adult and pediatric patients receive all recommended vaccinations, 
as appropriate, including pneumococcal vaccine and inactivated influenza vaccine. (See current 
Recommended Immunizations schedules at the website of the Centers for Disease Control and 
Prevention. http://www.cdc.gov/vaccines/schedules/index.html). 
5.4 
Lipid Profile Changes 
Patients should be monitored for changes in their lipid profiles and provided with medical treatment if 
warranted [see Adverse Reactions (6.7)]. 
5.5 
Hypersensitivity 
Hypersensitivity reactions associated with ARCALYST administration in the clinical studies were rare. If 
a hypersensitivity reaction occurs, administration of ARCALYST should be discontinued and appropriate 
therapy initiated. 
6 
ADVERSE REACTIONS 
Six serious adverse reactions were reported by four patients during the clinical program. These serious 
adverse reactions were Mycobacterium intracellulare infection; gastrointestinal bleeding and colitis; 
sinusitis and bronchitis; and Streptococcus pneumoniae meningitis [see Adverse Reactions (6.3)]. 
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Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
The most commonly reported adverse reaction associated with ARCALYST was injection-site reaction 
(ISR) [see Adverse Reactions (6.2)]. The next most commonly reported adverse reaction was upper 
respiratory infection [see Adverse Reactions (6.3)]. 
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in 
the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and 
may not reflect the rates observed in practice. 
The data described herein reflect exposure to ARCALYST in 600 patients, including 85 exposed for at 
least 6 months and 65 exposed for at least one year. These included patients with CAPS, patients with 
other diseases, and healthy volunteers. Approximately 60 patients with CAPS have been treated weekly 
with 160 mg of ARCALYST. The pivotal trial population included 47 patients with CAPS. These patients 
were between the ages of 22 and 78 years (average 51 years). Thirty-one patients were female and 16 
were male. All of the patients were White/Caucasian. Six pediatric patients (12-17 years) were enrolled 
directly into the open-label extension phase. 
6.1 
Clinical Trial Experience 
Part A of the clinical trial was conducted in patients with CAPS who were naïve to treatment with 
ARCALYST. Part A of the study was a randomized, double-blind, placebo-controlled, six-week study 
comparing ARCALYST to placebo [see Clinical Studies (14)]. Table 1 reflects the frequency of 
adverse events reported by at least two patients during Part A. 
Table 1: 
Most Frequent Adverse Reactions (Part A, Reported by at Least Two Patients) 
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Adverse Event 
 
ARCALYST 
160 mg 
(n = 23) 
Placebo 
(n= 24) 
 
Any AE 
17 (74%) 
13 (54%) 
Injection-site reactions 
11 (48%) 
3 (13%) 
Upper respiratory tract infection 
6 (26%) 
1 (4%) 
Nausea 
1 (4%) 
3 (13%) 
Diarrhea 
1 (4%) 
3 (13%) 
Sinusitis 
2 (9%) 
1 (4%) 
Abdominal pain upper 
0 
2 (8%) 
Cough 
2 (9%) 
0 
Hypoesthesia 
2 (9%) 
0 
Stomach discomfort 
1 (4%) 
1 (4%) 
Urinary tract infection 
1 (4%) 
1 (4%) 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
6.2 
Injection-Site Reactions 
In patients with CAPS, the most common and consistently reported adverse event associated with 
ARCALYST was injection-site reaction (ISR). The ISRs included erythema, swelling, pruritus, mass, 
bruising, inflammation, pain, edema, dermatitis, discomfort, urticaria, vesicles, warmth and hemorrhage. 
Most injection-site reactions lasted for one to two days. No ISRs were assessed as severe, and no patient 
discontinued study participation due to an ISR. 
6.3 
Infections 
During Part A, the incidence of patients reporting infections was greater with ARCALYST (48%) than 
with placebo (17%). In Part B, randomized withdrawal, the incidence of infections were similar in the 
ARCALYST (18%) and the placebo patients (22%). Part A of the trial was initiated in the winter months, 
while Part B was predominantly performed in the summer months. 
In placebo-controlled studies across a variety of patient populations encompassing 360 patients treated 
with rilonacept and 179 treated with placebo, the incidence of infections was 34% and 27% (2.15 per 
patient-exposure year and 1.81 per patient-exposure year), respectively, for rilonacept and placebo. 
Serious Infections: One patient receiving ARCALYST for an unapproved indication in another study 
developed an infection in his olecranon bursa with Mycobacterium intracellulare. The patient was on 
chronic glucocorticoid treatment. The infection occurred after an intraarticular glucocorticoid injection 
into the bursa with subsequent local exposure to a suspected source of mycobacteria. The patient 
recovered after the administration of the appropriate antimicrobial therapy. One patient treated for another 
unapproved indication developed bronchitis/sinusitis, which resulted in hospitalization. One patient died 
in an open-label study of CAPS from Streptococcus pneumoniae meningitis. 
6.4 
Malignancies 
[see Warnings and Precautions (5.2)]. 
6.5 
Hematologic Events 
One patient in a study in an unapproved indication developed transient neutropenia (ANC < 1 x 109/L) 
after receiving a large dose (2000 mg intravenously) of ARCALYST. The patient did not experience any 
infection associated with the neutropenia. 
6.6 
Immunogenicity 
Antibodies directed against the receptor domains of rilonacept were detected by an ELISA assay in 
patients with CAPS after treatment with ARCALYST. Nineteen of 55 patients (35%) who had received 
ARCALYST for at least 6 weeks tested positive for treatment-emergent binding antibodies on at least one 
occasion. Of the 19, seven tested positive at the last assessment (Week 18 or 24 of the open-label 
extension period), and five patients tested positive for neutralizing antibodies on at least one occasion. 
There was no correlation of antibody activity and either clinical effectiveness or safety. 
The data reflect the percentage of patients whose test results were positive for antibodies to the rilonacept 
receptor domains in specific assays, and are highly dependent on the sensitivity and specificity of the 
assays. The observed incidence of antibody (including neutralizing antibody) positivity in an assay is 
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Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
highly dependent on several factors including assay sensitivity and specificity, assay methodology, 
sample handling, timing of sample collection, concomitant medications, and underlying disease. For these 
reasons, comparison of the incidence of antibodies to rilonacept with the incidence of antibodies to other 
products may be misleading. 
6.7 
Lipid Profiles 
Cholesterol and lipid levels may be reduced in patients with chronic inflammation. Patients with CAPS 
treated with ARCALYST experienced increases in their mean total cholesterol, HDL cholesterol, LDL 
cholesterol, and triglycerides. The mean increases from baseline for total cholesterol, HDL cholesterol, 
LDL cholesterol, and triglycerides were 19 mg/dL, 2 mg/dL, 10 mg/dL, and 57 mg/dL respectively after 6 
weeks of open-label therapy. Physicians should monitor the lipid profiles of their patients (for example 
after 2-3 months) and consider lipid-lowering therapies as needed based upon cardiovascular risk factors 
and current guidelines. 
7 
7.1 
DRUG INTERACTIONS 
TNF-Blocking Agent and IL-1 Blocking Agent 
Specific drug interaction studies have not been conducted with ARCALYST. Concomitant administration 
of another drug that blocks IL-1 with a TNF-blocking agent in another patient population has been 
associated with an increased risk of serious infections and an increased risk of neutropenia. The 
concomitant administration of ARCALYST with TNF-blocking agents may also result in similar toxicities 
and is not recommended [see Warnings and Precautions (5.1)]. The concomitant administration of 
ARCALYST with other drugs that block IL-1 has not been studied. Based upon the potential for 
pharmacologic interactions between rilonacept and a recombinant IL-1ra, concomitant administration of 
ARCALYST and other agents that block IL-1 or its receptors is not recommended. 
7.2 
Cytochrome P450 Substrates 
The formation of CYP450 enzymes is suppressed by increased levels of cytokines (e.g., IL-1) during 
chronic inflammation. Thus it is expected that for a molecule that binds to IL-1, such as rilonacept, the 
formation of CYP450 enzymes could be normalized. This is clinically relevant for CYP450 substrates 
with a narrow therapeutic index, where the dose is individually adjusted (e.g., warfarin). Upon initiation 
of ARCALYST, in patients being treated with these types of medicinal products, therapeutic monitoring 
of the effect or drug concentration should be performed and the individual dose of the medicinal product 
may need to be adjusted as needed. 
8 
8.1 
USE IN SPECIFIC POPULATIONS 
Pregnancy 
Pregnancy Category C. There are no adequate and well-controlled studies of ARCALYST in pregnant 
women. Based on animal data, ARCALYST may cause fetal harm. An embryo-fetal developmental 
toxicity study was performed in cynomolgus monkeys treated with 0, 5, 15 or 30 mg/kg given twice a 
week (highest dose is approximately 3.7-fold higher than the human doses of 160 mg based on body 
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Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
surface area). The fetus of the only monkey with exposure to rilonacept during the later period of 
gestation showed multiple fusion and absence of the ribs and thoracic vertebral bodies and arches. 
Exposure to rilonacept during this time period was below that expected clinically. Likewise, in the 
cynomolgus monkey, all doses of rilonacept reduced serum levels of estradiol up to 64% compared to 
controls and increased the incidence of lumbar ribs compared to both control animals and historical 
control incidences. In perinatal and postnatal developmental toxicology studies in the mouse model using 
a murine analog of rilonacept (0, 20, 100 or 200 mg/kg), there was a 3-fold increase in the number of 
stillbirths in dams treated with 200 mg/kg three times per week (the highest dose is approximately 6-fold 
higher than the 160 mg maintenance dose based on body surface area). ARCALYST should be used 
during pregnancy only if the benefit justifies the potential risk to the fetus. 
Nonteratogenic effects. A peri- and post-natal reproductive toxicology study was performed in which 
mice were subcutaneously administered a murine analog of rilonacept at doses of 20, 100, 200 mg/kg 
three times per week (the highest dose is approximately 6-fold higher than the 160 mg maintenance dose 
based on body surface area). Results indicated an increased incidence in unscheduled deaths of the F1 
offspring during maturation at all doses tested. 
8.3 
Nursing Mothers 
It is not known whether rilonacept is excreted in human milk. Because many drugs are excreted in human 
milk, caution should be exercised when ARCALYST is administered to a nursing woman. 
8.4 
Pediatric Use 
Six pediatric patients with CAPS between the ages of 12 and 16 were treated with ARCALYST at a 
weekly, subcutaneous dose of 2.2 mg/kg (up to a maximum of 160 mg) for 24-weeks during the open- 
label extension phase. These patients showed improvement from baseline in their symptom scores and in 
objective markers of inflammation (e.g. Serum Amyloid A and C-Reactive Protein). The adverse events 
included injection site reactions and upper respiratory symptoms as were commonly seen in the adult 
patients. 
The trough drug levels for four pediatric patients measured at the end of the weekly dose interval (mean 
20 mcg/mL, range 3.6 to 33 mcg/mL) were similar to those observed in adult patients with CAPS (mean 
24 mcg/mL, range 7 to 56 mcg/mL). 
Safety and effectiveness in pediatric patients below the age of 12 have not been established. 
When administered to pregnant primates, rilonacept treatment may have contributed to alterations in bone 
ossification in the fetus. It is not known if ARCALYST will alter bone development in pediatric patients. 
Pediatric patients treated with ARCALYST should undergo appropriate monitoring for growth and 
development. [see Use in Specific Populations (8.1)] 
8.5 
Geriatric Use 
In the placebo-controlled clinical studies in patients with CAPS and other indications, 70 patients 
randomized to treatment with ARCALYST were  65 years of age, and 6 were  75 years of age. In the 
CAPS clinical trial, efficacy, safety and tolerability were generally similar in elderly patients as compared 
to younger adults; however, only ten patients  65 years old participated in the trial. In an open-label 
extension study of CAPS, a 71 year old woman developed bacterial meningitis and died [see Adverse 
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Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
Reactions (6.3)]. Age did not appear to have a significant effect on steady-state trough concentrations in 
the clinical study. 
8.6 
Patients with Renal Impairment 
No formal studies have been conducted to examine the pharmacokinetics of rilonacept administered 
subcutaneously in patients with renal impairment. 
8.7 
Patients with Hepatic Impairment 
No formal studies have been conducted to examine the pharmacokinetics of rilonacept administered 
subcutaneously in patients with hepatic impairment. 
10 
OVERDOSAGE 
There have been no reports of overdose with ARCALYST. Maximum weekly doses of up to 320 mg have 
been administered subcutaneously for up to approximately 18 months in a small number of patients with 
CAPS and up to 6 months in patients with an unapproved indication in clinical trials without evidence of 
dose-limiting toxicities. In addition, ARCALYST given intravenously at doses up to 2000 mg monthly in 
another patient population for up to six months were tolerated without dose-limiting toxicities. The 
maximum amount of ARCALYST that can be safely administered has not been determined. 
In case of overdose, it is recommended that the patient be monitored for any signs or symptoms of 
adverse reactions or effects, and appropriate symptomatic treatment instituted immediately. 
11 
DESCRIPTION 
Rilonacept is a dimeric fusion protein consisting of the ligand-binding domains of the extracellular 
portions of the human interleukin-1 receptor component (IL-1RI) and IL-1 receptor accessory protein (IL- 
1RAcP) linked in-line to the Fc portion of human IgG1. Rilonacept has a molecular weight of 
approximately 251 kDa. Rilonacept is expressed in recombinant Chinese hamster ovary (CHO) cells. 
ARCALYST is supplied in single-use, 20-mL glass vials containing a sterile, white to off-white, 
lyophilized powder. Each vial of ARCALYST is to be reconstituted with 2.3 mL of Sterile Water for 
Injection. A volume of up to 2 mL can be withdrawn, which is designed to deliver 160 mg for 
subcutaneous administration only. The resulting solution is viscous, clear, colorless to pale yellow, and 
essentially free from particulates. Each vial contains 220 mg rilonacept. After reconstitution, each vial 
contains 80 mg/mL rilonacept, 46 mM histidine, 50 mM arginine, 3.0% (w/v) polyethylene glycol 3350, 
2.0% (w/v) sucrose, and 1.0% (w/v) glycine at a pH of 6.5 ± 0.3. No preservatives are present. 
12 
12.1 
CLINICAL PHARMACOLOGY 
Mechanism of Action 
CAPS refer to rare genetic syndromes generally caused by mutations in the NLRP-3 [Nucleotide-binding 
domain, leucine rich family (NLR), pyrin domain containing 3] gene (also known as Cold-Induced Auto- 
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Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
inflammatory Syndrome-1 [CIAS1]). CAPS disorders are inherited in an autosomal dominant pattern with 
male and female offspring equally affected. Features common to all disorders include fever, urticaria-like 
rash, arthralgia, myalgia, fatigue, and conjunctivitis. 
In most cases, inflammation in CAPS is associated with mutations in the NLRP-3 gene which encodes the 
protein cryopyrin, an important component of the inflammasome. Cryopyrin regulates the protease 
caspase-1 and controls the activation of interleukin-1 beta (IL-1β). Mutations in NLRP-3 result in an 
overactive inflammasome resulting in excessive release of activated IL-1β that drives inflammation. 
Rilonacept blocks IL-1β signaling by acting as a soluble decoy receptor that binds IL-1β and prevents its 
interaction with cell surface receptors. Rilonacept also binds IL-1α and IL-1 receptor antagonist (IL-1ra) 
with reduced affinity. The equilibrium dissociation constants for rilonacept binding to IL-1β, IL-1α and 
IL-1ra were 0.5 pM, 1.4 pM and 6.1 pM, respectively. 
12.2 
Pharmacodynamics 
C-Reactive Protein (CRP) and Serum Amyloid A (SAA) are indicators of inflammatory disease activity 
that are elevated in patients with CAPS. Elevated SAA has been associated with the development of 
systemic amyloidosis in patients with CAPS. Compared to placebo, treatment with ARCALYST resulted 
in sustained reductions from baseline in mean serum CRP and SAA to normal levels during the clinical 
trial. ARCALYST also normalized mean SAA from elevated levels. 
12.3 
Pharmacokinetics 
The average trough levels of rilonacept were approximately 24 mcg/mL at steady-state following weekly 
subcutaneous doses of 160 mg for up to 48 weeks in patients with CAPS. The steady-state appeared to be 
reached by 6 weeks. 
No pharmacokinetic data are available in patients with hepatic or renal impairment. 
No study was conducted to evaluate the effect of age, gender, or body weight on rilonacept exposure. 
Based on limited data obtained from the clinical study, steady state trough concentrations were similar 
between male and female patients. Age (26-78 years old) and body weight (50-120 kg) did not appear to 
have a significant effect on trough rilonacept concentrations. The effect of race could not be assessed 
because only Caucasian patients participated in the clinical study, reflecting the epidemiology of the 
disease. 
13 
13.1 
NONCLINICAL TOXICOLOGY 
Carcinogenesis, Mutagenesis, Impairment of Fertility 
Long-term animal studies have not been performed to evaluate the carcinogenic potential of rilonacept. 
The mutagenic potential of rilonacept was not evaluated. 
Male and female fertility was evaluated in a mouse surrogate model using a murine analog of rilonacept. 
Male mice were treated beginning 8 weeks prior to mating and continuing through female gestation day 
15. Female mice were treated for 2 weeks prior to mating and on gestation days 0, 3, and 6. The murine 
analog of rilonacept did not alter either male or female fertility parameters at doses up to 200 mg/kg (this 
dose is approximately 6-fold higher than the 160 mg maintenance dose based on body surface area). 
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Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
14 
CLINICAL STUDIES 
The safety and efficacy of ARCALYST for the treatment of CAPS was demonstrated in a randomized, 
double-blind, placebo-controlled study with two parts (A and B) conducted sequentially in the same 
patients with FCAS and MWS. 
Part A was a 6-week, randomized, double-blind, parallel-group period comparing ARCALYST at a dose 
of 160 mg weekly after an initial loading dose of 320 mg to placebo. Part B followed immediately after 
Part A and consisted of a 9-week, patient-blind period during which all patients received ARCALYST 
160 mg weekly, followed by a 9-week, double-blind, randomized withdrawal period in which patients 
were randomly assigned to either remain on ARCALYST 160 mg weekly or to receive placebo. Patients 
were then given the option to enroll in a 24-week, open-label treatment extension phase in which all 
patients were treated with ARCALYST 160 mg weekly. 
Using a daily diary questionnaire, patients rated the following five signs and symptoms of CAPS: joint 
pain, rash, feeling of fever/chills, eye redness/pain, and fatigue, each on a scale of 0 (none, no severity) to 
10 (very severe). The study evaluated the mean symptom score using the change from baseline to the end 
of treatment. 
The changes in mean symptom scores for the randomized parallel-group period (Part A) and the 
randomized withdrawal period (Part B) of the study are shown in Table 2. ARCALYST-treated patients 
had a larger reduction in the mean symptom score in Part A compared to placebo-treated patients. In Part 
B, mean symptom scores increased more in patients withdrawn to placebo compared to patients who 
remained on ARCALYST. 
Table 2: Mean Symptom Scores 
*Differences are adjusted using an analysis of covariance model with terms for treatment and Part A baseline. 
**A confidence interval lying entirely below zero indicates a statistical difference favoring ARCALYST versus 
placebo. 
Daily mean symptom scores over time for Part A are shown in Figure 1. 
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Part A 
 
Placebo 
(n=24) 
ARCALYST 
(n=23) 
Part B 
 
Placebo 
(n=23) 
ARCALYST 
(n=22) 
Pre-treatment 
Baseline Period 
(Weeks -3 to 0) 
2.4 
 
3.1 
 
Active 
ARCALYST 
Baseline Period 
(Weeks 13 to 15) 
0.2 
 
0.3 
 
Endpoint Period 
(Weeks 4 to 6) 
2.1 
 
0.5 
 
Endpoint Period 
(Weeks 22 to 24) 
1.2 
 
0.4 
 
LS* Mean Change 
from Baseline to 
Endpoint 
-0.5 
 
-2.4 
 
LS* Mean Change 
from Baseline to 
Endpoint 
0.9 
 
0.1 
 
95% confidence 
interval for 
difference between 
treatment groups 
(-2.4, -1.3)** 
 
95% confidence 
interval for 
difference between 
treatment groups 
(-1.3, -0.4)** 
 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
Figure 1: Group Mean Daily Symptom Scores by Treatment Group in Part A and 
Single-blind ARCALYST Treatment Phase from Week -3 to Week 15 
Improvement in symptom scores was noted within several days of initiation of ARCALYST therapy in 
most patients. 
In Part A, patients treated with ARCALYST experienced more improvement in each of the five 
components of the composite endpoint (joint pain, rash, feeling of fever/chills, eye redness/pain, and 
fatigue) than placebo-treated patients. 
In Part A, a higher proportion of patients in the ARCALYST group experienced improvement from 
baseline in the composite score by at least 30% (96% vs. 29% of patients), by at least 50% (87% vs. 8%) 
and by at least 75% (70% vs. 0%) compared to the placebo group. 
Serum Amyloid A (SAA) and C-Reactive Protein (CRP) levels are acute phase reactants that are typically 
elevated in patients with CAPS with active disease. During Part A, mean levels of CRP decreased versus 
baseline for the ARCALYST treated patients, while there was no change for those on placebo (Table 3). 
ARCALYST also led to a decrease in SAA versus baseline to levels within the normal range. 
Table 3. Mean Serum Amyloid A and C-Reactive Protein Levels Over Time in Part A 
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Part A 
ARCALYST 
Placebo 
SAA 
(normal range: 0.7 – 6.4 mg/L) 
(n=22) 
(n=24) 
Pre-treatment Baseline 
60 
110 
Week 6 
4 
110 
CRP 
(normal range: 0.0 – 8.4 mg/L) 
(n= 21) 
(n=24) 
Pre-treatment Baseline 
22 
30 
Week 6 
2 
28 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
During the open-label extension, reductions in mean symptom scores, serum CRP, and serum SAA levels 
were maintained for up to one year. 
16 
HOW SUPPLIED/STORAGE AND HANDLING 
Each 20-mL glass vial of ARCALYST contains a sterile, white to off-white, preservative-free, lyophilized 
powder. ARCALYST is supplied in a carton containing four vials (NDC 61755-001-01). 
The lyophilized ARCALYST product is to be stored refrigerated at 2° to 8°C (36° to 46°F) inside the 
original carton to protect from light. Do not use beyond the date stamped on the label. After 
reconstitution, ARCALYST may be kept at room temperature, should be kept from light, and should be 
used within three hours of reconstitution. ARCALYST does not contain preservatives; therefore, unused 
portions of ARCALYST should be discarded. Discard the vial after a single withdrawal of drug. 
17 
PATIENT COUNSELING INFORMATION 
See FDA-approved patient labeling. 
The first injection of ARCALYST should be performed under the supervision of a qualified healthcare 
professional. If a patient or caregiver is to administer ARCALYST, he/she should be instructed on aseptic 
reconstitution of the lyophilized product and injection technique. The ability to inject subcutaneously 
should be assessed to ensure proper administration of ARCALYST, including rotation of injection sites. 
(See Patient Information Leaflet for ARCALYST®). ARCALYST should be reconstituted with 
preservative-free Sterile Water for Injection to be provided by the pharmacy. A puncture-resistant 
container for disposal of vials, needles and syringes should be used. Patients or caregivers should be 
instructed in proper vial, syringe, and needle disposal, and should be cautioned against reuse of these 
items. 
Injection-site Reactions: Physicians should explain to patients that almost half of the patients in the 
clinical trials experienced a reaction at the injection site. Injection-site reactions may include pain, 
erythema, swelling, pruritus, bruising, mass, inflammation, dermatitis, edema, urticaria, vesicles, warmth, 
and hemorrhage. Patients should be cautioned to avoid injecting into an area that is already swollen or 
red. Any persistent reaction should be brought to the attention of the prescribing physician. 
Infections: Patients should be cautioned that ARCALYST has been associated with serious, 
life-threatening infections, and not to initiate treatment with ARCALYST if they have a chronic or active 
infection. Patients should be counseled to contact their healthcare professional immediately if they 
develop an infection after starting ARCALYST. Treatment with ARCALYST should be discontinued if a 
patient develops a serious infection. Patients should be counseled not to take any IL-1 blocking drug, 
including ARCALYST, if they are also taking a drug that blocks TNF such as etanercept, infliximab, or 
adalimumab. Use of ARCALYST with other IL-1 blocking agents, such as anakinra, is not recommended. 
Vaccinations: Prior to initiation of therapy with ARCALYST physicians should review with adult and 
pediatric patients their vaccination history relative to current medical guidelines for vaccine use, including 
taking into account the potential of increased risk of infection during treatment with ARCALYST. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
Manufactured and distributed by: 
Regeneron Pharmaceuticals, Inc. 
777 Old Saw Mill River Road, 
Tarrytown, NY 10591-6707, 1-877-REGN-777 (1-877-734-6777) 
U.S. License Number 1760 
NDC 61755-001-01 
© 2016, Regeneron Pharmaceuticals, Inc. 
All rights reserved. 
V 5.0 
Patient Information 
ARCALYST® (ARK-a-list) 
(rilonacept) 
Injection for Subcutaneous Use 
Read the patient information that comes with ARCALYST before you start taking it and each time 
you refill your prescription. There may be new information. The information in this leaflet does not 
take the place of talking with your healthcare provider about your medical condition and your 
treatment. 
What is the most important information I should know about ARCALYST? 
ARCALYST can affect your immune system. ARCALYST can lower the ability of your immune 
system to fight infections. Serious infections, including life-threatening infections and death have 
happened in patients taking ARCALYST. Taking ARCALYST can make you more likely to get 
infections, including life-threatening serious infections, or may make any infection that you 
have worse. 
You should not begin treatment with ARCALYST if you have an infection or have infections 
that keep coming back (chronic infection). 
After starting ARCALYST, if you get an infection, any sign of an infection including a fever, 
cough, flu-like symptoms, or have any open sores on your body, call your healthcare provider right 
away. Treatment with ARCALYST should be stopped if you develop a serious infection. 
You should not take medicines that block Tumor Necrosis Factor (TNF), such as Enbrel® 
(etanercept), Humira® (adalimumab), or Remicade® (infliximab), while you are taking 
ARCALYST. You should also not take other medicines that block Interleukin-1 (IL-1), such as 
Kineret  (anakinra), while taking ARCALYST. Taking ARCALYST with any of these 
medicines may increase your risk of getting a serious infection. 
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Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
Before starting treatment with ARCALYST, tell your healthcare provider if you: 
• 
• 
• 
• 
• 
• 
• 
think you have an infection 
are being treated for an infection 
have signs of an infection, such as fever, cough, or flu-like symptoms 
have any open sores on your body 
have a history of infections that keep coming back 
have asthma. Patients with asthma may have an increased risk of infection. 
have diabetes or an immune system problem. People with these conditions have a higher 
chance for infections. 
have tuberculosis (TB), or if you have been in close contact with someone who has had 
tuberculosis. 
have or have had HIV, Hepatitis B, or Hepatitis C 
take other medicines that affect your immune system 
• 
• 
• 
Before you begin treatment with ARCALYST, talk with your healthcare provider about your 
vaccination history. Ask your healthcare provider whether you should receive any vaccinations, 
including pneumonia vaccine and flu vaccine, before you begin treatment with ARCALYST. 
What is ARCALYST? 
ARCALYST is a prescription medicine called an interleukin-1 (IL-1) blocker. ARCALYST is used to 
treat adults and children 12 years and older with Cryopyrin-Associated Periodic Syndromes (CAPS), 
including Familial Cold Auto-inflammatory Syndrome (FCAS) and Muckle Wells Syndrome (MWS). 
ARCALYST can help lessen the signs and symptoms of CAPS, such as rash, joint pain, fever, and 
tiredness, but it can also lead to serious side effects because of the effects on your immune system. 
What should I tell my healthcare provider before taking ARCALYST? 
ARCALYST may not be right for you. Before taking ARCALYST, tell your healthcare provider 
about all of your medical conditions, including if you: 
• are scheduled to receive any vaccines. You should not receive live vaccines if you take 
ARCALYST. 
are pregnant or planning to become pregnant. It is not known if ARCALYST will harm 
your unborn child. Tell your healthcare provider right away if you become pregnant while 
taking ARCALYST. 
are breast-feeding or planning to breast-feed. It is not known if ARCALYST passes into 
your breast milk. 
• 
• 
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Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
See “What is the most important information I should know about ARCALYST?” 
Tell your healthcare provider about all the medicines you take, including prescription and 
non-prescription medicines, vitamins, and herbal supplements. Especially tell your healthcare 
provider if you take other medicines that affect your immune system, such as: 
• other medicines that block IL-1, such as Kineret  (anakinra). 
• medicines that block Tumor Necrosis Factor (TNF), such as Enbrel  (etanercept), Humira  
(adalimumab), or Remicade  (infliximab). 
• corticosteroids. 
See “What is the most important information I should know about ARCALYST?” 
Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider 
and pharmacist every time you get a new prescription. 
If you are not sure or have any questions about any of this information, ask your healthcare provider. 
How should I take ARCALYST? 
See the “Patient Instructions for Use” at the end of this leaflet. 
• 
• 
• 
Take ARCALYST exactly as prescribed by your healthcare provider. 
ARCALYST is given by injection under the skin (subcutaneous injection) one time each week. 
Your healthcare provider will tell and show you or your caregiver: 
▪ 
▪ 
▪ 
how much ARCALYST to inject 
how to prepare your dose 
how to give the injection 
• 
Do not try to give ARCALYST injections until you are sure that you or your caregiver 
understands how to prepare and inject your dose. Call your healthcare provider or pharmacist if 
you have any questions about preparing and injecting your dose, or if you or your caregiver 
would like more training. 
If you miss a dose of ARCALYST, inject it as soon as you remember, up to the day before your 
next scheduled dose. The next dose should be taken at the next regularly scheduled time. If you 
have any questions, contact your healthcare provider. 
If you accidentally take more ARCALYST than prescribed, call your healthcare provider. 
• 
• 
What are the possible side effects of ARCALYST? 
Serious side effects may occur while you are taking and after you finish taking ARCALYST 
including: 
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Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
• Serious Infections. See “What is the most important information I should know about 
taking ARCALYST?” Treatment with ARCALYST should be discontinued if you 
develop a serious infection. 
• Allergic Reaction. Call your healthcare provider or seek emergency care right away if you 
get any of the following symptoms of an allergic reaction while taking ARCALYST: 
• 
• 
• 
rash 
swollen face 
trouble breathing 
Common side effects with ARCALYST include: 
• Injection-site reaction. This includes: pain, redness, swelling, itching, bruising, lumps, 
inflammation, skin rash, blisters, warmth, and bleeding at the injection site. 
Upper respiratory infection. 
Changes in your blood cholesterol and triglycerides (lipids). Your healthcare provider 
will check you for this. 
• 
• 
These are not all the possible side effects of ARCALYST. Tell your healthcare provider about any 
side effects that bother you or that do not go away. For more information ask your healthcare provider 
or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to 
FDA at 1-800-FDA-1088. 
How should I store ARCALYST? 
• 
• 
Keep ARCALYST in the carton it comes in. 
Store ARCALYST in a refrigerator between 36°F to 46°F (2°C to 8°C). Call your pharmacy if 
you have any questions. 
Always keep ARCALYST away from light. 
Refrigerated ARCALYST can be used until the expiration date printed on the vial and carton. 
ARCALYST may be kept at room temperature after mixing. ARCALYST should be used within 
three hours of mixing. Keep ARCALYST away from light. 
If you need to take ARCALYST with you when traveling, store the carton in a cool carrier with a 
cold pack and protect it from light. 
• 
• 
• 
• 
Keep ARCALYST, injection supplies, and all other medicines out of reach of children. 
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Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
What are the ingredients in ARCALYST? 
Active ingredient: rilonacept. 
Inactive ingredients: histidine, arginine, polyethylene glycol 3350, sucrose, and glycine. 
General Information about ARCALYST 
Medicines are sometimes prescribed for conditions other than those listed in patient information 
leaflets. Do not use ARCALYST for a condition for which it was not prescribed. Do not give 
ARCALYST to other people even if they have the same condition. It may harm them. 
This leaflet summarizes the most important information about ARCALYST. If you would like more 
information, speak with your healthcare provider. You can ask your healthcare provider or pharmacist 
for information about ARCALYST that was written for healthcare professionals. For more 
information about ARCALYST, call 1-877-REGN-777 (1-877-734-6777), or visit 
www.ARCALYST.com. 
Patient Instructions for Use 
It is important for you to read, understand and follow the instructions below exactly. Following the 
instructions correctly will help to make sure that you use, prepare and inject the medicine the right 
way to prevent infection. 
How do I prepare and give an injection of ARCALYST? 
STEP 1: Setting up for an injection 
1. Choose a table or other flat surface area to set up the supplies for your injection. Be sure that 
the area is clean or clean it with an antiseptic or soap and water first. 
Wash your hands well with soap and water, and dry with a clean towel. 
Put the following items on a table, or other flat surface, for each injection (see Figure 1): 
2. 
3. 
Figure 1 
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Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
• 
2 sterile, 3-milliliter (mL) disposable syringes with markings at each 0.1 mL (see Figure 
2): 
• 
• 
one needed for mixing (reconstitution) ARCALYST 
one needed for injection 
Figure 2 
2 sterile disposable needles (27-gauge, ½-inch) 
• 
• 
• 
one needed for mixing 
one needed for injection 
• 
• 
• 
• 
• 
Note: 
• 
4 alcohol wipes 
1 2x2 gauze pad 
1 vial of ARCALYST (powder in vial) 
1 vial of preservative-free Sterile Water for Injection 
1 puncture-resistant container for disposal of used needles, syringes, and vials 
Do not use Sterile Water for Injection, syringes or needles other than those provided by 
your pharmacy. Contact your pharmacy if you need replacement syringes or needles. 
Do not touch the needles or the rubber stoppers on the vials with your hands. If you do 
touch a stopper, clean it with a fresh alcohol wipe. 
If you touch a needle or the needle touches any surface, throw away the entire syringe 
into the puncture-resistant container and start over with a new syringe. 
Do not reuse needles or syringes. 
• 
• 
• 
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Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
• 
To protect yourself and others from possible needle sticks, it is very important to throw 
away every syringe, with the needle attached, in the puncture proof container right after 
use. Do not try to recap the needle. 
STEP 2: Preparing Vials 
1. Check the expiration date on the carton of ARCALYST. Do not use the vial if the expiration 
date has passed. Contact your pharmacy for assistance. 
Check the expiration date on the vial of Sterile Water for Injection. Do not use the vial if the 
expiration date has passed. Contact your pharmacy for assistance. 
Remove the protective plastic cap from both vials. 
Clean the top of each vial with an alcohol wipe. Use one wipe for each vial and wipe in one 
direction around the top of the vial (see Figure 3). 
2. 
3. 
4. 
Figure 3 
Open the wrapper that contains the 27-gauge needle by pulling apart the tabs and set it aside 
for later use. Do not remove the needle cover. This needle will be used to mix the water with 
powder. Open the wrapper that contains the syringe by pulling apart the tabs. Hold the barrel 
of the syringe with one hand and twist the 27-gauge needle onto the tip of the syringe until it 
fits snugly with the other hand (see Figure 4). 
5. 
Figure 4 
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Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
6. Hold the syringe at eye level. With the needle covered pull back the plunger to the 2.3 mL 
mark, filling the syringe with air (see Figure 5). 
Figure 5 
Hold the syringe in one hand, use the other hand to pull the needle cover straight off. Do not 
twist the needle as you pull off the cover. Place the needle cover aside. Hold the syringe in 
the hand that you will use to mix (reconstitute) your medicine. Hold the Sterile Water vial on 
a firm surface with your other hand. Slowly insert the needle straight through the rubber 
stopper. Do not bend the needle. Push the plunger in all the way to push the air into the vial 
(see Figure 6). 
7. 
Figure 6 
Hold the vial in one hand and the syringe in the other hand and carefully turn the vial upside 
down so that the needle is pointing straight up. 
Make sure the tip of the needle is covered by the liquid and slowly pull back on the plunger to 
the 2.3 mL mark to withdraw the Sterile Water from the vial (see Figure 7). 
8. 
9. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
Figure 7 
10. Keep the vial upside down and tap or flick the syringe with your fingers until any air bubbles 
rise to the top of the syringe. 
11. To remove the air bubbles, gently push in the plunger so only the air is pushed out of the 
syringe and back into the bottle. 
12. After removing the bubbles, check the syringe to be sure that the right amount of Sterile 
Water has been drawn into the syringe (see Figure 8). 
Figure 8 
13. Carefully remove the syringe with needle from the Sterile Water vial. Do not touch the 
needle. 
STEP 3: Mixing (Reconstituting) ARCALYST 
1. With one hand, hold the ARCALYST vial on a firm surface. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
2. With the other hand, take the syringe with the Sterile Water and the same needle, and slowly 
insert the needle straight down through the rubber stopper of the ARCALYST vial. Push the 
plunger in all the way to inject the Sterile Water into the vial. 
Direct the water stream to gently go down the side of the vial into the powder (see Figure 9). 
3. 
Figure 9 
Remove the syringe and needle from the stopper and throw away the needle, syringe, and 
Sterile Water vial in the puncture-resistant container. Do not try to put the needle cover back 
on the needle. 
Hold the vial containing the ARCALYST and sterile water for injection sideways (not 
upright) with your thumb and a finger at the top and bottom of the vial, and quickly shake the 
vial back and forth (side-to-side) for about 1 minute (see Figure 10). 
4. 
5. 
Figure 10 
Put the vial back on the table and let the vial sit for about 1 minute. 
Look at the vial for any particles or clumps of powder which have not dissolved. 
6. 
7. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
8. If the powder has not completely dissolved, shake the vial quickly back and forth for 
30 seconds more. Let the vial sit for about 1 minute. 
9. Repeat Step 8 until the powder is completely dissolved and the solution is clear. 
10. The mixed ARCALYST should be thick, clear, and colorless to pale yellow. Do not use the 
mixed liquid if it is discolored or cloudy, or if small particles are in it (see Figure 11). 
NOTE: Contact your pharmacy to report any mixed ARCALYST that is discolored or 
contains particles. 
Figure 11 
11. ARCALYST may be kept at room temperature after mixing. ARCALYST should be used 
within three hours of mixing. Keep ARCALYST away from light. 
STEP 4: Preparing the injection 
1. Hold the ARCALYST vial on a firm surface and wipe the top of the ARCALYST vial with a 
new alcohol wipe (see Figure 12). 
Figure 12 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
2. Take a new sterile, disposable needle and attach securely to a new syringe without removing 
the needle cover (see Figure 13). 
Figure 13 
The amount of air you draw into the syringe should equal the amount of mixed ARCALYST 
that your healthcare provider has prescribed for you to inject. 
To draw air into the syringe, hold the syringe at eye level. Do not remove the needle cover. 
Pull back the plunger on the syringe to the mark that is equal to the amount of mixed 
ARCALYST that your healthcare provider has prescribed for you to inject (see Figure 14). 
3. 
4. 
Figure 14 
Remove the needle cover and be careful not to touch the needle. Keep the ARCALYST vial 
on a flat surface and slowly insert the needle straight down through the stopper. Push the 
plunger down and inject all the air into the vial (see Figure 15). 
5. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
Figure 15 
Hold the vial in one hand and the syringe in the other hand and carefully turn the vial upside 
down so that the needle is pointing straight up. Hold the vial at eye level. 
Keep the tip of the needle in the liquid and slowly pull back on the plunger to the mark on the 
syringe that matches the amount of medicine prescribed by your healthcare provider (see 
Figure 16). 
6. 
7. 
Figure 16 
NOTE: The maximum adult dose of ARCALYST is 2 mL. 
Keep the vial upside down with the needle straight up, and gently tap the syringe until any air 
bubbles rise to the top of the syringe (see Figure 17). 
It is important to remove air bubbles so that you withdraw up the right amount of medicine 
from the vial. 
8. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
Figure 17 
9. To remove the air bubbles, slowly and gently push in the plunger so only the air is pushed 
through the needle. 
10. Check to make sure that you have the amount of medicine prescribed by your healthcare 
provider in the syringe. 
11. Throw away the ARCALYST vial in the puncture-resistant container even if there is any 
medicine left in the vial (see Figure 18). Do not use any vial of ARCALYST more than one 
time. 
Figure 18 
STEP 5: Giving the Injection 
1. ARCALYST is given by subcutaneous injection, an injection that is given into the tissue 
directly below the layers of skin. It is not meant to go into any muscle, vein, or artery. 
You should change (rotate) the sites and inject in a different place each time in order to 
keep your skin healthy. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
Rotating injection sites helps to prevent irritation and allows the medicine to be completely 
absorbed. Ask your healthcare provider any questions that you have about rotating injection 
sites. 
• 
Do not inject into skin that is tender, red, or hard. If an area is tender or feels 
hardened, choose another site for injection until the tenderness or "hardening" 
goes away. 
Tell your healthcare provider about any skin reactions including redness, 
swelling, or hardening of the skin. 
Areas where you may inject ARCALYST include the left and right sides of the 
abdomen, and left and right thighs. If someone else is giving the injection, the 
upper left and right arms may also be used for injection (see Figure 19): 
(Do not inject within a 2-inch area around the navel) 
• 
• 
Figure 19 
Choose the area for the injection. Clean the area in a circular motion with a new alcohol wipe. 
Begin at the center of the site and move outward. Let the alcohol air dry completely. 
Take the cover off the needle and be careful not to touch the needle. 
Hold the syringe in one hand like you would hold a pencil. 
With the other hand gently pinch a fold of skin at the cleaned site for injection (see Figure 
20). 
2. 
3. 
4. 
5. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
Figure 20 
Use a quick “dart like” motion to insert the needle straight into the skin (90 degree angle) (see 
Figure 21). Do not push down on the plunger while inserting the needle into the skin. 
For small children or persons with little fat under the skin, you may need to hold the syringe 
and needle at a 45 degree angle (see Figure 21). 
6. 
Figure 21 
After the needle is completely in the skin, let go of the skin that you are pinching. 
With your free hand hold the syringe near its base. Gently pull back the plunger. If blood 
comes into the syringe, the needle has entered a blood vessel. Remove the needle, discard the 
syringe and needle. Start over with “STEP 1: Setting up for an injection” using new supplies 
(syringes, needles, vials, alcohol swabs and gauze pad). 
If no blood appears, inject all the medicine in the syringe at a slow, steady rate, pushing the 
plunger all the way down. It may take up to 30 seconds to inject the entire dose. 
7. 
8. 
9. 
10. Pull the needle out of the skin, and hold a piece of sterile gauze over the injection site for 
several seconds (see Figure 22). 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
Figure 22 
11. Do not replace the needle cover. Throw away the vials, used syringes and needles in the 
puncture-resistant container (see Figure 23). Do not recycle the container. DO NOT throw 
away vials, needles, or syringes in the household trash or recycle. 
Figure 23 
12. Keep the puncture-resistant container out of reach of children. When the container is about 
two-thirds full, dispose of it as instructed by your healthcare provider. Follow any special 
state or local laws about the right way to throw away needles and syringes. 
13. Used alcohol wipes can be thrown away in the household trash. 
Contact your healthcare provider right away with any questions or concerns about ARCALYST. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
Notes: 1. Enbrel , Humira , Kineret , and Remicade , respectively, are trademarks of Immunex 
Corporation, AbbVie Biotechnology Ltd., Amgen Inc., and Janssen Biotech, Inc., respectively. 
Manufactured and distributed by: 
Regeneron Pharmaceuticals, Inc. 
777 Old Saw Mill River Road 
Tarrytown, NY 10591-6707 
U.S. License Number 1760 
NDC 61755-001-01 
© 2016, Regeneron Pharmaceuticals, Inc. 
All rights reserved. 
V 4.0 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002 
Version 1.1, 05 Oct 2018 
13.2 Appendix: 11-point 
Pericarditis Pain 
Numerical Rating Scale (NRS) for Assessment of 
Subjects will be asked to select the score that best describes their average level of pericarditis 
pain over the previous 24 hours using an 11-point NRS, where zero (0) indicates ‘no pain’ 
and ten (10) means indicates ‘pain as bad as it could be’. 
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K"
l IKSA 
'-' 
NOTE TO FILE: 
TO: 
KPL-914-C002 
IND#: 
EudraCT Number: 
eTMF 
136.896 
2018-002719-87 
FROM: 
DATE: 
SUBJECT: 
Justification  for the  administrative  changes   made   to 
KPL-914-C002, Vl.0 dated 26 Sep 2018 
To whom it may concern, 
This note to file provides documentation to summarizing the changes made to the protocol 
KPL-9l4-C002, 
RANDOMIZED 
ASSESS THE 
Vl.0 titled ·'PHASE 3, DOUBLE-BLIND. PLACEBO-CONTROLLED, 
WITHDRAW AL STUDY WITH OPEN-LABEL EXTENSION , TO 
EFFICACY AND SAFETY OF RILONACEPT TREATMENT IN 
SUBJECTS WITH RECURRENT PERICARDITIS - Rilonacept inHibition of interleukin-1 
Alpha and beta for recurrent Pericarditis: a pivotal Symptomatology and Outcomes stuDY 
(RHAPSODY)"' finalized and signed on 26 Sep 2018. The PDF fiie containing the protocol 
KPL-914-C002. V1.0 document was transferred to Regulatory Affairs for publishing and 
filing to the applicable Regulatory Authorities. During the publishing process, minor 
administrative issues were noted by the publishing vendor, and as a result, the protocol 
document was updated as described in the table below. 
Page 286 
 
 
 


l 
KPL-914-C002, Vl.0 
FROM: 
KPL-914-C002, Vl.1 
TO: 
Global document change: 
Version 1.0, 26 September 2018 
Version 1.1. 05 October 2018 
- 
------ - 
Added   ·This   page   was 
Pg 12 vvas blank except for the header 
intentionally   left 
blank.'' 
In Section 
Brucato 
12 Reference List. Imazio M, Two references were added to the Section 12 
Reference List: 
Imazio M, Brucato A, Trinchero R, et al. 
Corticosteroid therapy for pericarditis: a 
double-edged sword. Nature Clinical 
Practice Cardiovascular Medicine. 
2008;5(3):188-119 and Imazio M, Cecchi E, 
Demichelis B, et al. Myopericarditis versus 
viral or idiopathic acute pericarditis. 
Hea11. 2008;94:498-501 
A, 
Cumetti 
D, 
et 
al. 
Corticosteroids for recurrent pericarditis: 
high versus low doses: a nonrandomized 
observation. Circulation. 2008; 118(6):667- 
671. was removed. 
Pg 91 
Pg 91 
6.5.4 Pharmacogenomics 
6.5.4 Pharmacogenomics 
Whole blood will be collected for 
pharmacogenomics assessments after signing the 
separate 
Pharmacogenomics ICF. 
Whole blood for peripheral blood mononuclear 
cell   (PBMC)   isolation   will   be   collected   for 
pharmacogenomics assessments after signing the 
separate Pharmacogenomics ICF. 
Page 287 
2. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Kiniksa Pharmaceuticals, Ltd. 
CLINICAL STUDY PROTOCOL 
PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
RANDOMIZED WITHDRAWAL STUDY WITH OPEN-LABEL 
EXTENSION, TO ASSESS THE EFFICACY AND SAFETY OF 
RILONACEPT TREATMENT IN SUBJECTS WITH 
RECURRENT PERICARDITIS – Rilonacept inHibition of 
interleukin-1 Alpha and beta for recurrent Pericarditis: a pivotal 
Symptomatology and Outcomes stuDY 
(RHAPSODY) 
Amendment #1; Protocol Version 2.0 
12 April 2019 
IND: 
EudraCT: 
136,896 
2018-002719-87 
1 
Page 288 
CONFIDENTIALITY STATEMENT 
The information contained in this document, particularly unpublished data, is the property of Kiniksa Pharmaceuticals, 
Ltd., and is provided to you in confidence as an investigator, potential investigator, or consultant, for review by you, 
members of your staff who have a need to know the information, and an applicable Institutional Review Board or 
Independent Ethics Committee. You agree that the information contained herein shall be held in strict confidence and is 
only to be used by you and your staff as necessary to conduct the authorized clinical studies of the investigational drug 
described in the protocol. Documentation, data, and all other information generated during the study is the property of 
Kiniksa Pharmaceuticals, Ltd. and will be held in strict confidence by you and members of your staff. You further agree 
to not publish or otherwise disclose any of the information to others without written authorization from Kiniksa 
Pharmaceuticals, Ltd., except to the extent necessary to obtain informed consent from those persons to whom the drug 
may be administered. 
 


KPL-914-C002 
Sponsor: 
Kiniksa Pharmaceuticals, Ltd. 
Sponsor Study Contact: 
Sponsor Medical Contact 
Medical Monitor: 
Protocol Number: 
Protocol Date: 
KPL-914-C002-Amendment 1, Protocol Version 2.0 
12 April 2019 
2 
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Protocol KPL-914-C002-Amendmcnt   I 
Version 2.0, 12 Apr 2019 
Kiniksa Phannaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol Approval - Sponsor Signatory 
Phase 3, double-blind, placebo-controlled, randomized withdrawal study with 
open-label extension, to assess the efficacy and safety of rilonacept treatment 
in subjects with recurrent pericarditis (RHAPSODY) 
Study Title 
KPL-9 I 4-C002- Amendment 1, Protocol Version 2.0 
Protocol Numher 
12 April 2019 
Protocol Date 
Protocol accepted and approved by: 
Chief Medical Officer 
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Kiniksa Phannaceuticals, 
Rilonacept (KPL-914) 
Ltd. 
Protocol KPL-914 -C002 -Amendmcnt 1 
Version 2.0, 12 Apr 2019 
Protocol Approval - Lead Statistician 
Phase 3, double-blind, placebo-controlled, randomized withdrawal study with 
open-label extension, to assess the efficacy and safety of rilonacept treatment 
in subjects with recurrent pericarditis (RHAPSODY) 
Study Title 
Protocol Number 
KPL-9 14-C002-Amendment 1, Protocol Version 2.0 
Protocol Date 
12 April 2019 
Protocol accepted and approved by: 
Lead Statistician 
- - 
4 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
Declaration of Investigator 
I have read and understood all Sections of the protocol entitled “Phase 3, double-blind, placebo-
controlled, randomized withdrawal study with open-label extension, to assess the efficacy and safety of 
rilonacept treatment in subjects with recurrent pericarditis (RHAPSODY)” and the accompanying 
Investigator’s Brochure. 
I agree to supervise all aspects of the protocol and to conduct the clinical investigation in accordance 
with the Final Protocol Version 2.0, dated 12 April 2019, the International Council for Harmonisation 
tripartite guideline E6(R2): Good Clinical Practice and all applicable government regulations. I will not 
make changes to the protocol before consulting with Kiniksa Pharmaceuticals or implement protocol 
changes without Institutional Review Board Independent Ethics Committee approval except to 
eliminate an immediate risk to subjects. I agree to administer study drug only to subjects under my 
personal supervision or the supervision of a sub-investigator. 
I will not supply the investigational drug to any person not authorized to receive it. Confidentiality will 
be protected. Subject identity will not be disclosed to third parties or appear in any study reports or 
publications. 
I will not disclose information regarding this clinical investigation or publish results of the investigation 
without authorization from Kiniksa Pharmaceuticals. 
Signature of Principal Investigator 
Date 
Printed Name of Principal Investigator 
5 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
TABLE OF CONTENTS 
TABLE OF CONTENTS ..................................................................................................... 6 
LIST OF TABLES .............................................................................................................. 13 
LIST OF FIGURES ............................................................................................................ 13 
PROTOCOL SYNOPSIS ................................................................................................... 14 
STUDY SCHEDULE OF ACTIVITIES ............................................................................ 21 
LIST OF ABBREVIATIONS ............................................................................................. 29 
1 
Introduction ................................................................................................................ 30 
1.1 
1.2 
1.3 
Current Therapeutic Management of Pericarditis .......................................... 31 
Pathogenesis of Recurrent Pericarditis: Role of IL-1 ..................................... 32 
Rilonacept (KPL-914) .................................................................................. 34 
1.3.1 
1.3.2 
Safety of Rilonacept .............................................................................. 35 
KPL-914-C001 Study with Rilonacept (KPL-914) in Recurrent 
Pericarditis ............................................................................................ 36 
2 
Study Objectives and Endpoints ................................................................................ 37 
2.1 
2.2 
Primary Objective......................................................................................... 37 
Secondary Objective ..................................................................................... 37 
3 
Investigational Plan .................................................................................................... 37 
3.1 
Study Design ................................................................................................ 37 
3.1.1 
3.1.2 
3.1.3 
Screening Period (up to 4 weeks)........................................................... 37 
Single-blind Run-In (RI) Period (12 weeks)........................................... 38 
Double-blind Placebo-controlled RW Period (pericarditis recurrence 
event-driven duration with a minimum of 24 weeks) ............................. 38 
Long Term Extension Treatment Period (LTE-TP) (24 weeks) .............. 39 
Long Term Extension Follow-Up Period (LTE-FUP) (24 weeks)........... 40 
Rationale of Study Design ..................................................................... 42 
Justification for Rilonacept Dose Selection ............................................ 43 
3.1.4 
3.1.5 
3.1.6 
3.1.7 
4 
Subject Selection and Withdrawal Criteria ............................................................... 43 
4.1 
Selection of Study Population ....................................................................... 44 
4.1.1 
4.1.2 
Inclusion Criteria ................................................................................... 45 
Exclusion Criteria.................................................................................. 46 
4.2 
Subject Completion, Withdrawal from Study, and Study Drug 
Discontinuation ............................................................................................ 48 
4.2.1 
Completion ........................................................................................... 48 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
4.2.2 
4.2.2.1 
4.2.2.2 
Reasons for Discontinuation of Study Drug and Study Withdrawal ........ 49 
Discontinuation of Study Drug .............................................................. 49 
Withdrawal from the Study ................................................................... 50 
5 
Study Treatments ........................................................................................................ 51 
5.1 
5.2 
5.3 
5.4 
Method of Assigning Subjects to Treatment Groups...................................... 51 
Treatments Administered .............................................................................. 51 
Identity of Investigational Medicinal Product ............................................... 53 
Management of Clinical Supplies ................................................................. 53 
5.4.1 
5.4.2 
5.4.3 
Study Drug Product Packaging and Storage ........................................... 53 
Study Drug Accountability .................................................................... 54 
Other Supplies ....................................................................................... 54 
5.5 
Study Drug Overdose ................................................................................... 54 
5.5.1 
5.5.2 
Treatment of Study Drug Overdose ....................................................... 55 
Other Study Drug Errors........................................................................ 55 
5.6 
5.7 
5.8 
Transmission of Infectious Agents ................................................................ 55 
Misuse for Illegal Purposes ........................................................................... 55 
Prior and Concomitant Medications .............................................................. 55 
5.8.1 
5.8.2 
5.8.3 
5.8.3.1 
5.8.4 
5.8.5 
5.8.6 
Screening .............................................................................................. 56 
Single-blind RI Period ........................................................................... 56 
Double-blind Placebo-controlled RW Period ......................................... 57 
Concomitant Medication Upon Pericarditis Recurrence ......................... 57 
Long Term Extension Treatment Period (LTE-TP) ................................ 58 
Long Term Extension Follow-Up Period (LTE-FUP) ............................ 58 
Prohibited Concomitant Medicines During the Study ............................ 58 
5.9 
Blinding ....................................................................................................... 59 
5.9.1 
Breaking the Blind ................................................................................ 59 
5.10 
Treatment Compliance.................................................................................. 59 
6 
Study Assessments and Procedures ............................................................................ 60 
6.1 
Study Visits .................................................................................................. 60 
6.1.1 
6.1.2 
6.1.2.1 
6.1.2.2 
6.1.2.3 
6.1.2.4 
6.1.2.5 
Screening: Clinic and Remote as Needed............................................... 60 
Single-blind Treatment: Run-In ............................................................. 62 
Enrollment (RI Baseline): Clinic Visit ................................................... 62 
RI Day 2: Clinic Visit (24-hour PK Sub-study Participants Only) .......... 63 
RI Day 4: TC/RN Visit .......................................................................... 63 
RI Week 1: TC/RN Visit ....................................................................... 63 
RI Week 2: TC/RN Visit ....................................................................... 64 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
6.1.2.6 
6.1.2.7 
6.1.2.8 
6.1.2.9 
6.1.3 
6.1.3.1 
6.1.3.2 
6.1.4 
6.1.4.1 
6.1.4.2 
6.1.5 
6.1.5.1 
6.1.5.2 
6.1.6 
6.1.6.1 
6.1.6.2 
6.1.6.3 
RI Week 4: TC/RN Visit ....................................................................... 65 
RI Week 6: Clinic Visit ......................................................................... 65 
RI Week 10: TC Visit ............................................................................ 66 
Randomization (RI Week 12/RW Baseline): Clinic Visit ....................... 66 
Randomized-Withdrawal (RW) Period .................................................. 68 
RW WEEK 24: Clinic Visit ................................................................... 69 
EORW (End of RW Period/LTE Baseline): Clinic Visit ......................... 70 
Long Term Extension ............................................................................ 71 
LTE Weeks 8 and 16: Clinic Visit ......................................................... 71 
LTE Week 24 Clinic Visit ..................................................................... 72 
LTE Follow-Up Period .......................................................................... 72 
LTE Week 30 Visit: Clinic .................................................................... 73 
LTE Week 48 End of Study Visit: TC.................................................... 73 
Supplemental Visits ............................................................................... 73 
Pericarditis Recurrence Assessment: Clinic Visit.................................... 73 
End of Treatment Visit: Clinic ............................................................... 74 
Safety Follow-Up Visit: Clinic or TC/RN .............................................. 75 
6.2 
Efficacy Assessments ................................................................................... 75 
6.2.1 
6.2.1.1 
6.2.1.2 
6.2.1.3 
6.2.1.4 
6.2.1.5 
6.2.1.6 
6.2.1.7 
6.2.1.8 
6.2.1.9 
6.2.1.10 
6.2.2 
Individual Efficacy Assessments ........................................................... 76 
C-Reactive Protein ................................................................................ 76 
11-Point Pericarditis Pain Numerical Rating Scale ................................ 76 
Electrocardiogram ................................................................................. 76 
Echocardiogram .................................................................................... 76 
Patient Global Impression of Pericarditis Severity ................................. 76 
Physician Global Assessment of Pericarditis Activity ............................ 77 
36-Item Short Form Health Survey ........................................................ 77 
EQ-5D-5L ............................................................................................. 78 
Insomnia Severity Index ........................................................................ 78 
Cardiac MRI ......................................................................................... 78 
Assessment of Clinical Response at the End of the Run-In Period 
Week 12/RW Baseline .......................................................................... 78 
Management of Suspected Pericarditis Recurrence in the RW Period .... 79 
6.2.3 
6.3 
Safety Assessments ....................................................................................... 80 
6.3.1 
6.3.2 
6.3.3 
6.3.4 
Physical Examination ............................................................................ 81 
Vital Signs ............................................................................................ 81 
Chest X-ray ........................................................................................... 81 
Tuberculosis Screening ......................................................................... 81 
6.4 
Adverse Events ............................................................................................. 81 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
6.4.1 
6.4.1.1 
6.4.1.2 
6.4.1.3 
6.4.1.4 
6.4.1.5 
6.4.1.6 
6.4.2 
6.4.2.1 
6.4.2.2 
6.4.3 
6.4.3.1 
6.4.3.2 
6.4.3.3 
6.4.4 
6.4.5 
6.4.6 
6.4.6.1 
6.4.7 
6.4.8 
Definitions ............................................................................................ 82 
Adverse Event ....................................................................................... 82 
Treatment-emergent Adverse Event ....................................................... 82 
Serious Adverse Event ........................................................................... 82 
Adverse Event of Special Interest .......................................................... 83 
Adverse Reaction .................................................................................. 83 
Suspected Unexpected Serious Adverse Reaction .................................. 83 
Assessing Adverse Events ..................................................................... 84 
Relationship to Study Drug ................................................................... 84 
Intensity ................................................................................................ 84 
Recording Adverse Events ..................................................................... 84 
Adverse Events Based on Signs and Symptoms ..................................... 85 
Adverse Events Based on Examinations and Tests ................................. 86 
Pericarditis Disease Related Events ....................................................... 86 
Time Period for Collection of Adverse Events ....................................... 86 
Follow-Up of Unresolved Adverse Events ............................................. 86 
Reporting Serious Adverse Events ......................................................... 86 
Other Reasons for Immediate Reporting ................................................ 87 
Pregnancy ............................................................................................. 87 
Evaluating and Reporting SUSARs ....................................................... 88 
6.5 
Other Assessments ........................................................................................ 88 
6.5.1 
6.5.2 
6.5.3 
6.5.4 
Pharmacokinetic Sample ....................................................................... 88 
Anti-Drug Antibodies (ADAs) against Rilonacept (KPL-914) ............... 89 
Biomarkers ............................................................................................ 89 
Pharmacogenomics................................................................................ 89 
6.6 
Laboratory Analyses ..................................................................................... 89 
6.6.1 
6.6.2 
6.6.3 
6.6.4 
6.6.5 
6.6.6 
6.6.7 
Serology ................................................................................................ 89 
Hematology ........................................................................................... 89 
Chemistry .............................................................................................. 89 
Non-fasting Lipid Panel ........................................................................ 90 
Urinalysis .............................................................................................. 90 
Pregnancy Test ...................................................................................... 90 
Sample Collection ................................................................................. 90 
6.7 
Committees .................................................................................................. 90 
6.7.1 
6.7.2 
Independent Data Monitoring Committee (DMC) .................................. 90 
Clinical Endpoint Committee (CEC) ..................................................... 91 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
7 
Statistical and Analytical Plan .................................................................................... 91 
7.1 
7.2 
Primary Efficacy Endpoint ........................................................................... 91 
Secondary Efficacy Endpoints for the RW Period ......................................... 91 
7.2.1 
7.2.2 
Major Secondary Efficacy Endpoints..................................................... 91 
Other Secondary Endpoints ................................................................... 91 
7.3 
Other Endpoints............................................................................................ 92 
7.3.1 
7.3.2 
Efficacy Endpoints for the RI Period ..................................................... 93 
Efficacy Endpoints for the LTE-TP ....................................................... 93 
7.4 
7.5 
7.6 
7.7 
Sample Size Calculations.............................................................................. 94 
Analysis Sets ................................................................................................ 94 
Description of Subgroups to be Analyzed ..................................................... 95 
Statistical Analysis Methodology .................................................................. 95 
7.7.1 
7.7.2 
7.7.3 
7.7.4 
7.7.5 
7.7.5.1 
7.7.5.2 
7.7.6 
7.7.7 
7.7.8 
7.7.9 
General Methods ................................................................................... 95 
Stratified Analysis ................................................................................. 96 
Testing Hypotheses and Multiplicity Adjustment ................................... 96 
Analysis of Primary Efficacy Endpoint .................................................. 96 
Analysis of Secondary Efficacy Endpoints ............................................ 97 
Analysis of the Major Secondary Endpoints .......................................... 97 
Analyses of Other Secondary Endpoints in the RW Period .................... 97 
Analyses of Other Endpoints ................................................................. 98 
Pharmacokinetic Analyses ..................................................................... 98 
Safety Analyses ..................................................................................... 98 
Interim Analyses.................................................................................... 99 
8 
Data Quality Assurance .............................................................................................. 99 
8.1 
Data Management......................................................................................... 99 
9 
Ethics ......................................................................................................................... 100 
9.1 
9.2 
9.3 
Independent Ethics Committee or Institutional Review Board .................... 100 
Ethical Conduct of the Study ...................................................................... 100 
Subject Information and Consent ................................................................ 100 
10 Investigator’s Obligations ......................................................................................... 101 
10.1 
10.2 
10.3 
10.4 
Confidentiality............................................................................................ 101 
Financial Disclosure and Obligations .......................................................... 102 
Investigator Documentation ........................................................................ 102 
Study Conduct ............................................................................................ 102 
10 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
10.5 
10.6 
10.7 
10.8 
10.9 
Adherence to Protocol ................................................................................ 102 
Adverse Events and Study Report Requirements ........................................ 103 
Investigator’s Final Report ......................................................................... 103 
Records Retention ...................................................................................... 103 
Publications ................................................................................................ 103 
11 Study Management ................................................................................................... 103 
11.1 
Monitoring ................................................................................................. 103 
11.1.1 
11.1.2 
Monitoring of the Study ...................................................................... 103 
Inspection of Records .......................................................................... 104 
11.2 
Management of Protocol Amendments and Deviations ............................... 104 
11.2.1 
11.2.2 
Modification of the Protocol ................................................................ 104 
Protocol Deviations ............................................................................. 104 
11.3 
11.4 
Study Termination ...................................................................................... 104 
Final Report................................................................................................ 105 
12 
13 
Reference List ........................................................................................................... 105 
Appendices ................................................................................................................ 108 
Appendix: ARCALYST® Prescribing Information. ...................................... 108 
13.1 
1 
2 
Indications and Usage ............................................................................................... 109 
Dosage and administration ....................................................................................... 109 
2.1 
2.2 
2.3 
2.4 
2.5 
General Dosing Information ....................................................................... 109 
Dosing ........................................................................................................ 109 
Preparation for Administration .................................................................... 109 
Administration............................................................................................ 109 
Stability and Storage ................................................................................... 110 
3 
4 
5 
Dosage Forms and Strengths .................................................................................... 110 
Contraindications...................................................................................................... 110 
Warnings and Precautions ....................................................................................... 110 
5.1 
5.2 
5.3 
5.4 
5.5 
Infections ................................................................................................... 110 
Immunosuppression .................................................................................... 111 
Immunizations ............................................................................................ 111 
Lipid Profile Changes ................................................................................. 111 
Hypersensitivity ......................................................................................... 111 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
6 
Adverse Reactions .....................................................................................................111 
6.1 
6.2 
6.3 
6.4 
6.5 
6.6 
6.7 
Clinical Trial Experience ............................................................................ 112 
Injection-Site Reactions .............................................................................. 113 
Infections ................................................................................................... 113 
Malignancies .............................................................................................. 113 
Hematologic Events.................................................................................... 113 
Immunogenicity ......................................................................................... 113 
Lipid Profiles .............................................................................................. 114 
7 
Drug Interactions ...................................................................................................... 114 
7.1 
7.2 
TNF-Blocking Agent and IL-1 Blocking Agent ........................................... 114 
Cytochrome P450 Substrates ...................................................................... 114 
8 
Use in Specific Populations ....................................................................................... 114 
8.1 
8.3 
8.4 
8.5 
8.6 
8.7 
Pregnancy ................................................................................................... 114 
Nursing Mothers ......................................................................................... 115 
Pediatric Use .............................................................................................. 115 
Geriatric Use .............................................................................................. 115 
Patients with Renal Impairment .................................................................. 116 
Patients with Hepatic Impairment ............................................................... 116 
10 
11 
12 
Overdosage ................................................................................................................ 116 
Description ................................................................................................................ 116 
Clinical Pharmacology .............................................................................................. 116 
12.1 
12.2 
12.3 
Mechanism of Action .................................................................................. 116 
Pharmacodynamics ..................................................................................... 117 
Pharmacokinetics........................................................................................ 117 
13 Nonclinical Toxicology .............................................................................................. 117 
13.1 
Carcinogenesis, Mutagenesis, Impairment of Fertility ................................. 117 
14 
16 
17 
Clinical Studies ......................................................................................................... 118 
How Supplied/Storage and Handling ....................................................................... 120 
Patient Counseling Information ............................................................................... 120 
13.2 
Appendix: 11-point Numerical Rating Scale (NRS) for Assessment of 
Pericarditis Pain.......................................................................................... 138 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
LIST OF TABLES 
Study Schedule of Activities – Screening and Run-In Period (Part 1 of 2) .......... 21 
Table 1–1 
Table 1–2 
Study Schedule of Activities – Randomized Withdrawal (Part 1 of 2) ................. 23 
Table 1–3 
Study Schedule of Activities – Long Term Extension (Part 1 of 2)...................... 25 
Table 1–4 
Study Schedule of Activities – Supplemental Visits (Part 1 of 2) ....................... 27 
Table 5–1: 
Study Drug Dose Volume (After Reconstitution) by Body Weight in Kilograms 
for Pediatric Subjects Aged ≥12 and <18 Years .................................................. 52 
LIST OF FIGURES 
Schematic of Rilonacept (KPL-914) ................................................................... 34 
Figure 1: 
Figure 2: 
Overview of KPL-914-C002 Trial Design .......................................................... 41 
Figure 3: 
Management of Suspected Pericarditis Recurrence in the Randomized- 
Withdrawal Period ............................................................................................. 80 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
PROTOCOL SYNOPSIS 
14 
Page 301 
Protocol Number: 
KPL-914-C002-Amendment 1 
Title: 
Phase 3, double-blind, placebo-controlled, randomized withdrawal study with open-label extension, to 
assess the efficacy and safety of rilonacept treatment in subjects with recurrent pericarditis 
 
Study Acronym: 
Rilonacept inHibition of interleukin-1 Alpha and beta for recurrent Pericarditis: a pivotal 
Symptomatology and Outcomes stuDY 
RHAPSODY 
Sponsor: 
 
Study Phase: 
3 
Study Sites: 
Multicenter, global 
Indication: 
Recurrent pericarditis 
Study Rationale: 
Recurrent pericarditis is a rare autoinflammatory condition with no approved therapies. Current 
treatments, utilizing nonspecific inhibitors of inflammation (nonsteroidal anti-inflammatory drugs 
[NSAIDs], colchicine, corticosteroids [CS]), result in significant morbidity with chronic use. Some 
patients develop CS dependency or require surgical pericardiectomy to treat the symptoms of their 
disease. 
The interleukin-1 (IL-1) pathway plays a major role in the pathophysiology of recurrent pericarditis. 
Rilonacept (KPL-914) is a recombinant fusion protein that blocks IL-1 signaling. It is currently approved 
for treatment of another autoinflammatory condition, Cryopyrin-Associated Periodic Syndrome (CAPS). 
Based on its IL-1–antagonistic properties and pharmacokinetics (PK), which allow for once-weekly 
subcutaneous (SC) injections, it is reasonable to evaluate the efficacy and safety of rilonacept in subjects 
with recurrent pericarditis to address the unmet need in treatment of this disease. 
 
Study Objectives: 
Primary: 
To assess the efficacy of rilonacept treatment in subjects with recurrent 
pericarditis. 
Secondary: 
To assess the safety of rilonacept treatment in subjects with recurrent 
pericarditis. 
 
 
 
 
 
 
 
 
 
 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
15 
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Study Population: 
Subjects eligible for the study are subjects with recurrent pericarditis who do not have pericarditis 
secondary to prohibited conditions. The study population includes both adult subjects ≥18 years old and 
pediatric subjects ≥12 and <18 years old with a history of at least 2 prior pericarditis episodes (including 
the first episode and 1 recurrence). Enrollment of pediatric subjects will be limited to up to 20% of the 
study population. To be eligible for the study, subjects must present at screening with at least a third 
pericarditis episode, defined as at least 1 day with pericarditis pain measurement ≥4 on the 11-point 
Numerical Rating Scale (NRS) and C-reactive protein (CRP) value ≥1 mg/dL (either on the same day or 
separated by no more than 7 days) within 7 days prior to first study drug administration. 
Subjects included in the study may be receiving concomitant NSAIDs and/or colchicine and/or oral CS 
treatment in any combination, provided that the dosages of these medications have been stable (or not 
increased) for at least 3 days prior to first administration of study drug, and that changes in medications 
made within this time period (for instance, 1-time use of NSAIDs) are not anticipated by the investigator 
to significantly alter assessments of baseline disease activity. 
 
Study Design: 
This study has 5 periods: 
(1) Screening period, during which assessment of disease characteristics, baseline therapy, and the 
pretreatment workup is completed (up to 4 weeks). 
(2) Single-blind Run-In (RI) period (12 weeks), during which blinded rilonacept is administered SC 
once weekly in all subjects. The RI period includes the following: 
• 1-week Stabilization period, during which blinded rilonacept is administered in addition to 
standard of care (SOC) pericarditis therapy and the ongoing pericarditis episode is treated 
• 9-week Weaning period, during which subjects are weaned off background SOC pericarditis 
therapy, as applicable, while treatment with blinded rilonacept continues 
• 2-week Monotherapy period during which subjects who have successfully weaned off background 
SOC pericarditis therapy will continue to receive blinded rilonacept 
In the single-blind RI period (subjects are blinded regarding the time of transition from the 
single-blind to the double-blind period), adult subjects ≥18 years old will receive rilonacept as an 
initial loading dose of 320 mg (2 SC injections of 160 mg each) at the RI baseline visit (2 × 2 ml), 
followed by a 160 mg (2 ml) SC dose once weekly throughout the RI period. Pediatric subjects (≥12 and 
<18 years old) will receive an initial loading dose of rilonacept 4.4 mg/kg (2 SC injections of 2.2 mg/kg 
each) at the RI baseline visit (maximum 2 × 2 ml), and then 2.2 mg/kg (maximum 2 ml) SC once weekly 
throughout RI period. 
Subjects who stopped background SOC pericarditis therapy and who achieve Clinical Response at RI 
Week 12, defined as the weekly average of daily pericarditis pain score ≤2.0 on the 11-point NRS within 
the 7 days prior to and including the day of randomization on RI Week 12/Randomization Withdrawal 
(RW) baseline and a CRP level ≤0.5 mg/dL at the RI Week 12/RW baseline visit, will proceed into the 
double-blind placebo-controlled RW period. Subjects who do not achieve Clinical Response at 
 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
16 
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Study Design Continued 
RI Week 12/RW baseline on rilonacept monotherapy will be discontinued from study drug, transitioned 
to SOC pericarditis therapy at the investigator’s discretion and followed through the end of the RW 
period. 
(3) Double-blind placebo-controlled RW period (pericarditis recurrence event-driven duration, with a 
minimum of 24 weeks), during which subjects who were able to stop background SOC pericarditis 
therapy and who achieve Clinical Response at RI Week 12/RW baseline are randomized in a double-
blind manner at a 1:1 ratio to the following: 
• Rilonacept 160 mg (2.2 mg/kg in pediatric subjects) SC injections once weekly 
• Matching placebo SC injections once weekly 
Pericarditis Recurrence in the RW Period 
Pericarditis recurrence is defined as the recurrence of typical pericarditis pain associated with supportive 
objective evidence of pericarditis. Upon pericarditis recurrence, subjects who report at least 1 day with 
pericarditis pain measurement ≥4 on the 11point NRS and have 1 CRP value ≥1 mg/dL (either on the 
same day or separated by no more than 7 days) will receive bailout rilonacept (2 open-label injections 
of 160 mg rilonacept [or 4.4 mg/kg for pediatric subjects] followed by once weekly open-label 
rilonacept SC injections of 160 mg [or 2.2 mg/kg for pediatric subjects]) irrespective of randomized 
treatment assignment and as soon as at least 5 days have passed since the last study drug injection. 
Sequential Oral Rescue Therapy (ORT), i.e., analgesics first, then NSAIDs, and then colchicine, can be 
added if needed at the discretion of the investigator, as outlined in the protocol and Pharmacy Manual. 
Subjects with pericarditis recurrence and who do not meet the protocol criteria for bailout rilonacept will 
continue blinded study drug until the protocol criteria for bailout rilonacept are met or through the end 
of the RW period. For those subjects, sequential ORT can be added to blinded study drug at the discretion 
of the investigator, as outlined in the protocol and Pharmacy Manual. 
All suspected pericarditis recurrence events in the RW period will be formally adjudicated by the Clinical 
Endpoint Committee (CEC), and only events that are confirmed by the CEC as pericarditis recurrences 
will be used in the Primary Endpoint analysis. 
(4) Long Term Extension Treatment Period (LTE-TP) (24 weeks), during which all subjects 
completing the RW period (including subjects transitioned to open-label rilonacept upon pericarditis 
recurrence) will have an option to receive up to 24 weeks of open-label rilonacept 160 mg (or 2.2 mg/kg 
for pediatric subjects) SC injections once weekly based on their clinical status and at the discretion of 
the investigator, after signing LTE informed consent. Any subject who, in the opinion of investigator, 
should not continue open-label rilonacept will be offered participation in the LTE off study drug and 
after signing LTE informed consent. 
(5) Long Term Extension Follow-Up Period (LTE-FUP) (24 weeks), during which all subjects in the 
LTE-TP will be followed in the LTE-FUP for safety and potential pericarditis recurrences. 
 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
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Estimated Study Duration: 
Subjects completing LTE-TP are projected to be dosed with rilonacept for a minimum of approximately 
1.2 years and up to 3 years based on enrollment assumptions and pericarditis recurrence events accrual 
time. 
 
Study Efficacy Assessments: 
• Daily pericarditis pain on the 11-point NRS in the subject’s electronic diary 
• CRP level 
• Electrocardiogram (ECG) 
• Echocardiography (ECHO) 
• Patient Global Impression of Pericarditis Severity (PGIPS) 
• Physician Global Assessment of Pericarditis Activity (PGA-PA) 
• 36-Item Short Form Health Survey (SF-36) 
• 5-Level EuroQoL-5D (EQ-5D-5L) 
• Insomnia Severity Index (ISI) 
• Cardiac magnetic resonance imaging (in a substudy) 
 
Study Pharmacokinetic or Pharmacodynamic Assessments: 
Pharmacokinetic or pharmacodynamic assessments will include: 
• PK analysis 
• Anti-rilonacept antibodies 
• Biomarkers 
• Pharmacogenomics (for subjects who sign the separate informed consent for pharmacogenomics 
assessments) 
 
Study Safety Assessments: 
Safety assessments during the study will include: 
• Physical examination 
• Vital signs measurements 
• Adverse event (AE) monitoring 
• Chest x-ray 
• Tuberculosis screening 
• Laboratory tests 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
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Investigational Medicinal Product, Dosage, and Route of Administration: 
Rilonacept (KPL-914) is a recombinant fusion protein consisting of the extracellular domains of human 
IL-1 cytokine receptor and the Fc portion of human immunoglobulin G1 (IgG1). It acts as a soluble decoy 
receptor binding IL-1α/IL-1β and prevents their interaction with the IL-1 cell-surface receptor. 
Study drug (rilonacept or placebo) is supplied in a single use, 20 ml glass vial containing a sterile, white 
to off-white, lyophilized powder. Each vial is to be reconstituted with 2.3 ml sterile Water for Injection 
(WFI). A volume up to 2 ml can be withdrawn, which is designated to deliver up to 160 mg of rilonacept 
or up to 2 ml of placebo for SC injection only. The resulting solution is clear, colorless to pale yellow, 
and essentially free of particulates. 
Each rilonacept vial contains 220 mg of rilonacept lyophilized powder. After reconstitution with 2.3 ml 
WFI, the rilonacept vial contains 80 mg/ml rilonacept, 40 mM histidine, 50 mM arginine, 3.0% (w/v) 
polyethylene glycol 3350, 2.0% (w/v) sucrose, and 1.0% (w/v) glycine at a pH of 6.5. No preservatives 
are present. 
The first injection of rilonacept loading dose at the RI baseline visit will be administered at the study site 
by study site staff. The second injection of rilonacept loading dose at the RI baseline visit will be prepared 
and administered by the subject or the subject’s caregiver after adequate training and under the 
supervision of study site personnel. Subsequent once-weekly study drug doses will be self-administered 
SC by the subject or administered to the subject by a trained caregiver as an outpatient SC administration. 
 
Sample Size: 
Approximately 56 subjects (not to exceed 75 subjects) with recurrent pericarditis will be enrolled, which 
will allow approximately 50 subjects to be randomly assigned to blinded treatment. 
 
Statistical Methods: 
The primary efficacy endpoint is time to pericarditis recurrence, defined as the time from randomization 
to the date of the first pericarditis recurrence for each subject. Only CEC-confirmed pericarditis 
recurrence will be considered as an event for the primary efficacy analysis. A sensitivity analysis will be 
done based on the investigator’s assessment of the pericarditis recurrence. 
In order to control the overall 1-sided type I error rate at the 0.025 level, a gatekeeping procedure in 
combination with Hochberg’s procedure will be applied to testing the primary and major secondary 
efficacy endpoints. 
Major secondary efficacy endpoints for the RW period include: 
• Proportion of subjects who maintained Clinical Response at Week 24 of the RW period 
• Percentage of days with no or minimal pain (pain ≤1 on the 11-point NRS) in the first 24 weeks of 
the RW period 
• Proportion of subjects with absent or minimal pericarditis symptoms (based on the 7-point rating 
scale of PGIPS) at Week 24 of the RW period 
Other secondary efficacy endpoints for the RW period include: 
• Proportion of subjects without pericarditis recurrence in the first 24 weeks of the RW period 
• Time to pericarditis pain NRS ≥4 
 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
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Statistical Methods Continued: 
• Time to CRP level ≥1 mg/dL 
• Time to pericardial rub 
• Time to widespread ST-segment elevation or PR-segment depression on ECG 
• Time to new or worsening pericardial effusion on ECHO 
• Change over time in CRP levels 
• Change over time in subject’s assessments of pericarditis pain (weekly average) 
• Proportion of subjects with absent or minimal pericarditis activity based on Physician Global 
Assessment of Pericarditis Activity (PGA-PA) 
• Change over time in SF-36 Physical Component Score 
• Change over time in SF-36 Mental Component Score 
• Change in EQ-5D-5L 
• Change over time in subject’s sleep quality assessed with the ISI 
• Change over time in ISI categories 
• Number (percentage) of subjects who receive sequential ORT therapy for pericarditis recurrence 
(analgesics, NSAIDs, and/or colchicine) in the RW period 
Efficacy endpoints for the RI period include: 
• Proportion of subjects who achieved Clinical Response at the RI Week 12 visit 
• Time to CRP normalization 
• Number (percentage) of subjects with normalization of CRP at RI Week 12 
• Change from baseline in pericarditis pain at RI Week 12 
• Change from baseline in CRP level at RI Week 12 
• Resolution of echocardiographic and ECG abnormalities (yes/no) at RI Week 12 
• Percentage of days with no or minimal pain 
• Proportion of subjects with absent or minimal pericarditis symptoms based on the PGIPS 
• Proportion of subjects with absent or minimal pericarditis activity based on the PGA-PA 
• Change over time in SF-36 Physical Component Score 
• Change over time in SF-36 Mental Component Score 
• Change in EQ-5D-5L 
• Change over time in subject’s sleep quality assessed with the ISI 
• Change over time in ISI categories 
• Number (percentage) of subjects who were off background SOC pericarditis therapy at 
RI Week 12 
Efficacy endpoints for the LTE-TP include: 
• Number (percentage) of subjects with pericarditis recurrences 
• Proportion of subjects with Clinical Response 
• Change over time in CRP levels 
• Change over time in subject’s assessments of pericarditis pain 
• Percentage of days with no or minimal pain 
• Proportion of subjects with absent or minimal pericarditis symptoms based on PGIPS 
• Proportion of subjects with absent or minimal pericarditis activity based on PGA-PA 
 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
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Statistical Methods Continued: 
• Change over time in SF-36 Physical Component Score 
• Change over time in SF-36 Mental Component Score 
• Change in EQ-5D-5L 
• Change over time in subject’s sleep quality assessed with the ISI 
• Change over time in ISI categories 
• Number (percentage) of subjects requiring addition of SOC pericarditis therapy 
Primary analysis of this study will be done after the 22nd CEC-confirmed pericarditis recurrence and after 
all subjects in the RW period have been treated for 24 weeks. Subjects who have not had an adjudicated 
pericarditis recurrence will be censored on the day of the last available assessment before data cutoff. 
Details of the analyses will be specified in the Statistical Analysis Plan. 
 
Protocol Version 
Version 2.0 
and Date: 
12 April 2019 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
STUDY SCHEDULE OF ACTIVITIES 
Table 1–1 
Study Schedule of Activities – Screening and Run-In Period (Part 1 of 2) 
a 
The screening and enrollment visit can be combined. 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Full physical examination includes at minimum evaluation of vital signs, head, eye, ear, nose, and throat as well as cardiovascular, dermatological, musculoskeletal, respiratory, GI, 
genitourinary, and neurological systems. The decision to perform examination of genitourinary system should be guided by clinical judgement. 
Abbreviated physical examination includes at minimum evaluation of vital signs, lung and heart sounds, including evaluation for pericardial rub. 
ECHO is required to be obtained according to the central core lab parameters and then read locally and submitted to the central core lab for separate review and analysis. 
Both a documented CRP > 1.0 mg/dL AND a pericarditis pain level of > 4 is required 7 days prior to and including the Run-In Baseline visit. These are not required to occur on the same day. 
Subjects missing ≥ 4 daily pain measurements during the 7 days prior to and including the Randomization Withdrawal baseline visit will be unable to proceed to randomization due to lack of 
data required for treatment response evaluation. 
All procedures are to be completed prior to study drug administration. 
b 
c 
d 
e 
f 
g 
m 
q 
The Randomization visit serves as both the RI Week 12 visit and the RW baseline visit. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Table 1–1 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
Study Schedule of Activities – Screening and Run-In Period (Part 2 of 2) 
a 
The screening and enrollment visit can be combined. 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Both a documented CRP > 1.0 mg/dL AND a pericarditis pain level of > 4 is required 7 days prior to and including the Run-In Baseline visit. These are not required to occur on the same day. 
Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the randomization withdrawal and LTE periods, or more frequently as needed, with mandated evaluations as detailed in the 
schedule of events. 
Applicable to 24-hour post dose PK sub-study participants only. 
For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout the course of the study and serum pregnancy can be drawn as needed; urine pregnancy is required to be performed 
at enrollment and 6 weeks after the last dose of study drug. 
Pharmacogenomics informed consent and subsequent sampling can be performed at any time in the study however, it is preferable to have this completed at the beginning of the study. 
Adverse event reporting begins following the subject providing informed consent. 
All procedures are to be completed prior to study drug administration. 
The first dose of study drug is a loading dose. Adult subjects receive 2 SC doses 160 mg (total 320 mg); pediatric subjects (subjects ≥12 and <18 years of age) receive 2 SC doses of 2 x 2.2 mg/kg. 
Study drug administration is once weekly with a minimum of 5 days required between doses. 
Randomization and subsequent study drug dispensing to occur after confirmation of Clinical Response (see definition of Clinical Response in Section 6.2.2). 
b 
f 
h 
i 
j 
k 
l 
m 
n 
o 
p 
q 
The Randomization visit serves as both the RI Week 12 visit and the RW baseline visit. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
Table 1–2 
Study Schedule of Activities – Randomized Withdrawal (Part 1 of 2) 
b 
c 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Full physical examination includes at minimum evaluation of vital signs, head, eye, ear, nose, and throat as well as cardiovascular, dermatological, musculoskeletal, respiratory, GI, 
genitourinary, and neurological systems. The decision to perform examination of genitourinary system should be guided by clinical judgement. 
Abbreviated physical examination includes at minimum evaluation of vital signs, lung and heart sounds, including evaluation for pericardial rub. 
ECHO is required to be obtained according to the central core lab parameters and then read locally and submitted to the central core lab for separate review and analysis. 
All procedures are to be completed prior to study drug administration. 
The EORW visit serves as both the last visit of the RW period and the baseline visit of the LTE period. 
For all subjects, the final clinic visit of the end of RW period is to be scheduled once the End of the Randomization Withdrawal end date is announced by Sponsor. This includes subjects that 
are taking blinded study drug, open-label rilonacept, or who have prematurely discontinued study drug. 
d 
e 
m 
t 
u 
23 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Table 1–2 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
Study Schedule of Activities – Randomized Withdrawal (Part 2 of 2) 
b 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the randomization withdrawal and LTE periods, or more frequently as needed, with mandated evaluations as detailed in the 
schedule of events. 
For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout the course of the study and serum pregnancy can be drawn as needed; urine pregnancy is required to be performed 
at enrollment and 6 weeks after the last dose of study drug. 
Adverse event reporting begins following the subject providing informed consent. 
All procedures are to be completed prior to study drug administration. 
Study drug administration is once weekly with a minimum of 5 days required between doses. 
The EORW visit serves as both the last visit of the RW period and the baseline visit of the LTE period. 
For all subjects, the final clinic visit of the end of RW period is to be scheduled once the End of the Randomization Withdrawal end date is announced by Sponsor. This includes subjects that are taking blinded study 
drug, open-label rilonacept, or who have prematurely discontinued study drug. 
Study drug administration to occur only after subject provides informed consent for the open-label extension period. 
h 
j 
l 
m 
o 
t 
u 
v 
24 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
Table 1–3 
Study Schedule of Activities – Long Term Extension (Part 1 of 2) 
b 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Full physical examination includes at minimum evaluation of vital signs, head, eye, ear, nose, and throat as well as cardiovascular, dermatological, musculoskeletal, respiratory, GI, 
genitourinary, and neurological systems. The decision to perform examination of genitourinary system should be guided by clinical judgement. 
ECHO is required to be obtained according to the central core lab parameters and then read locally and submitted to the central core lab for separate review and analysis. 
All procedures are to be completed prior to study drug administration. 
c 
e 
m 
25 
24 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Table 1–3 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
Study Schedule of Activities – Long Term Extension (Part 2 of 2) 
b 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the randomization withdrawal and LTE periods, or more frequently as needed, with mandated 
evaluations as detailed in the schedule of events. 
For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout the course of the study and serum pregnancy can be drawn as needed; urine pregnancy 
is required to be performed at enrollment and 6 weeks after the last dose of study drug. 
Adverse event reporting begins following the subject providing informed consent. 
All procedures are to be completed prior to study drug administration. 
Study drug administration is once weekly with a minimum of 5 days required between doses. 
h 
j 
l 
m 
o 
26 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
Table 1–4 
Study Schedule of Activities – Supplemental Visits (Part 1 of 2) 
b 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Full physical examination includes at minimum evaluation of vital signs, head, eye, ear, nose, and throat as well as cardiovascular, dermatological, musculoskeletal, respiratory, GI, 
genitourinary, and neurological systems. The decision to perform examination of genitourinary system should be guided by clinical judgement. 
Abbreviated physical examination includes at minimum evaluation of vital signs, lung and heart sounds, including evaluation for pericardial rub. 
ECHO is required to be obtained according to the central core lab parameters and then read locally and submitted to the central core lab for separate review and analysis. 
An EOT visit is to be conducted throughout the course of the study when a subject permanently discontinues study drug. 
An SFU is required to be conducted within 6 weeks of the last dose of rilonacept at any time throughout the course of the study including the RI period, the RW period, and the LTE period. 
The MRI to occur only if the previous MRI was done longer than 6 months ago. 
c 
d 
e 
x 
y 
z 
27 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Table 1–4 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
Study Schedule of Activities – Supplemental Visits (Part 2 of 2) 
b 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the randomization withdrawal and LTE periods, or more frequently as needed, with mandated evaluations 
as detailed in the schedule of events. 
For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout the course of the study and serum pregnancy can be drawn as needed; urine pregnancy is 
required to be performed at enrollment and 6 weeks after the last dose of study drug. 
Adverse event reporting begins following the subject providing informed consent. 
Upon investigator confirmation of pericarditis recurrence, the IWRS is to be updated. 
An EOT visit is to be conducted throughout the course of the study when a subject permanently discontinues study drug. 
An SFU is required to be conducted within 6 weeks of the last dose of rilonacept at any time throughout the course of the study including the RI period, the RW period, and the LTE period. 
h 
j 
l 
s 
x 
y 
28 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
LIST OF ABBREVIATIONS 
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Abbreviation 
Definition 
ADA 
anti-drug antibodies 
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
CAPS 
Cryopyrin Associated Periodic Syndrome 
CEC 
Clinical Endpoint Committee 
CFR 
Code of Federal Regulations 
CMH 
Cochran–Mantel–Haenszel 
CRP 
C-reactive protein 
CS 
corticosteroids 
DMC 
Data Monitoring Committee 
ECG 
electrocardiogram 
ECHO 
echocardiography; echocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
eDiary 
electronic diary 
EORW 
End of Randomized-Withdrawal(visit) 
EOS 
End of Study 
EOT 
End of Treatment (visit) 
EQ-5D-5L 
5-level EuroQoL-5D 
ESC 
European Society of Cardiology 
ESR 
erythrocyte sedimentation rate 
FCAS 
Familial Cold Auto-Inflammatory Syndrome 
FDA 
US Food and Drug Administration 
GCP 
Good Clinical Practice 
GI 
gastrointestinal 
HDL 
high-density lipoprotein 
HIV 
human immunodeficiency virus 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
independent ethics committee 
IgG1 
human immunoglobulin G1 
IGRA 
Interferon Gamma Release Assay 
IL-1 
interleukin-1 
IRB 
Institutional Review Board 
ISI 
Insomnia Severity Index 
ISR 
injection site reaction 
ITT 
intent to treat 
IV 
intravenous(ly) 
IWRS 
interactive web response system 
KPL-914 
rilonacept 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
1 
Introduction 
Pericarditis is inflammation of the pericardium, the double-walled sac surrounding the heart. Etiologies 
of pericarditis include infectious causes (viral, bacterial, fungal, and parasitic) and non-infectious 
causes (idiopathic, autoimmune, neoplastic, metabolic, traumatic, post-surgical, and drug-related) 
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LDL 
low-density lipoprotein 
LTE-FUP 
Long Term Extension Follow-Up Period 
LTE-TP 
Long Term Extension Treatment Period 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
magnetic resonance imaging 
MWS 
Muckle-Wells Syndrome 
NSAID 
nonsteroidal anti-inflammatory drug 
NRS 
Numerical Rating Scale 
ORT 
Oral Rescue Therapy 
PHV 
Pharmacovigilance 
PGA-PA 
Physician Global Assessment of Pericarditis Activity 
PGIPS 
Patient Global Impression of Pericarditis Severity 
PK 
pharmacokinetic(s) 
POC 
point of care 
PRO 
patient-reported outcome 
RI 
Run-In (period) 
RN 
visiting registered nurse 
RW 
Randomized-Withdrawal (period) 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SC 
subcutaneous(ly) 
SF-36 
36-Item Short Form Health Survey 
SFU 
safety follow-up 
SOC 
standard of care 
SUSAR 
suspected unexpected serious adverse reaction 
TB 
tuberculosis 
TC 
site telephone visit (telephone contact) 
TEAE 
treatment-emergent adverse event 
TNF 
tumor necrosis factor 
ULN 
upper limit of normal 
WBC 
white blood cell 
WFI 
Water for Injection 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
(Adler et al 2015). In 80% of cases in developed countries, the cause of pericarditis is either post-viral 
or “idiopathic” in that it cannot be attributed to a specific condition (Imazio et al 2010; Zayas et al 
1995). 
The underlying pathogenesis of recurrent pericarditis remains unclear, although a growing body of 
evidence suggests that abnormal immune responses play a role in the pathogenic processes. While the 
adaptive immune system plays a role in autoimmune disorders that manifest with pericarditis as one of 
the many organ systems involved (such as in systemic lupus erythematosus or rheumatoid arthritis), the 
innate immune system, including interleukin 1 (IL-1) signaling, is often the major effector in 
autoinflammatory disorders, such as isolated pericarditis (Baskar et al 2016; Brucato et al 2016; Imazio 
et al 2016, Dinarello et al 2012). 
Diagnosis of pericarditis is based on the presence of typical chest pain (improved by sitting up and 
leaning forward) along with fever, pericardial friction rub, electrocardiographic changes, pericardial 
effusion, or elevated levels of inflammation markers (white blood cell [WBC] count, C-reactive protein 
[CRP], or erythrocyte sedimentation rate [ESR]) (Adler et al 2015). The European Society of 
Cardiology (ESC) Guidelines for the Diagnosis and Management of Pericardial Diseases define an 
acute pericarditis episode as the presence of at least 2 of the 4 following criteria: pericarditic chest pain, 
pericardial rubs, new widespread ST-segment elevation or PR-segment depression based on 
electrocardiogram (ECG) findings, and pericardial effusion (new or worsening). Elevations of certain 
markers of inflammation (i.e., CRP, ESR, and WBC) or evidence of pericardial inflammation by an 
imaging technique (e.g., magnetic resonance imaging [MRI]) are used as supportive findings (Adler et 
al 2015). 
Recurrent pericarditis is characterized by the recurrence of pericarditis signs and symptoms after a 
symptom-free period of at least 4 to 6 weeks (Adler et al 2015). Recurrent pericarditis affects 20% to 
30% of patients with acute pericarditis (Imazio 2014) and can be debilitating for patients due to pain 
and limitations in physical function during pericarditis episodes. Pericarditis recurrences result in 
increased emergency room admissions and hospitalizations. In the United States, 5% of patients 
presenting to the emergency room with non-ischemic chest pain are diagnosed with pericarditis 
(Agarwal et al 2015). 
The estimated prevalence of recurrent pericarditis in the US and Europe is 70,000 to 160,000 patients 
including approximately 8,000 to 21,000 patients who are refractory or intolerant to current therapies 
or who require long-term administration of corticosteroids (CS) to control their disease (Brucato et al 
2016; Lazaros et al 2016; Imazio et al 2010; Khandaker et al 2010; Imazio et al 2008). 
1.1 
Current Therapeutic Management of Pericarditis 
There are no approved therapies for the treatment of recurrent pericarditis. Current treatments include 
nonspecific inhibitors of inflammation, i.e., aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), 
colchicine, and CS (Lilly et al 2013). 
Aspirin and other NSAIDs are the first-line approach. Because high doses of aspirin and NSAIDs are 
often required, consideration must be given to gastric protection therapy, as potential risks of therapy 
include stomach ulcers and gastrointestinal (GI) bleeding, as well as renal and cardiovascular toxicity. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
Colchicine is another mainstay therapy for pericarditis and is commonly used with NSAIDs to hasten 
the response to NSAIDs and reduce the risk of subsequent recurrences. However, its use may be 
associated with the risk of fatal overdosing, significant drug interactions, and neuromuscular toxicity. 
In addition, approximately 10% to 15% of patients experience significant GI side effects with 
colchicine, including GI intolerance or severe diarrhea, requiring treatment discontinuation (Imazio et 
al 2016). 
Available ESC guidelines stipulate that CS should be prescribed for the management of pericarditis 
episodes only in cases of incomplete response, intolerance, or contraindications to NSAIDs and 
colchicine because of their unfavorable long-term benefit-risk profile. Corticosteroid use is associated 
with side effects, including weight gain, diabetes, osteoporosis, avascular bone necrosis, and increased 
risk for infections (Imazio et al 2008). For the management of pericarditis, CS are usually administered 
at low to moderate doses and can provide rapid control of symptoms. However, they often require many 
months of tapering after the normalization of CRP levels. In addition, there is a high rate of pericarditis 
relapse when CS use is tapered or stopped (Lotrionte et al 2010; Imazio et al 2005; Maisch et al 2004), 
particularly in the absence of concurrent colchicine treatment. 
Patients with recurrent pericarditis who are refractory or intolerant to current therapeutic management 
options or who require long-term administration of CS to control their disease can be particularly 
challenging to manage. As a last resort, some refractory patients are being referred to the surgical 
procedure of pericardiectomy, with variable outcomes. Multiple immunosuppressive medications have 
been used without consistent benefit (Baskar et al 2016). 
1.2 
Pathogenesis of Recurrent Pericarditis: Role of IL-1 
Interleukin-1 is a key cytokine that drives the pathophysiology of many inflammatory processes, and it 
is implicated as a causative factor in various inflammatory diseases in humans. 
The two distinct IL-1 genes, IL1A and IL1B, encode IL-1α and IL-1β, respectively. IL-1α and IL-1β 
bind to the universally-expressed cell surface receptor, IL-1 receptor type-1, triggering a cascade of 
inflammatory mediators. The precursor form of IL-1α is expressed in keratinocytes, mucous membrane 
epithelial cells, and organs such as the liver and vascular endothelium in healthy individuals. During 
pathological states, IL-1α moves to the cell surface or is released after cell death to activate IL-1 
receptors in adjacent cells, thus beginning the cascade of sterile inflammation. IL-1β, however, is not 
expressed in healthy individuals until a stimulus, such as microbial products or other chemokines, 
triggers its transcription in monocytes, tissue macrophages, and dendritic cells via the inflammasome. 
IL-1 drives the inflammatory cascade in classic autoinflammatory conditions, such as tumor necrosis 
factor (TNF)-associated periodic syndrome (TRAPS) and familial Mediterranean fever (FMF) and 
plays a significant role in systemic onset of juvenile idiopathic arthritis and in autoimmune diseases 
such as rheumatoid arthritis (Baskar et al 2016). 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
IL-1–blocking therapies are effective at controlling end-organ disease and damage in patients with 
various autoinflammatory disorders, and different strategies to block IL-1 have been used in clinical 
trials and demonstrated substantial success in controlling episodes of fever and elevations in 
acute-phase reactants (Cantarini et al 2015). 
This mechanistic plausibility of IL-1 antagonism in addressing pathophysiology related to the 
inflammasome extends to other conditions characterized by sterile acute inflammation, such as 
33 
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recurrent pericarditis. 
 
 
 
 
 
 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
1.3 
Rilonacept (KPL-914) 
Rilonacept (designated in Kiniksa Pharmaceutical’s development program as KPL-914) was developed 
by Regeneron Pharmaceuticals, Inc. (Regeneron) of Tarrytown, NY, and is approved with the trade 
name ARCALYST® in the US for the treatment of CAPS, including Familial Cold Auto-Inflammatory 
Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and children age 12 and older. 
Rilonacept is currently manufactured and marketed as ARCALYST® by Regeneron. Rilonacept 
received marketing authorization in the European Union for the treatment of CAPS with severe 
symptoms, including FCAS and MWS in adults and children aged 12 years and older, but based on a 
request from Regeneron, the marketing authorization was withdrawn. The withdrawal was a business 
decision and was not related to any concern with the safety or efficacy of rilonacept. 
Rilonacept is a recombinant fusion protein consisting of human cytokine receptor extracellular domains 
and the Fc portion of human IgG1. Rilonacept is a dimeric glycoprotein with a total molecular weight 
of approximately 250 kDa. The dimer is covalently linked by disulfide bonds in the Fc region. 
Rilonacept incorporates in a single molecule the extracellular domains of both receptors required for 
IL-1 signaling: the IL-1 type I receptor (IL-1R1) and the IL-1 receptor accessory protein (IL-1R-AcP) 
(Figure 1). 
Rilonacept is expressed in recombinant Chinese hamster ovary (CHO) cells. Rilonacept blocks IL-1 by 
acting as a soluble decoy receptor that binds IL-1 and prevents its interaction with cell surface receptors. 
Figure 1: 
Schematic of Rilonacept (KPL-914) 
IL-1R Type 1 
IL-1R-AcP 
- 
IL-1R-AcP 
Extracellular 
Domains 
Extracellular 
Domains 
Cell Membrane 
IL-1R Type 1 
Cytoplasmic 
Domains 
s s 
s s 
hIgG Fc 
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CH2 
CH3 
 
 
 
 
1 
 
 
IL
 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
1.3.1 Safety of Rilonacept 
For a detailed review of the available rilonacept safety data, please refer to the current Investigator 
Brochure and the ARCALYST® package insert (Section 13.1: ARCALYST® Prescribing Information). 
The available rilonacept safety data is summarized below. 
Rilonacept has been evaluated in 23 studies, including 22 complete and 1 ongoing. In the completed 
studies, 2243 subjects (2152 patients and 91 healthy volunteers) were exposed to rilonacept. Thirty of 
these patients were pediatric (<18 years of age). 
Doses up to 320 mg subcutaneously (SC) once weekly and 2000 mg intravenously (IV) monthly have 
been studied for different indications, including CAPS, gout, and other inflammatory disorders. 
Injection Site Reactions 
In clinical studies with rilonacept, the most common and consistently reported AE associated with 
rilonacept was injection site reaction (ISR). The ISRs included erythema, swelling, pruritus, mass, 
bruising, inflammation, pain, edema, dermatitis, discomfort, urticaria, vesicles, warmth, and 
hemorrhage. Most ISRs were mild to moderate. In the gout clinical studies, approximately 1% of 
subjects treated with rilonacept discontinued due to ISRs. Similar results have been seen in other patient 
populations. 
Infections 
Interleukin-1 blockade may interfere with immune response to infections. Serious life-threatening 
infections have been reported in clinical trials in subjects treated with rilonacept. 
Changes in Laboratory Parameters 
Cholesterol and lipid levels may be reduced in patients with chronic inflammation. Subjects treated 
with rilonacept in clinical trials experienced increases in their mean total cholesterol, high-density 
lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides. 
Immunogenicity 
As with all therapeutic proteins, there is a potential for immunogenicity. Antibodies directed against 
the receptor domains of rilonacept were detected using an enzyme-linked immunosorbent assay 
(ELISA). In clinical trials with rilonacept, approximately 30% to 35% of subjects tested positive for 
treatment-emergent antibodies to rilonacept on at least 1 occasion. 
Systemic Hypersensitivity Reactions 
Hypersensitivity reactions are a potential risk with protein therapeutics in general. In clinical studies 
with rilonacept, systemic hypersensitivity reactions have been rare. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
Malignancies 
Although malignancies have been reported in some subjects treated with rilonacept during clinical 
trials, the effect of rilonacept on the development of cancer is not known. Treatment with 
immunosuppressants, including rilonacept, may result in an increase in the risk of malignancies. 
Fetal Defects 
There are no adequate and well-controlled studies of rilonacept in pregnant women. Based on animal 
data, rilonacept may cause fetal harm. An embryo-fetal developmental toxicity study was performed in 
cynomolgus monkeys treated with 0, 5, 15, or 30 mg/kg given twice a week (highest dose is 
approximately 3.7-fold higher than the human dose of 160 mg based on body surface area). The fetus 
of the only monkey with exposure to rilonacept during the later period of gestation showed multiple 
fusion and absence of the ribs and thoracic vertebral bodies and arches. Exposure to rilonacept during 
this time period was below that expected clinically. Likewise, in the cynomolgus monkey, all doses of 
rilonacept reduced serum levels of estradiol up to 64% compared to controls and increased the incidence 
of lumbar ribs compared to both control animals and historical control incidences. In perinatal and 
postnatal developmental toxicology studies in the mouse model using a murine analog of rilonacept (0, 
20, 100, or 200 mg/kg), there was a 3-fold increase in the number of stillbirths in dams treated with 200 
mg/kg 3 times per week (the highest dose is approximately 6-fold higher than the 160 mg maintenance 
dose based on body surface area). 
Nonteratogenic effects: A peri- and postnatal reproductive toxicology study was performed in which 
mice were administered a murine analog of rilonacept at doses of 20, 100, and 200 mg/kg SC 3 times 
per week (the highest dose is approximately 6-fold higher than the 160 mg maintenance dose based on 
body surface area). Results indicated an increased incidence in unscheduled deaths of the F1 offspring 
during maturation at all doses tested. 
1.3.2 KPL-914-C001 Study with Rilonacept (KPL-914) in Recurrent Pericarditis 
KPL-914-C001 is an open-label, single active-arm Phase 2 proof-of-concept study in subjects age ≥6 
to 75 years old with recurrent idiopathic or post-pericardiotomy syndrome (PPS) pericarditis. The study 
includes a 6-week Treatment Period in which all the subjects receive once-weekly rilonacept 160 mg 
SC (2.2 mg/kg for subjects ≥6 and <18 years old) following a loading dose of 320 mg SC in subjects 
≥18 years old (4.4 mg/kg in subjects ≥6 and <18 years old) in addition to background pericarditis 
therapies (NSAIDS, colchicine, CS). After completing the 6-week Treatment Period and based on 
response status, the subjects have the option to enter the 18-week Extension Period during which they 
continue to receive rilonacept at the same dose, but during which investigators are encouraged to wean 
and stop background pericarditis medications. 
The primary objectives of the study are to explore clinical and biochemical endpoints of recurrent 
pericarditis symptomatology, as well as to assess feasibility to wean from concomitant pericarditis 
medication in the Extension Period while continuing treatment with rilonacept. The study population 
includes the following 5 subject categories (Parts): 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
• 
Part 1 enrolls symptomatic subjects with recurrent idiopathic pericarditis with an elevated marker 
of systemic inflammation (CRP level >1 mg/dL). 
Part 2 enrolls symptomatic subjects with recurrent idiopathic pericarditis with CRP level ≤1 mg/dL 
that, in the opinion of the investigator, can be attributed to concomitant medications (e.g., CS) and 
with pericardial inflammation present on cardiac MRI confirmed by the imaging core lab. 
Part 3 enrolls subjects with CS-dependent recurrent idiopathic pericarditis not experiencing 
symptoms that would meet the diagnostic criteria for a recurrence of pericarditis. 
Part 4 enrolls symptomatic subjects with recurrent PPS with an elevated marker of systemic 
inflammation (CRP level >1 mg/dL). 
Part 5 enrolls subjects with CS-dependent recurrent PPS not experiencing symptoms that would 
meet the diagnostic criteria for a recurrence of pericarditis. 
• 
• 
• 
• 
Preliminary data in this ongoing study suggest that subjects enrolled in Part 1 experience 
improvements in pain, CRP levels, and other pericarditis parameters compared to baseline. 
Adverse events observed in the study are consistent with the overall rilonacept safety profile. 
2 
Study Objectives and Endpoints 
2.1 
Primary Objective 
The primary objective of this study is to assess the efficacy of rilonacept treatment in subjects with 
recurrent pericarditis. 
2.2 
Secondary Objective 
The secondary objective of this study is to assess the safety of rilonacept treatment in subjects with 
recurrent pericarditis. 
3 
Investigational Plan 
3.1 
Study Design 
This is a Phase 3, multi-center, double-blind, placebo-controlled, randomized withdrawal study with 
open-label extension, to assess the efficacy and safety of rilonacept treatment in subjects with recurrent 
pericarditis. This study has 5 periods (Figure 2). 
3.1.1 Screening Period (up to 4 weeks) 
During the screening period, assessment of disease characteristics, baseline therapy, and the pre-
treatment workup will be completed during a period of up to 4 weeks. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
3.1.2 Single-blind Run-In (RI) Period (12 weeks) 
During the single-blind RI period, treatment with blinded rilonacept is administered and subjects are 
weaned off background standard of care (SOC) therapy for their pericarditis disease. Subjects will be 
blinded regarding the time of transition from the single-blind to the double-blind period; i.e., they will 
not be aware of the duration of the RI period. 
In the single-blind RI period, subjects ≥18 years old will receive blinded rilonacept as an initial loading 
dose of 320 mg (2 SC injections of 160 mg each) at the RI baseline visit (2 × 2 ml), followed by a 160 
mg (2 ml) SC dose once weekly throughout the RI period. Pediatric subjects (≥12 and <18 years old) 
will receive an initial loading dose of blinded rilonacept 4.4 mg/kg (2 SC injections of 2.2 mg/kg each) 
at the RI baseline visit (maximum 2 × 2 ml), and then 2.2 mg/kg (maximum 2 ml) SC once weekly 
throughout the RI period. 
The RI period includes: 
• 
1-week Stabilization period, during which blinded rilonacept is administered in addition to SOC 
pericarditis therapy, and the ongoing pericarditis episode is treated. 
9-week Weaning period, during which subjects are weaned off background SOC pericarditis 
therapy, as applicable, while treatment with blinded rilonacept continues. The dosages of CS, 
NSAIDs, and colchicine will be tapered according to the weaning protocol in the Pharmacy Manual 
(for the purpose of the protocol, aspirin is considered an NSAID). In general, CS doses will be 
tapered off starting at RI Week 1 and will be withdrawn by RI Week 10 (over a total of 9 weeks). 
NSAID and colchicine doses will be tapered off starting at RI Week 4 and will be withdrawn by 
RI Week 10 (over a total of 6 weeks). 
2-week Monotherapy period: Subjects who have been successfully weaned off background SOC 
pericarditis therapy will continue to receive blinded rilonacept. 
• 
• 
Subjects who stopped background pericarditis medications and achieve Clinical Response on rilonacept 
monotherapy at RI Week 12/RW baseline will proceed into the double-blind placebo-controlled 
Randomized-Withdrawal (RW) period of the study. For definition of Clinical Response, refer to Section 
6.2.2. 
Subjects who are unable   to   achieve   Clinical   Response   on   rilonacept   monotherapy   at 
RI Week 12/RW baseline are to be discontinued from study drug, transitioned to SOC pericarditis 
therapy at the investigator’s discretion, and followed through the end of the RW period. 
3.1.3 Double-blind Placebo-controlled RW Period (pericarditis recurrence 
event-driven duration with a minimum of 24 weeks) 
During the RW period, subjects who were able to stop background pericarditis medications and who 
achieve Clinical Response on rilonacept monotherapy at RI Week 12/RW baseline will be randomized 
1:1 to double-blinded administration of study drug: 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
• 
Rilonacept 160 mg (or 2.2 mg/kg in pediatric subjects ≥12 and <18 years old) SC injections once 
weekly OR 
Matching placebo SC injections once weekly 
• 
Pericarditis Recurrence in the RW Period 
For the definition of pericarditis recurrence, refer to Section 6.2.3. 
Upon pericarditis recurrence, subjects who report at least 1 day with pericarditis pain measurement ≥4 
on the 11-point Numerical Rating Scale [NRS] and have 1 CRP value ≥1 mg/dL (either on the same 
day or separated by no more than 7 days) will receive bailout rilonacept (2 open-label injections of 160 
mg rilonacept [or 4.4 mg/kg for pediatric subjects]) irrespective of randomized treatment assignment 
and as soon as at least 5 days have passed since the last study drug injection. The subjects transitioning 
to bailout rilonacept will remain blinded to their prior RW period treatment assignment. Sequential 
Oral Rescue Therapy (ORT), i.e., analgesics first, then NSAIDs, and then colchicine, can be added, if 
needed, at the discretion of the investigator, as outlined in Section 5.8.3 and detailed in the Pharmacy 
Manual. 
Subjects with pericarditis recurrence who do not meet the protocol criteria for bailout rilonacept will 
continue blinded study drug until they meet the protocol criteria for bailout rilonacept or through the 
end of the RW period. For those subjects, sequential ORT can be added to blinded study drug at the 
discretion of the investigator, as outlined in Section 5.8.3 and detailed in the Pharmacy Manual. 
All suspected pericarditis recurrence events in the RW period will be formally adjudicated by the 
Clinical Endpoint Committee (CEC), and only events that are confirmed by the CEC as pericarditis 
recurrences will be used in the Primary Endpoint analysis. 
The RW period will continue until the prespecified number of primary endpoint (CEC-confirmed 
pericarditis recurrence) events have occurred and approximately 50 randomized subjects have achieved 
a minimum of 24 weeks of treatment in the RW period. Based on projected event accrual and subject 
randomization, Kiniksa Pharmaceutical will determine the end of the RW period and announce to sites 
so that subject End of Randomized Withdrawal (EORW) visits can occur. All subjects, including those 
who have transitioned to open-label rilonacept or who prematurely discontinued study drug, should 
complete an EORW visit. 
3.1.4 Long Term Extension Treatment Period (LTE-TP) (24 weeks) 
Upon completion of the RW period and the EORW visit (site and subject unblinding), all subjects 
completing the RW period (including subjects transitioned to open-label rilonacept upon pericarditis 
recurrence) will have an option to receive up to 24 weeks of open-label rilonacept 160 mg (or 2.2 mg/kg 
for pediatric subjects) SC injections once weekly based on their clinical status and at the discretion of 
the investigator, after signing LTE informed consent. Any subject who, in the opinion of investigator, 
should not continue open-label rilonacept will be offered participation in the LTE off study drug after 
signing LTE informed consent. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
3.1.5 Long Term Extension Follow-Up Period (LTE-FUP) (24 weeks) 
All subjects in the LTE-TP will be followed in the LTE-FUP for an additional 24 weeks for safety and 
for potential pericarditis recurrence assessments. 
The total duration of the study will be determined by the rate of enrollment, the rate of first recurrence 
of pericarditis events during the RW period, and the minimum duration of follow-up in the RW of 
24 weeks. It is anticipated that study completers (including LTE-TP) will be dosed with rilonacept for 
approximately 1.2 years and up to 3 years based on enrollment assumptions and pericarditis recurrence 
events accrual time. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr 2019 
Figure 2: 
Overview of KPL-914-C002 Trial Design 
End of Study 
(EOS) 
a 
Enrollment 
First Dose 
Randomization 
1:1 
End of RW 
LTE Week 24 
(Last Dose) 
Screening 
Up to 
4 weeks 
Single-blind Run In 
(RI) 
12 Weeks 
Event Driven Double-blind Randomized- 
b 
Withdrawal Period (RW) 
(Until 22 confirmed recurrence events) 
Anticipated minimum of 24 Weeks 
LTE Follow-Up 
(LTE-FUP) 
24 Weeks 
Long Term Extension Treatment Period 
(LTE-TP) 
24 Weeks 
1 
Week 
9 
Weeks 
2 
Weeks 
c 
Blinded rilonacept 160 mg SC once weekly 
Blinded rilonacept 160 mg 
c 
Open-label rilonacept 160 mg SC once weekly 
c 
SC once weekly 
Blinded placebo SC once weekly 
Stabilization 
while on 
background 
medication 
Monotherapy 
with rilonacept 
Weaning 
of NSAID, 
Colchicine, 
CS 
Primary Endpoint 
Abbreviations: CS=corticosteroid; EOS=end of study, LTE=Long Term Extension; NSAID=nonsteroidal anti-inflammatory drug; RI=run in, RW=randomized withdrawal, SC=subcutaneously, TP=treatment period 
a. The first dose given is a loading dose of rilonacept. In adult subjects ≥18 years old, 320 mg is given as 2 SC doses of 160 mg. In pediatric subjects ≥12 and <18 years old, 4.4 mg/kg is given as 2 SC doses of 2.2 
mg/kg. After the loading dose, rilonacept will be administered as a 160 mg (adults) or 2.2 mg/kg (pediatric subjects) SC dose once weekly. 
b. Subject’s treatment duration will depend on when the subject is enrolled relative to the end of RW. 
c. The adult dose is 160 mg SC once weekly. The pediatric dose is 2.2 mg/kg SC once weekly. 
Note: This picture is not drawn to scale. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr2019 
3.1.6 Rationale of Study Design 
Subjects eligible for this KPL-914-C002 study will be subjects with recurrent pericarditis presenting 
with an acute pericarditis episode at screening. 
The KPL-914-C002 study design ensures that during the RI period all subjects will receive rilonacept, 
a drug with evidence supporting clinical activity based on the preliminary clinical data with rilonacept 
from Part 1 of the ongoing Phase 2 proof-of-concept study (KPL-914-C001) obtained to date. During 
the RI period, pericarditis will be stabilized with symptoms controlled and background pericarditis 
medications (NSAIDs, colchicine, CS) will be tapered and withdrawn, while rilonacept treatment 
continues. 
The design then allows half of the subjects to continue receiving active treatment after having achieved 
Clinical Response on that treatment, which maximizes subject exposure to a potentially beneficial 
therapy. The temporary withdrawal of rilonacept (by switching to placebo) in the half of the subjects 
who were randomly assigned to placebo is expected to result in an accelerated time to pericarditis 
recurrence and a higher recurrence rate compared to those who continue on active treatment, a finding 
that demonstrates that the underlying pericarditis etiology is still ongoing and will provide further 
support for the anticipated observation of the clinical effect of rilonacept during the RI period of the 
study. The period of exposure to an ineffective treatment is minimized in this design, as subjects will 
be removed from blinded treatment when the condition returns to a specified severity (i.e., for having 
met the criteria of pericarditis pain ≥4 on the 11-point NRS and CRP level ≥1 mg/dL) without 
unblinding them to prior treatment assignment, thus protecting the primary efficacy endpoint of the 
study. All subjects who meet the pain and CRP criteria described above will be treated with open-label 
bailout rilonacept using a loading dose, followed by once-weekly SC injections. In addition, sequential 
ORT such as NSAIDs and/or colchicine will be allowed upon recurrence at the investigator’s discretion 
based on the subject’s clinical status, as outlined in Section 5.8.3 and as stipulated in the Pharmacy 
Manual. Subjects with pericarditis recurrence not meeting criteria for bailout rilonacept, can be treated 
with sequential ORT based on investigator judgement and as described in protocol Section 5.8.3 and 
the Pharmacy Manual. If the subject requires the addition of CS treatment to control the pericarditis 
recurrence, the subject will be discontinued from study drug. All subjects will be followed for the 
duration of RW period. 
In summary, the proposed RW trial with rilonacept allows all enrolled subjects an opportunity to receive 
the active drug during the acute episode of pericarditis yet provides pivotal-quality data on the efficacy 
of rilonacept in this enriched cohort by subsequently randomly assigning subjects to placebo versus 
active treatment after they achieve a predefined clinical response. Subjects with pericarditis recurrences 
after randomization will receive bailout rilonacept treatment and/or sequential ORT according to the 
protocol. This approach minimizes the exposure to placebo, which is important for a study that requires 
active disease upon enrollment and includes a pediatric population. The available regulatory guidance 
supports the use of an RW study design in the setting of recurrent pericarditis as a means of establishing 
the long-term effectiveness of rilonacept, an approved product for the treatment of another rare 
autoinflammatory condition (CAPS). 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr2019 
3.1.7 Justification for Rilonacept Dose Selection 
loading dose (4.4 mg/kg in subjects ≥12 and <18 years old), followed by once-weekly SC doses at 160 
mg (2.2 mg/kg in subjects ≥12 and <18 years old). 
In the rilonacept development program in CAPS, gout, rheumatoid arthritis, and other inflammatory 
conditions, over 2000 subjects were exposed to rilonacept, including 1650 subjects receiving a 
rilonacept dose of 160 mg or higher. A total of 103 and 169 subjects were exposed to any rilonacept 
dose for at least 1 year or 6 months, respectively. Most of the real-life experience with rilonacept comes 
from the CAPS population treated at this marketed dose. As of March 2018, approximately 365 CAPS 
patients have been exposed to rilonacept in the post-marketing setting since 2008. The safety data 
accumulated so far support the benefit/risk ratio for the rilonacept dose intended to be evaluated in 
subjects with recurrent pericarditis. 
Based on the preliminary clinical data with rilonacept from Part 1 of the Phase 2 proof of concept study 
(KPL-914-C001) obtained to date, it is expected that rilonacept doses 
(320 mg 
followed by 160 mg SC once weekly and corresponding pediatric doses), and evaluated in the KPL-
914-C001 study, will consistently provide adequate suppression of clinical inflammatory response, 
including CRP levels, in patients with recurrent pericarditis. 
Bailout Rilonacept Dose 
Subjects who meet the protocol criteria for bailout rilonacept upon pericarditis recurrence in the RW 
period of the study (Sections 3.1 and 6.2.3), irrespective of treatment assignment at randomization, will 
receive open-label rilonacept (loading dose of 320 mg SC followed by once-weekly SC injections of 
160 mg, or the corresponding pediatric doses). 
The rationale for bailout rilonacept treatment upon pericarditis recurrence for subjects who were 
randomly assigned to placebo is that rilonacept had controlled their disease activity during the RI 
period; therefore, re-initiation of rilonacept is justified to regain control of pericarditis signs and 
symptoms upon recurrence. Subjects who were randomly assigned to rilonacept and qualify for bailout 
rilonacept upon pericarditis recurrence in the RW period were initial responders to rilonacept treatment 
during the RI period; thus it could be assumed that the loss of response during the RW period could be 
due to development of resistance to rilonacept due to different mechanisms, e.g., higher IL-1 levels or 
a change in rilonacept pharmacokinetics (PK)/ pharmacodynamics. Therefore, re-administration of a 
loading dose of rilonacept may help to restore Clinical Response. 
4 
Subject Selection and Withdrawal Criteria 
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, i.e., 320 mg SC
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr2019 
4.1 
Selection of Study Population 
Approximately 56 subjects will be enrolled (and not more than 75 subjects), which will allow at least 
50 subjects to be randomized at approximately 50 sites globally. Subjects will be assigned to study drug 
only if they meet all of the inclusion criteria and none of the exclusion criteria. 
Deviations from the inclusion and exclusion criteria are not allowed because they can potentially 
jeopardize the scientific integrity of the study, regulatory acceptability, or subject safety. Therefore, 
adherence to the criteria as specified in the protocol is essential. 
Subjects eligible for the study are subjects with recurrent pericarditis who do not have pericarditis 
secondary to prohibited conditions. The study population includes both adult subjects ≥18 years old 
and pediatric subjects ≥12 and <18 years old with a history of at least 2 pericarditis episodes (including 
the first episode and 1 recurrence) prior to screening. Enrollment of pediatric subjects will be limited 
to up to 20% of the study population. To be eligible for the study, subjects must present with at least a 
third pericarditis episode, defined as at least 1 day with pericarditis pain measurement ≥4 on the 11-
point NRS and CRP level ≥1 mg/dL within 7 days prior to the first study drug administration. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr2019 
4.1.1 Inclusion Criteria 
Each subject must meet all of the following criteria to be enrolled in this study: 
1. Is capable of understanding the written informed consent form (ICF) or assent form (for 
pediatric subjects ≥12 and <18 years old), has provided signed and witnessed written informed 
consent or assent (as applicable), and agrees to comply with protocol requirements. 
Is male or female 12 years of age or older with body weight of at least 23.6 kg (52 Lbs). 
Has a diagnosis of recurrent pericarditis. 
At least 1 of the pericarditis episodes experienced prior to screening has met at least 2 of the 
following 4 criteria, in the opinion of the investigator and based on the documented available 
data, according to the 2015 ESC Guidelines for the Diagnosis and Management of Pericardial 
Diseases (Adler et al 2015): 
2. 
3. 
4. 
a. 
b. 
c. 
Pericarditic chest pain 
Pericardial rub 
New widespread ST-segment elevation or PR-segment depression according to ECG 
findings 
Pericardial effusion (new or worsening) 
d. 
5. Presents with at least the third episode of pericarditis during screening (i.e., at least the second 
pericarditis recurrence following the first pericarditis episode), and within 7 days* prior to and 
including RI baseline (first administration of study drug) has: 
a. At least 1 day with pericarditis pain ≥4 on the 11-point NRS, AND 
b. CRP level ≥1.0 mg/dL (for details of CRP collection see Section 6.1.1) 
*Pericarditis pain ≥4 and CRP ≥1 mg/dL are not required to be present on the same day. 
6. Has received NSAIDs and/or colchicine and/or CS (in any combination), if used, at stable dose 
levels (or at least not increased) for at least 3 days prior to and including RI baseline (first 
administration of study drug), and changes in medications made within this time period (e.g., 
1-time use of NSAIDs) are not anticipated, in the opinion of the investigator, to significantly 
alter assessments of baseline disease activity. 
If using NSAIDs and/or colchicine and/or CS at the time of RI baseline (first administration of 
study drug), is willing and able, in the opinion of the investigator, to taper and discontinue those 
medications within the 9-week weaning time in the RI period of the study while continuing 
rilonacept treatment. 
Female subjects must be: 
a. Postmenopausal, defined as at least 12 months after the cessation of menses (without an 
alternative medical cause) OR 
b. Incapable of pregnancy OR 
7. 
8. 
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Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr2019 
c. Permanently sterile following documented hysterectomy, bilateral salpingectomy, bilateral 
oophorectomy, or bilateral tubal ligation or having a male partner with vasectomy as 
affirmed by the subject OR 
d. If of childbearing potential, must agree to use a highly effective method of contraception 
during the study and for 3 months after the last study drug administration (i.e., hormonal 
contraceptives associated with inhibition of ovulation, intrauterine device [IUD], 
intrauterine hormone-releasing system [IUS], or sexual abstinence) 
If male and sexually active, must have documented vasectomy or must practice birth control 
and not donate sperm during the study and for 3 months after the last study drug administration. 
Must be up-to-date with all immunizations, in agreement with current local immunization 
guidelines for immunosuppressed subjects, before RI baseline (first administration of study 
drug). 
Is able to adequately maintain a daily subject diary according to protocol. 
Must be able to adhere to the study visit schedule and understand and comply with the other 
protocol requirements. 
Agrees to refrain from making any new, major lifestyle changes that may affect pericarditis 
symptoms (e.g., changing exercise pattern) from the time of the ICF is signed through the end 
of the double-blind RW period. 
9. 
10. 
11. 
12. 
13. 
4.1.2 Exclusion Criteria 
Subjects meeting any of the following criteria will be excluded from the study: 
1. Has a diagnosis of pericarditis that is secondary to specific prohibited etiologies, including 
tuberculosis (TB); neoplastic, purulent, or radiation etiologies; post-thoracic blunt trauma (e.g., 
motor vehicle accident); myocarditis; or systemic autoimmune diseases with exception of Still’s 
disease. 
Is pregnant, breastfeeding, or planning a pregnancy or fathering a child during the study or 
within 3 months after the last study drug administration. 
Has a history of immunosuppression, including positive human immunodeficiency virus (HIV) 
test results. 
Is currently receiving CS at a dose of >60 mg/day prednisone (or equivalent) for adult subjects, 
or >0.5 mg/kg/day (or >60 mg/day, whichever is lower) prednisone (or equivalent) in pediatric 
subjects (≥12 and <18 years old). 
Has ever received cytotoxic drugs, including cyclophosphamide, chlorambucil, nitrogen 
mustard, or other alkylating agents. 
Has ever received agents that deplete B or T cells (e.g., rituximab, alemtuzumab). 
2. 
3. 
4. 
5. 
6. 
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7. Has received systemic immunomodulatory agents (with exception of CS) within the following 
time frames prior to RI baseline (first administration of study drug): 
a. Azathioprine, 
mycophenolate 
mofetil, 
cyclosporine, 
tacrolimus, 
sirolimus, 
or 
mercaptopurine within 24 weeks. 
TNF inhibitors, IL-6 inhibitors, or janus-activating kinase inhibitors within 12 weeks. 
Canakinumab within 12 weeks. Canakinumab could not have been discontinued due to 
safety unless it was discontinued due to local injection site reactions. 
Rilonacept within 6 weeks. Rilonacept could not have been discontinued due to lack of 
efficacy or due to safety. 
Methotrexate within 2 weeks. 
Anakinra within 5 days. Anakinra could not have been discontinued due to lack of efficacy 
or due to safety unless it was discontinued due to local injection site reactions. 
b. 
c. 
d. 
e. 
f. 
8. 
9. 
10. 
Has a history of myeloproliferative disorder. 
Has a history of demyelinating disease or symptoms suggestive of multiple sclerosis. 
Meets the following TB criteria: 
a. 
b. 
c. 
History of active TB prior to screening OR 
History of latent TB that was not adequately treated prior to screening OR 
Signs or symptoms suggestive of active TB (e.g., new cough of >14 days in duration or a 
change in chronic cough, persistent fever, unintentional weight loss, or night sweats) upon 
review of medical history and/or physical examination at screening OR 
Recent close contact with a person with active TB OR 
Positive or indeterminate Interferon Gamma Release Assay (IGRA) test results or results 
from another positive TB test at screening based on acceptable clinical practice for the 
country in which the subject is enrolling. 
d. 
e. 
11. Has chest x-ray (posterior-anterior view) at screening (or history of results within 12 weeks 
before receiving first administration of study drug), with evidence of malignancy or abnormality 
consistent with prior or active TB infection. 
Has received immunization with a live (attenuated) vaccine within 12 weeks before screening 
or is expected to receive live (attenuated) vaccine during the study or within 12 weeks after the 
last study drug administration. 
Has a history of positive or intermediate results for hepatitis B surface antigen, hepatitis B core 
antibody, or hepatitis C virus antibody at screening. 
Has an estimated glomerular filtration rate (eGFR) <30 ml/min. 
Has a history of malignancy of any organ system within the past 5 years before screening (other 
than a successfully treated non-metastatic cutaneous squamous cell carcinoma or basal cell 
carcinoma and/or localized carcinoma in situ of the cervix). 
12. 
13. 
14. 
15. 
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16. Has a known or suspected current active infection or a history of chronic or recurrent infectious 
disease, including, but not limited to, chronic renal infection, chronic chest infection, sinusitis, 
recurrent urinary tract infection, or an open, draining infected skin wound. 
Has had a serious infection, has been admitted to the hospital for an infection, has been treated 
with oral antibiotics within 2 weeks of RI baseline (first administration of study drug), or has 
been treated with IV antibiotics for an infection within 8 weeks of RI baseline. 
Has had an organ transplant. 
Has screening laboratory test results meeting any of the following criteria: 
17. 
18. 
19. 
a. 
b. 
c. 
d. 
e. 
Hemoglobin level <10.0 g/dL; 
WBC count <3.0 × 103/µL 
Neutrophil count <1.5 × 103/µL 
Platelet count <100 × 103/µL 
Total bilirubin level >1.5 × the upper limit of normal (ULN) unless the test results are 
consistent with those for Gilbert’s syndrome 
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values >2 × ULN 
f. 
20. In the investigator’s opinion, has a history of alcoholism or drug/chemical abuse within 2 years 
before screening. 
Has a known hypersensitivity to ARCALYST® (rilonacept) or to any of its excipients. 
Has received an investigational drug during the 30 days (or 5 half-lives, whichever is longer) 
before screening or is planning to receive an investigational drug (other than that administered 
during this study) or use an investigational device at any time during the study. 
In the investigator’s opinion, has any other medical condition that could adversely affect the 
subject’s participation or interfere with study evaluations. This includes significant concomitant 
illnesses such as, but not limited to, cardiac, renal, neurological, endocrinological, metabolic, 
pulmonary, GI, or psychiatric diseases. 
In the opinion of the investigator, is not likely to be compliant with the study protocol. 
In the opinion of the investigator, should not participate in this study. 
21. 
22. 
23. 
24. 
25. 
4.2 
Subject Completion, Withdrawal from Study, and Study Drug 
Discontinuation 
4.2.1 Completion 
A subject will be considered to have completed the study if she/he has completed the RW period and 
has completed assessments at the EORW visit. At the EORW visit, subjects who were randomly 
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assigned to rilonacept or subjects who transitioned to open-label rilonacept upon protocol-defined 
pericarditis recurrence (Section 6.2.3) in the RW period will be offered an opportunity to receive an 
additional 24 weeks of open-label rilonacept treatment based on their clinical status and at the discretion 
of the investigator, and after signing the LTE informed consent. 
At the EORW visit, subjects who were randomly assigned to placebo and did not transition to bailout 
rilonacept will be offered an opportunity to receive an additional 24 weeks of open-label rilonacept 
treatment based on their clinical status and at the discretion of the investigator, after signing the LTE 
informed consent. 
Any subject who in the opinion of investigator should not continue open-label rilonacept in LTE will 
be offered the opportunity to continue follow-up off study drug treatment in LTE, after signing the LTE 
informed consent. 
Subjects who elect not to enter LTE will be followed for 6 weeks after receiving the last study drug 
administration. 
4.2.2 Reasons for Discontinuation of Study Drug and Study Withdrawal 
Subjects have the right to stop taking study drug before the end of the study or to withdraw their consent 
for further participation in the study (i.e., precluding continued data collection). A subject also may be 
asked to stop study drug at the investigator’s discretion. In the event that a subject permanently 
discontinues study drug but does not withdraw the informed consent, the investigator should continue 
to follow up with the subject by telephone contact (TC) visits, in the clinic, or by other means through 
the EORW visit if the subject discontinues in RI or RW, or through the end of LTE-FUP if the subject 
discontinues in LTE-TP, unless consent is withdrawn. 
The reasons for premature study drug discontinuation will be recorded in the electronic case report form 
(eCRF). 
4.2.2.1 
Discontinuation of Study Drug 
The study drug dosing will be permanently stopped if any of the following occurs: 
• 
The subject develops TB or malignancy, excluding non-metastatic cutaneous squamous cell 
carcinoma or basal cell carcinoma 
Initiation of protocol-prohibited medication (Section 5.8.6) 
Subject requires treatment with CS for pericarditis during RW or LTE-TP periods of the study 
Pregnancy or pregnancy planned during the study or within 3 months after the last study drug 
administration 
ALT or AST values ≥3 × ULN associated with total bilirubin ≥2 × ULN, with no underlying 
medical conditions to explain the elevated values 
• 
• 
• 
• 
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• 
• 
Treatment with a live (attenuated) vaccine during the study 
Investigator or Sponsor’s medical monitor or 
medical monitor decides that, for 
safety reasons, it is in the subject’s best interest 
Termination of the study by Kiniksa Pharmaceuticals 
• 
Permanent or temporary study drug discontinuation should be strongly considered at the time if any of 
the following occurs: 
• 
• 
• 
• 
• 
Subject develops an opportunistic infection. 
Subject develops moderate or severe infection 
Neutrophil count <1.0 × 103/µL 
Isolated ALT or AST values >5 × ULN 
Surgical procedure 
The Sponsor has the right to terminate the study at any time in case of safety concerns (e.g., suspected 
unexpected serious adverse reactions [SUSARs]) or if special circumstances concerning the study drug 
or the company itself occur. In this event, the investigator(s) will be informed of the reason for study 
termination. 
4.2.2.2 
Withdrawal from the Study 
Subjects may withdraw from the study at any time and for any reason, without prejudice to their future 
medical care by the investigator or at the study site. However, prior to withdrawal of consent, it should 
be confirmed that the subject will not allow any form of follow-up including options such as less 
frequent follow-up calls or visits, follow-up with a family member or friend, or follow-up through a 
local physician or medical records. Follow-up options will be summarized on a withdrawal of consent 
checklist source document that must be reviewed and signed by the investigator for any subject who 
withdraws consent for further participation in the study. The checklist must be completed for all 
enrolled subjects who have withdrawn consent. The reasons for a subject’s withdrawal from the study 
are also required to be recorded in the eCRF. 
A subject may be considered withdrawn from the study for any of the following reasons: 
• 
• 
• 
Lost to follow-up 
Documented withdrawal of informed consent 
Death 
If a subject is lost to follow-up, every reasonable effort must be made by the study site personnel to 
contact the subject and re-engage the subject in the study or determine the reason for withdrawal. The 
measures taken are to continue until study end and are required to be recorded in source documentation. 
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In subjects who are documented as having withdrawn consent from all study activities, no further study 
visits or study-related TCs can be conducted. All data collected prior to the date of the subject’s 
confirmed withdrawal of consent will be included in the study, as specified in the subject’s signed ICF. 
5 
Study Treatments 
5.1    Method of Assigning Subjects to Treatment Groups 
In the single-blind RI period, all subjects will receive blinded rilonacept at the same dose through 
Week 12; subjects will be blinded to the time of transitioning to RW. Subjects who stopped background 
SOC pericarditis therapy and who achieve Clinical Response on rilonacept at RI Week 12/RW baseline 
will be randomly assigned in a double-blind manner to continue to receive blinded rilonacept or 
matching placebo using a 1:1 allocation ratio. The definition of Clinical Response is provided in Section 
6.2.2. An interactive web response system (IWRS) will be used to administer the randomization 
schedule. Biostatistics will generate the randomization schedule using SAS® software Version 9.4 or 
later (SAS Institute Inc, Cary, North Carolina) for the IWRS, which will link sequential subject 
randomization numbers to treatment codes. The randomization schedule will be stratified by 2 factors: 
• 
• 
Oral CS use at baseline (RI baseline, i.e., beginning of RI period): yes or no 
Diagnosis of recurrent idiopathic pericarditis (RI baseline): yes or no 
5.2 
Treatments Administered 
Throughout this protocol, “study drug” refers to the investigational medicinal products: rilonacept and 
matching placebo. Both will be administered as applicable by SC injection. 
Study drug administration will be performed once a week (every 7 ± 2 days). The interval between 
study drug administrations must be at least 5 days. 
Study drug will be dosed as follows: 
Adult Subjects (≥18 years old): 
Rilonacept: Loading dose 320 mg administered as 2 SC injections, 160 mg each (2 ml) at RI baseline, 
followed by once-weekly SC injections of 160 mg (2ml). 
Placebo: administered as once-weekly SC injections of 2 ml each in the RW period 
Upon meeting protocol criteria for bailout rilonacept (Sections 3.1 and 6.2.3) in the RW period, subjects 
will be transitioned to open-label rilonacept 320 mg administered as 2 SC injections, 160 mg each 
(2 ml) at the next scheduled study drug administration date, followed by once-weekly SC injections of 
160 mg (2ml). 
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Pediatric Subjects (≥12 and <18 years old): 
Rilonacept: Loading dose 4.4 mg/kg administered as 2 SC injections, 2.2 mg/kg each (maximum 
160 mg each) at RI baseline, followed by once-weekly SC injections of 2.2 mg/kg (maximum 160 mg). 
The volume of injections will be based on the subject’s weight (Table 5–1). 
Placebo (in RW): once-weekly SC injections with volume based on the subject’s weight (Table 5–1, 
maximum 2 ml). 
Upon meeting protocol criteria for bailout rilonacept (Sections 3.1 and 6.2.3) in the RW period, subjects 
will be transitioned to open-label rilonacept 4.4 mg/kg administered as 1 (maximum 2 ml) or 2 SC 
injections at the next scheduled study drug administration date, followed by once-weekly SC injections 
of 2.2 mg/kg (maximum 2 ml). The volume of injections will be based on the subject’s weight (Table 5– 
1). 
Study drug dose/volume will be calculated by the investigator or pharmacist during site clinic visits 
based on body weight (as specified in the Study Schedule of Activities) using a weight-based dosing 
chart in kilograms (Table 5–1). 
Table 5–1: 
Study Drug Dose Volume (After Reconstitution) by Body 
Kilograms for Pediatric Subjects Aged ≥12 and <18 Years 
Weight in 
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Weight Range (kg) 
 
Loading Dose Volume (ml) 
 
Weekly Dose Volume (ml) 
 
23.6 to 27.2 
2 x 0.7 
0.7 
27.3 to 30.8 
2 x 0.8 
0.8 
30.9 to 34.4 
2 x 0.9 
0.9 
34.5 to 38.1 
2 x 1.0 
1.0 
38.2 to 41.7 
2 x 1.1 
1.1 
41.8 to 45.4 
2 x 1.2 
1.2 
45.5 to 49.0 
2 x 1.3 
1.3 
49.1 to 52.6 
2 x 1.4 
1.4 
52.7 to 56.3 
2 x 1.5 
1.5 
56.4 to 59.9 
2 x 1.6 
1.6 
60.0 to 63.5 
2 x 1.7 
1.7 
63.6 to 67.2 
2 x 1.8 
1.8 
67.3 to 70.8 
2 x 1.9 
1.9 
70.9 or greater 
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Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr2019 
Study Drug Self-Administration 
The first study drug dose on RI baseline will be administered at the study site. During this visit, the 
subject will be trained on study drug preparation and injection. In case the subject is unwilling or unable 
to prepare and self-inject the study drug, the subject’s caregiver will be trained. 
The first study drug administration for adult and pediatric subjects on RI baseline will consist of 2 SC 
injections, constituting a loading dose. The first injection will be prepared and administered by study 
site staff. The second injection will be prepared and administered by the subject or the subject’s 
caregiver after adequate training and under the supervision of study site personnel. Subsequent once-
weekly study drug doses will be self-administered SC by the subject or administered to the subject by a 
trained caregiver as an outpatient SC administration. If the subject or subject’s caregiver is unable to 
prepare and inject the study dug, the subject may report for once-weekly injections to a study site, or 
injections can be administered by the visiting registered nurse (RN). 
5.3 
Identity of Investigational Medicinal Product 
Rilonacept (KPL-914) is the drug being evaluated in the current study. Refer to Section 1.3 for a 
detailed description of rilonacept’s mechanism of action. 
Study drug (rilonacept or placebo) is supplied in a single-use, 20 ml glass vial containing a sterile, white 
to off-white, lyophilized powder. Each vial is to be reconstituted with 2.3 ml sterile Water for Injection 
(WFI). A volume up to 2 ml can be withdrawn, which is designated to deliver up to 160 mg of rilonacept 
or up to 2 ml placebo for SC injection only. The resulting solution is clear, colorless to pale yellow, and 
essentially free of particulates. 
Each rilonacept vial contains 220 mg of rilonacept lyophilized powder. After reconstitution with 2.3 ml 
sterile WFI, the rilonacept vial contains 80 mg/ml rilonacept, 40 mM histidine, 50 mM arginine, 3.0% 
(w/v) polyethylene glycol 3350, 2.0% (w/v) sucrose, and 1.0% (w/v) glycine at a pH of 6.5. No 
preservatives are present. 
Each placebo vial contains lyophilized powder. After reconstitution with 2.3 ml sterile WFI, the placebo 
vial contains 40 mM histidine, 50 mM arginine, 3.0% (w/v) polyethylene glycol 3350, 2.0% (w/v) 
sucrose, and 1.0% (w/v) glycine at a pH of 6.5. No preservatives are present. 
5.4 
Management of Clinical Supplies 
5.4.1 Study Drug Product Packaging and Storage 
Additional information regarding the preparation, dispensation, administration, and storage of 
rilonacept or placebo will be described in the Pharmacy Manual. 
Study drug will be provided by Kiniksa Pharmaceuticals to the study sites in the lyophilized formulation 
in glass vials as described in Section 5.3. Each single-use vial will have a clinical label adhered to the 
vial. One labeled vial will be placed into a carton. Each carton will have a clinical label adhered to the 
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outside of the carton. One tamper-evident seal will be placed on the top of the carton to securely close 
the lid. 
Study drug is to be stored and shipped refrigerated at 2°C to 8°C (36°F to 46°F) inside the original 
carton to protect it from light. 
5.4.2 Study Drug Accountability 
The sites will receive study drug for on-site administration at study site visits. Upon receipt of study 
drug, the investigator (or delegate) will conduct an inventory of the supplies and verify that the supplies 
are received intact, at the appropriate temperature, and in the correct amounts prior to completing a 
supplies receipt. The investigator will confirm receipt of study drug in the IWRS and retain a copy of 
this receipt at the study site. The inventory of supplies at each study site will be reviewed by the study 
monitor. 
Study drug will be dispensed to the study subjects for outpatient self-administration according to the 
supply chain described in the Pharmacy Manual. 
The investigator will maintain accurate records of receipt of all test articles, including dates of receipt. 
In addition, accurate records will be kept regarding when and how much study drug is dispensed and 
used by each subject in the study. Reasons for deviating from the expected dispensing regimen must 
also be recorded. At the completion of the study, to satisfy regulatory requirements regarding drug 
accountability, all used and unused study drug containers must be retained by the study site/clinic and 
subject for cataloguing and documentation of compliance. The full process for drug dispensing, 
documentation, and destruction will be described in the Pharmacy Manual. 
A full drug accountability log will be maintained at the study site at all times. 
5.4.3 Other Supplies 
Rilonacept should be reconstituted with preservative-free WFI that will be provided by Kiniksa 
Pharmaceuticals or designee along with 27-gauge, ½-inch needles, 3-ml syringes, alcohol wipes, gauze 
pads, bandages, and a puncture resistant container for disposal of needles and syringes. Only the 
syringes and needles provided by the Sponsor or its designee should be used to prepare and inject the 
study drug. The Sponsor also will provide coolers and refrigerated gel packs to ensure that the subjects 
transport the study drug at the proper temperature. On occasion, sites may be asked to locally procure 
ancillary materials. 
5.5 
Study Drug Overdose 
An overdose is any dose of study drug given to a subject or taken by a subject that exceeds the dose 
described in the protocol. Any overdose must be promptly reported to the 
Pharmacovigilance 
(PHV) in the same way and using the  same procedures  as  for  a serious adverse event (SAE) 
(Section 6.4.6), regardless of whether any AEs are associated with the overdose. 
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If there are AEs associated with the overdose, these should be recorded on the relevant AE/SAE 
Sections in the eCRF; however, overdoses without signs or symptoms do not need to be recorded as 
AEs in the eCRF. 
5.5.1 Treatment of Study Drug Overdose 
The maximum amount of rilonacept that can be safely administered has not been determined. Maximum 
once-weekly doses of rilonacept up to 320 mg have been administered SC for up to approximately 18 
months in a small number of subjects with CAPS, and for up to 6 months in subjects in an unapproved 
indication in clinical trials without evidence of dose-limiting toxicities. In addition, rilonacept given IV 
at doses up to 2000 mg monthly for up to 6 months in another subject population was tolerated without 
dose-limiting toxicities (Rilonacept IB). In case of overdose, it is recommended that the subject be 
monitored for any signs or symptoms of AEs and appropriate symptomatic treatment instituted 
immediately (Section 13.1, ARCALYST® Prescribing Information). 
5.5.2 Other Study Drug Errors 
To avoid study drug errors, it is important to note the following: 
• 
In this study, rilonacept is designated for SC injections only. It should be taken only by the subjects 
participating in the study and as instructed by study site personnel. 
Guidelines regarding the management of temperature excursions during storage will be detailed in 
the Pharmacy Manual. 
Pediatric dosing is calculated based on body weight in kilograms, not pounds. 
• 
• 
Any study drug error must be promptly reported to the 
same procedures as for an SAE (Section 6.4.6) 
PHV, in the same way and using the 
5.6 
Transmission of Infectious Agents 
The lyophilized study drug is to be stored refrigerated at 2°C to 8°C (36°F to 46°F) inside the original 
carton to protect it from light. Study drug should not be used beyond the date stamped on the label. 
After reconstitution, study drug may be kept at room temperature, should be protected from light, and 
should be used within 3 hours of reconstitution. Study drug does not contain preservatives; therefore, 
unused portions of study drug should be discarded. 
5.7 
Misuse for Illegal Purposes 
Rilonacept does not have addicting potential, and the risk of misuse for illegal purposes is minimal. 
5.8 
Prior and Concomitant Medications 
Use of all concomitant medications and any changes in concomitant medications will be recorded in 
the subject’s eCRF. The minimum requirement is that drug name and dates of administration are to be 
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recorded. This will include 
over-the-counter medications. 
all prescription drugs, herbal products, vitamins, minerals, and 
Any concomitant medication deemed necessary for the welfare of the subject during the study may be 
given at the discretion of the investigator. However, it is the responsibility of the investigator to ensure 
that details regarding the medication are recorded in full in the eCRF. The initiation of protocol 
prohibited medication (Section 5.8.6) requires discontinuation of study drug. 
Guidelines regarding the use of concomitant medication will be detailed in the Pharmacy Manual and 
are summarized in the following Sections. 
5.8.1 Screening 
Subjects included in the study may be receiving concomitant NSAIDs and/or colchicine, and/or oral 
CS treatment in any combination, provided that the dosages of these medications have been stable (or 
not increased) for at least 3 days prior to and including RI baseline (first administration of study drug), 
and changes in medications made within this time period (e.g., 1-time use of NSAIDs), in the opinion 
of the investigator, are not anticipated to significantly alter assessments of baseline disease activity. 
Analgesics can be used at the discretion of the investigator during screening activities prior to the first 
study drug dose, but only after the subject has documented a pericarditis pain level ≥4 on the 11-point 
NRS within 7 days prior to and including RI baseline (first administration of study drug). 
Subjects can enter the study on prednisone (or equivalent dose) not exceeding 60 mg/day for adults and 
not exceeding 0.5 mg/kg/day (with a maximum dose of 60 mg/day) in pediatric subjects. 
5.8.2 Single-blind RI Period 
• 
1-week Stabilization period, during which rilonacept is administered in addition to SOC pericarditis 
therapy and ongoing pericarditis episode is treated. All concomitant pericarditis medications 
including NSAIDs, analgesics, colchicine and CS will remain stable, unless the dosing must be 
decreased or stopped in the judgement of the investigator due to an AE. 
9-week background medication Weaning period, during which subjects are weaned off background 
SOC pericarditis therapy, as applicable, while treatment with blinded rilonacept continues. The 
guidelines for background medication taper and discontinuation will be provided in the Pharmacy 
Manual. 
Corticosteroids 
Starting at Week 1 and through Week 10, CS will be tapered and discontinued at a rate dependent 
on the dose at study entry. 
Analgesics 
• 
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Starting at Week 1 and through Week 10, analgesics (non-opioid and opioid) will be tapered and 
discontinued. Opioid analgesics can continue beyond Week 10 at stable doses through the end of 
the RW period if it is not feasible to discontinue them without causing withdrawal symptoms. 
NSAIDs and Colchicine 
Starting at Week 4 and through Week 10, NSAIDs and colchicine will be tapered and discontinued. 
• 
2-week Monotherapy period during which rilonacept administration continues: Subjects are 
required to be off all background SOC pericarditis therapy, with the exception of opioid analgesics 
if their discontinuation is not feasible. 
5.8.3 Double-blind Placebo-controlled RW Period 
During the RW period, subjects should not be receiving any concomitant medications for pericarditis, 
with the exception of opioid analgesics in case their taper down and discontinuation was not feasible in 
the RI period. 
5.8.3.1 
Concomitant Medication Upon Pericarditis Recurrence 
Subjects meeting protocol criteria for bailout rilonacept 
Upon pericarditis recurrence and meeting protocol criteria for bailout rilonacept (Sections 3.1 and 6.2.3) 
and completing the diagnostic workup as confirmed by the 
medical monitor, subjects 
will be transitioned to open-label rilonacept, as described in Section 3.1. Because open-label rilonacept 
can be administered only if at least 5 days have passed from the last blinded study drug administration, 
the investigators are allowed to use sequential ORT, i.e., analgesics, NSAIDs, and colchicine if 
necessary at their discretion. The use of those medications will be detailed in the Pharmacy Manual; it 
is briefly given as follows: 
• 
Analgesics (including non-opioid and opioid) can be used for pain control prior to completing the 
diagnostic workup for a recurrent pericarditis episode. The use of analgesics during pericarditis 
recurrence evaluation will provide pain relief for subjects without impacting their CRP levels or 
other objective components of the diagnostic workup. 
• 
After the diagnostic workup is completed based on the 
medical monitor’s 
assessment, NSAIDs followed by colchicine can be added to open-label rilonacept based on the 
subject’s clinical status and at the discretion of the investigator. 
If, after transition to open-label rilonacept, the investigator decides that the subject requires CS for 
pericarditis therapy, the subject will be discontinued from rilonacept and followed through the 
EORW visit. 
• 
Subjects not meeting protocol criteria for bailout rilonacept 
If, based on the investigator’s judgement, the subject is experiencing pericarditis recurrence that does 
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not meet the protocol criteria for bailout rilonacept (Sections 3.1 and 6.2.3) but does require additional 
treatment, the subject will continue blinded study drug, and the investigator should manage the 
pericarditis recurrence using sequential ORT for pericarditis, i.e., analgesics, NSAIDs, colchicine as 
described in the Pharmacy Manual and outlined briefly below: 
• 
Analgesics (including non-opioid and opioid) can be used for pain control prior to completing the 
diagnostic workup for a recurrent pericarditis episode. The use of analgesics during pericarditis 
recurrence evaluation will provide pain relief for subjects without impacting their CRP levels or 
other objective components of the diagnostic workup. 
• 
After the diagnostic workup is completed based on the 
medical monitor’s 
assessment, NSAIDs followed by colchicine can be added to blinded study drug based on the 
subject’s clinical status and at the discretion of the investigator. 
If, after the addition of NSAIDs and colchicine, the investigator decides that the subject requires 
CS for pericarditis therapy, the subject will be discontinued from blinded study drug and followed 
through the EORW visit. 
• 
5.8.4 Long Term Extension Treatment Period (LTE-TP) 
Subjects who opt to continue open-label rilonacept in the LTE-TP will have their concomitant 
pericarditis medications managed at the discretion of the investigator and based on the subject’s clinical 
status. If CS are required in addition to rilonacept to manage recurrent pericarditis, rilonacept should 
be discontinued. 
5.8.5 Long Term Extension Follow-Up Period (LTE-FUP) 
During LTE-FUP, pericarditis medication can be managed at the investigator’s discretion. 
5.8.6 Prohibited Concomitant Medicines During the Study 
Prohibited medications during the study and throughout the end of LTE-TP include the following: 
• 
• 
• 
• 
• 
Interleukin (IL) blockers other than rilonacept 
IL-6 blockers 
Janus-activating kinase inhibitors 
TNF inhibitors 
Potent immunosuppressants (azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, 
sirolimus, mercaptopurine, cyclophosphamide, chlorambucil, nitrogen mustard, or other alkylating 
agents, agents that deplete B or T cells [e.g., rituximab, alemtuzumab]) 
Live (attenuated) vaccines, which are prohibited during the study and within 12 weeks after the last 
study drug administration 
• 
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5.9 
Blinding 
In the single-blind RI period, all subjects will receive rilonacept but will be blinded to the duration of 
the RI period and the timing of randomization. 
The RW period is a double-blind period in which rilonacept and placebo are identical in appearance. 
Neither the subject nor any of the investigator/site staff, 
, or Sponsor staff who are involved in the 
treatment or clinical evaluation of the subjects will be aware of the treatment received (International 
Council for Harmonisation [ICH] E9). 
In the event of a pericarditis recurrence that meets the criteria for bailout rilonacept (Sections 3.1 and 
6.2.3), the subject will be transitioned to open-label rilonacept but will remain blinded to their prior 
RW treatment assignment. 
At the end of the RW period, all sites and subjects will be unblinded. Subjects will be offered 
participation in the LTE-TP, in which once-weekly open-label rilonacept can be continued for an 
additional 24 weeks. 
5.9.1 Breaking the Blind 
A subject’s treatment assignment will not be broken until the end of the RW period. 
If the treatment allocation for a subject becomes known to the investigator or other study staff involved 
in the management of study subjects, the Sponsor must be notified immediately. If the investigator 
intends to unblind treatment allocation for a subject, then the Sponsor should be notified immediately. 
The investigator may unblind a subject’s treatment assignment only in the case of an emergency, when 
knowledge of the study drug is essential for the appropriate clinical management or welfare of the 
subject. In most cases, the management of a medical emergency would be the same, regardless of 
whether the subject received active drug. The treatment assignment will be unblinded through the 
IWRS. The investigator must notify Kiniksa Pharmaceuticals and 
medical monitors as soon as 
possible but without revealing the treatment assignment of the unblinded subject, unless that 
information is important for the safety of subjects currently in the study. The date and reason for the 
unblinding must be recorded in the eCRF. 
The 
PHV staff may unblind the treatment assignment for any subject with an SAE. If the SAE 
requires that an expedited regulatory report be sent to one or more regulatory agencies, a copy of the 
blinded report may be sent to clinical investigators in accordance with local regulations. 
5.10 Treatment Compliance 
Subjects will record the administration of all doses of study drug (whether as an outpatient or in the 
clinic) in a subject’s diary. In addition, throughout all study periods, adherence to study drug 
administration will be assessed by the study site in collaboration with the visiting RN (Section 6). 
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6 
Study Assessments and Procedures 
Before performing any study procedures, all potential subjects will provide informed consent or an 
assent, if applicable. Potential subjects will have the study risks and benefits explained to them, the 
associated ICF reviewed with them, and all questions answered for them. Subjects will undergo 
screening procedures specific to the study only after the ICF has been provided by the subject unless 
performed as part of SOC practice. The investigator or designee will also sign the ICF. 
6.1 
Study Visits 
The schedule of assessments for the study site visits is summarized in the Study Schedule of 
Activities. Following screening assessments, qualifying subjects will be enrolled and enter the 
RI period. Subjects who stop background pericarditis medications and achieve Clinical Response at 
RI Week 12 (Section 6.2.2), will be randomized and enter the RW period. During both the RI and 
RW period, a combination of clinic and outpatient visits will occur. Outpatient visits may consist of 
telephone or virtual contacts as well as home visits conducted by a visiting nurse. For each scheduled 
visit of the study (including outpatient and clinic), assessments should occur prior to scheduled 
injections of study drug. Subjects can be brought to the clinic in place of a scheduled outpatient visit, 
for an unscheduled visit at the discretion of the investigator, or if arranging a visiting nurse for an at 
home visit is logistically not feasible. 
The visit schedule is derived from the day of the RI baseline visit. One week is equal to 7 calendar days. 
Although visits do not occur every week, subjects are required to record pericarditis pain NRS 
measurements on a daily basis in their study device and to administer study drug on a once-weekly 
basis and record it in their study electronic diary (eDiary). If a subject is unable to independently 
complete the daily eDiary, a caregiver may help enter the data. 
Upon completion of the RI and RW periods, all subjects will have the opportunity to continue 
participating in the LTE. This will require each subject again providing informed consent prior to LTE 
participation. The LTE period will have a treatment period (LTE-TP) and an off treatment follow-up 
period (LTE-FUP). 
Any subject who prematurely discontinues study drug will be followed for the duration of the trial as 
specified in Section 4.2.2. In addition, throughout all study periods, compliance with study drug 
administration will be assessed by the site in collaboration with the visiting RN. 
6.1.1 Screening: Clinic and Remote as Needed 
A study screening eCRF is required to be completed for every subject with a signed ICF. For each 
subject, the subject identification is obtained from the IWRS. 
It is anticipated that some subjects may have a portion of the study screening procedures done as part 
of routine care outside the auspices of this study. As long as these procedures were done within the 
allotted screening period timeframe, the results of these procedures may be used to support study 
screening and completion of the study screening eCRF. Any protocol-specified study qualification 
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procedures/tests not already done as part of routine care will need to be conducted after the subject 
provides informed consent and before enrollment. It is possible that the screening and enrollment visit 
will occur on the same day. 
The below procedures are required to be completed to screen a subject ≤28 days prior to enrollment. 
All assessments and procedures are not required to be completed on-site; however, the site is expected 
to obtain the medical records for subject source documentation. 
• 
• 
• 
Obtain the ICF. 
Enter the subject into the IWRS. 
Review inclusion/exclusion criteria; ensure that the subject has a diagnosis of recurrent pericarditis 
based and is presenting with at least the third pericarditis episode. 
Record: demographic information, medical/surgical history, concomitant medications, all prior and 
current concomitant pericarditis medications, a detailed pericarditis history including all recurrent 
pericarditis events. 
Perform a full physical examination (may be performed by an investigator or other healthcare 
provider designated by the investigator). 
Perform/obtain: 
• 
• 
• 
- 
11-point pericarditis pain NRS assessment – required to be >4 within 7 days prior to and 
including the day of RI baseline. The qualifying NRS assessment and CRP are not required to 
occur on the same day. 
CRP (mg/dL) – required within 7 days prior to and including the day of RI baseline. For study 
qualification purposes, the CRP may be assessed using 1 of 4 approaches: 
- 
▪ 
▪ 
▪ 
Point of care (POC) device provided by Sponsor (preferred method) 
Blood sample sent to the local laboratory 
CRP measurement taken as part of the subject’s routine care (e.g., not specifically obtained 
for this study) 
Blood sample sent to the central laboratory 
▪ 
- 
- 
- 
- 
Local laboratory hematology, chemistry, IGRA, hepatitis serology, HIV test 
Chest x-ray (unless performed and available within the past 12 weeks) 
Local or central laboratory urine pregnancy test for women of childbearing potential 
AE collection 
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6.1.2 Single-blind Treatment: Run-In 
6.1.2.1 
Enrollment (RI Baseline): Clinic Visit 
For subjects who meet study entry criteria, enrollment commences at the RI baseline visit. The 
following procedures occur: 
• 
• 
• 
• 
Review inclusion and exclusion criteria to confirm subject qualification. 
Review and record updates to recurrent pericarditis history since the screening visit. 
Revise IWRS status change to enrollment. 
Assess and record all concomitant medications as well as all prior and concomitant pericarditis 
medication. 
Perform an abbreviated physical examination, height and body weight. 
Acquire a 12-lead ECG. 
Acquire and submit a cardiac ECHO to the core laboratory per the core laboratory imaging 
guidelines; the ECHO is to be read locally prior to sending to the core lab. 
Perform cardiac MRI (for substudy participants only). 
Provide the subject with their study device and complete the following: 
• 
• 
• 
• 
• 
- 
For subjects ≥18 years, have them complete the 36-Item Short Form Health Survey (SF-36), 
5-level EuroQoL-5D (EQ-5D-5L), Insomnia Severity Index (ISI) 
For all subjects, instruct how to complete the 11-point pericarditis pain NRS (as outlined in 
Section 6.2.1.2) and the medication diary. 
Have all subjects complete the Patient Global Impression of Pericarditis Severity (PGIPS) 
score. 
- 
- 
• 
The investigator is to complete the Physician Global Assessment of Pericarditis Activity (PGA-
PA). 
Obtain the Pharmacogenomics ICF. 
Obtain a local or central laboratory urine pregnancy test for women of childbearing potential. 
Obtain central laboratory chemistry, hematology, lipid panel, CRP, anti-drug antibodies (ADAs 
[ADA sample will be also used for PK measurement]), biomarkers, and urinalysis (laboratory tests 
should be drawn prior to the first study drug administration, but results of those tests are not 
required before enrollment). 
AE reporting. 
Additional discussion/assessment as needed. 
• 
• 
• 
• 
• 
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Upon completion of the above study activities, study drug dispensing can commence. The following 
procedures occur: 
• 
Complete the IWRS to dispense assigned study drug; record the amount (number of vials) 
dispensed. 
Explain the study drug, proper once-weekly dosing, proper study drug administration technique, 
study drug administration documentation, and confirm that the subject (and subject’s caregiver as 
applicable) understands. 
For pediatric subjects, body weight (in kilograms) obtained at the RI baseline visit is to be used to 
determine appropriate study drug dosing in the RI period. Please refer to the pediatric study drug 
dosing Table 5–1 as well as the Study Schedule of Activities for subsequent visits with weight 
assessments for pediatric dosing. 
Prepare and administer the first injection of study drug and train the subject or caregiver to prepare 
and administer the second dose of study drug. 
Instruct the subject to bring to each clinic visit all medications the subject is taking, including used 
and unused study drug vials. 
Arrange upcoming study visits (as many visits as possible that can be arranged ahead of time is 
advised). 
• 
• 
• 
• 
• 
6.1.2.2 
RI Day 2: Clinic Visit (24-hour PK Sub-study Participants Only) 
The RI Day 2 visit includes a PK sample that is collected 24 hours after the loading dose of study drug 
and then sent to the central laboratory. 
6.1.2.3 
RI Day 4: TC/RN Visit 
The timing of the site TC visit on the RI Day 4 visit can occur independently of the RN visit. During 
the site TC visit, the subject is contacted to assess for AEs in follow-up to the initial injections received, 
to review the daily input of the pericarditis pain NRS score, as well as to review all concomitant 
medications, including concomitant pericarditis medication. The site then dispenses study drug (along 
with ancillary supplies) through the IWRS and coordinates shipment as outlined in the Pharmacy 
Manual. During the visiting RN visit, a CRP sample is drawn and sent to the central lab. 
6.1.2.4 
RI Week 1: TC/RN Visit 
It is preferred that the site TC occur prior to the RN visits. It is required that visit assessments occur 
prior to scheduled study drug dosing. The RI Week 1 visit is as follows: 
Site TC visit: 
• 
• 
Assess for AEs. 
Evaluate all concomitant medications as well as pericarditis concomitant medications. 
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• 
Provide instruction on the pericarditis concomitant medication oral corticosteroid tapering if 
applicable. 
Confirm and review upcoming visit arrangements. 
Additional discussion/assessment as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
• 
• 
RN home visit: 
• 
Obtain the central laboratory samples for CRP, PK, and biomarkers (these are collected prior to 
study drug administration). 
Provide review of self-administration of the study drug. 
Monitor administration of the study drug (whenever possible). 
Ensure the subject records study drug administration in the medication diary. 
Obtain used study drug vials and materials. 
Confirm upcoming visit arrangements. 
• 
• 
• 
• 
• 
6.1.2.5 
RI Week 2: TC/RN Visit 
It is required that visit assessments occur prior to scheduled study drug dosing. The RI Week 2 visit is 
as follows: 
Site TC visit: 
• 
• 
• 
• 
• 
• 
Assess for AEs. 
Evaluate all concomitant medications as well as pericarditis concomitant medications. 
Assess subject progress on the oral pericarditis corticosteroid tapering, if applicable. 
Review study drug administration and documentation compliance. 
Confirm and review upcoming visit arrangements. 
Additional discussion/assessment as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
RN home visit: 
• 
• 
Record study drug dispensing to the subject. 
Obtain central laboratory samples for CRP, PK, and ADAs (these are drawn prior to study drug 
administration). 
Provide review of self-administration of the study drug. 
Monitor administration of the study drug (whenever possible). 
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• 
• 
Obtain used study drug vials and materials. 
Confirm upcoming visit arrangements. 
6.1.2.6 
RI Week 4: TC/RN Visit 
It is required that visit assessments occur prior to scheduled study drug dosing. The RI Week 4 visit is 
as follows: 
Site TC visit: 
• 
• 
• 
Assess for AEs. 
Evaluate all concomitant medications as well as pericarditis concomitant medications. 
Assess subject progress on the oral corticosteroid tapering if applicable and provide instruction on 
NSAID and/or colchicine tapering if applicable. 
Additional discussion/assessment as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
Confirm and review upcoming visit arrangements. 
Instruct the subject to bring used and unused study drug vials (those not yet obtained by the visiting 
RN) to the next clinic visit. 
• 
• 
• 
RN home visit: 
• 
Obtain central laboratory samples for CRP, PK, and biomarkers (these are drawn prior to study 
drug administration). 
Obtain a pharmacogenomics sample for those subjects who have provided informed consent. 
Provide review of self-administration of the study drug. 
Monitor administration of the study drug (whenever possible). 
Obtain used study drug vials and materials. 
Confirm upcoming visit arrangements. 
• 
• 
• 
• 
• 
6.1.2.7 
RI Week 6: Clinic Visit 
The RI Week 6 visit in the clinic includes the following assessments and procedures: 
• 
• 
• 
Assess for AEs. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Assess subject progress on the concomitant oral corticosteroid, NSAID and/or colchicine tapering 
if applicable. 
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• 
• 
• 
• 
• 
Obtain used and unused study drug vials for study drug compliance evaluation. 
Have all subjects complete the PGIPS score. 
The investigator is to complete the PGA-PA. 
Obtain central laboratory samples for hematology, chemistry, CRP, and ADAs. 
Additional discussion/assessment as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
Upon completion of the above study activities, the study drug dispensing can commence. The following 
procedures occur: 
• 
• 
Dispense study drug through the IWRS and record the amount (number of vials) dispensed. 
Have the subject administer the next scheduled injection of study drug (if within the study drug 
window) and have the subject record in the medication diary. 
Review the study drug dosing schedule, administration techniques, and documentation. 
Confirm upcoming visit arrangements. 
• 
• 
6.1.2.8 
RI Week 10: TC Visit 
The following assessments and procedures are to be completed: 
• 
• 
• 
• 
• 
• 
Assess for AEs. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Assess concomitant oral corticosteroid, NSAID and/or colchicine tapering completion. 
Assess study drug administration documentation. 
Confirm the RI Week 12/RW baseline clinic visit arrangements. 
Additional discussion/assessments as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
6.1.2.9 
Randomization (RI Week 12/RW Baseline): Clinic Visit 
The following assessments and procedures are conducted at the RI Week 12 visit, prior to 
randomization: 
• 
CRP assessment (local and central) (the POC device provided for the study is the preferred method 
for local laboratory CRP assessment). 
Obtain a pericarditis pain NRS average score for the prior 7 days, including the day of the visit 
(4 missing NRS values within this week may result in an inability to move forward with 
randomization). 
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• 
• 
Acquire a 12-lead ECG. 
Acquire and submit a cardiac ECHO to the core laboratory per the core laboratory imaging 
guidelines; ECHO is read locally prior to submission to the core lab. 
Abbreviated physical examination, height and body weight. 
For subjects ≥18 years, complete on their device SF-36, EQ-5D-5L, ISI. 
For all subjects, complete the PGIPS score. 
The investigator is to complete the PGA-PA. 
Obtain central laboratory samples for chemistry, hematology, lipid panel, PK, and ADAs. 
Evaluate concomitant medications including pericarditis concomitant medication. 
Assess for AEs. 
Obtain used and unused study drug vials for study drug compliance evaluation. 
Additional discussion/assessments as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
Assess for Clinical Response (refer to Section 6.2.2). 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
For subjects who have successfully completed the RI period and are assessed as achieving Clinical 
Response at the RI Week 12 visit, the RW baseline visit commences. 
The following assessments and procedures are conducted at the RW baseline visit: 
• 
• 
Update the subject status in the IWRS by randomizing the subject in the IWRS. 
Obtain weight for pediatric drug dispensing and dosing (Table 5–1). Please refer to the pediatric 
study drug dosing Table 5–1 as well as the Study Schedule of Activities for subsequent visits with 
weight assessments for pediatric dosing during RW. 
Dispense study drug and record the amount (number of vials) dispensed. 
Have the subject administer the study drug and record in the diary (if within the study drug 
window). 
Instruct the subject to bring all medications including used and unused study drug to each clinic 
visit. 
Instruct the subjects on the process to follow for a pericarditis recurrence event. 
Arrange upcoming visits. 
• 
• 
• 
• 
• 
For subjects that do not qualify for randomization per the IWRS, the 
medical monitor is to be 
immediately contacted to evaluate the reasons for non-qualification. Following medical monitor 
consultation, if the subject is deemed to not be a treatment responder, the RI Week 12 visit will be 
completed, study drug will be discontinued, and the subject will not proceed to randomization. The 
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subject will be requested to perform a 6-week safety follow-up (SFU) visit after his/her last dose of 
study drug as well as continue with follow-up as agreed upon until the EORW period. 
6.1.3 Randomized-Withdrawal (RW) Period 
During the RW period, subjects will continue with once-weekly study drug administration as well as 
daily 11-point pericarditis pain NRS scoring. Visits will occur every 4 weeks, alternating TC/RN visits 
and clinic visits, with the first visit during the RW period (RW Week 4) being a TC/RN visit. Additional 
unscheduled visits may occur at any time for evaluation of suspected pericarditis recurrence (Section 
6.1.6.1) or for other reasons as deemed necessary by the study investigator. 
The following procedures are to occur during the TC/RN visits: 
Site TC visits: 
• 
• 
• 
• 
• 
• 
Assess for AEs. 
Assess for suspected pericarditis recurrence events. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Additional discussion/assessment as needed. 
Confirm and review upcoming visit arrangements. 
Instruct the subject to bring used and unused study drug vials (those not yet obtained by visiting 
RN) to the next clinic visit. 
RN home visits: 
• 
• 
• 
• 
Obtain central laboratory samples for CRP. 
Provide review of self-administration of the study drug as needed. 
Monitor administration of the study drug (whenever possible). 
Obtain used study drug vials and materials. 
The following procedures are to occur during the clinic visits (except for Week 24; see below): 
• 
• 
• 
• 
• 
• 
Assess for AEs. 
Assess for suspected pericarditis recurrence events. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Record height and body weight. 
Obtain central laboratory samples for chemistry, hematology, and CRP. 
Obtain central laboratory sample for PK and biomarkers (Weeks 8 and 24 only). 
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• 
• 
• 
• 
Obtain central laboratory sample for ADAs (Week 24 only). 
Have all subjects complete the PGIPS score. 
The investigator is to complete the PGA-PA. 
Additional discussion/assessment as needed (i.e., remind the subject about daily pericarditis pain 
NRS entry). 
Obtain used and unused study drug vials for study drug compliance evaluation. 
• 
Upon completion of the above study activities, study drug dispensing can commence. The following 
procedures occur: 
• 
• 
Obtain weight for pediatric drug dispensing and dosing (Table 5–1). 
Monitor administration of the study drug dose (whenever possible) and have the subject record in 
the medication diary. 
Dispense study drug through the IWRS and record the amount (number of vials) dispensed. 
Review the study drug dosing schedule, administration techniques, and documentation. 
Confirm upcoming visit arrangements. 
• 
• 
• 
6.1.3.1 
RW WEEK 24: Clinic Visit 
The Week 24 visit in the clinic includes the following assessments and procedures: 
• 
• 
• 
• 
• 
• 
Assess for AEs. 
Assess for suspected pericarditis recurrences. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Perform a full physical examination, height and body weight. 
Acquire a 12-lead ECG. 
Acquire a cardiac ECHO for core laboratory central review; the ECHO is to be read locally before 
sending to the core lab. 
Obtain an MRI (for substudy participants only). 
For subjects >18 years, complete the SF-36, EQ-5D-5L, ISI. 
For all subjects, complete the PGIPS score. 
The investigator is to complete the PGA-PA. 
Obtain central laboratory samples for chemistry, hematology, lipid panel, CRP, PK, ADAs, and 
biomarkers. 
Obtain used and unused study drug vials for study drug compliance evaluation. 
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• 
Additional discussion/assessment as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
Upon completion of the above study activities, the study drug dispensing can commence. The following 
procedures occur: 
• 
• 
Obtain weight for pediatric drug dispensing and dosing (Table 5–1). 
Have the subject administer the RW Week 24 study drug dose (if within the study drug window) 
and have the subject record it in the medication diary. 
Dispense study drug through the IWRS and record the amount (number of vials) dispensed. 
Review the study drug dosing schedule, administration techniques, and documentation. 
Confirm upcoming study visits. 
• 
• 
• 
6.1.3.2 
EORW (End of RW Period/LTE Baseline): Clinic Visit 
The EORW visit will be same day as LTE-TP baseline visit. 
All randomized subjects, including those that have had pericarditis recurrence or have permanently 
discontinued study drug will have an EORW visit at the end of the RW period. The EORW activities 
are listed below: 
• 
• 
• 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Acquire a 12-lead ECG. 
Acquire and submit a cardiac ECHO to the core laboratory per the core laboratory imaging 
guidelines; the EHCO is to be read locally prior to submission to the core lab. 
Perform a full physical examination, height and body weight. 
For subjects >18 years, complete the SF-36, EQ-5D-5L, ISI. 
For all subjects, complete the PGIPS score. 
The investigator is to complete the PGA-PA. 
Obtain central laboratory samples for chemistry, hematology, lipid panel, CRP, PK, ADAs, and 
urinalysis. 
Assess for AEs. 
Assess for pericarditis recurrences. 
Obtain informed consent for participation in the LTE period. 
Additional discussion/assessment as needed. 
• 
• 
• 
• 
• 
• 
• 
• 
• 
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Upon completion of the EORW visit procedures and obtaining subject informed consent to participate 
in the LTE period, the LTE baseline visit procedures are as follows: 
• 
Change the subject’s status in the IWRS and obtain unblinding information; proceed with subject 
unblinding. 
Obtain weight for pediatric drug dispensing and dosing (Table 5–1). 
Dispense study drug and record the amount (number of vials) dispensed. 
Have the subject administer the LTE-TP Day 1 study drug dose as applicable (if within the study 
drug window) and have the subject record it in the medication diary. 
Instruct subjects on continuing the 11-point pericarditis pain NRS score daily entry. 
Review the study drug dosing schedule, administration techniques, and documentation. 
Additional discussion/assessments as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
Confirm the upcoming study visits. 
• 
• 
• 
• 
• 
• 
• 
6.1.4 Long Term Extension 
6.1.4.1 
LTE Weeks 8 and 16: Clinic Visit 
The LTE Weeks 8 and 16 clinic visit procedures are as follows: 
• 
• 
• 
• 
• 
• 
• 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Have all subjects complete the PGIPS score. 
The investigator is to complete the PGA-PA. 
Obtain central laboratory samples for chemistry, hematology, and CRP. 
Assess for AEs. 
Assess for pericarditis recurrence events. 
Additional discussion/assessment as needed (i.e., remind the subject about daily pericarditis pain 
NRS input). 
Confirm upcoming visit arrangements. 
Obtain weight for pediatric drug dispensing and dosing (Table 5–1). 
Dispense study drug through the IWRS and record the amount (number of vials) dispensed. 
Review the study drug dosing schedule, administration techniques, and documentation. 
• 
• 
• 
• 
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• 
Have the subject administer the regularly scheduled study drug dose as applicable (if within the 
study drug window) and have the subject record it in the medication diary. 
Confirm the upcoming study visits. 
• 
6.1.4.2 
LTE Week 24 Clinic Visit 
The LTE Week 24 visit is the final visit of the LTE-TP. However, if at any time throughout the course 
of the study a subject prematurely discontinues study drug, an End of Treatment (EOT) visit is to occur. 
The visit procedures are as follows: 
• 
• 
• 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Acquire a 12-lead ECG. 
Acquire a cardiac ECHO for core laboratory central review; the EHCO is to be read locally prior 
to submission to the core lab. 
Obtain cardiac MRI (substudy participants only). 
Perform a full physical examination. 
For subjects >18 years, complete the SF-36, EQ-5D-5L, ISI. 
For all subjects, complete the PGIPS score. 
The investigator is to complete the PGA-PA. 
Obtain central laboratory samples for chemistry, hematology, lipid panel, CRP, PK, ADAs, 
biomarkers, and urinalysis. 
Assess for AEs. 
Assess for pericarditis recurrence events. 
Have the subject administer the regularly scheduled study drug as applicable (if within study drug 
window), and have the subject record it in the medication diary. 
Change the subject status in the IWRS. 
Arrange an LTE Week 30 visit. 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
6.1.5 
LTE Follow-Up Period 
Upon completion of the LTE Week 24 EOT visit, subjects continue long term follow-up until the end 
of the study (EOS). The LTE-FUP includes 2 visits. 
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6.1.5.1 
LTE Week 30 Visit: Clinic 
The LTE Week 30 visit is a clinic visit. Visit activities are as follows: 
• 
• 
• 
• 
• 
• 
Assess for AEs. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Assess for pericarditis recurrence events. 
Additional discussion/assessment as needed. 
Obtain central laboratory samples for CRP, ADAs, and urine pregnancy test. 
Any left-over ancillary supplies are to be returned to the site. 
6.1.5.2 
LTE Week 48 End of Study Visit: TC 
The LTE Week 48 EOS TC visit procedures are as follows: 
• 
• 
• 
Assess for AEs. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Assess pericarditis recurrence. 
6.1.6 Supplemental Visits 
6.1.6.1 
Pericarditis Recurrence Assessment: Clinic Visit 
If a subject experiences symptoms consistent with pericarditis recurrence, he/she should contact the 
study investigator immediately for evaluation. It is possible that a subject may have assessments 
performed remotely, however, assessments are also expected be performed at the study site as soon as 
possible. Required assessments include: 
• 
• 
• 
Evaluate pericarditis pain on the 11-point NRS. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Obtain laboratory samples for CRP (local and central) (the POC device provided by Kiniksa 
Pharmaceuticals is the preferred method for local laboratory CRP assessment). 
Acquire a 12 lead ECG. 
Acquire a cardiac ECHO per core laboratory imaging parameters; this ECHO is read locally for the 
purpose of pericarditis recurrence assessment and is then submitted to the ECHO core laboratory 
for central review. 
Perform an abbreviated physical examination, height and body weight. 
For subjects >18 years, complete the SF 36, EQ-5D 5L, ISI. 
• 
• 
• 
• 
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• 
• 
• 
• 
For all subjects, complete the PGIPS score. 
The investigator is to complete the PGA PA. 
Obtain central laboratory samples for PK, ADAs, and biomarkers. 
Other procedures deemed necessary per the investigator or delegated site personnel. 
Upon having completed the evaluation, if the investigator makes a clinical diagnosis that the subject is 
having a pericarditis recurrence event, he/she should contact the 
medical monitor to review and 
confirm that all assessments have been performed and collected. Upon 
medical monitor 
confirmation of completion of the assessment, the investigator commences as described in Section 
6.2.3. 
Subjects treated for a pericarditis recurrence event will continue to follow the same visit schedule 
described for the RW period (Section 6.1.3). 
Source documentation including the assessments and evaluations used to confirm a pericarditis 
recurrence event, are required to be sent to CEC. 
6.1.6.2 
End of Treatment Visit: Clinic 
The EOT visit is to be conducted when a subject permanently discontinues study drug. For subjects 
who complete the RW period but do not consent to participate in the LTE period, the EORW and EOT 
visit can be combined. For those subjects who do consent to participate in the LTE period, the EOT 
visit can be combined with the LTE Week 24 visit. In the event that a subject prematurely discontinues 
study drug, it is expected that the subject will have an EOT visit as soon as possible and continue to be 
followed as described in Section 4.2.2. 
The EOT visit procedures are as follows: 
• 
• 
• 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Acquire a 12 lead ECG. 
Acquire a cardiac ECHO for core laboratory central review; the ECHO is to be read locally prior 
to submission to the core lab. 
Perform a cardiac MRI (for sub-study participants only) only if the previous MRI was done longer 
than 6 months ago. 
Perform a full physical examination. 
For subjects >18 years, complete the SF-36, EQ-5D-5L, ISI. 
For all subjects, complete the PGIPS score. 
The investigator is to complete the PGA PA. 
• 
• 
• 
• 
• 
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• 
Obtain central laboratory 
biomarkers, and urinalysis. 
Assess for AEs. 
samples for chemistry, hematology, lipid panel, CRP, PK, ADAs, 
• 
• 
• 
Assess for pericarditis recurrence events. 
Arrange SFU visit. 
6.1.6.3 
Safety Follow-Up Visit: Clinic or TC/RN 
The SFU visit is to be conducted 6 weeks after the last dose of study drug. For those subjects who 
discontinue study drug at the LTE Week 24 visit, the SFU visit is to occur as a clinic visit. However, 
for those subjects who prematurely discontinue study drug during the study, the visit may be conducted 
in the clinic or as an outpatient (TC/RN visit) based on investigator discretion. The visit activities are 
as follows: 
Site TC visit: 
• 
• 
• 
• 
Assess for AEs. 
Evaluate concomitant medications as well as pericarditis concomitant medications. 
Assess for pericarditis recurrence events. 
Remind the subject to continue daily pericarditis pain NRS input if the SFU is occurring prior to 
the LTE Week 24 visit. 
Additional discussion/assessment as needed. 
• 
RN home visit: 
• 
• 
Obtain central laboratory samples for CRP, ADAs, and urine pregnancy test. 
Collect any leftover ancillary supplies and return to the site. 
When the visit is conducted as a clinic visit, all of the RN visit activities are to be performed during the 
clinic visit. 
6.2 
Efficacy Assessments 
Efficacy assessments to be performed at study visits are summarized in the Study Schedule of Activities 
and include: CRP, daily pericarditis pain assessment (11-point NRS), ECG, ECHO, Patient Global 
Impression of Pericarditis Severity (PGIPS), Physician Global Assessment of Pericarditis Activity 
(PGA-PA), and subject’s quality of life assessments (SF-36, EQ-5D-5L) and insomnia questionnaire 
(ISI). In a substudy at selected sites, a cardiac MRI will be performed. 
Note that in case the electronic versions of the PROs and assessments/questionnaires (PGIPS, PGA-PA, 
SF-36, EQ-5D-5L, and ISI) are not available, the paper forms must be completed until the electronic 
versions are available again. 
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6.2.1 Individual Efficacy Assessments 
6.2.1.1 
C-Reactive Protein 
Central and local laboratory assessments of CRP will be performed at study visits as described in the 
Study Schedule of Activities. Centrally assayed CRP values will be used for statistical evaluations of 
changes from baseline. Locally assayed CRP will be used for screening, evaluation of treatment 
response prior to randomization, and assessment of suspected pericarditis recurrence in the RW period. 
The POC device provided by Kiniksa Pharmaceuticals is the preferred method for local laboratory CRP 
assessment. 
6.2.1.2 
11-Point Pericarditis Pain Numerical Rating Scale 
Subjects will be asked to provide a daily assessment of pericarditis pain starting at RI baseline. A 
validated 11-point pericarditis NRS (Section 13.2) will be used to measure the subject’s level of pain 
intensity on a daily basis throughout the study (Hawker et al 2011; Mannion et al 2007; Dworkin et al 
2005). 
It is recommended that daily pericarditis pain measurements using the 11-point NRS are performed by 
subjects at the same time of the day each day, and prior to study drug injection on days with study drug 
administration. 
6.2.1.3 
Electrocardiogram 
Twelve-lead ECGs will be performed at study visits as described in the Study Schedule of Activities. 
Pericarditis commonly involves changes in the electrophysiologic activity of the heart, resulting in 
typical ECG findings, namely widespread ST-segment elevation or PR-segment depression. 
6.2.1.4 
Echocardiogram 
Echocardiographic assessment of presence of pericardial effusion including new or worsening of 
pericardial effusion should be obtained at study visits as described in the Study Schedule of Activities. 
Pericardial effusion is characterized by accumulation of excess fluid in the pericardial space 
surrounding the heart, and pericarditis is one of the main causes of pericardial effusion. 
Echocardiography is a sensitive tool and the most widely used imaging technique for the detection of 
pericardial effusion and/or thickening. Echocardiograms are to be acquired per the ECHO core imaging 
parameters. Upon local assessment and interpretation, the ECHO is then to be submitted to the 
designated central imaging laboratory. 
6.2.1.5 
Patient Global Impression of Pericarditis Severity 
Patient Global Impression questionnaires have been developed for a variety of indications. The PGIPS 
is a single-item PRO measure that assesses the subject’s impression of overall severity of pericarditis 
symptoms at the time the questionnaire is administered, using a 7-point rating scale ranging from absent 
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(no recurrent pericarditis symptoms) to very severe (recurrent pericarditis symptoms cannot be ignored) 
(Guy 1976). The PGIPS can be completed in less than 30 seconds. 
The subject will select the box that best describes the severity of pericarditis symptoms right now: 
 
 
 
 
 
 
 
Absent: no symptoms 
Minimal: can be easily ignored without effort 
Mild: can be ignored with effort 
Moderate: cannot be ignored but does not influence my daily activities 
Moderately severe: cannot be ignored and occasionally limits my daily activities 
Severe: cannot be ignored and often limits my concentration on daily activities 
Very severe: cannot be ignored and markedly limits my daily activities 
The PGIPS will be collected as described in the Study Schedule of Activities. 
6.2.1.6 
Physician Global Assessment of Pericarditis Activity 
Physician Global Assessment questionnaires have been developed for a variety of indications. The 
PGA-PA is a single-item clinician-reported outcome measure that investigators use to rate their 
impression of the patient’s overall pericarditis disease activity at the time the assessment is completed, 
using a 7-point rating scale ranging from absent to very severe (Guy 1976). Like the PGIPS, the 
PGA-PA can be completed in less than 30 seconds. 
The investigator will select the box that best describes subject’s pericarditis activity right now. 
 
 
 
 
 
 
 
Absent 
Minimal 
Mild 
Moderate 
Moderately severe 
Severe 
Very severe 
The PGA-PA will be collected as described in the Study Schedule of Activities. 
6.2.1.7 
36-Item Short Form Health Survey 
The SF-36 is a set of generic, coherent, and easily administered quality-of-life measures. The SF-36 
was developed at RAND Corporation as part of its Medical Outcomes Study. The SF-36 assesses 
8 health domains: physical functioning, bodily pain, role limitations due to physical health problems, 
role limitations due to personal or emotional problems, general mental health, social functioning, 
energy/fatigue, and general health perceptions. It also includes a single item that provides an indication 
of perceived change in health. 
SF-36 will be collected in subjects ≥18 years or older as described in the Study Schedule of Activities. 
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6.2.1.8 
EQ-5D-5L 
The EQ-5D-5L is a standardized instrument developed by the EuroQol Group as a measure of 
health-related quality of life that can be used in a wide range of health conditions and treatments. The 
EQ-5D-5L consists of a descriptive system and the EQ VAS. The descriptive system comprises 
5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The rating 
scale records the subject’s self-rated health on a vertical VAS. This can be used as a quantitative 
measure of health outcome that reflects the subject’s own judgement. The scores on these 5 dimensions 
can be presented as a health profile or can be converted to a single summary index number (utility) 
reflecting preferability compared to other health profiles (https://euroqol.org/eq-5d-instruments). 
The EQ-5D-5L will be collected in subjects ≥18 years or older as described in Study Schedule of 
Activities. 
6.2.1.9 
Insomnia Severity Index 
The ISI is a 7-item self-report questionnaire assessing the nature, severity, and impact of insomnia. The 
usual recall period is the “last 2 weeks” and the dimensions evaluated are severity of sleep onset, sleep 
maintenance, early morning awakening problems, sleep dissatisfaction, interference of sleep difficulties 
with daytime functioning, noticeability of sleep problems by others, and distress caused by the sleep 
difficulties. A 5-point Likert scale is used to rate each item (e.g., 0=no problem; 4=very severe 
problem), yielding a total score ranging from 0 to 28. The total score is interpreted as follows: no 
clinically significant insomnia (0–7); subthreshold insomnia (8–14); clinical (moderate) insomnia (15– 
21); and clinical (severe) insomnia (22–28) (Morin et al 2011). 
The ISI will be collected in subjects ≥18 years or older as described in Study Schedule of Activities. 
6.2.1.10 Cardiac MRI 
Cardiac MRI will be performed as described in the Study Schedule of Activities in subjects at selected 
sites in the cardiac MRI substudy. Cardiac MRI will be performed to assess any changes in pericardial 
inflammation. Cardiac MRI readings will be performed by a central imaging laboratory. The study 
site/clinic reading of the MRI at the time of the examination may be used by the investigator for clinical 
decision-making. 
6.2.2 Assessment of Clinical Response at the End of the Run-In Period Week 
12/RW Baseline 
At RI Week 12/RW baseline visit, all subjects receiving rilonacept who are able to discontinue 
background SOC pericarditis therapy during the RI period (Section 3.1) are assessed for Clinical 
Response. Only subjects who achieve Clinical Response at RI Week 12 and have discontinued 
background medications for pericarditis are eligible for randomization in the RW period. 
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Clinical Response at RI Week 12 is defined as follows: 
• 
A weekly average of daily pericarditis pain of ≤2.0 on the 11-point NRS during the 7 days prior to 
and including the day of randomization, AND 
CRP level ≤0.5 mg/dL at the RI Week 12/RW baseline visit. 
• 
6.2.3 Management of Suspected Pericarditis Recurrence in the RW Period 
Pericarditis Recurrence Definition: Pericarditis recurrence, for the purpose of the protocol, is defined 
as the recurrence of typical pericarditis pain associated with supportive objective evidence of 
pericarditis. 
At any time point during the RW period, subjects who experience suspected recurrence of their 
pericarditis will have been instructed to inform their site investigator as soon as possible. Subjects who 
experience a suspected recurrence of pericarditis symptoms will be requested to report to the study 
site/clinic for a scheduled or unscheduled visit, during which clinical assessments will be performed to 
gather all the necessary diagnostic data to confirm or rule out the presence of pericarditis recurrence 
(Section 6.1.6.1). The investigator will evaluate all assessments performed for a diagnostic workup, 
whether at the study site or at locations outside. 
Upon completion of pericarditis workup, the investigator is required to contact the 
medical monitor to confirm that the protocol required diagnostic workup is complete prior to 
implementing treatment for the event. 
Following communication with the 
medical monitor, if the event meets the criteria for 
bailout rilonacept (at least 1 day with pericarditis pain measurement ≥4 on the 11-point NRS and 
one CRP value ≥1 mg/dL either on the same day or separated by no more than 7 days), and after the 
medical monitor has confirmed with the investigator that the diagnostic workup is 
complete, the attainment of bailout criteria is confirmed in the IWRS, blinded study drug is 
discontinued, and open-label rilonacept treatment is dispensed. If needed, sequential ORT is allowed 
as outlined in Section 5.8.3. The subject will continue to be followed up according to the Study 
Schedule of Activities for the RW period. 
Following communication with the 
medical monitor, if the event does not meet the 
protocol criteria for bailout rilonacept but in the judgement of investigator requires treatment, after the 
medical monitor has confirmed with the investigator that the diagnostic workup is 
complete, the investigator is allowed to add sequential ORT to blinded study drug, and as outlined in 
Section 5.8.3. Blinded study drug treatment will continue until a pericarditis recurrence that meets 
criteria for bailout rilonacept, or until the end of the RW period. 
For a summary of management of suspected pericarditis recurrence, refer to Figure 3. 
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Upon suspected pericarditis recurrence, the event is required to be captured in the electronic data 
capture (EDC) system within 24 hours of learning of the event, and a pericarditis recurrence event 
adjudication package must be prepared for adjudication by CEC. The event package will include, but 
may not be limited to, data on the subject’s pericarditis pain level, CRP value, ECG tracing, ECHO 
result, the presence or absence of pericardial rub, and any additional source documentation relevant to 
the assessment of the suspected event. Details on endpoint package requirements will be described in 
the CEC charter. The CEC-confirmed pericarditis recurrences will be used for Primary Endpoint 
efficacy analysis. For more details on the CEC, refer to Section 6.7.2 
Figure 3: 
Management of Suspected Pericarditis Recurrence in the Randomized- 
Withdrawal Period 
Pericarditis 
Recurrence * 
*Per protocol: CRP, ECG, ECHO, and pericardial rub assessment 
to be completed prior to treatment intervention 
NRS ≥ 4 
NO 
NO 
Able to observe 
event without 
treatment 
YES 
CRP ≥ 1.0 mg/dL 
YES 
YES 
YES 
Symptom 
Progression 
ORT=Oral Rescue Therapy 
6.3 
Safety Assessments 
Safety assessments to be performed at study visits are summarized in Study Schedule of Activities and 
include: assessment of AEs (Section 6.4), physical examinations (full and abbreviated) including vital 
signs measurements, chest x-ray, TB screening, and clinical laboratory tests (serology, hematology, 
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Bailout open-label 
rilonacept; and 
sequential ORT if 
needed 
(per Section 5.8.3) 
Continue 
observation and 
blinded study drug 
 
 
 
 
Continue blinded 
study drug; and 
sequential ORT if 
needed 
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chemistry, urinalysis) (Section 6.6). A pregnancy test (Section 6.6.6) will be conducted at screening 
and as needed during the study and must be performed 6 weeks after the last study drug administration. 
6.3.1 Physical Examination 
A full physical examination should include at minimum an evaluation of vital signs, head, eyes, ears, 
nose, and throat as well as cardiovascular, dermatological, musculoskeletal, respiratory, GI, 
genitourinary, and neurological systems. The decision to perform examination of genitourinary system 
should be guided by clinical judgement. Body weight and height will be measured as per the Study 
Schedule of Activities and will be recorded in the eCRF. Any abnormality identified at baseline should 
be recorded on the medical history and physical examination eCRFs. At selected visits as specified in 
the Study Schedule of Activities, an abbreviated physical examination will be performed to evaluate 
vital signs, lung and heart sounds, including evaluation for pericardial rub. 
At all visits at the study site, limited symptom-directed physical examinations may need to be 
performed in order to determine changes from baseline or abnormalities and should be recorded in the 
subject’s trial notes. New or worsened abnormalities should be recorded as AEs on the Adverse Event 
eCRF. 
6.3.2 Vital Signs 
Vital signs include measurements of respiratory rate, pulse rate, systolic and diastolic blood pressure, 
and temperature. Blood pressure measurements should be obtained after the subject has been seated for 
at least 5 minutes. 
6.3.3 Chest X-ray 
Chest x-rays in accordance with local requirements will be obtained at screening (or an existing chest 
x-ray within 12 weeks of first study drug administration can be used) according to the Study Schedule 
of Activities. Chest x-rays should be reviewed by a qualified radiologist for clinically significant 
abnormalities and evidence of pulmonary disease that would exclude the potential subject. 
6.3.4 Tuberculosis Screening 
An IGRA test or another TB test based on acceptable clinical practice in each country will be performed 
in order to evaluate for the presence of active or latent TB infection at screening. 
6.4 
Adverse Events 
The investigator is responsible for reporting all AEs that are observed or reported during the study, 
regardless of their relationship to study drug or their clinical significance. 
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6.4.1 Definitions 
6.4.1.1 
Adverse Event 
An AE is any untoward medical occurrence in a subject or clinical investigation subject administered 
a pharmaceutical product. An AE does not necessarily have a causal relationship with this treatment. 
An AE can therefore be any unfavorable sign (including an abnormal laboratory finding), symptom or 
disease temporally associated with the use of a medicinal (investigational) product, whether or not 
related to the medicinal (investigational) product. AEs also include: any worsening (i.e., any clinically 
significant change in frequency and/or intensity) of a pre-existing condition that is temporally 
associated with the use of the study drug; abnormal laboratory findings considered by the reporting 
investigator to be clinically significant; and any untoward medical occurrence. 
6.4.1.2 
Treatment-emergent Adverse Event 
A treatment-emergent AE (TEAE) is defined as any event not present before exposure to the study drug 
or any event already present that worsens in either intensity or frequency after exposure to the study 
drug. 
6.4.1.3 
Serious Adverse Event 
A serious adverse event (SAE) is any untoward medical occurrence or effect that, at any dose: 
• 
Results in death. Includes all deaths, even those that appear to be completely unrelated to the study 
drug (e.g., car accident where the subject is a passenger). 
Is life-threatening. In the view of the investigator, the subject was at immediate risk of death from 
the event at the time of the event (i.e., it does not include an AE that might have caused death if it 
had occurred in a more serious form). 
Requires in-patient hospitalization or prolongs an existing hospitalization. (Complications 
occurring during hospitalization are AEs and are SAEs if they cause prolongation of the current 
hospitalization. Hospitalization for elective treatment of a pre-existing non-worsening condition is 
not, however, considered an AE. The details of such pre-existing condition must be recorded on 
the medical history or physical examination page of the eCRF. Hospitalization is defined as an 
admission to the hospital ward, a short-stay type unit, or Emergency Room for longer than 24 hours. 
Prolongation of existing hospitalization is defined as a hospital stay longer than originally 
anticipated for the event or development of a new AE as determined by the Investigator or treating 
physician.) 
Results in persistent or significant disability/incapacity. (An AE is incapacitating or disabling if it 
results in a substantial and/or permanent disruption of the subject’s ability to carry out normal life 
functions.) 
Is a congenital anomaly/birth defect. 
• 
• 
• 
• 
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• 
Is an important medical event. Important medical events may not be immediately life-threatening 
or result in death or hospitalization but may jeopardize the subject or may require intervention to 
prevent one of the other serious outcomes listed above (e.g., intensive treatment in an emergency 
room or at home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in 
hospitalization; or development of drug dependency or drug abuse). 
In addition, medical and scientific judgment is required to decide if prompt notification is required in 
situations other than those defined for SAEs above, i.e., any event that the investigator regards as 
serious that did not strictly meet the criteria above but may have jeopardized the subject or required 
intervention to prevent one of the outcomes listed above, or that would suggest any significant hazard, 
contraindication, side effect, or precaution that may be associated with the use of the study drug. 
All SAEs that occur after signing of study-related informed consent, whether or not the SAEs are related 
to the study drug or study procedures, must be reported. 
6.4.1.4 
Adverse Event of Special Interest 
An adverse event of special interest (AESI) is defined as an AE of scientific and medical interest 
specific to the understanding of the study drug and requiring close monitoring and rapid communication 
by the investigator to the Sponsor. An AESI may be serious or non-serious. The rapid reporting of 
AESIs allows ongoing analysis of these events in order to characterize and understand them in 
association with the use of the study drug. 
Treatments with immunosuppressants, including rilonacept, may result in an increase in the risk of 
malignancies. Therefore, malignancy is an AESI for rilonacept. Any AE of malignancy (excluding 
basal cell carcinoma of the skin) requires reporting to the 
Pharmacovigilance (PHV) within 
24 hours after the time the site personnel first learn about the event, following the process as described 
in Section 6.4.6. 
6.4.1.5 
Adverse Reaction 
Any noxious and unintended response to the study drug (i.e., where a causal relationship between the 
study drug and an AE is at least a reasonable possibility) related to any dose should be considered 
adverse drug reaction. 
6.4.1.6 
Suspected Unexpected Serious Adverse Reaction 
Suspected Unexpected Serious Adverse Reaction (SUSAR) is an adverse reaction that is “unexpected”, 
i.e., it is not listed (or not listed at the severity that has been observed) in the designated Reference 
Safety Information of the Investigator’s Brochure. Evaluation and reporting requirements for SUSARs 
are detailed in Section 6.4.8. 
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6.4.2 Assessing Adverse Events 
6.4.2.1 
Relationship to Study Drug 
The investigator’s assessment of an AE’s relationship to the study drug is part of the documentation 
process, but it is not a factor in determining what is or is not reported in the study. If there is any doubt 
as to whether a clinical observation is an AE, the event should be reported. 
The relationship or association of the study drug in causing or contributing to the AE will be 
characterized by investigator using the following classification and criteria: 
• 
Not Related: when the AE is definitely caused by the subject’s clinical state or the study 
procedure/conditions 
Unlikely Related: when the temporal association between the AE and the study drug is such that 
the drug is not likely to have any reasonable association with the AE 
Possibly Related: when the AE follows a reasonable temporal sequence from the time of study 
drug administration but could have been produced by the subject’s clinical state or the study 
procedures/conditions 
Related: when the AE follows a reasonable temporal sequence from administration of the study 
drug, abates upon discontinuation of the drug, follows a known or hypothesized cause-effect 
relationship, and (if appropriate) reappears when the drug is reintroduced 
• 
• 
• 
6.4.2.2 
Intensity 
The severity of an AE will be recorded as one of the following: 
• 
• 
Mild: easily tolerated, does not interfere with normal daily activities, does not require intervention 
Moderate: causes some interference with daily activities; minimal, local, or noninvasive 
intervention indicated 
Severe: as a consequence of the event, daily activities are limited or completely halted; 
hospitalization or prolongation of hospitalization indicated 
• 
Changes in the severity of an AE should be documented to allow an assessment of the duration of the 
event at each level of intensity to be performed. Adverse events characterized as intermittent do not 
require documentation of onset and duration of each episode. 
6.4.3 Recording Adverse Events 
Each subject should be monitored for the development of any AEs. This information should be collected 
by asking nonleading questions (such as “How are you feeling?”) and from observations of and 
conversations with patients. AEs may also be collected by direct physical exam, diagnostic procedures, 
or any other appropriate source. 
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At every study visit (telephone or at the site), subjects will be asked a standard nonleading question to 
elicit any medically related changes in their well-being. They will also be asked if they have been 
admitted to the hospital, had any accidents, used any new medications, or changed concomitant 
medication regimens (both prescription and over-the-counter medications). 
All AEs (serious and non-serious) will be documented in the subject’s source documents and recorded 
in the eCRF. Any clinically relevant (as determined by the investigator) deterioration in laboratory 
assessments or other clinical findings is considered an AE and must be recorded in the subject’s source 
documents and in the eCRF. 
The AE term should be reported in standard medical terminology when possible. Also, when 
possible, signs and symptoms indicating a common underlying pathology should be noted as 
one comprehensive event. Information to be collected includes the following: 
• 
• 
• 
• 
• 
• 
• 
• 
• 
Event term 
Date and time of onset 
Investigator-specified assessment of severity and relationship study drug 
Date of resolution of the event 
Seriousness 
Any required treatment or actions 
Outcome 
Whether or not it caused the subject to discontinue the study drug. 
Whether or not the AE is an Injection Site Reaction (ISR). ISR is defined as any AE that occurs at 
the study drug injection site. If an ISR is observed, the subject may be treated at the discretion of 
the investigator. 
Adverse events resulting from concurrent illnesses, reactions to concurrent illnesses, reactions to 
concurrent medications, or progression of disease states must also be reported. All AEs will be followed 
to adequate resolution. The Medical Dictionary for Regulatory Activities (MedDRA) will be used to 
code all AEs. 
Any medical condition that is present at the time that the subject is screened but does not deteriorate 
should not be reported as an AE. However, if the condition deteriorates at any time during the study, it 
should be recorded as an AE. 
6.4.3.1 
Adverse Events Based on Signs and Symptoms 
All AEs spontaneously reported by the subject or reported in response to the open question from the 
study personnel or revealed by observation will be collected and recorded in the eCRF. When collecting 
AEs, the recording of a diagnosis is preferred (when possible) to the recording of a list of signs and 
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symptoms. However, if a diagnosis is known and there are other signs or symptoms that are not 
generally part of the diagnosis, the diagnosis and each sign or symptom will be recorded separately. 
6.4.3.2 
Adverse Events Based on Examinations and Tests 
If an abnormal laboratory value/vital sign is associated with clinical signs and symptoms, the sign or 
symptom will be reported as an AE and the associated laboratory result/vital sign will be considered as 
additional information. Wherever possible the reporting investigator uses the clinical rather than the 
laboratory term (e.g., anemia vs low hemoglobin value). In the absence of clinical signs or symptoms, 
clinically significant findings on examinations and tests should be reported as AEs. 
Any new or aggravated clinically significant abnormal medical finding at a physical examination as 
compared with the baseline assessment will be reported as an AE. 
6.4.3.3 
Pericarditis Disease Related Events 
Signs, symptoms, and abnormal findings associated with pericarditis are to be captured as a pericarditis 
recurrence event rather than as an AE unless the event is more severe than expected for the subject. In 
any case, pericarditis recurrence is required to be captured in the eCRF (see Section 6.2.3) within 
24 hours of learning of the event. 
6.4.4 Time Period for Collection of Adverse Events 
Adverse events will be assessed from the time the subjects signs the ICF and through the duration of 
the study, or at least through the SFU period (6 weeks after the last dose of study drug). 
6.4.5 Follow-Up of Unresolved Adverse Events 
Every reasonable effort will be made to follow subjects who have AEs. 
Any AEs that are unresolved at the subject’s SFU visit are to be followed up by the investigator until 
resolution or for as long as medically indicated. Additional information for any subject with an ongoing 
AE at the end of the SFU period may be requested by the 
PHV, as needed. 
6.4.6 Reporting Serious Adverse Events 
Any AE that meets SAE criteria (Section 6.4.1.3) must be reported to the 
PHV using the EDC 
system, immediately (i.e., within 24 hours) after the time site personnel first learn about the event. 
In the event the EDC entry is not possible (e.g., system failure or access problems), the study site should 
complete the paper SAE report form and fax the form to the 
PHV within 24 hours of awareness. 
The EDC system should be updated as soon as it is available. 
A full description of every SAE will need to be provided to the 
PHV (this may be supported by 
source documentation such as discharge summary or laboratory report should these documents be 
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requested by the 
PHV). Additional follow-up information, if required or available, should be sent 
to the 
PHV as soon as possible and placed with the original SAE information. 
The following contact information is to be used for SAE reporting: 
Information on non-serious AEs that become serious must also be reported to the 
it is available. 
PHV as soon as 
Investigators must report SAEs and follow-up information to their responsible Institutional Review 
Board (IRB) or Independent Ethics Committee (IEC) as applicable per institutional policy. 
The Sponsor or designee will provide regulatory authorities, IRBs, IECs, and principal investigators 
with clinical safety updates/reports according to local requirements. 
6.4.6.1 
Other Reasons for Immediate Reporting 
The following events require reporting to the 
first learn about the event: 
PHV within 24 hours after the time the site personnel 
• 
• 
• 
• 
Pregnancy in subject or female partner of male subject 
Overdose of the study drug or concomitant medication, regardless of whether it is considered AE 
Other study drug errors 
Any AE of malignancy (excluding basal cell carcinoma of the skin) 
6.4.7 Pregnancy 
Pregnancy is regarded as an AE only if there is a suspicion that study drug may have interfered with 
the effectiveness of a contraceptive medication. Nonetheless, any pregnancy that occurs during study 
participation (including pregnancy in a female partner of a male subject) must be reported to the 
PHV in the same way and using the same procedures as for an SAE (Section 6.4.6). The subject with 
pregnancy must not receive (additional) study drug. The pregnancy must be followed up to determine 
outcome (including spontaneous miscarriage, elective termination, normal birth, or congenital 
abnormality) and status of mother and child, even if the subject was discontinued from the study. 
Pregnancy complications and elective terminations for medical reasons must be reported as an AE or 
SAE. Spontaneous miscarriage must be reported as an SAE. 
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Any SAE occurring in association with a pregnancy, brought to the investigator’s attention after the 
subject has completed the study, and considered by the investigator as possibly related to the study 
drug, must be promptly reported to the 
PHV. 
In the event that a subject is found to be pregnant after having received at least 1 study drug dose, the 
study drug must be discontinued, and the pregnancy will be followed to term and the status of mother 
and child will be reported to the 
PHV after delivery. Instances of perinatal death or congenital 
abnormality, if brought to the attention of the investigator at any time after cessation of study drug, will 
be reported to the 
PHV within 24 hours. 
6.4.8 Evaluating and Reporting SUSARs 
Pharmacovigilance will promptly evaluate all SUSARs and nonserious AEs of special interest 
against cumulative product experience to identify and expeditiously communicate possible new safety 
findings to investigators, IRBs/IECs, and applicable health authorities based on applicable legislation. 
To determine reporting requirements for single AE cases, 
PHV staff in collaboration with Kiniksa 
Pharmaceuticals will assess the expectedness of these events using the Reference Safety Information 
(Section 6.2) of the rilonacept Investigator’s Brochure. 
PHV will compare the severity of each SUSAR and the cumulative event frequency reported for 
the study with the severity and frequency reported in the applicable reference document. 
Reporting requirements will also be based on the investigator’s assessment of causality and seriousness, 
with allowance for upgrading by 
PHV and Kiniksa Pharmaceuticals as needed. 
All relevant information about suspected SUSARs that are fatal or life-threatening will be recorded and 
reported to the competent authorities in all the applicable countries, and IRBs/IECs in conjunction with 
Directive 2001/20/EC. 
6.5 
Other Assessments 
6.5.1 Pharmacokinetic Sample 
All subjects will have PK samples obtained according to the Study Schedule of Activities. For PK 
analyses, it is important that the exact time of the SC injection is recorded for each subject. When PK 
samples are to be collected on dosing days, serum will be collected pre-dose to measure rilonacept 
concentrations. Specific procedures for sample collection, processing, storage, and shipment can be 
found in a separate Laboratory Manual provided to sites. 
A PK substudy will be conducted in a subset of subjects agreeing to provide a PK sample 24 hours after 
the first dose of study drug in the RI period. Specific procedures for sample collection, processing, 
storage, and shipment can be found in a separate Laboratory Manual provided to sites. 
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6.5.2 Anti-Drug Antibodies (ADAs) against Rilonacept (KPL-914) 
Serum samples to measure the presence of ADAs against rilonacept will be collected according to the 
Study Schedule of Activities. Instructions for sample collection, processing, storage, and shipment can 
be found in a separate Laboratory Manual provided to the site. 
6.5.3 Biomarkers 
Serum and plasma will be collected according to the Study Schedule of Activities for biomarker 
analysis. 
6.5.4 Pharmacogenomics 
Whole blood will be collected for pharmacogenomics assessments after signing the separate 
Pharmacogenomics ICF. 
6.6 
Laboratory Analyses 
Any abnormal laboratory test results (hematology, chemistry, or urinalysis) or other safety assessments 
(e.g., physical examination, vital signs measurements), including those that worsen from baseline, felt 
to be clinically significant in the medical and scientific judgement of the investigator are to be recorded 
as AEs or SAEs. 
Laboratory assessments will be performed at study visits as summarized in Study Schedule of 
Activities. Unscheduled laboratory assessments for safety issues are permitted as deemed necessary by 
the investigator. 
Whenever possible in pediatric subjects, local laboratory tests should be drawn using pediatric tubes. 
6.6.1 Serology 
Samples for local laboratory assessment of hepatitis B surface antigen, hepatitis B core antibody, 
hepatitis C virus antibody, and HIV test will be collected at screening. If clinically indicated, those tests 
may be also collected during the study. 
6.6.2 Hematology 
Hematology tests performed at central study laboratory include WBC count with differential, platelet 
count, red blood cell count, mean corpuscular volume, hemoglobin, mean corpuscular hemoglobin 
concentration. 
6.6.3 Chemistry 
Blood chemistry tests performed in the central study laboratory include albumin, total protein, alkaline 
phosphatase, ALT/SGPT, AST/SGOT, direct bilirubin, total bilirubin, bicarbonate, chloride, 
potassium, sodium, creatinine, glucose. 
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In addition, the following chemistry tests may be performed together with local CRP measurement 
when using POC device: chloride, creatine kinase, creatinine, glucose, potassium, sodium, total carbon 
dioxide, blood urea nitrogen. 
6.6.4 Non-fasting Lipid Panel 
Subjects treated with rilonacept may experience increases in their lipids, including total cholesterol, 
LDL, HDL, and triglycerides. 
Non fasting measurements of total cholesterol, triglycerides, HDL, and direct LDL will be performed 
by central study laboratory as described in the Study Schedule of Activities. 
Investigators should monitor the lipid profiles in study subjects and consider ordering fasting lipid panel 
and/or lipid lowering therapies as needed based on cardiovascular risk factors and current guidelines. 
6.6.5 Urinalysis 
Urinalysis performed by the central study laboratory includes specific gravity, pH, protein, 
urobilinogen, ketones, glucose, blood, bilirubin, nitrites, leukocyte esterase. It will be performed as 
described in the Study Schedule of Activities. 
6.6.6 
Pregnancy Test 
For women of child-bearing potential, a urine pregnancy test using a licensed test (dipstick) should be 
performed prior to receiving the first administration of study drug, and as needed during the study, and 
also at the SFU visit. When needed, serum pregnancy test should be performed. The purpose of 
pregnancy test is to prevent embryo/fetal exposure to study drug. Subjects with positive or 
indeterminate pregnancy test during the screening are not eligible for the study. 
6.6.7 Sample Collection 
The procedures for the collection, handling, and shipment of laboratory samples are specified in the 
Laboratory Manual supplied to sites by the central laboratory. 
6.7 
Committees 
6.7.1 Independent Data Monitoring Committee (DMC) 
A DMC will be utilized in this study to ensure external objective medical and/or statistical (if needed) 
review of safety data in order to protect the ethical and safety interests of subjects. The DMC will 
review unblinded aggregate (and, where necessary, individual) subject safety data at pre-defined 
intervals according to a DMC charter. The analysis plan for the DMC review will be described in the 
DMC charter, which will also contain details of the composition and the responsibilities of the DMC. 
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6.7.2 Clinical Endpoint Committee (CEC) 
An independent CEC will review and adjudicate all suspected recurrent pericarditis events that occur 
during the RW period of the study. The procedures for adjudicating events will be described in the CEC 
Charter. This will be done independent of the investigators, and in a manner blinded to treatment 
assignment. The CEC will complete assessments on an ongoing basis. 
7 
Statistical and Analytical Plan 
7.1 
Primary Efficacy Endpoint 
The primary efficacy endpoint is time to pericarditis recurrence, defined as the time from randomization 
to the date of the first pericarditis recurrence for each subject. Only CEC-confirmed pericarditis 
recurrence will be considered as an event for the primary analysis. 
A sensitivity analysis will be done based on the investigator’s assessment of the event. 
Pericarditis recurrence is defined in Section 6.2.3. 
Subjects who do not have a pericarditis recurrence will be censored at the date of the last available 
assessment during the RW period before data cutoff. Detailed censoring rules will be specified in the 
Statistical Analysis Plan (SAP). 
7.2 
Secondary Efficacy Endpoints for the RW Period 
This Section defines secondary efficacy endpoints for the RW period. Endpoints for the RI period and 
for the LTE-TP are defined in Section 7.3. 
7.2.1 
1. 
Major Secondary Efficacy Endpoints 
Proportion of subjects who maintained Clinical Response at Week 24 of the RW period. Clinical 
Response is defined as a weekly average of daily pericarditis pain on the 11-point NRS ≤2.0 
and CRP level ≤0.5 mg/dL. 
Percentage of days with no or minimal pain in the first 24 weeks of the RW period. No or 
minimal pain is defined as non-missing NRS ≤1. 
Proportion of subjects with absent or minimal pericarditis symptoms (based on the 7-point 
PGIPS) at Week 24 of the RW period. 
2. 
3. 
7.2.2 Other Secondary Endpoints 
All time-to-event endpoints start from the day of randomization. The following variables will be 
analyzed: 
• 
Proportion of subjects without pericarditis recurrence in the first 24 weeks of the RW period 
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• 
• 
• 
• 
• 
• 
• 
• 
Time to pericarditis pain NRS ≥4 
Time to CRP level ≥1 mg/dL 
Time to pericardial rub 
Time to widespread ST-segment elevation or PR-segment depression on ECG 
Time to new or worsening pericardial effusion on ECHO 
Change over time in CRP levels 
Change over time in the subject’s assessments of pericarditis pain (weekly average) 
Number (percentage) of subjects with absent or minimal pericarditis activity based on the 
PGA-PA 
Change over time in the SF-36 Physical Component Score 
Change over time in the SF-36 Mental Component Score 
Change in EQ-5D-5L. There are 6 questions in this instrument (Section 6.2.1.8). Each of the first 
5 questions has 5 levels, from level 1 (best) to level 5 (worst). They are mobility, self-care, usual 
activities, pain/discomfort, and anxiety/depression. The sixth question is the health on the day, from 
0 (the worst) to 100 (the best) (van Reenen and Janssen 2015). The levels of the first 5 questions 
(EQ-5D-5L profile) will be converted to an index value. Change from baseline in each one of these 
7 values will be an endpoint. 
Change over time in subject’s sleep quality assessed with the ISI (Section 6.2.1.9). There are 
7 items in the ISI. Change in ISI total score, which is the sum of the 7 items over time, will be the 
endpoint. 
Change over time in ISI categories. The ISI total scores are divided to 4 categories: 
• 
• 
• 
• 
• 
- 
- 
- 
- 
0–7 = No clinically significant insomnia 
8–14 = Subthreshold insomnia 
15–21 = Clinical insomnia (moderate severity) 
22–28 = Clinical insomnia (severe) 
• 
Number (percentage) of subjects who receive sequential ORT for pericarditis (analgesics, NSAIDs, 
and/or colchicine) in the RW period 
7.3 
Other Endpoints 
These include efficacy endpoints in the RI period and the LTE-TP. Since there is no control arm in 
these 2 periods, only descriptive statistics will be provided. All time-to-event endpoints start from the 
day of receiving rilonacept in that period. 
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7.3.1 Efficacy Endpoints for the RI Period 
The following efficacy endpoints are included in this period: 
• 
Proportion of subjects who achieved Clinical Response at the RI Week 12/RW baseline visit. 
Clinical Response is defined as a weekly average of daily pericarditis pain of ≤2.0 on the 11-point 
NRS and CRP level ≤0.5 mg/dL at the RI Week 12/RW baseline visit. 
Time to CRP normalization (≤0.5 mg/dL) 
Number (percentage) of subjects with normalization of CRP at RI Week 12 
Change from baseline in pericarditis pain at RI Week 12 
Change from baseline in CRP level at RI Week 12 
Resolution of ECHO and ECG abnormalities (yes/no) at RI Week 12 
Percentage of days with no or minimal pain 
Proportion of subjects with absent or minimal pericarditis symptoms based on PGIPS 
Proportion of subjects with absent or minimal pericarditis activity based on the PGA-PA 
Change over time in the SF-36 Physical Component Score 
Change over time in the SF-36 Mental Component Score 
Change in the EQ-5D-5L (Section 7.2.2 contains details about calculation) 
Change over time in the subject’s sleep quality assessed with the ISI (Section 7.2.2 contains details 
about calculation) 
Change over time in ISI categories 
Number (percentage) of subjects who were off background pericarditis medication at RI Week 12 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
7.3.2 Efficacy Endpoints for the LTE-TP 
The efficacy endpoints below are included in this period. Each endpoint will be summarized through 
Week 24, by subjects who did and did not have an adjudicated pericarditis recurrence in the RW period, 
respectively, and overall: 
• 
• 
• 
• 
• 
• 
Number (percentage) of subjects with pericarditis recurrences 
Proportion of subjects with Clinical Response 
Change over time in CRP levels 
Change over time in the subject’s assessments of pericarditis pain 
Percentage of days with no or minimal pain 
Proportion of subjects with absent or minimal pericarditis symptoms based on PGIPS 
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• 
• 
• 
• 
• 
Proportion of subjects with absent or minimal pericarditis activity based on the PGA-PA 
Change over time in the SF-36 Physical Component Score 
Change over time in the SF-36 Mental Component Score 
Change in the EQ-5D-5L (Section 7.2.2 contains details about calculation) 
Change over time in the subject’s sleep quality assessed with the ISI (Section 7.2.2 contains details 
about calculation) 
Change over time in ISI categories 
Number (percentage) of subjects requiring addition of SOC pericarditis therapy 
• 
• 
7.4 
Sample Size Calculations 
For the purpose of sample size estimation, time to pericarditis recurrence is assumed to follow an 
exponential distribution. An event of interest is defined as a subject’s first adjudicated recurrence of 
pericarditis. The following assumptions are used in the sample size calculation using EAST 6.4.1: 
• 
• 
• 
• 
• 
2.5% 
90% 
8 
0.244 
10% 
1-sided significance level 
Power 
Median time to event (in weeks) in placebo 
Hazard ratio (rilonacept/placebo) 
Percentage of subjects in the RI period that will not reach RW 
Given these assumptions, a total of 22 adjudicated pericarditis recurrence events is required to achieve 
the power. About 25 subjects per arm (a total of 50 subjects) will be randomized. Considering 10% of 
subjects in the RI period that will not reach the RW period, approximately 56 subjects will be enrolled 
in this study. 
Patient enrollment and the pericarditis recurrence event accrual will be closely monitored during the 
study. The monitoring activities will be done in a blinded fashion during the RW period. If the number 
of patients randomized is less than 50 and/or the time anticipated for the number of events required for 
the analysis of primary efficacy endpoint significantly exceeds the projected timeline, additional 
patients may be enrolled and/or randomized at Kiniksa Pharmaceutical’s discretion. However, at this 
time it is anticipated that no more than 75 subjects will be enrolled into this study. Since the data cutoff 
will be the event date of the 22nd adjudicated pericarditis recurrence AND all subjects still in the RW 
period have been treated for 24 weeks, the actual power could be higher if the assumed hazard ratio 
holds. 
7.5 
Analysis Sets 
The following analysis sets will be used in the statistical analyses. 
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Intent-to-Treat (ITT) Analysis Set: All subjects who are randomized in the RW period will be included 
in the ITT analysis set. The primary analysis for efficacy endpoints in the RW period will be based on 
the ITT analysis set. Treatment comparisons for all ITT analyses will be based on each subject’s 
treatment assignment from randomization. 
Safety Analysis Set: All subjects who take at least 1 dose of study drug in the RI period will be included 
in the safety analysis set (SS). Safety analyses will be based on the actual treatment a subject received. 
Run-in Analysis Set: All subjects who received at least 1 dose of study drug in the RI period will be 
included in the RI analysis set (RIS). 
Per-protocol Analysis Set: The per protocol (PP) analysis set is a subset of the ITT analysis set with the 
exclusion of subjects with major protocol violations or violations that may potentially bias statistical 
analyses or the ethical conduct of the study. The criteria of these violations will be determined prior to 
unblinding. This analysis set may be used for sensitivity analyses for efficacy endpoints in the RW 
period. 
Pharmacokinetic Analysis Set: The PK analysis set includes subjects who receive at least 1 dose of 
study drug and have at least 1 PK sample. The PK analysis set will be used for all PK analyses. 
7.6 
Description of Subgroups to be Analyzed 
Subgroup analyses for the primary endpoint will be performed by the stratification variable for 
randomization, as well as by important variables for baseline demographics and patient characteristics. 
These analyses are for the RW period only. Details will be provided in the SAP. 
7.7 
Statistical Analysis Methodology 
This Section outlines the overall methodologies. Details of the statistical analyses, methods, and data 
conventions will be described in the SAP. 
7.7.1 General Methods 
Statistical analysis will be performed using SAS® software Version 9.4 or later. Continuous variables 
will be summarized using the mean, the standard deviation, median, minimum value, and maximum 
value. Time-to-event variables will be summarized using percent censored, event rate, and 25th, 50th, 
75th 
and 
percentiles with 95% CI, if estimable. Categorical variables will be summarized using 
frequency counts and percentages. Data will be listed in data listings. 
At each of RI and RW periods and in the LTE-TP, baseline will be the last value before the first dose 
of study drug within each individual period unless otherwise specified. For change-over-time endpoints 
in the RW period, by-visit analysis will be performed at each scheduled visit for at least 24 weeks. 
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7.7.2 Stratified Analysis 
There will be 2 stratification variables for randomization: 
• 
• 
Oral CS use at RI baseline: yes or no 
Diagnosis of recurrent idiopathic pericarditis at RI baseline: yes or no 
When a stratified analysis is used in the analysis and a stratum has no event of interest or no responder, 
the stratum will be pooled with the other stratum in the same stratification variable. 
7.7.3 Testing Hypotheses and Multiplicity Adjustment 
All statistical tests for the treatment comparison of efficacy endpoints in the RW period will be based 
on the ITT analysis set with 1-sided α=0.025. For each endpoint, the null hypothesis is that the effects 
of rilonacept and placebo are the same. The alternative hypothesis is that rilonacept is better than the 
placebo. 
In order to control the overall 1-sided type I error rate at the 0.025 level, a gatekeeping procedure in 
combination with Hochberg’s procedure will be applied to testing the primary and major secondary 
endpoints. If the 1-sided p-value for testing the primary endpoint is ≤0.025, a significant treatment 
effect on the primary endpoint will be claimed. 
Section 7.2.1 provides the order of major secondary endpoints. If the primary endpoint is significant, 
the first major secondary endpoint, i.e., proportion of subjects who maintained Clinical Response at 
Week 24 of RW period will be tested at 1-sided α=0.025. A significant treatment effect on this major 
secondary endpoint will be claimed if the 1-sided p-value is ≤0.025. If the treatment effect is not 
significant on the primary endpoint, significance on this major secondary endpoint cannot be claimed 
regardless of the result. 
If both primary and first major secondary endpoints are significant following the above procedure, the 
second and third major secondary endpoints defined in Section 7.2.1 will be tested with Hochberg’s 
procedure at overall 1-sided α=0.025. If both 1-sided unadjusted p-values are ≤0.025, claim significance 
of rilonacept for both endpoints. If the larger 1-sided p-value is >0.025, compare the smaller 1-sided 
p-value with 0.0125. If the smaller 1-sided p-value is ≤0.0125, claim significance of rilonacept on this 
endpoint. 
7.7.4 Analysis of Primary Efficacy Endpoint 
Primary analysis of this study will be done after 22nd CEC-confirmed pericarditis recurrence AND after 
all subjects in the RW period have been treated for 24 weeks. The log rank test will be the primary 
method for the analysis of time to recurrence, stratified by the stratification variables for randomization. 
A sensitivity analysis will be performed based on the investigator’s judgement of pericarditis 
recurrence. Additional sensitivity may be defined in the SAP. 
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7.7.5 Analysis of Secondary Efficacy Endpoints 
7.7.5.1 
Analysis of the Major Secondary Endpoints 
1. Proportion of subjects who maintained Clinical Response at Week 24 of the RW period (defined 
as a weekly average of daily pericarditis pain ≤2.0 on the 11-point NRS and CRP ≤0.5 mg/dL 
at Week 24). The Cochran–Mantel–Haenszel (CMH) test will be used in this analysis, stratified 
by the stratification variables for randomization. 
Percentage of days with minimal or no pain in the first 24 weeks post randomization. Minimal 
or no pain is defined as non-missing daily NRS ≤1. This endpoint will be analyzed with an 
analysis of covariance. In addition to treatment arm, the following covariates will be included 
in this analysis: the stratification variables for randomization, and baseline NRS weekly average 
in 2 categories: NRS ≤1 versus NRS >1. 
Proportion of subjects with absent or minimal pericarditis symptoms (based on the 7-point 
PGIPS) at Week 24 of the RW period. The CMH test will be used in this analysis, stratified by 
the stratification variables for randomization. 
2. 
3. 
7.7.5.2 
Analyses of Other Secondary Endpoints in the RW Period 
The following endpoints will be analyzed using the same method for the primary endpoint: 
• 
• 
• 
• 
• 
Time to pericarditis pain NRS ≥4 
Time to CRP level ≥1 mg/dL 
Time to pericardial rub 
Time to widespread ST-segment elevation or PR-segment depression on ECG 
Time to new or worsening pericardial effusion on ECHO 
A mixed model with repeated measures (MMRM) will be used in the analysis of the endpoints below. 
In the model, subjects will have repeated measures for the response variable change from baseline of 
the endpoint. The explanatory variables will include the baseline value, treatment arm, and the variables 
for stratification at randomization. The p-value for treatment comparison will be calculated at each 
scheduled assessment for at least 24 weeks as part of the summary statistics. This is done with the 
understanding that the comparison could be biased due to dropouts or subjects with pericarditis 
recurrence. 
• 
• 
• 
• 
• 
Change over time in CRP levels 
Change over time in the subject’s assessments of pericarditis pain (weekly average) 
Change over time in the SF-36 Physical Component Score 
Change over time in the SF-36 Mental Component Score 
Change in the EQ-5D-5L: Health score and Index value, respectively 
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• 
Change over time in the subject’s sleep quality: sum of the ISI scores. 
The CMH test will be used in the analysis of the endpoints below, stratified by the stratification 
variables for randomization. 
• 
• 
Proportion of patients without pericarditis recurrence in the first 24 weeks of the RW period 
Number (percent) of subjects with absent or minimal pericarditis activity based on the 
investigator’s assessment 
Number (percentage) of subjects who receive SOC pericarditis therapy in the RW period 
• 
The following endpoints will be analyzed using the Mantel-Haenszel test with 1 degree of freedom: 
• 
Change in each 1 of the first 5 questions in the EQ-5D-5L, i.e., mobility, self-care, usual activities, 
pain/discomfort, and anxiety/depression 
Change over time in ISI categories 
• 
7.7.6 Analyses of Other Endpoints 
Endpoints listed in Section 7.3 for the RI period and the LTE-TP will be descriptive in nature since 
there is no control arm. Summary statistics will be generated following the methodologies stated in 
Section 7.7. 
Other analyses include anti-rilonacept antibodies and biomarker analyses. These analyses will be 
described in the SAP. 
7.7.7 Pharmacokinetic Analyses 
For all subjects, serum samples will be collected at time points shown in the Study Schedule of 
Activities in order to quantify concentrations of rilonacept. Descriptive statistics will be calculated for 
the serum concentrations of rilonacept by visit. Individual listings of serum concentrations will be 
provided. 
Pharmacokinetic data may be used in a subsequent population PK evaluation that will be conducted 
outside of this study and described in a separate report. 
7.7.8 Safety Analyses 
Treatment-emergent AEs (TEAEs), defined as AEs that start or increase in severity after the first dose 
of study drug and before 6 weeks after the last dose of study drug, will be coded to system organ class 
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and preferred term using the most recent version of MedDRA. TEAEs will be analyzed for all subjects 
combined and by treatment group in the RW period. Further analyses by severity and relationship to 
study drug as well as analyses of serious TEAEs will be presented. 
Descriptive statistics will be used to summarize safety endpoints by visit for all subjects combined in 
the RI period and by treatment group in the RW period. Two-sided 95% CIs will be presented where 
meaningful. Data summaries will be displayed for clinical laboratory analyses (including safety 
laboratory measurements, ADAs, etc.), vital signs measurements, ECGs, and physical examination 
findings. 
7.7.9 Interim Analyses 
No interim analyses are planned for this study. 
8 
Data Quality Assurance 
Assessment of subject compliance and adherence to study drug administration will be assessed by the 
site in collaboration with the visiting RN. 
This study will be conducted according to the ICH E6(R2) risk and quality processes described in the 
applicable procedural documents. The quality management approach to be implemented in this study 
will be documented and will comply with the current ICH guidance on quality and risk management 
(ICH Q9). 
8.1 
Data Management 
As part of the responsibilities assumed by participating in the study, the investigator agrees to maintain 
adequate case histories for the subjects treated as part of the research under this protocol. The 
investigator agrees to maintain accurate eCRFs and source documentation as part of the case histories. 
These source documents may include laboratory reports, ECG strips, etc. 
will be responsible for activities associated with the data management of this study. This will 
include setting up a relevant database and data transfer mechanisms, along with appropriate validation 
of data and resolution of queries. Data generated within this clinical study will be handled according to 
the relevant Standard Operating Procedures (SOPs) of 
Investigative site personnel will enter subject data into an EDC system. The analysis data sets will be a 
combination of these data and data from other sources (e.g., laboratory data). 
Clinical data management will be performed in accordance with applicable 
standards and data 
cleaning procedures to ensure the integrity of the data, e.g., removing errors and inconsistencies in the 
data. Adverse event terms will be coded using MedDRA, an internal validated medical dictionary, and 
concomitant medications will be coded using the World Health Organization Drug Dictionary. 
After the last study database lock, each study site will receive a CD-ROM containing all of their site 
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specific eCRF data as entered into Medidata Rave for the study, including full discrepancy and audit 
history. Additionally, a Master DVD/CD-ROM copy of all of the site data from the study will be created 
and sent to Kiniksa for storage. 
will maintain a duplicate Master DVD/CD-ROM copy for their 
records. In all cases, subject initials will not be collected or transmitted to Kiniksa Pharmaceuticals. 
9 
Ethics 
9.1 
Independent Ethics Committee or Institutional Review Board 
Regulatory agencies and the ICH guidelines require that approval be obtained from an IRB/IEC before 
participation of human subjects in research studies. Before study onset, the protocol, informed consent, 
informed assent, advertisements to be used for the recruitment of study subjects, and any other written 
information regarding this study to be provided to the subject or the subject’s legal guardian must be 
approved by the IRB/IEC. Documentation of all IRB/IEC approvals and of the IRB/IEC compliance 
with ICH harmonised tripartite guideline E6(R2): Good Clinical Practice (GCP) will be maintained by 
the site and will be available for review by Kiniksa Pharmaceutical or its designee. 
All IRB/IEC approvals should be signed by the IRB/IEC chairman or designee and must identify the 
IRB/IEC name and address, the clinical protocol by title or protocol number or both, and the date 
approval or a favorable opinion was granted. 
The investigator is responsible for providing written summaries of the progress and status of the study 
at intervals not exceeding 1 year or otherwise specified by the IRB/IEC. The investigator must promptly 
supply Kiniksa Pharmaceutical or its designee, the IRB/IEC, and, where applicable, the institution, with 
written reports on any changes significantly affecting the conduct of the study or increasing the risk to 
subjects. 
9.2 
Ethical Conduct of the Study 
The study will be performed in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki, ICH GCP, the protocol, and all applicable regulations. 
9.3 
Subject Information and Consent 
A written informed consent in compliance approved by an IRB/IEC, as appropriate, at each 
center/country shall be obtained from each subject before entering the study or performing any unusual 
or nonroutine procedure that involves risk to the subject. An informed consent for (or assent form, as 
applicable) template may be provided by Kiniksa Pharmaceutical or its designee to investigative sites. 
If any institution-specific modifications to study-related procedures are proposed or made by the site, 
the consent should be reviewed by Kiniksa Pharmaceutical or its designee or both before IRB/IEC 
submission. Once reviewed, the consent will be submitted by the investigator to his or her IRB/IEC for 
review and approval before the start of the study. If the ICF is revised during the course of the study, 
all active participating subjects must sign the revised form. 
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Before screening, each prospective subject or his or her legal guardian will be given a full explanation 
of the study and be allowed to read the approved ICF. Once the investigator is assured that the 
subject/legal guardian understands the implications of participating in the study, the subject/legal 
guardian will be asked to give consent to participate in the study by signing the ICF. 
It should be emphasized to the subjects that they may withdraw from the study at any time and for any 
reason without prejudice to their future medical care by the investigator or at the study site. Subjects 
who refuse to give or who withdraw written informed consent should not be included or continue in the 
study. 
For potential subjects under the age of 18, a parent or legal guardian is required to sign and date the 
ICF and the potential subject is also required to sign and date an informed assent form. The informed 
assent form explains the trial, it’s purpose, procedures as well as risk and benefits in age-appropriate 
language. Both the ICF and informed assent form, as applicable, are required prior to participation in 
the trial. The investigator shall retain the signed original ICF(s)/assent form(s), as applicable, and give 
a copy of the signed original form to the subject or legal guardian. 
For this study subjects will be required to sign and date the ICF (or assent form, if applicable) prior to 
entry to the study and prior to entry to LTE. 
In addition, a separate ICF (assent, if applicable) will be needed for subjects participating in 
pharmacogenomic testing. 
10 Investigator’s Obligations 
The following administrative items are meant to guide the investigator in the conduct of the study but 
may be subject to change based on local or country-specific industry and government standard 
operating procedures, working practice documents, or guidelines. 
10.1 Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records will be identified in a manner 
designed to maintain subject confidentiality. All records will be kept in a secure storage area with 
limited access. Clinical information will not be released without the written permission of the subject 
(or the subject’s legal guardian), except as necessary for monitoring and auditing by Kiniksa 
Pharmaceuticals, its designee, the regulatory agencies/authorities, or the IRB/IEC. 
The Investigator and all employees and co-workers involved with this study may not disclose or use 
for any purpose other than performance of the study any data, record, or other unpublished, confidential 
information disclosed to those individuals for the purpose of the study. Prior written agreement from 
Kiniksa Pharmaceuticals or its designee must be obtained for the disclosure of any said confidential 
information to other parties. 
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10.2 Financial Disclosure and Obligations 
Investigators are required to provide financial disclosure information to allow Kiniksa Pharmaceuticals 
or its designee to submit the complete and accurate certification or disclosure statements required under 
US Title 21 Code of Federal Regulations (CFR) Part 54. In addition, the investigator must provide to 
Kiniksa Pharmaceuticals a commitment to promptly update this information if any relevant changes 
occur during the course of the investigation and for 1 year following the completion of the study. 
Neither Kiniksa Pharmaceuticals nor 
is financially responsible for further testing or treatment of 
any medical condition that may be detected during the screening process. In addition, in the absence of 
specific arrangements, neither Kiniksa Pharmaceuticals nor 
treatment of the subject’s disease. 
is financially responsible for further 
10.3 Investigator Documentation 
Prior to beginning the study, the investigator will be asked to comply with ICH E6(R2) 8.2 and Title 
21 of the CFR by providing the following essential documents, including but not limited to: 
• 
• 
• 
IRB/IEC approval 
Original investigator-signed investigator agreement page of the protocol 
Form FDA 1572, fully executed, and all updates on a new fully executed Form FDA 1572 or local 
country-specific equivalent for outside the US 
Curriculum vitae for the investigator and each sub-investigator listed on Form FDA 1572 or local 
country-specific equivalent for outside the US 
Financial disclosure information 
IRB/IEC-approved ICFs/assent forms, as applicable, samples of site advertisements for recruitment 
for this study, and any other written information regarding this study that is to be provided to the 
subject or legal guardian 
Laboratory certifications and normal ranges for any local laboratories used by the site, in 
accordance with 42 CFR 493 
• 
• 
• 
• 
10.4 Study Conduct 
The investigator agrees that the study will be conducted according to the principles of ICH E6(R2). The 
investigator will conduct all aspects of this study in accordance with all national, state, and local laws 
or regulations. Study information from this protocol will be posted on publicly available clinical trial 
registers before enrollment of subjects begins. 
10.5 Adherence to Protocol 
The investigator agrees to conduct the study as outlined in this protocol in accordance with ICH E6(R2) 
and all applicable guidelines and regulations. 
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10.6 Adverse Events and Study Report Requirements 
By participating in this study, the investigator agrees to submit reports of SAEs to 
and/or IRB/IEC 
according to the time line and method outlined in the protocol. In addition, the investigator agrees to 
submit annual reports to the study site IRB/IEC as appropriate. 
10.7 Investigator’s Final Report 
Upon completion of the study, the investigator, where applicable, should inform the institution; the 
investigator/institution should provide the IRB/IEC with a summary of the study’s outcome and Kiniksa 
Pharmaceuticals and regulatory authority(ies) with any reports required. 
10.8 Records Retention 
It is the responsibility of the investigator to ensure all essential trial documentation and source records 
(e.g., signed ICFs, study site/clinic files, subjects’ hospital notes, copies of eCRFs) at their site are 
securely retained. The Sponsor will inform the investigator of the time periods for retaining study 
records to comply with all applicable regulatory requirements. The minimum retention time will meet 
the strictest standard applicable to that site for the study, as dictated by any institutional requirements 
or local laws or regulations; otherwise, the retention period by default will be 15 years. 
10.9 Publications 
Kiniksa shall have the sole and exclusive right to publish information obtained from the study, including 
any data, results, and conclusions. Investigators are encouraged to participate in the study execution 
such that they may be invited to participate in the authorship of a potential publication in a manner 
commensurate with their participation in the study execution in accordance with International 
Committee of Medicinal Journal Editors standards. Any publication of the results will be subject to the 
terms and conditions provided in the study agreement. 
11 Study Management 
The administrative structure will include a Data Monitoring Committee (DMC) and a Clinical Endpoint 
Committee (CEC). Please refer to Section 6.7 for further details. 
11.1 Monitoring 
11.1.1 Monitoring of the Study 
Data for each subject will be recorded in source records and in the eCRF. Data collection must be 
completed for each subject who signs an ICF. 
For each subject enrolled, the investigator or designee will document in the source records of the subject 
that the subject is enrolled in this study along with all safety and efficacy information. The investigator 
is responsible for maintaining adequate case histories in the source records of each subject. Source data 
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should be preserved for the maximum period of time permitted by the hospital/institution and made 
available by the investigator in the cases described above. 
In accordance with current GCP and ICH guidelines, the study monitor will carry out source document 
verification at regular intervals to ensure that the data collected in the eCRF are accurate and reliable. 
11.1.2 Inspection of Records 
Investigators and institutions involved in the study will permit study-related monitoring, audits, 
IRB/IEC review, and regulatory inspections by providing direct access to all study records. In the event 
of an audit, the investigator agrees to allow Kiniksa Pharmaceuticals, representatives of Kiniksa 
Pharmaceuticals, or a regulatory agency(ies) access to all study records. 
The investigator should promptly notify Kiniksa Pharmaceuticals and 
of any audits scheduled by 
any regulatory authorities and promptly forward copies of any audit reports received to Kiniksa 
Pharmaceuticals and 
11.2 Management of Protocol Amendments and Deviations 
11.2.1 Modification of the Protocol 
Sponsor initiated amendments to the protocol must be submitted in writing to the investigator’s 
IRB/IEC for approval and to the regulatory authorities, if required, before subjects can be enrolled into 
an amended protocol. 
11.2.2 Protocol Deviations 
A deviation from the protocol is any change, divergence, or departure from the study design or 
procedures defined in the protocol. No waivers will be granted for exemptions to inclusion/exclusion 
criteria. The Investigator will conduct the study in compliance with the protocol agreed to with the 
Sponsor and, if required, the regulatory authorities, and which was given approval/favorable opinion 
by the IRB/IEC. In the event of a protocol deviation, the Sponsor or a designee must be notified. 
The Investigator, or person designated by the Investigator, must document and explain any deviation 
from the approved protocol. The Investigator will notify the IRB/IEC of deviations from the protocol 
in accordance with local procedures. 
11.3 Study Termination 
Although Kiniksa Pharmaceuticals has every intention of completing the study, Kiniksa 
Pharmaceuticals reserves the right to discontinue the study at any time in case of safety concerns (e.g., 
SUSARs) or if special circumstances concerning the study drug or the company itself occur, making 
further treatment of subjects impossible. In this event, the investigator(s) will be informed of the reason 
for study termination. 
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The end of the study is defined as the date on which the last subject completes the last visit (includes 
follow-up visit). 
11.4 Final Report 
Whether the study is completed or prematurely terminated, Kiniksa Pharmaceutical will ensure that the 
clinical study report(s) are prepared and provided to the regulatory agency(ies) as required by the 
applicable regulatory requirement(s). The Sponsor will also ensure that the clinical study reports in 
marketing applications meet the standards of the ICH harmonised tripartite guideline E3: Structure and 
content of clinical study reports. 
Where required by applicable regulatory requirements, an investigator signatory will be identified to 
approve the clinical study report. The investigator will be provided reasonable access to statistical 
tables, figures, and relevant reports and will have the opportunity to review the complete study results. 
Upon completion of the clinical study report, Kiniksa Pharmaceutical will provide the investigator(s) 
with the full summary of the study results. The investigator(s) are encouraged to share the summary 
results with the study subjects, as appropriate. The study results will be posted on publicly available 
clinical trial registers, as applicable. 
12 Reference List 
Adler Y, Charron P, Imazio M, et al. 2015 ESC Guidelines for the diagnosis and management of 
pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the 
European Society of Cardiology (ESC) Endorsed by: The European Association for Cardio-Thoracic 
Surgery (EACTS). Eur Heart J. 2015;36(42):2921-2964. 
Agarwal SK, Vallurupalli S, Uretsky BF, et al. Effectiveness of colchicine for the prevention of 
recurrent pericarditis and post-pericardiotomy syndrome: an updated meta-analysis of randomized 
clinical data. Eur Heart J Cardiovasc Pharmacother. 2015;1(2):117-125. 
Baskar S, Klein AL, Zeft A. The use of IL-1 receptor antagonist (anakinra) in idiopathic recurrent 
pericarditis: A narrative review. Cardiol Res Pract. 2016;2016:7840724. 
Brucato A, Imazio M, Gattorno M, et al. Effect of anakinra on recurrent pericarditis among patients 
with colchicine resistance and corticosteroid dependence: The AIRTRIP randomized clinical trial. 
JAMA. 2016;316(18):1906-1912. 
Cantarini L, Lopalco G, Selmi C, et al. Autoimmunity and autoinflammation as the yin and yang of 
idiopathic recurrent acute pericarditis. Autoimmun Rev. 2015;14(2):90-97. 
Dinarello CA, Simon A, van der Meer JW. Treating inflammation by blocking interleukin-1 in a broad 
spectrum of diseases. Nat. Rev. Drug Discov. 2012; 11(8):633-652. 
Dworkin RH, Turk DC, Farrar JT, et al. Core outcome measures for chronic pain clinical trials: 
IMMPACT recommendations. Pain. 2005;113(1-2):9-19. 
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Garg M, de Jesus AA, Chapelle D, et al. Rilonacept maintains long-term inflammatory remission in 
patients with deficiency of the IL-1 receptor antagonist. JCI Insight. 2017;2(16):e94838. 
Goldbach-Mansky R, Shroff S, Wilson M, et al. A pilot study to evaluate the safety and efficacy of the 
long-acting IL-1 inhibitor, rilonacept (IL-1 Trap) in patients with familial cold autoinflammatory 
syndrome (FCAS). Arthritis Rheum. 2008;58(8):2432-2442. 
Guy W. Clinical global impressions. In: U.S. Department of Health, Education, and Welfare, Public 
Health Service, Alcohol, Drug Abuse, and Mental Health Administration, NIMH Psychopharmacology 
Research Branch, Division of Extramural Research Programs, eds. ECDEU Assessment Manual for 
Psychopharmacology. Rockville, MD: National Institute for Mental Health; 1976:218–22. Revised 
DHEW Pub No ADM 76–338. 
Hawker GA, Mian S, Kendzerska T, et al. Measures of adult pain: visual analog scale for pain (VAS 
Pain), numeric rating scale for pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill 
Pain Questionnaire (SF-MPQ), chronic pain grade scale (CPGS), Short Form-36 Bodily Pain Scale (SF- 
36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care Res. 
2011;63(Suppl 11):S240-S252. 
Imazio M, Brucato A, Pluymaekers N, et al. Recurrent pericarditis in children and adolescents:a 
multicenter cohort study. J Cardiovasc Med 2016; 17(9):707-712. 
Imazio M. Treatment of recurrent pericarditis. Rev Esp Cardiol. 2014;67(5):345-348. 
Imazio M, Spodick DH, Brucato A, et al. Controversial issues in the management of pericardial 
diseases. Circulation. 2010; 121(7):916-928. 
Imazio M, Brucato A, Trinchero R, et al. Corticosteroid therapy for pericarditis: a double-edged sword. 
Nature Clinical Practice Cardiovascular Medicine. 2008;5(3):118-119. 
Imazio M, Cecchi E, Demichelis B, et al. Myopericarditis versus viral or idiopathic acute 
pericarditis. Heart. 2008;94:498-501. 
Imazio M, Demichelis B, Parrini I, et al. Management, risk factors, and outcomes in recurrent 
pericarditis. Am J Cardiol. 2005;96(5):736-739. 
Khandaker MH, Espinosa RE, Nishimura RA, et al. Pericardial disease: diagnosis and management. 
Mayo Clin Proc. 2010; 85(6):572-593. 
Lazaros G, Imazio M, Brucato A, et al. Anakinra: an emerging option for refractory idiopathic recurrent 
pericarditis: a systematic review of published evidence. J Cardiovasc Med. 2016;17(4):256-262. 
Lilly SL. Treatment of acute and recurrent idiopathic pericarditis. Circulation. 2013;127(16):1723- 
1726. 
Lotrionte M, Biondi-Zoccai G, Imazio M, et al. International collaborative systematic review of 
controlled clinical trials on pharmacologic treatments for acute pericarditis and its recurrences. Am 
Heart J. 2010; 160(4):662-670. 
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Maisch B, Seferović PM, Ristić AD, et al. Guidelines on the diagnosis and management of pericardial 
diseases executive summary: The Task Force on the Diagnosis and Management of Pericardial Diseases 
of the European Society of Cardiology. Eur Heart J. 2004;25(7):587-610. 
Mannion AF, Balagué F, Pellisé F, et al. Pain measurement in patients with low back pain. Nat Clin 
Practice Rheumatol. 2007;3(11):610-618. 
Morin CM, Belleville G, Bélanger L, et al. The insomnia severity index: psychometric indicators to 
detect insomnia cases and evaluate treatment response. Sleep. 2011;34(5):601-608. 
Theodoropoulou K, von Scheven-Gête A, Bressieux-Degueldre S, et al. A case of corticosteroid- 
dependent recurrent pericarditis with different response to two IL-1 blocking agents. Pediatr Rheumatol 
Online J. 2015;13(Suppl 1):P155. 
van Reenen M, Janssen B. EQ-5D-5L User Guide. Version 2.1. April 2015. Available from: 
https://euroqol.org/wp-content/uploads/2016/09/EQ-5D-5L_UserGuide_2015.pdf. 
Zayas R, Anguita M, Torres F, et al. Incidence of specific etiology and role of methods for specific 
etiologic diagnosis of primary acute pericarditis. Am J Cardiol. 1995;75(5):378-382. 
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13 Appendices 
13.1 Appendix: ARCALYST® Prescribing 
Information 
CONTRAINDICATIONS 
HIGHLIGHTS OF PRESCRIBING INFORMATION 
These highlights do not include all the information needed 
to use ARCALYST safely and effectively. See full 
prescribing information for ARCALYST. 
None. (4) 
  
 WARNINGS AND PRECAUTIONS 
• Interleukin-1 blockade may interfere with immune 
response to infections. Serious, life-threatening infections 
have been reported in patients taking ARCALYST. 
Discontinue treatment with ARCALYST if a patient 
develops a serious infection. Do not initiate treatment with 
ARCALYST in patients with active or chronic infections. 
(5.1) 
Hypersensitivity reactions associated with ARCALYST 
administration have been rare. If a hypersensitivity 
reaction occurs, discontinue administration of 
ARCALYST and initiate appropriate therapy. (5.5) 
Live vaccines should not be given concurrently with 
ARCALYST. Prior to initiation of therapy with 
ARCALYST, patients should receive all recommended 
vaccinations. (5.3) 
ARCALYST® (rilonacept) 
Injection for Subcutaneous Use 
Initial U.S. Approval: 2008 
INDICATIONS AND USAGE 
ARCALYST (rilonacept) is an interleukin-1 blocker indicated 
for the treatment of Cryopyrin-Associated Periodic Syndromes 
(CAPS), including Familial Cold Auto-inflammatory 
Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in 
adults and children 12 and older. (1) 
• 
• 
DOSAGE AND ADMINISTRATION 
• Adult patients 18 yrs and older: Initiate treatment with a 
loading dose of 320 mg delivered as two, 2-mL, 
subcutaneous injections of 160 mg on the same day at two 
different sites. Continue dosing with a once-weekly 
injection of 160 mg administered as a single, 2-mL, 
subcutaneous injection. Do not administer ARCALYST 
more often than once weekly. (2) 
Pediatric patients aged 12 to 17 years: Initiate treatment 
with a loading dose of 4.4 mg/kg, up to a maximum of 320 
mg, delivered as one or two subcutaneous injections with a 
maximum single-injection volume of 2 mL. Continue 
dosing with a once-weekly injection of 2.2 mg/kg, up to a 
maximum of 160 mg, administered as a single 
subcutaneous injection, up to 2 mL. If the initial dose is 
given as two injections, they should be given on the same 
day at two different sites. Do not administer ARCALYST 
more often than once weekly. (2) 
ADVERSE REACTIONS 
The most common adverse reactions reported by patients with 
CAPS treated with ARCALYST are injection-site reactions 
and upper respiratory tract infections. (6.2, 6.3) 
• 
To report SUSPECTED ADVERSE REACTIONS, contact 
Regeneron at 1-877-REGN-777 (1-877-734-6777) or FDA 
at 1-800-FDA-1088 or www.fda.gov/medwatch. 
  
 DRUG INTERACTIONS 
No formal drug interaction studies have been conducted with 
ARCALYST. (7) 
  
 USE IN SPECIFIC POPULATIONS 
Pregnancy – No human data. Based on animal data, may cause 
fetal harm. (8.1) 
DOSAGE FORMS AND STRENGTHS 
Sterile, single-use 20-mL, glass vial containing 220 mg of 
rilonacept as a lyophilized powder for reconstitution. (3) 
See 17 for PATIENT COUNSELING INFORMATION 
and FDA-approved patient labeling. 
Revised: 9/2016 
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FULL PRESCRIBING INFORMATION 
1 
INDICATIONS AND USAGE 
ARCALYST® (rilonacept) is an interleukin-1 blocker indicated for the treatment of Cryopyrin-Associated 
Periodic Syndromes (CAPS), including Familial Cold Auto-inflammatory Syndrome (FCAS) and 
Muckle-Wells Syndrome (MWS) in adults and children 12 and older. 
2 
2.1 
DOSAGE AND ADMINISTRATION 
General Dosing Information 
Injection for Subcutaneous Use Only. 
2.2 
Dosing 
Adult patients 18 years and older: Treatment should be initiated with a loading dose of 320 mg delivered 
as two, 2-mL, subcutaneous injections of 160 mg each given on the same day at two different sites. 
Dosing should be continued with a once-weekly injection of 160 mg administered as a single, 2-mL, 
subcutaneous injection. ARCALYST should not be given more often than once weekly. Dosage 
modification is not required based on advanced age or gender. 
Pediatric patients aged 12 to 17 years: Treatment should be initiated with a loading dose of 4.4 mg/kg, up 
to a maximum of 320 mg, delivered as one or two subcutaneous injections with a maximum single- 
injection volume of 2 mL. Dosing should be continued with a once-weekly injection of 2.2 mg/kg, up to a 
maximum of 160 mg, administered as a single subcutaneous injection, up to 2 mL. If the initial dose is 
given as two injections, they should be given on the same day at two different sites. ARCALYST should 
not be given more often than once weekly. 
2.3 
Preparation for Administration 
Each single-use vial of ARCALYST contains a sterile, white to off-white, preservative-free, lyophilized 
powder. Reconstitution with 2.3 mL of preservative-free Sterile Water for Injection (supplied separately) 
is required prior to subcutaneous administration of the drug. 
2.4 
Administration 
Using aseptic technique, withdraw 2.3 mL of preservative-free Sterile Water for Injection through a 27- 
gauge, ½-inch needle attached to a 3-mL syringe and inject the preservative-free Sterile Water for 
Injection into the drug product vial for reconstitution. The needle and syringe used for reconstitution with 
preservative-free Sterile Water for Injection should then be discarded and should not be used for 
subcutaneous injections. After the addition of preservative-free Sterile Water for Injection, the vial 
contents should be reconstituted by shaking the vial for approximately one minute and then allowing it to 
sit for one minute. The resulting 80-mg/mL solution is sufficient to allow a withdrawal volume of up to 2 
mL for subcutaneous administration. The reconstituted solution is viscous, clear, colorless to pale yellow, 
and essentially free from particulates. Prior to injection, the reconstituted solution should be carefully 
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inspected for any discoloration or particulate matter. If there is discoloration or particulate matter in the 
solution, the product in that vial should not be used. 
Using aseptic technique, withdraw the recommended dose volume, up to 2 mL (160 mg), of the solution 
with a new 27-gauge, ½-inch needle attached to a new 3-mL syringe for subcutaneous injection. EACH 
VIAL SHOULD BE USED FOR A SINGLE DOSE ONLY. Discard the vial after withdrawal of drug. 
Sites for subcutaneous injection, such as the abdomen, thigh, or upper arm, should be rotated. Injections 
should never be made at sites that are bruised, red, tender, or hard. 
2.5 
Stability and Storage 
The lyophilized ARCALYST product is to be stored refrigerated at 2° to 8°C (36° to 46°F) inside the 
original carton to protect it from light. Do not use beyond the date stamped on the label. After 
reconstitution, ARCALYST may be kept at room temperature, should be protected from light, and should 
be used within three hours of reconstitution. ARCALYST does not contain preservatives; therefore, 
unused portions of ARCALYST should be discarded. 
3 
DOSAGE FORMS AND STRENGTHS 
ARCALYST is supplied in sterile, single-use, 20-mL, glass vials. Each vial contains 220 mg of rilonacept 
as a white to off-white, preservative-free, lyophilized powder. Reconstitution with 2.3 mL of 
preservative-free Sterile Water for Injection is required prior to subcutaneous administration of the drug. 
The reconstituted ARCALYST is a viscous, clear, colorless to pale yellow, essentially free from 
particulates, 80-mg/mL solution. 
4 
None. 
CONTRAINDICATIONS 
5 
5.1 
WARNINGS AND PRECAUTIONS 
Infections 
Interleukin-1 (IL-1) blockade may interfere with the immune response to infections. Treatment with 
another medication that works through inhibition of IL-1 has been associated with an increased risk of 
serious infections, and serious infections have been reported in patients taking ARCALYST [see Clinical 
Studies (14)]. There was a greater incidence of infections in patients on ARCALYST compared with 
placebo. In the controlled portion of the study, one infection was reported as severe, which was bronchitis 
in a patient on ARCALYST. 
In an open-label extension study, one patient developed bacterial meningitis and died [see Adverse 
Reactions (6.3)]. ARCALYST should be discontinued if a patient develops a serious infection. Treatment 
with ARCALYST should not be initiated in patients with an active or chronic infection. 
In clinical studies, ARCALYST has not been administered concomitantly with tumor necrosis factor 
(TNF) inhibitors. An increased incidence of serious infections has been associated with administration of 
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an IL-1 blocker in combination with TNF inhibitors. Taking ARCALYST with TNF inhibitors is not 
recommended because this may increase the risk of serious infections. 
Drugs that affect the immune system by blocking TNF have been associated with an increased risk of 
reactivation of latent tuberculosis (TB). It is possible that taking drugs such as ARCALYST that block IL- 
1 increases the risk of TB or other atypical or opportunistic infections. Healthcare providers should follow 
current CDC guidelines both to evaluate for and to treat possible latent tuberculosis infections before 
initiating therapy with ARCALYST. 
5.2 
Immunosuppression 
The impact of treatment with ARCALYST on active and/or chronic infections and the development of 
malignancies is not known [see Adverse Reactions (6.3)]. However, treatment with immunosuppressants, 
including ARCALYST, may result in an increase in the risk of malignancies. 
5.3 
Immunizations 
Since no data are available on either the efficacy of live vaccines or on the risks of secondary 
transmission of infection by live vaccines in patients receiving ARCALYST, live vaccines should not be 
given concurrently with ARCALYST. In addition, because ARCALYST may interfere with normal 
immune response to new antigens, vaccinations may not be effective in patients receiving ARCALYST. 
No data are available on the effectiveness of vaccination with inactivated (killed) antigens in patients 
receiving ARCALYST. 
Because IL-1 blockade may interfere with immune response to infections, it is recommended that prior to 
initiation of therapy with ARCALYST adult and pediatric patients receive all recommended vaccinations, 
as appropriate, including pneumococcal vaccine and inactivated influenza vaccine. (See current 
Recommended Immunizations schedules at the website of the Centers for Disease Control and 
Prevention. http://www.cdc.gov/vaccines/schedules/index.html). 
5.4 
Lipid Profile Changes 
Patients should be monitored for changes in their lipid profiles and provided with medical treatment if 
warranted [see Adverse Reactions (6.7)]. 
5.5 
Hypersensitivity 
Hypersensitivity reactions associated with ARCALYST administration in the clinical studies were rare. If 
a hypersensitivity reaction occurs, administration of ARCALYST should be discontinued and appropriate 
therapy initiated. 
6 
ADVERSE REACTIONS 
Six serious adverse reactions were reported by four patients during the clinical program. These serious 
adverse reactions were Mycobacterium intracellulare infection; gastrointestinal bleeding and colitis; 
sinusitis and bronchitis; and Streptococcus pneumoniae meningitis [see Adverse Reactions (6.3)]. 
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The most commonly reported adverse reaction associated with ARCALYST was injection-site reaction 
(ISR) [see Adverse Reactions (6.2)]. The next most commonly reported adverse reaction was upper 
respiratory infection [see Adverse Reactions (6.3)]. 
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in 
the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and 
may not reflect the rates observed in practice. 
The data described herein reflect exposure to ARCALYST in 600 patients, including 85 exposed for at 
least 6 months and 65 exposed for at least one year. These included patients with CAPS, patients with 
other diseases, and healthy volunteers. Approximately 60 patients with CAPS have been treated weekly 
with 160 mg of ARCALYST. The pivotal trial population included 47 patients with CAPS. These patients 
were between the ages of 22 and 78 years (average 51 years). Thirty-one patients were female and 16 
were male. All of the patients were White/Caucasian. Six pediatric patients (12-17 years) were enrolled 
directly into the open-label extension phase. 
6.1 
Clinical Trial Experience 
Part A of the clinical trial was conducted in patients with CAPS who were naïve to treatment with 
ARCALYST. Part A of the study was a randomized, double-blind, placebo-controlled, six-week study 
comparing ARCALYST to placebo [see Clinical Studies (14)]. Table 1 reflects the frequency of adverse 
events reported by at least two patients during Part A. 
Table 1: 
Most Frequent Adverse Reactions (Part A, Reported by at Least Two Patients) 
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Adverse Event 
 
ARCALYST 
160 mg 
(n = 23) 
Placebo 
(n= 24) 
 
Any AE 
17 (74%) 
13 (54%) 
Injection-site reactions 
11 (48%) 
3 (13%) 
Upper respiratory tract infection 
6 (26%) 
1 (4%) 
Nausea 
1 (4%) 
3 (13%) 
Diarrhea 
1 (4%) 
3 (13%) 
Sinusitis 
2 (9%) 
1 (4%) 
Abdominal pain upper 
0 
2 (8%) 
Cough 
2 (9%) 
0 
Hypoesthesia 
2 (9%) 
0 
Stomach discomfort 
1 (4%) 
1 (4%) 
Urinary tract infection 
1 (4%) 
1 (4%) 
 


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6.2 
Injection-Site Reactions 
In patients with CAPS, the most common and consistently reported adverse event associated with 
ARCALYST was injection-site reaction (ISR). The ISRs included erythema, swelling, pruritus, mass, 
bruising, inflammation, pain, edema, dermatitis, discomfort, urticaria, vesicles, warmth and hemorrhage. 
Most injection-site reactions lasted for one to two days. No ISRs were assessed as severe, and no patient 
discontinued study participation due to an ISR. 
6.3 
Infections 
During Part A, the incidence of patients reporting infections was greater with ARCALYST (48%) than 
with placebo (17%). In Part B, randomized withdrawal, the incidence of infections were similar in the 
ARCALYST (18%) and the placebo patients (22%). Part A of the trial was initiated in the winter months, 
while Part B was predominantly performed in the summer months. 
In placebo-controlled studies across a variety of patient populations encompassing 360 patients treated 
with rilonacept and 179 treated with placebo, the incidence of infections was 34% and 27% (2.15 per 
patient-exposure year and 1.81 per patient-exposure year), respectively, for rilonacept and placebo. 
Serious Infections: One patient receiving ARCALYST for an unapproved indication in another study 
developed an infection in his olecranon bursa with Mycobacterium intracellulare. The patient was on 
chronic glucocorticoid treatment. The infection occurred after an intraarticular glucocorticoid injection 
into the bursa with subsequent local exposure to a suspected source of mycobacteria. The patient 
recovered after the administration of the appropriate antimicrobial therapy. One patient treated for another 
unapproved indication developed bronchitis/sinusitis, which resulted in hospitalization. One patient died 
in an open-label study of CAPS from Streptococcus pneumoniae meningitis. 
6.4 
Malignancies 
[see Warnings and Precautions (5.2)]. 
6.5 
Hematologic Events 
One patient in a study in an unapproved indication developed transient neutropenia (ANC < 1 x 109/L) 
after receiving a large dose (2000 mg intravenously) of ARCALYST. The patient did not experience any 
infection associated with the neutropenia. 
6.6 
Immunogenicity 
Antibodies directed against the receptor domains of rilonacept were detected by an ELISA assay in 
patients with CAPS after treatment with ARCALYST. Nineteen of 55 patients (35%) who had received 
ARCALYST for at least 6 weeks tested positive for treatment-emergent binding antibodies on at least one 
occasion. Of the 19, seven tested positive at the last assessment (Week 18 or 24 of the open-label 
extension period), and five patients tested positive for neutralizing antibodies on at least one occasion. 
There was no correlation of antibody activity and either clinical effectiveness or safety. 
The data reflect the percentage of patients whose test results were positive for antibodies to the rilonacept 
receptor domains in specific assays, and are highly dependent on the sensitivity and specificity of the 
assays. The observed incidence of antibody (including neutralizing antibody) positivity in an assay is 
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highly dependent on several factors including assay sensitivity and specificity, assay methodology, 
sample handling, timing of sample collection, concomitant medications, and underlying disease. For these 
reasons, comparison of the incidence of antibodies to rilonacept with the incidence of antibodies to other 
products may be misleading. 
6.7 
Lipid Profiles 
Cholesterol and lipid levels may be reduced in patients with chronic inflammation. Patients with CAPS 
treated with ARCALYST experienced increases in their mean total cholesterol, HDL cholesterol, LDL 
cholesterol, and triglycerides. The mean increases from baseline for total cholesterol, HDL cholesterol, 
LDL cholesterol, and triglycerides were 19 mg/dL, 2 mg/dL, 10 mg/dL, and 57 mg/dL respectively after 6 
weeks of open-label therapy. Physicians should monitor the lipid profiles of their patients (for example 
after 2-3 months) and consider lipid-lowering therapies as needed based upon cardiovascular risk factors 
and current guidelines. 
7 
7.1 
DRUG INTERACTIONS 
TNF-Blocking Agent and IL-1 Blocking Agent 
Specific drug interaction studies have not been conducted with ARCALYST. Concomitant administration 
of another drug that blocks IL-1 with a TNF-blocking agent in another patient population has been 
associated with an increased risk of serious infections and an increased risk of neutropenia. The 
concomitant administration of ARCALYST with TNF-blocking agents may also result in similar 
toxicities and is not recommended [see Warnings and Precautions (5.1)]. The concomitant administration 
of ARCALYST with other drugs that block IL-1 has not been studied. Based upon the potential for 
pharmacologic interactions between rilonacept and a recombinant IL-1ra, concomitant administration of 
ARCALYST and other agents that block IL-1 or its receptors is not recommended. 
7.2 
Cytochrome P450 Substrates 
The formation of CYP450 enzymes is suppressed by increased levels of cytokines (e.g., IL-1) during 
chronic inflammation. Thus it is expected that for a molecule that binds to IL-1, such as rilonacept, the 
formation of CYP450 enzymes could be normalized. This is clinically relevant for CYP450 substrates 
with a narrow therapeutic index, where the dose is individually adjusted (e.g., warfarin). Upon initiation 
of ARCALYST, in patients being treated with these types of medicinal products, therapeutic monitoring 
of the effect or drug concentration should be performed and the individual dose of the medicinal product 
may need to be adjusted as needed. 
8 
8.1 
USE IN SPECIFIC POPULATIONS 
Pregnancy 
Pregnancy Category C. There are no adequate and well-controlled studies of ARCALYST in pregnant 
women. Based on animal data, ARCALYST may cause fetal harm. An embryo-fetal developmental 
toxicity study was performed in cynomolgus monkeys treated with 0, 5, 15 or 30 mg/kg given twice a 
week (highest dose is approximately 3.7-fold higher than the human doses of 160 mg based on body 
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surface area). The fetus of the only monkey with exposure to rilonacept during the later period of 
gestation showed multiple fusion and absence of the ribs and thoracic vertebral bodies and arches. 
Exposure to rilonacept during this time period was below that expected clinically. Likewise, in the 
cynomolgus monkey, all doses of rilonacept reduced serum levels of estradiol up to 64% compared to 
controls and increased the incidence of lumbar ribs compared to both control animals and historical 
control incidences. In perinatal and postnatal developmental toxicology studies in the mouse model using 
a murine analog of rilonacept (0, 20, 100 or 200 mg/kg), there was a 3-fold increase in the number of 
stillbirths in dams treated with 200 mg/kg three times per week (the highest dose is approximately 6-fold 
higher than the 160 mg maintenance dose based on body surface area). ARCALYST should be used 
during pregnancy only if the benefit justifies the potential risk to the fetus. 
Nonteratogenic effects. A peri- and post-natal reproductive toxicology study was performed in which 
mice were subcutaneously administered a murine analog of rilonacept at doses of 20, 100, 200 mg/kg 
three times per week (the highest dose is approximately 6-fold higher than the 160 mg maintenance dose 
based on body surface area). Results indicated an increased incidence in unscheduled deaths of the F1 
offspring during maturation at all doses tested. 
8.3 
Nursing Mothers 
It is not known whether rilonacept is excreted in human milk. Because many drugs are excreted in human 
milk, caution should be exercised when ARCALYST is administered to a nursing woman. 
8.4 
Pediatric Use 
Six pediatric patients with CAPS between the ages of 12 and 16 were treated with ARCALYST at a 
weekly, subcutaneous dose of 2.2 mg/kg (up to a maximum of 160 mg) for 24-weeks during the open- 
label extension phase. These patients showed improvement from baseline in their symptom scores and in 
objective markers of inflammation (e.g. Serum Amyloid A and C-Reactive Protein). The adverse events 
included injection site reactions and upper respiratory symptoms as were commonly seen in the adult 
patients. 
The trough drug levels for four pediatric patients measured at the end of the weekly dose interval (mean 
20 mcg/mL, range 3.6 to 33 mcg/mL) were similar to those observed in adult patients with CAPS (mean 
24 mcg/mL, range 7 to 56 mcg/mL). 
Safety and effectiveness in pediatric patients below the age of 12 have not been established. 
When administered to pregnant primates, rilonacept treatment may have contributed to alterations in bone 
ossification in the fetus. It is not known if ARCALYST will alter bone development in pediatric patients. 
Pediatric patients treated with ARCALYST should undergo appropriate monitoring for growth and 
development. [see Use in Specific Populations (8.1)] 
8.5 
Geriatric Use 
In the placebo-controlled clinical studies in patients with CAPS and other indications, 70 patients 
randomized to treatment with ARCALYST were  65 years of age, and 6 were  75 years of age. In the 
CAPS clinical trial, efficacy, safety and tolerability were generally similar in elderly patients as compared 
to younger adults; however, only ten patients  65 years old participated in the trial. In an open-label 
extension study of CAPS, a 71 year old woman developed bacterial meningitis and died [see Adverse 
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Reactions (6.3)]. Age did not appear to have a significant effect on steady-state trough concentrations in 
the clinical study. 
8.6 
Patients with Renal Impairment 
No formal studies have been conducted to examine the pharmacokinetics of rilonacept administered 
subcutaneously in patients with renal impairment. 
8.7 
Patients with Hepatic Impairment 
No formal studies have been conducted to examine the pharmacokinetics of rilonacept administered 
subcutaneously in patients with hepatic impairment. 
10 
OVERDOSAGE 
There have been no reports of overdose with ARCALYST. Maximum weekly doses of up to 320 mg have 
been administered subcutaneously for up to approximately 18 months in a small number of patients with 
CAPS and up to 6 months in patients with an unapproved indication in clinical trials without evidence of 
dose-limiting toxicities. In addition, ARCALYST given intravenously at doses up to 2000 mg monthly in 
another patient population for up to six months were tolerated without dose-limiting toxicities. The 
maximum amount of ARCALYST that can be safely administered has not been determined. 
In case of overdose, it is recommended that the patient be monitored for any signs or symptoms of 
adverse reactions or effects, and appropriate symptomatic treatment instituted immediately. 
11 
DESCRIPTION 
Rilonacept is a dimeric fusion protein consisting of the ligand-binding domains of the extracellular 
portions of the human interleukin-1 receptor component (IL-1RI) and IL-1 receptor accessory protein (IL- 
1RAcP) linked in-line to the Fc portion of human IgG1. Rilonacept has a molecular weight of 
approximately 251 kDa. Rilonacept is expressed in recombinant Chinese hamster ovary (CHO) cells. 
ARCALYST is supplied in single-use, 20-mL glass vials containing a sterile, white to off-white, 
lyophilized powder. Each vial of ARCALYST is to be reconstituted with 2.3 mL of Sterile Water for 
Injection. A volume of up to 2 mL can be withdrawn, which is designed to deliver 160 mg for 
subcutaneous administration only. The resulting solution is viscous, clear, colorless to pale yellow, and 
essentially free from particulates. Each vial contains 220 mg rilonacept. After reconstitution, each vial 
contains 80 mg/mL rilonacept, 46 mM histidine, 50 mM arginine, 3.0% (w/v) polyethylene glycol 3350, 
2.0% (w/v) sucrose, and 1.0% (w/v) glycine at a pH of 6.5 ± 0.3. No preservatives are present. 
12 
12.1 
CLINICAL PHARMACOLOGY 
Mechanism of Action 
CAPS refer to rare genetic syndromes generally caused by mutations in the NLRP-3 [Nucleotide-binding 
domain, leucine rich family (NLR), pyrin domain containing 3] gene (also known as Cold-Induced Auto- 
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inflammatory Syndrome-1 [CIAS1]). CAPS disorders are inherited in an autosomal dominant pattern with 
male and female offspring equally affected. Features common to all disorders include fever, urticaria-like 
rash, arthralgia, myalgia, fatigue, and conjunctivitis. 
In most cases, inflammation in CAPS is associated with mutations in the NLRP-3 gene which encodes the 
protein cryopyrin, an important component of the inflammasome. Cryopyrin regulates the protease 
caspase-1 and controls the activation of interleukin-1 beta (IL-1β). Mutations in NLRP-3 result in an 
overactive inflammasome resulting in excessive release of activated IL-1β that drives inflammation. 
Rilonacept blocks IL-1β signaling by acting as a soluble decoy receptor that binds IL-1β and prevents its 
interaction with cell surface receptors. Rilonacept also binds IL-1α and IL-1 receptor antagonist (IL-1ra) 
with reduced affinity. The equilibrium dissociation constants for rilonacept binding to IL-1β, IL-1α and 
IL-1ra were 0.5 pM, 1.4 pM and 6.1 pM, respectively. 
12.2 
Pharmacodynamics 
C-Reactive Protein (CRP) and Serum Amyloid A (SAA) are indicators of inflammatory disease activity 
that are elevated in patients with CAPS. Elevated SAA has been associated with the development of 
systemic amyloidosis in patients with CAPS. Compared to placebo, treatment with ARCALYST resulted 
in sustained reductions from baseline in mean serum CRP and SAA to normal levels during the clinical 
trial. ARCALYST also normalized mean SAA from elevated levels. 
12.3 
Pharmacokinetics 
The average trough levels of rilonacept were approximately 24 mcg/mL at steady-state following weekly 
subcutaneous doses of 160 mg for up to 48 weeks in patients with CAPS. The steady-state appeared to be 
reached by 6 weeks. 
No pharmacokinetic data are available in patients with hepatic or renal impairment. 
No study was conducted to evaluate the effect of age, gender, or body weight on rilonacept exposure. 
Based on limited data obtained from the clinical study, steady state trough concentrations were similar 
between male and female patients. Age (26-78 years old) and body weight (50-120 kg) did not appear to 
have a significant effect on trough rilonacept concentrations. The effect of race could not be assessed 
because only Caucasian patients participated in the clinical study, reflecting the epidemiology of the 
disease. 
13 
13.1 
NONCLINICAL TOXICOLOGY 
Carcinogenesis, Mutagenesis, Impairment of Fertility 
Long-term animal studies have not been performed to evaluate the carcinogenic potential of rilonacept. 
The mutagenic potential of rilonacept was not evaluated. 
Male and female fertility was evaluated in a mouse surrogate model using a murine analog of rilonacept. 
Male mice were treated beginning 8 weeks prior to mating and continuing through female gestation day 
15. Female mice were treated for 2 weeks prior to mating and on gestation days 0, 3, and 6. The murine 
analog of rilonacept did not alter either male or female fertility parameters at doses up to 200 mg/kg (this 
dose is approximately 6-fold higher than the 160 mg maintenance dose based on body surface area). 
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14 
CLINICAL STUDIES 
The safety and efficacy of ARCALYST for the treatment of CAPS was demonstrated in a randomized, 
double-blind, placebo-controlled study with two parts (A and B) conducted sequentially in the same 
patients with FCAS and MWS. 
Part A was a 6-week, randomized, double-blind, parallel-group period comparing ARCALYST at a dose 
of 160 mg weekly after an initial loading dose of 320 mg to placebo. Part B followed immediately after 
Part A and consisted of a 9-week, patient-blind period during which all patients received ARCALYST 
160 mg weekly, followed by a 9-week, double-blind, randomized withdrawal period in which patients 
were randomly assigned to either remain on ARCALYST 160 mg weekly or to receive placebo. Patients 
were then given the option to enroll in a 24-week, open-label treatment extension phase in which all 
patients were treated with ARCALYST 160 mg weekly. 
Using a daily diary questionnaire, patients rated the following five signs and symptoms of CAPS: joint 
pain, rash, feeling of fever/chills, eye redness/pain, and fatigue, each on a scale of 0 (none, no severity) to 
10 (very severe). The study evaluated the mean symptom score using the change from baseline to the end 
of treatment. 
The changes in mean symptom scores for the randomized parallel-group period (Part A) and the 
randomized withdrawal period (Part B) of the study are shown in Table 2. ARCALYST-treated patients 
had a larger reduction in the mean symptom score in Part A compared to placebo-treated patients. In Part 
B, mean symptom scores increased more in patients withdrawn to placebo compared to patients who 
remained on ARCALYST. 
Table 2: Mean Symptom Scores 
*Differences are adjusted using an analysis of covariance model with terms for treatment and Part A baseline. 
**A confidence interval lying entirely below zero indicates a statistical difference favoring ARCALYST versus 
placebo. 
Daily mean symptom scores over time for Part A are shown in Figure 1. 
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Part A 
 
Placebo 
(n=24) 
ARCALYST 
(n=23) 
Part B 
 
Placebo 
(n=23) 
ARCALYST 
(n=22) 
Pre-treatment 
Baseline Period 
(Weeks -3 to 0) 
2.4 
 
3.1 
 
Active 
ARCALYST 
Baseline Period 
(Weeks 13 to 15) 
0.2 
 
0.3 
 
Endpoint Period 
(Weeks 4 to 6) 
2.1 
 
0.5 
 
Endpoint Period 
(Weeks 22 to 24) 
1.2 
 
0.4 
 
LS* Mean Change 
from Baseline to 
Endpoint 
-0.5 
 
-2.4 
 
LS* Mean Change 
from Baseline to 
Endpoint 
0.9 
 
0.1 
 
95% confidence 
interval for 
difference between 
treatment groups 
(-2.4, -1.3)** 
 
95% confidence 
interval for 
difference between 
treatment groups 
(-1.3, -0.4)** 
 
 


Kiniksa Pharmaceuticals, Ltd. 
Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
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Figure 1: Group Mean Daily Symptom Scores by Treatment Group in Part A and 
Single-blind ARCALYST Treatment Phase from Week -3 to Week 15 
Improvement in symptom scores was noted within several days of initiation of ARCALYST therapy in 
most patients. 
In Part A, patients treated with ARCALYST experienced more improvement in each of the five 
components of the composite endpoint (joint pain, rash, feeling of fever/chills, eye redness/pain, and 
fatigue) than placebo-treated patients. 
In Part A, a higher proportion of patients in the ARCALYST group experienced improvement from 
baseline in the composite score by at least 30% (96% vs. 29% of patients), by at least 50% (87% vs. 8%) 
and by at least 75% (70% vs. 0%) compared to the placebo group. 
Serum Amyloid A (SAA) and C-Reactive Protein (CRP) levels are acute phase reactants that are typically 
elevated in patients with CAPS with active disease. During Part A, mean levels of CRP decreased versus 
baseline for the ARCALYST treated patients, while there was no change for those on placebo (Table 3). 
ARCALYST also led to a decrease in SAA versus baseline to levels within the normal range. 
Table 3. Mean Serum Amyloid A and C-Reactive Protein Levels Over Time in Part A 
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Part A 
ARCALYST 
Placebo 
SAA 
(normal range: 0.7 – 6.4 mg/L) 
(n=22) 
(n=24) 
Pre-treatment Baseline 
60 
110 
Week 6 
4 
110 
CRP 
(normal range: 0.0 – 8.4 mg/L) 
(n= 21) 
(n=24) 
Pre-treatment Baseline 
22 
30 
Week 6 
2 
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During the open-label extension, reductions in mean symptom scores, serum CRP, and serum SAA levels 
were maintained for up to one year. 
16 
HOW SUPPLIED/STORAGE AND HANDLING 
Each 20-mL glass vial of ARCALYST contains a sterile, white to off-white, preservative-free, lyophilized 
powder. ARCALYST is supplied in a carton containing four vials (NDC 61755-001-01). 
The lyophilized ARCALYST product is to be stored refrigerated at 2° to 8°C (36° to 46°F) inside the 
original carton to protect from light. Do not use beyond the date stamped on the label. After 
reconstitution, ARCALYST may be kept at room temperature, should be kept from light, and should be 
used within three hours of reconstitution. ARCALYST does not contain preservatives; therefore, unused 
portions of ARCALYST should be discarded. Discard the vial after a single withdrawal of drug. 
17 
PATIENT COUNSELING INFORMATION 
See FDA-approved patient labeling. 
The first injection of ARCALYST should be performed under the supervision of a qualified healthcare 
professional. If a patient or caregiver is to administer ARCALYST, he/she should be instructed on aseptic 
reconstitution of the lyophilized product and injection technique. The ability to inject subcutaneously 
should be assessed to ensure proper administration of ARCALYST, including rotation of injection sites. 
(See Patient Information Leaflet for ARCALYST®). ARCALYST should be reconstituted with 
preservative-free Sterile Water for Injection to be provided by the pharmacy. A puncture-resistant 
container for disposal of vials, needles and syringes should be used. Patients or caregivers should be 
instructed in proper vial, syringe, and needle disposal, and should be cautioned against reuse of these 
items. 
Injection-site Reactions: Physicians should explain to patients that almost half of the patients in the 
clinical trials experienced a reaction at the injection site. Injection-site reactions may include pain, 
erythema, swelling, pruritus, bruising, mass, inflammation, dermatitis, edema, urticaria, vesicles, warmth, 
and hemorrhage. Patients should be cautioned to avoid injecting into an area that is already swollen or 
red. Any persistent reaction should be brought to the attention of the prescribing physician. 
Infections: Patients should be cautioned that ARCALYST has been associated with serious, 
life-threatening infections, and not to initiate treatment with ARCALYST if they have a chronic or active 
infection. Patients should be counseled to contact their healthcare professional immediately if they 
develop an infection after starting ARCALYST. Treatment with ARCALYST should be discontinued if a 
patient develops a serious infection. Patients should be counseled not to take any IL-1 blocking drug, 
including ARCALYST, if they are also taking a drug that blocks TNF such as etanercept, infliximab, or 
adalimumab. Use of ARCALYST with other IL-1 blocking agents, such as anakinra, is not recommended. 
Vaccinations: Prior to initiation of therapy with ARCALYST physicians should review with adult and 
pediatric patients their vaccination history relative to current medical guidelines for vaccine use, including 
taking into account the potential of increased risk of infection during treatment with ARCALYST. 
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Rilonacept (KPL-914) 
Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr2019 
Manufactured and distributed by: 
Regeneron Pharmaceuticals, Inc. 
777 Old Saw Mill River Road, 
Tarrytown, NY 10591-6707, 1-877-REGN-777 (1-877-734-6777) 
U.S. License Number 1760 
NDC 61755-001-01 
© 2016, Regeneron Pharmaceuticals, Inc. 
All rights reserved. 
V 5.0 
Patient Information 
ARCALYST® (ARK-a-list) 
(rilonacept) 
Injection for Subcutaneous Use 
Read the patient information that comes with ARCALYST before you start taking it and each time 
you refill your prescription. There may be new information. The information in this leaflet does not 
take the place of talking with your healthcare provider about your medical condition and your 
treatment. 
What is the most important information I should know about ARCALYST? 
ARCALYST can affect your immune system. ARCALYST can lower the ability of your immune 
system to fight infections. Serious infections, including life-threatening infections and death have 
happened in patients taking ARCALYST. Taking ARCALYST can make you more likely to get 
infections, including life-threatening serious infections, or may make any infection that you 
have worse. 
You should not begin treatment with ARCALYST if you have an infection or have infections 
that keep coming back (chronic infection). 
After starting ARCALYST, if you get an infection, any sign of an infection including a fever, 
cough, flu-like symptoms, or have any open sores on your body, call your healthcare provider right 
away. Treatment with ARCALYST should be stopped if you develop a serious infection. 
You should not take medicines that block Tumor Necrosis Factor (TNF), such as Enbrel® 
(etanercept), Humira® (adalimumab), or Remicade® (infliximab), while you are taking 
ARCALYST. You should also not take other medicines that block Interleukin-1 (IL-1), such as 
Kineret  (anakinra), while taking ARCALYST. Taking ARCALYST with any of these 
medicines may increase your risk of getting a serious infection. 
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Before starting treatment with ARCALYST, tell your healthcare provider if you: 
• 
• 
• 
• 
• 
• 
• 
think you have an infection 
are being treated for an infection 
have signs of an infection, such as fever, cough, or flu-like symptoms 
have any open sores on your body 
have a history of infections that keep coming back 
have asthma. Patients with asthma may have an increased risk of infection. 
have diabetes or an immune system problem. People with these conditions have a higher 
chance for infections. 
have tuberculosis (TB), or if you have been in close contact with someone who has had 
tuberculosis. 
have or have had HIV, Hepatitis B, or Hepatitis C 
take other medicines that affect your immune system 
• 
• 
• 
Before you begin treatment with ARCALYST, talk with your healthcare provider about your 
vaccination history. Ask your healthcare provider whether you should receive any vaccinations, 
including pneumonia vaccine and flu vaccine, before you begin treatment with ARCALYST. 
What is ARCALYST? 
ARCALYST is a prescription medicine called an interleukin-1 (IL-1) blocker. ARCALYST is used to 
treat adults and children 12 years and older with Cryopyrin-Associated Periodic Syndromes (CAPS), 
including Familial Cold Auto-inflammatory Syndrome (FCAS) and Muckle Wells Syndrome (MWS). 
ARCALYST can help lessen the signs and symptoms of CAPS, such as rash, joint pain, fever, and 
tiredness, but it can also lead to serious side effects because of the effects on your immune system. 
What should I tell my healthcare provider before taking ARCALYST? 
ARCALYST may not be right for you. Before taking ARCALYST, tell your healthcare provider 
about all of your medical conditions, including if you: 
• are scheduled to receive any vaccines. You should not receive live vaccines if you take 
ARCALYST. 
are pregnant or planning to become pregnant. It is not known if ARCALYST will harm 
your unborn child. Tell your healthcare provider right away if you become pregnant while 
taking ARCALYST. 
are breast-feeding or planning to breast-feed. It is not known if ARCALYST passes into 
your breast milk. 
• 
• 
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See “What is the most important information I should know about ARCALYST?” 
Tell your healthcare provider about all the medicines you take, including prescription and 
non-prescription medicines, vitamins, and herbal supplements. Especially tell your healthcare 
provider if you take other medicines that affect your immune system, such as: 
• 
• 
other medicines that block IL-1, such as Kineret  (anakinra). 
medicines that block Tumor Necrosis Factor (TNF), such as Enbrel  (etanercept), Humira  
(adalimumab), or Remicade  (infliximab). 
corticosteroids. 
• 
See “What is the most important information I should know about ARCALYST?” 
Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider 
and pharmacist every time you get a new prescription. 
If you are not sure or have any questions about any of this information, ask your healthcare provider. 
How should I take ARCALYST? 
See the “Patient Instructions for Use” at the end of this leaflet. 
• 
• 
• 
Take ARCALYST exactly as prescribed by your healthcare provider. 
ARCALYST is given by injection under the skin (subcutaneous injection) one time each week. 
Your healthcare provider will tell and show you or your caregiver: 
▪ 
▪ 
▪ 
how much ARCALYST to inject 
how to prepare your dose 
how to give the injection 
• 
Do not try to give ARCALYST injections until you are sure that you or your caregiver 
understands how to prepare and inject your dose. Call your healthcare provider or pharmacist if 
you have any questions about preparing and injecting your dose, or if you or your caregiver 
would like more training. 
If you miss a dose of ARCALYST, inject it as soon as you remember, up to the day before your 
next scheduled dose. The next dose should be taken at the next regularly scheduled time. If you 
have any questions, contact your healthcare provider. 
If you accidentally take more ARCALYST than prescribed, call your healthcare provider. 
• 
• 
What are the possible side effects of ARCALYST? 
Serious side effects may occur while you are taking and after you finish taking ARCALYST 
including: 
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• Serious Infections. See “What is the most important information I should know about 
taking ARCALYST?” Treatment with ARCALYST should be discontinued if you 
develop a serious infection. 
• Allergic Reaction. Call your healthcare provider or seek emergency care right away if you 
get any of the following symptoms of an allergic reaction while taking ARCALYST: 
• 
• 
• 
rash 
swollen face 
trouble breathing 
Common side effects with ARCALYST include: 
• Injection-site reaction. This includes: pain, redness, swelling, itching, bruising, lumps, 
inflammation, skin rash, blisters, warmth, and bleeding at the injection site. 
Upper respiratory infection. 
Changes in your blood cholesterol and triglycerides (lipids). Your healthcare provider 
will check you for this. 
• 
• 
These are not all the possible side effects of ARCALYST. Tell your healthcare provider about any 
side effects that bother you or that do not go away. For more information ask your healthcare provider 
or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to 
FDA at 1-800-FDA-1088. 
How should I store ARCALYST? 
• 
• 
Keep ARCALYST in the carton it comes in. 
Store ARCALYST in a refrigerator between 36°F to 46°F (2°C to 8°C). Call your pharmacy if 
you have any questions. 
Always keep ARCALYST away from light. 
Refrigerated ARCALYST can be used until the expiration date printed on the vial and carton. 
ARCALYST may be kept at room temperature after mixing. ARCALYST should be used within 
three hours of mixing. Keep ARCALYST away from light. 
If you need to take ARCALYST with you when traveling, store the carton in a cool carrier with a 
cold pack and protect it from light. 
• 
• 
• 
• 
Keep ARCALYST, injection supplies, and all other medicines out of reach of children. 
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What are the ingredients in ARCALYST? 
Active ingredient: rilonacept. 
Inactive ingredients: histidine, arginine, polyethylene glycol 3350, sucrose, and glycine. 
General Information about ARCALYST 
Medicines are sometimes prescribed for conditions other than those listed in patient information 
leaflets. Do not use ARCALYST for a condition for which it was not prescribed. Do not give 
ARCALYST to other people even if they have the same condition. It may harm them. 
This leaflet summarizes the most important information about ARCALYST. If you would like more 
information, speak with your healthcare provider. You can ask your healthcare provider or pharmacist 
for information about ARCALYST that was written for healthcare professionals. For more 
information about ARCALYST, call 1-877-REGN-777 (1-877-734-6777), or visit 
www.ARCALYST.com. 
Patient Instructions for Use 
It is important for you to read, understand and follow the instructions below exactly. Following the 
instructions correctly will help to make sure that you use, prepare and inject the medicine the right 
way to prevent infection. 
How do I prepare and give an injection of ARCALYST? 
STEP 1: Setting up for an injection 
1. Choose a table or other flat surface area to set up the supplies for your injection. Be sure that 
the area is clean or clean it with an antiseptic or soap and water first. 
Wash your hands well with soap and water, and dry with a clean towel. 
Put the following items on a table, or other flat surface, for each injection (see Figure 1): 
2. 
3. 
Figure 1 
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Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr2019 
• 
2 sterile, 3-milliliter (mL) disposable syringes with markings at each 0.1 mL (see Figure 
2): 
• 
• 
one needed for mixing (reconstitution) ARCALYST 
one needed for injection 
Figure 2 
2 sterile disposable needles (27-gauge, ½-inch) 
• 
• 
• 
one needed for mixing 
one needed for injection 
• 
• 
• 
• 
• 
Note: 
• 
4 alcohol wipes 
1 2x2 gauze pad 
1 vial of ARCALYST (powder in vial) 
1 vial of preservative-free Sterile Water for Injection 
1 puncture-resistant container for disposal of used needles, syringes, and vials 
Do not use Sterile Water for Injection, syringes or needles other than those provided by 
your pharmacy. Contact your pharmacy if you need replacement syringes or needles. 
Do not touch the needles or the rubber stoppers on the vials with your hands. If you do 
touch a stopper, clean it with a fresh alcohol wipe. 
If you touch a needle or the needle touches any surface, throw away the entire syringe 
into the puncture-resistant container and start over with a new syringe. 
Do not reuse needles or syringes. 
• 
• 
• 
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• 
To protect yourself and others from possible needle sticks, it is very important to throw 
away every syringe, with the needle attached, in the puncture proof container right after 
use. Do not try to recap the needle. 
STEP 2: Preparing Vials 
1. Check the expiration date on the carton of ARCALYST. Do not use the vial if the expiration 
date has passed. Contact your pharmacy for assistance. 
Check the expiration date on the vial of Sterile Water for Injection. Do not use the vial if the 
expiration date has passed. Contact your pharmacy for assistance. 
Remove the protective plastic cap from both vials. 
Clean the top of each vial with an alcohol wipe. Use one wipe for each vial and wipe in one 
direction around the top of the vial (see Figure 3). 
2. 
3. 
4. 
Figure 3 
Open the wrapper that contains the 27-gauge needle by pulling apart the tabs and set it aside 
for later use. Do not remove the needle cover. This needle will be used to mix the water with 
powder. Open the wrapper that contains the syringe by pulling apart the tabs. Hold the barrel 
of the syringe with one hand and twist the 27-gauge needle onto the tip of the syringe until it 
fits snugly with the other hand (see Figure 4). 
5. 
Figure 4 
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6. Hold the syringe at eye level. With the needle covered pull back the plunger to the 2.3 mL 
mark, filling the syringe with air (see Figure 5). 
Figure 5 
Hold the syringe in one hand, use the other hand to pull the needle cover straight off. Do not 
twist the needle as you pull off the cover. Place the needle cover aside. Hold the syringe in 
the hand that you will use to mix (reconstitute) your medicine. Hold the Sterile Water vial on 
a firm surface with your other hand. Slowly insert the needle straight through the rubber 
stopper. Do not bend the needle. Push the plunger in all the way to push the air into the vial 
(see Figure 6). 
7. 
Figure 6 
Hold the vial in one hand and the syringe in the other hand and carefully turn the vial upside 
down so that the needle is pointing straight up. 
Make sure the tip of the needle is covered by the liquid and slowly pull back on the plunger to 
the 2.3 mL mark to withdraw the Sterile Water from the vial (see Figure 7). 
8. 
9. 
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Figure 7 
10. Keep the vial upside down and tap or flick the syringe with your fingers until any air bubbles 
rise to the top of the syringe. 
11. To remove the air bubbles, gently push in the plunger so only the air is pushed out of the 
syringe and back into the bottle. 
12. After removing the bubbles, check the syringe to be sure that the right amount of Sterile 
Water has been drawn into the syringe (see Figure 8). 
Figure 8 
13. Carefully remove the syringe with needle from the Sterile Water vial. Do not touch the 
needle. 
STEP 3: Mixing (Reconstituting) ARCALYST 
1. With one hand, hold the ARCALYST vial on a firm surface. 
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2. With the other hand, take the syringe with the Sterile Water and the same needle, and slowly 
insert the needle straight down through the rubber stopper of the ARCALYST vial. Push the 
plunger in all the way to inject the Sterile Water into the vial. 
Direct the water stream to gently go down the side of the vial into the powder (see Figure 9). 
3. 
Figure 9 
Remove the syringe and needle from the stopper and throw away the needle, syringe, and 
Sterile Water vial in the puncture-resistant container. Do not try to put the needle cover back 
on the needle. 
Hold the vial containing the ARCALYST and sterile water for injection sideways (not 
upright) with your thumb and a finger at the top and bottom of the vial, and quickly shake the 
vial back and forth (side-to-side) for about 1 minute (see Figure 10). 
4. 
5. 
Figure 10 
Put the vial back on the table and let the vial sit for about 1 minute. 
Look at the vial for any particles or clumps of powder which have not dissolved. 
6. 
7. 
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Protocol KPL-914-C002-Amendment 1 
Version 2.0, 12 Apr2019 
8. If the powder has not completely dissolved, shake the vial quickly back and forth for 
30 seconds more. Let the vial sit for about 1 minute. 
9. Repeat Step 8 until the powder is completely dissolved and the solution is clear. 
10. The mixed ARCALYST should be thick, clear, and colorless to pale yellow. Do not use the 
mixed liquid if it is discolored or cloudy, or if small particles are in it (see Figure 11). 
NOTE: Contact your pharmacy to report any mixed ARCALYST that is discolored or 
contains particles. 
Figure 11 
11. ARCALYST may be kept at room temperature after mixing. ARCALYST should be used 
within three hours of mixing. Keep ARCALYST away from light. 
STEP 4: Preparing the injection 
1. Hold the ARCALYST vial on a firm surface and wipe the top of the ARCALYST vial with a 
new alcohol wipe (see Figure 12). 
Figure 12 
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2. Take a new sterile, disposable needle and attach securely to a new syringe without removing 
the needle cover (see Figure 13). 
Figure 13 
The amount of air you draw into the syringe should equal the amount of mixed ARCALYST 
that your healthcare provider has prescribed for you to inject. 
To draw air into the syringe, hold the syringe at eye level. Do not remove the needle cover. 
Pull back the plunger on the syringe to the mark that is equal to the amount of mixed 
ARCALYST that your healthcare provider has prescribed for you to inject (see Figure 14). 
3. 
4. 
Figure 14 
Remove the needle cover and be careful not to touch the needle. Keep the ARCALYST vial 
on a flat surface and slowly insert the needle straight down through the stopper. Push the 
plunger down and inject all the air into the vial (see Figure 15). 
5. 
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Figure 15 
Hold the vial in one hand and the syringe in the other hand and carefully turn the vial upside 
down so that the needle is pointing straight up. Hold the vial at eye level. 
Keep the tip of the needle in the liquid and slowly pull back on the plunger to the mark on the 
syringe that matches the amount of medicine prescribed by your healthcare provider (see 
Figure 16). 
6. 
7. 
Figure 16 
NOTE: The maximum adult dose of ARCALYST is 2 mL. 
Keep the vial upside down with the needle straight up, and gently tap the syringe until any air 
bubbles rise to the top of the syringe (see Figure 17). 
It is important to remove air bubbles so that you withdraw up the right amount of medicine 
from the vial. 
8. 
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Figure 17 
9. To remove the air bubbles, slowly and gently push in the plunger so only the air is pushed 
through the needle. 
10. Check to make sure that you have the amount of medicine prescribed by your healthcare 
provider in the syringe. 
11. Throw away the ARCALYST vial in the puncture-resistant container even if there is any 
medicine left in the vial (see Figure 18). Do not use any vial of ARCALYST more than one 
time. 
Figure 18 
STEP 5: Giving the Injection 
1. ARCALYST is given by subcutaneous injection, an injection that is given into the tissue 
directly below the layers of skin. It is not meant to go into any muscle, vein, or artery. 
You should change (rotate) the sites and inject in a different place each time in order to 
keep your skin healthy. 
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Rotating injection sites helps to prevent irritation and allows the medicine to be completely 
absorbed. Ask your healthcare provider any questions that you have about rotating injection 
sites. 
• 
Do not inject into skin that is tender, red, or hard. If an area is tender or feels 
hardened, choose another site for injection until the tenderness or "hardening" 
goes away. 
Tell your healthcare provider about any skin reactions including redness, 
swelling, or hardening of the skin. 
Areas where you may inject ARCALYST include the left and right sides of the 
abdomen, and left and right thighs. If someone else is giving the injection, the 
upper left and right arms may also be used for injection (see Figure 19): 
(Do not inject within a 2-inch area around the navel) 
• 
• 
Figure 19 
Choose the area for the injection. Clean the area in a circular motion with a new alcohol wipe. 
Begin at the center of the site and move outward. Let the alcohol air dry completely. 
Take the cover off the needle and be careful not to touch the needle. 
Hold the syringe in one hand like you would hold a pencil. 
With the other hand gently pinch a fold of skin at the cleaned site for injection (see Figure 
20). 
2. 
3. 
4. 
5. 
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Figure 20 
Use a quick “dart like” motion to insert the needle straight into the skin (90 degree angle) (see 
Figure 21). Do not push down on the plunger while inserting the needle into the skin. 
For small children or persons with little fat under the skin, you may need to hold the syringe 
and needle at a 45 degree angle (see Figure 21). 
6. 
Figure 21 
After the needle is completely in the skin, let go of the skin that you are pinching. 
With your free hand hold the syringe near its base. Gently pull back the plunger. If blood 
comes into the syringe, the needle has entered a blood vessel. Remove the needle, discard the 
syringe and needle. Start over with “STEP 1: Setting up for an injection” using new supplies 
(syringes, needles, vials, alcohol swabs and gauze pad). 
If no blood appears, inject all the medicine in the syringe at a slow, steady rate, pushing the 
plunger all the way down. It may take up to 30 seconds to inject the entire dose. 
7. 
8. 
9. 
10. Pull the needle out of the skin, and hold a piece of sterile gauze over the injection site for 
several seconds (see Figure 22). 
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Figure 22 
11. Do not replace the needle cover. Throw away the vials, used syringes and needles in the 
puncture-resistant container (see Figure 23). Do not recycle the container. DO NOT throw 
away vials, needles, or syringes in the household trash or recycle. 
Figure 23 
12. Keep the puncture-resistant container out of reach of children. When the container is about 
two-thirds full, dispose of it as instructed by your healthcare provider. Follow any special 
state or local laws about the right way to throw away needles and syringes. 
13. Used alcohol wipes can be thrown away in the household trash. 
Contact your healthcare provider right away with any questions or concerns about ARCALYST. 
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Notes: 1. Enbrel , Humira , Kineret , and Remicade , respectively, are trademarks of Immunex 
Corporation, AbbVie Biotechnology Ltd., Amgen Inc., and Janssen Biotech, Inc., respectively. 
Manufactured and distributed by: 
Regeneron Pharmaceuticals, Inc. 
777 Old Saw Mill River Road 
Tarrytown, NY 10591-6707 
U.S. License Number 1760 
NDC 61755-001-01 
© 2016, Regeneron Pharmaceuticals, Inc. 
All rights reserved. 
V 4.0 
13.2 Appendix: 11-point Numerical Rating Scale (NRS) for Assessment of 
Pericarditis Pain 
Subjects will be asked to select the score that best describes their average level of pericarditis 
pain over the previous 24 hours using an 11-point NRS, where zero (0) indicates ‘no pain’ and 
ten (10) means indicates ‘pain as bad as it could be’. 
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Kiniksa Pharmaceuticals, Ltd. 
KPL-914-C002 Amendment 1 Summary of Changes 
Page 1 of 7 
Kiniksa Pharmaceuticals, Ltd 
Protocol KPL-914-C002 
Amendment 1 Summary of Changes 
Version 1.1. 05 October 2018 to Version 2.0 dated 12 Apr 2019 
Rationale for Amendment 
This is an amendment to revise one of the criteria for permanent study drug discontinuation, add baseline 
PK drug level measurement, remove the 10 subject cap in the cardiac MRI substudy, revise full physical 
examination text, revise statement on FDA Form 1572 outside the US, and correct minor inconsistencies 
among the protocol synopsis and protocol text, and among protocol text and Informed Consent and 
Investigators Brochure. In addition, Kiniksa study contacts were updated to reflect changes in study 
personnel. 
Table 1 lists the modifications made in Amendment 1 along with the rationale for each change. 
Minor editorial changes for improved readability are not included in the table. 
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KPL-914-C002 Amendment 1 (Version 2) Summary of Changes 
Page 2 of 7 
Table 1 
List of Changes 
Change 
Section 
Current Text 
Revised Text 
Rationale 
1 
KPL-914-C002 
Update reflects changes in 
Kiniksa study personnel. 
m 
Text in the 4th bullet 
(Pharmacogenomics) in the 
synopsis was updated to 
remove “peripheral blood 
mononuclear cells isolation” 
for consistency with main 
protocol. Collection of 
nucleated cells for DNA 
isolation is stipulated in the 
protocol as a “whole blood 
for pharmacogenomics 
assessment.” 
2 
Study Synopsis 
Study Pharmacokinetic or Pharmacodynamic 
Assessments: 
Study Pharmacokinetic or 
Pharmacodynamic Assessments: 
Pharmacokinetic or pharmacodynamic 
assessments will include: 
Pharmacokinetic or pharmacodynamic 
assessments will include: 
• 
• 
• 
• 
PK analysis 
Anti-rilonacept antibodies 
Biomarkers 
Peripheral blood mononuclear cell 
isolation (for subjects who sign the 
separate informed consent 
for pharmacogenomics assessments) 
• 
• 
• 
• 
PK analysis 
Anti-rilonacept antibodies 
Biomarkers 
Pharmacogenomics (for subjects who 
sign the separate informed consent for 
pharmacogenomics assessments) 
CONFIDENTIAL 
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Kiniksa Pharmaceuticals, Ltd. 
KPL-914-C002 Amendment 1 (Version 2) Summary of Changes 
Page 3 of 7 
CONFIDENTIAL 
Page 428 
Change 
Section 
Current Text 
Revised Text 
Rationale 
3 
 
Table 1-1 Study 
Schedule of Activities- 
Screening and Run-In 
Period (Part 1 of 2) 
Table 1-2 Study 
Schedule of activities- 
Randomized 
Withdrawal (part 1 of 
2) 
Table 1-3 Study 
Schedule of Activities- 
Long Term Extension 
(Part 1 of 2) 
Table 1-4 Study 
Schedule of Activities- 
Supplemental Visits 
(Part 1 of 2) 
6.3.1 Physical 
Examination 
 
Footnotes: 
c Full physical examination includes at minimum 
evaluation of vital signs, head, eye, ear, nose, and 
throat as well as cardiovascular, dermatological, 
musculoskeletal, respiratory, GI, genitourinary, 
and neurological systems. 
Full physical examination includes at minimum 
evaluation of vital signs, head, eye, ear, nose, and 
throat as well as cardiovascular, dermatological, 
musculoskeletal, respiratory, GI, genitourinary, 
and neurological systems. 
 
Footnotes: 
c Full physical examination includes at 
minimum evaluation of vital signs, head, 
eye, ear, nose, and throat as well as 
cardiovascular, dermatological, 
musculoskeletal, respiratory, GI, 
genitourinary, and neurological systems. 
The decision to perform examination of 
genitourinary system should be guided by 
clinical judgment. 
Full physical examination includes at 
minimum evaluation of vital signs, head, 
eye, ear, nose, and throat as well as 
cardiovascular, dermatological, 
musculoskeletal, respiratory, GI, 
genitourinary, and neurological systems. 
The decision to perform examination of 
genitourinary system should be guided by 
clinical judgment. 
 
Change was done to allow 
genitourinary system 
examination to be performed 
as a part of full physical 
examination, based on 
clinical judgement. 
 
 


Kiniksa Pharmaceuticals, Ltd. 
KPL-914-C002 Amendment 1 (Version 2) Summary of Changes 
Page 4 of 7 
CONFIDENTIAL 
Page 429 
Change 
Section 
Current Text 
Revised Text 
Rationale 
4 
 
1.3.1 Safety of 
Rilonacept 
 
Malignancies 
The impact of treatment with rilonacept on the 
development of malignancies is not known. 
However, treatment with immunosuppressants, 
including rilonacept, may result in an increase in 
the risk for malignancies. 
 
Malignancies 
Although malignancies have been reported in 
some subjects treated with rilonacept during 
clinical trials, the effect of rilonacept on the 
development of cancer is not known. 
Treatment with immunosuppressants, 
including rilonacept, may result in an 
increase in the risk of malignancies. 
Change was done to 
coordinate the protocol 
content with current 
Informed Consent and 
Investigator Brochure 
content. 
 
 


Kiniksa Pharmaceuticals, Ltd. 
KPL-914-C002 Amendment 1 (Version 2) Summary of Changes 
Page 5 of 7 
CONFIDENTIAL 
Page 430 
Change 
Section 
Current Text 
Revised Text 
Rationale 
5 
 
4.2.2.1 
Discontinuation of 
Study Drug 
 
The study drug dosing will be permanently 
stopped if any of the following occurs: 
• 
The subject develops a serious or intolerable 
AE, TB, or malignancy, excluding non- 
metastatic cutaneous squamous cell 
carcinoma or basal cell carcinoma 
• 
Initiation of protocol-prohibited medication 
(Section 5.8.6) 
• 
Subject requires treatment with CS for 
pericarditis during RW or LTE-TP periods of 
the study 
• 
Pregnancy or pregnancy planned during the 
study or within 3 months after the last study 
drug administration 
• 
ALT or AST values ≥3 × ULN associated 
with total bilirubin ≥2 × ULN, with no 
underlying medical conditions to explain the 
elevated values 
• 
Treatment with a live (attenuated) vaccine 
during the study 
• 
Investigator or Sponsor’s medical monitor or 
medical monitor decides 
that, for safety reasons, it is in the subject’s 
best interest 
• 
Termination of the study by Kiniksa 
Pharmaceuticals 
Permanent 
or 
temporary 
study 
drug 
discontinuation should be strongly considered at 
the time if any of the following occurs: 
• 
Subject develops an opportunistic infection. 
• 
Subject develops moderate or severe 
infection 
• 
Neutrophil count <1.0 × 103/µL 
• 
Isolated ALT or AST values >5 × ULN 
• 
Surgical procedure 
 
The study drug dosing will be permanently 
stopped if any of the following occurs: 
• 
The subject develops TB or malignancy, 
excluding non-metastatic cutaneous 
squamous cell carcinoma or basal cell 
carcinoma 
• 
Initiation of protocol-prohibited 
medication (Section 5.8.6) 
• 
Subject requires treatment with CS for 
pericarditis during RW or LTE-TP 
periods of the study 
• 
Pregnancy or pregnancy planned during 
the study or within 3 months after the 
last study drug administration 
• 
ALT or AST values ≥3 × ULN 
associated with total bilirubin ≥2 × 
ULN, with no underlying medical 
conditions to explain the elevated values 
• 
Treatment with a live (attenuated) 
vaccine during the study 
• 
Investigator or Sponsor’s medical 
monitor or 
medical 
monitor decides that, for safety reasons, 
it is in the subject’s best interest 
• 
Termination of the study by Kiniksa 
Pharmaceuticals 
Permanent 
or 
temporary 
study 
drug 
discontinuation should be strongly considered 
at the time if any of the following occurs: 
• 
Subject develops an opportunistic 
infection 
• 
Subject develops moderate or severe 
infection 
• 
Neutrophil count <1.0 × 103/µL 
• 
Isolated ALT or AST values >5 × ULN 
• 
Surgical procedure 
First bullet was modified to 
remove: 
- requirement for permanent 
study drug discontinuation 
for any SAE. This is done to 
avoid stopping the drug in 
case of hospitalization for 
recurrent pericarditis or other 
events which would 
otherwise not require study 
drug discontinuation 
- requirement for permanent 
study drug discontinuation 
for intolerable AE, as this 
concept is covered in bullet 
#7 where it’s stated that 
Investigator or Sponsor’s 
medical monitor or 
medical monitor 
can decide that 
discontinuation of study drug 
for safety reasons is in the 
subject’s best interest 
 
 
 
 
 
 


Kiniksa Pharmaceuticals, Ltd. 
KPL-914-C002 Amendment 1 (Version 2) Summary of Changes 
Page 6 of 7 
CONFIDENTIAL 
Page 431 
Change 
Section 
Current Text 
Revised Text 
Rationale 
6 
 
6.1 Study Visits 
 
Subjects can be brought to the clinic in place of a 
scheduled outpatient visit or for an unscheduled 
visit at the discretion of the investigator. 
 
Subjects can be brought to the clinic in place 
of a scheduled outpatient visit or for an 
unscheduled visit at the discretion of the 
investigator or if arranging a visiting nurse 
for an at-home visit is logistically not 
feasible. 
The statement was added to 
allow clinic visit in case 
arranging a nurse home visit 
is logistically not feasible. 
 
7 
 
6.1.2.1 Enrollment 
(Run-In Baseline): 
Clinic Visit 
 
• 
Obtain 
central 
laboratory 
chemistry, 
hematology, lipid panel, CRP, anti-drug 
antibodies 
(ADAs), 
biomarkers, 
and 
urinalysis (laboratory tests should be drawn 
prior to the first study drug administration, but 
results of those tests are not required before 
enrollment). 
 
• 
Obtain central laboratory chemistry, 
hematology, lipid panel, CRP, anti-drug 
antibodies (ADAs [ADA sample will be 
also 
used 
for 
PK measurement]), 
biomarkers, and urinalysis (laboratory 
tests should be drawn prior to the first 
study drug administration, but results of 
those tests are not required before 
enrollment). 
Statement added that Run-In 
Baseline ADA sample will 
be also used for PK 
measurement. 
 
8 
 
6.1.2.7 RI Week 6: 
Clinic Visit 
 
Upon completion of the above study 
activities, the study drug dispensing can 
commence. The following procedures occur: 
• 
Have the subject administer the next 
scheduled injection of study drug (if 
within the study drug window) and have 
the subject record in the medication diary. 
• 
Dispense study drug through the IWRS 
and record the amount (number of vials) 
dispensed. 
• 
Review the study drug dosing schedule, 
administration 
techniques, 
and 
documentation. 
 
Upon completion of the above study 
activities, the study drug dispensing can 
commence. The following procedures 
occur: 
• 
Dispense study drug through the 
IWRS 
and 
record 
the 
amount 
(number of vials) dispensed. 
• 
Have the subject administer the next 
scheduled injection of study drug (if 
within the study drug window) and 
have the subject record in the 
medication diary. 
• 
Review the study drug dosing 
schedule, administration techniques, 
and documentation. 
First and second bullet were 
switched to clarify order of 
procedures. Site should 
dispense study drug through 
the IWRS prior to the subject 
administering the next 
injection of study drug. 
 
 


Kiniksa Pharmaceuticals, Ltd. 
KPL-914-C002 Amendment 1 (Version 2) Summary of Changes 
Page 7 of 7 
CONFIDENTIAL 
Page 432 
Change 
Section 
Current Text 
Revised Text 
Rationale 
9 
 
6.2 Efficacy 
Assessments 
 
In a substudy at selected sites in approximately 
10 subjects, a cardiac MRI will be performed. 
 
In a substudy at selected sites, a cardiac MRI 
will be performed. 
 
Removed the limitation of 10 
subjects in the MRI 
substudy. 
10 
 
10.3 Investigator 
Documentation 
 
• 
Curriculum vitae for the investigator and 
each sub-investigator listed on Form 
FDA 1572 
 
• 
Curriculum vitae for the investigator and 
each sub-investigator listed on Form 
FDA 1572 or local country-specific 
equivalent for outside the US 
 
Added statement that in lieu 
of FDA1572 Form, outside 
the US, a local country- 
specific equivalent of 1572 
Form can be used. 
 
 


Rilonacept (KPL-914) 
Study KPL-914-C002 
Kiniksa Pharmaceuticals, Ltd 
Clinical Study Protocol 
CLINICAL STUDY PROTOCOL 
PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
RANDOMIZED WITHDRAWAL STUDY WITH OPEN-LABEL 
EXTENSION, TO ASSESS THE EFFICACY AND SAFETY OF 
RILONACEPT TREATMENT IN SUBJECTS WITH 
RECURRENT PERICARDITIS – Rilonacept inHibition of 
interleukin-1 Alpha and beta for recurrent Pericarditis: a pivotal 
Symptomatology and Outcomes stuDY 
(RHAPSODY) 
AMENDMENT #2; PROTOCOL VERSION 3.0 
10 MARCH 2020 
IND: 136,896 
EudraCT: 2018-002719-87 
CONFIDENTIALITY STATEMENT 
The information in this document is the property of Kiniksa Pharmaceuticals, Ltd. and contains proprietary and 
confidential information to be held in strict confidence and not disclosed to any third party, without prior written 
consent of Kiniksa Pharmaceuticals, Ltd. Persons within your organization to whom any information herein is 
disclosed is on a need-to-know basis solely to carry out the purpose of this document, and be informed that such 
information is confidential and shall not be further disclosed by them without Kiniksa’s prior written consent. 
Documentation, data, and all other information generated during the clinical study is proprietary and confidential 
information of Kiniksa Pharmaceuticals, Ltd. and shall not be disclosed to any third party, without prior written 
consent of Kiniksa Pharmaceuticals, Ltd. 
Version 3.0; 10 March 2020 
Page 1 of 97 
Page 433 
 
 
 


Rilonacept (KPL-914) 
Study KPL-914-C002 
Kiniksa Pharmaceuticals, Ltd 
Clinical Study Protocol 
KPL-914-C002 
Sponsor: 
Sponsor Study Contact: 
Sponsor Medical Contact: 
Medical Monitor: 
Protocol Version: 
Amendment 2 / Version 3.0 
(Supersedes Version 2.0 dated 12 April 2019) 
10 March 2020 
Protocol Date: 
Version 3.0; 10 March 2020 
Page 2 of 97 
Page 434 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Rilonacept (KPL-914) 
Study KPL-914-C002 
Kiniksa Pharmaceuticals, Ltd 
Clinical Study Protocol 
PROTOCOL APPROVAL - SPONSOR SIGNATORY 
Protocol Number: 
KPL-914-C002 
Phase 3, Double-Blind, Placebo-Controlled, Randomized 
Withdrawal Study with Open-Label Extension, to Assess 
the Efficacy and Safety of Rilonacept Treatment in 
Subjects with Recurrent Pericarditis (RHAPSODY) 
Protocol Title: 
Amendment 2 / Version 3.0 
Protocol Version: 
(Supersedes Version 2.0 dated 12 April 2019) 
Protocol Date: 
10 March 2020 
Signature 
Date 
Version 3.0; 10 March 2020 
Page 3 of 97 
Page 435 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Rilonacept (KPL-914) 
Study KPL-914-C002 
Kiniksa Pharmaceuticals, Ltd 
Clinical Study Protocol 
PROTOCOL APPROVAL – LEAD STATISTICIAN 
Protocol Number: 
KPL-914-C002 
Protocol Title: 
Phase 3, Double-Blind, Placebo-Controlled, Randomized 
Withdrawal Study with Open-Label Extension, to Assess the 
Efficacy and Safety of Rilonacept Treatment in Subjects with 
Recurrent Pericarditis (RHAPSODY) 
Amendment 2 / Version 3.0 
Protocol Version: 
(Supersedes Version 2.0 dated 12 April 2019) 
Protocol Date: 
10 March 2020 
Protocol accepted and approved by: 
Lead Statistician 
Signature 
Date 
Version 3.0; 10 March 2020 
Page 4 of 97 
Page 436 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Rilonacept (KPL-914) 
Study KPL-914-C002 
Kiniksa Pharmaceuticals, Ltd 
Clinical Study Protocol 
DECLARATION OF INVESTIGATOR 
Protocol Number: 
Protocol Title: 
KPL-914-C002 
Phase 3, Double-Blind, Placebo-Controlled, Randomized 
Withdrawal Study with Open-Label Extension, to Assess the 
Efficacy and Safety of Rilonacept Treatment in Subjects with 
Recurrent Pericarditis (RHAPSODY) 
Amendment 2 / Version 3.0 
(Supersedes Version 2.0 dated 12 April 2019) 
10 March 2020 
Protocol Version: 
Protocol Date: 
I, the undersigned, am responsible for the conduct of the trial at this site and affirm that: 
• 
I understand and will conduct the trial according to the clinical trial protocol, any 
approved protocol amendments, International Conference on Harmonisation (ICH) 
Good Clinical Practice (ICH Topic E6 GCP) and all applicable Health Authority 
requirements and national laws. 
I will not deviate from the clinical trial protocol without prior written permission from 
the Sponsor and prior review and written approval from the Institutional Review Board 
or Independent Ethics Committee, except where necessary to prevent immediate 
danger to the subject. 
I will not supply the investigational drug to any person not authorized to receive it. 
Confidentiality will be protected. Subject identity will not be disclosed to third parties 
or appear in any study reports or publications. I will not disclose information regarding 
this clinical investigation or publish results of the investigation without authorization 
from Kiniksa Pharmaceuticals. 
• 
• 
Signature of Investigator: 
Signature 
Date 
Name, academic qualification 
Position (job title) 
Address of Institution 
Phone, fax, email information 
  
 
  
 
  
 
  
 
Version 3.0; 10 March 2020 
Page 5 of 97 
Page 437 
 
 
 
 
 
 
 
 
 


Rilonacept (KPL-914) 
Study KPL-914-C002 
Kiniksa Pharmaceuticals, Ltd 
Clinical Study Protocol 
PROTOCOL SYNOPSIS 
Version 3.0; 10 March 2020 
Page 6 of 97 
Page 438 
Protocol Number: 
KPL-914-C002 
Title: 
Phase 3, double-blind, placebo-controlled, randomized withdrawal study with open-label extension, to 
assess the efficacy and safety of rilonacept treatment in subjects with recurrent pericarditis 
Study Acronym: 
RHAPSODY (Rilonacept inHibition of interleukin-1 Alpha and beta for recurrent Pericarditis: a 
pivotal Symptomatology and Outcomes stuDY) 
Sponsor: 
 
Study Phase: 
3 
Study Sites: 
Multicenter, global 
Indication: 
Recurrent pericarditis 
Study Rationale: 
Recurrent pericarditis is a rare autoinflammatory condition with no approved therapies. Current 
treatments, utilizing nonspecific inhibitors of inflammation (nonsteroidal anti-inflammatory drugs 
[NSAIDs], colchicine, corticosteroids [CS]), result in significant morbidity with chronic use. Some 
patients develop CS dependency or require surgical pericardiectomy to treat the symptoms of their 
disease. 
The interleukin-1 (IL-1) pathway plays a major role in the pathophysiology of recurrent pericarditis. 
Rilonacept (KPL-914) is a recombinant fusion protein that blocks IL-1 signaling. It is currently 
approved for treatment of another autoinflammatory condition, Cryopyrin-Associated Periodic 
Syndrome (CAPS). Based on its IL-1–antagonistic properties and pharmacokinetics (PK), which allow 
for once-weekly subcutaneous (SC) injections, it is reasonable to evaluate the efficacy and safety of 
rilonacept in subjects with recurrent pericarditis to address the unmet need in treatment of this disease. 
Study Objectives: 
Primary Objective: To assess the efficacy of rilonacept treatment in subjects with recurrent 
pericarditis. 
 
 
 
 
 
 
 
 
 
 
 
 


Rilonacept (KPL-914) 
Study KPL-914-C002 
Kiniksa Pharmaceuticals, Ltd 
Clinical Study Protocol 
Version 3.0; 10 March 2020 
Page 7 of 97 
Page 439 
Secondary Objective: To assess the safety of rilonacept treatment in subjects with recurrent 
pericarditis. 
Study Population: 
Subjects eligible for the study are subjects with recurrent pericarditis who do not have pericarditis 
secondary to prohibited conditions. The study population includes both adult subjects ≥18 years old 
and pediatric subjects ≥12 and <18 years old with a history of at least 2 prior pericarditis episodes 
(including the first episode and 1 recurrence). Enrollment of pediatric subjects will be limited to up to 
20% of the study population. To be eligible for the study, subjects must present at screening with at 
least a third pericarditis episode, defined as at least 1 day with pericarditis pain measurement ≥4 on the 
11-point Numerical Rating Scale (NRS) and C-reactive protein (CRP) value ≥1 mg/dL (either on the 
same day or separated by no more than 7 days) within 7 days prior to first study drug administration. 
Subjects included in the study may be receiving concomitant NSAIDs and/or colchicine and/or oral CS 
treatment in any combination, provided that the dosages of these medications have been stable (or not 
increased) for at least 3 days prior to first administration of study drug, and that changes in medications 
made within this time period (for instance, 1-time use of NSAIDs) are not anticipated by the 
Investigator to significantly alter assessments of baseline disease activity. 
 
Study Design: 
This study has 4 periods: 
(1) Screening period, during which assessment of disease characteristics, baseline therapy, and the 
pretreatment workup is completed (up to 4 weeks). 
(2) Single-blind Run-In (RI) period (12 weeks), during which blinded rilonacept is administered SC 
once weekly in all subjects. The RI period includes the following: 
• 
1-week Stabilization period, during which blinded rilonacept is administered in addition to 
standard of care (SOC) pericarditis therapy and the ongoing pericarditis episode is treated 
• 
9-week Weaning period, during which subjects are weaned off background SOC 
pericarditis therapy, as applicable, while treatment with blinded rilonacept continues 
• 
2-week Monotherapy period during which subjects who have successfully weaned off 
background SOC pericarditis therapy will continue to receive blinded rilonacept 
In the single-blind RI period (subjects are blinded regarding the time of transition from the single-blind 
to the double-blind period), adult subjects ≥18 years old will receive rilonacept as an initial loading 
dose of 320 mg (2 SC injections of 160 mg each) at the RI baseline visit (2 × 2 ml), followed by a 160 
mg (2 ml) SC dose once weekly throughout the RI period. Pediatric subjects (≥12 and <18 years old) 
will receive an initial loading dose of rilonacept 4.4 mg/kg (2 SC injections of 2.2 mg/kg each) at the 
RI baseline visit (maximum 2 × 2 ml), and then 2.2 mg/kg (maximum 2 ml) SC once weekly 
throughout RI period. 
Subjects who achieve Clinical Response at RI Week 12 defined as stopping background pericarditis 
therapy no later than Week 10 and weekly average of daily pericarditis pain score ≤2.0 on the 11-point 
NRS within the 7 days prior to and including the day of randomization on RI Week 12/Randomization 
 
 
 


Rilonacept (KPL-914) 
Study KPL-914-C002 
Kiniksa Pharmaceuticals, Ltd 
Clinical Study Protocol 
Version 3.0; 10 March 2020 
Page 8 of 97 
Page 440 
Withdrawal (RW) baseline and a CRP level ≤0.5 mg/dL at the RI Week 12/RW baseline visit, will 
proceed into the double-blind placebo-controlled RW period. Subjects who do not achieve Clinical 
Response at RI Week 12/RW baseline on rilonacept monotherapy will be discontinued from study 
drug, transitioned to SOC pericarditis therapy at the Investigator’s discretion and followed through the 
end of the RW period. Additionally, after the randomized withdrawal period has been closed when at 
least 22 confirmed recurrent pericarditis events have been accrued, subjects who have not yet 
completed the full 12 weeks of RI period at that time will be allowed to continue tapering of 
concomitant meds in the RI period; those subjects who achieved clinical response by Week 12 will be 
given the option to receive open-label rilonacept in the LTE without having to proceed through the RW 
period. 
(3) Double-blind placebo-controlled RW period (Pericarditis recurrence event-driven duration) 
during which subjects who were able to stop background SOC pericarditis therapy and who achieve 
Clinical Response at RI Week 12/RW baseline are randomized in a double-blind manner at a 1:1 ratio 
to the following: 
• 
Rilonacept 160 mg (2.2 mg/kg in pediatric subjects) SC injections once weekly 
• 
Matching placebo SC injections once weekly 
Pericarditis Recurrence in the RW Period: Pericarditis recurrence is defined as the recurrence of 
typical pericarditis pain associated with supportive objective evidence of pericarditis. Upon pericarditis 
recurrence, subjects who report at least 1 day with pericarditis pain measurement ≥4 on the 11point 
NRS and have 1 CRP value ≥1 mg/dL (either on the same day or separated by no more than 7 days) 
will receive bailout rilonacept (2 open-label injections of 160 mg rilonacept [or 4.4 mg/kg for pediatric 
subjects] followed by once weekly open-label rilonacept SC injections of 160 mg [or 2.2 mg/kg for 
pediatric subjects]) irrespective of randomized treatment assignment and as soon as at least 5 days have 
passed since the last study drug injection. Sequential Oral Rescue Therapy (ORT), i.e., analgesics first, 
then NSAIDs, and then colchicine, can be added if needed at the discretion of the Investigator, as 
outlined in the protocol and Pharmacy Manual. 
Subjects with pericarditis recurrence and who do not meet the protocol criteria for bailout rilonacept 
will continue blinded study drug until the protocol criteria for bailout rilonacept are met or through the 
end of the RW period. For those subjects, sequential ORT can be added to blinded study drug at the 
discretion of the Investigator, as outlined in the protocol and Pharmacy Manual. 
All suspected pericarditis recurrence events in the RW period will be formally adjudicated by the 
Clinical Endpoint Committee (CEC), and only events that are confirmed by the CEC as pericarditis 
recurrences will be used in the Primary Endpoint analysis. 
(4) Long Term Extension Treatment Period (LTE) (variable, up to 24 months), during which all 
subjects in the RW period (including subjects transitioned to open-label rilonacept upon pericarditis 
recurrence) and subjects who are in the Run-In period after closure of the RW period, will have an 
option to receive up to 24 months of open-label rilonacept 160 mg (or 2.2 mg/kg for pediatric subjects) 
SC injections once weekly based on their clinical status and at the discretion of the Investigator, after 
signing LTE informed consent. Subjects will be reviewed again at 18 months after their most recent 
recurrence, (i.e., the qualifying episode for their original study enrollment prior to enrolling in the RI 
period or a recurrence in RW which was treated with bailout rilonacept, whichever is the later). During 
this visit, the Investigator and subject will decide whether to continue treatment with open-label 
 
 
 


Rilonacept (KPL-914) 
Study KPL-914-C002 
Kiniksa Pharmaceuticals, Ltd 
Clinical Study Protocol 
Version 3.0; 10 March 2020 
Page 9 of 97 
Page 441 
rilonacept, to continue in the study off-treatment for observation and rilonacept bailout upon 
subsequent recurrence, or discontinuation from the LTE. This review may be supplemented by cMRI 
and/or echocardiogram and/or additional diagnostic testing as determined by the Investigator. Subjects 
may also be unblinded at that time (if available) at the request of the Investigator per procedures 
outlined in the Unblinding Plan to assist in clinical decision-making. 
Safety data will be reviewed throughout the long-term extension by the Data Monitoring Committee. 
Estimated Study Duration: 
Subjects completing the randomized withdrawal period are projected to be dosed with rilonacept for a 
minimum of approximately 36 weeks and a maximum of 2 years based on enrollment assumptions and 
pericarditis recurrence events accrual time. Subjects who enter the long-term extension period will be 
dosed for up to 24-months longer. 
Study Efficacy Assessments: 
• 
Daily pericarditis pain on the 11-point NRS 
• 
CRP level 
• 
Electrocardiogram (ECG) 
• 
Echocardiography (ECHO) 
• 
Patient Global Impression of Pericarditis Severity (PGIPS) 
• 
Physician Global Assessment of Pericarditis Activity (PGA-PA) 
• 
36-Item Short Form Health Survey (SF-36) 
• 
5-Level EuroQoL-5D (EQ-5D-5L) 
• 
Insomnia Severity Index (ISI) 
• 
Cardiac magnetic resonance imaging 
Study Pharmacokinetic or Pharmacodynamic Assessments: 
• 
PK analysis 
• 
Anti-rilonacept antibodies 
• 
Biomarkers 
• 
Pharmacogenomics (for subjects who sign the separate informed consent for 
pharmacogenomics assessments) 
Study Safety Assessments: 
• 
Physical examination 
• 
Vital signs measurements 
• 
Adverse event (AE) monitoring 
• 
Chest x-ray 
 
 
 


Rilonacept (KPL-914) 
Study KPL-914-C002 
Kiniksa Pharmaceuticals, Ltd 
Clinical Study Protocol 
Version 3.0; 10 March 2020 
Page 10 of 97 
Page 442 
• 
Tuberculosis screening 
• 
Laboratory tests 
Investigational Medicinal Product, Dosage, and Route of Administration: 
Rilonacept (KPL-914) is a recombinant fusion protein consisting of the extracellular domains of human 
IL-1 cytokine receptor and the Fc portion of human immunoglobulin G1 (IgG1). It acts as a soluble 
decoy receptor binding IL-1α/IL-1β and prevents their interaction with the IL-1 cell-surface receptor. 
Study drug (rilonacept or placebo) is supplied in a single use, 20 ml glass vial containing a sterile, 
white to off-white, lyophilized powder. Each vial is to be reconstituted with 2.3 ml sterile Water for 
Injection (WFI). A volume up to 2 ml can be withdrawn, which is designated to deliver up to 160 mg 
of rilonacept or up to 2 ml of placebo for SC injection only. The resulting solution is clear, colorless to 
pale yellow, and essentially free of particulates. 
Each rilonacept vial contains 220 mg of rilonacept lyophilized powder. After reconstitution with 2.3 ml 
WFI, the rilonacept vial contains 80 mg/ml rilonacept, 40 mM histidine, 50 mM arginine, 3.0% (w/v) 
polyethylene glycol 3350, 2.0% (w/v) sucrose, and 1.0% (w/v) glycine at a pH of 6.5. No preservatives 
are present. 
The first injection of rilonacept loading dose at the RI baseline visit will be administered at the study 
site by study site staff. The second injection of rilonacept loading dose at the RI baseline visit will be 
prepared and administered by the subject or the subject’s caregiver after adequate training and under 
the supervision of study site personnel. Subsequent once-weekly study drug doses will be 
self-administered SC by the subject or administered to the subject by a trained caregiver as an 
outpatient SC administration. 
Sample Size: Up to approximately 100 subjects with recurrent pericarditis will be enrolled, which will 
allow accrual of at least 22 adjudicated primary efficacy endpoint (pericarditis recurrence) events. 
Statistical Methods: The primary efficacy endpoint is time to pericarditis recurrence, defined as the 
time from randomization to the date of the first pericarditis recurrence for each subject. Only 
CEC-confirmed pericarditis recurrence will be considered as an event for the primary efficacy analysis. 
A sensitivity analysis will be done based on the Investigator’s assessment of the pericarditis recurrence. 
In order to control the overall 1-sided type I error rate at the 0.025 level, a gatekeeping procedure in 
combination with Hochberg’s procedure will be applied to testing the primary and major secondary 
efficacy endpoints. 
Major secondary efficacy endpoints for the RW period include: 
• 
Proportion of subjects who maintained Clinical Response at Week 16 of the RW period 
• 
Percentage of days with no or minimal pain (pain ≤2 on the 11-point NRS) in the first 16 weeks 
of the RW period 
• 
Proportion of subjects with absent or minimal pericarditis symptoms (based on the 7-point 
rating scale of PGIPS) at Week 16 of the RW period 
 
 
 
 
 
 
 
 


Rilonacept (KPL-914) 
Study KPL-914-C002 
Kiniksa Pharmaceuticals, Ltd 
Clinical Study Protocol 
Version 3.0; 10 March 2020 
Page 11 of 97 
Page 443 
Other secondary efficacy endpoints for the RW period include: 
• 
Proportions of subjects who maintained Clinical Response at Week 8 and Week 24 of the RW 
period, respectively 
• 
Percentages of days with no or minimal pain (pain ≤2 on the 11-point NRS) in the first 8 weeks 
and 24 weeks of the RW period, respectively 
• 
Proportions of subjects with absent or minimal pericarditis symptoms (based on the 7-point 
rating scale of PGIPS) at Week 8 and Week 24 of the RW period, respectively 
• 
Proportion of subjects without pericarditis recurrence in the first 24 weeks of the RW period 
• 
Time to pericarditis pain NRS ≥4 
• 
Time to CRP level ≥1 mg/dL 
• 
Time to pericardial rub 
• 
Time to widespread ST segment elevation or PR segment depression on ECG 
• 
Time to new or worsening pericardial effusion on ECHO 
• 
Change in category of ECHO pericardial effusion size at week 24 and end of RW based on 
central labs 
• 
Change over time in CRP levels 
• 
Change over time in subject’s assessments of pericarditis pain (weekly average) 
• 
Proportion of subjects with absent or minimal pericarditis activity based on Physician Global 
Assessment of Pericarditis Activity (PGA PA) over time 
• 
Proportion of subjects with absent or minimal pericarditis activity over time based on the 
PGIPS over time 
• 
Change over time in SF 36 Physical and Mental Component Scores and domain scores 
• 
Changes in SF-6D, 6 domain scores and utility index 
• 
Change in EQ-5D-5L individual scores and index value 
• 
Change over time in subject’s sleep quality assessed with the ISI 
• 
Change over time in ISI categories 
• 
Cumulative number (percentage) of subjects who receive sequential ORT, prednisone, or 
bailout rilonacept for pericarditis every 4 weeks in the RW period 
Efficacy endpoints for the RI period include: 
• Time to pain response defined as a rolling average of NRS score of 2 or less on three 
consecutive days. 
• Time to CRP normalization (≤0.5 mg/dL) 
• 
Time to monotherapy 
 
 
 
 
 
 
 


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• 
Time to clinical response (monotherapy + NRS ≤2 + CRP ≤0.5 mg/dL) 
• 
Proportion of subjects who achieved Clinical Response at the RI Week 12. Clinical Response is 
defined as reaching monotherapy on or before week 10 and a weekly average of daily 
pericarditis pain of ≤2.0 on the 11-point NRS and CRP level ≤0.5 mg/dL at the RI Week 
12/RW baseline visit. 
• 
Number (percentage) of subjects with normalization of CRP at RI Week 12 
• 
Change from baseline in pericarditis pain at RI Week 12 and over time 
• 
Change from baseline in CRP level at RI Week 12 and over time 
• 
Resolution of echocardiographic and ECG abnormalities (yes/no) at RI Week 12 
• 
Percentage of days with no or minimal pain (NRS≤2) while on treatment 
• 
Proportion of subjects with absent or minimal pericarditis symptoms based on the PGIPS 
• 
Proportion of subjects with absent or minimal pericarditis activity based on the PGA-PA 
• 
Change over time in SF-36 Physical and Mental Component Scores and domain scores 
• Change in the SF-6D 6 domain scores and the utility index 
• 
Change in EQ-5D-5L individual scores and index value 
• 
Change over time in subject’s sleep quality assessed with the ISI 
• 
Change over time in ISI categories 
• Number (percentage) of subjects who were off background pericarditis medication on 
or before weeks 4, 8, 10, and 12 
The analysis for treatment comparison will be triggered after at least the 22nd CEC-confirmed 
pericarditis recurrence events have been accrued. At that time, randomization will be closed, 
and subjects will return to study sites for the EORW visit. At that point study treatment will 
stop (completing the database for the primary efficacy endpoint analysis), and subjects will 
either continue into the LTE or complete their study participation. Missing data due to end of 
RW period will be considered as missing at random. Handling of missing values will be 
described in the SAP. 
Details of the analyses will be specified in the Statistical Analysis Plan. 
Protocol Version and Date: 
Version 3.0 dated 10 March 2020 
 
 
 


Rilonacept (KPL-914) 
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Clinical Study Protocol 
TABLE OF CONTENTS 
PROTOCOL APPROVAL - SPONSOR SIGNATORY ........................................... 3 
PROTOCOL APPROVAL – LEAD STATISTICIAN .............................................. 4 
DECLARATION OF INVESTIGATOR .................................................................. 5 
PROTOCOL SYNOPSIS ......................................................................................... 6 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ........................... 19 
1. 
1.1. 
1.2. 
1.3. 
1.3.1. 
1.3.2. 
INTRODUCTION ............................................................................... 22 
Current Therapeutic Management of Pericarditis .................................. 22 
Pathogenesis of Recurrent Pericarditis: Role of IL-1 ............................ 23 
Rilonacept (KPL-914) .......................................................................... 25 
Safety of Rilonacept ............................................................................. 26 
KPL-914-C001 (Study with Rilonacept [KPL-914] in Recurrent 
Pericarditis) ......................................................................................... 27 
STUDY OBJECTIVES ........................................................................ 28 
Primary Objective ................................................................................ 28 
Secondary Objective ............................................................................ 28 
INVESTIGATIONAL PLAN .............................................................. 29 
Study Design ....................................................................................... 29 
Screening Period (up to 4 weeks) ......................................................... 29 
Single-blind Run-In (RI) Period (12 weeks) ......................................... 29 
Double-blind Placebo-controlled RW Period (pericarditis recurrence 
event-driven duration) .......................................................................... 30 
Long Term Extension Treatment Period (LTE) (up to 24 months) ........ 31 
Rationale of Study Design .................................................................... 34 
Justification for Dose Selection ............................................................ 35 
SELECTION OF STUDY POPULATION ........................................... 36 
Inclusion Criteria ................................................................................. 36 
Exclusion Criteria ................................................................................ 38 
Subject Completion, Withdrawal from Study, and Study Drug 
Discontinuation .................................................................................... 40 
Completion .......................................................................................... 40 
Reasons for Discontinuation of Study Drug and Study Withdrawal ...... 40 
Discontinuation of Study Drug ............................................................. 41 
2. 
2.1. 
2.2. 
3. 
3.1. 
3.1.1. 
3.1.2. 
3.1.3. 
3.1.4. 
3.2. 
3.3. 
4. 
4.1. 
4.2. 
4.3. 
4.3.1. 
4.3.2. 
4.3.2.1. 
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4.3.2.2. 
5. 
5.1. 
5.2. 
5.2.1. 
5.2.2. 
5.2.3. 
5.3. 
5.4. 
5.4.1. 
5.4.2. 
5.4.3. 
5.5. 
5.6. 
5.6.1. 
5.6.2. 
5.6.3. 
5.6.4. 
5.6.5. 
5.7. 
5.8. 
6. 
6.1. 
6.1.1. 
6.1.2. 
6.1.3. 
6.1.4. 
6.1.5. 
6.1.6. 
Subject Withdrawal from the Study...................................................... 41 
STUDY TREATMENTS ..................................................................... 42 
Method of Assigning Subjects to Treatment Groups ............................. 42 
Treatments Administered ..................................................................... 42 
Adult Subjects (≥18 years old) ............................................................. 42 
Pediatric Subjects (≥12 and <18 years old) ........................................... 43 
Study Drug Self-Administration ........................................................... 44 
Identity of Investigational Medicinal Product ....................................... 44 
Management of Clinical Supplies ......................................................... 44 
Study Drug Product Packaging and Storage ......................................... 44 
Study Drug Accountability ................................................................... 45 
Other Supplies ..................................................................................... 45 
Study Drug Overdose ........................................................................... 45 
Prior and Concomitant Medications ..................................................... 45 
Screening ............................................................................................. 46 
Single-blind RI Period ......................................................................... 46 
Double-blind Placebo-controlled RW Period ........................................ 47 
Long Term Extension........................................................................... 48 
Prohibited Concomitant Medicines During the Study ........................... 48 
Method of Blinding .............................................................................. 49 
Treatment Compliance ......................................................................... 49 
STUDY ASSESSMENTS AND PROCEDURES................................. 50 
Study Visits ......................................................................................... 50 
Screening Visit(s) ................................................................................ 50 
Enrollment (RI Baseline Visit) ............................................................. 51 
Randomization (RI Week 12/RW Baseline Visit) ................................. 51 
Pericarditis Recurrence Assessment: Clinic Visit ................................. 51 
Randomized Withdrawal Period Visits ................................................. 52 
End of Randomized Withdrawal and LTE Baseline (EORW and LTE 
Baseline Visits) .................................................................................... 53 
End of Treatment Visit ......................................................................... 53 
Safety Follow-up Visit ......................................................................... 53 
Efficacy Assessments ........................................................................... 53 
6.1.7. 
6.1.8. 
6.2. 
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6.2.1. 
6.2.1.1. 
6.2.1.2. 
6.2.1.3. 
6.2.1.4. 
6.2.1.5. 
6.2.1.6. 
6.2.1.7. 
6.2.1.8. 
6.2.1.9. 
6.2.1.10. 
6.2.2. 
Individual Efficacy Assessments .......................................................... 53 
C-Reactive Protein ............................................................................... 53 
11-Point Pericarditis Pain Numerical Rating Scale ............................... 54 
Electrocardiogram ................................................................................ 54 
Echocardiogram ................................................................................... 54 
Patient Global Impression of Pericarditis Severity ................................ 54 
Physician Global Assessment of Pericarditis Activity ........................... 55 
36-Item Short Form Health Survey ...................................................... 55 
EQ-5D-5L............................................................................................ 55 
Insomnia Severity Index ...................................................................... 56 
Cardiac Magnetic Resonance Imaging ................................................. 56 
Assessment of Clinical Response at the End of the Run-In Period Week 
12/RW Baseline ................................................................................... 56 
Management of Suspected Pericarditis Recurrence in the RW Period ... 57 
Safety Assessments .............................................................................. 58 
Physical Examination ........................................................................... 58 
Vital Signs ........................................................................................... 59 
Chest X-ray.......................................................................................... 59 
Tuberculosis Screening ........................................................................ 59 
Adverse Events .................................................................................... 59 
Definitions ........................................................................................... 59 
Adverse Event...................................................................................... 59 
Treatment-emergent Adverse Event ..................................................... 60 
Serious Adverse Event ......................................................................... 60 
Adverse Event of Special Interest ......................................................... 61 
Adverse Reaction ................................................................................. 61 
Suspected Unexpected Serious Adverse Reaction................................. 61 
Assessing Adverse Events .................................................................... 61 
Relationship to Study Drug .................................................................. 61 
Intensity ............................................................................................... 62 
Recording Adverse Events ................................................................... 62 
Adverse Events Based on Signs and Symptoms.................................... 63 
Adverse Events Based on Examinations and Tests ............................... 63 
6.2.3. 
6.3. 
6.3.1. 
6.3.2. 
6.3.3. 
6.3.4. 
6.4. 
6.4.1. 
6.4.1.1. 
6.4.1.2. 
6.4.1.3. 
6.4.1.4. 
6.4.1.5. 
6.4.1.6. 
6.4.2. 
6.4.2.1. 
6.4.2.2. 
6.4.3. 
6.4.3.1. 
6.4.3.2. 
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6.4.3.3. 
6.4.4. 
6.4.5. 
6.4.6. 
6.4.6.1. 
6.4.7. 
6.4.8. 
6.5. 
6.5.1. 
6.5.2. 
6.5.3. 
6.5.4. 
6.6. 
6.6.1. 
6.6.2. 
6.6.3. 
6.6.4. 
6.6.5. 
6.6.6. 
6.6.7. 
6.7. 
6.7.1. 
6.7.2. 
7. 
7.1. 
7.2. 
7.2.1. 
7.2.2. 
7.3. 
7.3.1. 
7.3.2. 
7.4. 
7.5. 
Pericarditis Disease-related Events ....................................................... 63 
Time Period for Collection of Adverse Events ..................................... 64 
Follow-Up of Unresolved Adverse Events ........................................... 64 
Reporting Serious Adverse Events ....................................................... 64 
Other Reasons for Immediate Reporting............................................... 64 
Pregnancy ............................................................................................ 65 
Evaluating and Reporting SUSARs ...................................................... 65 
Other Assessments ............................................................................... 66 
Pharmacokinetic Sample ...................................................................... 66 
Anti-Drug Antibodies (ADAs) against Rilonacept (KPL-914) .............. 66 
Biomarkers .......................................................................................... 66 
Pharmacogenomics .............................................................................. 66 
Laboratory Analyses ............................................................................ 66 
Serology .............................................................................................. 67 
Hematology ......................................................................................... 67 
Chemistry ............................................................................................ 67 
Non-fasting Lipid Panel ....................................................................... 67 
Urinalysis ............................................................................................ 67 
Pregnancy Test .................................................................................... 67 
Sample Collection ................................................................................ 68 
Committees .......................................................................................... 68 
Independent Data Monitoring Committee (DMC) ................................ 68 
Clinical Endpoint Committee (CEC) .................................................... 68 
STATISTICAL AND ANALYTICAL PLAN ...................................... 68 
Primary Efficacy Endpoint ................................................................... 68 
Secondary Efficacy Endpoints for the RW Period ................................ 68 
Major Secondary Efficacy Endpoints ................................................... 69 
Other Secondary Endpoints .................................................................. 69 
Other Endpoints ................................................................................... 70 
Efficacy Endpoints for the RI Period .................................................... 71 
Efficacy Endpoints for the LTE Period ................................................. 71 
Sample Size Calculations ..................................................................... 72 
Analysis Sets ....................................................................................... 72 
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7.6. 
7.7. 
7.7.1. 
7.7.2. 
7.7.3. 
7.7.4. 
7.7.5. 
7.7.5.1. 
7.7.5.2. 
7.7.6. 
7.7.7. 
7.7.8. 
7.7.9. 
8. 
8.1. 
9. 
9.1. 
9.2. 
9.3. 
10. 
10.1. 
10.2. 
10.3. 
10.4. 
10.5. 
10.6. 
10.7. 
10.8. 
10.9. 
11. 
11.1. 
11.1.1. 
11.1.2. 
Description of Subgroups to be Analyzed............................................. 73 
Statistical Analysis Methodology ......................................................... 73 
General Methods .................................................................................. 73 
Stratified Analysis................................................................................ 74 
Testing Hypotheses and Multiplicity Adjustment ................................. 74 
Analysis of Primary Efficacy Endpoint ................................................ 75 
Analysis of Secondary Efficacy Endpoints ........................................... 75 
Analysis of the Major Secondary Endpoints ......................................... 75 
Analyses of Other Secondary Endpoints in the RW Period ................... 75 
Analyses of Other Endpoints ................................................................ 77 
Pharmacokinetic Analyses ................................................................... 77 
Safety Analyses ................................................................................... 77 
Interim Analyses .................................................................................. 77 
DATA QUALITY ASSURANCE ........................................................ 77 
Data Management ................................................................................ 78 
ETHICS ............................................................................................... 78 
Independent Ethics Committee or Institutional Review Board .............. 78 
Ethical Conduct of the Study ................................................................ 79 
Subject Information and Consent ......................................................... 79 
INVESTIGATOR’S OBLIGATIONS .................................................. 80 
Confidentiality ..................................................................................... 80 
Financial Disclosure and Obligations ................................................... 80 
Investigator Documentation ................................................................. 80 
Study Conduct ..................................................................................... 81 
Adherence to Protocol .......................................................................... 81 
Adverse Events and Study Report Requirements .................................. 81 
Investigator’s Final Report ................................................................... 81 
Records Retention ................................................................................ 81 
Publications ......................................................................................... 82 
STUDY MANAGEMENT ................................................................... 82 
Monitoring ........................................................................................... 82 
Monitoring of the Study ....................................................................... 82 
Inspection of Records........................................................................... 82 
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11.2. 
11.2.1. 
11.2.2. 
11.3. 
11.4. 
12. 
13. 
13.1. 
13.2. 
Management of Protocol Amendments and Deviations ........................ 83 
Modification of the Protocol ................................................................ 83 
Protocol Deviations .............................................................................. 83 
Study Termination ............................................................................... 83 
Final Report ......................................................................................... 83 
REFERENCE LIST ............................................................................. 85 
APPENDICES ..................................................................................... 87 
Study Schedule of Activities ................................................................ 87 
Appendix: 11-point Numerical Rating Scale (NRS) for Assessment of 
Pericarditis Pain ................................................................................... 97 
Summary of Changes ........................................................................... 97 
13.3. 
LIST OF TABLES 
Study Drug Dose Volume (After Reconstitution) by Body Weight in 
Kilograms for Pediatric Subjects Aged ≥12 and <18 Years .................. 43 
Study Schedule of Activities – Screening and Run In Period ................ 87 
Study Schedule of Activities – Randomized Withdrawal ...................... 91 
Study Schedule of Activities – Long Term Extension Treatment Period 
................................................................................................................ 94 
Study Schedule of Activities – Supplemental Visits ............................. 95 
Table 1: 
Table 2: 
Table 3: 
Table 4: 
Table 5: 
LIST OF FIGURES 
Schematic of Rilonacept (KPL-914) ..................................................... 26 
Overview of KPL-914-C002 Study Design .......................................... 33 
Management of Suspected Pericarditis Recurrence in the Randomized- 
Withdrawal Period ............................................................................... 58 
Figure 1: 
Figure 2: 
Figure 3: 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
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Abbreviation or Specialist Term 
Definition/ Explanation 
ADA 
anti-drug antibodies 
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
CAPS 
Cryopyrin Associated Periodic Syndrome 
CEC 
Clinical Endpoint Committee 
CFR 
Code of Federal Regulations 
CMH 
Cochran–Mantel–Haenszel 
CRP 
C-reactive protein 
CS 
corticosteroids 
DMC 
Data Monitoring Committee 
ECG 
electrocardiogram 
ECHO 
echocardiography; echocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
eDiary 
electronic diary 
EORW 
End of Randomized-Withdrawal(visit) 
EOS 
End of Study 
EOT 
End of Treatment (visit) 
EQ-5D-5L 
5-level EuroQoL-5D 
ESC 
European Society of Cardiology 
ESR 
erythrocyte sedimentation rate 
FCAS 
Familial Cold Auto-Inflammatory Syndrome 
FDA 
US Food and Drug Administration 
GCP 
Good Clinical Practice 
GI 
gastrointestinal 
HDL 
high-density lipoprotein 
HIV 
human immunodeficiency virus 
ICF 
informed consent form 
 
 
 


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Abbreviation or Specialist Term 
Definition/ Explanation 
ICH 
International Council for Harmonisation 
IEC 
independent ethics committee 
IgG1 
human immunoglobulin G1 
IGRA 
Interferon Gamma Release Assay 
IL-1 
interleukin-1 
IRB 
Institutional Review Board 
ISI 
Insomnia Severity Index 
ISR 
injection site reaction 
ITT 
intent to treat 
IV 
intravenous(ly) 
IWRS 
interactive web response system 
KPL-914 
rilonacept 
LDL 
low-density lipoprotein 
LTE 
Long Term Extension Treatment Period 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
magnetic resonance imaging 
MWS 
Muckle-Wells Syndrome 
NSAID 
nonsteroidal anti-inflammatory drug 
NRS 
Numerical Rating Scale 
ORT 
Oral Rescue Therapy 
PHV 
Pharmacovigilance 
PGA-PA 
Physician Global Assessment of Pericarditis Activity 
PGIPS 
Patient Global Impression of Pericarditis Severity 
PK 
pharmacokinetic(s) 
POC 
point of care 
PRO 
patient-reported outcome 
RI 
Run-In (period) 
RN 
visiting registered nurse 
RW 
Randomized-Withdrawal (period) 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SC 
subcutaneous(ly) 
 
 
 


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Abbreviation or Specialist Term 
Definition/ Explanation 
SF-36 
36-Item Short Form Health Survey 
SFU 
safety follow-up 
SOC 
standard of care 
SUSAR 
suspected unexpected serious adverse reaction 
TB 
tuberculosis 
TC 
site telephone visit (telephone contact) 
TEAE 
treatment-emergent adverse event 
TNF 
tumor necrosis factor 
ULN 
upper limit of normal 
WBC 
white blood cell 
WFI 
Water for Injection 
 
 
 


Rilonacept (KPL-914) 
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Kiniksa Pharmaceuticals, Ltd 
Clinical Study Protocol 
1. 
INTRODUCTION 
Pericarditis is inflammation of the pericardium, the double-walled sac surrounding the heart. 
Etiologies of pericarditis include infectious causes (viral, bacterial, fungal, and parasitic) and 
non-infectious causes (idiopathic, autoimmune, neoplastic, metabolic, traumatic, 
post-surgical, and drug-related) (Adler et al 2015). In 80% of cases in developed countries, 
the cause of pericarditis is either post-viral or “idiopathic” in that it cannot be attributed to a 
specific condition (Imazio et al 2010; Zayas et al 1995). 
The underlying pathogenesis of recurrent pericarditis remains unclear, although a growing 
body of evidence suggests that abnormal immune responses play a role in the pathogenic 
processes. While the adaptive immune system plays a role in autoimmune disorders that 
manifest with pericarditis as one of the many organ systems involved (such as in systemic 
lupus erythematosus or rheumatoid arthritis), the innate immune system, including 
interleukin-1 (IL-1) signaling, is often the major effector in autoinflammatory disorders, such 
as isolated pericarditis (Baskar et al 2016; Brucato et al 2016; Imazio et al 2016, Dinarello et 
al 2012). 
Diagnosis of pericarditis is based on the presence of typical chest pain (improved by sitting 
up and leaning forward) along with fever, pericardial friction rub, electrocardiographic 
changes, pericardial effusion, or elevated levels of inflammation markers (white blood cell 
[WBC] count, C-reactive protein [CRP], or erythrocyte sedimentation rate [ESR]) (Adler et 
al 2015). The European Society of Cardiology (ESC) Guidelines for the Diagnosis and 
Management of Pericardial Diseases define an acute pericarditis episode as the presence of at 
least 2 of the 4 following criteria: pericarditic chest pain, pericardial rubs, new widespread 
ST-segment elevation or PR-segment depression based on electrocardiogram (ECG) findings, 
and pericardial effusion (new or worsening). Elevations of certain markers of inflammation 
(i.e., CRP, ESR, and WBC) or evidence of pericardial inflammation by an imaging technique 
(e.g., magnetic resonance imaging [MRI]) are used as supportive findings (Adler et al 2015). 
Recurrent pericarditis is characterized by the recurrence of pericarditis signs and symptoms 
after a symptom-free period of at least 4 to 6 weeks (Adler et al 2015). Recurrent pericarditis 
affects 20% to 30% of patients with acute pericarditis (Imazio 2014) and can be debilitating 
for patients due to pain and limitations in physical function during pericarditis episodes. 
Pericarditis recurrences result in increased emergency room admissions and hospitalizations. 
In the United States, 5% of patients presenting to the emergency room with non-ischemic 
chest pain are diagnosed with pericarditis (Agarwal et al 2015). 
The estimated prevalence of recurrent pericarditis in the US and Europe is 70,000 to 160,000 
patients including approximately 8,000 to 21,000 patients who are refractory or intolerant to 
current therapies or who require long-term administration of corticosteroids (CS) to control 
their disease (Brucato et al 2016; Lazaros et al 2016; Imazio et al 2010; Khandaker et al 
2010; Imazio et al 2008). 
1.1. 
Current Therapeutic Management of Pericarditis 
There are no approved therapies for the treatment of recurrent pericarditis. Current treatments 
include nonspecific inhibitors of inflammation, i.e., aspirin, nonsteroidal anti-inflammatory 
drugs (NSAIDs), colchicine, and CS (Lilly et al 2013). 
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Aspirin and other NSAIDs are the first-line approach. Because high doses of aspirin and 
NSAIDs are often required, consideration must be given to gastric protection therapy, as 
potential risks of therapy include stomach ulcers and gastrointestinal (GI) bleeding, as well as 
renal and cardiovascular toxicity. Colchicine is another mainstay therapy for pericarditis and 
is commonly used with NSAIDs to hasten the response to NSAIDs and reduce the risk of 
subsequent recurrences. However, its use may be associated with the risk of fatal overdosing, 
significant drug interactions, and neuromuscular toxicity. In addition, approximately 10% to 
15% of patients experience significant GI side effects with colchicine, including GI 
intolerance or severe diarrhea, requiring treatment discontinuation (Imazio et al 2016). 
Available ESC guidelines stipulate that CS should be prescribed for the management of 
pericarditis episodes only in cases of incomplete response, intolerance, or contraindications 
to NSAIDs and colchicine because of their unfavorable long-term benefit-risk profile. 
Corticosteroid use is associated with side effects, including weight gain, diabetes, 
osteoporosis, avascular bone necrosis, and increased risk for infections (Imazio et al 2008). 
For the management of pericarditis, CS are usually administered at low to moderate doses 
and can provide rapid control of symptoms. However, they often require many months of 
tapering after the normalization of CRP levels. In addition, there is a high rate of pericarditis 
relapse when CS use is tapered or stopped (Lotrionte et al 2010; Imazio et al 2005; Maisch et 
al 2004), particularly in the absence of concurrent colchicine treatment. 
Patients with recurrent pericarditis who are refractory or intolerant to current therapeutic 
management options or who require long-term administration of CS to control their disease 
can be particularly challenging to manage. As a last resort, some refractory patients are being 
referred to the surgical procedure of pericardiectomy, with variable outcomes. Multiple 
immunosuppressive medications have been used without consistent benefit (Baskar et al 
1.2. 
Pathogenesis of Recurrent Pericarditis: Role of IL-1 
Interleukin-1 is a key cytokine that drives the pathophysiology of many inflammatory 
processes, and it is implicated as a causative factor in various inflammatory diseases in 
humans. 
The two distinct IL-1 genes, IL1A and IL1B, encode IL-1α and IL-1β, respectively. IL-1α and 
IL-1β bind to the universally-expressed cell surface receptor, IL-1 receptor type-1, triggering 
a cascade of inflammatory mediators. The precursor form of IL-1α is expressed in 
keratinocytes, mucous membrane epithelial cells, and organs such as the liver and vascular 
endothelium in healthy individuals. During pathological states, IL-1α moves to the cell 
surface or is released after cell death to activate IL-1 receptors in adjacent cells, thus 
beginning the cascade of sterile inflammation. IL-1β, however, is not expressed in healthy 
individuals until a stimulus, such as microbial products or other chemokines, triggers its 
transcription in monocytes, tissue macrophages, and dendritic cells via the inflammasome. 
IL-1 drives the inflammatory cascade in classic autoinflammatory conditions, such as tumor 
necrosis factor (TNF)-associated periodic syndrome (TRAPS) and familial Mediterranean 
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fever (FMF) and plays a significant role in systemic onset of juvenile idiopathic arthritis and 
in autoimmune diseases such as rheumatoid arthritis (Baskar et al 2016). 
IL-1–blocking therapies are effective at controlling end-organ disease and damage in patients 
with various autoinflammatory disorders, and different strategies to block IL-1 have been 
used in clinical trials and demonstrated substantial success in controlling episodes of fever 
and elevations in acute-phase reactants (Cantarini et al 2015). 
This mechanistic plausibility of IL-1 antagonism in addressing pathophysiology related to the 
inflammasome extends to other conditions characterized by sterile acute inflammation, such 
as recurrent pericarditis. 
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1.3. 
Rilonacept (KPL-914) 
Rilonacept (designated as KPL-914 in the development program by Kiniksa Pharmaceuticals, 
Ltd) was developed by Regeneron Pharmaceuticals, Inc. (Regeneron) of Tarrytown, NY, and 
is approved with the trade name ARCALYST® in the US for the treatment of CAPS, 
including Familial Cold Auto-Inflammatory Syndrome (FCAS) and Muckle-Wells Syndrome 
(MWS) in adults and children age 12 and older. Rilonacept is currently manufactured and 
marketed as ARCALYST® by Regeneron. Rilonacept received marketing authorization in the 
European Union for the treatment of CAPS with severe symptoms, including FCAS and 
MWS in adults and children aged 12 years and older, but based on a request from Regeneron, 
the marketing authorization was withdrawn. The withdrawal was a business decision and was 
not related to any concern with the safety or efficacy of rilonacept. 
Rilonacept is a recombinant fusion protein consisting of human cytokine receptor 
extracellular domains and the Fc portion of human IgG1. Rilonacept is a dimeric 
glycoprotein with a total molecular weight of approximately 250 kDa. The dimer is 
covalently linked by disulfide bonds in the Fc region. Rilonacept incorporates in a single 
molecule the extracellular domains of both receptors required for IL-1 signaling: the IL-1 
type I receptor (IL-1R1) and the IL-1 receptor accessory protein (IL-1R-AcP) (Figure 1). 
Rilonacept is expressed in recombinant Chinese hamster ovary (CHO) cells. Rilonacept 
blocks IL-1 by acting as a soluble decoy receptor that binds IL-1 and prevents its interaction 
with cell surface receptors. 
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Figure 1: 
Schematic of Rilonacept (KPL-914) 
IL-1R Type 1 
IL-1R-AcP 
- 
IL-1R-AcP 
Extracellular 
Domains 
Extracellular 
Domains 
Cell Membrane 
IL-1R Type 1 
Cytoplasmic 
Domains 
s s 
s s 
hIgG Fc 
1.3.1. 
Safety of Rilonacept 
For a detailed review of the available rilonacept safety data, please refer to the current 
Investigator Brochure and the ARCALYST® package insert located in the Pharmacy Manual. 
Rilonacept has been evaluated in 23 studies, including 22 complete and 1 ongoing. In the 
completed studies, 2243 subjects (2152 patients and 91 healthy volunteers) were exposed to 
rilonacept. Thirty of these patients were pediatric (<18 years of age). Doses up to 320 mg 
subcutaneously (SC) once weekly and 2000 mg intravenously (IV) monthly have been 
studied for different indications, including CAPS, gout, and other inflammatory disorders. 
Injection Site Reactions 
In clinical studies with rilonacept, the most common and consistently reported AE associated 
with rilonacept was injection site reaction (ISR). The ISRs included erythema, swelling, 
pruritus, mass, bruising, inflammation, pain, edema, dermatitis, discomfort, urticaria, 
vesicles, warmth, and hemorrhage. Most ISRs were mild to moderate. In the gout clinical 
studies, approximately 1% of subjects treated with rilonacept discontinued due to ISRs. 
Similar results have been seen in other patient populations. 
Infections 
Interleukin-1 blockade may interfere with immune response to infections. Serious life- 
threatening infections have been reported in clinical trials in subjects treated with rilonacept. 
Changes in Laboratory Parameters 
Cholesterol and lipid levels may be reduced in patients with chronic inflammation. Subjects 
treated with rilonacept in clinical trials experienced increases in their mean total cholesterol, 
high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and 
triglycerides. 
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Immunogenicity 
As with all therapeutic proteins, there is a potential for immunogenicity. Antibodies directed 
against the receptor domains of rilonacept were detected using an enzyme-linked 
immunosorbent assay (ELISA). In clinical trials with rilonacept, approximately 30% to 35% 
of subjects tested positive for treatment-emergent antibodies to rilonacept on at least 
1 occasion. 
Systemic Hypersensitivity Reactions 
Hypersensitivity reactions are a potential risk with protein therapeutics in general. In clinical 
studies with rilonacept, systemic hypersensitivity reactions have been rare. 
Malignancies 
Although malignancies have been reported in some subjects treated with rilonacept during 
clinical trials, the effect of rilonacept on the development of cancer is not known. Treatment 
with immunosuppressants, including rilonacept, may result in an increase in the risk of 
malignancies. 
Fetal Defects 
There are no adequate and well-controlled studies of rilonacept in pregnant women. Based on 
animal data, rilonacept may cause fetal harm. An embryo-fetal developmental toxicity study 
was performed in cynomolgus monkeys treated with 0, 5, 15, or 30 mg/kg given twice a 
week (highest dose is approximately 3.7-fold higher than the human dose of 160 mg based on 
body surface area). The fetus of the only monkey with exposure to rilonacept during the later 
period of gestation showed multiple fusion and absence of the ribs and thoracic vertebral 
bodies and arches. Exposure to rilonacept during this time period was below that expected 
clinically. Likewise, in the cynomolgus monkey, all doses of rilonacept reduced serum levels 
of estradiol up to 64% compared to controls and increased the incidence of lumbar ribs 
compared to both control animals and historical control incidences. In perinatal and postnatal 
developmental toxicology studies in the mouse model using a murine analog of rilonacept (0, 
20, 100, or 200 mg/kg), there was a 3-fold increase in the number of stillbirths in dams 
treated with 200 mg/kg 3 times per week (the highest dose is approximately 6-fold higher 
than the 160 mg maintenance dose based on body surface area). 
Nonteratogenic effects: A peri- and postnatal reproductive toxicology study was performed 
in which mice were administered a murine analog of rilonacept at doses of 20, 100, and 
200 mg/kg SC 3 times per week (the highest dose is approximately 6-fold higher than the 
160 mg maintenance dose based on body surface area). Results indicated an increased 
incidence in unscheduled deaths of the F1 offspring during maturation at all doses tested. 
1.3.2. 
KPL-914-C001 (Study with Rilonacept [KPL-914] in Recurrent Pericarditis) 
Study KPL-914-C001 is an open-label, single active-arm Phase 2 proof-of-concept study in 
subjects age ≥6 to 75 years old with recurrent idiopathic or post-pericardiotomy syndrome 
(PPS) pericarditis. The study includes a 6-week Treatment Period in which all the subjects 
receive once-weekly rilonacept 160 mg SC (2.2 mg/kg for subjects ≥6 and <18 years old) 
following a loading dose of 320 mg SC in subjects ≥18 years old (4.4 mg/kg in subjects ≥6 
and <18 years old) in addition to background pericarditis therapies (NSAIDS, colchicine, 
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CS). After completing the 6-week Treatment Period and based on response status, the 
subjects have the option to enter the 18-week Extension Period during which they will 
continue to receive rilonacept at the same dose, but during which time Investigators are 
encouraged to wean and stop background pericarditis medications. 
The primary objectives of the study are to explore clinical and biochemical endpoints of 
recurrent pericarditis symptomatology, as well as to assess feasibility to wean from 
concomitant pericarditis medication in the Extension Period while continuing treatment with 
rilonacept. The study population includes the following 5 subject categories (Parts): 
• Part 1 enrolls symptomatic subjects with recurrent idiopathic pericarditis with an 
elevated marker of systemic inflammation (CRP level >1 mg/dL). 
Part 2 enrolls symptomatic subjects with recurrent idiopathic pericarditis with 
CRP level ≤1 mg/dL that, in the opinion of the Investigator, can be attributed to 
concomitant medications (e.g., CS) and with pericardial inflammation present on 
cardiac MRI confirmed by the imaging core lab. 
Part 3 enrolls subjects with CS-dependent recurrent idiopathic pericarditis not 
experiencing symptoms that would meet the diagnostic criteria for a recurrence of 
pericarditis. 
Part 4 enrolls symptomatic subjects with recurrent PPS with an elevated marker of 
systemic inflammation (CRP level >1 mg/dL). 
Part 5 enrolls subjects with CS-dependent recurrent PPS not experiencing 
symptoms that would meet the diagnostic criteria for a recurrence of pericarditis. 
• 
• 
• 
• 
The clinical phase of the study was completed in May 2019 
(clinicaltrials.gov/NCT03980522); the final clinical study report is in preparation. 
2. 
2.1. 
STUDY OBJECTIVES 
Primary Objective 
The primary objective of this study is to assess the efficacy of rilonacept treatment in 
subjects with recurrent pericarditis. 
2.2. 
Secondary Objective 
The secondary objective of this study is to assess the safety of rilonacept treatment in 
subjects with recurrent pericarditis. 
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3. 
3.1. 
INVESTIGATIONAL PLAN 
Study Design 
This is a Phase 3, multi-center, double-blind, placebo-controlled, randomized withdrawal 
study with open-label extension, to assess the efficacy and safety of rilonacept treatment in 
subjects with recurrent pericarditis. This study has 4 periods (Figure 2). 
3.1.1. 
Screening Period (up to 4 weeks) 
During the screening period, assessment of disease characteristics, baseline therapy, and the 
pre-treatment workup will be completed during a period of up to 4 weeks. Additional 
information provided in Section 6.1.2. 
3.1.2. 
Single-blind Run-In (RI) Period (12 weeks) 
During the single-blind RI period, treatment with blinded rilonacept is administered and 
subjects are weaned off background standard of care (SOC) therapy for their pericarditis 
disease. Subjects will be blinded regarding the time of transition from the single-blind to the 
double-blind period; i.e., they will not be aware of the duration of the RI period. 
In the single-blind RI period, subjects ≥18 years old will receive blinded rilonacept as an 
initial loading dose of 320 mg (2 SC injections of 160 mg each) at the RI baseline visit (2 × 2 
ml), followed by a 160 mg (2 ml) SC dose once weekly throughout the RI period. Pediatric 
subjects (≥12 and <18 years old) will receive an initial loading dose of blinded rilonacept 4.4 
mg/kg (2 SC injections of 2.2 mg/kg each) at the RI baseline visit (maximum 2 × 2 ml), and 
then 2.2 mg/kg (maximum 2 ml) SC once weekly throughout the RI period. 
The RI period includes: 
• 1-week Stabilization period, during which blinded rilonacept is administered in 
addition to SOC pericarditis therapy, and the ongoing pericarditis episode is 
treated. 
9-week Weaning period, during which subjects are weaned off background SOC 
pericarditis therapy, as applicable, while treatment with blinded rilonacept 
continues. The dosages of CS, NSAIDs, and colchicine will be tapered according 
to the guidelines for weaning in the Pharmacy Manual (for the purpose of the 
protocol, aspirin is considered an NSAID). In general, CS doses will be tapered 
off starting at RI Week 1 and will be withdrawn by RI Week 10 (over a total of 
9 weeks). NSAID and colchicine doses will be tapered off starting at RI Week 4 
and will be withdrawn by RI Week 10 (over a total of 6 weeks). 
2-week Monotherapy period: Subjects who have been successfully weaned off 
background SOC pericarditis therapy will continue to receive blinded rilonacept. 
• 
• 
Subjects who stopped background pericarditis medications and achieve Clinical Response on 
rilonacept monotherapy at RI Week 12/RW baseline will proceed into the double-blind 
placebo-controlled Randomized-Withdrawal (RW) period of the study. For definition of 
Clinical Response, refer to Section 6.2.2. 
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Subjects who are unable to achieve Clinical Response on rilonacept monotherapy at 
RI Week 12/RW baseline are to be discontinued from study drug, transitioned to SOC 
pericarditis therapy at the Investigator’s discretion, and followed through the end of the RW 
period. 
Additionally, after the randomized withdrawal period has been closed when at least 22 confirmed 
recurrent pericarditis events have been accrued, subjects who have not yet completed the full 12 
weeks of RI period at that time will be allowed to continue tapering of concomitant meds in the RI 
period; those subjects who achieved clinical response by Week 12 will be given the option to receive 
open-label rilonacept in the LTE without having to proceed through the RW period. 
3.1.3. 
Double-blind Placebo-controlled RW Period (pericarditis recurrence 
event-driven duration) 
During the RW period, subjects who were able to stop background pericarditis medications 
and who achieve Clinical Response on rilonacept monotherapy at RI Week 12/RW baseline 
will be randomized 1:1 to double-blinded administration of study drug: 
• Rilonacept 160 mg (or 2.2 mg/kg in pediatric subjects ≥12 and <18 years old) SC 
injections once weekly OR 
Matching placebo SC injections once weekly 
• 
Pericarditis Recurrence in the RW Period: For the definition of pericarditis recurrence, 
refer to Section 6.2.3. 
Upon pericarditis recurrence, subjects who report at least 1 day with pericarditis pain 
measurement ≥4 on the 11-point Numerical Rating Scale [NRS] and have 1 CRP value 
≥1 mg/dL (either on the same day or separated by no more than 7 days) will receive bailout 
rilonacept (2 open-label injections of 160 mg rilonacept [or 4.4 mg/kg for pediatric 
subjects]) irrespective of randomized treatment assignment and as soon as at least 5 days 
have passed since the last study drug injection. The subjects transitioning to bailout 
rilonacept will remain blinded to their prior RW period treatment assignment. Sequential 
Oral Rescue Therapy (ORT), i.e., analgesics first, then NSAIDs, and then colchicine, can be 
added, if needed, at the discretion of the Investigator, as outlined in Section 5.6.3 and 
detailed in the Pharmacy Manual. 
Subjects with pericarditis recurrence who do not meet the protocol criteria for bailout 
rilonacept will continue blinded study drug until they meet the protocol criteria for bailout 
rilonacept or through the end of the RW period. For those subjects, sequential ORT can be 
added to blinded study drug at the discretion of the Investigator, as outlined in Section 5.6.3 
and detailed in the Pharmacy Manual. 
All suspected pericarditis recurrence events in the RW period will be formally adjudicated by 
the Clinical Endpoint Committee (CEC), and only events that are confirmed by the CEC as 
pericarditis recurrences will be used in the Primary Endpoint analysis. 
The RW period will continue until the prespecified number of primary efficacy endpoint 
(CEC-confirmed pericarditis recurrence) events has occurred. Based on projected event 
accrual and subject randomization, Kiniksa Pharmaceutical will determine the end of the RW 
period and announce to sites so that subject End of Randomized Withdrawal (EORW) visits 
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can occur. All subjects, including those who have transitioned to open-label rilonacept or 
who prematurely discontinued study drug, should complete an EORW visit. 
3.1.4. 
Long Term Extension Treatment Period (LTE) (up to 24 months) 
Upon completion of the RW period and the EORW visit, all subjects that did not discontinue 
study drug will have an option to continue treatment with open-label rilonacept in the LTE or 
to withdraw from the study. Subjects still in the RI period at the time that the RW period has 
ended and the LTE is opened will have the option to enter the LTE directly when they have 
completed the RI period and have met the definition of clinical response or to withdraw from 
the study. 
Treatment in the extension period may continue until the earliest of the following dates: 
• 
Rilonacept is approved for commercial use or is available for reimbursement to treat 
pericarditis in the region 
The subject has received 24 months of treatment in the LTE or the Investigator and 
subject decide to continue in the study off-treatment 
Additional reasons for discontinuation of treatment can be found in section 4.3.1. 
• 
• 
Any subject who, in the opinion of the Investigator, should not continue open-label 
rilonacept will be withdrawn from the study. 
Subjects will be reviewed again at 18 months after their most recent recurrence, (i.e., the 
qualifying episode for their original study enrollment prior to enrolling in the RI period or a 
recurrence in RW which was treated with bailout rilonacept, whichever is the later). During 
this visit, the Investigator and subject will decide whether to continue treatment with open- 
label rilonacept, to continue in the study off-treatment for observation and rilonacept bailout 
upon subsequent recurrence, or discontinuation from the LTE. This review may be 
supplemented by cMRI and/or echocardiogram and/or additional diagnostic testing as 
determined by the Investigator. Subjects may also be unblinded at that time (if available) at 
the request of the Investigator per procedures outlined in the Unblinding Plan to assist in 
clinical decision-making. 
Subjects completing the RW period are projected to be dosed with rilonacept for a minimum 
of approximately 36 weeks and a maximum of 2 years based on enrollment assumptions and 
pericarditis recurrence events accrual time. Subjects who enter the LTE will be dosed for up 
to 24-months longer. 
Pericarditis Recurrence in the LTE Period (Observation arm) 
For those subjects who, upon the 18-month post-most-recent-recurrence assessment, opt to 
continue in the LTE for observation only while off-treatment: should they have a further 
pericarditis recurrence, in the opinion of the Investigator, during that observation period, may 
resume open-label rilonacept after completion of a recurrence visit as outlined in 
Section 6.1.4. Resumption of rilonacept will follow the procedures for bailout as outlined in 
Section 3.1.3. 
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Subjects who experience a recurrence of pericarditis in the LTE while receiving open label 
rilonacept will attend for a recurrence visit and may then continue on rilonacept or transition 
to SOC treatment at the discretion of the investigator. 
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Figure 2: 
Overview of KPL-914-C002 Study Design 
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3.2. 
Rationale of Study Design 
Subjects eligible for this KPL-914-C002 study will be subjects with recurrent pericarditis 
presenting with an acute pericarditis episode at screening. 
The KPL-914-C002 study design ensures that during the RI period all subjects will receive 
rilonacept, a drug with evidence supporting clinical activity based on the clinical data with 
rilonacept from the Phase 2 proof-of-concept study (KPL-914-C001). During the RI period, 
pericarditis will be stabilized with symptoms controlled and background pericarditis 
medications (NSAIDs, colchicine, CS) will be tapered and withdrawn, while rilonacept 
treatment continues. 
The design then allows half of the subjects to continue receiving active treatment after having 
achieved Clinical Response on that treatment, which maximizes subject exposure to a 
potentially beneficial therapy. The temporary withdrawal of rilonacept (by switching to 
placebo) in the half of the subjects who were randomly assigned to placebo is expected to 
result in an accelerated time to pericarditis recurrence and a higher recurrence rate compared 
to those who continue on active treatment, a finding that demonstrates that the underlying 
pericarditis etiology is still ongoing and will provide further support for the anticipated 
observation of the clinical effect of rilonacept during the RI period of the study. The period 
of exposure to an ineffective treatment is minimized in this design, as subjects will be 
removed from blinded treatment when the condition returns to a specified severity (i.e., for 
having met the criteria of pericarditis pain ≥4 on the 11-point NRS and CRP level ≥1 mg/dL) 
without unblinding them to prior treatment assignment, thus protecting the primary efficacy 
endpoint of the study. All subjects who meet the pain and CRP criteria described above will 
be treated with open-label bailout rilonacept using a loading dose, followed by once-weekly 
SC injections. In addition, sequential ORT such as NSAIDs and/or colchicine will be allowed 
upon recurrence at the Investigator’s discretion based on the subject’s clinical status, as 
outlined in Section 5.6.3 and as stipulated in the Pharmacy Manual. Subjects with pericarditis 
recurrence not meeting criteria for bailout rilonacept, can be treated with sequential ORT 
based on Investigator judgement and as described in protocol Section 5.6.3 and the Pharmacy 
Manual. If the subject requires the addition of CS treatment to control the pericarditis 
recurrence, the subject will be discontinued from study drug. All subjects will be followed 
for the duration of RW period. 
In summary, the proposed RW trial with rilonacept allows all enrolled subjects an 
opportunity to receive the active drug during the acute episode of pericarditis yet provides 
pivotal-quality data on the efficacy of rilonacept in this enriched cohort by subsequently 
randomly assigning subjects to placebo versus active treatment after they achieve a 
predefined clinical response. Subjects with pericarditis recurrences after randomization will 
receive bailout rilonacept treatment and/or sequential ORT according to the protocol. This 
approach minimizes the exposure to placebo, which is important for a study that requires 
active disease upon enrollment and includes a pediatric population. The available regulatory 
guidance supports the use of an RW study design in the setting of recurrent pericarditis as a 
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means of establishing the long-term effectiveness of rilonacept, an approved product for the 
treatment of another rare autoinflammatory condition (CAPS). 
3.3. 
Justification for Dose Selection 
i.e., 320 mg SC loading dose (4.4 mg/kg in subjects ≥12 and <18 years old), followed 
by once-weekly SC doses at 160 mg (2.2 mg/kg in subjects ≥12 and <18 years old). 
In the rilonacept development program in CAPS, gout, rheumatoid arthritis, and other 
inflammatory conditions, over 2000 subjects were exposed to rilonacept, including 
1650 subjects receiving a rilonacept dose of 160 mg or higher. A total of 103 and 169 
subjects were exposed to any rilonacept dose for at least 1 year or 6 months, respectively. 
Most of the real-life experience with rilonacept comes from the CAPS population treated at 
this marketed dose. As of March 2018, approximately 365 CAPS patients have been exposed 
to rilonacept in the post-marketing setting since 2008. The safety data accumulated so far 
support the benefit/risk ratio for the rilonacept dose intended to be evaluated in subjects with 
recurrent pericarditis. 
Based on the clinical data with rilonacept from the Phase 2 proof of concept study 
(KPL-914-C001), it is expected that rilonacept doses 
(320 mg followed 
by 160 mg SC once weekly and corresponding pediatric doses), and evaluated in the 
KPL-914-C001 study, will consistently provide adequate suppression of clinical 
inflammatory response, including CRP levels, in patients with recurrent pericarditis. 
Subjects who meet the protocol criteria for bailout rilonacept upon pericarditis recurrence in 
the RW period of the study (Sections 3.1 and 6.2.3), irrespective of treatment assignment at 
randomization, will receive open-label rilonacept (loading dose of 320 mg SC followed by 
once-weekly SC injections of 160 mg, or the corresponding pediatric doses). 
The rationale for bailout rilonacept treatment upon pericarditis recurrence for subjects who 
were randomly assigned to placebo is that rilonacept had controlled their disease activity 
during the RI period; therefore, re-initiation of rilonacept is justified to regain control of 
pericarditis signs and symptoms upon recurrence. Subjects who were randomly assigned to 
rilonacept and qualify for bailout rilonacept upon pericarditis recurrence in the RW period 
were initial responders to rilonacept treatment during the RI period; thus it could be assumed 
that the loss of response during the RW period could be due to development of resistance to 
rilonacept due to different mechanisms, e.g., higher IL-1 levels or a change in rilonacept 
pharmacokinetics (PK)/ pharmacodynamics. Therefore, re-administration of a loading dose 
of rilonacept may help to restore Clinical Response. 
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4. 
SELECTION OF STUDY POPULATION 
Up to approximately 100 subjects with recurrent pericarditis will be enrolled, which will 
allow accrual of at least 22 adjudicated pericarditis recurrence events in randomized subjects 
at approximately 50 sites globally. Subjects will be assigned to study drug only if they meet 
all of the inclusion criteria and none of the exclusion criteria. 
Deviations from the inclusion and exclusion criteria are not allowed because they can 
potentially jeopardize the scientific integrity of the study, regulatory acceptability, or subject 
safety. Therefore, adherence to the criteria as specified in the protocol is essential. 
Subjects eligible for the study are subjects with recurrent pericarditis who do not have 
pericarditis secondary to prohibited conditions. The study population includes both adult 
subjects ≥18 years old and pediatric subjects ≥12 and <18 years old with a history of at least 
2 pericarditis episodes (including the first episode and 1 recurrence) prior to screening. 
Enrollment of pediatric subjects will be limited to up to 20% of the study population. To be 
eligible for the study, subjects must present with at least a third pericarditis episode, defined 
as at least 1 day with pericarditis pain measurement ≥4 on the 11-point NRS and CRP level 
≥1 mg/dL within 7 days prior to the first study drug administration. 
4.1. 
Inclusion Criteria 
Each subject must meet all of the following criteria to be enrolled in this study: 
1. Is capable of understanding the written informed consent form (ICF) or assent form 
(for pediatric subjects ≥12 and <18 years old), has provided signed and witnessed 
written informed consent or assent (as applicable), and agrees to comply with 
protocol requirements. 
Is male or female 12 years of age or older with body weight of at least 23.6 kg 
(52 Lbs). 
Has a diagnosis of recurrent pericarditis. 
At least 1 of the pericarditis episodes experienced prior to screening has met at least 
2 of the following 4 criteria, in the opinion of the Investigator and based on the 
documented available data, according to the 2015 ESC Guidelines for the Diagnosis 
and Management of Pericardial Diseases (Adler et al 2015): 
a. Pericarditic chest pain 
b. Pericardial rub 
c. New widespread ST-segment elevation or PR-segment depression according to 
ECG findings 
d. Pericardial effusion (new or worsening) 
Presents with at least the third episode of pericarditis during screening (i.e., at least 
the second pericarditis recurrence following the first pericarditis episode), and within 
7 days* prior to and including RI baseline (first administration of study drug) has: 
a. At least 1 day with pericarditis pain ≥4 on the 11-point NRS, AND 
2. 
3. 
4. 
5. 
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b. CRP level ≥1.0 mg/dL (for details of CRP collection see Section 6.1.1) 
*Pericarditis pain ≥4 and CRP ≥1 mg/dL are not required to be present on the 
same day. 
Has received NSAIDs and/or colchicine and/or CS (in any combination), if used, at 
stable dose levels (or at least not increased) for at least 3 days prior to and including 
RI baseline (first administration of study drug), and changes in medications made 
within this time period (e.g., 1-time use of NSAIDs) are not anticipated, in the 
opinion of the Investigator, to significantly alter assessments of baseline disease 
activity. 
If using NSAIDs and/or colchicine and/or CS at the time of RI baseline (first 
administration of study drug), is willing and able, in the opinion of the Investigator, to 
taper and discontinue those medications within the 9-week weaning time in the RI 
period of the study while continuing rilonacept treatment. 
Female subjects must be: 
6. 
7. 
8. 
a. Postmenopausal, defined as at least 12 months after the cessation of menses 
(without an alternative medical cause) OR 
Incapable of pregnancy OR 
Permanently sterile following documented hysterectomy, bilateral salpingectomy, 
bilateral oophorectomy, or bilateral tubal ligation or having a male partner with 
vasectomy as affirmed by the subject OR 
If of childbearing potential, must agree to use a highly effective method of 
contraception during the study and for 3 months after the last study drug 
administration (e.g., hormonal contraceptives associated with inhibition of 
ovulation, intrauterine device [IUD], intrauterine hormone-releasing system 
[IUS], or sexual abstinence) 
b. 
c. 
d. 
9. If male and sexually active, must have documented vasectomy or must practice birth 
control and not donate sperm during the study and for 3 months after the last study 
drug administration. 
10. Must be up-to-date with all immunizations, in agreement with current local 
immunization guidelines for immunosuppressed subjects, before RI baseline (first 
administration of study drug). 
11. Is able to adequately maintain a daily subject diary according to protocol. 
12. Must be able to adhere to the study visit schedule and understand and comply with 
the other protocol requirements. 
13. Agrees to refrain from making any new, major lifestyle changes that may affect 
pericarditis symptoms (e.g., changing exercise pattern) from the time of the ICF is 
signed through the end of the double-blind RW period. 
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4.2. 
Exclusion Criteria 
Subjects meeting any of the following criteria will be excluded from the study: 
1. Has a diagnosis of pericarditis that is secondary to specific prohibited etiologies, 
including tuberculosis (TB); neoplastic, purulent, or radiation etiologies; post-thoracic 
blunt trauma (e.g., motor vehicle accident); myocarditis; or systemic autoimmune 
diseases with exception of Still’s disease. 
Is pregnant, breastfeeding, or planning a pregnancy or fathering a child during the 
study or within 3 months after the last study drug administration. 
Has a history of immunosuppression, including positive human immunodeficiency 
virus (HIV) test results. 
Is currently receiving CS at a dose of >60 mg/day prednisone (or equivalent) for adult 
subjects, or >0.5 mg/kg/day (or >60 mg/day, whichever is lower) prednisone (or 
equivalent) in pediatric subjects (≥12 and <18 years old). 
Has ever received cytotoxic drugs, including cyclophosphamide, chlorambucil, 
nitrogen mustard, or other alkylating agents. 
Has ever received agents that deplete B or T cells (e.g., rituximab, alemtuzumab). 
Has received systemic immunomodulatory agents (with exception of CS) within the 
following time frames prior to RI baseline (first administration of study drug): 
2. 
3. 
4. 
5. 
6. 
7. 
a. Azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, sirolimus, or 
mercaptopurine within 24 weeks. 
TNF inhibitors, IL-6 inhibitors, or janus-activating kinase inhibitors within 
12 weeks. 
Canakinumab within 12 weeks. Canakinumab could not have been discontinued 
due to safety unless it was discontinued due to local injection site reactions. 
Rilonacept within 6 weeks. Rilonacept could not have been discontinued due to 
lack of efficacy or due to safety. 
Methotrexate within 2 weeks. 
Anakinra within 5 days. Anakinra could not have been discontinued due to lack of 
efficacy or due to safety unless it was discontinued due to local injection site 
reactions. 
b. 
c. 
d. 
e. 
f. 
8. 
9. 
Has a history of myeloproliferative disorder. 
Has a history of demyelinating disease or symptoms suggestive of multiple sclerosis. 
10. Meets the following TB criteria: 
a. 
b. 
c. 
History of active TB prior to screening OR 
History of latent TB that was not adequately treated prior to screening OR 
Signs or symptoms suggestive of active TB (e.g., new cough of >14 days in 
duration or a change in chronic cough, persistent fever, unintentional weight loss, 
or night sweats) upon review of medical history and/or physical examination at 
screening OR 
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d. Recent close contact with a person with active TB OR 
e. Positive or indeterminate Interferon Gamma Release Assay (IGRA) test results or 
results from another positive TB test at screening based on acceptable clinical 
practice for the country in which the subject is enrolling. 
11. Has chest x-ray (posterior-anterior view) at screening (or history of results within 
12 weeks before receiving first administration of study drug), with evidence of 
malignancy or abnormality consistent with prior or active TB infection. 
12. Has received immunization with a live (attenuated) vaccine within 12 weeks before 
screening or is expected to receive live (attenuated) vaccine during the study or 
within 12 weeks after the last study drug administration. 
13. Has a history of positive or intermediate results for hepatitis B surface antigen, 
hepatitis B core antibody, or hepatitis C virus antibody at screening. 
14. Has an estimated glomerular filtration rate (eGFR) <30 ml/min. 
15. Has a history of malignancy of any organ system within the past 5 years before 
screening (other than a successfully treated non-metastatic cutaneous squamous cell 
carcinoma or basal cell carcinoma and/or localized carcinoma in situ of the cervix). 
16. Has a known or suspected current active infection or a history of chronic or recurrent 
infectious disease, including, but not limited to, chronic renal infection, chronic chest 
infection, sinusitis, recurrent urinary tract infection, or an open, draining infected skin 
wound. 
17. Has had a serious infection, has been admitted to the hospital for an infection, has 
been treated with oral antibiotics for a documented infection within 2 weeks of RI 
baseline (first administration of study drug), or has been treated with IV antibiotics 
for an infection within 8 weeks of RI baseline. 
18. Has had an organ transplant. 
19. Has screening laboratory test results meeting any of the following criteria: 
• 
• 
• 
• 
• 
Hemoglobin level <10.0 g/dL 
WBC count <3.0 × 103/µL 
Neutrophil count <1.5 × 103/µL 
Platelet count <100 × 103/µL 
Total bilirubin level >1.5 × the upper limit of normal (ULN) unless the test results 
are consistent with those for Gilbert’s syndrome 
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values >2 × 
ULN 
• 
20. In the Investigator’s opinion, has a history of alcoholism or drug/chemical abuse 
within 2 years before screening. 
21. Has a known hypersensitivity to ARCALYST® (rilonacept) or to any of its excipients. 
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22. Has received an investigational drug during the 30 days (or 5 half-lives, whichever is 
longer) before screening or is planning to receive an investigational drug (other than 
that administered during this study) or use an investigational device at any time 
during the study. 
23. In the Investigator’s opinion, has any other medical condition that could adversely 
affect the subject’s participation or interfere with study evaluations. This includes 
significant concomitant illnesses such as, but not limited to, cardiac, renal, 
neurological, endocrinological, metabolic, pulmonary, GI, or psychiatric diseases. 
24. In the opinion of the Investigator, is not likely to be compliant with the study 
protocol. 
25. In the opinion of the Investigator, should not participate in this study. 
4.3. 
Subject Completion, Withdrawal from Study, and Study Drug 
Discontinuation 
Completion 
4.3.1. 
A subject will be considered to have completed the study if she/he has completed the RW 
period and has completed assessments at the EORW visit. At the EORW visit all subjects 
who are still receiving study treatment (blinded therapy or open-label bailout) will be offered 
an opportunity to receive up to an additional 24 months of open-label rilonacept treatment 
based on their clinical status and at the discretion of the investigator, and after signing the 
LTE informed consent. 
Additionally, after the randomized withdrawal period has been closed when at least 22 
confirmed recurrent pericarditis events have been accrued, subjects who have not yet 
completed the full 12 weeks of RI period at that time will be allowed to continue tapering of 
concomitant meds in the RI period; those subjects who achieved clinical response by Week 
12 will be given the option to receive open-label rilonacept in the LTE without having to 
proceed through the RW period. 
Any subject who in the opinion of the Investigator should not continue open-label rilonacept 
in LTE will be withdrawn from the study. 
Subjects who elect not to enter the LTE will be followed for 6 weeks (safety follow up) after 
receiving the last study drug administration. 
4.3.2. 
Reasons for Discontinuation of Study Drug and Study Withdrawal 
Subjects have the right to stop taking study drug before the end of the study or to withdraw 
their consent for further participation in the study (i.e., precluding continued data collection). 
A subject also may be asked to stop study drug at the investigator’s discretion. In the event 
that a subject permanently discontinues study drug but does not withdraw the informed 
consent, the investigator should continue to follow up with the subject by telephone contact 
(TC) visits, in the clinic, or by other means through the EORW visit if the subject 
discontinues in RI, RW, or LTE unless consent is withdrawn. 
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The reasons for premature study drug discontinuation will be recorded in the electronic case 
report form (eCRF). 
4.3.2.1. 
Discontinuation of Study Drug 
The study drug dosing will be permanently stopped if any of the following occurs: 
• The subject develops TB or malignancy, excluding non-metastatic cutaneous 
squamous cell carcinoma or basal cell carcinoma 
Initiation of protocol-prohibited medication (Section 5.6.5) 
Subject requires treatment with CS for pericarditis during RW or LTE periods of 
the study 
Pregnancy or pregnancy planned during the study or within 3 months after the last 
study drug administration 
ALT or AST values ≥3 × ULN associated with total bilirubin ≥2 × ULN, with no 
underlying medical conditions to explain the elevated values 
Treatment with a live (attenuated) vaccine during the study 
• 
• 
• 
• 
• 
• Investigator or Sponsor’s medical monitor or 
medical monitor 
decides that, for safety reasons, it is in the subject’s best interest 
Termination of the study by Kiniksa Pharmaceuticals 
• 
Permanent or temporary study drug discontinuation should be strongly considered at the time 
if any of the following occurs: 
• 
• 
• 
• 
• 
Subject develops an opportunistic infection. 
Subject develops moderate or severe infection 
Neutrophil count <1.0 × 103/µL 
Isolated ALT or AST values >5 × ULN 
Surgical procedure 
4.3.2.2. 
Subject Withdrawal from the Study 
Subjects may withdraw from the study at any time and for any reason, without prejudice to 
their future medical care by the Investigator or at the study site. However, prior to 
withdrawal of consent, it should be confirmed that the subject will not allow any form of 
follow up including options such as less frequent follow up calls or visits, follow up with a 
family member or friend, or follow up through a local physician or medical records. Follow 
up options will be summarized on a withdrawal of consent checklist source document that 
must be reviewed and signed by the Investigator for any subject who withdraws consent for 
further participation in the study. The checklist must be completed for all enrolled subjects 
who have withdrawn consent. The reasons for a subject’s withdrawal from the study are also 
required to be recorded in the eCRF. 
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A subject may be considered withdrawn from the study for any of the following reasons: 
• 
• 
• 
Lost to follow-up 
Documented withdrawal of informed consent 
Death 
In subjects who are documented as having withdrawn consent from all study activities, no 
further study visits or study-related TCs can be conducted. All data collected prior to the date 
of the subject’s confirmed withdrawal of consent will be included in the study, as specified in 
the subject’s signed ICF. 
5. 
5.1. 
STUDY TREATMENTS 
Method of Assigning Subjects to Treatment Groups 
In the single-blind RI period, all subjects will receive blinded rilonacept at the same dose 
through Week 12; subjects will be blinded to the time of transitioning to RW. Subjects who 
stopped background SOC pericarditis therapy and who achieve Clinical Response on 
rilonacept at RI Week 12/RW baseline will be randomly assigned in a double-blind manner 
to continue to receive blinded rilonacept or matching placebo using a 1:1 allocation ratio. 
The definition of Clinical Response is provided in Section 6.2.2. An interactive web response 
system (IWRS) will be used to administer the randomization schedule. Biostatistics will 
generate the randomization schedule using SAS® software Version 9.4 or later (SAS Institute 
Inc, Cary, North Carolina) for the IWRS, which will link sequential subject randomization 
numbers to treatment codes. The randomization schedule will be stratified by 2 factors: 
• 
• 
Oral CS use at baseline (RI baseline, i.e., beginning of RI period): yes or no 
Diagnosis of recurrent idiopathic pericarditis (RI baseline): yes or no 
5.2. 
Treatments Administered 
Throughout this protocol, “study drug” refers to the investigational medicinal products: 
rilonacept and matching placebo. Both will be administered as applicable by SC injection. 
For additional information on rilonacept please refer to the Prescribing Information for 
Arcalyst® located in the Pharmacy Manual. 
Study drug administration will be performed once a week (every 7 ± 2 days). The interval 
between study drug administrations must be at least 5 days. 
5.2.1. 
Adult Subjects (≥18 years old) 
Rilonacept: Loading dose 320 mg administered as 2 SC injections, 160 mg each (2 ml) at RI 
baseline, followed by once-weekly SC injections of 160 mg (2ml). 
Placebo: administered as once-weekly SC injections of 2 ml each in the RW period 
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Upon meeting protocol criteria for bailout rilonacept (Sections 3.1 and 6.2.3) in the RW 
period, subjects will be transitioned to open-label rilonacept 320 mg administered as 2 SC 
injections, 160 mg each (2 ml) at the next scheduled study drug administration date, followed 
by once-weekly SC injections of 160 mg (2ml). 
5.2.2. 
Pediatric Subjects (≥12 and <18 years old) 
Rilonacept: Loading dose 4.4 mg/kg administered as 2 SC injections, 2.2 mg/kg each 
(maximum 160 mg each) at RI baseline, followed by once-weekly SC injections of 2.2 mg/kg 
(maximum 160 mg). The volume of injections will be based on the subject’s weight 
(Table 1). 
Placebo (in RW): once-weekly SC injections with volume based on the subject’s weight 
(Table 1 , maximum 2 ml). 
Upon meeting protocol criteria for bailout rilonacept (Sections 3.1 and 6.2.3) in the RW 
period, subjects will be transitioned to open-label rilonacept 4.4 mg/kg administered as 
1 (maximum 2 ml) or 2 SC injections at the next scheduled study drug administration date, 
followed by once-weekly SC injections of 2.2 mg/kg (maximum 2 ml). The volume of 
injections will be based on the subject’s weight (Table 1). 
Study drug dose/volume will be calculated by the Investigator or pharmacist during site 
clinic visits based on body weight (as specified in Section 13.1) using a weight-based dosing 
chart in kilograms (Table 1). 
Table 1: 
Study Drug Dose Volume (After Reconstitution) by Body Weight in 
Kilograms for Pediatric Subjects Aged ≥12 and <18 Years 
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Weight Range (kg) 
Loading Dose Volume (ml) 
Weekly Dose Volume (ml) 
23.6 to 27.2 
2 x 0.7 
0.7 
27.3 to 30.8 
2 x 0.8 
0.8 
30.9 to 34.4 
2 x 0.9 
0.9 
34.5 to 38.1 
2 x 1.0 
1.0 
38.2 to 41.7 
2 x 1.1 
1.1 
41.8 to 45.4 
2 x 1.2 
1.2 
45.5 to 49.0 
2 x 1.3 
1.3 
49.1 to 52.6 
2 x 1.4 
1.4 
52.7 to 56.3 
2 x 1.5 
1.5 
56.4 to 59.9 
2 x 1.6 
1.6 
60.0 to 63.5 
2 x 1.7 
1.7 
63.6 to 67.2 
2 x 1.8 
1.8 
67.3 to 70.8 
2 x 1.9 
1.9 
70.9 or greater 
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5.2.3. 
Study Drug Self-Administration 
The first study drug dose on RI baseline will be administered at the study site. During this 
visit, the subject will be trained on study drug preparation and injection. In case the subject is 
unwilling or unable to prepare and self-inject the study drug, the subject’s caregiver will be 
trained. 
The first study drug administration for adult and pediatric subjects on RI baseline will consist 
of 2 SC injections, constituting a loading dose. The first injection will be prepared and 
administered by study site staff. The second injection will be prepared and administered by 
the subject or the subject’s caregiver after adequate training and under the supervision of 
study site personnel. Subsequent once-weekly study drug doses will be self-administered SC 
by the subject or administered to the subject by a trained caregiver as an outpatient SC 
administration. If the subject or subject’s caregiver is unable to prepare and inject the study 
dug, the subject may report for once-weekly injections to a study site, or injections can be 
administered by the visiting registered nurse (RN). 
5.3. 
Identity of Investigational Medicinal Product 
Rilonacept (KPL-914) is the drug being evaluated in the current study. Refer to Section 1.3 
for a detailed description of rilonacept’s mechanism of action. 
Study drug (rilonacept or placebo) is supplied in a single-use, 20 ml glass vial containing a 
sterile, white to off-white, lyophilized powder. Each vial is to be reconstituted with 2.3 ml 
sterile Water for Injection (WFI). A volume up to 2 ml can be withdrawn, which is 
designated to deliver up to 160 mg of rilonacept or up to 2 ml placebo for SC injection only. 
The resulting solution is clear, colorless to pale yellow, and essentially free of particulates. 
Each rilonacept vial contains 220 mg of rilonacept lyophilized powder. After reconstitution 
with 2.3 ml sterile WFI, the rilonacept vial contains 80 mg/ml rilonacept, 40 mM histidine, 
50 mM arginine, 3.0% (w/v) polyethylene glycol 3350, 2.0% (w/v) sucrose, and 1.0% (w/v) 
glycine at a pH of 6.5. No preservatives are present. 
Each placebo vial contains lyophilized powder. After reconstitution with 2.3 ml sterile WFI, 
the placebo vial contains 40 mM histidine, 50 mM arginine, 3.0% (w/v) polyethylene glycol 
3350, 2.0% (w/v) sucrose, and 1.0% (w/v) glycine at a pH of 6.5. No preservatives are 
present. 
5.4. 
5.4.1. 
Management of Clinical Supplies 
Study Drug Product Packaging and Storage 
Additional information regarding the preparation, dispensation, administration, and storage 
of rilonacept or placebo will be described in the Pharmacy Manual. 
Study drug will be provided by Kiniksa Pharmaceuticals to the study sites in the lyophilized 
formulation in glass vials as described in Section 5.3. Each single-use vial will have a clinical 
label adhered to the vial. One labeled vial will be placed into a carton. Each carton will have 
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a clinical label adhered to the outside of the carton. One tamper-evident seal will be placed 
on the top of the carton to securely close the lid. 
Study drug is to be stored and shipped refrigerated at 2°C to 8°C (36°F to 46°F) inside the 
original carton to protect it from light. 
5.4.2. 
Study Drug Accountability 
The sites will receive study drug for on-site administration at study site visits. Upon receipt 
of study drug, the Investigator (or delegate) will conduct an inventory of the supplies and 
verify that the supplies are received intact, at the appropriate temperature, and in the correct 
amounts prior to completing a supplies receipt. The Investigator will confirm receipt of study 
drug in the IWRS and retain a copy of this receipt at the study site. The inventory of supplies 
at each study site will be reviewed by the study monitor. 
Study drug will be dispensed to the study subjects for outpatient self-administration 
according to the supply chain described in the Pharmacy Manual. 
The Investigator will maintain accurate records of receipt of all test articles, including dates 
of receipt. In addition, accurate records will be kept regarding when and how much study 
drug is dispensed and used by each subject in the study. Reasons for deviating from the 
expected dispensing regimen must also be recorded. The full process for drug dispensing, 
documentation, and destruction will be described in the Pharmacy Manual. 
A full drug accountability log will be maintained at the study site at all times. 
5.4.3. 
Other Supplies 
The Sponsor will provide the materials needed to prepare and administer study drug. The 
Sponsor also will provide coolers and refrigerated gel packs to ensure that the subjects 
transport the study drug at the proper temperature. On occasion, sites may be asked to locally 
procure ancillary materials. Please see the Pharmacy Manual for additional information. 
5.5. 
Study Drug Overdose 
An overdose is any dose of study drug given to a subject or taken by a subject that exceeds 
the dose described in the protocol. Any overdose must be promptly reported to the 
Pharmacovigilance (PHV) in the same way and using the same procedures as for a serious 
adverse event (SAE) (Section 6.4.6), regardless of whether any AEs are associated with the 
overdose. 
If there are AEs associated with the overdose, these should be recorded on the relevant 
AE/SAE Sections in the eCRF; however, overdoses without signs or symptoms do not need 
to be recorded as AEs in the eCRF. 
5.6. 
Prior and Concomitant Medications 
Use of all concomitant medications and any changes in concomitant medications will be 
recorded in the subject’s eCRF. This will include all prescription drugs, herbal products, 
vitamins, minerals, and over-the-counter medications. 
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Any concomitant medication deemed necessary for the welfare of the subject during the 
study may be given at the discretion of the Investigator. However, it is the responsibility of 
the Investigator to ensure that details regarding the medication are recorded in full in the 
eCRF. The initiation of protocol prohibited medication (Section 5.6.5) requires 
discontinuation of study drug. 
Guidelines regarding the use of concomitant medication will be detailed in the Pharmacy 
Manual and are summarized in the following Sections. 
5.6.1. 
Screening 
Subjects included in the study may be receiving concomitant NSAIDs and/or colchicine, 
and/or oral CS treatment in any combination, provided that the dosages of these medications 
have been stable (or not increased) for at least 3 days prior to and including RI baseline (first 
administration of study drug), and changes in medications made within this time period (e.g., 
1-time use of NSAIDs), in the opinion of the Investigator, are not anticipated to significantly 
alter assessments of baseline disease activity. 
Analgesics can be used at the discretion of the Investigator during screening activities prior 
to the first study drug dose, but only after the subject has documented a pericarditis pain level 
≥4 on the 11-point NRS within 7 days prior to and including RI baseline (first administration 
of study drug). 
Subjects can enter the study on prednisone (or equivalent dose) not exceeding 60 mg/day for 
adults and not exceeding 0.5 mg/kg/day (with a maximum dose of 60 mg/day) in pediatric 
subjects. 
5.6.2. 
Single-blind RI Period 
1-week Stabilization period, during which rilonacept is administered in addition 
to SOC pericarditis therapy and ongoing pericarditis episode is treated. All 
concomitant pericarditis medications including NSAIDs, analgesics, colchicine 
and CS will remain stable, unless the dosing must be decreased or stopped in the 
judgement of the Investigator due to an AE. 
9-week background medication Weaning period, during which subjects are 
weaned off background SOC pericarditis therapy, as applicable, while treatment 
with blinded rilonacept continues. The guidelines for background medication 
taper and discontinuation will be provided in the Pharmacy Manual. 
− Corticosteroids 
• 
• 
▪ Starting at Week 1 and through Week 10, CS will be tapered and 
discontinued at a rate dependent on the dose at study entry. 
− Analgesics 
▪ Starting at Week 1 and through Week 10, analgesics (non-opioid and 
opioid) will be tapered and discontinued. Opioid analgesics can 
continue beyond Week 10 at stable doses through the end of the RW 
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period if it is not feasible to discontinue them without causing 
withdrawal symptoms. 
− NSAIDs and Colchicine 
▪ Starting at Week 4 and through Week 10, NSAIDs and colchicine will 
be tapered and discontinued. 
• 2-week Monotherapy period during which rilonacept administration continues: 
Subjects are required to be off all background SOC pericarditis therapy, with the 
exception of opioid analgesics if their discontinuation is not feasible. 
5.6.3. 
Double-blind Placebo-controlled RW Period 
During the RW period, subjects should not be receiving any concomitant medications for 
pericarditis, with the exception of opioid analgesics in case their taper down and 
discontinuation was not feasible in the RI period. 
The use of concomitant medication is permitted upon pericarditis recurrence based on the 
subject meeting protocol criteria for bailout rilonacept as follows: 
Subjects meeting protocol criteria for bailout rilonacept 
Upon pericarditis recurrence and meeting protocol criteria for bailout rilonacept (Sections 3.1 
and 6.2.3) and completing the diagnostic workup as confirmed by the 
medical monitor, subjects will be transitioned to open-label rilonacept, as described in 
Section 3.1. Because open-label rilonacept can be administered only if at least 5 days have 
passed from the last blinded study drug administration, the Investigators are allowed to use 
sequential ORT, i.e., analgesics, NSAIDs, and colchicine, if necessary, at their discretion. 
The use of those medications will be detailed in the Pharmacy Manual; it is briefly given as 
follows: 
• Analgesics (including non-opioid and opioid) can be used for pain control prior to 
completing the diagnostic workup for a recurrent pericarditis episode. The use of 
analgesics during pericarditis recurrence evaluation will provide pain relief for 
subjects without impacting their CRP levels or other objective components of the 
diagnostic workup. 
• After the diagnostic workup is completed based on the 
medical 
monitor’s assessment, NSAIDs followed by colchicine can be added to open-label 
rilonacept based on the subject’s clinical status and at the discretion of the 
Investigator. 
If, after transition to open-label rilonacept, the Investigator decides that the 
subject requires CS for pericarditis therapy, the subject will be discontinued from 
rilonacept and followed through the EORW visit. 
• 
Subjects not meeting protocol criteria for bailout rilonacept 
If, based on the Investigator’s judgement, the subject is experiencing pericarditis recurrence 
that does not meet the protocol criteria for bailout rilonacept (Sections 3.1 and 6.2.3) but does 
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require additional treatment, the subject will continue blinded study drug, and the 
Investigator should manage the pericarditis recurrence using sequential ORT for pericarditis, 
i.e., analgesics, NSAIDs, colchicine as described in the Pharmacy Manual and outlined 
briefly below: 
• Analgesics (including non-opioid and opioid) can be used for pain control prior to 
completing the diagnostic workup for a recurrent pericarditis episode. The use of 
analgesics during pericarditis recurrence evaluation will provide pain relief for 
subjects without impacting their CRP levels or other objective components of the 
diagnostic workup. 
• After the diagnostic workup is completed based on the 
medical 
monitor’s assessment, NSAIDs followed by colchicine can be added to blinded 
study drug based on the subject’s clinical status and at the discretion of the 
Investigator. 
• If, after the addition of NSAIDs and colchicine, the Investigator decides that the 
subject requires CS for pericarditis therapy, the subject will be discontinued from 
blinded study drug and followed through the EORW visit. 
5.6.4. 
Long Term Extension 
Subjects who opt to continue open-label rilonacept in the LTE will have their concomitant 
pericarditis medications managed at the discretion of the Investigator and based on the 
subject’s clinical status. If addition of CS is required to manage recurrent pericarditis, 
rilonacept should be discontinued. 
5.6.5. 
Prohibited Concomitant Medicines During the Study 
The following concomitant medications are prohibited throughout the duration of the study 
including the LTE: 
• 
• 
• 
• 
• 
Interleukin-1 (IL-1) blockers other than rilonacept 
IL-6 blockers 
Janus-activating kinase inhibitors 
TNF inhibitors 
Potent immunosuppressants (azathioprine, mycophenolate mofetil, cyclosporine, 
tacrolimus, sirolimus, mercaptopurine, cyclophosphamide, chlorambucil, nitrogen 
mustard, or other alkylating agents, agents that deplete B or T cells [e.g., 
rituximab, alemtuzumab]) 
Live (attenuated) vaccines, which are prohibited during the study and within 12 
weeks after the last study drug administration 
• 
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5.7. 
Method of Blinding 
In the single-blind RI period, all subjects will receive rilonacept but will be blinded to the 
duration of the RI period and the timing of randomization. The RW period is a double-blind 
period in which rilonacept and placebo are identical in appearance. Neither the subject nor 
any of the Investigator/site staff, 
or Sponsor staff who are involved in the treatment or 
clinical evaluation of the subjects will be aware of the treatment received (International 
Council for Harmonisation [ICH] E9). 
In the event of a pericarditis recurrence that meets the criteria for bailout rilonacept (Sections 
3.1 and 6.2.3), the subject will be transitioned to open-label rilonacept but will remain 
blinded to their prior RW treatment assignment. 
If the treatment allocation for a subject becomes known to the Investigator or other study 
staff involved in the management of study subjects, the Sponsor and 
must be notified 
immediately. The Investigator may unblind a subject’s treatment assignment only in the case 
of an emergency, when knowledge of the study drug is essential for the appropriate clinical 
management or welfare of the subject. In most cases, the management of a medical 
emergency would be the same, regardless of whether the subject received active drug. The 
treatment assignment will be unblinded through the IWRS. 
The 
PHV staff may unblind the treatment assignment for any subject with an SAE. If 
the SAE requires that an expedited regulatory report be sent to one or more regulatory 
agencies, a copy of the blinded report may be sent to clinical Investigators in accordance with 
local regulations. 
5.8. 
Treatment Compliance 
Subjects will record the administration of all doses of study drug (whether as an outpatient or 
in the clinic) in a subject’s diary. In addition, throughout all study periods, adherence to study 
drug administration will be assessed by the study site in collaboration with the visiting RN, if 
applicable (Section 6). 
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6. 
STUDY ASSESSMENTS AND PROCEDURES 
Before performing any study procedures, all potential subjects will provide informed consent 
or an assent, if applicable. Potential subjects will have the study risks and benefits explained 
to them, the associated ICF reviewed with them, and all questions answered for them. 
Subjects will undergo screening procedures specific to the study only after the ICF has been 
provided by the subject unless performed as part of SOC practice. The investigator or 
designee will also sign the ICF. 
6.1. 
Study Visits 
Refer to Section 13.1 for a comprehensive list of procedures in the Schedule of Activities. 
Following screening assessments, qualifying subjects will be enrolled and enter the 
RI period. Subjects who stop background pericarditis medications and achieve Clinical 
Response at RI Week 12 (Section 6.2.2), will be randomized and enter the RW period. 
During both the RI and RW period, a combination of clinic and outpatient visits will occur. 
Outpatient visits may consist of telephone or virtual contacts as well as home visits 
conducted by a visiting nurse. For each scheduled visit of the study (including outpatient and 
clinic), assessments should occur prior to scheduled injections of study drug. Subjects can be 
brought to the clinic in place of a scheduled outpatient visit, for an unscheduled visit at the 
discretion of the Investigator, or if arranging a visiting nurse for an at home visit is 
logistically not feasible. 
The visit schedule is derived from the day of the RI baseline visit. One week is equal to 
7 calendar days. Although visits do not occur every week, subjects will be provided an 
electronic device to record daily pericarditis pain NRS measurements and administration of 
study drug from the beginning of the RI period through the end of the RW period. If a subject 
is unable to independently complete the daily entries, a caregiver may help the subject with 
data entry only. Throughout all study periods, compliance with study drug administration 
will be assessed by the site in collaboration with the visiting RN. 
Any subject who prematurely discontinues study drug will complete an EOT visit and will be 
followed for the duration of the trial according to the SOA unless the subject withdraws 
consent. In addition, throughout all study periods, compliance with study drug 
administration will be assessed by the site in collaboration with the visiting RN. 
6.1.1. 
Screening Visit(s) 
Subjects will undergo screening procedures for the study only after the signing of informed 
consent or assent by the subject. Potential subjects will have the study risks and benefits 
explained to them, the associated ICF reviewed with them, and all questions answered for 
them. The Investigator or designee will also sign the ICF. All subjects that sign the informed 
consent will be registered in IWRS and will be assigned a unique subject ID. 
The screening period begins at the signing of the ICF and must be completed within 28 days. 
Procedures performed per SOC prior to consent for the study, may be used for screening and 
do not need to be repeated for the study if performed within the 28 days of enrollment, except 
for the following procedures below: 
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• 
• 
• 
IGRA, hepatitis serology and HIV within 8 weeks of enrollment 
Chest X-ray within 12 weeks enrollment 
Qualifying 11-point pericarditis pain NRS assessment >4 and CRP ≥ 1 mg/dL within 
7 days prior to enrollment (the qualifying NRS assessment and CRP are not required 
to occur on the same day.) 
Procedures may be repeated at the discretion of the Investigator during the screening period. 
Subjects that are deemed not eligible must be screen failed in IWRS and can be rescreened at 
the discretion of the Investigator. Rescreened subjects will receive a new Subject ID through 
IWRS at the re-screening visit. 
It is possible that the screening and enrollment visit will occur on the same day. If the 
screening and the enrollment visit (RI Baseline Visit) is performed on the same day, 
procedures that are required at both visits do not need to be repeated. Refer to Section 13.1 
for a comprehensive list of procedures in the Schedule of Activities for this visit. 
6.1.2. 
Enrollment (RI Baseline Visit) 
Subjects meeting entry criteria will be enrolled at the RI Baseline visit. All procedures for the 
RI Baseline visit should be performed prior to enrollment in IWRS and the first 
administration of study drug. Refer to Section 13.1 for a comprehensive list of procedures in 
the Schedule of Activities for this visit. 
6.1.3. 
Randomization (RI Week 12/RW Baseline Visit) 
All procedures for the RI Week 12 visit should be performed prior to randomization in 
IWRS. Subjects who stopped background SOC pericarditis therapy and who achieve Clinical 
Response (see Section 6.2.2) at RI Week 12 visit will be randomized in the IWRS and will 
complete the procedures for the RW Baseline visit. If randomization has been closed, 
subjects achieving Clinical Response after completing the RI period may transition directly 
to the LTE. 
For subjects that do not qualify for randomization, the Sponsor or 
medical monitor is to 
be immediately contacted to evaluate the reasons for non-qualification. Following medical 
monitor consultation, if the subject is deemed to not be a treatment responder, study drug will 
be discontinued, and the subject will not proceed to randomization. The subject will complete 
the EOT visit and continue with follow-up according to the SOA until the end of the RW 
period. Refer to Section 13.1 for a comprehensive list of procedures in the Schedule of 
Activities for this visit. 
6.1.4. 
Pericarditis Recurrence Assessment: Clinic Visit 
If a subject experiences symptoms consistent with pericarditis recurrence, he/she should 
contact the study Investigator immediately for evaluation (including in the LTE). It is 
possible that a subject may have assessments performed remotely, however, assessments are 
also expected be performed at the study site as soon as possible. Required assessments 
include: 
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• 
• 
Evaluate pericarditis pain on the 11-point NRS. 
Evaluate concomitant medications as well as pericarditis concomitant 
medications. 
Obtain laboratory samples for CRP (local and central) (the POC device provided 
by Kiniksa Pharmaceuticals is the preferred method for local laboratory CRP 
assessment). 
Acquire a 12 lead ECG. 
Acquire a cardiac ECHO per core laboratory imaging parameters; this ECHO is 
read locally for the purpose of pericarditis recurrence assessment and is then 
submitted to the ECHO core laboratory for central review. 
Perform an abbreviated physical examination, height and body weight. 
For subjects >18 years, complete the SF-36, EQ-5D-5L, ISI. 
For all subjects, complete the PGIPS score. 
The Investigator is to complete the PGA PA. 
Obtain central laboratory samples for PK, ADAs, and biomarkers. 
Other procedures deemed necessary per the Investigator or delegated site 
personnel (e.g. MRI for sub-study subjects). 
• 
• 
• 
• 
• 
• 
• 
• 
• 
Upon having completed the evaluation, if the Investigator makes a clinical diagnosis that the 
subject is having a pericarditis recurrence event, he/she should contact the 
medical 
monitor to review and confirm that all assessments have been performed and collected. Upon 
medical monitor confirmation of completion of the assessment, the Investigator 
commences as described in Section 6.2.3. 
Subjects treated for a pericarditis recurrence event will continue to follow the same visit 
schedule described for the RW period (Section 6.1.5). 
Source documentation including the assessments and evaluations used to confirm a 
pericarditis recurrence event, are required to be sent to CEC. 
6.1.5. 
Randomized Withdrawal Period Visits 
During the RW period, subjects will continue with once-weekly study drug administration as 
well as daily 11-point pericarditis pain NRS scoring. Visits will occur every 4 weeks, 
alternating TC/RN visits and clinic visits, with the first visit during the RW period (RW 
Week 4) being a TC/RN visit. Additional unscheduled visits may occur at any time for 
evaluation of suspected pericarditis recurrence (Section 6.1.4) or for other reasons as deemed 
necessary by the study Investigator. Refer to Section 13.1 for a comprehensive list of 
procedures in the Schedule of Activities for these visits. 
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6.1.6. 
End of Randomized Withdrawal and LTE Baseline (EORW and LTE 
Baseline Visits) 
All subjects, including those that have had pericarditis recurrence or have permanently 
discontinued study drug will have an EORW visit at the end of the RW period. Upon 
completion of the EORW visit procedures those subjects who have not discontinued 
treatment previously will provide informed consent to participate in the LTE period. The 
LTE Baseline visit will be completed on the same day as the EORW visit. During the LTE 
subjects will return to the site every 12 weeks for up to 24 months thereafter from the first 
dose of open-label rilonacept in the LTE. Refer to Section 13.1 for a comprehensive list of 
procedures in the Schedule of Activities for these visits. 
6.1.7. 
End of Treatment Visit 
If at any time throughout the course of the study a subject prematurely discontinues study 
drug, an End of Treatment (EOT) visit is to occur as soon as possible. If the EOT visit 
coincides with the last study visit completed by the subject, procedures that are required at 
both visits do not need to be repeated and should be applied to complete the EOT 
requirements. Refer to Section 13.1 for a comprehensive list of procedures in the Schedule of 
Activities for this visit. 
6.1.8. 
Safety Follow-up Visit 
The SFU visit is to be conducted 6 weeks after the last dose of study drug. In the event that a 
subject permanently discontinues study drug but does not withdraw the informed consent, the 
Investigator should continue to follow the subject per protocol for the remainder of that study 
period. Refer to Section 13.1 for a comprehensive list of procedures in the Schedule of 
Activities for this visit. 
6.2. 
Efficacy Assessments 
Efficacy assessments to be performed at study visits are summarized in Section 13.1 and 
include: CRP, daily pericarditis pain assessment (11-point NRS), ECG, ECHO, Patient 
Global Impression of Pericarditis Severity (PGIPS), Physician Global Assessment of 
Pericarditis Activity (PGA-PA), and subject’s quality of life assessments (SF-36, EQ-5D-5L) 
and insomnia questionnaire (ISI). In a sub-study at selected sites, a cardiac MRI will be 
performed. 
Note that in case the electronic versions of the PROs and assessments/questionnaires (PGIPS, 
PGA-PA, SF-36, EQ-5D-5L, and ISI) are not available, the paper forms must be completed 
until the electronic versions are available again. 
6.2.1. 
Individual Efficacy Assessments 
6.2.1.1. 
C-Reactive Protein 
Central and local laboratory assessments of CRP will be performed at study visits as 
described in Section 13.1. Centrally assayed CRP values will be used for statistical 
evaluations of changes from baseline. Locally assayed CRP will be used for screening, 
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evaluation of treatment response prior to randomization, and assessment of suspected 
pericarditis recurrence in the RW period. The POC device provided by Kiniksa 
Pharmaceuticals is the preferred method for local laboratory CRP assessment. 
6.2.1.2. 
11-Point Pericarditis Pain Numerical Rating Scale 
Subjects will be asked to provide a daily assessment of pericarditis pain starting at 
RI baseline until EORW visit. A validated 11-point pericarditis NRS (see Section 13.2) will 
be used to measure the subject’s level of pain intensity on a daily basis throughout the study 
(Hawker et al 2011; Mannion et al 2007; Dworkin et al 2005). 
It is recommended that daily pericarditis pain measurements using the 11-point pericarditis 
NRS are performed by subjects at the same time of the day each day, and prior to study drug 
injection on days with study drug administration. 
6.2.1.3. 
Electrocardiogram 
Twelve-lead ECGs will be performed at study visits as described in Section 13.1. Pericarditis 
commonly involves changes in the electrophysiologic activity of the heart, resulting in 
typical ECG findings, namely widespread ST-segment elevation or PR-segment depression. 
6.2.1.4. 
Echocardiogram 
Echocardiographic assessment of presence of pericardial effusion including new or 
worsening of pericardial effusion should be obtained at study visits as described in 
Section 13.1. Pericardial effusion is characterized by accumulation of excess fluid in the 
pericardial space surrounding the heart, and pericarditis is one of the main causes of 
pericardial effusion. Echocardiography is a sensitive tool and the most widely used imaging 
technique for the detection of pericardial effusion and/or thickening. Echocardiograms are to 
be acquired per the ECHO core imaging parameters. Upon local assessment and 
interpretation, the ECHO is then to be submitted to the designated central imaging 
laboratory. 
6.2.1.5. 
Patient Global Impression of Pericarditis Severity 
Patient Global Impression questionnaires have been developed for a variety of indications. 
The PGIPS is a single-item PRO measure that assesses the subject’s impression of overall 
severity of pericarditis symptoms at the time the questionnaire is administered, using a 
7-point rating scale ranging from absent (no recurrent pericarditis symptoms) to very severe 
(recurrent pericarditis symptoms cannot be ignored) (Guy 1976). The PGIPS can be 
completed in less than 30 seconds. 
The subject will select from the following that best describes the severity of pericarditis 
symptoms at the time of occurrence of the event: 
• 
• 
• 
Absent: no symptoms 
Minimal: can be easily ignored without effort 
Mild: can be ignored with effort 
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• 
• 
• 
• 
Moderate: cannot be ignored but does not influence my daily activities 
Moderately severe: cannot be ignored and occasionally limits my daily activities 
Severe: cannot be ignored and often limits my concentration on daily activities 
Very severe: cannot be ignored and markedly limits my daily activities 
The PGIPS will be collected as described in Section 13.1. 
6.2.1.6. 
Physician Global Assessment of Pericarditis Activity 
Physician Global Assessment questionnaires have been developed for a variety of 
indications. The PGA-PA is a single-item clinician-reported outcome measure that 
Investigators use to rate their impression of the patient’s overall pericarditis disease activity 
at the time the assessment is completed, using a 7-point rating scale ranging from absent to 
very severe (Guy 1976). Like the PGIPS, the PGA-PA can be completed in less than 30 
seconds. 
The Investigator will select the box that best describes subject’s pericarditis activity at the 
time of occurrence of the assessment. 
• 
• 
• 
• 
• 
• 
• 
Absent 
Minimal 
Mild 
Moderate 
Moderately severe 
Severe 
Very severe 
The PGA-PA will be collected as described in Section 13.1. 
6.2.1.7. 
36-Item Short Form Health Survey 
The SF-36 is a set of generic, coherent, and easily administered quality-of-life measures. The 
SF-36 was developed at RAND Corporation as part of its Medical Outcomes Study. The 
SF-36 assesses 8 health domains: physical functioning, bodily pain, role limitations due to 
physical health problems, role limitations due to personal or emotional problems, general 
mental health, social functioning, energy/fatigue, and general health perceptions. It also 
includes a single item that provides an indication of perceived change in health. 
SF-36 will be collected in subjects ≥18 years or older as described in Section 13.1. 
6.2.1.8. 
EQ-5D-5L 
The EQ-5D-5L is a standardized instrument developed by the EuroQol Group as a measure 
of health-related quality of life that can be used in a wide range of health conditions and 
treatments. The EQ-5D-5L consists of a descriptive system and the EQ VAS. The descriptive 
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system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and 
anxiety/depression. The rating scale records the subject’s self-rated health on a vertical VAS. 
This can be used as a quantitative measure of health outcome that reflects the subject’s own 
judgement. The scores on these 5 dimensions can be presented as a health profile or can be 
converted to a single summary index number (utility) reflecting preferability compared to 
other health profiles (https://euroqol.org/eq-5d-instruments). 
The EQ-5D-5L will be collected in subjects ≥18 years or older as described in Section 13.1. 
6.2.1.9. 
Insomnia Severity Index 
The ISI is a 7-item self-report questionnaire assessing the nature, severity, and impact of 
insomnia. The usual recall period is the “last 2 weeks” and the dimensions evaluated are 
severity of sleep onset, sleep maintenance, early morning awakening problems, sleep 
dissatisfaction, interference of sleep difficulties with daytime functioning, noticeability of 
sleep problems by others, and distress caused by the sleep difficulties. A 5-point Likert scale 
is used to rate each item (e.g., 0=no problem; 4=very severe problem), yielding a total score 
ranging from 0 to 28. The total score is interpreted as follows: no clinically significant 
insomnia (0–7); subthreshold insomnia (8–14); clinical (moderate) insomnia (15–21); and 
clinical (severe) insomnia (22–28) (Morin et al 2011). 
The ISI will be collected in subjects ≥18 years or older as described in Section 13.1. 
6.2.1.10. Cardiac Magnetic Resonance Imaging 
Cardiac MRI will be performed as described in Section 13.1 in subjects at selected sites in 
the cardiac MRI substudy. Cardiac MRI will be performed to assess any changes in 
pericardial inflammation. Cardiac MRI readings will be performed by a central imaging 
laboratory. The study site/clinic reading of the MRI at the time of the examination may be 
used by the Investigator for clinical decision-making. 
6.2.2. 
Assessment of Clinical Response at the End of the Run-In Period Week 
12/RW Baseline 
At RI Week 12/RW baseline visit, all subjects receiving rilonacept who are able to 
discontinue background SOC pericarditis therapy during the RI period (Section 3.1) are 
assessed for Clinical Response. Only subjects who achieve Clinical Response at RI Week 12 
and have discontinued background medications for pericarditis are eligible for randomization 
in the RW period. 
Clinical Response at RI Week 12 is defined as follows: 
• A weekly average of daily pericarditis pain of ≤2.0 on the 11-point NRS during 
the 7 days prior to and including the day of randomization, AND 
CRP level ≤0.5 mg/dL at the RI Week 12/RW baseline visit. 
• 
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6.2.3. 
Management of Suspected Pericarditis Recurrence in the RW Period 
Pericarditis Recurrence Definition: Pericarditis recurrence, for the purpose of the protocol, 
is defined as the recurrence of typical pericarditis pain associated with supportive objective 
evidence of pericarditis. 
At any time point during the RW period, subjects who experience suspected recurrence of 
their pericarditis will have been instructed to inform their site Investigator as soon as 
possible. Subjects who experience a suspected recurrence of pericarditis symptoms will be 
requested to report to the study site/clinic for a scheduled or unscheduled visit, during which 
clinical assessments will be performed to gather all the necessary diagnostic data to confirm 
or rule out the presence of pericarditis recurrence (Section 6.1.4). The Investigator will 
evaluate all assessments performed for a diagnostic workup, whether at the study site or at 
locations outside. 
Upon completion of pericarditis workup, the Investigator is required to contact the 
medical monitor to confirm that the protocol required diagnostic workup is 
complete prior to implementing treatment for the event. 
Following communication with the 
medical monitor, if the event meets the 
criteria for bailout rilonacept (at least 1 day with pericarditis pain measurement ≥4 on the 
11-point NRS and one CRP value ≥1 mg/dL either on the same day or separated by no more 
than 7 days), and after the 
medical monitor has confirmed with the 
Investigator that the diagnostic workup is complete, the attainment of bailout criteria is 
confirmed in the IWRS, blinded study drug is discontinued, and open-label rilonacept 
treatment is dispensed. If needed, sequential ORT is allowed as outlined in Section 5.6.3. The 
subject will continue to be followed up according to Section 13.1 for the RW period. 
Following communication with the 
medical monitor, if the event does not 
meet the protocol criteria for bailout rilonacept but in the judgement of Investigator requires 
treatment, after the 
medical monitor has confirmed with the Investigator that 
the diagnostic workup is complete, the Investigator is allowed to add sequential ORT to 
blinded study drug, and as outlined in Section 5.6.3. Blinded study drug treatment will 
continue until a pericarditis recurrence that meets criteria for bailout rilonacept, or until the 
end of the RW period. 
For a summary of management of suspected pericarditis recurrence, refer to Figure 3. 
Upon suspected pericarditis recurrence, the event is required to be captured in the electronic 
data capture (EDC) system within 24 hours of learning of the event, and a pericarditis 
recurrence event adjudication package must be prepared for adjudication by CEC. The event 
package will include, but may not be limited to, data on the subject’s pericarditis pain level, 
CRP value, ECG tracing, ECHO result, the presence or absence of pericardial rub, and any 
additional source documentation relevant to the assessment of the suspected event. Details on 
endpoint package requirements will be described in the CEC charter. The CEC-confirmed 
pericarditis recurrences will be used for Primary Endpoint efficacy analysis. For more details 
on the CEC, refer to Section 6.7.2 
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Figure 3: 
Management of Suspected Pericarditis Recurrence in the Randomized- 
Withdrawal Period 
Pericarditis 
Recurrence * 
*Per protocol: CRP, ECG, ECHO, and pericardial rub 
assessment to be completed prior to treatment intervention 
NRS ≥ 
4 
NO 
NO 
Able to observe 
event without 
treatment 
YES 
CRP ≥ 1.0 
mg/dL 
YES 
YES 
Symptom 
Progression 
YES 
ORT=Oral Rescue Therapy 
6.3. 
Safety Assessments 
Safety assessments to be performed at study visits are summarized in Section 13.1 and 
include: assessment of AEs (Section 6.4), physical examinations (full and abbreviated) 
including vital signs measurements, chest x-ray, TB screening, and clinical laboratory tests 
(serology, hematology, chemistry, urinalysis) (Section 6.6). A pregnancy test (Section 6.6.6) 
will be conducted at screening and as needed during the study and must be performed 
6 weeks after the last study drug administration. 
6.3.1. 
Physical Examination 
A full physical examination should include at minimum an evaluation of vital signs, head, 
eyes, ears, nose, and throat as well as cardiovascular, dermatological, musculoskeletal, 
respiratory, GI, genitourinary, and neurological systems. The decision to perform 
examination of genitourinary system should be guided by clinical judgement. Body weight 
and height will be measured as per Section 13.1 and will be recorded in the eCRF. Any 
abnormality identified at baseline should be recorded on the medical history and physical 
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Bailout open-label 
rilonacept; and 
sequential ORT if 
needed 
(per Section 5.8.3) 
Continue 
observation and 
blinded study drug 
 
 
 
 
Continue blinded 
study drug; and 
sequential ORT if 
needed 
(per Section 5.8.3) 
 
 
 
 
 
 
 
 
 
 
 
 
 


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examination eCRFs. At selected visits as specified in Section 13.1, an abbreviated physical 
examination will be performed to evaluate vital signs, lung and heart sounds, including 
evaluation for pericardial rub. 
At all visits at the study site, limited symptom-directed physical examinations may need to be 
performed in order to determine changes from baseline or abnormalities and should be 
recorded in the subject’s trial notes. New or worsened abnormalities should be recorded as 
AEs on the Adverse Event eCRF. 
6.3.2. 
Vital Signs 
Vital signs include measurements of respiratory rate, pulse rate, systolic and diastolic blood 
pressure, and temperature. Blood pressure measurements should be obtained after the subject 
has been seated for at least 5 minutes. 
6.3.3. 
Chest X-ray 
Chest x-rays in accordance with local requirements will be obtained at screening (or an 
existing chest x-ray within 12 weeks of first study drug administration can be used) 
according to Section 13.1. Chest x-rays should be reviewed by a qualified radiologist for 
clinically significant abnormalities and evidence of pulmonary disease that would exclude 
the potential subject. 
6.3.4. 
Tuberculosis Screening 
An IGRA test or another TB test based on acceptable clinical practice in each country will be 
performed in order to evaluate for the presence of active or latent TB infection at screening 
(see Section 4.2). 
6.4. 
Adverse Events 
The Investigator is responsible for reporting all AEs that are observed or reported during the 
study, regardless of their relationship to study drug or their clinical significance. 
6.4.1. 
Definitions 
6.4.1.1. 
Adverse Event 
An AE is any untoward medical occurrence in a subject or clinical investigation subject 
administered a pharmaceutical product. An AE does not necessarily have a causal 
relationship with this treatment. An AE can therefore be any unfavorable sign (including an 
abnormal laboratory finding), symptom or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product. AEs also include: any worsening (i.e., any clinically significant change in frequency 
and/or intensity) of a pre-existing condition that is temporally associated with the use of the 
study drug; abnormal laboratory findings considered by the reporting Investigator to be 
clinically significant; and any untoward medical occurrence. 
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6.4.1.2. 
Treatment-emergent Adverse Event 
A treatment-emergent AE (TEAE) is defined as any event not present before exposure to the 
study drug or any event already present that worsens in either intensity or frequency after 
exposure to the study drug. 
6.4.1.3. 
Serious Adverse Event 
A serious adverse event (SAE) is any untoward medical occurrence or effect that, at any dose: 
• Results in death. Includes all deaths, even those that appear to be completely 
unrelated to the study drug (e.g., car accident where the subject is a passenger). 
Is life-threatening. In the view of the Investigator, the subject was at immediate 
risk of death from the event at the time of the event (i.e., it does not include an AE 
that might have caused death if it had occurred in a more serious form). 
Requires in-patient hospitalization or prolongs an existing hospitalization. 
(Complications occurring during hospitalization are AEs and are SAEs if they 
cause prolongation of the current hospitalization. Hospitalization for elective 
treatment of a pre-existing non-worsening condition is not, however, considered 
an AE. The details of such pre-existing condition must be recorded on the medical 
history or physical examination page of the eCRF. Hospitalization is defined as an 
admission to the hospital ward, a short-stay type unit, or Emergency Room for 
longer than 24 hours. Prolongation of existing hospitalization is defined as a 
hospital stay longer than originally anticipated for the event or development of a 
new AE as determined by the Investigator or treating physician.) 
Results in persistent or significant disability/incapacity. (An AE is incapacitating 
or disabling if it results in a substantial and/or permanent disruption of the 
subject’s ability to carry out normal life functions.) 
Is a congenital anomaly/birth defect. 
Is an important medical event. Important medical events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject 
or may require intervention to prevent one of the other serious outcomes listed 
above (e.g., intensive treatment in an emergency room or at home for allergic 
bronchospasm; blood dyscrasias or convulsions that do not result in 
hospitalization; or development of drug dependency or drug abuse). 
• 
• 
• 
• 
• 
In addition, medical and scientific judgment is required to decide if prompt notification is 
required in situations other than those defined for SAEs above, i.e., any event that the 
Investigator regards as serious that did not strictly meet the criteria above but may have 
jeopardized the subject or required intervention to prevent one of the outcomes listed above, 
or that would suggest any significant hazard, contraindication, side effect, or precaution that 
may be associated with the use of the study drug. 
All SAEs that occur after signing of study-related informed consent, whether or not the SAEs 
are related to the study drug or study procedures, must be reported. 
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6.4.1.4. 
Adverse Event of Special Interest 
An adverse event of special interest (AESI) is defined as an AE of scientific and medical 
interest specific to the understanding of the study drug and requiring close monitoring and 
rapid communication by the Investigator to the Sponsor. An AESI may be serious or non- 
serious. The rapid reporting of AESIs allows ongoing analysis of these events in order to 
characterize and understand them in association with the use of the study drug. 
Treatments with immunosuppressants, including rilonacept, may result in an increase in the 
risk of malignancies. Therefore, malignancy is an AESI for rilonacept. Any AE of 
malignancy (excluding basal cell carcinoma of the skin) requires reporting to the 
Pharmacovigilance (PHV) within 24 hours after the time the site personnel first learn about 
the event, following the process as described in Section 6.4.6. 
6.4.1.5. 
Adverse Reaction 
Any noxious and unintended response to the study drug (i.e., where a causal relationship 
between the study drug and an AE is at least a reasonable possibility) related to any dose 
should be considered adverse drug reaction. 
6.4.1.6. 
Suspected Unexpected Serious Adverse Reaction 
Suspected Unexpected Serious Adverse Reaction (SUSAR) is an adverse reaction that is 
“unexpected”, i.e., it is not listed (or not listed at the severity that has been observed) in the 
designated Reference Safety Information of the Investigator’s Brochure. Evaluation and 
reporting requirements for SUSARs are detailed in Section 6.4.8. 
6.4.2. 
Assessing Adverse Events 
6.4.2.1. 
Relationship to Study Drug 
The Investigator’s assessment of an AE’s relationship to the study drug is part of the 
documentation process, but it is not a factor in determining what is or is not reported in the 
study. If there is any doubt as to whether a clinical observation is an AE, the event should be 
reported. 
The relationship or association of the study drug in causing or contributing to the AE will be 
characterized by Investigator using the following classification and criteria: 
• Not Related: when the AE is definitely caused by the subject’s clinical state or 
the study procedure/conditions 
Unlikely Related: when the temporal association between the AE and the study 
drug is such that the drug is not likely to have any reasonable association with the 
AE 
Possibly Related: when the AE follows a reasonable temporal sequence from the 
time of study drug administration but could have been produced by the subject’s 
clinical state or the study procedures/conditions 
• 
• 
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• Related: when the AE follows a reasonable temporal sequence from 
administration of the study drug, abates upon discontinuation of the drug, follows 
a known or hypothesized cause-effect relationship, and (if appropriate) reappears 
when the drug is reintroduced 
6.4.2.2. 
Intensity 
The severity of an AE will be recorded as one of the following: 
• Mild: easily tolerated, does not interfere with normal daily activities, does not 
require intervention 
Moderate: causes some interference with daily activities; minimal, local, or 
noninvasive intervention indicated 
Severe: as a consequence of the event, daily activities are limited or completely 
halted; hospitalization or prolongation of hospitalization indicated 
• 
• 
Changes in the severity of an AE should be documented to allow an assessment of the 
duration of the event at each level of intensity to be performed. Adverse events characterized 
as intermittent do not require documentation of onset and duration of each episode. 
6.4.3. 
Recording Adverse Events 
Each subject should be monitored for the development of any AEs. This information should 
be collected by asking nonleading questions (such as “How are you feeling?”) and from 
observations of and conversations with patients. AEs may also be collected by direct physical 
exam, diagnostic procedures, or any other appropriate source. 
At every study visit (telephone or at the site), subjects will be asked a standard nonleading 
question to elicit any medically related changes in their well-being. They will also be asked if 
they have been admitted to the hospital, had any accidents, used any new medications, or 
changed concomitant medication regimens (both prescription and over-the-counter 
medications). 
All AEs (serious and non-serious) will be documented in the subject’s source documents and 
recorded in the eCRF. Any clinically relevant (as determined by the Investigator) 
deterioration in laboratory assessments or other clinical findings is considered an AE and 
must be recorded in the subject’s source documents and in the eCRF. 
The AE term should be reported in standard medical terminology when possible. Also, when 
possible, signs and symptoms indicating a common underlying pathology should be noted as 
one comprehensive event. Information to be collected includes the following: 
• 
• 
• 
• 
Event term 
Date and time of onset 
Investigator-specified assessment of severity and relationship study drug 
Date of resolution of the event 
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• 
• 
• 
• 
• 
Seriousness 
Any required treatment or actions 
Outcome 
Whether or not it caused the subject to discontinue the study drug. 
Whether or not the AE is an Injection Site Reaction (ISR). ISR is defined as any 
AE that occurs at the study drug injection site. If an ISR is observed, the subject 
may be treated at the discretion of the Investigator. 
Adverse events resulting from concurrent illnesses, reactions to concurrent illnesses, 
reactions to concurrent medications, or progression of disease states must also be reported. 
All AEs will be followed to adequate resolution. The Medical Dictionary for Regulatory 
Activities (MedDRA) will be used to code all AEs. 
Any medical condition that is present at the time that the subject is screened but does not 
deteriorate should not be reported as an AE. However, if the condition deteriorates at any 
time during the study, it should be recorded as an AE. 
6.4.3.1. 
Adverse Events Based on Signs and Symptoms 
All AEs spontaneously reported by the subject or reported in response to the open question 
from the study personnel or revealed by observation will be collected and recorded in the 
eCRF. When collecting AEs, the recording of a diagnosis is preferred (when possible) to the 
recording of a list of signs and symptoms. However, if a diagnosis is known and there are 
other signs or symptoms that are not generally part of the diagnosis, the diagnosis and each 
sign or symptom will be recorded separately. 
6.4.3.2. 
Adverse Events Based on Examinations and Tests 
If an abnormal laboratory value/vital sign is associated with clinical signs and symptoms, the 
sign or symptom will be reported as an AE and the associated laboratory result/vital sign will 
be considered as additional information. Wherever possible the reporting Investigator uses 
the clinical rather than the laboratory term (e.g., anemia vs low hemoglobin value). In the 
absence of clinical signs or symptoms, clinically significant findings on examinations and 
tests should be reported as AEs. 
Any new or aggravated clinically significant abnormal medical finding at a physical 
examination as compared with the baseline assessment will be reported as an AE. 
6.4.3.3. 
Pericarditis Disease-related Events 
Signs, symptoms, and abnormal findings associated with pericarditis are to be captured as a 
pericarditis recurrence event rather than as an AE unless the event is more severe than 
expected for the subject. In any case, pericarditis recurrence is required to be captured in the 
eCRF (see Section 6.2.3) within 24 hours of learning of the event. 
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6.4.4. 
Time Period for Collection of Adverse Events 
Adverse events will be assessed from the time the subject’s signs the ICF and through 
6 weeks after the last dose of study drug. 
6.4.5. 
Follow-Up of Unresolved Adverse Events 
Every reasonable effort will be made to follow subjects who have AEs. 
Any AEs that are unresolved at the end of the subject’s SFU visit are to be followed up by 
the Investigator until resolution or for as long as medically indicated. Additional information 
for any subject with an ongoing AE at the end of the SFU period may be requested by the 
PHV, as needed. 
6.4.6. 
Reporting Serious Adverse Events 
Any AE that meets SAE criteria (Section 6.4.1.3) must be reported to the 
PHV using the 
EDC system, immediately (i.e., within 24 hours) after the time site personnel first learn about 
the event. 
In the event the EDC entry is not possible (e.g., system failure or access problems), the study 
site should complete the paper SAE report form and fax the form to the 
PHV within 
24 hours of awareness. The EDC system should be updated as soon as it is available. 
A full description of every SAE will need to be provided to the 
PHV (this may be 
supported by source documentation such as discharge summary or laboratory report should 
these documents be requested by the 
PHV). Additional follow-up information, if 
required or available, should be sent to the 
original SAE information. 
PHV as soon as possible and placed with the 
The following contact information is to be used for SAE reporting: 
Information on non-serious AEs that become serious must also be reported to the 
PHV 
as soon as it is available. 
Investigators must report SAEs and follow-up information to their responsible Institutional 
Review Board (IRB) or Independent Ethics Committee (IEC) as applicable per institutional 
policy. 
The Sponsor or designee will provide regulatory authorities, IRBs, IECs, and principal 
Investigators with clinical safety updates/reports according to local requirements. 
6.4.6.1. 
Other Reasons for Immediate Reporting 
The following events require reporting to the 
site personnel first learn about the event: 
PHV within 24 hours after the time the 
• Pregnancy in subject or female partner of male subject 
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• Overdose of the study drug or concomitant medication, regardless of whether it is 
considered AE 
Other study drug errors 
Any AE of malignancy (excluding basal cell carcinoma of the skin) 
• 
• 
6.4.7. 
Pregnancy 
Pregnancy is regarded as an AE only if there is a suspicion that study drug may have 
interfered with the effectiveness of a contraceptive medication. Nonetheless, any pregnancy 
that occurs during study participation (including pregnancy in a female partner of a male 
subject) must be reported to the 
PHV in the same way and using the same procedures as 
for an SAE (Section 6.4.6). The subject with pregnancy must not receive (additional) study 
drug. The pregnancy must be followed up to determine outcome (including spontaneous 
miscarriage, elective termination, normal birth, or congenital abnormality) and status of 
mother and child, even if the subject was discontinued from the study. Pregnancy 
complications and elective terminations for medical reasons must be reported as an AE or 
SAE. Spontaneous miscarriage must be reported as an SAE. 
Any SAE occurring in association with a pregnancy, brought to the Investigator’s attention 
after the subject has completed the study, and considered by the Investigator as possibly 
related to the study drug, must be promptly reported to the 
PHV. 
In the event that a subject is found to be pregnant after having received at least 1 study drug 
dose, the study drug must be discontinued, and the pregnancy will be followed to term and 
the status of mother and child will be reported to the 
PHV after delivery. Instances of 
perinatal death or congenital abnormality, if brought to the attention of the Investigator at any 
time after cessation of study drug, will be reported to the 
PHV within 24 hours. 
6.4.8. 
Evaluating and Reporting SUSARs 
Pharmacovigilance will promptly evaluate all SUSARs and nonserious AEs of special 
interest against cumulative product experience to identify and expeditiously communicate 
possible new safety findings to Investigators, IRBs/IECs, and applicable health authorities 
based on applicable legislation. 
To determine reporting requirements for single SAE cases, 
PHV staff in collaboration 
with Kiniksa Pharmaceuticals will assess the expectedness of these events using the 
Reference Safety Information (Section 6.2) of the rilonacept Investigator’s Brochure. 
PHV will compare the severity of each SUSAR and the cumulative event frequency 
reported for the study with the severity and frequency reported in the applicable reference 
document. 
Reporting requirements will also be based on the Investigator’s assessment of causality and 
seriousness, with allowance for upgrading by 
needed. 
PHV and Kiniksa Pharmaceuticals as 
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All relevant information about suspected SUSARs that are fatal or life-threatening will be 
recorded and reported to the competent authorities in all the applicable countries, and 
IRBs/IECs in conjunction with Directive 2001/20/EC. 
6.5. 
6.5.1. 
Other Assessments 
Pharmacokinetic Sample 
All subjects will have PK samples obtained according to Section 13.1. For PK analyses, it is 
important that the exact time of the SC injection is recorded for each subject. When PK 
samples are to be collected on dosing days, serum will be collected pre-dose to measure 
rilonacept concentrations. Specific procedures for sample collection, processing, storage, and 
shipment can be found in a separate Laboratory Manual provided to sites. 
A PK substudy will be conducted in a subset of subjects agreeing to provide a PK sample 
24 hours after the first dose of study drug in the RI period. Specific procedures for sample 
collection, processing, storage, and shipment can be found in a separate Laboratory Manual 
provided to sites. 
6.5.2. 
Anti-Drug Antibodies (ADAs) against Rilonacept (KPL-914) 
Serum samples to measure the presence of ADAs against rilonacept will be collected 
according to Section 13.1. Instructions for sample collection, processing, storage, and 
shipment can be found in a separate Laboratory Manual provided to the site. 
6.5.3. 
Biomarkers 
Serum and plasma will be collected according to Section 13.1 for biomarker analysis. 
6.5.4. 
Pharmacogenomics 
Whole blood will be collected for pharmacogenomics assessments after signing the separate 
Pharmacogenomics ICF. 
6.6. 
Laboratory Analyses 
Any abnormal laboratory test results (hematology, chemistry, or urinalysis) or other safety 
assessments (e.g., physical examination, vital signs measurements), including those that 
worsen from baseline, felt to be clinically significant in the medical and scientific judgement 
of the Investigator are to be recorded as AEs or SAEs. 
Laboratory assessments will be performed at study visits as summarized in Section 13.1. 
Unscheduled laboratory assessments for safety issues are permitted as deemed necessary by 
the Investigator. 
Whenever possible in pediatric subjects, local laboratory tests should be drawn using 
pediatric tubes. 
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6.6.1. 
Serology 
Samples for local or central laboratory assessment of hepatitis B surface antigen, hepatitis B 
core antibody, hepatitis C virus antibody, and HIV test will be collected at screening. If 
clinically indicated, those tests may be also collected during the study. 
6.6.2. 
Hematology 
Hematology tests performed at central study laboratory include WBC count with differential, 
platelet count, red blood cell count, mean corpuscular volume, hemoglobin, mean 
corpuscular hemoglobin concentration. 
6.6.3. 
Chemistry 
Blood chemistry tests performed in the central study laboratory include albumin, total 
protein, alkaline phosphatase, ALT/SGPT, AST/SGOT, direct bilirubin, total bilirubin, 
bicarbonate, chloride, potassium, sodium, creatinine, glucose. 
In addition, the following chemistry tests may be performed together with local CRP 
measurement when using POC device: chloride, creatine kinase, creatinine, glucose, 
potassium, sodium, total carbon dioxide, blood urea nitrogen. 
6.6.4. 
Non-fasting Lipid Panel 
Subjects treated with rilonacept may experience increases in their lipids, including total 
cholesterol, LDL, HDL, and triglycerides. 
Non fasting measurements of total cholesterol, triglycerides, HDL, and direct LDL will be 
performed by central study laboratory as described in Section 13.1. 
Investigators should monitor the lipid profiles in study subjects and consider ordering fasting 
lipid panel and/or lipid lowering therapies as needed based on cardiovascular risk factors and 
current guidelines. 
6.6.5. 
Urinalysis 
Urinalysis performed by the central study laboratory includes specific gravity, pH, protein, 
urobilinogen, ketones, glucose, blood, bilirubin, nitrites, leukocyte esterase. It will be 
performed as described in Section 13.1. 
6.6.6. 
Pregnancy Test 
For women of child-bearing potential, a urine pregnancy test using a licensed test (dipstick) 
should be performed prior to receiving the first administration of study drug and as needed 
during the study. When needed, serum pregnancy test should be performed. The purpose of 
pregnancy test is to prevent embryo/fetal exposure to study drug. Subjects with positive or 
indeterminate pregnancy test during the screening are not eligible for the study. 
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6.6.7. 
Sample Collection 
The procedures for the collection, handling, and shipment of laboratory samples are specified 
in the Laboratory Manual supplied to sites by the central laboratory. 
6.7. 
6.7.1. 
Committees 
Independent Data Monitoring Committee (DMC) 
A DMC will be utilized in this study to ensure external objective medical and/or statistical (if 
needed) review of safety data in order to protect the ethical and safety interests of subjects. 
The DMC will review unblinded aggregate (and, where necessary, individual) subject safety 
data at pre-defined intervals according to a DMC charter. The analysis plan for the DMC 
review will be described in the DMC charter, which will also contain details of the 
composition and the responsibilities of the DMC. 
6.7.2. 
Clinical Endpoint Committee (CEC) 
An independent CEC will review and adjudicate all suspected recurrent pericarditis events 
that occur during the RW period of the study. The procedures for adjudicating events will be 
described in the CEC Charter. This will be done independent of the Investigators, and in a 
manner blinded to treatment assignment. The CEC will complete assessments on an ongoing 
basis. 
7. 
7.1. 
STATISTICAL AND ANALYTICAL PLAN 
Primary Efficacy Endpoint 
The primary efficacy endpoint is time to pericarditis recurrence, defined as the time from 
randomization to the date of the first pericarditis recurrence for each subject. Only 
CEC-confirmed pericarditis recurrence will be considered as an event for the primary 
analysis. 
A sensitivity analysis will be done based on the Investigator’s assessment of the event. 
Pericarditis recurrence is defined in Section 6.2.3. 
Subjects who do not have a pericarditis recurrence will be censored at the date of the last 
available assessment for pericarditis recurrence during the RW period before data cutoff. 
Detailed censoring rules will be specified in the Statistical Analysis Plan (SAP). 
7.2. 
Secondary Efficacy Endpoints for the RW Period 
This Section defines secondary efficacy endpoints for the RW period. Endpoints for the RI 
period and for the LTE are defined in Section 7.3. 
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7.2.1. 
• 
Major Secondary Efficacy Endpoints 
Proportion of subjects who maintained Clinical Response at Week 16 of the RW 
period. Clinical Response is defined as a weekly average of daily pericarditis pain on 
the 11-point NRS ≤2.0 and CRP level ≤0.5 mg/dL, and on monotherapy of 
randomized study drug at Week 16. 
Percentage of days with no or minimal pain in the first 16 weeks of the RW period. 
No or minimal pain is defined as non-missing NRS ≤2. 
Proportion of subjects with absent or minimal pericarditis symptoms (based on the 
7-point PGIPS) at Week 16 of the RW period. 
• 
• 
7.2.2. 
Other Secondary Endpoints 
All time-to-event endpoints start from the day of randomization. The following variables will 
be analyzed: 
• Proportion of subjects who maintained Clinical Response at Week 8 and Week 24 
of the RW period, respectively 
Percentage of days with no or minimal pain (pain ≤2 on the 11-point NRS) in the 
first 8 weeks and 24 weeks of the RW period, respectively 
Proportions of subjects with absent or minimal pericarditis symptoms (based on 
the 7 point rating scale of PGIPS) at Week 8 and Week 24 of the RW period, 
respectively 
Proportion of subjects without pericarditis recurrence in the first 24 weeks of the 
RW period 
Time to pericarditis pain NRS ≥4 
Time to CRP level ≥1 mg/dL. This is for elevation of CRP for which no other 
cause other than pericarditis was identified. 
Time to pericardial rub 
Time to widespread ST-segment elevation or PR-segment depression on ECG, 
whichever occurs first 
Time to new or worsening pericardial effusion on ECHO 
Change in category of ECHO pericardial effusion size at week 24 and end of RW 
based on central labs 
Change over time in CRP levels 
Change over time in the subject’s assessments of pericarditis pain (weekly 
average) 
Proportion of subjects with absent or minimal pericarditis activity based on the 
PGA-PA over time 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
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• Proportion of subjects with absent or minimal pericarditis activity over time based 
on the PGIPS over time 
Change over time in SF-36 Physical and Mental Component Scores and domain 
scores (Physical Functioning, Role-Physical, Bodily Pain, General Health, 
Vitality, Social Functioning, Role-Emotional, and Mental Health domains) 
Changes in SF-6D, 6 domain scores and utility index 
Change in EQ-5D-5L. There are 6 questions in this instrument (Section 6.2.1.8). 
Each of the first 5 questions has 5 levels, from level 1 (best) to level 5 (worst). 
They are mobility, self-care, usual activities, pain/discomfort, and 
anxiety/depression. The sixth question is the health on the day, from 0 (the worst) 
to 100 (the best) (van Reenen and Janssen 2015). The levels of the first 
5 questions (EQ-5D-5L profile) will be converted to an index value. Change from 
baseline in each one of these 7 values will be an endpoint. 
Change in subject’s sleep quality assessed with the ISI (Section 6.2.1.9). There 
are 7 items in the ISI. Change in ISI total score, which is the sum of the 7 items 
over time, will be the endpoint. 
Change in ISI categories. The ISI total scores are divided to 4 categories: 
• 
• 
• 
• 
• 
− 
− 
− 
− 
0–7 = No clinically significant insomnia 
8–14 = Subthreshold insomnia 
15–21 = Clinical insomnia (moderate severity) 
22–28 = Clinical insomnia (severe) 
• Cumulative number (percentage) of subjects who received sequential ORT, 
prednisone, or bailout rilonacept for pericarditis period every 4 weeks 
cumulatively in the RW period 
The following endpoints are for subjects enrolled in the MRI substudy. There will 
be no hypothesis testing performed. Only summary statistics will be provided. 
• 
− Proportion of subjects with pericardial Delayed Hyperenhancement at RW 
baseline and week 24 based on the MRI assessment 
Proportion of subjects with Myocardial Delayed Hyperenhancement at RW 
baseline and week 24 based on the MRI assessment 
Proportion of subjects with pericardial Effusion and Effusion size at RW 
baseline and week 24 based on the MRI assessment 
− 
− 
7.3. 
Other Endpoints 
These include efficacy endpoints in the RI period and the LTE. Since there is no control arm 
in these 2 periods, only descriptive statistics will be provided. All time-to-event endpoints 
start from the day of receiving rilonacept in that period. 
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The annualized event rate for recurrence of pericarditis will be calculated for the combined 
RW and LTE periods. 
7.3.1. 
Efficacy Endpoints for the RI Period 
The following efficacy endpoints are included in this period: 
• Time to pain response. Pain response is defined as a rolling average of NRS score 
of 2 or less on three consecutive days 
Time to CRP normalization (≤0.5 mg/dL) 
Time to monotherapy 
Time to clinical response (monotherapy + NRS ≤2 + CRP ≤0.5 mg/dL) 
Proportion of subjects who achieved Clinical Response at the RI Week 12. 
Clinical Response is defined as reaching monotherapy on or before week 10 and a 
weekly average of daily pericarditis pain of ≤2.0 on the 11-point NRS and CRP 
level ≤0.5 mg/dL at the RI Week 12/RW baseline visit. 
Number (percentage) of subjects with normalization of CRP at RI Week 12 
Change from baseline in pericarditis pain at RI Week 12 and over time 
Change from baseline in CRP level at RI Week 12 and over time 
Resolution of ECHO and ECG abnormalities (yes/no) at RI Week 12 
Percentage of days with no or minimal pain while on treatment 
Proportion of subjects with absent or minimal pericarditis symptoms based on 
PGIPS over time 
Proportion of subjects with absent or minimal pericarditis activity based on the 
PGA-PA over time 
Change over time in the SF-36 Physical and Mental Component Scores and 
domain scores 
Change in the SF-6D 6 domain scores and the utility index 
Change in the EQ-5D-5L (Section 7.2.2 contains details about calculation) 
Change in the subject’s sleep quality assessed with the ISI (Section 7.2.2 contains 
details about calculation) 
Change in ISI categories 
Number (percentage) of subjects who were off background pericarditis 
medication on or before weeks 4, 8, 10, and 12 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
7.3.2. 
Efficacy Endpoints for the LTE Period 
Efficacy endpoints for the LTE will be defined in the Statistical Analysis Plan. 
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7.4. 
Sample Size Calculations 
For the purpose of sample size estimation, time to pericarditis recurrence is assumed to 
follow an exponential distribution. An event of interest is defined as a subject’s first 
adjudicated recurrence of pericarditis. The following assumptions are used in the sample size 
calculation using EAST 6.4.1: 
• 
• 
• 
• 
• 
1-sided significance level 
Power 
Median time to event (in weeks) in placebo 
Hazard ratio (rilonacept/placebo) 
Percentage of subjects in the RI period that will not reach RW 
2.5% 
90% 
8 
0.244 
10% 
Given these assumptions, a total of 22 adjudicated pericarditis recurrence events is required 
to achieve the power. About 25 subjects per arm (a total of 50 subjects) will be randomized. 
Considering 10% of subjects in the RI period that will not reach the RW period, 
approximately 56 subjects will be enrolled in this study. 
Patient enrollment and the pericarditis recurrence event accrual will be closely monitored 
during the study. The monitoring activities will be done in a blinded fashion during the RW 
period. If the number of patients randomized is less than 50 and/or the time anticipated for 
the number of events required for the analysis of primary efficacy endpoint significantly 
exceeds the projected timeline, additional patients may be enrolled and/or randomized at 
Kiniksa Pharmaceutical’s discretion. However, at this time it is anticipated that no more than 
100 subjects will be enrolled into this study. 
7.5. 
Analysis Sets 
The following analysis sets will be used in the statistical analyses. 
Intent-to-Treat (ITT) Analysis Set: All subjects who are randomized in the RW period will be 
included in the ITT analysis set. The primary analysis for efficacy endpoints in the RW 
period will be based on the ITT analysis set. Treatment comparisons for all ITT analyses will 
be based on each subject’s treatment assignment from randomization. 
ITT Week 24 analysis set: All subjects randomized at least 24 weeks before data cutoff will 
be included. This analysis set will be used for secondary efficacy endpoints measured at 
week 24 in the RW period. 
ITT Week 16 analysis set: All subjects randomized at least 16 weeks before data cutoff will 
be included. This analysis set will be used for secondary efficacy endpoints measured at 
week 16 in the RW period. 
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ITT Week 8 analysis set: All subjects randomized at least 8 weeks before data cutoff will be 
included. This analysis set will be used for secondary efficacy endpoints measured at week 8 
in the RW period. 
Safety Analysis Set: All subjects who received at least 1 dose of study drug in the RI period 
will be included in the safety analysis set (SS). Safety analyses will be based on the actual 
treatment a subject received. 
Run-in Analysis Set: All subjects who received at least 1 dose of study drug in the RI period 
will be included in the RI analysis set (RIS). 
Run-in Week 12 Analysis Set: All subjects who received the first dose in the RI period at 
least 12 weeks before data cutoff. This analysis set will be used for secondary efficacy 
endpoints measured at Week 12 in the RI period. 
Long Term Extension Analysis Set: All subjects who received at least 1 dose of study drug in 
the long-term extension period will be included in the long-term extension analysis set 
Per-protocol Analysis Set: The per protocol (PP) analysis set is a subset of the ITT analysis 
set with the exclusion of subjects with major protocol violations or violations that may 
potentially bias statistical analyses or the ethical conduct of the study. The criteria of these 
violations will be determined prior to unblinding. This analysis set may be used for 
sensitivity analyses for efficacy endpoints in the RW period. 
Pharmacokinetic Analysis Set: The PK analysis set includes subjects who receive at least 
1 dose of study drug and have at least 1 PK sample. The PK analysis set will be used for all 
PK analyses. 
7.6. 
Description of Subgroups to be Analyzed 
Subgroup analyses for the primary endpoint will be performed by the stratification variable 
for randomization, as well as by important variables for baseline demographics and patient 
characteristics. These analyses are for the RW period only. Details will be provided in the 
SAP. 
7.7. 
Statistical Analysis Methodology 
This Section outlines the overall methodologies. Details of the statistical analyses, methods, 
and data conventions will be described in the SAP. 
7.7.1. 
General Methods 
Statistical analysis will be performed using SAS® software Version 9.4 or later. Continuous 
variables will be summarized using the mean, the standard deviation, median, minimum 
value, and maximum value. Time-to-event variables will be summarized using percent 
censored, event rate, and 25th, 50th, and 75th percentiles with 95% CI, if estimable. 
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Categorical variables will be summarized using frequency counts and percentages. Data will 
be listed in data listings. 
At each of RI and RW periods and in the LTE, baseline will be the last value before the first 
dose of study drug within each individual period unless otherwise specified. For 
change-over-time endpoints in the RW period, by-visit analysis will be performed at each 
scheduled visit for at least 24 weeks. 
The analysis for treatment comparison will be triggered after at least the 22nd CEC- 
confirmed pericarditis recurrence events have been accrued. At that time, randomization will 
be closed, and subjects will return to study sites for the EORW visit. At that point study 
treatment will stop (completing the database for the primary efficacy endpoint analysis), and 
subjects will either continue into the LTE or complete their study participation. Missing data 
due to end of RW period will be considered as missing at random. Handling of missing 
values will be described in the SAP. 
7.7.2. 
Stratified Analysis 
There will be 2 stratification variables for randomization: 
• 
• 
Oral CS use at RI baseline: yes or no 
Diagnosis of recurrent idiopathic pericarditis at RI baseline: yes or no 
When a stratified analysis is used in the analysis and a stratum has no event of interest or no 
responder, the stratum will be pooled with the other stratum in the same stratification 
variable. 
7.7.3. 
Testing Hypotheses and Multiplicity Adjustment 
All statistical tests for the treatment comparison of efficacy endpoints in the RW period will 
be based on the ITT analysis set with 1-sided α=0.025 unless otherwise specified. For each 
endpoint, the null hypothesis is that the effects of rilonacept and placebo are the same. The 
alternative hypothesis is that rilonacept is better than the placebo. 
In order to control the overall 1-sided type I error rate at the 0.025 level, a gatekeeping 
procedure in combination with Hochberg’s procedure will be applied to testing the primary 
and major secondary endpoints. If the 1-sided p-value for testing the primary endpoint is 
≤0.025, a significant treatment effect on the primary endpoint will be claimed. 
Section 7.2.1 provides the order of major secondary endpoints. If the primary endpoint is 
significant, the first major secondary endpoint, i.e., proportion of subjects who maintained 
Clinical Response at Week 24 of RW period will be tested at 1-sided α=0.025. A significant 
treatment effect on this major secondary endpoint will be claimed if the 1-sided p-value is 
≤0.025. If the treatment effect is not significant on the primary endpoint, significance on this 
major secondary endpoint cannot be claimed regardless of the result. 
If both primary and first major secondary endpoints are significant following the above 
procedure, the second and third major secondary endpoints defined in Section 7.2.1 will be 
tested with Hochberg’s procedure at overall 1-sided α=0.025. If both 1-sided unadjusted 
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p-values are ≤0.025, claim significance of rilonacept for both endpoints. If the larger 1-sided 
p-value is >0.025, compare the smaller 1-sided p-value with 0.0125. If the smaller 1-sided 
p-value is ≤0.0125, claim significance of rilonacept on this endpoint. 
7.7.4. 
Analysis of Primary Efficacy Endpoint 
Primary analysis of this study will be triggered after at least the 22nd CEC-confirmed 
pericarditis recurrence events have been accrued. The log rank test will be the primary 
method for the analysis of time to recurrence, stratified by the stratification variables for 
randomization. Detailed censoring rules will be described in the SAP. 
A sensitivity analysis will be performed based on the Investigator’s judgement of pericarditis 
recurrence. Additional sensitivity analyses may be defined in the SAP. 
7.7.5. 
Analysis of Secondary Efficacy Endpoints 
7.7.5.1. 
Analysis of the Major Secondary Endpoints 
The analyses for the 3 major secondary endpoints will be based on the ITT Week 16 analysis 
set, with the Week 8 and Week 24 ITT analysis sets providing supportive sensitivity 
analyses. 
• Proportion of subjects who maintained Clinical Response at Week 16 of the RW 
period (defined as a weekly average of daily pericarditis pain ≤2.0 on the 11-point 
NRS, CRP ≤0.5 mg/dL, and on monotherapy of randomized study drug at Week 24). 
The Cochran–Mantel–Haenszel (CMH) test will be used in this analysis, stratified by 
the stratification variables for randomization. 
Percentage of days with no or minimal pain in the first 16 weeks post randomization. 
Minimal or no pain is defined as non-missing daily NRS ≤2 on the 11-point NRS. 
This endpoint will be analyzed with an analysis of covariance. In addition to 
treatment arm, the following covariates will be included in this analysis: the 
stratification variables for randomization, and RI baseline NRS weekly average in 
2 categories: NRS ≤2 versus NRS >2. 
Proportion of subjects with absent or minimal pericarditis symptoms (based on the 
7-point PGIPS) at Week 16 of the RW period. The CMH test will be used in this 
analysis, stratified by the stratification variables for randomization. 
• 
• 
7.7.5.2. 
Analyses of Other Secondary Endpoints in the RW Period 
The following endpoints will be analyzed using the same method for the major secondary 
endpoints: 
• 
Proportion of subjects who maintained Clinical Response at Week 8 and Week 24 of the RW 
period 
Percentage of days with no or minimal pain (pain ≤2 on the 11 point NRS) in the first 8 
weeks and 24 weeks of the RW period 
• 
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• 
Proportion of subjects with absent or minimal pericarditis symptoms (based on the 7-point 
rating scale of PGIPS) at Week 8 and Week 24 of the RW period 
The following endpoints will be analyzed using the same method for the primary endpoint: 
• 
• 
Time to pericarditis pain NRS ≥4 
Time to CRP level ≥1 mg/dL. This is for elevation of CRP for which no other cause other 
than pericarditis was identified. 
Time to pericardial rub 
Time to widespread ST segment elevation or PR segment depression on ECG 
Time to new or worsening pericardial effusion on ECHO 
• 
• 
• 
A mixed model with repeated measures (MMRM) will be used in the analysis of the 
endpoints below. In the model, subjects will have repeated measures for the response 
variable change from baseline of the endpoint. For endpoints without repeated measures with 
subjects, e.g., health-related quality-of-life assessment, the analysis of covariance will be 
applied. The explanatory variables will include the baseline value, treatment arm, and the 
variables for stratification at randomization. The p-value for treatment comparison will be 
calculated at each scheduled assessment for at least 24 weeks as part of the summary 
statistics. This is done with the understanding that the comparison could be biased due to 
dropouts or subjects with pericarditis recurrence. 
• 
• 
Change over time in CRP levels 
Change over time in the subject’s assessments of pericarditis pain (weekly average) 
The CMH test will be used in the analysis of the endpoints below, stratified by the 
stratification variables for randomization. 
• Proportion of patients without pericarditis recurrence in the first 24 weeks of the 
RW period 
Number (percent) of subjects with absent or minimal pericarditis activity based on the 
PGA-PA 
• 
The following endpoints will be summarized without formal hypothesis testing: 
• 
• 
• 
Change in the SF 36 Physical and Mental Component Scores and domain scores 
Change in the EQ 5D 5L: Health score and Index value, respectively 
Change in the subject’s sleep quality: sum of the ISI scores. 
The following exploratory endpoint in the MRI sub-study will be summarized by treatment 
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7.7.6. 
Analyses of Other Endpoints 
Endpoints listed in Section 7.3 for the RI period and the LTE will be descriptive in nature 
since there is no control arm. Summary statistics will be generated following the 
methodologies stated in Section 7.7. Analysis for efficacy endpoints measured at week 12 
will be done using the run-in Week 12 analysis set. 
Other analyses include anti-rilonacept antibodies and biomarker analyses. These analyses 
will be described in the SAP. 
7.7.7. 
Pharmacokinetic Analyses 
For all subjects, serum samples will be collected at time points shown in the Schedule of 
Activities in order to quantify concentrations of rilonacept. Descriptive statistics will be 
calculated for the serum concentrations of rilonacept by visit. Individual listings of serum 
concentrations will be provided. 
Pharmacokinetic data may be used in a subsequent population PK evaluation that will 
be conducted outside of this study and described in a separate report. 
7.7.8. 
Safety Analyses 
Treatment-emergent AEs (TEAEs), defined as AEs that start or increase in severity after the 
first dose of study drug and before 6 weeks after the last dose of study drug, will be coded to 
system organ class and preferred term using the most recent version of MedDRA. TEAEs 
will be analyzed for all subjects combined and by treatment group in the RW period. Further 
analyses by severity and relationship to study drug as well as analyses of serious TEAEs will 
be presented. 
Descriptive statistics will be used to summarize safety endpoints by visit for all subjects 
combined in the RI period and by treatment group in the RW period. Two-sided 95% CIs 
will be presented where meaningful. Data summaries will be displayed for clinical laboratory 
analyses (including safety laboratory measurements, ADAs, etc.), vital signs measurements, 
ECGs, and physical examination findings. 
7.7.9. 
Interim Analyses 
No interim analyses are planned for this study. 
8. 
DATA QUALITY ASSURANCE 
Assessment of subject compliance and adherence to study drug administration will be 
assessed by the site in collaboration with the visiting RN. 
This study will be conducted according to the ICH E6(R2) risk and quality processes 
described in the applicable procedural documents. The quality management approach to be 
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implemented in this study will be documented and will comply with the current ICH 
guidance on quality and risk management (ICH Q9). 
8.1. 
Data Management 
As part of the responsibilities assumed by participating in the study, the Investigator agrees 
to maintain adequate case histories for the subjects treated as part of the research under this 
protocol. The Investigator agrees to maintain accurate eCRFs and source documentation as 
part of the case histories. These source documents may include laboratory reports, ECG 
strips, etc. 
will be responsible for activities associated with the data management of this study. 
This will include setting up a relevant database and data transfer mechanisms, along with 
appropriate validation of data and resolution of queries. Data generated within this clinical 
study will be handled according to the relevant Standard Operating Procedures (SOPs) of 
Investigative site personnel will enter subject data into an EDC system. The analysis data sets 
will be a combination of these data and data from other sources (e.g., laboratory data). 
Clinical data management will be performed in accordance with applicable 
standards 
and data cleaning procedures to ensure the integrity of the data, e.g., removing errors and 
inconsistencies in the data. Adverse event terms will be coded using MedDRA, an internal 
validated medical dictionary, and concomitant medications will be coded using the World 
Health Organization Drug Dictionary. 
After the last study database lock, each study site will receive a CD-ROM containing all of 
their site specific eCRF data as entered into Medidata Rave for the study, including full 
discrepancy and audit history. Additionally, a Master DVD/CD-ROM copy of all of the site 
data from the study will be created and sent to Kiniksa for storage. 
will maintain a 
duplicate Master DVD/CD-ROM copy for their records. In all cases, subject initials will not 
be collected or transmitted to Kiniksa Pharmaceuticals. 
9. 
9.1. 
ETHICS 
Independent Ethics Committee or Institutional Review Board 
Regulatory agencies and the ICH guidelines require that approval be obtained from an 
IRB/IEC before participation of human subjects in research studies. Before study onset, the 
protocol, informed consent, informed assent, advertisements to be used for the recruitment of 
study subjects, and any other written information regarding this study to be provided to the 
subject or the subject’s legal guardian must be approved by the IRB/IEC. Documentation of 
all IRB/IEC approvals and of the IRB/IEC compliance with ICH harmonised tripartite 
guideline E6(R2): Good Clinical Practice (GCP) will be maintained by the site and will be 
available for review by Kiniksa Pharmaceutical or its designee. 
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All IRB/IEC approvals should be signed by the IRB/IEC chairman or designee and must 
identify the IRB/IEC name and address, the clinical protocol by title or protocol number or 
both, and the date approval or a favorable opinion was granted. 
The Investigator is responsible for providing written summaries of the progress and status of 
the study at intervals not exceeding 1 year or otherwise specified by the IRB/IEC. The 
Investigator must promptly supply Kiniksa Pharmaceutical or its designee, the IRB/IEC, and, 
where applicable, the institution, with written reports on any changes significantly affecting 
the conduct of the study or increasing the risk to subjects. 
9.2. 
Ethical Conduct of the Study 
The study will be performed in accordance with the ethical principles that have their origin in 
the Declaration of Helsinki, ICH GCP, the protocol, and all applicable regulations. 
9.3. 
Subject Information and Consent 
A written informed consent in compliance approved by an IRB/IEC, as appropriate, at each 
center/country shall be obtained from each subject before entering the study or performing 
any unusual or nonroutine procedure that involves risk to the subject. An informed consent 
for (or assent form, as applicable) template may be provided by Kiniksa Pharmaceutical or its 
designee to investigative sites. If any institution-specific modifications to study-related 
procedures are proposed or made by the site, the consent should be reviewed by Kiniksa 
Pharmaceutical or its designee or both before IRB/IEC submission. Once reviewed, the 
consent will be submitted by the Investigator to his or her IRB/IEC for review and approval 
before the start of the study. If the ICF is revised during the course of the study, all active 
participating subjects must sign the revised form. 
Before screening, each prospective subject or his or her legal guardian will be given a full 
explanation of the study and be allowed to read the approved ICF. Once the Investigator is 
assured that the subject/legal guardian understands the implications of participating in the 
study, the subject/legal guardian will be asked to give consent to participate in the study by 
signing the ICF. 
It should be emphasized to the subjects that they may withdraw from the study at any time 
and for any reason without prejudice to their future medical care by the Investigator or at the 
study site. Subjects who refuse to give or who withdraw written informed consent should not 
be included or continue in the study. 
For potential subjects under the age of 18, a parent or legal guardian is required to sign and 
date the ICF and the potential subject is also required to sign and date an informed assent 
form. The informed assent form explains the trial, it’s purpose, procedures as well as risk and 
benefits in age-appropriate language. Both the ICF and informed assent form, as applicable, 
are required prior to participation in the trial. The Investigator shall retain the signed original 
ICF(s)/assent form(s), as applicable, and give a copy of the signed original form to the 
subject or legal guardian. 
For this study, subjects will be required to sign and date the ICF (or assent form, if 
applicable) prior to entry to the study and prior to entry to LTE. 
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In addition, a separate ICF (assent, if applicable) will be needed for subjects participating in 
pharmacogenomic testing or the MRI sub-study. 
10. 
INVESTIGATOR’S OBLIGATIONS 
The following administrative items are meant to guide the Investigator in the conduct of the 
study but may be subject to change based on local or country-specific industry and 
government standard operating procedures, working practice documents, or guidelines. 
10.1. 
Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records will be identified in a 
manner designed to maintain subject confidentiality. All records will be kept in a secure 
storage area with limited access. Clinical information will not be released without the written 
permission of the subject (or the subject’s legal guardian), except as necessary for monitoring 
and auditing by Kiniksa Pharmaceuticals, its designee, the regulatory agencies/authorities, or 
the IRB/IEC. 
The Investigator and all employees and co-workers involved with this study may not disclose 
or use for any purpose other than performance of the study any data, record, or other 
unpublished, confidential information disclosed to those individuals for the purpose of the 
study. Prior written agreement from Kiniksa Pharmaceuticals or its designee must be 
obtained for the disclosure of any said confidential information to other parties. 
10.2. 
Financial Disclosure and Obligations 
Investigators are required to provide financial disclosure information to allow Kiniksa 
Pharmaceuticals or its designee to submit the complete and accurate certification or 
disclosure statements required under US Title 21 Code of Federal Regulations (CFR) Part 54. 
In addition, the Investigator must provide to Kiniksa Pharmaceuticals a commitment to 
promptly update this information if any relevant changes occur during the course of the 
investigation and for 1 year following the completion of the study. 
Neither Kiniksa Pharmaceuticals nor 
is financially responsible for further testing or 
treatment of any medical condition that may be detected during the screening process. In 
addition, in the absence of specific arrangements, neither Kiniksa Pharmaceuticals nor 
is financially responsible for further treatment of the subject’s disease. 
10.3. 
Investigator Documentation 
Prior to beginning the study, the Investigator will be asked to comply with ICH E6(R2) 8.2 
and Title 21 of the CFR by providing the following essential documents, including but not 
limited to: 
• 
• 
IRB/IEC approval 
Original Investigator-signed Investigator agreement page of the protocol 
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• Form FDA 1572, fully executed, and all updates on a new fully executed Form 
FDA 1572 or local country-specific equivalent for outside the US 
Curriculum vitae for the Investigator and each sub-Investigator listed on Form 
FDA 1572 or local country-specific equivalent for outside the US 
Financial disclosure information 
IRB/IEC-approved ICFs/assent forms, as applicable, samples of site 
advertisements for recruitment for this study, and any other written information 
regarding this study that is to be provided to the subject or legal guardian 
Laboratory certifications and normal ranges for any local laboratories used by the 
site, in accordance with 42 CFR 493 
• 
• 
• 
• 
10.4. 
Study Conduct 
The Investigator agrees that the study will be conducted according to the principles of ICH 
E6(R2). The Investigator will conduct all aspects of this study in accordance with all 
national, state, and local laws or regulations. Study information from this protocol will be 
posted on publicly available clinical trial registers before enrollment of subjects begins. 
10.5. 
Adherence to Protocol 
The Investigator agrees to conduct the study as outlined in this protocol in accordance with 
ICH E6(R2) and all applicable guidelines and regulations. 
10.6. 
Adverse Events and Study Report Requirements 
By participating in this study, the Investigator agrees to submit reports of SAEs to 
and/or IRB/IEC according to the time line and method outlined in the protocol and as per 
local requirements. In addition, the Investigator agrees to submit annual reports to the study 
site IRB/IEC as appropriate. 
10.7. 
Investigator’s Final Report 
Upon completion of the study, the Investigator, where applicable, should inform the 
institution; the Investigator/institution should provide the IRB/IEC with a summary of the 
study’s outcome and Kiniksa Pharmaceuticals and regulatory authority(ies) with any reports 
required. 
10.8. 
Records Retention 
It is the responsibility of the Investigator to ensure all essential trial documentation and 
source records (e.g., signed ICFs, study site/clinic files, subjects’ hospital notes, copies of 
eCRFs) at their site are securely retained. The Sponsor will inform the Investigator of the 
time periods for retaining study records to comply with all applicable regulatory 
requirements. The minimum retention time will meet the strictest standard applicable to that 
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site for the study, as dictated by any institutional requirements or local laws or regulations; 
otherwise, the retention period by default will be 15 years. 
10.9. 
Publications 
. Investigators are encouraged to 
participate in the study execution such that they may be invited to participate in the 
authorship of a potential publication in a manner commensurate with their participation in the 
study execution in accordance with International Committee of Medicinal Journal Editors 
standards. Any publication of the results will be subject to the terms and conditions provided 
in the study agreement. 
11. 
STUDY MANAGEMENT 
The administrative structure will include a Data Monitoring Committee (DMC) and a 
Clinical Endpoint Committee (CEC). Please refer to Section 6.7 for further details. 
11.1. 
11.1.1. 
Monitoring 
Monitoring of the Study 
Data for each subject will be recorded in source records and in the eCRF. Data collection 
must be completed for each subject who signs an ICF. 
For each subject enrolled, the Investigator or designee will document in the source records of 
the subject that the subject is enrolled in this study along with all safety and efficacy 
information. The Investigator is responsible for maintaining adequate case histories in the 
source records of each subject. Source data should be preserved for the maximum period of 
time permitted by the hospital/institution and made available by the Investigator in the cases 
described above. 
In accordance with current GCP and ICH guidelines, the study monitor will carry out source 
document verification at regular intervals to ensure that the data collected in the eCRF are 
accurate and reliable. 
11.1.2. 
Inspection of Records 
Investigators and institutions involved in the study will permit study-related monitoring, 
audits, IRB/IEC review, and regulatory inspections by providing direct access to all study 
records. In the event of an audit, the Investigator agrees to allow Kiniksa Pharmaceuticals, 
representatives of Kiniksa Pharmaceuticals, or a regulatory agency(ies) access to all study 
records. 
The Investigator should promptly notify Kiniksa Pharmaceuticals and 
of any audits 
scheduled by any regulatory authorities and promptly forward copies of any audit reports 
received to Kiniksa Pharmaceuticals and 
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11.2. 
11.2.1. 
Management of Protocol Amendments and Deviations 
Modification of the Protocol 
Sponsor initiated amendments to the protocol must be submitted in writing to the 
Investigator’s IRB/IEC for approval and to the regulatory authorities, if required, before 
subjects can be enrolled into an amended protocol. 
11.2.2. 
Protocol Deviations 
A deviation from the protocol is any change, divergence, or departure from the study design 
or procedures defined in the protocol. No waivers will be granted for exemptions to 
inclusion/exclusion criteria. The Investigator will conduct the study in compliance with the 
protocol agreed to with the Sponsor and, if required, the regulatory authorities, and which 
was given approval/favorable opinion by the IRB/IEC. In the event of a protocol deviation, 
the Sponsor or a designee must be notified. 
The Investigator, or person designated by the Investigator, must document and explain any 
deviation from the approved protocol. The Investigator will notify the IRB/IEC of deviations 
from the protocol in accordance with local procedures. 
11.3. 
Study Termination 
The Sponsor has the right to terminate the study at any time due to the following reasons: 
• New information leading to unfavorable risk-benefit judgment of the study drug, 
for example, due to occurrence of significant previously unknown adverse 
reactions or unexpectedly high intensity or incidence of known adverse reactions, 
or other unfavorable safety findings; 
Sponsor’s decision that continuation of the study is unjustifiable for medical or 
ethical reasons; 
Discontinuation of the study drug development program by the Sponsor. 
• 
• 
Health Authorities and Independent Ethics Committees (IECs)/Institutional Review Boards 
(IRBs) will be informed about the termination of the trial in accordance with applicable 
regulations. 
The whole trial may be terminated or suspended upon request of Health Authorities. 
11.4. 
Final Report 
Whether the study is completed or prematurely terminated, Kiniksa Pharmaceutical will 
ensure that the clinical study report(s) are prepared and provided to the regulatory 
agency(ies) as required by the applicable regulatory requirement(s). The Sponsor will also 
ensure that the clinical study reports in marketing applications meet the standards of the ICH 
harmonised tripartite guideline E3: Structure and content of clinical study reports. 
Where required by applicable regulatory requirements, an Investigator signatory will be 
identified to approve the clinical study report. The Investigator will be provided reasonable 
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access to statistical tables, figures, and relevant reports and will have the opportunity to 
review the complete study results. 
Upon completion of the clinical study report, Kiniksa Pharmaceutical will provide the 
Investigator(s) with the full summary of the study results. The Investigator(s) are encouraged 
to share the summary results with the study subjects, as appropriate. The study results will be 
posted on publicly available clinical trial registers, as applicable. 
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12. 
REFERENCE LIST 
Adler Y, Charron P, Imazio M, et al. 2015 ESC Guidelines for the diagnosis and management 
of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial 
Diseases of the European Society of Cardiology (ESC) Endorsed by: The European 
Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2015;36(42):2921-2964. 
Agarwal SK, Vallurupalli S, Uretsky BF, et al. Effectiveness of colchicine for the prevention 
of recurrent pericarditis and post-pericardiotomy syndrome: an updated meta-analysis of 
randomized clinical data. Eur Heart J Cardiovasc Pharmacother. 2015;1(2):117-125. 
Baskar S, Klein AL, Zeft A. The use of IL-1 receptor antagonist (anakinra) in idiopathic 
recurrent pericarditis: A narrative review. Cardiol Res Pract. 2016;2016:7840724. 
Brucato A, Imazio M, Gattorno M, et al. Effect of anakinra on recurrent pericarditis among 
patients with colchicine resistance and corticosteroid dependence: The AIRTRIP randomized 
clinical trial. JAMA. 2016;316(18):1906-1912. 
Cantarini L, Lopalco G, Selmi C, et al. Autoimmunity and autoinflammation as the yin and 
yang of idiopathic recurrent acute pericarditis. Autoimmun Rev. 2015;14(2):90-97. 
Dinarello CA, Simon A, van der Meer JW. Treating inflammation by blocking interleukin-1 
in a broad spectrum of diseases. Nat. Rev. Drug Discov. 2012; 11(8):633-652. 
Dworkin RH, Turk DC, Farrar JT, et al. Core outcome measures for chronic pain clinical 
trials: IMMPACT recommendations. Pain. 2005;113(1-2):9-19. 
Garg M, de Jesus AA, Chapelle D, et al. Rilonacept maintains long-term inflammatory 
remission in patients with deficiency of the IL-1 receptor antagonist. JCI Insight. 
2017;2(16):e94838. 
Goldbach-Mansky R, Shroff S, Wilson M, et al. A pilot study to evaluate the safety and 
efficacy of the long-acting IL-1 inhibitor, rilonacept (IL-1 Trap) in patients with familial cold 
autoinflammatory syndrome (FCAS). Arthritis Rheum. 2008;58(8):2432-2442. 
Guy W. Clinical global impressions. In: U.S. Department of Health, Education, and Welfare, 
Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, NIMH 
Psychopharmacology Research Branch, Division of Extramural Research Programs, eds. 
ECDEU Assessment Manual for Psychopharmacology. Rockville, MD: National Institute for 
Mental Health; 1976:218–22. Revised DHEW Pub No ADM 76–338. 
Hawker GA, Mian S, Kendzerska T, et al. Measures of adult pain: visual analog scale for 
pain (VAS Pain), numeric rating scale for pain (NRS Pain), McGill Pain Questionnaire 
(MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), chronic pain grade scale (CPGS), 
Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant 
Osteoarthritis Pain (ICOAP). Arthritis Care Res. 2011;63(Suppl 11):S240-S252. 
Imazio M, Brucato A, Pluymaekers N, et al. Recurrent pericarditis in children and 
adolescents:a multicenter cohort study. J Cardiovasc Med 2016; 17(9):707-712. 
Imazio M. Treatment of recurrent pericarditis. Rev Esp Cardiol. 2014;67(5):345-348. 
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Clinical Study Protocol 
Imazio M, Spodick DH, Brucato A, et al. Controversial issues in the management of 
pericardial diseases. Circulation. 2010; 121(7):916-928. 
Imazio M, Brucato A, Trinchero R, et al. Corticosteroid therapy for pericarditis: a double- 
edged sword. Nature Clinical Practice Cardiovascular Medicine. 2008;5(3):118-119. 
Imazio M, Cecchi E, Demichelis B, et al. Myopericarditis versus viral or idiopathic acute 
pericarditis. Heart. 2008;94:498-501. 
Imazio M, Demichelis B, Parrini I, et al. Management, risk factors, and outcomes in recurrent 
pericarditis. Am J Cardiol. 2005;96(5):736-739. 
Khandaker MH, Espinosa RE, Nishimura RA, et al. Pericardial disease: diagnosis and 
management. Mayo Clin Proc. 2010; 85(6):572-593. 
Lazaros G, Imazio M, Brucato A, et al. Anakinra: an emerging option for refractory 
idiopathic recurrent pericarditis: a systematic review of published evidence. J Cardiovasc 
Med. 2016;17(4):256-262. 
Lilly SL. Treatment of acute and recurrent idiopathic pericarditis. Circulation. 
2013;127(16):1723-1726. 
Lotrionte M, Biondi-Zoccai G, Imazio M, et al. International collaborative systematic review 
of controlled clinical trials on pharmacologic treatments for acute pericarditis and its 
recurrences. Am Heart J. 2010; 160(4):662-670. 
Maisch B, Seferović PM, Ristić AD, et al. Guidelines on the diagnosis and management of 
pericardial diseases executive summary: The Task Force on the Diagnosis and Management 
of Pericardial Diseases of the European Society of Cardiology. Eur Heart J. 2004;25(7):587- 
610. 
Mannion AF, Balagué F, Pellisé F, et al. Pain measurement in patients with low back pain. 
Nat Clin Practice Rheumatol. 2007;3(11):610-618. 
Morin CM, Belleville G, Bélanger L, et al. The insomnia severity index: psychometric 
indicators to detect insomnia cases and evaluate treatment response. Sleep. 2011;34(5):601- 
608. 
Theodoropoulou K, von Scheven-Gête A, Bressieux-Degueldre S, et al. A case of 
corticosteroid-dependent recurrent pericarditis with different response to two IL-1 blocking 
agents. Pediatr Rheumatol Online J. 2015;13(Suppl 1):P155. 
van Reenen M, Janssen B. EQ-5D-5L User Guide. Version 2.1. April 2015. Available from: 
https://euroqol.org/wp-content/uploads/2016/09/EQ-5D-5L_UserGuide_2015.pdf. 
Zayas R, Anguita M, Torres F, et al. Incidence of specific etiology and role of methods for specific 
etiologic diagnosis of primary acute pericarditis. Am J Cardiol. 1995;75(5):378-382. 
Version 3.0; 10 March 2020 
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Rilonacept (KPL-914) 
Study KPL-914-C002 
Kiniksa Pharmaceuticals, Ltd 
Clinical Study Protocol 
13. 
13.1. 
APPENDICES 
Study Schedule of Activities 
Table 2: 
Study Schedule of Activities – Screening and Run In Period 
Version 3.0; 10 March 2020 
Page 87 of 97 
Page 519 
Trial Period 
SCREENINGa 
 
RUN-IN (12 weeks)m 
 
ENROLLMENT 
 
 
RANDOMIZATION 
-q 
Visit Name 
 
Screening 
Visit 
RI 
Baseline 
RI 
Day 2 
RI 
Day 4 
RI 
Week 1 
RI 
Week 2 
RI 
Week 4 
RI 
Week 6 
RI 
Week 10 
RI Week 12/ 
RW Baseline 
Visit Windowb (days) 
(-28) 
NA 
NA 
+/- 1 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 3 
Visit Type 
Clinic 
Clinic 
Clinic 
TC/RN 
TC/RN 
TC/RN 
TC/RN 
Clinic 
TC 
Clinic 
Informed Consent Form 
X 
 
 
 
 
 
 
 
 
 
Inclusion and Exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Medical/Surgical History 
X 
 
 
 
 
 
 
 
 
 
Pericarditits Diagnosis & 
History 
X 
 
X 
 
 
 
 
 
 
 
 
 
Concomitant medications 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
Pericarditis Concomitant 
medications 
X 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Pericarditis Concomitant 
medication tapering 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Full Physical Examinationc 
X 
 
 
 
 
 
 
 
 
 
Abbreviated Physical 
Examinationd 
 
X 
 
 
 
 
 
 
 
 
X 
 
Body weight and height 
 
X 
 
 
 
 
 
 
 
X 
12-Lead ECG 
 
X 
 
 
 
 
 
 
 
X 
Echoe 
 
Xe 
 
 
 
 
 
 
 
Xe 
MRI (substudy only) 
 
X 
 
 
 
 
 
 
 
 
 
 
 


Rilonacept (KPL-914) 
Study KPL-914-C002 
Kiniksa Pharmaceuticals, Ltd 
Clinical Study Protocol 
Version 3.0; 10 March 2020 
Page 88 of 97 
Page 520 
Trial Period 
SCREENINGa 
 
RUN-IN (12 weeks)m 
 
ENROLLMENT 
 
 
RANDOMIZATION 
-q 
Visit Name 
 
Screening 
Visit 
RI 
Baseline 
RI 
Day 2 
RI 
Day 4 
RI 
Week 1 
RI 
Week 2 
RI 
Week 4 
RI 
Week 6 
RI 
Week 10 
RI Week 12/ 
RW Baseline 
Visit Windowb (days) 
(-28) 
NA 
NA 
+/- 1 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 3 
Visit Type 
Clinic 
Clinic 
Clinic 
TC/RN 
TC/RN 
TC/RN 
TC/RN 
Clinic 
TC 
Clinic 
Pericardial pain (11-point NRS) 
Xf 
DAILYg 
Xg 
EQ-5D 
 
X 
 
 
 
 
 
 
 
X 
SF-36 
 
X 
 
 
 
 
 
 
 
X 
ISI 
 
X 
 
 
 
 
 
 
 
X 
PGIPS 
 
X 
 
 
 
 
 
X 
 
X 
PGA-PA 
 
X 
 
 
 
 
 
X 
 
X 
Hematology, Chemistry Labs 
(Central) 
 
X 
 
 
 
 
 
 
X 
 
 
X 
 
Lipid Panel (Central)h 
 
X 
 
 
 
 
 
 
 
X 
CRP (Local) 
Xf 
 
 
 
 
 
 
 
 
X 
CRP (Central) 
(X) 
X 
 
X 
X 
X 
X 
X 
 
X 
Hematology, Chemistry, 
IGRAr, hepatitis serology, HIV 
(Local) 
X 
 
 
 
 
 
 
 
 
 
 
Chest X-Ray 
X 
 
 
 
 
 
 
 
 
 
Urine Pregnancy (Local or 
Central)j 
X 
 
X 
 
 
 
 
 
 
 
 
 
Urinalysis (Central) 
 
X 
 
 
 
 
 
 
 
 
PK (Central)s 
 
 
Xi 
 
X 
X 
X 
 
 
 
ADA (Central)s 
 
X 
 
 
 
X 
 
X 
 
 
Biomarkers (Central) 
 
X 
 
 
X 
 
X 
 
 
 
Pharmacogenomics Informed 
Consentk 
 
X 
 
 
 
 
 
 
 
 
 
Pharmacogenomics Sampling 
(Central)k 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 


Rilonacept (KPL-914) 
Study KPL-914-C002 
Kiniksa Pharmaceuticals, Ltd 
Clinical Study Protocol 
a 
b 
c 
The screening and enrollment visit can be combined. 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Full physical examination includes at minimum evaluation of vital signs, head, eye, ear, nose, and throat as well as cardiovascular, dermatological, musculoskeletal, 
respiratory, GI, genitourinary, and neurological systems. The decision to perform examination of genitourinary system should be guided by clinical judgement. 
Abbreviated physical examination includes at minimum evaluation of vital signs, lung and heart sounds, including evaluation for pericardial rub. 
ECHO is required to be obtained according to the central core lab parameters and then read locally and submitted to the central core lab for separate review and analysis. 
Both a documented CRP > 1.0 mg/dL AND a pericarditis pain level of > 4 is required 7 days prior to and including the Run-In Baseline visit. These are not required to occur 
on the same day. 
Subjects missing ≥ 4 daily pain measurements during the 7 days prior to and including the Randomization Withdrawal baseline visit will be unable to proceed to 
randomization due to lack of data required for treatment response evaluation. 
Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the randomization withdrawal and LTE periods, or more frequently as needed, with 
mandated evaluations as detailed in the schedule of events. 
Applicable to 24-hour post dose PK sub-study participants only. 
For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout the course of the study and serum pregnancy can be drawn as needed; 
urine pregnancy is required to be performed at enrollment and 6 weeks after the last dose of study drug. 
Pharmacogenomics informed consent and subsequent sampling can be performed at any time in the study however, it is preferable to have this completed at the beginning of 
the study. 
d 
e 
f 
g 
h 
i 
j 
k 
Version 3.0; 10 March 2020 
Page 89 of 97 
Page 521 
Trial Period 
SCREENINGa 
 
RUN-IN (12 weeks)m 
 
ENROLLMENT 
 
 
RANDOMIZATION 
-q 
Visit Name 
 
Screening 
Visit 
RI 
Baseline 
RI 
Day 2 
RI 
Day 4 
RI 
Week 1 
RI 
Week 2 
RI 
Week 4 
RI 
Week 6 
RI 
Week 10 
RI Week 12/ 
RW Baseline 
Visit Windowb (days) 
(-28) 
NA 
NA 
+/- 1 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 3 
Visit Type 
Clinic 
Clinic 
Clinic 
TC/RN 
TC/RN 
TC/RN 
TC/RN 
Clinic 
TC 
Clinic 
IWRS Subject Status Update 
X 
X 
 
 
 
 
 
 
 
X 
IWRS Weight Input (pediatric 
only) 
 
X 
 
 
 
 
 
 
 
 
X 
 
IWRS Drug Dispensing 
 
X 
 
X 
 
 
 
X 
 
X 
In Clinic Study Drug 
Administrationo 
 
Xn 
 
 
 
 
 
 
X 
 
 
X 
 
Outpatient Study Drug 
Administrationo 
 
 
 
 
WEEKLY 
 
Study Drug Compliance 
Review 
 
X 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Clinical Response Evaluation 
 
 
 
 
 
 
 
 
 
Xp 
Adverse Event Reportingl 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 


Rilonacept (KPL-914) 
Study KPL-914-C002 
Kiniksa Pharmaceuticals, Ltd 
Clinical Study Protocol 
l 
m 
n 
Adverse event reporting begins following the subject providing informed consent. 
All procedures are to be completed prior to study drug administration. 
The first dose of study drug is a loading dose. Adult subjects receive 2 SC doses 160 mg (total 320 mg); pediatric subjects (subjects ≥12 and <18 years of age) receive 2 SC 
doses of 2 x 2.2 mg/kg. 
Study drug administration is once weekly with a minimum of 5 days required between doses. 
Randomization and subsequent study drug dispensing to occur after confirmation of Clinical Response (see definition of Clinical Response in Section 6.2.2). 
The Randomization visit serves as both the RI Week 12 visit and the RW baseline visit. 
PK and ADA samples will be collected prior to study drug administration. PK at enrollment/baseline will be taken from ADA 
o 
p 
q 
s 
Version 3.0; 10 March 2020 
Page 90 of 97 
Page 522 
 
 
 


Rilonacept (KPL-914) 
Study KPL-914-C002 
Kiniksa Pharmaceuticals, Ltd 
Clinical Study Protocol 
Table 3: 
Study Schedule of Activities – Randomized Withdrawal 
Version 3.0; 10 March 2020 
Page 91 of 97 
Page 523 
Trial Period 
RANDOMIZED WITHDRAWAL (event-driven)m 
 
 
END OF 
RANDOMIZED 
WITHDRAWAL 
(EORW)t 
 
Visit Name 
 
RW 
Week 4 
 
RW 
Week 8 
 
RW 
Week 12 
 
RW 
Week 16 
 
RW 
Week 20 
 
RW 
Week 24 
 
RW 
Every 8 
Weeks 
 
RW 
Every 
8 
Weeks 
Per Announced 
End Dateu/ 
LTE-Baseline 
 
Visit Windowb (days) 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 7 
Visit Type 
TC/RN 
Clinic 
TC/RN 
Clinic 
TC/RN 
Clinic 
TC/RN 
Clinic 
Clinic 
Informed Consent Form 
 
 
 
 
 
 
 
 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pericarditis Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Full Physical Examinationc 
 
 
 
 
 
X 
 
 
X 
Abbreviated Physical Examinationd 
 
 
 
 
 
 
 
 
 
Body weight and height 
 
X 
 
X 
 
X 
 
X 
X 
12-Lead ECG 
 
 
 
 
 
X 
 
 
X 
Echoe 
 
 
 
 
 
Xe 
 
 
Xe 
MRI (substudy only) 
 
 
 
 
 
X 
 
 
 
Pericardial pain (11-point NRS) 
DAILY 
EQ-5D 
 
 
 
 
 
X 
 
 
X 
SF-36 
 
 
 
 
 
X 
 
 
X 
ISI 
 
 
 
 
 
X 
 
 
X 
PGIPS 
 
X 
 
X 
 
X 
 
X 
X 
PGA-PA 
 
X 
 
X 
 
X 
 
X 
X 
Hematology, Chemistry Labs (Central) 
 
X 
 
 
 
X 
 
X 
X 
Lipid Panel (Central)h 
 
 
 
 
 
X 
 
 
X 
CRP (Local) 
 
 
 
 
 
 
 
 
 
 
 
 


Rilonacept (KPL-914) 
Study KPL-914-C002 
Kiniksa Pharmaceuticals, Ltd 
Clinical Study Protocol 
b 
c 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to subject evaluation and study drug treatment. 
Full physical examination includes at minimum evaluation of vital signs, head, eye, ear, nose, and throat as well as cardiovascular, dermatological, musculoskeletal, 
respiratory, GI, genitourinary, and neurological systems. The decision to perform examination of genitourinary system should be guided by clinical judgement. 
Abbreviated physical examination includes at minimum evaluation of vital signs, lung and heart sounds, including evaluation for pericardial rub. 
ECHO is required to be obtained according to the central core lab parameters and then read locally and submitted to the central core lab for separate review and analysis. 
Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the randomization withdrawal and LTE periods, or more frequently as needed, with 
mandated evaluations as detailed in the schedule of events. 
d 
e 
h 
Version 3.0; 10 March 2020 
Page 92 of 97 
Page 524 
Trial Period 
RANDOMIZED WITHDRAWAL (event-driven)m 
 
 
END OF 
RANDOMIZED 
WITHDRAWAL 
(EORW)t 
 
Visit Name 
 
RW 
Week 4 
 
RW 
Week 8 
 
RW 
Week 12 
 
RW 
Week 16 
 
RW 
Week 20 
 
RW 
Week 24 
 
RW 
Every 8 
Weeks 
 
RW 
Every 
8 
Weeks 
Per Announced 
End Dateu/ 
LTE-Baseline 
 
Visit Windowb (days) 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 2 
+/- 7 
Visit Type 
TC/RN 
Clinic 
TC/RN 
Clinic 
TC/RN 
Clinic 
TC/RN 
Clinic 
Clinic 
CRP(Central 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PK (Central)s 
 
X 
 
 
 
X 
 
 
X 
ADA (Central)s 
 
 
 
 
 
X 
 
 
X 
Biomarkers (Central) 
 
X 
 
 
 
X 
 
 
 
Urine Pregnancyj (Local or Central) 
 
 
 
 
 
 
 
 
X 
Urinalysis 
 
 
 
 
 
 
 
 
X 
IWRS Subject Status Update 
 
 
 
 
 
 
 
 
X 
IWRS Weight Input (pediatric only) 
 
X 
 
X 
 
X 
 
X 
X 
IWRS Drug Dispensing 
 
X 
 
X 
 
X 
 
X 
Xv 
In Clinic Study Drug Administrationo 
 
X 
 
X 
 
X 
 
X 
Xv 
Outpatient Study Drug Administrationo 
X 
WEEKLY 
Study Drug Compliance Review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assessment of Pericarditis Recurrence 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Event Reportingl 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 


Rilonacept (KPL-914) 
Study KPL-914-C002 
Kiniksa Pharmaceuticals, Ltd 
Clinical Study Protocol 
j 
For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout the course of the study and serum pregnancy can be drawn as needed; 
urine pregnancy is required to be performed at enrollment and 6 weeks after the last dose of study drug. 
Adverse event reporting begins following the subject providing informed consent. 
All procedures are to be completed prior to study drug administration. 
Study drug administration is once weekly with a minimum of 5 days required between doses. 
PK and ADA samples will be collected prior to study drug administration. PK at enrollment/baseline will be taken from ADA. As required, ADA samples will be collected at 
EOS, ET, and Unscheduled visits. 
The EORW visit serves as both the last visit of the RW period and the baseline visit of the LTE period. 
For all subjects, the final clinic visit of the end of RW period is to be scheduled once the End of the Randomization Withdrawal end date is announced by Sponsor. This 
includes subjects that are taking blinded study drug, open-label rilonacept, or who have prematurely discontinued study drug. 
Study drug administration to occur only after subject provides informed consent for the open-label extension period. 
l 
m 
o 
s 
t 
u 
v 
Version 3.0; 10 March 2020 
Page 93 of 97 
Page 525 
 
 
 


Rilonacept (KPL-914) 
Study KPL-914-C002 
Kiniksa Pharmaceuticals, Ltd 
Clinical Study Protocol 
Table 4: 
Study Schedule of Activities – Long Term Extension Treatment Period 
Version 3.0; 10 March 2020 
Page 94 of 97 
Page 526 
Trial Period 
LONG TERM EXTENSION (up to 24 months) 
 
Long Term Extension Treatment (up to 24 Months)m 
Visit Name 
 
LTE 
Week 12 
 
LTE 
Week 24 
 
LTE 
Every 12 
Weeks 
LTE 18- 
month 
Assessmentaa 
Visit Windowb (days) 
+/- 2 
+/- 2 
+/- 2 
+/- 45 
Visit Type 
Clinic 
Clinic 
Clinic 
Clinic 
Concomitant medications 
X 
X 
X 
X 
Pericarditis Concomitant medications 
X 
X 
X 
X 
Full Physical Examinationc 
 
X 
 
X 
12-Lead ECG 
 
X 
 
X 
Echoe 
 
X 
 
X 
MRI 
 
Xz 
 
Xz 
EQ-5D 
 
X 
 
 
SF-36 
 
X 
 
 
ISI 
 
X 
 
 
PGIPS 
X 
X 
X 
 
PGA-PA 
X 
X 
X 
 
Hematology, Chemistry Labs (Central) 
X 
X 
X 
 
Lipid Panel (Central)h 
 
X 
 
 
CRP (Central) 
X 
X 
X 
X 
PK (Central)s 
 
X 
 
X 
ADA (Central)s 
 
X 
Xbb 
 
Biomarkers (Central) 
 
X 
 
 
Urine Pregnancyj (Local or Central) 
 
X 
 
X 
Urinalysis 
 
X 
 
 
IWRS Subject Status Update 
 
X 
 
X 
IWRS Weight Input (pediatric only) 
X 
 
X 
X 
IWRS Drug Dispensing 
X 
X 
X 
X 
In Clinic Study Drug Administrationo 
X 
X 
X 
 
Outpatient Study Drug Administrationo 
WEEKLY 
Study Drug Compliance Review 
X 
X 
X 
X 
Assessment of Pericarditis Recurrence 
X 
X 
X 
X 
Adverse Event Reportingl 
X 
X 
X 
X 
 
 
 


Rilonacept (KPL-914) 
Study KPL-914-C002 
Kiniksa Pharmaceuticals, Ltd 
Clinical Study Protocol 
a 
b 
The screening and enrollment visit can be combined. 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to 
subject evaluation and study drug treatment. 
Full physical examination includes at minimum evaluation of vital signs, head, eye, ear, nose, and throat as 
well as cardiovascular, dermatological, musculoskeletal, respiratory, GI, genitourinary, and neurological 
systems. The decision to perform examination of genitourinary system should be guided by clinical 
judgement. 
ECHO is required to be obtained according to the central core lab parameters and then read locally and 
submitted to the central core lab for separate review and analysis. 
Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the randomization 
withdrawal and LTE periods, or more frequently as needed, with mandated evaluations as detailed in the 
schedule of events. 
For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout the 
course of the study and serum pregnancy can be drawn as needed; urine pregnancy is required to be 
performed at enrollment and 6 weeks after the last dose of study drug. 
Adverse event reporting begins following the subject providing informed consent. 
All procedures are to be completed prior to study drug administration. 
Study drug administration is once weekly with a minimum of 5 days required between doses. 
PK and ADA samples will be collected prior to study drug administration. PK at enrollment/baseline will 
be taken from ADA. As required, ADA samples will be collected at EOS, ET, and Unscheduled visits. 
The MRI to occur only if the previous MRI was done longer than 6 months ago. 
Visit to occur 18 months from most recent documented recurrence. 
Samples collected every 24 weeks. 
c 
e 
h 
j 
l 
m 
o 
s 
z 
aa 
bb 
Table 5: 
Study Schedule of Activities – Supplemental Visits 
Version 3.0; 10 March 2020 
Page 95 of 97 
Page 527 
Visit Name 
 
PERICARDITIS 
RECURRENCE 
ASSESSMENT 
 
END of 
TREATMENT 
(EOT)x 
 
SAFETY FOLLOW 
UP (SFU)y 
(6 weeks post last 
dose) 
Visit Windowb (days) 
N/A 
N/A 
+/- 2 
Visit Type 
Clinic 
Clinic 
Clinic or TC/RN 
Concomitant medications 
X 
X 
X 
Pericarditis Concomitant 
medications 
X 
 
X 
 
X 
 
Full Physical Examinationc 
 
X 
 
Abbreviated Physical Examinationd 
X 
 
 
Body weight and height 
X 
 
 
12-Lead ECG 
X 
X 
 
Echoe 
Xe 
X 
 
MRI (substudy only) 
 
Xz 
 
Pericardial pain (11-point NRS) 
X 
X 
 
EQ-5D 
X 
X 
 
SF-36 
X 
X 
 
 
 
 


Rilonacept (KPL-914) 
Study KPL-914-C002 
Kiniksa Pharmaceuticals, Ltd 
Clinical Study Protocol 
b 
Scheduling of visits within visit windows requires cautious planning to ensure there is no interruption to 
subject evaluation and study drug treatment. 
Lipid panels are non-fasting and are to be drawn at a minimum of every 6months during the randomization 
withdrawal and LTE periods, or more frequently as needed, with mandated evaluations as detailed in the 
schedule of events. 
For women of child bearing potential - urine pregnancy testing can be repeated as needed throughout the 
course of the study and serum pregnancy can be drawn as needed; urine pregnancy is required to be 
performed at enrollment and 6 weeks after the last dose of study drug. 
Adverse event reporting begins following the subject providing informed consent. 
PK and ADA samples will be collected prior to study drug administration. PK at enrollment/baseline will 
be taken from ADA. 
An EOT visit is to be conducted throughout the course of the study when a subject permanently 
discontinues study drug. 
An SFU is required to be conducted within 6 weeks of the last dose of rilonacept at any time throughout the 
course of the study including the RI period, the RW period, and the LTE period. 
The MRI to occur only if the previous MRI was done longer than 6 months ago. 
h 
j 
l 
s 
x 
y 
z 
Version 3.0; 10 March 2020 
Page 96 of 97 
Page 528 
Visit Name 
 
PERICARDITIS 
RECURRENCE 
ASSESSMENT 
 
END of 
TREATMENT 
(EOT)x 
 
SAFETY FOLLOW 
UP (SFU)y 
(6 weeks post last 
dose) 
Visit Windowb (days) 
N/A 
N/A 
+/- 2 
Visit Type 
Clinic 
Clinic 
Clinic or TC/RN 
ISI 
X 
X 
 
PGIPS 
X 
X 
 
PGA-PA 
X 
X 
 
Hematology, Chemistry Labs 
(Central) 
 
X 
 
 
Lipid Panel (Central)h 
 
X 
 
CRP (Local) 
X 
 
 
CRP(Central 
X 
X 
 
PK (Central)s 
X 
X 
X 
ADA (Central)s 
X 
X 
X 
Biomarkers (Central) 
X 
X 
 
Urine Pregnancyj (Local or Central) 
 
 
X 
Urinalysis 
 
X 
 
IWRS Subject Status Update 
Xs 
X 
 
IWRS Weight Input (pediatric only) 
X 
 
 
IWRS Drug Dispensing 
X 
 
 
Study Drug Compliance Review 
X 
X 
 
Assessment of Pericarditis 
Recurrence 
X 
 
X 
 
X 
 
Adverse Event Reportingl 
X 
X 
X 
 
 
 


Rilonacept (KPL-914) 
Study KPL-914-C002 
Kiniksa Pharmaceuticals, Ltd 
Clinical Study Protocol 
13.2. 
Appendix: 11-point Numerical Rating Scale (NRS) for Assessment 
of Pericarditis Pain 
Subjects will be asked to select the score that best describes their average level of pericarditis 
pain over the previous 24 hours using an 11-point NRS, where zero (0) indicates ‘no pain’ 
and ten (10) means indicates ‘pain as bad as it could be’. 
13.3. 
Summary of Changes 
This summary of changes document has been prepared to summarize changes to clinical 
protocol study KPL-914-C002 Amendment 2 (Version 3.0) when compared with the 
previous amendment (Version 2.0) dated 12 April 2019. The primary reason for this protocol 
amendment is to increase the ability to assess impact of length of treatment. A summary of 
the major protocol changes is described below including a rationale for change. In addition, 
the presentation of content was revised according to the Sponsor’s template; no changes to 
the content of the study were altered as a result of this change unless otherwise specified 
below. 
Version 3.0; 10 March 2020 
Page 97 of 97 
Page 529 
Section(s) 
Impacted 
Protocol Change 
 
Reason for Change 
 
Global 
 
Primary efficacy endpoint analysis 
triggered at 22 CEC events. 
Requirement for a full 24 weeks 
follow-up dropped for all subjects. 
Study powered for time to event; 
increased enrolment ensures safety 
exposures are adequate. 
 
Global 
 
LTE extended to 24 months. 
Observation follow-up dropped. 
Provide longer access to study drug for 
study participants. 
Global 
 
Other minor administrative and 
editorial changes were made 
throughout the protocol. 
Provided for consistency and clarification 
purposes.