An Open-Label Pilot Study of KPL-914 in Recurrent Pericarditis
Phase: PHASE2
Conditions: Recurrent Pericarditis
Sponsor: Kiniksa Pharmaceuticals (UK), Ltd.

KPL-914-C001 Protocol and Amendments 
16.1.1 Protocol and Amendments  .........................................................................................................
Original Protocol: 25 September 2017 .........................................................................................
Protocol Version 2: 17 January 2018 .........................................................................................
Protocol Version 3: 14 February 2018 .....................................................................................
Protocol Version 4: 19 February 2019 .....................................................................................
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3 Synopsis 
Trial Number: 
KPL-914-C001 
Trial Title: 
An open-label, pilot study of KPL-914 in symptomatic recurrent idiopathic pericarditis 
Trial Centers: 
Approximately 15 sites in the United States 
Development Phase: 2 
Objective(s): 
Primary: 
To collect inter- and intra-subject variability data on C-reactive protein (CRP) measurements and the 
11-point Numerical Rating Scale (NRS) instrument for assessment of pericardial pain in subjects with
recurrent idiopathic pericarditis (RIP) both at baseline and on treatment with KPL-914 in order to
inform power calculations for future trials in RIP.
Secondary: 
To explore the time course to improvement of pericarditis parameters in symptomatic patients with RIP 
treated with KPL-914. 
To evaluate the safety of KPL-914 in symptomatic patients with RIP. 
Methodology: 
This is an open-label single-active-arm pilot study to explore clinical and biochemical endpoints of 
improvement of pericarditis symptomatology and to collect inter- and intra-subject variability data on 
both at-baseline and on-treatment parameters in symptomatic patients with RIP who will be treated with 
once-weekly subcutaneously (SC)-administered injections of KPL-914.   
Patients identified for participation in this trial will present during a symptomatic episode of RIP, 
having previously experienced a first (index) episode of acute pericarditis followed by at least 1 
recurrent episode before the current enrollment-qualifying episode, using the 2015 European Society of 
Cardiology (ESC) Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 
2015) as a frame of reference: 
-
The index episode of acute pericarditis would have been characterized by an inflammatory
pericardial syndrome with at least 2 of the 4 following criteria: pericarditic chest pain, pericardial
rub, new widespread ST-segment elevation or PR-segment depression on electrocardiogram
(ECG), and pericardial effusion (new or worsening).  Additional supportive findings would have
included elevations of markers of inflammation (i.e., CRP, erythrocyte sedimentation rate [ESR],
and white blood cell [WBC] count) or evidence of pericardial inflammation by an imaging
technique (e.g., magnetic resonance imaging [MRI]).
-
Recurrence of RIP would have been characterized as a subsequent episode of pericarditis
occurring after a symptom-free interval of 4-6 weeks or longer.
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For the purposes of this study, the Investigator will determine, based on his/her judgement of the 
available data, if a subject has met these criteria for having experienced a previous index episode of 
acute pericarditis followed by at least 1 recurrent episode of pericarditis prior to the presenting 
symptomatic episode of RIP and will record the criteria supporting this diagnosis in the electronic case 
report form (eCRF). 
Study subjects will be enrolled (Screening Visit 1 [SCV1]) at the time of a symptomatic episode.  In 
addition to meeting the criteria for pericarditis in the judgement of the Investigator, all subjects must 
present with a CRP value ≥1 mg/dL at the time of study enrollment.  Subjects included in the study may 
be receiving concomitant nonsteroidal anti-inflammatory drugs (NSAIDs), and/or colchicine, and/or 
oral corticosteroid treatment in any combination, provided the dosages of these medications have been 
stable for at least 7 days, although stable doses for at least 3 days will be acceptable if in the opinion of 
the Investigator, in consultation with the Sponsor, a shorter period of stability is not anticipated to alter 
the baseline CRP values.  
Baseline therapy and disease characteristics will be determined during a Screening Period of up to 
72 hours, as needed, to confirm the pre-treatment diagnostic workup.  At the SCV1, baseline patient 
and disease characteristics will be determined and captured in the eCRF.  Persistence of diagnostic 
criteria for pericarditis will be confirmed (Screening Visit 2 [SCV2]) within the 24 - 72 hour period 
before subjects advance to the Treatment Period of the study. Under special circumstances, the 
Investigator, in consultation with the Sponsor, can combine SCV1 and SCV2, and the subject can 
proceed directly to the Day 0 dosing visit. 
Approximately 10 subjects will participate in the active Treatment Period of the study.  Following 
review of the ongoing data by the Sponsor and the Investigators, the sample size may be increased to a 
total of up to 20 subjects. After having met all the entry criteria during the Screening Period, the 
subjects entering the Treatment Period will receive a loading dose of KPL-914 (2 x 160 mg SC) on Day 
0, then 160 mg SC weekly for 5 additional doses.  
The first Study Drug dose on Day 0 will be administered at the Study Site/Clinic (Visit 1).  Subsequent 
weekly Study Drug doses from Weeks 2 to 5 will be self-administered by the patient as an outpatient 
SC administration. A visiting study nurse will assess and record compliance with Study Drug 
administration at the subject’s home as well as provide guidance and training on Study Drug 
administration as needed. At Week 6/End of Trial, Study Drug may be self-administered or 
administered at the study site.  Weekly assessments of safety and treatment response, including 
administration of the 11-point NRS instrument to assess pericardial pain, will be done at the Study 
Site/Clinic at Visit 1 (Day 0) and Visit 7 (Week 6/End-of-Trial), and via Investigator (or designee) 
phone calls/ virtual visits at Weeks 2 to 5 (Visits 2 to 5). Weekly outpatient blood samples for central 
laboratory testing will be collected at the Study Site/Clinic, or at a qualified laboratory site in the 
vicinity of the patient, or by a visiting study nurse. 
Investigators are encouraged to schedule subjects at the Study Site/Clinic for an in-person Interval 
Evaluation Visit during approximately Weeks 3-4 to assist the Investigator in the clinical management 
of the subject.  During this visit a full assessment including physical examination, vital signs, ECG, 
echocardiogram, and laboratory testing can be performed as well as the recording of adverse events 
(AEs) and other study-related assessments as needed.   
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At any time point during the Treatment Period, subjects reporting worsening of pericarditis symptoms 
or AEs may be brought into the Study Site/Clinic at the discretion of the Investigator for an 
Unscheduled Visit, in which select or comprehensive clinical assessments can be performed.  Any 
subject who is determined by the Investigator as not responding to treatment (e.g., no reduction in 
pericardial pain compared to baseline, no decrease in CRP levels, etc.) and who is therefore considered 
by the Investigator to be a “Treatment Failure” may be withdrawn from further Study Drug treatment at 
the discretion of the Investigator and may receive rescue therapy for their pericarditis according to 
standard of care as per Investigator decision; these subjects will be followed for safety for the 
remainder of the 6-week Treatment Period.  Subjects identified as “Treatment Failures” may be 
replaced at the discretion of the Sponsor in order to provide an adequate sampling of subjects 
completing the active Treatment Period. 
Subjects participating for the complete length of the active study Treatment Period will receive a total 
of 6 doses of KPL-914.  For the duration of the Treatment Period, concomitant NSAIDs and/or 
colchicine and/or corticosteroids, if present, should be continued at pre-study dose levels until after the 
6-dose Study Drug Treatment Period has concluded; however, should the Investigator determine that a
reduction/tapering of the NSAID, colchicine, and/or corticosteroid dose is medically indicated, the
NSAID, colchicine, and/or corticosteroid dose can be down-titrated in consultation with the Sponsor,
and the modification of dose should be recorded in the source records and the eCRF.
Opioid analgesics, non-narcotic analgesics (e.g., tramadol), and acetaminophen are allowed as rescue 
medication for ancillary pain control on an as-needed basis throughout the Treatment Period.  Although 
it is recommended that NSAID dose levels (if present) should remain constant during the active 
Treatment Period, the concomitant NSAID dose may be temporarily increased (or an NSAID initiated) 
for ancillary pain control if deemed necessary by the Investigator, after consultation with the Sponsor. 
Any rescue medication use must be recorded in source records, eCRF, and medication diary.  
At the discretion of the Investigator, “Treatment Responders” (defined by the Investigator as a 
clinically significant reduction in pericardial pain using the 11-point NRS, normal or near-normal CRP 
levels, and/or absent or decreasing echocardiographic effusion at the End-of-Trial Visit), will be offered 
participation in an optional 18-week Extension Period (EP), in which weekly open-label KPL-914 
administration can be continued at the same dose as in the Treatment Period for a total duration of 
Study Drug treatment of up to 24 weeks. Weekly Study Drug administrations during the EP are by self-
administration, and study nurse visits to the patient’s home as well as Investigator (or designee) 
telephone calls/virtual visits are to continue on a monthly basis. 
During the EP, the Investigator may choose to wean concomitant NSAIDs, colchicine, and/or 
corticosteroids according to standard of care paradigms; all medication changes must be recorded in 
source records and the eCRF.  Investigators are encouraged to schedule subjects at the Study Site/Clinic 
for an in-person Interval Evaluation Visit between Weeks 15 to 20 (8 to 13 weeks after the Week 7 
Visit) to assist the Investigator in the clinical management of the subject.  During this visit a physical 
examination, vital signs, ECG, echocardiogram (ECHO), and laboratory testing can be performed at the 
discretion of the Investigator. 
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Available safety, tolerability, and efficacy data for each subject will be reviewed by the Investigator as 
part of ongoing patient management.  A Safety Review Committee (SRC) including selected 
Investigator(s) and Sponsor representatives will review on a monthly basis (at a minimum) all available 
data for all subjects, considering trends across each.  
Given the following occurrences, dosing may be halted or reduced, in accordance with an SRC 
recommendation, confirmed by the Sponsor: 
- 
One or more subjects experience a serious and unexpected adverse event that is considered by 
the Investigator to be related to Study Drug (SUSAR), or 2 or more subjects experience similar 
severe (non-serious) and unexpected AEs that are considered by the Investigator to be related to 
Study Drug. 
After an initial group of subjects has been treated, depending on the safety profile observed as well as 
the magnitude and speed of treatment response (e.g., if an informative number of subjects achieve 
treatment response early in the Treatment Period), the Sponsor in collaboration with the Investigators 
may elect to decrease the KPL-914 dose administered to a subsequent consecutive group of subjects to 
a loading dose of 2 x 80 mg administered SC on Day 0, then 80 mg administered SC weekly for 5 
additional weeks, in order to explore efficacy at a lower dose.  Depending on treatment response 
observed with the 80 mg dose, the weekly dose administered to either these subjects or subsequent 
subjects may be changed back to 160 mg by the Investigator in collaboration with the Sponsor.  For any 
given subject, the KPL-914 dose level received at the end of the Treatment Period should be continued 
into the EP (if administration is continued); however, a change in the KPL-914 dose level during the EP 
for any individual subject can be made at the discretion of the Investigator in consultation with the 
Sponsor, and the modification of dose should be recorded in the source records and the eCRF. 
During the Screening and Treatment Periods, subjects will enter information concerning the use of 
pericarditis and rescue (pain) medication into a medication diary.  Such information will be entered by 
the subject on a daily basis. 
Number of Patients: 
Approximately 10 symptomatic patients with RIP will be enrolled as study subjects.  Following review 
of the available data, the Sponsor, in collaboration with the Investigators, may increase the sample size 
to up to 20 subjects to address additional hypotheses. 
Subjects who discontinue the study (withdrawals and Treatment Failures) may be replaced at the 
Sponsor’s discretion in order to provide an adequate sampling of subjects completing the active 
Treatment Period. 
 
Diagnosis and Main Criteria for Inclusion: 
Inclusion Criteria 
To be eligible to participate in the trial, a patient must meet all of the following criteria: 
1. Has given consent and signed an Informed Consent Form (ICF). 
2. Male or female, of any ethnic origin. 
3. 18 to 70 years of age, inclusive. 
4. Has had a prior index episode of pericarditis which, in the judgement of the Investigator based on 
the available data, met the criteria for an acute pericarditis event, using the 2015 ESC Guidelines 
for the Diagnosis and Management of Pericardial Diseases (Adler et al, 2015) as a frame of 
reference --  i.e., met at least 2 of the 4 following criteria: pericarditic chest pain, pericardial rub, 
new widespread ST-segment elevation or PR-segment depression on ECG, and pericardial 
effusion (new or worsening).  Additional supportive findings could include elevations of markers 
of inflammation (i.e., CRP, erythrocyte sedimentation rate, and white blood cell count) or 
evidence of pericardial inflammation by an imaging technique (e.g., MRI). 
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5. Has had at least one prior recurrent episode of pericarditis, in the judgement of the Investigator, 
based upon the available diagnostic information. 
6. Has an ongoing symptomatic episode of pericarditis at the time of study enrollment in the 
judgement of the Investigator, based upon the available diagnostic information. 
7. Has an elevated CRP value (i.e., >1 mg/dL) at the time of study enrollment. 
8. If used, has received NSAIDs, and/or colchicine and/or corticosteroids (in any combination) at 
stable dose levels for at least 7 days (although stable doses for at least 3 days will be acceptable if 
in the opinion of the Investigator, in consultation with the Sponsor, a shorter period of stability is 
not anticipated to alter the baseline CRP values) and is anticipated to continue these concomitant 
medications at these dose levels for the duration of the active Treatment Period.  
9. If female, must be nonpregnant and nonlactating and must agree to use an effective method of 
contraception, e.g., hormonal contraception or double-barrier birth control.  
10. Is able to adequately maintain a daily medication diary. 
11. Agrees to refrain from making any new, major life-style changes that may affect pericarditis 
symptoms (e.g., starting a new diet or changing exercise pattern) from the time of signature of the 
ICF to the End-of-Trial Visit (Week 7). 
Exclusion Criteria 
A patient who meets any of the following criteria will not be eligible to participate in the trial: 
1. Has a diagnosis of pericarditis that was secondary to specific etiologies, including tuberculous, 
neoplastic, or purulent etiologies, post cardiac injury syndromes, myocarditis, or systemic 
diseases including autoinflammatory diseases, autoimmune diseases (e.g., rheumatoid arthritis, 
systemic lupus erythematosus, etc.). 
2. Has a history of immunodepression, including a positive human immunodeficiency virus test 
result. 
3. Has received treatment with any systemic immunosuppressants (other than, for example, 
corticosteroids or mycophenolate) which, in the opinion of the Investigator (in consultation with 
the Sponsor), may interfere with the study endpoints within the 6-month period before dosing.  
4. Currently receiving other interleukin (IL)-1 or IL-6 blockers, janus-activating kinase (JAK) or 
tumor necrosis factor (TNF) inhibitors. 
5. Has a history of myeloproliferative disorder, demyelinating disease, or symptoms suggestive of 
multiple sclerosis. 
6. Female patient who is pregnant or lactating or who does not agree to use an effective method of 
contraception, e.g., hormonal contraception or double-barrier birth control. 
7. Has a history of active or latent treated tuberculosis (TB), or had a positive QuantiFERON (QFT-
TB G In-Tube) test result, or a chest radiograph during the 3 months prior to Study Drug dosing 
suggestive of prior TB infection. A patient with a positive purified protein derivative (PPD) test 
result (≥5-mm induration) after the first attack of pericarditis is excluded unless he/she has had 
either a negative chest x-ray result or a negative QuantiFERON test result. 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, night sweats) upon review of medical history and/or 
physical exam.  Have recent close contact with a person with active TB.  
8. Chest radiograph (or historic results within 3 months of SCV1) that shows evidence of 
malignancy or any abnormalities suggestive of prior TB infection, including, but not limited to, 
apical scarring, apical fibrosis, or multiple calcified granulomata.  This does not include non-
caseating granulomata. 
9. Has received immunization with a live (attenuated) vaccine within 12 weeks before the start of 
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the study. 
10. Has history of or positive or intermediate results for hepatitis B surface antigen (HBsAg),
hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at SCV1.
11. Has an estimated glomerular filtration rate (eGFR) <30 mL/min.
12. Has a history of malignancy of any organ system within the past 5 years (other than a
successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or
localized carcinoma in situ of the cervix).
13. 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.
14. Has had a serious infection, has been hospitalized for an infection, has been treated with oral
antibiotics within 2 weeks of Study Drug administration, or has been treated with intravenous
(IV) antibiotics for an infection within 2 months of first Study Drug administration.
15. Has had an organ transplant.
16. In the Investigator's judgement, has a history of alcoholism or drug/chemical abuse within 2 years
prior to Study Drug administration.
17. Has a drug screen positive for amphetamines, cocaine, or phencyclidine or positive alcohol test at
SCV1.  Exceptions may be made if a patient is on an approved medication for a stable
concomitant condition that explains the positive screen.
18. Has taken commercially-available rilonacept  (ARCALYST®) or participated in a rilonacept
clinical study during the 90 days before SCV1.  Has used anakinra within 30 days prior to Study
Drug administration.
19. Has a history of hypersensitivity to rilonacept or to any of the excipients contained in the Study
Drug.
20. Has received an investigational drug during the 30 days (or 5 half-lives, whichever is longer)
before SCV1 or is planning to receive an investigational drug (other than that administered during
this trial) or use an investigational device at any time during the trial.
21. In the Investigator's judgement, has any other medical condition that could adversely affect the
subject's participation or interfere with study evaluations.
22. Patient who, in the opinion of the Investigator, is not likely to be compliant with the study
protocol.
23. Patient who, in the opinion of the Investigator in consultation with the Sponsor, should not
participate in this study.
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Test Products, Dosage, and Mode of Administration: 
KPL-914 (rilonacept) will be provided in its commercially-available formulation as a lyophilized 
powder to be reconstituted for SC administration. 
KPL-914 will be administered as an initial loading dose of 2 x 160 mg SC on Day 0, then 160 mg SC 
dosed once weekly for 5 subsequent weeks.  After an initial group of subjects has been treated, 
depending on the safety profile observed as well as the magnitude and speed of treatment response 
(e.g., if an informative number of subjects achieve treatment response early in the Treatment Period), 
the Sponsor in collaboration with the Investigators may elect to decrease the KPL-914 dose 
administered to a subsequent consecutive group of subjects to a loading dose of 2 x 80 mg administered 
SC on Day 0, then 80 mg administered SC weekly for 5 additional weeks, in order to explore efficacy at 
a lower dose.  
Subjects will receive a total of 6 doses of KPL-914 during the study active Treatment Period.  Subjects 
who are considered to be “Treatment Responders” will be offered, at the discretion of the Investigator, 
participation in an optional 18-week Extension Period (EP), in which weekly open-label KPL-914 can 
be continued for a total duration of KPL-914 treatment of up to 24 weeks. 
Concomitant Medication 
•
There is no wash-out of concomitant therapy (NSAIDs/colchicine/corticosteroids) during the
Screening Period of the study.
•
For the duration of the Treatment Period, concomitant pericarditis medications (e.g., NSAIDs,
colchicine and corticosteroids), if used, should be continued at pre-study dose levels until after the
6-dose Study Drug Treatment Period has concluded; however, should the Investigator determine
that a reduction/tapering of the NSAIDs, colchicine, and/or corticosteroid dose is medically
necessary, the NSAID, colchicine and/or corticosteroid dose can be down-titrated according to
standard of care paradigms in consultation with the Sponsor, and the modification of dose should be
recorded in the source records and the eCRF.
•
Opioid analgesics, non-narcotic (non-NSAID) analgesics (e.g., tramadol), and acetaminophen are
allowed as rescue medication for ancillary pain control on an as needed basis throughout the
Treatment Period.  Although it is recommended that NSAID dose levels (if present) should remain
constant during the active Treatment Period, the concomitant NSAID dose may be temporarily
increased (or an NSAID initiated) for ancillary pain control if deemed necessary by the
Investigator, after consultation with the Sponsor.  Any rescue medication use must be recorded in
source records, the medication diary and the eCRF.
•
Medical management of pericarditis during the EP is based on Investigator discretion.  For
example, Investigators may continue subjects on KPL-914 at the same dosage level, wean-off or
discontinue Study Drug, or change (increase or decrease) the dosing of NSAIDs/colchicine/
corticosteroids.  Other pericarditis medications may also be initiated at the discretion of the
Investigator.  All changes to pericarditis-related medications should be captured in the source
records and eCRF.
•
Prohibited concomitant medicines: Other interleukin (IL)-1 or IL-6 blockers, janus-activating
kinase (JAK) or tumor necrosis factor (TNF) inhibitors.
Duration of Treatment: 
The Study Drug will be administered for 6 weeks in the base study Treatment Period. 
“Treatment Responders” will be offered participation in an optional 18-week EP at the discretion of the 
Investigator. 
Total subject participation is expected to last for up to 171 days for those that also participate in the 
18-week EP.
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Investigators are encouraged to schedule subjects at the Study Site/Clinic for an in-person 
Interval Evaluation Visit during approximately Weeks 3-4 to assist the Investigator in the 
clinical management of the subject.   
Subjects reporting worsening of pericarditis symptoms or AEs may be brought in for an 
unscheduled visit at the Study Site/Clinic at any time during the Treatment Period, at the 
discretion of the Investigator.  Any subject who is considered by the Investigator to be a 
“Treatment Failure” may be withdrawn from further Study Drug treatment at the discretion of 
the Investigator and receive rescue therapy for their pericarditis according to standard of care as 
per Investigator decision; these subjects will be followed for safety for the remainder of the 6-
week Treatment Period.  Subjects identified as “Treatment Failures” may be replaced at the 
discretion of the Sponsor in order to provide an adequate sampling of subjects completing the 
active Treatment Period. 
During the Treatment Period, subjects will continue documentation of pericarditis treatment 
medication use as well as rescue (pain) medication use in the medication diary.  Patient-
reported pericardial pain evaluations will be performed on-site at the Study Site/Clinic and by 
weekly Investigator (or designee) telephone calls/virtual visits using a validated 11-point NRS 
instrument.  A patient-reported QoL questionnaire will be administered at Visit 7 (Study 
Site/Clinic).  Weekly blood samples for central laboratory testing will be collected at the Study 
Site/Clinic or at a qualified laboratory site in the vicinity of the patient or by a visiting study 
nurse. 
 
3. Extension Period (EP): The EP is defined as the 18 weeks following the Treatment Period.  
Subjects who are considered to be “Treatment Responders” will be, at the discretion of the 
Investigator, offered participation in an optional 18-week EP, in which weekly administration 
of open-label KPL-914 may be continued for a total duration of 24 weeks.  The weekly KPL-
914 doses will be by self-administration, and study nurse visits to the patient’s home as well as 
Investigator (or designee) telephone calls/virtual visits  will continue on a monthly basis. 
During that EP, the Investigator may choose to change concomitant NSAID, colchicine, and/or 
corticosteroid treatment, recording all modifications in the source records and eCRF.  
Unscheduled clinic visits can be scheduled any time as determined by the Investigator/upon 
patient request. In addition, Investigators are encouraged to schedule subjects at the Study 
Site/Clinic for an in-person Interval Evaluation Visit between Weeks 15 to 20 (8 to 13 weeks 
after Visit 7) to assist the Investigator in the clinical management of the subject.  During this 
visit a physical examination, vital signs, ECG, echocardiogram, and laboratory testing can be 
performed. 
Patient-reported pericardial pain evaluations using a validated 11-point NRS instrument as well 
as AE monitoring will be performed during the EP at on-site clinic visits and/or during monthly 
Investigator (or designee) phone calls/virtual visits.  A patient-reported QoL questionnaire will 
be administered at the Interval Evaluation Visit and the Final Visit of the EP.  At the end of the 
EP, subjects will complete the Week 25/Final Visit.  
Statistical Methods: 
Analysis Populations 
The modified Intention to Treat (mITT) Population will consist of all subjects who received at least one 
dose of Study Drug.  The Per Protocol (PP) Population will consist of all subjects who received all 6 
doses of Study Drug during the active Treatment Period and were maintained at stable dose levels of 
concomitant pericarditis medications (e.g., NSAIDs, colchicine, corticosteroids) according to study 
protocol.  The Safety Population will be the same as the mITT Population. 
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Table 1: 
Schedule of Evaluations 
Trial Period → 
Run-In 
Period 
(Up to 3 days) 
Treatment Period 
(6 weeks) 
Extension Period 
(18 weeks) 
Visit Days/Weeks → 
Day -3 to 
Day 0a 
Day 0b 
Week 
2c 
Week 
3c 
W3-W4d 
Week 
4c 
Week 
5c 
Week 
6cc 
Week 6/ 
End-of-
Trialc 
 
 
W15-W20t 
Week 
25 
(Week 
7 +18 
weeks) 
Visit Number → 
SC 
Visit 
1 
SC 
Visit 
2 
Visit 1 
(Clinic) 
Visit 2 
(Outpt) 
Visit 3 
(Outpt)  
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 4 
(Outpt) 
Visit 5 
(Outpt) 
Visit 6 
(Outpt) 
Visit 7 
(Clinic) 
 Monthly 
Visits 
(Outpt) 
Un-
scheduled 
Visits 
(Clinic) 
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 8 
(Final, 
Clinic) 
Dose Number → 
 
 
Dose 1 
Dose 2 
Dose 3 
N/A 
Dose 4 
Dose 5 
Dose 6 
 
 
 
 
 
Trial Procedure ↓ 
 
 
 
Unscheduled Visitsu 
 
 
 
 
Signature of ICF 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion and exclusion 
criteria verification 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history e 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Drug admin. – On 
site f 
 
 
X 
 
 
 
 
 
 
(Xf) 
 
 
 
 
Study Drug admin. - 
Outpatient f 
 
 
 
X 
X 
 
X 
X 
X 
Xf 
X w 
(weekly) 
 
 
 
Physical examination g 
X 
X 
 
 
 
X  
 
 
 
X 
 
X 
X 
X 
Body weight and height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Vital Signs h 
X 
X 
 
 
 
X 
 
 
 
X 
 
X 
X 
X 
ECG/ECHO i 
X 
X 
(ECG) 
 
 
 
X 
 
 
 
X 
 
 
X 
X 
MRI j 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Prior and concomitant 
medicines k 
X 
X 
 
 
 
X 
 
 
 
X 
X  
X 
X 
X 
Drug and alcohol test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
QuantiFERON TB test  j 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Trial Period → 
Run-In 
Period 
(Up to 3 days) 
Treatment Period 
(6 weeks) 
Extension Period 
(18 weeks) 
Visit Days/Weeks → 
Day -3 to 
Day 0a 
Day 0b 
Week 
2c 
Week 
3c 
W3-W4d 
Week 
4c 
Week 
5c 
Week 
6cc 
Week 6/ 
End-of-
Trialc 
 
 
W15-W20t 
Week 
25 
(Week 
7 +18 
weeks) 
Visit Number → 
SC 
Visit 
1 
SC 
Visit 
2 
Visit 1 
(Clinic) 
Visit 2 
(Outpt) 
Visit 3 
(Outpt)  
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 4 
(Outpt) 
Visit 5 
(Outpt) 
Visit 6 
(Outpt) 
Visit 7 
(Clinic) 
 Monthly 
Visits 
(Outpt) 
Un-
scheduled 
Visits 
(Clinic) 
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 8 
(Final, 
Clinic) 
Dose Number → 
 
 
Dose 1 
Dose 2 
Dose 3 
N/A 
Dose 4 
Dose 5 
Dose 6 
 
 
 
 
 
Trial Procedure ↓ 
 
 
 
Unscheduled Visitsu 
 
 
 
 
Clinical laboratory tests 
(CRP)– Central 
laboratory l 
X 
X 
(X) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical laboratory tests 
– Study Site/Clinic  
laboratory l 
X 
X 
(X) 
 
 
X 
 
 
 
X 
 
X 
X 
X 
Biomarker testing, PK, 
and anti-rilonacept 
antibody m 
X 
 
(X) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy test n 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE evaluations o 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X  
X 
X 
X 
Medication diary 
dispensing p 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medication diary 
compliance verification 
and reminder q 
 
X 
(X) 
 
 
X 
 
 
 
X 
 
 
 
 
Pericardial pain (11-pt 
Numerical Rating Scale)r 
X 
X 
(X) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PGA (QoL 
questionnaire) s 
X 
 
(X) 
 
 
X 
 
 
 
X 
 
 
X 
X 
Investigator (or 
designee) phone 
call/virtual visitv 
 
 
 
X 
X 
 
X 
X 
X 
 
X 
(monthly) 
 
 
 
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ECHO = echocardiogram, ECG = electrocardiogram, ICF = informed consent form, MRI = magnetic resonance imaging, Outpt = outpatient, PGA = patient 
global assessment, pt = point, TB = tuberculosis, HBcAb = hepatitis B core antibody; HBsAb = hepatitis B surface antibody; HBsAg = hepatitis B surface 
antigen; HCVAb = hepatitis C virus antibody; HIV = human immunodeficiency virus 
a.
A second Screening visit (SCV2) should be performed within ~24h to 72h.  Under special circumstances, the Investigator, in consultation with the Sponsor,
can combine SCV1 and SCV2.  The last Screening and Day 0 procedures may be performed on the same day, but SCR procedures must be completed prior
to Study Drug administration.
b.
Subjects who do not complete the Treatment Period (withdraw consent or are discontinued before they have completed 6 weeks treatment), must be asked to
complete the procedures specified at the EoT Visit.
c.
Weekly intervals refer to 7 ± 1 days. The interval between Study Drug administrations must be at least 5 days.
d.
Subjects should return for an optional Interval Evaluation Visit at the clinic between approximately Week 3 and 4, as determined by the Investigator.
e.
Including age at first attack, number of previous attacks, and duration of attacks.
f.
Drug administration training of subjects is performed at Visit 1.  Study Drug will be administered in the Study Site/Clinic at Visit 1. Study Drug
administrations are performed by the subjects (self-administration) on Visits (Outpatient) 2, 3, 4, 5, and 6. Participation in the Extension Phase (optional) is
determined at the Week 6/EoT Visit 7 by the Investigator.  Subjects who are eligible and who are willing to participate will be consented during EoT Visit 7
at the Study Site/Clinic. Only subjects continuing treatment into the Extension Phase will receive Study Drug at Visit 7; Study Drug can be self-administered
either as an outpatient or at the Study Site/Clinic (Site to provide Study Drug) depending on the logistics/timing of the EoT Visit 7 relative to the timing of
weekly dosing. Timing for dose administration is per direction of the Investigator based upon the prescribing information and study-specified dosing
intervals. Continued weekly Study Drug treatment during the EP will be outpatient administration.
g.
Full physical examination including assessment of pericardial rub.
h.
Vital signs must be obtained in the seated position and include oral temperature, respiratory rate, blood pressure, and pulse.
i.
Central 12-lead ECG and echocardiogram reading (including assessment of pericardial effusion). At SCV2 only the ECG will be obtained. The Study
Site/Clinic reading of the ECG and the ECHO at the time of the examination will be used by the Investigator for clinical decision-making. In addition, both
the ECG and ECHO will be sent to a core laboratory for additional analysis.
j.
Optional.
k.
At the SCV1, information related to concomitant medicine that subjects were taking during at least the 2 weeks prior to the visit will be captured. During the
Treatment Period, changes in concomitant medication since the last Study Site/Clinic visit will be documented. During the EP, changes in
pericarditis/concomitant medication will be assessed at Study Site/Clinic Visits and in monthly outpatient phone calls/virtual visits.
l.
Hematology, chemistry, and urinalysis will be performed at the Study Site/Clinic laboratories, and results when available will be entered into the eCRF with
appropriate reference values. Serology (HCVAb, HBsAg, HBcAb, HBsAb and HIV) will be performed at SCV1 only. A Study Site/Clinic urine drug screen
will be performed at SCV1 only.  If SCV2 occurs at a different day than Visit 1 (Day 0), a sample for laboratory testing will also be taken at Visit 1, prior to
Study Drug treatment.  During each Visit at the Study Site/Clinic a sample for CRP will be obtained and sent to the central laboratory (or designated
qualified laboratory) for analysis; at each Outpatient Visit; blood for central laboratory measurement of CRP will be obtained as described in the Laboratory
Manual.
m. Biomarker and/or pharmacokinetics (PK) analysis samples will be drawn in all subjects and archived for future testing. If SCV2 occurs at a different day than
Visit 1 (Day 0), a sample for biomarker/PK testing will also be taken at Visit 1, prior to Study Drug treatment.  A blood sample to be archived for central
laboratory measurement of biomarkers and PK will be obtained as described in the Laboratory Manual.
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n.
To be eligible to continue in the trial, a negative urine pregnancy test must be documented at the SCV1. If the urine test is positive, additional Study
Site/Clinic and/or central serum tests may be performed.
o.
All AEs occurring after the subject receives the first dose of Study Drug will be captured in source records and eCRF.
p.
At the SCV1, the Investigator or designee will instruct the subject about the use of the medication diary.  The subject will be asked to complete an entry each
evening into the medication diary during the Screening Period and Treatment Period. Only information on pain/rescue medication will be collected. Other
concomitant treatments/medications are not required to be captured.
q.
At the SCV2 and all subsequent visits at the Study Center, the Investigator or designee will review the Diary entry information to verify patient compliance.
If the last screening visit occurs at a different day than Visit 1, the review will also be performed at Visit 1.  Diary documentation will end at the End-of-Trial
visit (Visit 7).
r.
Subject assessment of pericardial pain using a validated 11-point Numerical Rating Scale.  The assessment will be performed on-site during clinic visits and
as part of a telephone call/virtual visit during outpatient treatment weeks.  If the last screening visit occurs at a different day than Visit 1, the assessment will
also be performed at Visit 1, prior to Study Drug treatment.
s.
Subject global assessment of overall well-being will be assessed using a validated QoL Questionnaire (see Appendix 3). The assessment will be performed
on-site during clinic visits.  If SCV2 occurs at a different day than Visit 1 (Day 0), the global assessment will also be performed at Visit 1, prior to Study
Drug administration.
t.
Subjects may return for an optional EP Interval Evaluation Visit at the clinic between Week 15 and 20 (8 to 13 weeks after Visit 7), as determined by the
Investigator.
u.
Subjects reporting worsening of pericarditis symptoms or AEs may be brought in at the discretion of the Investigator for an Unscheduled Visit at any time
during the Treatment Period.  Any subject who is not responding to treatment (e.g., no reduction in pericardial pain compared to baseline, no decrease in CRP
levels, etc.) and who is therefore considered by the Investigator to be a “Treatment Failure” may be withdrawn from further Study Drug treatment at the
discretion of the Investigator and receive rescue therapy for their pericarditis according to standard of care as per Investigator decision; these subjects will be
followed for safety for the remainder of the 6-week Treatment Period.
v.
At weekly Investigator (or designee) phone calls/virtual visits during the Treatment Period, Study Drug compliance, medication diary compliance, and
laboratory sample collection will be checked. The subjects will be asked using non-leading questions about any AEs occurring since the last contact (phone
call/virtual visit or site visit), and NRS pain assessment will be performed.  Investigator (or designee) phone calls/virtual visits will be performed monthly
during the during the EP to perform NRS pain assessments, collect AE information, and review pericarditis/concomitant medications. If scheduled, in-person
Study Site/Clinic Visits (Unscheduled Visits or Evaluation Visits) can replace the phone calls/virtual visits.
w.
During the Extension Period, Study Drug treatment is weekly by self-administration, and the study nurse visits to the home and Investigator (or designee)
phone calls/virtual visits are monthly.
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4 Table of Contents 
1 
Protocol Approval Signatures ......................................................................................... 2 
1.1 
Sponsor Signature .......................................................................................................... 2 
2 
Investigator and Administrative Structure ...................................................................... 3 
3 
Synopsis ......................................................................................................................... 4 
4 
Table of Contents ......................................................................................................... 18 
5 
List of Abbreviations and Definition of Terms ............................................................... 21 
6 
Introduction ................................................................................................................. 23 
7 
Study Objectives ........................................................................................................... 25 
7.1 
Primary Objective ........................................................................................................ 25 
7.2 
Secondary Objective(s) ................................................................................................. 25 
8 
Investigational Plan ...................................................................................................... 26 
8.1 
Overall Study Design and Plan ...................................................................................... 26 
8.2 
Discussion of Study Design ............................................................................................ 29 
8.3 
Selection of Study Population ........................................................................................ 29 
8.3.1 
Number of Planned Subjects ........................................................................... 29 
8.3.2 
Inclusion Criteria ........................................................................................... 29 
8.3.3 
Exclusion Criteria .......................................................................................... 30 
8.3.4 
Vaccination History and Immune status ............................................................ 31 
8.3.5 
Removal of Subjects from Therapy or Assessments ........................................... 32 
8.4 
Investigational Medicinal Products................................................................................ 33 
8.4.1 
Investigational Medicinal Products Administered .............................................. 33 
8.4.2 
Identity of Investigational Medicinal Products ................................................... 34 
8.4.3 
Method of Assigning Subjects to Treatment Groups ........................................... 34 
8.4.4 
Selection of Doses in the Study ....................................................................... 34 
8.4.5 
Selection and Timing of Dose for Each Subject ................................................. 35 
8.4.6 
Blinding........................................................................................................ 35 
8.4.7 
Prior and Concomitant Therapy ....................................................................... 35 
8.4.8 
Treatment Compliance ................................................................................... 36 
8.5 
Study Procedures ......................................................................................................... 36 
8.5.1 
Screening Period ............................................................................................ 36 
8.5.1.1 
Screening Visit 1 (SCV1)................................................................................ 37 
8.5.1.2 
Screening Visit 2 (SCV2)................................................................................ 37 
8.5.2 
Treatment Period ........................................................................................... 38 
8.5.2.1 
Visit 1 (Study Site/Clinic) - Day 0 ................................................................... 38 
8.5.2.2 
Visits 2 to 6 (Outpatient) - Weeks 2, 3, 4, 5, 6 ................................................... 38 
8.5.2.3 
Interval Evaluation Visit (Study Site/Clinic) - Week 3-4 ..................................... 39 
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8.5.2.4 
Unscheduled Visits (Study Site/Clinic) During the Treatment Period ................... 39 
8.5.2.5 
Visit 7/ End-of-Trial (Study Site/Clinic) - Week 6 ............................................. 39 
8.5.3 
Extension Period ............................................................................................ 40 
8.5.3.1 
Unscheduled Visits (Study Site/Clinic) during the EP ......................................... 40 
8.5.3.2 
Interval Evaluation Visit During Extension Period (Study Site/Clinic) - 
Week 15-20................................................................................................... 41 
8.5.3.3 
Visit 8/Final Visit (Study Site/Clinic) - Week 25 ............................................... 41 
8.5.4 
Duration of Treatment .................................................................................... 42 
8.6 
Efficacy and Safety Variables ........................................................................................ 42 
8.6.1 
Individual Efficacy Assessments ...................................................................... 42 
8.6.1.1 
C-Reactive Protein, Biomarker, and PK Assessments ......................................... 42 
8.6.1.2 
Echocardiogram (Pericardial Effusion) ............................................................. 42 
8.6.1.3 
Electrocardiogram (Pericarditis Diagnostic Findings) ......................................... 43 
8.6.1.4 
Pericarditis Signs (Fever, Pericardial Rub) ........................................................ 43 
8.6.1.5 
Pericarditis Pain (Chest Pain) .......................................................................... 43 
8.6.1.6 
Magnetic Resonance Imaging .......................................................................... 44 
8.6.1.7 
Quality of Life Questionnaire .......................................................................... 44 
8.6.2 
Safety Assessments ........................................................................................ 45 
8.6.2.1 
Adverse Events .............................................................................................. 45 
8.6.2.2 
Serious Adverse Events .................................................................................. 46 
8.6.2.3 
Adverse Reactions ......................................................................................... 48 
8.6.2.4 
Clinical Laboratory Variables .......................................................................... 48 
8.6.2.5 
Other Laboratory Variables ............................................................................. 49 
8.6.2.6 
Vital Signs .................................................................................................... 50 
8.6.2.7 
Physical Examination ..................................................................................... 50 
8.6.2.8 
Body Weight and Height................................................................................. 50 
8.7 
Statistical Methods ....................................................................................................... 50 
8.7.1 
Statistical and Analytical Plans ........................................................................ 50 
8.7.1.1 
Datasets to be Analyzed .................................................................................. 50 
8.7.1.2 
General Statistical Methods ............................................................................. 50 
8.7.1.3 
Efficacy Endpoints ......................................................................................... 51 
8.7.1.4 
Safety Variables ............................................................................................ 51 
8.7.2 
Determination of Sample Size ......................................................................... 52 
8.8 
Quality Assurance and Quality Control ......................................................................... 52 
8.8.1 
Audit and Inspection ...................................................................................... 52 
8.8.2 
Monitoring .................................................................................................... 52 
8.8.3 
Data Management and Coding ......................................................................... 52 
8.8.4 
Record Keeping ............................................................................................. 53 
9 
Records and Supplies .................................................................................................... 53 
9.1 
Drug Accountability ..................................................................................................... 53 
10 
Ethics ........................................................................................................................... 53 
10.1 Institutional Review Board ........................................................................................... 53 
10.2 Ethical Conduct of the Study......................................................................................... 53 
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10.3 Subject Information and Consent .................................................................................. 54 
10.4 Subject Confidentiality (US Studies) .............................................................................. 54 
11 
Reporting and Publication ............................................................................................ 54 
12 
References .................................................................................................................... 55 
13 
Appendices ................................................................................................................... 57 
Appendix 1: Investigator Signature Page ................................................................................ 57 
Appendix 2: ARCALYST® Prescribing Information ............................................................... 58 
Appendix 3: Quality of Life Instrument .................................................................................. 59 
Appendix 4: 11-point Numerical Rating Scale (NRS) for Assessment of Pericarditis Pain ......... 61 
List of In-text Tables 
Table 1: 
Schedule of Evaluations .................................................................................. 14 
List of In-text Figures 
Figure 1: 
Schematic of KPL-914 (rilonacept) .................................................................. 24 
Figure 2: 
Overview of Trial Design................................................................................ 28 
Figure 3: 
11-point Numerical Rating Scale (NRS) for Assessment of Pericarditis Pain ......... 44 
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5 List of Abbreviations and Definition of Terms 
AcP 
accessory protein 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
BP 
blood pressure 
b.p.m.
beats per minute 
BUN 
blood urea nitrogen 
CAPS 
Cryopyrin Associated Periodic Syndrome 
CDC 
Centers for Disease Control 
CHO 
Chinese hamster ovary 
CI 
confidence interval 
CRO 
contract research organization 
CRP 
C-reactive protein
ECG 
electrocardiogram 
eCRF 
electronic case report form 
CTAD 
citrate, theophylline, adenosine, dipyridamole 
EoT 
End-of-Trial 
EP 
Extension Period 
ESC 
European Society of Cardiology 
ESR 
erythrocyte sedimentation rate 
FCAS 
Familial Cold Auto-Inflammatory Syndrome 
GCP 
Good Clinical Practice 
GGT 
gamma glutamyltransferase 
HBcAb 
hepatitis B core antibody 
HBsAb 
hepatitis B surface antibody 
HBsAg 
hepatitis B surface antigen 
HCVAb 
hepatitis C virus antibody 
HIV 
human immunodeficiency virus 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IgG 
immunoglobulin G 
IL-1 
Interleukin-1 
IL-1RA 
IL-1 receptor antagonist 
IL-1RI 
IL-1 type I receptor 
IMP 
Investigational Medicinal Product 
IRB 
Institutional Review Board 
IV 
intravenous 
kDa 
kilo Dalton 
KPL-914 
Study Drug; nomenclature of rilonacept (ARCALYST®) in this protocol 
LDH 
lactate dehydrogenase 
MCH 
mean cell hemoglobin 
MCHC 
MCH concentration 
MCV 
mean cell volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
magnetic resonance imaging 
mITT 
modified intent to treat 
MWS 
Muckle-Wells Syndrome 
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NRS 
Numerical Rating Scale 
NSAID 
nonsteroidal anti-inflammatory drugs 
PI 
Prescribing Information 
PP 
per protocol 
PPD 
purified protein derivative 
PRO 
patient-reported outcome 
PT 
prothrombin 
PTT 
prothrombin time 
QoL 
quality of life 
RBC 
red blood cell 
RIP 
recurrent idiopathic pericarditis 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SC 
subcutaneous 
SCR 
Safety Review Committee 
SCV 
screening visit 
SD 
standard deviation 
SOP 
standard operating procedure 
SRC 
Safety Review Committee 
SUSAR 
serious and unexpected and related adverse reaction 
TB 
tuberculosis 
 
 
TNF 
tumor necrosis factor 
US 
United States of America 
WBC 
white blood cells 
WHO 
World Health Organization 
WFI 
water for injection 
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and dose relationships will be assessed.  Commercially-available rilonacept (ARCALYST®) will be used in 
the study. 
The nonclinical development program for rilonacept (ARCALYST®) demonstrated biological activity and 
adequate safety across toxicity studies (Appendix 2: ARCALYST® Prescribing Information). 
The most common adverse reactions reported by patients with CAPS treated with ARCALYST® are 
injection-site reactions and upper respiratory tract infections.  Hypersensitivity reactions associated with 
rilonacept administration have been rare.  
Refer to the ARCALYST® PI for Important Safety Information regarding rilonacept (Appendix 2: 
ARCALYST® Prescribing Information).  
Based on its IL-1-antagonistic properties, its weekly-dosing pharmacokinetics, and its well-understood 
safety profile as shown in patients with CAPS, rilonacept (KPL-914) is a promising candidate for the 
treatment of RIP.  
 
7 Study Objectives 
7.1 
Primary Objective 
To collect inter- and intra-subject variability data on C-reactive protein (CRP) measurements and the 
11-point NRS instrument for assessment of pericardial pain in symptomatic subjects with recurrent 
idiopathic pericarditis (RIP) both at baseline and on treatment with KPL-914 in order to inform power 
calculations for future trials in RIP. 
7.2 
Secondary Objective(s) 
To explore the time course to improvement of pericarditis parameters in symptomatic patients with RIP 
treated with KPL-914. 
To evaluate the safety of KPL-914 in symptomatic patients with RIP. 
 
 
 
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8 Investigational Plan 
8.1 
Overall Study Design and Plan 
This is an open-label single-active-arm pilot study to explore clinical and biochemical endpoints of 
improvement of pericarditis symptomatology and to collect inter- and intra-subject variability data on both 
at-baseline and on-treatment parameters in symptomatic patients with RIP who will be treated with once-
weekly subcutaneously (SC)-administered injections of KPL-914.   
Patients identified for participation in this trial will present during a symptomatic episode of RIP, having 
previously experienced a first (index) episode of acute pericarditis followed by at least 1 recurrent episode 
before the current enrollment-qualifying episode, using the 2015 European Society of Cardiology (ESC) 
Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 2015) as a frame of 
reference: 
- 
The index episode of acute pericarditis would have been characterized by an inflammatory 
pericardial syndrome with at least 2 of the 4 following criteria: pericarditic chest pain, pericardial 
rub, new widespread ST-segment elevation or PR-segment depression on electrocardiogram (ECG), 
and pericardial effusion (new or worsening).  Additional supportive findings would have included 
elevations of markers of inflammation (i.e., CRP, erythrocyte sedimentation rate [ESR], and white 
blood cell [WBC] count) or evidence of pericardial inflammation by an imaging technique (e.g., 
magnetic resonance imaging [MRI]).   
- 
Recurrence of RIP would have been characterized as a subsequent episode of pericarditis occurring 
after a symptom-free interval of 4-6 weeks or longer.   
For the purposes of this study, the Investigator will determine, based on his/her judgement of the available 
data, if a subject has met these criteria for having experienced a previous index episode of acute pericarditis 
followed by at least 1 recurrent episode of pericarditis prior to the presenting symptomatic episode of RIP 
and will record the criteria supporting this diagnosis in the electronic case report form (eCRF). 
Study subjects will be enrolled (Screening Visit 1 [SCV1]) at the time of a symptomatic episode.  In addition 
to meeting the criteria for pericarditis in the judgement of the Investigator, all subjects must present with a 
CRP value ≥1 mg/dL at the time of study enrollment.  Subjects included in the study may be receiving 
concomitant nonsteroidal anti-inflammatory drugs (NSAIDs), and/or colchicine, and/or oral corticosteroid 
treatment in any combination, provided the dosages of these medications have been stable for at least 7 
days, although stable doses for at least 3 days will be acceptable if in the opinion of the Investigator, in 
consultation with the Sponsor, a shorter period of stability is not anticipated to alter the baseline CRP values.  
Baseline therapy and disease characteristics will be determined during a Screening Period of up to 72 hours, 
as needed, to confirm the pre-treatment diagnostic workup.  At the SCV1, baseline patient and disease 
characteristics will be determined and captured in the eCRF.  Persistence of diagnostic criteria for 
pericarditis will be confirmed (Screening Visit 2 [SCV2]) within the 24 - 72 hour period before subjects 
advance to the Treatment Period of the study. Under special circumstances, the Investigator, in consultation 
with the Sponsor, can combine SCV1 and SCV2, and the subject can proceed directly to the Day 0 dosing 
visit. 
Approximately 10 subjects will participate in the active Treatment Period of the study.  Following review 
of the ongoing data by the Sponsor and the Investigators, the sample size may be increased to a total of up 
to 20 subjects. After having met all the entry criteria during the Screening Period, the subjects entering the 
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Treatment Period will receive a loading dose of KPL-914 (2 x 160 mg SC) on Day 0, then 160 mg SC 
weekly for 5 additional doses.  
The first Study Drug dose on Day 0 will be administered at the Study Site/Clinic (Visit 1).  Subsequent 
weekly Study Drug doses from Weeks 2 to 5 will be self-administered by the patient as an outpatient SC 
administration. A visiting study nurse will assess and record compliance with Study Drug administration at 
the subject’s home as well as provide guidance and training on Study Drug administration as needed. At 
Week 6/End of Trial, Study Drug may be self-administered or administered at the study site.  Weekly 
assessments of safety and treatment response, including administration of the 11-point NRS instrument to 
assess pericardial pain, will be done at the Study Site/Clinic at Visit 1 (Day 0) and Visit 7 (Week 6/End-of-
Trial), and via Investigator (or designee) phone calls/ virtual visits at Weeks 2 to 5 (Visits 2 to 5). Weekly 
outpatient blood samples for central laboratory testing will be collected at the Study Site/Clinic, or at a 
qualified laboratory site in the vicinity of the patient, or by a visiting study nurse. 
Investigators are encouraged to schedule subjects at the Study Site/Clinic for an in-person Interval 
Evaluation Visit during approximately Weeks 3-4 to assist the Investigator in the clinical management of 
the subject.  During this visit a full assessment including physical examination, vital signs, ECG, 
echocardiogram, and laboratory testing can be performed as well as the recording of adverse events (AEs) 
and other study related assessments as needed.   
At any time point during the Treatment Period, subjects reporting worsening of pericarditis symptoms or 
AEs may be brought into the Study Site/Clinic at the discretion of the Investigator for an Unscheduled Visit, 
in which select or comprehensive clinical assessments can be performed.  Any subject who is determined 
by the Investigator as not responding to treatment (e.g., no reduction in pericardial pain compared to 
baseline, no decrease in CRP levels, etc.) and who is therefore considered by the Investigator to be a 
“Treatment Failure” may be withdrawn from further Study Drug treatment at the discretion of the 
Investigator and may receive rescue therapy for their pericarditis according to standard of care as per 
Investigator decision; these subjects will be followed for safety for the remainder of the 6-week Treatment 
Period.  Subjects identified as “Treatment Failures” may be replaced at the discretion of the Sponsor in order 
to provide an adequate sampling of subjects completing the active Treatment Period. 
Subjects participating for the complete length of the active study Treatment Period will receive a total of 6 
doses of KPL-914.  For the duration of the Treatment Period, concomitant NSAIDs and/or colchicine and/or 
corticosteroids, if present, should be continued at pre-study dose levels until after the 6-dose Study Drug 
Treatment Period has concluded; however, should the Investigator determine that a reduction/tapering of 
the NSAID, colchicine, and/or corticosteroid dose is medically indicated, the NSAID, colchicine, and/or 
corticosteroid dose can be down-titrated in consultation with the Sponsor, and the modification of dose 
should be recorded in the source records and the eCRF.  
Opioid analgesics, non-narcotic analgesics (e.g., tramadol), and acetaminophen are allowed as rescue 
medication for ancillary pain control on an as-needed basis throughout the Treatment Period.  Although it 
is recommended that NSAID dose levels (if present) should remain constant during the active Treatment 
Period, the concomitant NSAID dose may be temporarily increased (or an NSAID initiated) for ancillary 
pain control if deemed necessary by the Investigator, after consultation with the Sponsor. Any rescue 
medication use must be recorded in source records, eCRF and medication diary.  
At the discretion of the Investigator, “Treatment Responders” (defined by the Investigator as a clinically 
significant reduction in pericardial pain using the 11-point NRS, normal or near-normal CRP levels, and/or 
absent or decreasing echocardiographic effusion at the End-of-Trial Visit), will be offered participation in 
an optional 18-week Extension Period (EP), in which weekly open-label KPL-914 can be continued at the 
same dose as in the Treatment Period for a total duration of Study Drug treatment of up to 24 weeks. Weekly 
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7. Has an elevated CRP value (i.e., >1 mg/dL) at the time of study enrollment. 
8. If used, has received NSAIDs, and/or colchicine and/or corticosteroids (in any combination) at stable 
dose levels for at least 7 days prior to Study Drug dosing (although stable doses for at least 3 days will 
be acceptable if, in the opinion of the Investigator in consultation with the Sponsor, a shorter period of 
stability is not anticipated to alter the baseline CRP values) and is anticipated to continue these 
concomitant medications at these dose levels for the duration of the active Treatment Period.   
9. If female, must be nonpregnant and nonlactating and must agree to use an effective method of 
contraception, e.g., hormonal contraception or double-barrier birth control.  
10. Is able to adequately maintain a daily medication diary. 
11. Agrees to refrain from making any new, major life-style changes that may affect pericarditis 
symptoms (e.g., starting a new diet or change in exercise pattern) from the time of signature of the ICF 
to the End-of-Trial Visit (Week 7). 
8.3.3 
Exclusion Criteria 
A subject who meets any of the following criteria will not be eligible to participate in the trial: 
1. Has a diagnosis of pericarditis that was secondary to specific etiologies, including tuberculous, 
neoplastic, or purulent etiologies, post cardiac injury syndromes, myocarditis, or systemic diseases 
including autoinflammatory diseases, autoimmune diseases (e.g., rheumatoid arthritis, systemic 
lupus erythematosus, etc.). 
2. Has a history of immunodepression, including a positive human immunodeficiency virus test result. 
3. Has received treatment with any systemic immunosuppressants (other than, for example, 
corticosteroids or mycophenolate) which, in the opinion of the Investigator (in consultation with the 
Sponsor), may interfere with the study endpoints within the 6-month period before dosing.  
4. Currently receiving other interleukin (IL)-1 or IL-6 blockers, janus-activating kinase (JAK) or tumor 
necrosis factor (TNF) inhibitors. 
5. Has a history of myeloproliferative disorder, demyelinating disease, or symptoms suggestive of 
multiple sclerosis. 
6. Female patient who is pregnant or lactating or who does not agree to use an effective method of 
contraception, e.g., hormonal contraception or double-barrier birth control. 
7. Has a history of active or latent treated tuberculosis (TB), or had a positive QuantiFERON (QFT-TB 
G In-Tube) test result, or a chest radiograph during the 3 months prior to Study Drug dosing 
suggestive of prior TB infection. A patient with a positive purified protein derivative (PPD) test 
result (≥5-mm induration) after the first attack of pericarditis is excluded unless he/she has had 
either a negative chest x-ray result or a negative QuantiFERON test result. 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, night sweats) upon review of medical history and/or 
physical exam.  Have recent close contact with a person with active TB.  
8. Chest radiograph (or historic results within 3 months of SCV1) that shows evidence of malignancy 
or any abnormalities suggestive of prior TB infection, including, but not limited to, apical scarring, 
apical fibrosis, or multiple calcified granulomata.  This does not include non-caseating granulomata. 
9. Has received immunization with a live (attenuated) vaccine within 12 weeks before the start of the 
study. 
10. Has history of or positive or intermediate results for hepatitis B surface antigen (HBsAg), hepatitis 
B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at SCV1. 
11. Has an estimated glomerular filtration rate (eGFR) <30 mL/min.  
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12. Has a history of malignancy of any organ system within the past 5 years (other than a successfully 
treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma 
in situ of the cervix). 
13. 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. 
14. Has had a serious infection, has been hospitalized for an infection, has been treated with oral 
antibiotics within 2 weeks, or has been treated with IV antibiotics for an infection within 2 months 
of first Study Drug administration.  
15. Has had an organ transplant.  
16. In the Investigator's judgement, has a history of alcoholism or drug/chemical abuse within 2 years 
prior to Study Drug administration. 
17. Has a drug screen positive for amphetamines, cocaine, or phencyclidine or positive alcohol test at 
SCV1.  Exceptions may be made if a patient is on an approved medication for a stable concomitant 
condition that explains the positive screen. 
18. Has taken commercially-available rilonacept (ARCALYST®) or participated in a rilonacept clinical 
study during the 90 days before SCV1.  Has used anakinra within 30 days (or 5 half-lives, 
whichever is longer) prior to Study Drug administration. 
19. Has a history of hypersensitivity to rilonacept or to any of the excipients contained in the Study 
Drug. 
20. Has received an investigational drug during the 30 days before SCV1 or is planning to receive an 
investigational drug (other than that administered during this trial) or use an investigational device 
at any time during the trial. 
21. In the Investigator's judgement, has any other medical condition that could adversely affect the 
subject's participation or interfere with study evaluations.  
22. Patient who, in the opinion of the Investigator, is not likely to be compliant with the study protocol. 
23. Patient who, in the opinion of the Investigator in consultation with the Sponsor, should not 
participate in this study. 
 
8.3.4 
Vaccination History and Immune status 
IL-1 blockade may interfere with immune response to infections. Therefore, the Investigator should review 
with the subject the subject's vaccination history relative to the current medical guidelines for vaccine use.  
A recommended immunization schedule is available at the website of the Centers for Disease Control (CDC) 
(www.cdc.gov/vaccines/recs/scheduled/default.htm). 
It is recommended that, prior to or shortly after initiation of therapy with KPL-914, subjects be brought up 
to date with all vaccinations, as appropriate, including pneumococcal vaccine and inactivated influenza 
vaccine. In case a patient needs vaccination after initiation of KPL-914 treatment, vaccination with inactive 
vaccine(s) may be performed (e.g., at the Study Site/Clinic) after the 6-week active Treatment Period.  
However, to minimize the potential confounding of KPL-914-related Adverse Experience reporting at 
initiation of KPL-914 dosing or measurements of CRP during the treatment period, vaccination should not 
be performed within the first 6 weeks after initiation of KPL-914 administration.   
It is recommended that all vaccinations be documented as up-to-date at or shortly after Visit 7, at which 
point subjects are being considered for longer-term treatment with KPL-914.  
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Administration of KPL-914 is prohibited within 12 weeks of having received a live (attenuated) vaccine.  It 
is also possible that taking drugs that block IL-1 increases the risk of TB.  Healthcare providers should 
follow current CDC guidelines both to evaluate for and to treat possible latent TB infections before initiating 
therapy with KPL-914. 
8.3.5 
Removal of Subjects from Therapy or Assessments 
Subjects reporting worsening of pericarditis symptoms or AEs may be brought into the Study Site/Clinic at 
the discretion of the Investigator for an Unscheduled Visit at any time during the Treatment Period.  Any 
subject who is not responding to treatment (e.g., no reduction in pericardial pain compared to baseline, no 
decrease in CRP levels, etc.) and who is therefore considered by the Investigator to be a “Treatment Failure” 
may be withdrawn from further Study Drug treatment at the discretion of the Investigator and receive rescue 
therapy for their pericarditis according to standard of care as per Investigator decision; these subjects will 
be followed for safety for the remainder of the 6-week Treatment Period.  Subjects identified as “Treatment 
Failures” may be replaced at the discretion of the Sponsor in order to provide an adequate sampling of 
subjects completing the active Treatment Period. 
Safety, tolerability, and efficacy data for each subject will be reviewed by the Investigator on an ongoing 
basis as part of patient management.  An SRC including selected Investigator(s) and Sponsor representatives 
will review on a monthly basis (at a minimum) all available data for all subjects, considering trends across 
each.  
Given the following occurrences, dosing may be halted or or the dose reduced, in accordance with an SRC 
recommendation, confirmed by the Sponsor: 
• 
One or more subjects experience a serious and unexpected adverse event that is considered by the 
Investigator to be related to Study Drug (SUSAR), or 2 or more subjects experience similar severe 
(non-serious) and unexpected AEs that are considered by the Investigator to be related to Study 
Drug. 
In addition, subjects may stop study treatment or may be withdrawn from treatment for any of the following 
reasons: 
• 
Subject request.  Subjects are free to withdraw from the study at any time without providing 
reason(s) for withdrawal and without prejudice to further treatment 
• 
Use of non-permitted concurrent therapy 
• 
Non-compliance 
• 
Investigator request. 
Treatment Failures or subjects who are withdrawn from the study for safety reasons will be replaced at the 
discretion of the Sponsor.  Similarly, subjects who do not comply with the protocol or who withdraw from 
the study for other reasons can be replaced.  The reason(s) for withdrawal will be documented in the source 
records and the eCRF. 
Subjects withdrawing from the study during the Treatment Period will be asked to complete the End-of-
Trial evaluations to document the status of their pericarditis disease progression at the time of withdrawal 
from treatment.  Subjects will continue to be followed for vital status for the duration of intended treatment 
to address informative censoring.  Subjects withdrawing from the study during the EP will be asked to 
complete the Final Visit evaluations. 
All reasonable efforts will be made to contact subjects who are lost to follow-up.   
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The Sponsor has the right to terminate the study at any time in case of safety concerns (e.g., SUSARs) or if 
special circumstances concerning the Investigational Medicinal Product (IMP) 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. 
Pregnancy 
Pregnant or lactating female subjects are excluded from study enrollment.  While not explicitly stated in the 
rilonacept (ARCALYST®) PI (Appendix 2: ARCALYST® Prescribing Information), for the purposes of this 
experimental protocol, females of child-bearing potential (i.e., not postmenopausal and not sterilized) must 
use an active method of birth control during the course of the study, e.g., oral, implanted or injected 
contraceptive hormones, an intrauterine device, or a barrier method (e.g., diaphragm, condoms, 
spermicides).  
Subjects will be instructed that known or suspected pregnancy occurring during the study should be 
confirmed and reported to the Investigator without delay.  If pregnancy is confirmed, the Investigator must 
notify the Sponsor within 24 hours and the subject must not receive (additional) Study Drug and must be 
discharged from the study.  The subject must be asked regarding their willingness to complete the End-of-
Trial Visit. 
In the event that a subject is found to be pregnant after having received at least one Study Drug dose, the 
pregnancy will be followed to term and the status of mother and child will be reported to the Sponsor after 
delivery. 
Instances of perinatal death or congenital abnormality, if brought to the attention of the Investigator at any 
time after cessation of the study treatment, will be reported to the Sponsor within 24 hours. 
Full details will be recorded on the pregnancy form. 
8.4 
Investigational Medicinal Products 
8.4.1 
Investigational Medicinal Products Administered 
During the Treatment Period, KPL-914 will be administered as an initial loading dose of 2 x 160 mg SC on 
Day 0, then 160 mg SC dosed once weekly for up to 5 subsequent weeks.  At the discretion of the 
Investigator, subjects completing the Treatment Period may enter the 18-week Extension Period and receive 
up to 18 additional weekly doses of KPL-914. 
At the discretion of the Sponsor in collaboration with the Investigators, the Study Drug dosing regimen may 
be decreased in a consecutive group of subjects to a loading dose of 2 x 80 mg SC on Day 0, then 80 mg SC 
dosed once weekly for 5 subsequent weeks to explore efficacy at a lower dose. Depending on treatment 
response observed with the 80 mg dose, the dose administered to either these subjects or subsequent subjects 
may be changed back to 160 mg by the Investigator in collaboration with the Sponsor. For any given subject, 
the KPL-914 dose level received at the end of the Treatment Period should be continued into the EP (if 
administration is continued); however, a change in the KPL-914 dose level during the EP for any individual 
subject can be made at the discretion of the Investigator in consultation with the Sponsor, and the 
modification of dose should be recorded in the source records and the eCRF. 
Sites for SC 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. 
No placebo or active comparator drug will be used.  
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to decrease the KPL-914 dose administered to a subsequent consecutive group of subjects to a loading dose 
of 2 x 80 mg SC on Day 0, then 80 mg SC weekly (the dose tested in the Phase 3 program for gout) for 5 
additional weeks in order to explore efficacy at a lower dose. However, depending on treatment response 
observed with the 80 mg dose, the dose administered to either these subjects or subsequent subjects may be 
changed back to 160 mg by the Investigator in collaboration with the Sponsor. 
8.4.5 
Selection and Timing of Dose for Each Subject 
The first administration of KPL-914 (and training for outpatient self-administration) will be performed 
under the supervision of a qualified healthcare professional at Visit 1 (Day 0).  Afterwards, subjects will 
self-administer the Study Drug as an outpatient during the Treatment Period (and during the EP, as 
applicable).  Study Drug administration will be performed once a week (every 7 ± 1 days).  The interval 
between Study Drug administrations must be at least 5 days.  Subjects will be instructed to not administer 
KPL-914 more often than once weekly and to administer only one syringe of Study Drug per week. 
At Visit 1, subjects will be instructed on aseptic reconstitution of the lyophilized product and injection 
technique.  The ability to inject subcutaneously will be assessed to ensure proper administration of KPL-
914, including rotation of injection sites.  Patients will be instructed in proper vial, syringe, and needle 
disposal, and will be cautioned against reuse of these items.  All used and unused Study Drug vials must be 
returned to the Study Site/Clinic for drug accountability assessment.  
8.4.6 
Blinding 
Not applicable.  
8.4.7 
Prior and Concomitant Therapy 
Subjects enrolled into the study may be using NSAIDs, colchicine, and/or corticosteroids in any 
combination at the time of study enrollment, but the dose levels must be stable for have been stable for at 
least 7 days, although stable doses for at least 3 days will be acceptable if in the opinion of the Investigator, 
in consultation with the Sponsor, a shorter period of stability is not anticipated to alter the baseline CRP 
values.   
For the duration of the Treatment Period, pericarditis medications (e.g., concomitant NSAIDs, colchicine 
and/or corticosteroids, if used) should be continued at pre-study dose levels until after the 6-dose Study 
Drug Treatment Period has concluded; however, should the Investigator determine that a reduction/tapering 
of the NSAID, colchicine, and/or corticosteroid dose is medically indicated, the NSAID, colchicine and/or 
corticosteroid dose can be down-titrated in consultation with the Sponsor, and the modification of dose 
should be recorded in the source records and the eCRF. 
Subjects who received, within the 6-month period before dosing, immunomodulatory therapy other than, 
for example, corticosteroids or mycophenolate, which in the opinion of the Investigator (in consultation 
with the Sponsor) may interfere with the study endpoints, or subjects who used commercially-available 
rilonacept (ARCALYST®) within 90 days before the Screening Visit are excluded from participation.  
Throughout the Treatment Period opioid analgesics, non-narcotic analgesics (e.g., tramadol), and 
acetaminophen are allowed as rescue medication for ancillary pain control on an as-needed basis.  Although 
it is recommended that NSAID dose levels (if present) should remain constant during the active Treatment 
Period, the concomitant NSAID dose may be temporarily increased (or an NSAID initiated) for ancillary 
pain control if deemed necessary by the Investigator, after consultation with the Sponsor.  Any rescue 
medication use must be recorded in source records, the medication diary and the eCRF. Other interleukin 
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(IL)-1 or IL-6 blockers, janus-activating kinase (JAK) and tumor necrosis factor (TNF) inhibitors are 
prohibited for the duration of the study.  
Medical management of pericarditis during the EP is based on Investigator discretion.  He/she may continue 
subjects on KPL-914 at the same dosage level, wean-off or discontinue Study Drug in consultation with the 
Sponsor, or change (increase or decrease) the dosing of NSAIDs/colchicine/corticosteroids.  Other 
pericarditis medications may also be initiated at the discretion of the Investigator.  All changes to 
pericarditis-related medications should be captured in the source records and the eCRF. 
During the Screening and Treatment Periods, subjects will enter information concerning the use of 
pericarditis and rescue (pain) medication into a daily medication diary.  Such information will be entered 
by the subject on a daily basis (evening). 
8.4.8 
Treatment Compliance 
Study Drug will be administered to the patient by the Investigator or qualified study center staff at the Study 
Site/Clinic Visit 1 (Day 0).  Subsequent weekly Study Drug doses from Weeks 2 to 5 will be self-
administered by the patient as an outpatient SC administration. A visiting study nurse will assess and record 
compliance with Study Drug administration at the subject’s home as well as provide guidance and training 
on Study Drug administration as needed. At Week 6/End-of-Trial, Study Drug may be self-administered or 
administered at the study site. All medication use (for pericarditis and use of rescue [pain] medication) will 
be documented by the subject in the medication diary during the Treatment Period.  
All vials of used and unused Study Drug during the active Treatment Period and the EP must be retained by 
the Study Site/Clinic and the subject to allow for cataloguing and documentation of compliance. Subjects 
must return all used and unused medication to the Study Site/Clinic.  Drug accountability and documentation 
thereof is described in the Pharmacy Manual. 
Study Drug compliance by the subject will be monitored during the Treatment Period by phone calls/virtual 
visits (made by qualified site staff).  Subjects will be reminded of recording all medication information in 
the medication diary.  The medication diary will be returned to the site by the subject and reviewed by the 
Investigator/qualified staff.  During the EP, Study Drug use will be documented during monthly phone 
calls/virtual visits or Study Site/Clinic visits. 
8.5 
Study Procedures 
All data of Study Site/Clinic visit assessments as well as Investigator (or designee) phone calls/virtual visits 
will be documented in source records and in the eCRF. 
8.5.1 
Screening Period 
The Screening Period starts with the signature of the ICF and may last for up to 3 days.  During this period, 
patient eligibility for entry into the Treatment Period will be determined.  A rheumatology consultation 
during the Screening Period is optional. 
At SCV1, baseline patient and disease characteristics will be determined.  Persistence of diagnostic criteria 
for pericarditis will be confirmed within ~24 to 72 hours at SCV2.  Under special circumstances, the 
Investigator in consultation with the Sponsor, can combine SCV1 and SCV2. 
The end of the Screening Period may coincide with the start of the Treatment Period.   
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8.5.1.1 
Screening Visit 1 (SCV1) 
• At the SCV1, written informed consent will be obtained before any in-person assessments are made. 
• All subjects will be assessed for eligibility against the inclusion and exclusion criteria. 
• Demographic data, such as ethnic origin, date of birth and sex will be recorded. 
• The subject’s full medical history, including age at first attack, number of previous attacks, duration 
of attacks as well as concomitant illnesses/diseases will be documented. 
• Information related to concomitant medicine that subjects were taking during at least the 2 weeks 
prior to the visit will be captured. 
• A full physical examination will be performed, including assessment of pericardial rub. 
• Body weight and height will be assessed. 
• Vital signs will be obtained in the seated position and include oral temperature, respiratory rate, blood 
pressure, and pulse. 
• A pregnancy test (urine dip-stick) will be done. If the urine test is positive, additional Study 
Site/Clinic and/or central serum tests may be performed. 
• 12-lead ECG and full echocardiogram (ECHO) will be performed.  ECHO will include assessment 
of pericardial effusion.  The Study Site/Clinic readings at the time of the examination will be 
available to the Investigator for clinical decision-making. In addition, both the ECG and ECHO will 
be sent to a core laboratory for additional analysis. 
• A cardiac MRI may be performed (optional). If done, the images will be assessed by a central reader. 
The Study Site/Clinic reading at the time of the examination may be used by the Investigator for 
clinical decision-making. 
• Samples for Study Site/Clinic (safety and assessment) and central (CRP) clinical laboratory tests will 
be collected.  Full hematology, chemistry, and urinalysis will be performed at laboratories of the 
Study Site only. A sample for CRP will be obtained and sent to the central laboratory for analysis. 
Serology (HCVAb, HBsAg, HBcAB, HBsAb and HIV) will be performed. 
• Samples for archive biomarker and/or pharmacokinetics (PK) and anti-rilonacept (anti-KPL-914) 
antibody testing will be collected, sent to the central laboratory, and stored for analysis.  
• A QuantiFERON® test for tuberculosis (TB) can be performed (optional).  
• Screening for drugs of abuse and alcohol abuse will be performed on urine samples collected at this 
visit.  
• A medication diary for documentation of pericarditis medication use and use of any rescue (pain) 
medication will be handed to the subject.  The study Investigator or designated personnel will 
instruct the subject about the use of the medication diary.  The subjects will be asked to complete 
an evening entry each day. 
• The subjects will assess their pericardial pain based on a 11-point NRS. 
• The subject's global overall well-being will be assessed using a validated Quality of Life 
Questionnaire (Appendix 3). 
 
8.5.1.2 
Screening Visit 2 (SCV2) 
The end of the Screening Period (SCV2) coincides with the start of the Treatment Period (Day 0, Visit 1).  
All Screening assessments need to be completed prior to the first Study Drug administration.  
• SCV2 should take place when the laboratory test results from SCV1 are available. 
• Subjects will be reassessed for eligibility against the inclusion and exclusion criteria. 
• Any changes in concomitant medications since SCV1 will be documented. 
• A full physical examination will be performed, including re-assessment of pericardial rub.  
• Vital signs will be measured.  
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• 12-lead ECG will be performed.  The Study Site/Clinic reading at the time of the examination will be 
used by the Investigator for clinical decision-making. In addition, the ECG will be sent to a core 
laboratory for additional analysis. 
• Samples for Study Site/Clinic (safety and assessment) and central (CRP) clinical laboratory tests will 
be collected.   
• Medication diary compliance will be assessed by the Investigator/designated personnel and the 
subject reminded on the diary use. 
• The subjects will assess their pericardial pain based on the 11-point NRS (Figure 3). 
 
When all screening procedures have been performed and the Investigator has confirmed the subject’s 
eligibility for the study, the Study Drug will be administered to the subject (see Study Site/Clinic Visit 1). 
 
8.5.2 
Treatment Period 
8.5.2.1 
Visit 1 (Study Site/Clinic) - Day 0 
• Visit 1 will coincide with SCV2.  In case Visit 1 is separated from SCV2, SCV2 clinical laboratory 
blood sampling, medication diary compliance verification and reminding, and subject NRS 
pericardial pain rating (see Figure 3) must be repeated prior to Study Drug dosing.  
• Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody testing will be 
collected prior to Study Drug dosing, sent to the central laboratory, and stored for analysis.  
• The subject's global overall well-being will be assessed prior to Study Drug dosing using a validated 
Quality of Life Questionnaire (Appendix 3). 
• The initial dose of Study Drug will be administered at the Study Site/Clinic. 
• Subjects will be trained for outpatient Study Drug self-administration and reminded of completion of 
the daily medication diary. 
• Any AEs occurring during or after the subject receives the first dose of Study Drug will be captured. 
When all Visit 1 procedures have been performed, an appointment for the first weekly phone call/virtual 
visit will be scheduled. Study Drug for outpatient administration will be provided to the subjects according 
to a process laid out in the pharmacy manual. 
8.5.2.2 
Visits 2 to 6 (Outpatient) - Weeks 2, 3, 4, 5, 6 
• Visits 2, 3 4, 5, 6 will take place within intervals of 7 ± 1 days each after Visit 1. 
• Subjects self-administer the Study Drug during Weeks 2 to 5. At Week 6/End-of-Trial, Study Drug 
may be self-administered or administered at the study site. 
•  Blood samples for CRP laboratory analysis will be collected (either by a visiting study nurse or at 
the Study Site or at a qualified local laboratory) and will be sent to the central laboratory for analysis. 
• Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody testing will be 
collected (either by a visiting study nurse or at the Study Site or at a qualified local laboratory) and 
stored for analysis after shipment to the central laboratory.  
• Any AEs that have occurred since the last contact will be assessed by non-leading questions as part 
of the weekly telephone call/virtual visit from the Study Site/Clinic.  
• Compliance with self-administration of drug, compliance with the medication diary, and compliance 
with laboratory blood sampling will be assessed as part of the weekly telephone call/virtual visit 
from the Study Site/Clinic. 
• Pericardial pain based on the 11-point NRS (Figure 3) will be assessed as part of the weekly telephone 
call/virtual visit from the Study Site/Clinic. 
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Subjects withdrawing from the study any time during study weeks 2 to 6 will be asked to return to the Study 
Site/Clinic for the Visit 7/End-of-Trial visit assessments.  
8.5.2.3 
Interval Evaluation Visit (Study Site/Clinic) - Week 3-4 
An in-person Interval Evaluation Visit during approximately Weeks 3-4 of the Treatment Period is 
recommended to assist the Investigator in the clinical management of the subject. The visit can be held at 
the discretion of the Investigator. The Interval Evaluation Visit may also be used to review the vaccination 
status of a study subject. 
At the Interval Evaluation Visit, the following parameters will be assessed: 
• A full physical examination will be performed, including assessment of pericardial rub. 
• Vital signs will be measured.  
• A 12-lead ECG and a full ECHO will be performed.  The Study Site/Clinic readings at the time of 
the examination will be made available to the Investigator for clinical decision-making. In addition 
both the ECG and ECHO will be sent to a core laboratory for additional analysis. 
• Changes in concomitant medication since the last Study Site/Clinic visit will be documented. 
• Samples for Study Site/Clinic (safety and assessment) and central (CRP) clinical laboratory tests will 
be collected.  
• Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody testing will be 
collected, sent to the central laboratory, and stored for analysis.  
• Any AEs that have occurred since the last visit (Study Site/Clinic or outpatient) will be documented.  
• Medication diary compliance will be assessed by the Investigator/designated personnel and the 
subject reminded on the diary use. 
• Pericardial pain based on the 11-point NRS (Figure 3) will be assessed. 
• The subject's global overall well-being will be assessed using a validated Quality of Life 
Questionnaire (Appendix 3). 
8.5.2.4 
Unscheduled Visits (Study Site/Clinic) During the Treatment Period  
Subjects reporting worsening of pericarditis symptoms or AEs may be brought in at the discretion of the 
Investigator for an Unscheduled Visit at any time during the Treatment Period.  During the Unscheduled 
Visit, selected or comprehensive (see Interval Evaluation Visit) clinical and laboratory assessments may be 
performed.  
Any subject who is determined by the Investigator as not responding to treatment (e.g., no reduction in 
pericardial pain compared to baseline, no decrease in CRP levels, etc.) and who is therefore considered by 
the Investigator to be a “Treatment Failure” may be withdrawn from further Study Drug treatment at the 
discretion of the Investigator and receive rescue therapy for their pericarditis according to standard of care 
as per Investigator decision; these subjects will be followed for safety for the remainder of the 6-week 
Treatment Period.   
All study withdrawals must complete the Week 7/End-of-trial Visit either at the Unscheduled Visit or at a 
separate Week 7/End-of-trial Visit. 
8.5.2.5 
Visit 7/ End-of-Trial (Study Site/Clinic) - Week 6 
At Visit 7, “Treatment Responders” (defined by the Investigator as a clinically significant reduction in 
pericardial pain using the 11-point NRS, normal or near-normal CRP levels, and absent or decreasing 
echocardiographic effusion at the End-of-Trial Visit), will be offered participation in an optional 18-week 
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EP, at the discretion of the Investigator. During the EP, weekly open-label KPL-914 can be continued at the 
same dose as in the Treatment Period for a total duration of Study Drug treatment of up to 24 weeks.   
• Visit 7 will take place during Week 6 (or as soon as possible after study withdrawal if a subject has 
discontinued from Study Drug therapy).  
• A full physical examination will be performed, including assessment of pericardial rub. 
• Vital signs will be measured.  
• A 12-lead ECG and a full ECHO will be performed.  The Study Site/Clinic readings at the time of 
the examination will be made available to the Investigator for clinical decision-making.  In addition 
both the ECG and ECHO will be sent to a core laboratory for additional analysis. 
• Changes in concomitant medication since last Study Site visit will be documented. 
• Samples for Study Site/Clinic (safety and assessment) and central (CRP) clinical laboratory tests will 
be collected.  
• Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody testing will be 
collected, sent to the central laboratory, and stored for analysis. 
• Any AEs that have occurred since the last visit (Study Site/Clinic or outpatient) will be documented.  
• Medication diary compliance will be assessed by the Investigator/designated personnel. 
• Pericardial pain based on the 11-point NRS will be assessed (Figure 3). 
• The subject's global overall well-being will be assessed using a validated Quality of Life 
Questionnaire (Appendix 3). 
When all of these procedures have been performed, the next Study Site/Clinic visit should be scheduled for 
those who continue KPL-914 treatment during the EP (Treatment Responders).  Study Drug for outpatient 
administration will be provided to the subjects according to a process laid out in the pharmacy manual. 
Only subjects continuing treatment into the Extension Phase will receive Study Drug at Visit 7; Study Drug 
can be self-administered either as an outpatient or at the Clinic/Site (Site to provide Study Drug) depending 
on the logistics/timing of the EoT Visit 7. Continued weekly Study Drug treatment during the EP will be 
outpatient administration. 
8.5.3 
Extension Period 
Subjects will self-administer the Study Drug on a weekly basis during the Extension Period, and study nurse 
visits to the patient’s home will continue on a monthly basis. Investigator (or designee) phone calls/virtual 
visits will be performed monthly during the EP to perform NRS pain assessments, collect AE information, 
and document pericarditis/concomitant medication use. If scheduled, in-person Study Site/Clinic Visits 
(Unscheduled Visits or Evaluation Visits) can replace the phone calls/virtual visits. 
8.5.3.1 
Unscheduled Visits (Study Site/Clinic) during the EP 
Unscheduled Study Site/Clinic visits can take place during the Extension Period, as agreed upon by the 
Investigator and the subject or as needed.  
• A physical examination will be performed. 
• Vital signs will be measured.  
• Changes in concomitant medication since the last Study Site/Clinic visit will be documented. 
• Samples for Study Site/Clinic (safety and assessment) and central (CRP) clinical laboratory tests will 
be collected.  
• Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody testing will be 
collected, sent to the central laboratory, and stored for analysis.  
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• A 12-lead ECG and a full ECHO will be performed as determined by the Investigator.  The Study 
Site/Clinic readings at the time of the examination will be made available to the Investigator for 
clinical decision-making. In addition, both the ECG and ECHO will be sent to a core laboratory for 
additional analysis. 
• Any AEs that have occurred since the last visit (Study Site/Clinic or outpatient) will be documented.  
• Pericardial pain based on the 11-point NRS will be assessed (Figure 3).  
8.5.3.2 
Interval Evaluation Visit During Extension Period (Study Site/Clinic) - Week 15-20 
An in-person Interval Evaluation Visit during approximately Weeks 15-20 of the Extension Period is 
recommended to assist the Investigator in the clinical management of the subject. The visit can be held at 
the discretion of the Investigator.  
At the Extension Period Interval Evaluation Visit, the following parameters will be assessed: 
• A physical examination will be performed. 
• Vital signs will be measured.  
• A 12-lead ECG and a full ECHO will be performed.  The Study Site/Clinic readings at the time of 
the examination will be made available to the Investigator for clinical decision-making. In addition, 
both the ECG and ECHO will be sent to a core laboratory for additional analysis. 
• Changes in concomitant medication since the last Study Site/Clinic visit will be documented. 
• Samples for Study Site/Clinic (safety and assessment) and central (CRP) clinical laboratory tests will 
be collected.  
• Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody testing will be 
collected, sent to the central laboratory, and stored for analysis.  
• Any AEs that have occurred since the last visit (Study Site/Clinic or outpatient) will be documented.  
• Pericardial pain based on the 11-point NRS will be assessed (Figure 3). 
• The subject's global overall well-being will be assessed using a validated Quality of Life 
Questionnaire (Appendix 3). 
8.5.3.3 
Visit 8/Final Visit (Study Site/Clinic) - Week 25 
• Visit 8 will take place 18 weeks after Visit 7 (or as soon as possible after study withdrawal during the 
EP). 
• A full physical examination will be performed, including assessment of pericardial rub.  
• Body weight and height will be assessed. 
• Vital signs will be obtained in the seated position and include oral temperature, respiratory rate, blood 
pressure, and pulse. 
• 12-lead ECG and ECHO will be performed.  Echocardiogram will include assessment of pericardial 
effusion.  In addition, both the ECG and ECHO will be sent to a core laboratory for additional 
analysis. 
• An MRI can be performed (optional).  
• Changes in concomitant medication since the last Study Site/Clinic visit will be documented. 
• Samples for Study Site/Clinic (safety and assessment) and central (CRP) clinical laboratory tests will 
be collected.   
• Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody testing will be 
collected, sent to the central laboratory, and stored for analysis.  
• Any AEs that have occurred since the last visit (Study Site/Clinic or outpatient) will be documented.  
• Pericardial pain based on the 11-point NRS will be assessed (Figure 3). 
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• The subject's global overall well-being will be assessed using a validated Quality of Life 
Questionnaire (Appendix 3). 
8.5.4 
Duration of Treatment 
The overall study duration for subjects participating in the study until Visit 8 will be up to 171 days.  
The test product will be administered weekly for 6 weeks in the base study Treatment Period.  Treatment 
Responders will be offered participation in an optional 18-week EP at the discretion of the Investigator.  
During this EP the subject can receive 18 additional weekly doses of KPL-914.  
8.6 
Efficacy and Safety Variables 
The Schedule of Evaluations in Table 1 shows the planned study assessments. 
8.6.1 
Individual Efficacy Assessments 
8.6.1.1 
C-Reactive Protein, Biomarker, and PK Assessments 
CRP will be determined at Study Site/Clinic laboratory tests at Screening (SCV1 and SCV2) and during the 
Treatment Period (Visit 1 prior to dosing, if separate from SCV2, Interval Evaluation Visit [if applicable], 
and Visit 7/End-of-Trial).  Results from the Study Site/Clinic CRP testing will inform the Investigator on 
the subject's pericarditis status for clinical decision-making and support decisions on classifications of 
subjects as Treatment Responders or Treatment Failures and on subsequent disease management during the 
Extension Period.  
Central laboratory assessments of CRP will be performed at each Study Site/Clinic or outpatient study visit 
(samples collected by a visiting study nurse or at the Study Site/Clinic or a local laboratory).  Centrally 
determined CRP values will be used for statistical evaluations and report writing but will not be used as 
basis of the Investigator’s management the patient. 
All subjects must present with elevated CRP values ≥1 mg/dL at the time of study enrollment.  CRP changes 
and the time course to decrease and resolution of CRP to normal values ≤0.5 mg/dL will be assessed. 
Samples from each study visit will be archived at the central laboratory for potential biomarker and/or PK 
analysis.  
8.6.1.2 
Echocardiogram (Pericardial Effusion) 
Echocardiograms (ECHOs) including assessment of pericardial effusion will be performed at screening 
(SCV1), at Study Site/Clinic visits during the Treatment Period (Interval Evaluation Visit [if applicable] 
and Visit 7/End-of-Trial), at the Interval Evaluation Visit during the EP [if applicable], and at the Final 
Study Visit/Visit 8.  
Pericardial effusion is characterized by accumulation of excess fluid in the pericardial space surrounding 
the heart and is one of the common features of pericarditis.  Echocardiography is a sensitive tool and the 
most widely used imaging technique for the detection of pericardial effusion and/or thickening. 
For the purposes of the analysis of treatment response in all subjects at the end of the study, all ECHO 
images will be assessed by a central reader. The Study Site/Clinic reading of the ECHO at the time of the 
examination will be made available to the Investigator for clinical decision-making.  
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8.6.1.3 
Electrocardiogram (Pericarditis Diagnostic Findings) 
Twelve-lead ECGs will be performed at screening (SCV1 and SCV2), at Study Site/Clinic visits during the 
Treatment Period (Interval Evaluation Visit [if applicable] and Visit 7/End-of-Trial), at the Interval 
Evaluation Visit during the EP [if applicable], and at the Final Study Visit/Visit 8.  
Pericarditis commonly involves changes in the electrophysiologic activity of the heart, resulting in typical 
ECG findings, namely widespread ST-elevation or PR depression.  Changes in ECG findings will help 
determine the pericarditis status of a subject.  
The Study Site/Clinic reading of the ECG at the time of the examination will be made available to the 
Investigator for clinical decision-making. For the purposes of the analysis of treatment response in all 
subjects at the end of the study, all ECG tracings will be assessed by a central reader.   
8.6.1.4 
Pericarditis Signs (Fever, Pericardial Rub) 
Common pericarditis signs include fever and pericardial rub.  These pericarditis signs will be assessed via 
documentation of vital signs and physical examinations.  
Physical examinations and vital signs assessments for pericarditis signs will be performed at screening 
(SCV1 and SCV2), at Study Site/Clinic visits during the Treatment Period (Interval Evaluation Visit [if 
applicable] and Visit 7/End-of-Trial), at the Interval Evaluation Visit during the EP [if applicable], and the 
Final Study Visit/Visit 8.  If applicable, assessment of pericarditis signs will also be performed at 
unscheduled visits.  
8.6.1.5 
Pericarditis Pain (Chest Pain) 
Common pericarditis symptoms include chest discomfort (pericarditis pain).  A validated 11-point NRS will 
be used to measure the subject's level of pericarditis (chest) pain intensity (Dworkin et al 2005; Mannion et 
al 2007; Hawker et al 2011).  The assessment will be performed at all study visits - on-site during Study 
Site/Clinic visits and as part of telephone calls/virtual visits during outpatient visits/treatment weeks (weekly 
during the Treatment Period and monthly during the EP).  
Subjects will be asked to select the score that best describes their average level of pain over the previous 24 
hours using a validated 11-point NRS instrument (Figure 3), where zero (0) indicates ‘no pain’ and ten (10) 
means indicates ‘pain as bad as it could be’.   
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On this scale of 0-10, zero (0) indicates ‘no pain’ and ten (10) indicates ‘pain as bad as it could be’, 
please rate your pain on average in the last 24 hours 
Figure 3: 
11-point Numerical Rating Scale (NRS) for Assessment of Pericarditis Pain 
 
8.6.1.6 
Magnetic Resonance Imaging 
Cardiac MRI is an optional assessment and may be performed at study entry (SCV1) and at the final study 
visit (Visit 8) to assess any changes in pericardial inflammation.  
For the purposes of the analysis of treatment response in all subjects at the end of the study, all cardiac MRI 
images will be assessed by a central reader. The Study Site/Clinic reading of the MRI at the time of the 
examination may be used by the Investigator for clinical decision-making.  
8.6.1.7 
Quality of Life Questionnaire 
A validated Quality of Life Questionnaires will be used to assess changes in the subject's overall well-being 
(Hays et al 2009).  The patient's global assessment will be performed at screening (SCV1), at Visit 1 (Day 
0), at the Interval Evaluation Visit (Week 3-4), at the end of the Treatment Period (Visit 7/End-of-Trial), at 
the Interval Evaluation Visit during the EP, and at the Final Visit (Visit 8).  
The Quality of Life Questionnaire to be used is presented in Appendix 3.  
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8.6.2 
Safety Assessments 
8.6.2.1 
Adverse Events 
Adverse Event Definition 
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 and/or unintended 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. 
In this study, individual elements of pericarditis symptomatology (including pain) are captured as an 
efficacy parameter.  Pericarditis pain is not required to be reported as an AE.  However, if, in the opinion of 
the Investigator, the subject experiences new symptoms that had not been previously reported in the 
constellation of symptoms recorded at baseline, these new symptoms should be reported as an AE. 
The causal relationship between an AE and the Study Drug will be defined as below: 
• 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 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 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 drug, abates 
upon discontinuation of the drug, follows a known or hypothesized cause-effect relationship, and (if 
appropriate) reappears when the drug is reintroduced.   
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: medically significant event; daily activities limited or completely halted; hospitalization or 
prolongation of hospitalization indicated. 
Every reasonable effort will be made to follow subjects who have AEs.  Any subject who has an ongoing 
AE at study end or early withdrawal will be followed, where possible, until resolution.   
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Sponsor Reporting Responsibilities to Participating Investigators 
It is the responsibility of the Sponsor or designee to immediately notify all participating Investigators of any 
AE associated with the use of the drug that is both serious and unexpected, as well as any finding from tests 
in laboratory animals that suggest a significant risk for human subjects.   
8.6.2.3 
Adverse Reactions 
All noxious and unintended responses to an investigational medicinal product (IMP; i.e., where a causal 
relationship between an IMP and an AE is at least a reasonable possibility) related to any dose should be 
considered adverse drug reactions.   
Unexpected Adverse Reaction Definition 
An unexpected adverse drug reaction is defined as an adverse reaction, the nature or severity of which is 
not consistent with relevant product information for the IMP.  The current version of the ARCALYST® PI 
should be used as the Single Source Safety Reference Document when determining if an event is 
unexpected. Refer to the ARCALYST® PI (Appendix 2: ARCALYST® Prescribing Information) for a list 
of most frequent expected AEs.  All suspected adverse reactions related to an investigational medicinal 
product (the tested investigational medicinal products and comparators, if involved) which occur in the 
concerned trial, and that are both unexpected and serious are subject to expedited reporting. 
Warnings and Precautions 
Refer to the ARCALYST® PI (Appendix 2: ARCALYST® Prescribing Information) for Important Safety 
Information. 
IL-1 blockade may interfere with immune response to infections.  It is therefore recommended that prior to 
or shortly after initiation of therapy with KPL-914 patients receive all recommended vaccinations, as 
appropriate, including pneumococcal vaccine and inactivated influenza vaccine. In case a patient needs 
vaccination after initiation of KPL-914 treatment, vaccination with inactive vaccine(s) may be performed 
during the active Treatment Period. However, to minimize the potential confounding of KPL-914-related 
AE reporting or CRP measurements during the KPL-914 Treatment Period, vaccination should not be 
performed during the Treatment Period (see Section 8.3.4).  It is recommended that all vaccinations be 
documented as up-to-date at or shortly after Visit 7, at which point subjects are being considered for longer-
term treatment with KPL-914.   
It is recommended that all vaccinations be documented as up-to-date at or shortly after Visit 7, at which 
point subjects are being considered for longer-term treatment with KPL-914.  
Taking KPL-914 with TNF inhibitors is not recommended because simultaneous inhibition of these two 
pathways may increase the risk of serious infections.   
It is also possible that taking drugs 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 KPL-914.   
8.6.2.4 
Clinical Laboratory Variables 
Clinical laboratory analyses will be performed at Study Site/Clinic or local laboratory near the patient and, 
for some parameters, at a central laboratory.  Laboratory analyses will be used at Study Site/Clinic visits for 
the Investigator to assess disease status and to determine treatment response and study (drug) continuation 
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or withdrawal.  Results for analyses performed by the Study Site/Clinic laboratory together with the 
laboratory reference ranges will be recorded in the eCRF and the Investigator must use clinical judgment to 
determine if any abnormal values are clinically significant or not. 
Central laboratory samples for CRP analysis will be collected at both Study Site/Clinic and outpatient (by a 
visiting study nurse or at local contract laboratories) visits and the results will be used for statistical analyses 
and study reporting. Study Site/Clinic and local laboratory results will be used for clinical decision-making 
and will be available in the source documents and listed in the CSR).  
The following analyses will be done at the central laboratory:  
C-reactive protein (CRP)  
The CRP analyzed by the central laboratory will not be the basis of the Investigator's clinical management 
of the patient.  Results from the central laboratory will therefore not be transferred to the Investigator during 
the trial. 
The following laboratory analyses will be performed at the Study Site/Clinic laboratories in accordance 
with local procedures and guidelines: 
Hematology 
Hemoglobin, hematocrit, coagulation parameters (prothrombin [PT], prothrombin time [PTT], D-dimer), 
ESR, fibrinogen, WBC count (total and differential), red blood cell (RBC) count, ESR, platelet count, mean 
cell volume (MCV), mean cell hemoglobin (MCH), MCH concentration (MCHC). 
Clinical Chemistry 
CRP, troponin, creatinine, creatine kinase, urea, (or blood urea nitrogen [BUN]), aspartate aminotransferase 
(AST), alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), alkaline phosphatase, lactate 
dehydrogenase (LDH), total bilirubin, albumin, total protein, sodium, potassium, chloride, glucose, uric 
acid, total cholesterol*, triglycerides*, calcium, phosphorus. 
* Preferably fasting. 
Urinalysis 
pH, glucose, ketones, nitrites, leukocyte esterase, blood, protein and microscopy. 
Serology 
HCVAb, HBsAg, HBcAB, HBsAb and HIV tests (SCV 1 only) 
 
8.6.2.5 
Other Laboratory Variables 
Samples for biomarkers, PK, and anti-rilonacept (anti-KPL-914) antibody testing will be drawn and 
archived at all visits. For PK and anti-rilonacept (anti-KPL-914) antibody testing, whole blood from subjects 
will be collected in 5-mL red-top vacutainer tubes (US B-D Cat #367814). For biomarker assessments, 
blood is collected in a 4.0-mL vacutainer K2 EDTA tube. 
Urine drug screen (alcohol, amphetamines, cocaine, or phencyclidine) at SCV1 only.  
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Screening for tuberculosis (QuantiFERON test) at SCV1 only (optional). 
Screening for pregnancy (urine β-HCG) at SCV1 only. 
The amount of blood to be taken during screening will be approximately 37 mL at SCV1 and approximately 
17 mL at SCV2 (if done). The amount of blood to be taken at each Study Site/Clinic visit during the 
Treatment Period and EP will be approximately 31 mL.  The amount of blood to be taken at each outpatient 
visit will be approximately 21 mL. At the optional unscheduled visit, approximately 61 mL are planned. 
The total amount of blood to be taken during the study will be up to approximately 320 mL. 
8.6.2.6 
Vital Signs 
Vital signs will be recorded at Study Site/Clinic visits in a standardized manner, i.e., after the subject has 
rested in the sitting position for 5 minutes. 
The following measurements will be taken: oral temperature, respiratory rate, blood pressure, and pulse.  
Oral temperature (fever) will also be assessed as efficacy parameter (see Section 8.6.1.4). 
8.6.2.7 
Physical Examination 
At the Screening Visits 1 and 2, at the optional Evaluation Visit during the Treatment Period, at the End-of-
Trial Visit (Visit 7), at Unscheduled and Evaluation Visits during the EP and at the Final Visit (Visit 8) a 
full physical examination including the assessment of pericardial rub (efficacy parameter) will be performed 
(see also Section 8.6.1.4).   
8.6.2.8 
Body Weight and Height 
Body weight and height will be determined at SCV1 and at the final study visit.  
8.7 
Statistical Methods 
A full description of the statistical analyses to be performed together with the planned tables and figures 
will be given in a detailed document, the SAP, which will be developed and filed prior to data base lock.  
Any deviation(s) from the final SAP will be described and justified in the clinical study report. 
8.7.1 
Statistical and Analytical Plans 
8.7.1.1 
Datasets to be Analyzed 
The modified Intention to Treat (mITT) Population will consist of all subjects who received at least one 
dose of Study Drug.  The Per Protocol (PP) Population will consist of all subjects who received all 6 doses 
of Study Drug during the active Treatment Period and were maintained at stable dose levels of concomitant 
pericarditis medications (NSAIDs, colchicine, and/or corticosteroids, if used during screening) according to 
study protocol.  The Safety Population will be the same as the mITT Population. 
8.7.1.2 
General Statistical Methods 
Because of the small sample size, no inferential statistical analyses or hierarchical testing are planned. 
For analysis of continuous endpoints (e.g., change from baseline), summary statistics (n, mean, standard 
deviation, median, minimum, and maximum) will be calculated and presented for each treatment and/or 
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8.7.2 
Determination of Sample Size 
Approximately 10 symptomatic patients with RIP will be enrolled as study subjects.  Following review of 
the available data, the Sponsor, in collaboration with the Investigators, may increase the sample size to up 
to 20 subjects to address additional hypotheses. 
Subjects who discontinue the study (withdrawals and Treatment Early Failures) may be replaced at the 
Sponsor’s discretion. 
The sample size was chosen on an empirical basis, based on experience with other rilonacept trials and 
research in this patient population. 
8.8 
Quality Assurance and Quality Control 
8.8.1 
Audit and Inspection 
The study may be selected for audit originating from the Sponsor or external organizations acting on behalf 
of the Sponsor.  Audits will be followed by internal reports and corrective actions, if needed.  
The Investigator agrees to cooperate with the auditor to ensure that any problems detected in the course of 
these audit visits are resolved.  The anonymity of the patients must be safeguarded and data checked during 
audits remain confidential. 
8.8.2 
Monitoring 
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.  
The Investigator will permit study-related monitoring, audits, ethics committee review and regulatory 
inspection(s), providing direct access to source data and documents.  
For each patient enrolled, the Investigator or designee will document in the source records of the patient 
that the patient 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 patient.  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 Good Clinical Practice (GCP) and International Conference on Harmonisation 
(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.   
8.8.3 
Data Management and Coding 
The Sponsor or Clinical Research Organization (CRO) 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 the 
Sponsor or CRO. 
Medical coding will use Medical Dictionary for Regulatory Activities (MedDRA) for concomitant diseases 
and AEs and World Health Organization (WHO) Drug for therapies. 
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8.8.4 
Record Keeping 
It is the responsibility of the Investigator to ensure all essential trial documentation and source records (e.g., 
signed ICFs, Study Site/Clinic files, patients’ hospital notes, copies of eCRFs, etc.) 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. 
 
9 Records and Supplies 
9.1 
Drug Accountability 
On receipt of the IMP (including rescue medication, if relevant), the Investigator (or deputy) will conduct 
an inventory of the supplies and verify that IMP supplies are received intact and in the correct amounts prior 
to completing a supplies receipt.  The Investigator will retain a copy of this receipt at the study site and 
return the original receipt to the drug depot.  The inventory of supplies at each study site will be reviewed 
by the study monitor. 
KPL-914 (rilonacept) will be provided by the Sponsor to the study sites and to the study subjects in its 
commercially-available formulation (ARCALYST®).  All vials of used and unused Study Drug during the 
active Treatment Period 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.   
 
10 
Ethics 
10.1 Institutional Review Board 
Before initiation of the study at each investigational site, the protocol, all protocol amendments, the ICF, 
and any other relevant study documentation will be submitted to the appropriate IRB.  Written approval of 
the study and all relevant study information must be obtained before the study site can be initiated or the 
IMP is released to the Investigator.  Any necessary extensions or renewals of IRB approval must be obtained, 
in particular, for changes to the study such as modification of the protocol, the informed consent form, the 
written information provided to subjects and/or other procedures. 
The Investigator will report promptly to the IRB any new information that may adversely affect the safety 
of the subjects or the conduct of the study.  The Investigator will submit written summaries of the study 
status to the IRB annually, or more frequently if requested by the IRB.  On completion of the study, the 
Sponsor will notify the IRB that the study has ended. 
10.2 Ethical Conduct of the Study 
This study will be conducted in compliance with the protocol, the ICH-GCP guideline, the Declaration of 
Helsinki and local regulations. 
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10.3 Subject Information and Consent 
The Investigator is responsible for ensuring that no subject undergoes any study related examination or 
activity before that subject and/or legal guardian has given written informed consent to participate in the 
study.  The written consent must be given by the subject and/or the legal guardian of the subject, after 
detailed information about the study has been given and in accordance with any national provisions on the 
protection of clinical study subjects.  The verbal explanation will cover all the elements specified in the 
written information provided for the subject. 
Subjects and/or legal guardians will be required to sign and date the ICF.  After signatures are obtained, the 
ICF will be kept and archived by the Investigator in the Investigator’s study file for possible inspection by 
regulatory authorities, the IRB, Sponsor and/or CRO personnel. 
It should be emphasized to the subject that he/she is at liberty to withdraw from the study at any time, 
without penalty or loss of benefits to which the subject is otherwise entitled.  Subjects who refuse to give or 
who withdraw written informed consent should not be included or continue in the study. 
10.4 Subject Confidentiality (US Studies) 
All personal data collected and processed for the purposes of this study should be managed by the 
Investigator and his/her staff with adequate precautions to ensure confidentiality of those data, and in 
accordance with the Health Insurance Portability and Accountability Act (HIPAA), applicable to national 
and/or local laws and regulations on personal data protection. 
Monitors, auditors, and other authorized agents of the Sponsor and/or its designee, the ethics committees 
approving this research, and the United States (US) FDA, as well as that of any other applicable agency(ies), 
will be granted direct access to the study subjects’ original medical records for verification of clinical study 
procedures and/or data, without violating the confidentiality of the subjects to the extent permitted by the 
law and regulations.  In any presentations of the results of this study or in publications, the subjects’ identity 
will remain confidential. 
 
11 Reporting and Publication 
All data generated in this study are the property of the Sponsor.  An integrated clinical and statistical report 
will be prepared at the completion of the study. 
Publication of the results by the Investigator(s) will be subject to mutual agreement between the Investigator 
and Kiniksa as outlined in the study agreement. 
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12 References 
Adler Y, Charron P, Imazio M, Badano L, Barón-Esquivias G, Bogaert J, Brucato A, 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 Nov 7;36(42):2921-64. 
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, Lazaros G, Maestroni S, Carraro M, Finetti M et al. Effect of Anakinra 
on Recurrent Pericarditis Among Patients With Colchicine Resistance and Corticosteroid 
Dependence: The AIRTRIP Randomized Clinical Trial. JAMA. 2016 Nov 8;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. Autoimmunity Reviews 2015;14:90–97. 
Doria A, Zen M, Bettio S et al. Autoinflammation and autoimmunity: bridging the divide. Autoimmunity 
Reviews 2012;12:22–30. 
Dworkin RH, Turk DC, Farrar JT et al. Core outcome measures for chronic pain clinical trials: IMMPACT 
recommendations. Pain. 2005 Jan;113(1-2): 9-19. 
Hays RD, Bjorner JB, Revicki DA, Spritzer KL, Cella D. Development of physical and mental health 
summary scores from the patient-reported outcomes measurement information system (PROMIS) 
global items. Qual Life Res (2009) 18:873–880. 
Hawker GA, Mian S, Kendzerska T, French M. 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 & Research. 2011; 63: S240–S252. 
Hoffman HM, Patel DD. Genomic-based therapy: targeting interleukin-1 for auto-inflammatory diseases. 
Arthritis and Rheum. 2004 Feb; 50(2): 345-349. 
Imazio M, Spodick DH, Brucato A, Trinchero R, Adler Y. Controversial issues in the management of 
pericardial diseases. Circulation. 2010;121:916-928. 
Imazio M, Bobbio M, Cecchi E, Demarie D, Demichelis B, Pomari F, Moratti M, Gaschino G, Giammaria 
M, Ghisio A, Belli R, Trinche-ro R. Colchicine in addition to conventional therapy for acute 
pericarditis: results of the COlchicine for acute PEricarditis (COPE) trial. Circulation. 
2005;112:2012-2016. 
Imazio M, Demichelis B, Parrini I et al. Management, risk factors, and outcomes in recurrent pericarditis. 
American Journal of Cardiology, 2005;96(5):736–739. 
Imazio M. Treatment of recurrent pericarditis. Revista Espanola de Cardiologia. 2014;67(5):345–348. 
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Khandaker MH, Espinosa RE, Nishimura RA, Sinak LJ, Hayes SN, Melduni RM, Oh JK. Pericardial 
disease: diagnosis and management. Mayo Clin Proc. 2010;85:572-593. 
Lazaros G, Imazio M, Brucato A, Vassilopoulus D, Vasileiou P, Gattorno M, Tousoulis D et al. Anakinra: 
an emerging option for refractory idiopathic recurrent pericarditis: a systematic review of published 
evidence. J Cardiovasc Med 2016;17(4):256-62. 
Lilly SL. Treatment of Acute and Recurrent Idiopathic Pericarditis. Circulation. 2013;127:1723-1726. 
Lotrionte M, Biondi-Zoccai G, Imazio M, Castagno D, Moretti C, Abbate A, Agostoni P, Brucato AL, Di 
Pasquale P, Raatikka M, Sangiorgi G, Laudito A, Sheiban I, Gaita F. International collaborative 
systematic review of controlled clinical trials on pharmacologic treatments for acute pericarditis and 
its recurrences. Am Heart J. 2010;160:662-670. 
Maisch B, Seferovic PM, Ristic AD, Erbel R, Rienmüller R, Adler Y, Tomkowski WZ, Thiene G, Yacoub 
MH; Task Force on the Di-agnosis and Management of Pericardial Diseases of the European Society 
of Cardiology. Guidelines on the diagnosis and management of pericardial diseases executive 
summary: the Task Force on the Diagnosis and Man-agement of Pericardia! Diseases of the 
Eu-ropean Society of Cardiology. Eur Heart J. 2004;25:587-610. 
Mannion AF, Balagué F, Pellisé F, Cedraschi C. Pain measurement in patients with low back pain. Nature 
Clinical Practice Rheumatology 2007; 3 (11): 610-18. 
Pankuweit S, Wädlich A, Meyer E, Portig I, Hufnagel G, and Maisch B. Cytokine activation in pericardial 
fluids in different forms of pericarditis. Herz 2000;25:748–754. 
Zayas R, Anguita M, Torres F, Gimenez D, Bergillos F, Ruiz M, Ciudad M, Gallardo A, Valles F. Incidence 
of specific etiology and role of methods for specific etiologic diagnosis of primary acute pericarditis. 
Am J Cardiol. 1995;75:378-382. 
 
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13 Appendices 
Appendix 1: Investigator Signature Page 
Protocol Title: 
An open-label pilot study of KPL-914 in symptomatic Recurrent 
Idiopathic Pericarditis. 
Protocol Number: 
KPL-914-C001 
Confidentiality and cGCP Compliance Statement 
I, the undersigned, have reviewed this protocol, including appendices and I will conduct the study as 
described in compliance with this protocol, GCP, and relevant ICH guidelines. 
Once the protocol has been approved by the IEC/IRB, I will not modify this protocol without obtaining prior 
approval of Kiniksa Pharmaceuticals Ltd. (Kinksa) and of the IEC/IRB. I will submit the protocol 
modifications and/or any ICF modifications to Kiniksa and IEC/IRB, and approval will be obtained before 
any modifications are implemented. 
I understand that all information obtained during the conduct of the study with regard to the subjects’ state 
of health will be regarded as confidential. No subjects’ names will be disclosed.  All subjects will be 
identified by assigned numbers on all Case Report Forms, laboratory samples or source documents 
forwarded to the Sponsor.  Clinical information may be reviewed by the Sponsor or its agents or regulatory 
agencies.  Agreement must be obtained from the subject before disclosure of subject information to a third 
party. 
Information developed in this clinical study may be disclosed by Kiniksa, to other clinical Investigators, 
regulatory agencies, or other health authority or government agencies as required. 
Investigator Signature 
Date 
Printed Name 
Institution 
 
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Appendix 2: ARCALYST® Prescribing Information 
 
KPL-914-C001 Protocol and Amendments 
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		 38-	6			6'				.		 38-	
+		+		5!	+				.	/	
'"'!	+'	>	
	!			"		+					!		"
				"							.				
					/		'
3	/'	!)	'!&!	%/!%)
3"7	

 "	"	'				B		+					"
+'	;			!					'			.
5		+			"			+	-!	8!	8		,-	"4"	".	+	
+	
"			5	,'2	"						0-	"			
	'							+	5			"				
"	+										.			'
=5			"				+	+		5	'	+!		
"	!							.					03J		
														
	'	*				.	5"					
"			"			
-!	&-!	--		&--	"4"!		+		,				
					+	&--	"4"				+	
	"			5	0
	"			0-	"							'			
	"	"					/						'
7"	'					.	5"		+			+
.3/&3URWRFRODQG$PHQGPHQWV
3DJH

	+					"						&-!	--!	&--	"4"
			+	
	"			5	0	"			0-	"	
					'										
# 	"	"					'
3"9	)
	*

*			+	+			5			'	;		"		5		
!				5	+						"	+'
3":	
	/
5			+	 	+		"		&		0	+		+			
+!				&'&	"4"	
			5		0-	"		&3+	"		
	5	'			+	.								
/.				
'"'					.	 '		.	.
	/								+					
'
	"	"	.											+		.	

&-	"4!	"	,'0		,,	"4	+				.				+	 	

&3	"4!	"	2		80	"4'
		.				+		"		&	.			'
%			"	!				.					
			'	*			+			+			.			'
 			+			"		"		"+	
.'	G	'		
!(	%!	)H
3"@	$

	/
*							+	 			!	2-	
6			+		+	M	08			"!		0	+	M	28			"'	*	
 		!	!				+	"					
		"	F	+.!				M	08						'	*	
	5			 !		2			+	.		"			G
		H'	"					.		"				"
				'
3";				! 
 
7			.				5					
			+		'
3"8			#	! 
 
7			.				5					
			+		'
72	%6'4%$'
	.					.	+	'	$5	+					,&-	"
.							5	(							
+	 				0				+		.					+
.		"	5'	*	!		".	.					&---
"									5		+		+	"
5'		5											

.3/&3URWRFRODQG$PHQGPHQWV
3DJH

'
*			.!											"			
.			!						'
77	4'!!%)
						"			""				5
							
**		*			

* 					#				*"<'					+"	
5	&8	1'			5					.	
9A	'
				"!	&-	"	.	"		!	+		+!
6	+'	=	.							+	&',				%	
*/'		.				&				++!	+		"		.	0-	"	
		'		"			.!	!				+!	
			'	=	.		&&-	"	'		!		.
	(-	"4	!	30	$	!	8-	$	"!	,'-J	
+4.		"	,,8-!
&'-J	
+4.	!		'-J	
+4.	"			9		0'8	N	-','	7	..		'
71	!)!	#*%%$
71"7	* 		
 				"		"						7 ,	G7
"	!				
7!			"	,H	"	
	+		
*			G*
H'	 						
		+				"	B	'	#				
	.!		!	"!	"!	"!		/.'
*		!			 			+				7 ,	"	+	
		!						'		"		
				.				
*O'	$		7 ,			
..		"		5.			.	*O		.	'
		*O	""		"								*O		.
		+			'				*P		*		"	
*
	+		'		B					"		*O!	*P
	*	+	-'8	$!	'3	$		0'	$!	.'
71"1	
  
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								 					.	"		
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;								!			"		+	
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	+				"		"			'	9					"	+
			+		&2""							"				"	+		
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2'	 9		"			!									.	"	'	1		+
							.'	 			.	'	9		"				
	+			5	
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		'	+				"	"			'	1			
'	 		"				+							.	
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				"'
'	 	.			!	"				"										"
				'
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		"	+	"							.'	 		"		
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8'	 9		.	"					+		/	+	
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				"								.!		B			.			

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2'	 			.							+	+	.		.'
('	 *		+				.!			.	B					,-	
'			.					'
K'	 		(			+			.					'
-'	 	5				!	!					+'	1				5
B						!								
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Kiniksa Pharmaceuticals Ltd. 
 
25 September 2017 
KPL-914-C001 
Final 
Page 59 of 61 
 
CONFIDENTIAL 
Appendix 3: Quality of Life Instrument 
 
 
 
 
 
KPL-914-C001 Protocol and Amendments 
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Kiniksa Pharmaceuticals Ltd. 
25 September 2017 
KPL-914-C001 
Final 
Page 60 of 61 
CONFIDENTIAL 
KPL-914-C001 Protocol and Amendments 
Page 88

Kiniksa Pharmaceuticals Ltd. 
25 September 2017 
KPL-914-C001 
Final 
Page 61 of 61 
CONFIDENTIAL 
Appendix 4: 11-point Numerical Rating Scale (NRS) for Assessment of Pericarditis Pain 
Common pericarditis symptoms include chest discomfort (pericarditis pain).  A validated 11-point NRS will 
be used to measure the subject's level of pericarditis (chest) pain intensity (Dworkin et al 2005; Mannion et 
al 2007; Hawker et al 2011). 
Subjects will be asked to select the score that best describes their average level of 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’.   
On this scale of 0-10, zero (0) indicates ‘no pain’ and ten (10) indicates ‘pain as bad as it could be’, 
please rate your pain on average in the last 24 hours 
KPL-914-C001 Protocol and Amendments 
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Kiniksa Pharmaceuticals Ltd. 
 
17 January 2018 
KPL-914-C001 Amendment 1 
Final 
Page 4 of 64 
 
CONFIDENTIAL 
3 Synopsis 
Trial Number: 
KPL-914-C001 
Trial Title: 
An open-label, pilot study of KPL-914 in symptomatic recurrent idiopathic pericarditis 
Trial Centers: 
Approximately 15 sites in the United States 
Development Phase: 2 
Objective(s): 
Primary: 
To collect inter- and intra-subject variability data on C-reactive protein (CRP) measurements and the 
11-point Numerical Rating Scale (NRS) instrument for assessment of pericardial pain in subjects with 
recurrent idiopathic pericarditis (RIP) both at baseline and on treatment with KPL-914 in order to 
inform power calculations for future trials in RIP. 
Secondary: 
To explore the time course to improvement of pericarditis parameters in symptomatic subjects with RIP 
treated with KPL-914. 
To evaluate the safety of KPL-914 in symptomatic subjects with RIP. 
Methodology: 
This is an open-label single-active-arm pilot study to explore clinical and biochemical endpoints of 
improvement of pericarditis symptomatology and to collect inter- and intra-subject variability data on 
both at-baseline and on-treatment parameters in symptomatic subjects with RIP who will be treated 
with once-weekly subcutaneously (SC)-administered injections of KPL-914.   
Subjects identified for participation in this trial will present during a symptomatic episode of RIP, 
having previously experienced a first (index) episode of acute pericarditis followed by at least 1 
recurrent episode before the current enrollment-qualifying episode, using the 2015 European Society of 
Cardiology (ESC) Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 
2015) as a frame of reference: 
- 
The index episode of acute pericarditis would have been characterized by an inflammatory 
pericardial syndrome with at least 2 of the 4 following criteria: pericarditic chest pain, pericardial 
rub, new widespread ST-segment elevation or PR-segment depression on electrocardiogram 
(ECG), and pericardial effusion (new or worsening).  Additional supportive findings would have 
included elevations of markers of inflammation (i.e., CRP, erythrocyte sedimentation rate [ESR], 
and white blood cell [WBC] count) or evidence of pericardial inflammation by an imaging 
technique (e.g., magnetic resonance imaging [MRI]).   
- 
Recurrence of RIP would have been characterized as a subsequent episode of pericarditis 
occurring after a symptom-free interval of 4-6 weeks or longer.   
 
 
 
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17 January 2018 
KPL-914-C001 Amendment 1 
Final 
Page 5 of 64 
 
CONFIDENTIAL 
For the purposes of this study, the Investigator will determine, based on his/her judgement of the 
available data, if a subject has met these criteria for having experienced a previous index episode of 
acute pericarditis followed by at least 1 recurrent episode of pericarditis prior to the presenting 
symptomatic episode of RIP and will record the criteria supporting this diagnosis in the electronic case 
report form (eCRF). 
Prior to enrollment, potential subjects may enter an optional Prescreening Period after signing  a 
Prescreening ICFto allow monitoring for symptoms and inflammatory markers (CRP, ESR, etc) while 
existing medications for recurrent idiopathic pericarditis may be managed by the Investigator or their 
clinician according to standard of care. 
Study subjects will be enrolled (Screening Visit 1 [SCV1]) at the time of a symptomatic episode.  In 
addition to meeting the criteria for pericarditis in the judgement of the Investigator, all subjects must 
present with a CRP value ≥1 mg/dL at the time of study enrollment.  Subjects included in the study may 
be receiving concomitant nonsteroidal anti-inflammatory drugs (NSAIDs), and/or colchicine, and/or 
oral corticosteroid treatment in any combination, provided the dosages of these medications have been 
stable for at least 7 days, although stable doses for a shorter period will be acceptable if in the opinion 
of the Investigator, in consultation with the Sponsor, a shorter period of stability is not anticipated to 
alter the baseline CRP values.  
Baseline therapy and disease characteristics will be determined during a Screening Period of up to 
72 hours, as needed, to confirm the pre-treatment diagnostic workup.  At the SCV1, baseline subject 
and disease characteristics will be determined and captured in the eCRF.  Persistence of diagnostic 
criteria for pericarditis will be confirmed (Screening Visit 2 [SCV2]) within the 24 - 72 hour period 
before subjects advance to the Treatment Period of the study. Under special circumstances, the 
Investigator, in consultation with the Sponsor, can combine SCV1 and SCV2, and the subject can 
proceed directly to the Day 0 dosing visit. 
Approximately 10 subjects will participate in the active Treatment Period of the study.  Following 
review of the ongoing data by the Sponsor and the Investigators, the sample size may be increased to a 
total of up to 20 subjects. After having met all the entry criteria during the Screening Period, the 
subjects entering the Treatment Period will receive a loading dose of KPL-914 (2 x 160 mg SC) on Day 
0, then 160 mg SC weekly for 5 additional doses.  
The first Study Drug dose on Day 0 will be administered at the Study Site/Clinic (Visit 1).  Subsequent 
weekly Study Drug doses from Weeks 2 to 5 will be self-administered by the subject as an outpatient 
SC administration. A visiting study nurse will assess and record compliance with Study Drug 
administration at the subject’s home as well as provide guidance and training on Study Drug 
administration as needed. At Week 6/End of Trial, Study Drug may be self-administered or 
administered at the study site.  Weekly assessments of safety and treatment response, including 
administration of the 11-point NRS instrument to assess pericardial pain, will be done at the Study 
Site/Clinic at Visit 1 (Day 0) and Visit 7 (Week 6/End-of-Trial), and via Investigator (or designee) 
phone calls/ virtual visits at Weeks 2 to 5 (Visits 2 to 5). Weekly outpatient blood samples for central 
laboratory testing will be collected at the Study Site/Clinic, or at a qualified laboratory site in the 
vicinity of the subject, or by a visiting study nurse. 
Investigators are encouraged to schedule subjects at the Study Site/Clinic for an in-person Interval 
Evaluation Visit during approximately Weeks 3-4 to assist the Investigator in the clinical management 
of the subject.  During this visit a full assessment including physical examination, vital signs, ECG, 
echocardiogram, and laboratory testing can be performed as well as the recording of adverse events 
(AEs) and other study-related assessments as needed.   
 
 
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At any time point during the Treatment Period, subjects reporting worsening of pericarditis symptoms 
or AEs may be brought into the Study Site/Clinic at the discretion of the Investigator for an 
Unscheduled Visit, in which select or comprehensive clinical assessments can be performed.  Any 
subject who is determined by the Investigator as not responding to treatment (e.g., no reduction in 
pericardial pain compared to baseline, no decrease in CRP levels, etc.) and who is therefore considered 
by the Investigator to be a “Treatment Failure” may be withdrawn from further Study Drug treatment at 
the discretion of the Investigator and may receive rescue therapy for their pericarditis according to 
standard of care as per Investigator decision; these subjects will be followed for safety for the 
remainder of the 6-week Treatment Period.  Subjects identified as “Treatment Failures” may be 
replaced at the discretion of the Sponsor in order to provide an adequate sampling of subjects 
completing the active Treatment Period. 
Subjects participating for the complete length of the active study Treatment Period will receive a total 
of 6 doses of KPL-914.  For the duration of the Treatment Period, concomitant NSAIDs and/or 
colchicine and/or corticosteroids, if present, should be continued at pre-study dose levels until after the 
6-dose Study Drug Treatment Period has concluded; however, should the Investigator determine that a 
reduction/tapering of the NSAID, colchicine, and/or corticosteroid dose is medically indicated, the 
NSAID, colchicine, and/or corticosteroid dose can be down-titrated in consultation with the Sponsor, 
and the modification of dose should be recorded in the source records and the eCRF.  
Opioid analgesics, non-narcotic analgesics (e.g., tramadol), and acetaminophen are allowed as rescue 
medication for ancillary pain control on an as-needed basis throughout the Treatment Period.  Although 
it is recommended that NSAID dose levels (if present) should remain constant during the active 
Treatment Period, the concomitant NSAID dose may be temporarily increased (or an NSAID initiated) 
for ancillary pain control if deemed necessary by the Investigator, after consultation with the Sponsor. 
Any rescue medication use must be recorded in source records, eCRF, and medication diary.  
At the discretion of the Investigator, “Treatment Responders” (defined by the Investigator as a 
clinically significant reduction in pericardial pain using the 11-point NRS, normal or near-normal CRP 
levels, and/or absent or decreasing echocardiographic effusion at the End-of-Trial Visit), will be offered 
participation in an optional 18-week Extension Period (EP), in which weekly open-label KPL-914 
administration can be continued at the same dose as in the Treatment Period for a total duration of 
Study Drug treatment of up to 24 weeks. Weekly Study Drug administrations during the EP are by self-
administration, and study nurse visits to the subject’s home as well as Investigator (or designee) 
telephone calls/virtual visits are to continue on a monthly basis. 
During the EP, the Investigator may choose to wean concomitant NSAIDs, colchicine, and/or 
corticosteroids according to standard of care paradigms; all medication changes must be recorded in 
source records and the eCRF.  Investigators are encouraged to schedule subjects at the Study Site/Clinic 
for an in-person Interval Evaluation Visit between Weeks 15 to 20 (8 to 13 weeks after Visit 7/End of 
Trial Visit) to assist the Investigator in the clinical management of the subject.  During this visit a 
physical examination, vital signs, ECG, echocardiogram (ECHO), and laboratory testing can be 
performed at the discretion of the Investigator. 
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CONFIDENTIAL 
Available safety, tolerability, and efficacy data for each subject will be reviewed by the Investigator as 
part of ongoing subject management.  A Safety Review Committee (SRC) including selected 
Investigator(s) and Sponsor representatives will review on a monthly basis (at a minimum) all available 
data for all subjects, considering trends across each.  
Given the following occurrences, dosing may be halted or reduced, in accordance with an SRC 
recommendation, confirmed by the Sponsor: 
- 
One or more subjects experience a serious and unexpected adverse event that is considered by 
the Investigator to be related to Study Drug (SUSAR), or 2 or more subjects experience similar 
severe (non-serious) and unexpected AEs that are considered by the Investigator to be related to 
Study Drug. 
After an initial group of subjects has been treated, depending on the safety profile observed as well as 
the magnitude and speed of treatment response (e.g., if an informative number of subjects achieve 
treatment response early in the Treatment Period), the Sponsor in collaboration with the Investigators 
may elect to decrease the KPL-914 dose administered to a subsequent consecutive group of subjects to 
a loading dose of 2 x 80 mg administered SC on Day 0, then 80 mg administered SC weekly for 5 
additional weeks, in order to explore efficacy at a lower dose.  Depending on treatment response 
observed with the 80 mg dose, the weekly dose administered to either these subjects or subsequent 
subjects may be changed back to 160 mg by the Investigator in collaboration with the Sponsor.  For any 
given subject, the KPL-914 dose level received at the end of the Treatment Period should be continued 
into the EP (if administration is continued); however, a change in the KPL-914 dose level during the EP 
for any individual subject can be made at the discretion of the Investigator in consultation with the 
Sponsor, and the modification of dose should be recorded in the source records and the eCRF. 
During the Screening and Treatment Periods, subjects will enter information concerning the use of 
pericarditis and rescue (pain) medication into a medication diary.  Such information will be entered by 
the subject on a daily basis. 
Number of Subjects: 
Approximately 10 symptomatic subjects with RIP will be enrolled as study subjects.  Following review 
of the available data, the Sponsor, in collaboration with the Investigators, may increase the sample size 
to up to 20 subjects to address additional hypotheses. 
Subjects who discontinue the study (withdrawals and Treatment Failures) may be replaced at the 
Sponsor’s discretion in order to provide an adequate sampling of subjects completing the active 
Treatment Period. 
 
Diagnosis and Main Criteria for Inclusion: 
Inclusion Criteria 
To be eligible to participate in the trial, a subject must meet all of the following criteria: 
1. Has given consent and signed an Informed Consent Form (ICF). 
2. Male or female, of any ethnic origin. 
3. 18 to 70 years of age, inclusive. 
4. Has had a prior index episode of pericarditis which, in the judgement of the Investigator based on 
the available data, met the criteria for an acute pericarditis event, using the 2015 ESC Guidelines 
for the Diagnosis and Management of Pericardial Diseases (Adler et al, 2015) as a frame of 
reference --  i.e., met at least 2 of the 4 following criteria: pericarditic chest pain, pericardial rub, 
new widespread ST-segment elevation or PR-segment depression on ECG, and pericardial 
effusion (new or worsening).  Additional supportive findings could include elevations of markers 
of inflammation (i.e., CRP, erythrocyte sedimentation rate, and white blood cell count) or 
evidence of pericardial inflammation by an imaging technique (e.g., MRI). 
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CONFIDENTIAL 
5. Has had at least one prior recurrent episode of pericarditis, in the judgement of the Investigator, 
based upon the available diagnostic information. 
6. Has an ongoing symptomatic episode of pericarditis at the time of study enrollment in the 
judgement of the Investigator, based upon the available diagnostic information. 
7. Has an elevated CRP value (i.e., >1 mg/dL) at the time of study enrollment. 
8. If used, has received NSAIDs, and/or colchicine and/or corticosteroids (in any combination) at 
stable dose levels for at least 7 days (although stable doses for a shorter period will be acceptable 
if in the opinion of the Investigator, in consultation with the Sponsor, a shorter period of stability 
is not anticipated to alter the baseline CRP values) and is anticipated to continue these 
concomitant medications at these dose levels for the duration of the active Treatment Period.  
9. If female, must be nonpregnant and nonlactating and must agree to use an effective method of 
contraception, e.g., hormonal contraception or double-barrier birth control.  
10. Is able to adequately maintain a daily medication diary. 
11. Agrees to refrain from making any new, major life-style changes that may affect pericarditis 
symptoms (e.g., starting a new diet or changing exercise pattern) from the time of signature of the 
ICF to the End-of-Trial Visit (Week 6). 
Exclusion Criteria 
A subject who meets any of the following criteria will not be eligible to participate in the trial: 
1. Has a diagnosis of pericarditis that was secondary to specific etiologies, including tuberculous, 
neoplastic, or purulent etiologies, post cardiac injury syndromes, myocarditis, or systemic 
diseases including autoinflammatory diseases, autoimmune diseases (e.g., rheumatoid arthritis, 
systemic lupus erythematosus, etc.). 
2. Has a history of immunodepression, including a positive human immunodeficiency virus test 
result. 
3. Has received treatment with any systemic immunosuppressants (other than, for example, 
corticosteroids or mycophenolate) which, in the opinion of the Investigator (in consultation with 
the Sponsor), may interfere with the study endpoints within the 6-month period before dosing.  
4. Currently receiving other interleukin (IL)-1 or IL-6 blockers, janus-activating kinase (JAK) or 
tumor necrosis factor (TNF) inhibitors. 
5. Has a history of myeloproliferative disorder, demyelinating disease, or symptoms suggestive of 
multiple sclerosis. 
6. Female subject who is pregnant or lactating or who does not agree to use an effective method of 
contraception, e.g., hormonal contraception or double-barrier birth control. 
7. Has a history of active or latent treated tuberculosis (TB), or had a positive QuantiFERON (QFT-
TB G In-Tube) test result, or a chest radiograph during the 3 months prior to Study Drug dosing 
suggestive of prior TB infection. A subject with a positive purified protein derivative (PPD) test 
result (≥5-mm induration) after the first attack of pericarditis is excluded unless he/she has had 
either a negative chest x-ray result or a negative QuantiFERON test result. 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, night sweats) upon review of medical history and/or 
physical exam.  Have recent close contact with a person with active TB.  
8. Chest radiograph (or historic results within 3 months of SCV1) that shows evidence of 
malignancy or any abnormalities suggestive of prior TB infection, including, but not limited to, 
apical scarring, apical fibrosis, or multiple calcified granulomata.  This does not include non-
caseating granulomata. 
9. Has received immunization with a live (attenuated) vaccine within 12 weeks before the start of 
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CONFIDENTIAL 
the study. 
10. Has history of or positive or intermediate results for hepatitis B surface antigen (HBsAg), 
hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at SCV1. 
11. Has an estimated glomerular filtration rate (eGFR) <30 mL/min.  
12. Has a history of malignancy of any organ system within the past 5 years (other than a 
successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or 
localized carcinoma in situ of the cervix). 
13. 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. 
14. Has had a serious infection, has been hospitalized for an infection, has been treated with oral 
antibiotics within 2 weeks of Study Drug administration, or has been treated with intravenous 
(IV) antibiotics for an infection within 2 months of first Study Drug administration.  
15. Has had an organ transplant.  
16. In the Investigator's judgement, has a history of alcoholism or drug/chemical abuse within 2 years 
prior to Study Drug administration. 
17. Has a drug screen positive for amphetamines, cocaine, or phencyclidine or positive alcohol test at 
SCV1.  Exceptions may be made if a subject is on an approved medication for a stable 
concomitant condition that explains the positive screen. 
18. Has taken commercially-available rilonacept (ARCALYST®) or participated in a rilonacept 
clinical study during the 90 days before SCV1.  Has used anakinra within 30 days prior to Study 
Drug administration. 
19. Has a history of hypersensitivity to rilonacept or to any of the excipients contained in the Study 
Drug. 
20. Has received an investigational drug during the 30 days (or 5 half-lives, whichever is longer) 
before SCV1 or is planning to receive an investigational drug (other than that administered during 
this trial) or use an investigational device at any time during the trial. 
21. In the Investigator's judgement, has any other medical condition that could adversely affect the 
subject's participation or interfere with study evaluations.  
22. Subject who, in the opinion of the Investigator, is not likely to be compliant with the study 
protocol. 
23. Subject who, in the opinion of the Investigator in consultation with the Sponsor, should not 
participate in this study. 
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CONFIDENTIAL 
Test Products, Dosage, and Mode of Administration: 
KPL-914 (rilonacept) will be provided in its commercially-available formulation as a lyophilized 
powder to be reconstituted for SC administration. 
KPL-914 will be administered as an initial loading dose of 2 x 160 mg SC on Day 0, then 160 mg SC 
dosed once weekly for 5 subsequent weeks.  After an initial group of subjects has been treated, 
depending on the safety profile observed as well as the magnitude and speed of treatment response 
(e.g., if an informative number of subjects achieve treatment response early in the Treatment Period), 
the Sponsor in collaboration with the Investigators may elect to decrease the KPL-914 dose 
administered to a subsequent consecutive group of subjects to a loading dose of 2 x 80 mg administered 
SC on Day 0, then 80 mg administered SC weekly for 5 additional weeks, in order to explore efficacy at 
a lower dose.  
Subjects will receive a total of 6 doses of KPL-914 during the study active Treatment Period.  Subjects 
who are considered to be “Treatment Responders” will be offered, at the discretion of the Investigator, 
participation in an optional 18-week Extension Period (EP), in which weekly open-label KPL-914 can 
be continued for a total duration of KPL-914 treatment of up to 24 weeks. 
Concomitant Medication 
• There is no wash-out of concomitant therapy (NSAIDs/colchicine/corticosteroids) during the 
Screening Period of the study. 
• For the duration of the Treatment Period, concomitant pericarditis medications (e.g., NSAIDs, 
colchicine and corticosteroids), if used, should be continued at pre-study dose levels until after the 
6-dose Study Drug Treatment Period has concluded; however, should the Investigator determine 
that a reduction/tapering of the NSAIDs, colchicine, and/or corticosteroid dose is medically 
necessary, the NSAID, colchicine and/or corticosteroid dose can be down-titrated according to 
standard of care paradigms in consultation with the Sponsor, and the modification of dose should be 
recorded in the source records and the eCRF.  
• Opioid analgesics, non-narcotic (non-NSAID) analgesics (e.g., tramadol), and acetaminophen are 
allowed as rescue medication for ancillary pain control on an as needed basis throughout the 
Treatment Period.  Although it is recommended that NSAID dose levels (if present) should remain 
constant during the active Treatment Period, the concomitant NSAID dose may be temporarily 
increased (or an NSAID initiated) for ancillary pain control if deemed necessary by the 
Investigator, after consultation with the Sponsor.  Any rescue medication use must be recorded in 
source records, the medication diary and the eCRF. 
• Medical management of pericarditis during the EP is based on Investigator discretion.  For 
example, Investigators may continue subjects on KPL-914 at the same dosage level, wean-off or 
discontinue Study Drug, or change (increase or decrease) the dosing of NSAIDs/colchicine/ 
corticosteroids.  Other pericarditis medications may also be initiated at the discretion of the 
Investigator.  All changes to pericarditis-related medications should be captured in the source 
records and eCRF. 
• Prohibited concomitant medicines: Other interleukin (IL)-1 or IL-6 blockers, janus-activating 
kinase (JAK) or tumor necrosis factor (TNF) inhibitors. 
Duration of Treatment: 
The Study Drug will be administered for 6 weeks in the base study Treatment Period.  
“Treatment Responders” will be offered participation in an optional 18-week EP at the discretion of the 
Investigator. 
Total subject participation is expected to last for up to 171 days for those that also participate in the 
18-week EP. 
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CONFIDENTIAL 
assess and record compliance with Study Drug administration at the subject’s home as well as 
provide guidance and training on Study Drug administration as needed. At Week 6/End-of-
Trial, Study Drug may be self-administered at home or administered at the Study site/clinic.   
Investigators are encouraged to schedule subjects at the Study Site/Clinic for an in-person 
Interval Evaluation Visit during approximately Weeks 3-4 to assist the Investigator in the 
clinical management of the subject.   
Subjects reporting worsening of pericarditis symptoms or AEs may be brought in for an 
unscheduled visit at the Study Site/Clinic at any time during the Treatment Period, at the 
discretion of the Investigator.  Any subject who is considered by the Investigator to be a 
“Treatment Failure” may be withdrawn from further Study Drug treatment at the discretion of 
the Investigator and receive rescue therapy for their pericarditis according to standard of care as 
per Investigator decision; these subjects will be followed for safety for the remainder of the 6-
week Treatment Period.  Subjects identified as “Treatment Failures” may be replaced at the 
discretion of the Sponsor in order to provide an adequate sampling of subjects completing the 
active Treatment Period. 
During the Treatment Period, subjects will continue documentation of pericarditis treatment 
medication use as well as rescue (pain) medication use in the medication diary.  Patient-
reported pericardial pain evaluations will be performed on-site at the Study Site/Clinic and by 
weekly Investigator (or designee) telephone calls/virtual visits using a validated 11-point NRS 
instrument.  A patient-reported QoL questionnaire will be administered at Visit 7 (Study 
Site/Clinic).  Weekly blood samples for central laboratory testing will be collected at the Study 
Site/Clinic or at a qualified laboratory site in the vicinity of the subject or by a visiting study 
nurse. 
4. Extension Period (EP): The EP is defined as the 18 weeks following the Treatment Period.  
Subjects who are considered to be “Treatment Responders” will be, at the discretion of the 
Investigator, offered participation in an optional 18-week EP, in which weekly administration 
of open-label KPL-914 may be continued for a total duration of 24 weeks.  The weekly KPL-
914 doses will be by self-administration, and study nurse visits to the subject’s home as well as 
Investigator (or designee) telephone calls/virtual visits will continue on a monthly basis. During 
that EP, the Investigator may choose to change concomitant NSAID, colchicine, and/or 
corticosteroid treatment, recording all modifications in the source records and eCRF.  
Unscheduled clinic visits can be scheduled any time as determined by the Investigator/upon 
subject request. In addition, Investigators are encouraged to schedule subjects at the Study 
Site/Clinic for an in-person Interval Evaluation Visit between Weeks 15 to 20 (8 to 13 weeks 
after Visit 7) to assist the Investigator in the clinical management of the subject.  During this 
visit a physical examination, vital signs, ECG, echocardiogram, and laboratory testing can be 
performed. 
Patient-reported pericardial pain evaluations using a validated 11-point NRS instrument as well 
as AE monitoring will be performed during the EP at on-site clinic visits and/or during monthly 
Investigator (or designee) phone calls/virtual visits.  A patient-reported QoL questionnaire will 
be administered at the Interval Evaluation Visit and the Final Visit of the EP.  At the end of the 
EP, subjects will complete the Week 25/Final Visit.  
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CONFIDENTIAL 
Statistical Methods: 
Analysis Populations 
The modified Intention to Treat (mITT) Population will consist of all subjects who received at least one 
dose of Study Drug.  The Per Protocol (PP) Population will consist of all subjects who received all 6 
doses of Study Drug during the active Treatment Period and were maintained at stable dose levels of 
concomitant pericarditis medications (e.g., NSAIDs, colchicine, corticosteroids) according to study 
protocol without a major protocol violation.  The Safety Population will be the same as the mITT 
Population. 
General Methods 
Because of the small sample size no inferential statistical analyses or hierarchical testing are planned. 
For analysis of continuous endpoints (e.g., change from baseline), summary statistics (n, mean, standard 
deviation, median, minimum, and maximum) will be calculated and presented for each treatment and/or 
analysis group.  For categorical endpoints, summary statistics will be calculated and presented for each 
treatment and/or analysis group.  
Further details, including, for example, the process to be followed for reviewing individual pericarditis 
symptomatology endpoints to be used in the construction of a composite primary endpoint for 
subsequent trials, will be provided in the Statistical Analysis Plan (SAP). 
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KPL-914-C001 Amendment 1                                                                             Final 
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CONFIDENTIAL 
Table 1: 
Schedule of Evaluations 
Trial Period → 
Pre-
screening 
Period 
Run-In Period 
(Up to 3 days) 
Treatment Period 
(6 weeks) 
Extension Period 
(18 weeks) 
Visit Days/Weeks → 
Day -3 to 
Day 0a 
Day 
0b 
Week 
2c 
Week 
3c 
W3-W4d 
Week 
4c 
Week 
5c 
Week 
6cc 
Week 
6/ 
End-
of-
Trialc 
 
 
W15-W20t 
Week 25 
(Week 7 
+18 
weeks) 
Visit Number → 
SC 
Visit 
1 
SC 
Visit 
2 
Visit 
1 
Clinic 
Visit 2 
(Outpt) 
Visit 3 
(Outpt)  
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 4 
(Outpt) 
Visit 5 
(Outpt) 
Visit 6 
(Outpt) 
Visit 7 
Clinic 
 
Monthly 
Visits 
(Outpt) 
Un-
scheduled 
Visits 
(Clinic) 
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 8 
(Final, 
Clinic) 
Dose Number → 
 
 
Dose 
1 
Dose 2 
Dose 3 
N/A 
Dose 4 
Dose 5 
Dose 6 
 
 
 
 
 
Trial Procedure ↓ 
 
 
 
 
Unscheduled Visitsu 
 
 
 
 
Signature of ICF 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion and exclusion 
criteria verification 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history e 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Drug admin. – On 
site f 
 
 
 
X 
 
 
 
 
 
 
(Xf) 
 
 
 
 
Study Drug admin. - 
Outpatient f 
 
 
 
 
X 
X 
 
X 
X 
X 
Xf 
X w 
(weekly) 
 
 
 
Physical examination g 
 
X 
X 
 
 
 
X  
 
 
 
X 
 
X 
X 
X 
Body weight and height 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Vital Signs h 
 
X 
X 
 
 
 
X 
 
 
 
X 
 
X 
X 
X 
ECG/ECHO i 
 
X 
X 
(ECG) 
 
 
 
X 
 
 
 
X 
 
 
X 
X 
MRI j 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Prior and concomitant 
medicines k 
X 
X 
X 
 
 
 
X 
 
 
 
X 
X  
X 
X 
X 
Drug and alcohol test 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
QuantiFERON TB test  j 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
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KPL-914-C001 Amendment 1                                                                             Final 
Page 16 of 64 
 
CONFIDENTIAL 
Trial Period → 
Pre-
screening 
Period 
Run-In Period 
(Up to 3 days) 
Treatment Period 
(6 weeks) 
Extension Period 
(18 weeks) 
Visit Days/Weeks → 
Day -3 to 
Day 0a 
Day 
0b 
Week 
2c 
Week 
3c 
W3-W4d 
Week 
4c 
Week 
5c 
Week 
6cc 
Week 
6/ 
End-
of-
Trialc 
 
 
W15-W20t 
Week 25 
(Week 7 
+18 
weeks) 
Visit Number → 
SC 
Visit 
1 
SC 
Visit 
2 
Visit 
1 
Clinic 
Visit 2 
(Outpt) 
Visit 3 
(Outpt)  
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 4 
(Outpt) 
Visit 5 
(Outpt) 
Visit 6 
(Outpt) 
Visit 7 
Clinic 
 
Monthly 
Visits 
(Outpt) 
Un-
scheduled 
Visits 
(Clinic) 
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 8 
(Final, 
Clinic) 
Dose Number → 
 
 
Dose 
1 
Dose 2 
Dose 3 
N/A 
Dose 4 
Dose 5 
Dose 6 
 
 
 
 
 
Trial Procedure ↓ 
 
 
 
 
Unscheduled Visitsu 
 
 
 
 
Clinical laboratory tests 
(incl CRP)– Central 
laboratory l 
 
 
X 
X 
(X)x 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical laboratory tests 
(lipid panel) – Central 
Laboratory 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
X 
Clinical laboratory tests 
(incl CRP) – Study 
Site/Clinic laboratory m 
 
Xy 
X 
X 
(X)x 
 
 
X 
 
 
 
X 
 
X 
X 
X 
Biomarker testing, PK, 
and anti-rilonacept 
antibody – Central 
Laboratory l 
 
X 
 
(X) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy test n 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE evaluations o 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medication diary 
dispensing p 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medication diary 
compliance verification 
and reminder q 
 
 
X 
(X)x 
 
 
X 
 
 
 
X 
 
 
 
X 
Pericardial pain (11-pt 
Numerical Rating Scale)r 
X 
X 
X 
(X)x 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
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KPL-914-C001 Amendment 1                                                                             Final 
Page 17 of 64 
 
CONFIDENTIAL 
Trial Period → 
Pre-
screening 
Period 
Run-In Period 
(Up to 3 days) 
Treatment Period 
(6 weeks) 
Extension Period 
(18 weeks) 
Visit Days/Weeks → 
Day -3 to 
Day 0a 
Day 
0b 
Week 
2c 
Week 
3c 
W3-W4d 
Week 
4c 
Week 
5c 
Week 
6cc 
Week 
6/ 
End-
of-
Trialc 
 
 
W15-W20t 
Week 25 
(Week 7 
+18 
weeks) 
Visit Number → 
SC 
Visit 
1 
SC 
Visit 
2 
Visit 
1 
Clinic 
Visit 2 
(Outpt) 
Visit 3 
(Outpt)  
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 4 
(Outpt) 
Visit 5 
(Outpt) 
Visit 6 
(Outpt) 
Visit 7 
Clinic 
 
Monthly 
Visits 
(Outpt) 
Un-
scheduled 
Visits 
(Clinic) 
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 8 
(Final, 
Clinic) 
Dose Number → 
 
 
Dose 
1 
Dose 2 
Dose 3 
N/A 
Dose 4 
Dose 5 
Dose 6 
 
 
 
 
 
Trial Procedure ↓ 
 
 
 
 
Unscheduled Visitsu 
 
 
 
 
PGA (QoL 
questionnaire) s 
 
X 
 
X 
 
 
X 
 
 
 
X 
 
 
X 
X 
Dosing Procedure 
Questionnaire z 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
Investigator (or 
designee) phone 
call/virtual visit v 
 
 
 
 
X 
X 
 
X 
X 
X 
 
X 
(monthly) 
 
 
 
ECHO = echocardiogram, ECG = electrocardiogram, ICF = informed consent form, MRI = magnetic resonance imaging, Outpt = outpatient, PGA = patient 
global assessment, pt = point, TB = tuberculosis, HBcAb = hepatitis B core antibody; HBsAb = hepatitis B surface antibody; HBsAg = hepatitis B surface 
antigen; HCVAb = hepatitis C virus antibody; HIV = human immunodeficiency virus 
a. 
A second Screening visit (SCV2) should be performed within ~24h to 72h.  Under special circumstances, the Investigator, in consultation with the Sponsor, 
can combine SCV1 and SCV2.  The last Screening and Day 0 procedures may be performed on the same day, but SCR procedures must be completed prior 
to Study Drug administration.  
b. Subjects who do not complete the Treatment Period (withdraw consent or are discontinued before they have completed 6 weeks treatment), must be asked to 
complete the procedures specified at the EoT Visit. 
c. 
Weekly intervals refer to 7 ± 1 days. The interval between Study Drug administrations must be at least 5 days.  
d. Subjects should return for an optional Interval Evaluation Visit at the clinic between approximately Week 3 and 4, as determined by the Investigator. 
e. 
Including age at first attack, number of previous attacks, and duration of attacks.  
f. 
Drug administration training of subjects is performed at Visit 1.  Study Drug will be administered in the Study Site/Clinic at Visit 1. Study Drug 
administrations are performed by the subjects (self-administration) on Visits (Outpatient) 2, 3, 4, 5, and 6. Participation in the Extension Phase (optional) is 
determined at the Week 6/EoT Visit 7 by the Investigator.  Subjects who are eligible and who are willing to participate will be consented during EoT Visit 7 
at the Study Site/Clinic. Only subjects continuing treatment into the Extension Phase will receive Study Drug at Visit 7; Study Drug can be self-administered 
either as an outpatient or at the Study Site/Clinic (Site to provide Study Drug) depending on the logistics/timing of the EoT Visit 7 relative to the timing of 
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weekly dosing. Timing for dose administration is per direction of the Investigator based upon the prescribing information and study-specified dosing 
intervals. Continued weekly Study Drug treatment during the EP will be outpatient administration.    
g. Full physical examination including assessment of pericardial rub.    
h. Vital signs must be obtained in the seated position and include oral temperature, respiratory rate, blood pressure, and pulse. 
i. 
Central 12-lead ECG and echocardiogram reading (including assessment of pericardial effusion). At SCV2 only the ECG will be obtained. The Study 
Site/Clinic reading of the ECG and the ECHO at the time of the examination will be used by the Investigator for clinical decision-making. In addition, both 
the ECG and ECHO will be sent to a core laboratory for additional analysis. 
j. 
Optional.  
k. At the SCV1, information related to concomitant medicine that subjects were taking during at least the 2 weeks prior to the visit will be captured. During the 
Treatment Period, changes in concomitant medication since the last Study Site/Clinic visit will be documented. During the EP, changes in 
pericarditis/concomitant medication will be assessed at Study Site/Clinic Visits and in monthly outpatient phone calls/virtual visits.  
l. 
Biomarker, pharmacokinetics (PK) and anti-rilonacept antibody analysis samples will be drawn in all subjects and archived for future testing. . During each 
Visit at the Study Site/Clinic a sample for CRP will be obtained and sent to the central laboratory (or designated qualified laboratory) for analysis; at each 
Outpatient Visit; blood for central laboratory measurement of CRP will be obtained as described in the Laboratory Manual. 
m. Hematology, chemistry, and urinalysis will be performed at the Study Site/Clinic laboratories, and results when available will be entered into the eCRF with 
appropriate reference values. Serology (HCVAb, HBsAg, HBcAb, HBsAb and HIV) and urine drug screen will be performed at SCV1 only. 
n. To be eligible to continue in the trial, a negative urine pregnancy test must be documented at the SCV1. If the urine test is positive, additional Study 
Site/Clinic and/or central serum tests may be performed.  
o. All AEs occurring after the subject receives the first dose of Study Drug will be captured in source records and eCRF. 
p. At the SCV1, the Investigator or designee will instruct the subject about the use of the medication diary.  The subject will be asked to complete a entries   into 
the medication diary during the Screening Period and Treatment Period. Only information on pain/rescue medication will be collected. Other concomitant 
treatments/medications are not required to be captured. 
q. At the SCV2 and all subsequent visits at the Study Center, the Investigator or designee will review the Diary entry information to verify subject compliance.  
If the last screening visit occurs at a different day than Visit 1, the review will also be performed at Visit 1.  Diary documentation will end at the End-of-Trial 
visit (Visit 7).  
r. 
Subject assessment of pericardial pain using a validated 11-point Numerical Rating Scale.  The assessment will be performed on-site during clinic visits and 
as part of a telephone call/virtual visit during outpatient treatment weeks.  If the last screening visit occurs at a different day than Visit 1, the assessment will 
also be performed at Visit 1, prior to Study Drug treatment. 
s. 
Subject global assessment of overall well-being will be assessed using a validated QoL Questionnaire (see Appendix 3). The assessment will be performed 
on-site during clinic visits.  If SCV2 occurs at a different day than Visit 1 (Day 0), the global assessment will also be performed at Visit 1, prior to Study 
Drug administration. 
t. 
Subjects may return for an optional EP Interval Evaluation Visit at the clinic between Week 15 and 20 (8 to 13 weeks after Visit 7), as determined by the 
Investigator.  
u. Subjects reporting worsening of pericarditis symptoms or AEs may be brought in at the discretion of the Investigator for an Unscheduled Visit at any time 
during the Treatment Period.  Any subject who is not responding to treatment (e.g., no reduction in pericardial pain compared to baseline, no decrease in CRP 
levels, etc.) and who is therefore considered by the Investigator to be a “Treatment Failure” may be withdrawn from further Study Drug treatment at the 
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discretion of the Investigator and receive rescue therapy for their pericarditis according to standard of care as per Investigator decision; these subjects will be 
followed for safety for the remainder of the 6-week Treatment Period.  
v. At weekly Investigator (or designee) phone calls/virtual visits during the Treatment Period, Study Drug compliance, medication diary compliance, and 
laboratory sample collection will be checked. The subjects will be asked using non-leading questions about any AEs occurring since the last contact (phone 
call/virtual visit or site visit), and NRS pain assessment will be performed.  Investigator (or designee) phone calls/virtual visits will be performed monthly 
during the during the EP to perform NRS pain assessments, collect AE information, and review pericarditis/concomitant medications. If scheduled, in-person 
Study Site/Clinic Visits (Unscheduled Visits or Evaluation Visits) can replace the phone calls/virtual visits. 
w. During the Extension Period, Study Drug treatment is weekly by self-administration, and the study nurse visits to the home and Investigator (or designee) 
phone calls/virtual visits are monthly. 
x. Visit 1 will coincide with SCV2.  In case Visit 1 is separated from SCV2, SCV2 clinical laboratory blood sampling and subject NRS pericardial pain rating 
must be repeated prior to Study Drug dosing. 
y. Per Standard of Care. 
z. 
The dosing preparation and administration questionnaire must be completed in the presence of Study Staff (via virtual visit) or visiting nurse. 
 
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4 Table of Contents 
 
 
 
 
  
 
 
 
  
2 
Investigator and Administrative Structure ...................................................................... 3 
3 
Synopsis ......................................................................................................................... 4 
4 
Table of Contents ......................................................................................................... 20 
5 
List of Abbreviations and Definition of Terms ............................................................... 23 
6 
Introduction ................................................................................................................. 25 
7 
Study Objectives ........................................................................................................... 27 
7.1 
Primary Objective ........................................................................................................ 27 
7.2 
Secondary Objective(s) ................................................................................................. 27 
8 
Investigational Plan ...................................................................................................... 28 
8.1 
Overall Study Design and Plan ...................................................................................... 28 
8.2 
Discussion of Study Design ............................................................................................ 31 
8.3 
Selection of Study Population ........................................................................................ 31 
8.3.1 
Number of Planned Subjects ........................................................................... 31 
8.3.2 
Inclusion Criteria ........................................................................................... 31 
8.3.3 
Exclusion Criteria .......................................................................................... 32 
8.3.4 
Vaccination History and Immune status ............................................................ 33 
8.3.5 
Removal of Subjects from Therapy or Assessments ........................................... 34 
8.4 
Investigational Medicinal Products................................................................................ 35 
8.4.1 
Investigational Medicinal Products Administered .............................................. 35 
8.4.2 
Identity of Investigational Medicinal Products ................................................... 36 
8.4.3 
Method of Assigning Subjects to Treatment Groups ........................................... 36 
8.4.4 
Selection of Doses in the Study ....................................................................... 37 
8.4.5 
Selection and Timing of Dose for Each Subject ................................................. 37 
8.4.6 
Blinding........................................................................................................ 37 
8.4.7 
Prior and Concomitant Therapy ....................................................................... 37 
8.4.8 
Treatment Compliance ................................................................................... 38 
8.5 
Study Procedures ......................................................................................................... 39 
8.5.1 
Prescreening Period........................................................................................ 39 
8.5.2 
Screening Period ............................................................................................ 39 
8.5.2.1 
Screening Visit 1 (SCV1)................................................................................ 39 
8.5.2.2 
Screening Visit 2 (SCV2)................................................................................ 40 
8.5.3 
Treatment Period ........................................................................................... 41 
8.5.3.1 
Visit 1 (Study Site/Clinic) - Day 0 ................................................................... 41 
8.5.3.2 
Visits 2 to 6 (Outpatient) - Weeks 2, 3, 4, 5, 6 ................................................... 41 
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8.5.3.3 
Interval Evaluation Visit (Study Site/Clinic) - Week 3-4 ..................................... 42 
8.5.3.4 
Unscheduled Visits (Study Site/Clinic) During the Treatment Period ................... 42 
8.5.3.5 
Visit 7/ End-of-Trial (Study Site/Clinic) - Week 6 ............................................. 42 
8.5.4 
Extension Period ............................................................................................ 43 
8.5.4.1 
Unscheduled Visits (Study Site/Clinic) during the EP ......................................... 43 
8.5.4.2 
Interval Evaluation Visit During Extension Period (Study Site/Clinic) - 
Week 15-20................................................................................................... 44 
8.5.4.3 
Visit 8/Final Visit (Study Site/Clinic) - Week 25 ............................................... 44 
8.5.5 
Duration of Treatment .................................................................................... 45 
8.6 
Efficacy and Safety Variables ........................................................................................ 45 
8.6.1 
Individual Efficacy Assessments ...................................................................... 45 
8.6.1.1 
C-Reactive Protein, Biomarker, and PK Assessments ......................................... 45 
8.6.1.2 
Echocardiogram (Pericardial Effusion) ............................................................. 46 
8.6.1.3 
Electrocardiogram (Pericarditis Diagnostic Findings) ......................................... 46 
8.6.1.4 
Pericarditis Signs (Fever, Pericardial Rub) ........................................................ 46 
8.6.1.5 
Pericarditis Pain (Chest Pain) .......................................................................... 46 
8.6.1.6 
Magnetic Resonance Imaging .......................................................................... 47 
8.6.1.7 
Quality of Life Questionnaire .......................................................................... 47 
8.6.1.8 
Dosing Procedure Questionnaire ...................................................................... 47 
8.6.2 
Safety Assessments ........................................................................................ 48 
8.6.2.1 
Adverse Events .............................................................................................. 48 
8.6.2.2 
Serious Adverse Events .................................................................................. 49 
8.6.2.3 
Adverse Reactions ......................................................................................... 51 
8.6.2.4 
Clinical Laboratory Variables .......................................................................... 51 
8.6.2.5 
Vital Signs .................................................................................................... 53 
8.6.2.6 
Physical Examination ..................................................................................... 53 
8.6.2.7 
Body Weight and Height................................................................................. 53 
8.7 
Statistical Methods ....................................................................................................... 53 
8.7.1 
Statistical and Analytical Plans ........................................................................ 53 
8.7.1.1 
Datasets to be Analyzed .................................................................................. 53 
8.7.1.2 
General Statistical Methods ............................................................................. 53 
8.7.1.3 
Efficacy Endpoints ......................................................................................... 54 
8.7.1.4 
Safety Variables ............................................................................................ 54 
8.7.2 
Determination of Sample Size ......................................................................... 55 
8.8 
Quality Assurance and Quality Control ......................................................................... 55 
8.8.1 
Audit and Inspection ...................................................................................... 55 
8.8.2 
Monitoring .................................................................................................... 55 
8.8.3 
Data Management and Coding ......................................................................... 55 
8.8.4 
Record Keeping ............................................................................................. 56 
9 
Records and Supplies .................................................................................................... 56 
9.1 
Drug Accountability ..................................................................................................... 56 
10 
Ethics ........................................................................................................................... 56 
10.1 Institutional Review Board ........................................................................................... 56 
10.2 Ethical Conduct of the Study......................................................................................... 56 
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10.3 Subject Information and Consent .................................................................................. 57 
10.4 Subject Confidentiality (US Studies) .............................................................................. 57 
11 
Reporting and Publication ............................................................................................ 57 
12 
References .................................................................................................................... 58 
13 
Appendices ................................................................................................................... 60 
Appendix 1: Investigator Signature Page ................................................................................ 60 
Appendix 2: ARCALYST® Prescribing Information ............................................................... 61 
Appendix 3: Quality of Life Instrument .................................................................................. 62 
Appendix 4: 11-point Numerical Rating Scale (NRS) for Assessment of Pericarditis Pain ......... 64 
 
List of In-text Tables 
Table 1: 
Schedule of Evaluations .................................................................................. 15 
 
List of In-text Figures 
Figure 1: 
Schematic of KPL-914 (rilonacept) .................................................................. 26 
Figure 2: 
Overview of Trial Design................................................................................ 31 
Figure 3: 
11-point Numerical Rating Scale (NRS) for Assessment of Pericarditis Pain ......... 47 
 
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5 List of Abbreviations and Definition of Terms 
AcP 
accessory protein 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
BP 
blood pressure 
b.p.m. 
beats per minute 
BUN 
blood urea nitrogen 
CAPS 
Cryopyrin Associated Periodic Syndrome  
CDC 
Centers for Disease Control 
CHO 
Chinese hamster ovary 
CI 
confidence interval 
CRO 
contract research organization 
CRP 
C-reactive protein 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
CTAD 
citrate, theophylline, adenosine, dipyridamole 
EoT 
End-of-Trial 
EP 
Extension Period 
ESC 
European Society of Cardiology 
ESR 
erythrocyte sedimentation rate 
FCAS 
Familial Cold Auto-Inflammatory Syndrome 
GCP 
Good Clinical Practice 
GGT 
gamma glutamyltransferase 
HBcAb 
hepatitis B core antibody 
HBsAb  
hepatitis B surface antibody 
HBsAg 
hepatitis B surface antigen 
HCVAb 
hepatitis C virus antibody 
HIV 
human immunodeficiency virus 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IgG 
immunoglobulin G 
IL-1 
Interleukin-1 
IL-1RA 
IL-1 receptor antagonist 
IL-1RI 
IL-1 type I receptor 
IMP 
Investigational Medicinal Product 
IRB 
Institutional Review Board 
IV 
intravenous 
kDa 
kilo Dalton 
KPL-914 
Study Drug; nomenclature of rilonacept (ARCALYST®) in this protocol 
LDH 
lactate dehydrogenase 
MCH 
mean cell hemoglobin 
MCHC 
MCH concentration 
MCV 
mean cell volume  
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
magnetic resonance imaging 
mITT 
modified intent to treat 
MWS 
Muckle-Wells Syndrome 
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NRS 
Numerical Rating Scale 
NSAID 
nonsteroidal anti-inflammatory drugs 
PI 
Prescribing Information 
PP 
per protocol 
PPD 
purified protein derivative 
PRO 
patient-reported outcome 
PT 
prothrombin 
PTT 
prothrombin time 
QoL 
quality of life 
RBC 
red blood cell 
RIP 
recurrent idiopathic pericarditis 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SC 
subcutaneous 
SCR 
Safety Review Committee 
SCV 
screening visit 
SD 
standard deviation 
SOP 
standard operating procedure 
SRC 
Safety Review Committee 
SUSAR 
serious and unexpected and related adverse reaction 
TB 
tuberculosis 
 
 
TNF 
tumor necrosis factor 
US 
United States of America 
WBC 
white blood cells 
WHO 
World Health Organization 
WFI 
water for injection 
 
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and dose relationships will be assessed.  Commercially-available rilonacept (ARCALYST®) will be used in 
the study. 
The nonclinical development program for rilonacept (ARCALYST®) demonstrated biological activity and 
adequate safety across toxicity studies (Appendix 2: ARCALYST® Prescribing Information). 
The most common adverse reactions reported by patients with CAPS treated with ARCALYST® are 
injection-site reactions and upper respiratory tract infections.  Hypersensitivity reactions associated with 
rilonacept administration have been rare.  
Refer to the ARCALYST® PI for Important Safety Information regarding rilonacept (Appendix 2: 
ARCALYST® Prescribing Information).  
Based on its IL-1-antagonistic properties, its weekly-dosing pharmacokinetics, and its well-understood 
safety profile as shown in patients with CAPS, rilonacept (KPL-914) is a promising candidate for the 
treatment of RIP.  
 
7 Study Objectives 
7.1 
Primary Objective 
To collect inter- and intra-subject variability data on C-reactive protein (CRP) measurements and the 
11-point NRS instrument for assessment of pericardial pain in symptomatic subjects with recurrent 
idiopathic pericarditis (RIP) both at baseline and on treatment with KPL-914 in order to inform power 
calculations for future trials in RIP. 
7.2 
Secondary Objective(s) 
To explore the time course to improvement of pericarditis parameters in symptomatic subjects with RIP 
treated with KPL-914. 
To evaluate the safety of KPL-914 in symptomatic subjects with RIP. 
 
 
 
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8 Investigational Plan 
8.1 
Overall Study Design and Plan 
This is an open-label single-active-arm pilot study to explore clinical and biochemical endpoints of 
improvement of pericarditis symptomatology and to collect inter- and intra-subject variability data on both 
at-baseline and on-treatment parameters in symptomatic subjects with RIP who will be treated with once-
weekly subcutaneously (SC)-administered injections of KPL-914.   
Subjects identified for participation in this trial will present during a symptomatic episode of RIP, having 
previously experienced a first (index) episode of acute pericarditis followed by at least 1 recurrent episode 
before the current enrollment-qualifying episode, using the 2015 European Society of Cardiology (ESC) 
Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 2015) as a frame of 
reference: 
- 
The index episode of acute pericarditis would have been characterized by an inflammatory 
pericardial syndrome with at least 2 of the 4 following criteria: pericarditic chest pain, pericardial 
rub, new widespread ST-segment elevation or PR-segment depression on electrocardiogram (ECG), 
and pericardial effusion (new or worsening).  Additional supportive findings would have included 
elevations of markers of inflammation (i.e., CRP, erythrocyte sedimentation rate [ESR], and white 
blood cell [WBC] count) or evidence of pericardial inflammation by an imaging technique (e.g., 
magnetic resonance imaging [MRI]).   
- 
Recurrence of RIP would have been characterized as a subsequent episode of pericarditis occurring 
after a symptom-free interval of 4-6 weeks or longer.   
For the purposes of this study, the Investigator will determine, based on his/her judgement of the available 
data, if a subject has met these criteria for having experienced a previous index episode of acute pericarditis 
followed by at least 1 recurrent episode of pericarditis prior to the presenting symptomatic episode of RIP 
and will record the criteria supporting this diagnosis in the electronic case report form (eCRF). 
Prior to enrolment, potential subjects may enter an optional Prescreening Period, after signing a 
Prescreening ICFto allow monitoring for symptoms and inflammatory markers (CRP, ESR, etc) while 
existing medications for recurrent idiopathic pericarditis may be managed by the Investigator or their 
clinician according to standard of care. 
 
Study subjects will be enrolled (Screening Visit 1 [SCV1]) at the time of a symptomatic episode.  In addition 
to meeting the criteria for pericarditis in the judgement of the Investigator, all subjects must present with a 
CRP value ≥1 mg/dL at the time of study enrollment.  Subjects included in the study may be receiving 
concomitant nonsteroidal anti-inflammatory drugs (NSAIDs), and/or colchicine, and/or oral corticosteroid 
treatment in any combination, provided the dosages of these medications have been stable for at least 7 
days, although stable doses for a shorter period will be acceptable if in the opinion of the Investigator, in 
consultation with the Sponsor, a shorter period of stability is not anticipated to alter the baseline CRP values.  
Baseline therapy and disease characteristics will be determined during a Screening Period of up to 72 hours, 
as needed, to confirm the pre-treatment diagnostic workup.  At the SCV1, baseline subject and disease 
characteristics will be determined and captured in the eCRF.  Persistence of diagnostic criteria for 
pericarditis will be confirmed (Screening Visit 2 [SCV2]) within the 24 - 72 hour period before subjects 
advance to the Treatment Period of the study. Under special circumstances, the Investigator, in consultation 
with the Sponsor, can combine SCV1 and SCV2, and the subject can proceed directly to the Day 0 dosing 
visit. 
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Approximately 10 subjects will participate in the active Treatment Period of the study.  Following review 
of the ongoing data by the Sponsor and the Investigators, the sample size may be increased to a total of up 
to 20 subjects. After having met all the entry criteria during the Screening Period, the subjects entering the 
Treatment Period will receive a loading dose of KPL-914 (2 x 160 mg SC) on Day 0, then 160 mg SC 
weekly for 5 additional doses.  
The first Study Drug dose on Day 0 will be administered at the Study Site/Clinic (Visit 1).  Subsequent 
weekly Study Drug doses from Weeks 2 to 5 will be self-administered by the subject as an outpatient SC 
administration. A visiting study nurse will assess and record compliance with Study Drug administration at 
the subject’s home as well as provide guidance and training on Study Drug administration as needed. At 
Week 6/End of Trial, Study Drug may be self-administered or administered at the study site.  Weekly 
assessments of safety and treatment response, including administration of the 11-point NRS instrument to 
assess pericardial pain, will be done at the Study Site/Clinic at Visit 1 (Day 0) and Visit 7 (Week 6/End-of-
Trial), and via Investigator (or designee) phone calls/ virtual visits at Weeks 2 to 5 (Visits 2 to 5). Weekly 
outpatient blood samples for central laboratory testing will be collected at the Study Site/Clinic, or at a 
qualified laboratory site in the vicinity of the subject, or by a visiting study nurse. 
Investigators are encouraged to schedule subjects at the Study Site/Clinic for an in-person Interval 
Evaluation Visit during approximately Weeks 3-4 to assist the Investigator in the clinical management of 
the subject.  During this visit a full assessment including physical examination, vital signs, ECG, 
echocardiogram, and laboratory testing can be performed as well as the recording of adverse events (AEs) 
and other study related assessments as needed.   
At any time point during the Treatment Period, subjects reporting worsening of pericarditis symptoms or 
AEs may be brought into the Study Site/Clinic at the discretion of the Investigator for an Unscheduled Visit, 
in which select or comprehensive clinical assessments can be performed.  Any subject who is determined 
by the Investigator as not responding to treatment (e.g., no reduction in pericardial pain compared to 
baseline, no decrease in CRP levels, etc.) and who is therefore considered by the Investigator to be a 
“Treatment Failure” may be withdrawn from further Study Drug treatment at the discretion of the 
Investigator and may receive rescue therapy for their pericarditis according to standard of care as per 
Investigator decision; these subjects will be followed for safety for the remainder of the 6-week Treatment 
Period.  Subjects identified as “Treatment Failures” may be replaced at the discretion of the Sponsor in order 
to provide an adequate sampling of subjects completing the active Treatment Period. 
Subjects participating for the complete length of the active study Treatment Period will receive a total of 6 
doses of KPL-914.  For the duration of the Treatment Period, concomitant NSAIDs and/or colchicine and/or 
corticosteroids, if present, should be continued at pre-study dose levels until after the 6-dose Study Drug 
Treatment Period has concluded; however, should the Investigator determine that a reduction/tapering of 
the NSAID, colchicine, and/or corticosteroid dose is medically indicated, the NSAID, colchicine, and/or 
corticosteroid dose can be down-titrated in consultation with the Sponsor, and the modification of dose 
should be recorded in the source records and the eCRF.  
Opioid analgesics, non-narcotic analgesics (e.g., tramadol), and acetaminophen are allowed as rescue 
medication for ancillary pain control on an as-needed basis throughout the Treatment Period.  Although it 
is recommended that NSAID dose levels (if present) should remain constant during the active Treatment 
Period, the concomitant NSAID dose may be temporarily increased (or an NSAID initiated) for ancillary 
pain control if deemed necessary by the Investigator, after consultation with the Sponsor. Any rescue 
medication use must be recorded in source records, eCRF and medication diary.  
At the discretion of the Investigator, “Treatment Responders” (defined by the Investigator as a clinically 
significant reduction in pericardial pain using the 11-point NRS, normal or near-normal CRP levels, and/or 
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absent or decreasing echocardiographic effusion at the End-of-Trial Visit), will be offered participation in 
an optional 18-week Extension Period (EP), in which weekly open-label KPL-914 can be continued at the 
same dose as in the Treatment Period for a total duration of Study Drug treatment of up to 24 weeks. Weekly 
treatments during the EP are by self-administration, and study nurse visits to the subject’s home as well as 
Investigator (or designee) telephone calls/virtual visits are to continue on a monthly basis. 
During the EP, the Investigator may choose to wean concomitant NSAIDs, colchicine, and/or corticosteroids 
according to standard of care paradigms; all medication changes must be recorded in source records and the 
eCRF.  Investigators are encouraged to invite subjects to the Study Site/Clinic for an in-person Interval 
Evaluation Visit between Weeks 15 to 20 (8 to 13 weeks after the Visit 7/End of Trial Visit) to assist the 
Investigator in the clinical management of the subject.  During this visit a physical examination, vital signs, 
ECG, echocardiogram (ECHO), and laboratory testing can be performed at the discretion of the Investigator. 
Available safety, tolerability, and efficacy data for each subject will be reviewed by the Investigator as part 
of ongoing subject management.  A Safety Review Committee (SRC) including selected Investigator(s) and 
Sponsor representatives will review on a monthly basis (at a minimum) all available data for all subjects, 
considering trends across each.  
Given the following occurrences, dosing may be halted or reduced, in accordance with an SRC 
recommendation, confirmed by the Sponsor: 
- 
One or more subjects experience a serious and unexpected adverse event that is considered by the 
Investigator to be related to Study Drug (SUSAR), or 2 or more subjects experience similar severe 
(non-serious) and unexpected AEs that are considered by the Investigator to be related to Study 
Drug. 
After an initial group of subjects has been treated, depending on the safety profile observed as well as the 
magnitude and speed of treatment response (e.g., if an informative number of subjects achieve treatment 
response early in the Treatment Period), the Sponsor in collaboration with the Investigators may elect to 
decrease the KPL-914 dose administered to a subsequent consecutive group of subjects to a loading dose of 
2 x 80 mg administered SC on Day 0, then 80 mg administered SC weekly for 5 additional weeks, in order 
to explore efficacy at a lower dose.  Depending on treatment response observed with the 80 mg dose, the 
weekly dose administered to either these subjects or subsequent subjects may be changed back to 160 mg 
by the Investigator in collaboration with the Sponsor.  For any given subject, the KPL-914 dose level 
received at the end of the Treatment Period should be continued into the EP (if administration is continued); 
however, a change in the KPL-914 dose level during the EP for any individual subject can be made at the 
discretion of the Investigator in consultation with the Sponsor, and the modification of dose should be 
recorded in the source records and the eCRF. 
During the Screening and Treatment Periods, subjects will enter information concerning the use of 
pericarditis and rescue (pain) medication into a medication diary.  Such information will be entered by the 
subject on a daily basis. 
 
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Diagnosis and Management of Pericardial Diseases (Adler et al, 2015) as a frame of reference --  i.e., 
met at least 2 of the 4 following criteria: pericarditic chest pain, pericardial rub, new widespread ST-
segment elevation or PR-segment depression on ECG, and pericardial effusion (new or worsening).  
Additional supportive findings could include elevations of markers of inflammation (i.e., CRP, 
erythrocyte sedimentation rate, and white blood cell count) or evidence of pericardial inflammation by 
an imaging technique (e.g., MRI). 
5. Has had at least one prior recurrent episode of pericarditis, in the judgement of the Investigator, based 
upon the available diagnostic information. 
6. Has an ongoing symptomatic episode of pericarditis at the time of study enrollment in the judgement 
of the Investigator, based upon the available diagnostic information. 
7. Has an elevated CRP value (i.e., >1 mg/dL) at the time of study enrollment.  
8. If used, has received NSAIDs, and/or colchicine and/or corticosteroids (in any combination) at stable 
dose levels for at least 7 days prior to Study Drug dosing (although stable doses for a shorter period 
will be acceptable if, in the opinion of the Investigator in consultation with the Sponsor, a shorter 
period of stability is not anticipated to alter the baseline CRP values) and is anticipated to continue 
these concomitant medications at these dose levels for the duration of the active Treatment Period.   
9. If female, must be nonpregnant and nonlactating and must agree to use an effective method of 
contraception, e.g., hormonal contraception or double-barrier birth control.  
10. Is able to adequately maintain a daily medication diary. 
11. Agrees to refrain from making any new, major life-style changes that may affect pericarditis 
symptoms (e.g., starting a new diet or change in exercise pattern) from the time of signature of the ICF 
to the End-of-Trial Visit (Week 6). 
8.3.3 
Exclusion Criteria 
A subject who meets any of the following criteria will not be eligible to participate in the trial: 
1. Has a diagnosis of pericarditis that was secondary to specific etiologies, including tuberculous, 
neoplastic, or purulent etiologies, post cardiac injury syndromes, myocarditis, or systemic diseases 
including autoinflammatory diseases, autoimmune diseases (e.g., rheumatoid arthritis, systemic 
lupus erythematosus, etc.). 
2. Has a history of immunodepression, including a positive human immunodeficiency virus test result. 
3. Has received treatment with any systemic immunosuppressants (other than, for example, 
corticosteroids or mycophenolate) which, in the opinion of the Investigator (in consultation with the 
Sponsor), may interfere with the study endpoints within the 6-month period before dosing.  
4. Currently receiving other interleukin (IL)-1 or IL-6 blockers, janus-activating kinase (JAK) or tumor 
necrosis factor (TNF) inhibitors. 
5. Has a history of myeloproliferative disorder, demyelinating disease, or symptoms suggestive of 
multiple sclerosis. 
6. Female subject who is pregnant or lactating or who does not agree to use an effective method of 
contraception, e.g., hormonal contraception or double-barrier birth control. 
7. Has a history of active or latent treated tuberculosis (TB), or had a positive QuantiFERON (QFT-TB 
G In-Tube) test result, or a chest radiograph during the 3 months prior to Study Drug dosing 
suggestive of prior TB infection. A subject with a positive purified protein derivative (PPD) test 
result (≥5-mm induration) after the first attack of pericarditis is excluded unless he/she has had 
either a negative chest x-ray result or a negative QuantiFERON test result. 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, night sweats) upon review of medical history and/or 
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physical exam.  Have recent close contact with a person with active TB.  
8. Chest radiograph (or historic results within 3 months of SCV1) that shows evidence of malignancy 
or any abnormalities suggestive of prior TB infection, including, but not limited to, apical scarring, 
apical fibrosis, or multiple calcified granulomata.  This does not include non-caseating granulomata. 
9. Has received immunization with a live (attenuated) vaccine within 12 weeks before the start of the 
study. 
10. Has history of or positive or intermediate results for hepatitis B surface antigen (HBsAg), hepatitis 
B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at SCV1. 
11. Has an estimated glomerular filtration rate (eGFR) <30 mL/min.  
12. Has a history of malignancy of any organ system within the past 5 years (other than a successfully 
treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma 
in situ of the cervix). 
13. 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. 
14. Has had a serious infection, has been hospitalized for an infection, has been treated with oral 
antibiotics within 2 weeks, or has been treated with IV antibiotics for an infection within 2 months 
of first Study Drug administration.  
15. Has had an organ transplant.  
16. In the Investigator's judgement, has a history of alcoholism or drug/chemical abuse within 2 years 
prior to Study Drug administration. 
17. Has a drug screen positive for amphetamines, cocaine, or phencyclidine or positive alcohol test at 
SCV1.  Exceptions may be made if a subject is on an approved medication for a stable concomitant 
condition that explains the positive screen. 
18. Has taken commercially-available rilonacept (ARCALYST®) or participated in a rilonacept clinical 
study during the 90 days before SCV1.  Has used anakinra within 30 days (or 5 half-lives, 
whichever is longer) prior to Study Drug administration. 
19. Has a history of hypersensitivity to rilonacept or to any of the excipients contained in the Study 
Drug. 
20. Has received an investigational drug during the 30 days before SCV1 or is planning to receive an 
investigational drug (other than that administered during this trial) or use an investigational device 
at any time during the trial. 
21. In the Investigator's judgement, has any other medical condition that could adversely affect the 
subject's participation or interfere with study evaluations.  
22. Subject who, in the opinion of the Investigator, is not likely to be compliant with the study protocol. 
23. Subject who, in the opinion of the Investigator in consultation with the Sponsor, should not 
participate in this study. 
 
8.3.4 
Vaccination History and Immune status 
IL-1 blockade may interfere with immune response to infections. Therefore, the Investigator should review 
with the subject the subject's vaccination history relative to the current medical guidelines for vaccine use.  
A recommended immunization schedule is available at the website of the Centers for Disease Control (CDC) 
(www.cdc.gov/vaccines/recs/scheduled/default.htm). 
It is recommended that, prior to or shortly after initiation of therapy with KPL-914, subjects be brought up 
to date with all vaccinations, as appropriate, including pneumococcal vaccine and inactivated influenza 
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vaccine. In case a subject needs vaccination after initiation of KPL-914 treatment, vaccination with inactive 
vaccine(s) may be performed (e.g., at the Study Site/Clinic) after the 6-week active Treatment Period.  
However, to minimize the potential confounding of KPL-914-related Adverse Experience reporting at 
initiation of KPL-914 dosing or measurements of CRP during the treatment period, vaccination should not 
be performed within the first 6 weeks after initiation of KPL-914 administration.   
It is recommended that all vaccinations be documented as up-to-date at or shortly after Visit 7, at which 
point subjects are being considered for longer-term treatment with KPL-914.  
Administration of KPL-914 is prohibited within 12 weeks of having received a live (attenuated) vaccine.  It 
is also possible that taking drugs that block IL-1 increases the risk of TB.  Healthcare providers should 
follow current CDC guidelines both to evaluate for and to treat possible latent TB infections before initiating 
therapy with KPL-914. 
8.3.5 
Removal of Subjects from Therapy or Assessments 
Subjects reporting worsening of pericarditis symptoms or AEs may be brought into the Study Site/Clinic at 
the discretion of the Investigator for an Unscheduled Visit at any time during the Treatment Period.  Any 
subject who is not responding to treatment (e.g., no reduction in pericardial pain compared to baseline, no 
decrease in CRP levels, etc.) and who is therefore considered by the Investigator to be a “Treatment Failure” 
may be withdrawn from further Study Drug treatment at the discretion of the Investigator and receive rescue 
therapy for their pericarditis according to standard of care as per Investigator decision; these subjects will 
be followed for safety for the remainder of the 6-week Treatment Period.  Subjects identified as “Treatment 
Failures” may be replaced at the discretion of the Sponsor in order to provide an adequate sampling of 
subjects completing the active Treatment Period. 
Safety, tolerability, and efficacy data for each subject will be reviewed by the Investigator on an ongoing 
basis as part of subject management.  An SRC including selected Investigator(s) and Sponsor representatives 
will review on a monthly basis (at a minimum) all available data for all subjects, considering trends across 
each.  
Given the following occurrences, dosing may be halted or the dose reduced, in accordance with an SRC 
recommendation, confirmed by the Sponsor: 
• 
One or more subjects experience a serious and unexpected adverse event that is considered by the 
Investigator to be related to Study Drug (SUSAR), or 2 or more subjects experience similar severe 
(non-serious) and unexpected AEs that are considered by the Investigator to be related to Study 
Drug. 
In addition, subjects may stop study treatment or may be withdrawn from treatment for any of the following 
reasons: 
• 
Subject request.  Subjects are free to withdraw from the study at any time without providing 
reason(s) for withdrawal and without prejudice to further treatment 
• 
Use of non-permitted concurrent therapy 
• 
Non-compliance 
• 
Investigator request. 
Treatment Failures or subjects who are withdrawn from the study for safety reasons will be replaced at the 
discretion of the Sponsor.  Similarly, subjects who do not comply with the protocol or who withdraw from 
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the study for other reasons can be replaced.  The reason(s) for withdrawal will be documented in the source 
records and the eCRF. 
Subjects withdrawing from the study during the Treatment Period will be asked to complete the End-of-
Trial evaluations to document the status of their pericarditis disease progression at the time of withdrawal 
from treatment.  Subjects will continue to be followed for vital status for the duration of intended treatment 
to address informative censoring.  Subjects withdrawing from the study during the EP will be asked to 
complete the Final Visit evaluations. 
All reasonable efforts will be made to contact subjects who are lost to follow-up.   
The Sponsor has the right to terminate the study at any time in case of safety concerns (e.g., SUSARs) or if 
special circumstances concerning the Investigational Medicinal Product (IMP) 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. 
Pregnancy 
Pregnant or lactating female subjects are excluded from study enrollment.  While not explicitly stated in the 
rilonacept (ARCALYST®) PI (Appendix 2: ARCALYST® Prescribing Information), for the purposes of this 
experimental protocol, females of child-bearing potential (i.e., not postmenopausal and not sterilized) must 
use an active method of birth control during the course of the study, e.g., oral, implanted or injected 
contraceptive hormones, an intrauterine device, or a barrier method (e.g., diaphragm, condoms, 
spermicides).  
Subjects will be instructed that known or suspected pregnancy occurring during the study should be 
confirmed and reported to the Investigator without delay.  If pregnancy is confirmed, the Investigator must 
notify the Sponsor within 24 hours and the subject must not receive (additional) Study Drug and must be 
discharged from the study.  The subject must be asked regarding their willingness to complete the End-of-
Trial Visit. 
In the event that a subject is found to be pregnant after having received at least one Study Drug dose, the 
pregnancy will be followed to term and the status of mother and child will be reported to the Sponsor after 
delivery. 
Instances of perinatal death or congenital abnormality, if brought to the attention of the Investigator at any 
time after cessation of the study treatment, will be reported to the Sponsor within 24 hours. 
Full details will be recorded on the pregnancy form. 
8.4 
Investigational Medicinal Products 
8.4.1 
Investigational Medicinal Products Administered 
During the Treatment Period, KPL-914 will be administered as an initial loading dose of 2 x 160 mg SC on 
Day 0, then 160 mg SC dosed once weekly for up to 5 subsequent weeks.  At the discretion of the 
Investigator, subjects completing the Treatment Period may enter the 18-week Extension Period and receive 
up to 18 additional weekly doses of KPL-914. 
At the discretion of the Sponsor in collaboration with the Investigators, the Study Drug dosing regimen may 
be decreased in a consecutive group of subjects to a loading dose of 2 x 80 mg SC on Day 0, then 80 mg SC 
dosed once weekly for 5 subsequent weeks to explore efficacy at a lower dose. Depending on treatment 
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response observed with the 80 mg dose, the dose administered to either these subjects or subsequent subjects 
may be changed back to 160 mg by the Investigator in collaboration with the Sponsor. For any given subject, 
the KPL-914 dose level received at the end of the Treatment Period should be continued into the EP (if 
administration is continued); however, a change in the KPL-914 dose level during the EP for any individual 
subject can be made at the discretion of the Investigator in consultation with the Sponsor, and the 
modification of dose should be recorded in the source records and the eCRF. 
Sites for SC 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. 
No placebo or active comparator drug will be used.  
8.4.2 
Identity of Investigational Medicinal Products 
KPL-914 (rilonacept/ARCALYST®) is prepared as a lyophilized formulation containing histidine, 
polyethylene glycol 3350, glycine, arginine, and sucrose at pH 6.5.  It 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 WFI is required prior to SC 
administration of the drug.  The reconstituted drug product is a viscous, clear, colorless to pale yellow, 
essentially free from particulates, 80-mg/mL solution. 
After the addition of preservative-free sterile WFI, the vial contents should be reconstituted by gently 
shaking the vial for approximately 1 minute and then allowing it to sit for 1 minute.  A volume of up to 2 
mL can be withdrawn, which is designed to deliver 160 mg for SC administration only. 
KPL-914 (rilonacept) will be provided by the Sponsor to the study sites and to the study subjects in its 
commercially-available formulation (ARCALYST®) as a lyophilized powder to be reconstituted for SC 
administration.  The sites will receive Study Drug for on-site administration at Study Site/Clinic visits. Drug 
will be disseminated to the trial subjects for outpatient self-administration according to a supply chain 
described in the Pharmacy Manual.   
The lyophilized Study Drug (KPL-914 also called rilonacept, US tradename: ARCALYST®) is to be stored 
refrigerated at 2° to 8°C (36° to 46°F) inside the original carton to protect it from light.  After reconstitution, 
KPL-914 may be kept at room temperature, should be protected from light, and should be used within 3 
hours of reconstitution.  Unused portions of KPL-914 product must not be injected.  All vials of used and 
unused Study Drug during the active Treatment Period must be returned to the clinical site for cataloguing 
and documentation of compliance.   
The Sponsor through Regeneron Pharmaceuticals, Inc. will ensure that the Study Drug and certificates of 
analysis are available before the start of the study and at all times during the study. 
ARCALYST® is a registered trademark of Regeneron Pharmaceuticals, Inc. 
8.4.3 
Method of Assigning Subjects to Treatment Groups 
Subjects who meet all of the inclusion criteria and none of the exclusion criteria will enter the Treatment 
Period at Visit 1 (Day 0). 
Since this is an open-label, single-active-arm study, all subjects will receive KPL-914 active treatment.  
Assignment to treatment groups is not applicable. 
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corticosteroid dose can be down-titrated in consultation with the Sponsor, and the modification of dose 
should be recorded in the source records and the eCRF. 
Subjects who received, within the 6-month period before dosing, immunomodulatory therapy other than, 
for example, corticosteroids or mycophenolate, which in the opinion of the Investigator (in consultation 
with the Sponsor) may interfere with the study endpoints, or subjects who used commercially-available 
rilonacept (ARCALYST®) within 90 days before the Screening Visit are excluded from participation.  
Throughout the Treatment Period opioid analgesics, non-narcotic analgesics (e.g., tramadol), and 
acetaminophen are allowed as rescue medication for ancillary pain control on an as-needed basis.  Although 
it is recommended that NSAID dose levels (if present) should remain constant during the active Treatment 
Period, the concomitant NSAID dose may be temporarily increased (or an NSAID initiated) for ancillary 
pain control if deemed necessary by the Investigator, after consultation with the Sponsor.  Any rescue 
medication use must be recorded in source records, the medication diary and the eCRF. Other interleukin 
(IL)-1 or IL-6 blockers, janus-activating kinase (JAK) and tumor necrosis factor (TNF) inhibitors are 
prohibited for the duration of the study.  
Medical management of pericarditis during the EP is based on Investigator discretion.  He/she may continue 
subjects on KPL-914 at the same dosage level, wean-off or discontinue Study Drug in consultation with the 
Sponsor, or change (increase or decrease) the dosing of NSAIDs/colchicine/corticosteroids.  Other 
pericarditis medications may also be initiated at the discretion of the Investigator.  All changes to 
pericarditis-related medications should be captured in the source records and the eCRF. 
During the Screening and Treatment Periods, subjects will enter information concerning the use of 
pericarditis and rescue (pain) medication into a daily medication diary.  Such information will be entered 
by the subject on a real-time basis. 
8.4.8 
Treatment Compliance 
Study Drug will be administered to the subject by the Investigator or qualified study center staff at the Study 
Site/Clinic Visit 1 (Day 0).  Subsequent weekly Study Drug doses from Weeks 2 to 5 will be self-
administered by the subject as an outpatient SC administration. The study center staff or a  visiting study 
nurse will assess and record compliance with Study Drug administration at the subject’s home as well as 
provide guidance and training on Study Drug administration as needed. At Week 6/End-of-Trial, Study 
Drug may be self-administered or administered at the study site. All medication use (for pericarditis and use 
of rescue [pain] medication) will be documented by the subject in the medication diary during the Treatment 
Period.  
All vials of used and unused Study Drug during the active Treatment Period and the EP must be retained by 
the Study Site/Clinic and the subject to allow for cataloguing and documentation of compliance. Subjects 
must return all used and unused medication to the Study Site/Clinic.  Drug accountability and documentation 
thereof is described in the Pharmacy Manual. 
Study Drug compliance by the subject will be monitored during the Treatment Period by phone calls/virtual 
visits (made by qualified site staff).  Subjects will be reminded of recording all pericarditis and rescue pain 
medication information in the medication diary.  The medication diary will be returned to the site by the 
subject and reviewed by the Investigator/qualified staff.  During the EP, Study Drug use will be documented 
during monthly phone calls/virtual visits or Study Site/Clinic visits. 
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8.5 
Study Procedures 
All data of Study Site/Clinic visit assessments as well as Investigator (or designee) phone calls/virtual visits 
will be documented in source records and in the eCRF. 
8.5.1 
Prescreening Period 
Prior to enrollment, potential subjects may enter an optional Prescreening Period, after signing of a 
Prescreening ICF, to allow monitoring for symptoms, inflammatory markers (CRP, ESR, etc) while 
existing medications for recurrent idiopathic pericarditis may be managed by the Investigator or their 
clinician per standard of care. 
 
The Prescreening Period starts with the signing of the Prescreening ICF and lasts until the subject enters the 
Screening Period by signing the ICF for the full study or is withdrawn (see section 8.3.5).  
8.5.2 
Screening Period 
The Screening Period starts with the signature of the ICF and may last for up to 3 days.  During this period, 
subject eligibility for entry into the Treatment Period will be determined.  A rheumatology consultation 
during the Screening Period is optional. 
At SCV1, baseline subject and disease characteristics will be determined.  Persistence of diagnostic criteria 
for pericarditis will be confirmed within ~24 to 72 hours at SCV2.  Under special circumstances, the 
Investigator in consultation with the Sponsor, can combine SCV1 and SCV2. 
The end of the Screening Period may coincide with the start of the Treatment Period.   
8.5.2.1 
Screening Visit 1 (SCV1) 
• At the SCV1, written informed consent will be obtained before any protocol-specific assessments are 
made. 
• All subjects will be assessed for eligibility against the inclusion and exclusion criteria. 
• Demographic data, such as ethnic origin, date of birth and sex will be recorded. 
• The subject’s full medical history, including age at first attack, number of previous attacks, duration 
of attacks as well as concomitant illnesses/diseases will be documented. 
• Information related to concomitant medicine that subjects were taking during at least the 2 weeks 
prior to the visit will be captured. 
• A full physical examination will be performed, including assessment of pericardial rub. 
• Body weight and height will be assessed. 
• Vital signs will be obtained in the seated position and include oral temperature, respiratory rate, blood 
pressure, and pulse. 
• A pregnancy test (urine dip-stick) will be done. If the urine test is positive, additional Study 
Site/Clinic and/or central serum tests may be performed. 
• 12-lead ECG and full echocardiogram (ECHO) will be performed.  ECHO will include assessment 
of pericardial effusion.  The Study Site/Clinic readings at the time of the examination will be 
available to the Investigator for clinical decision-making. In addition, both the ECG and ECHO will 
be sent to a core laboratory for additional analysis. 
• A cardiac MRI may be performed (optional). If done, the images will be assessed by a central reader. 
The Study Site/Clinic reading at the time of the examination may be used by the Investigator for 
clinical decision-making. 
• Samples for laboratory tests will be collected. 
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o Local Lab Assessments: 
▪ 
Full hematology (including ESR), chemistry (including CRP), and urinalysis 
▪ 
Serology (HCVAb, HBsAg, HBcAB, HBsAb and HIV)  
▪ 
A QuantiFERON® test for tuberculosis (TB) can be performed (optional).  
Screening for drugs of abuse and alcohol abuse will be performed on urine samples collected at this visit.  
o Central Laboratory Assessments: 
▪ 
CRP/hsCRP  
• Samples for archive biomarker, pharmacokinetics (PK), and anti-rilonacept (anti-KPL-914) antibody 
testing will be collected, sent to the central laboratory, and stored for analysis.A medication diary 
for documentation of pericarditis medication use and use of any rescue (pain) medication will be 
handed to the subject.  The study Investigator or designated personnel will instruct the subject about 
the use of the medication diary.  The subjects will be asked to complete entries immediately 
following administration  . 
• The subjects will assess their pericardial pain based on a 11-point NRS. 
• The subject's global overall well-being will be assessed using a validated Quality of Life 
Questionnaire (Appendix 3). 
 
8.5.2.2 
Screening Visit 2 (SCV2) 
The end of the Screening Period (SCV2) coincides with the start of the Treatment Period (Day 0, Visit 1).  
All Screening assessments need to be completed prior to the first Study Drug administration.  
• SCV2 should take place when the laboratory test results from SCV1 are available. 
• Subjects will be reassessed for eligibility against the inclusion and exclusion criteria. 
• Any changes in concomitant medications since SCV1 will be documented. 
• A full physical examination will be performed, including re-assessment of pericardial rub.  
• Vital signs will be measured.  
• 12-lead ECG will be performed.  The Study Site/Clinic reading at the time of the examination will be 
used by the Investigator for clinical decision-making. In addition, the ECG will be sent to a core 
laboratory for additional analysis. 
• Samples for laboratory tests will be collected. 
o Local Lab Assessments: 
▪ 
Full hematology (including ESR), chemistry (including CRP), and urinalysis 
o Central Laboratory Assessments: 
▪ 
CRP/hsCRP  
▪ 
   
• Medication diary compliance will be assessed by the Investigator/designated personnel and the 
subject reminded on the diary use. 
• The subjects will assess their pericardial pain based on the 11-point NRS (Figure 3). 
 
When all screening procedures have been performed and the Investigator has confirmed the subject’s 
eligibility for the study, the Study Drug will be administered to the subject (see Study Site/Clinic Visit 1). 
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8.5.3 
Treatment Period 
8.5.3.1 
Visit 1 (Study Site/Clinic) - Day 0 
Visit 1 will coincide with SCV2.  In case Visit 1 is separated from SCV2, SCV2 clinical laboratory blood 
sampling (including CRP), medication diary compliance verification and reminding, and subject NRS 
pericardial pain rating (see Figure 3) must be repeated prior to Study Drug dosing.  
• Sample for lipid panel to be sent to the Central Laboratory for analysis 
• Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody testing will be 
collected prior to Study Drug dosing, sent to the central laboratory, and stored for analysis.  
• The subject's global overall well-being will be assessed prior to Study Drug dosing using a validated 
Quality of Life Questionnaire (Appendix 3). 
• The initial dose of Study Drug will be administered at the Study Site/Clinic. 
• Subjects will be trained for outpatient Study Drug self-administration and reminded of completion of 
the daily medication diary. 
• Any AEs occurring during or after the subject receives the first dose of Study Drug will be captured. 
When all Visit 1 procedures have been performed, an appointment for the first weekly phone call/virtual 
visit will be scheduled. Study Drug for outpatient administration will be provided to the subjects according 
to a process laid out in the pharmacy manual. 
8.5.3.2 
Visits 2 to 6 (Outpatient) - Weeks 2, 3, 4, 5, 6 
• Visits 2, 3, 4, 5, 6 will take place within intervals of 7 ± 1 days each after Visit 1. 
• Subjects self-administer the Study Drug during Weeks 2 to 5. At Week 6/End-of-Trial, Study Drug 
may be self-administered or administered at the study site. 
•  Samples for laboratory tests will be collected. 
o Central Laboratory Assessments: 
▪ 
CRP/hsCRP  
▪ 
 
▪ 
Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody 
testing will be collected (either by a visiting study nurse or at the Study Site or at a 
qualified local laboratory) and stored for analysis after shipment to the central 
laboratory.  
• After dosing at Week 3 and Week 6, a questionnaire to assess the dosing system will be completed 
by the subject and by the study center staff or visiting nurse observing the dosing 
• Any AEs that have occurred since the last contact will be assessed by non-leading questions as part 
of the weekly telephone call/virtual visit from the Study Site/Clinic.  
• Compliance with self-administration of drug, compliance with the medication diary, and compliance 
with laboratory blood sampling will be assessed as part of the weekly telephone call/virtual visit 
from the Study Site/Clinic. 
• Pericardial pain based on the 11-point NRS (Figure 3) will be assessed as part of the weekly telephone 
call/virtual visit from the Study Site/Clinic. 
Subjects withdrawing from the study any time during study weeks 2 to 6 will be asked to return to the Study 
Site/Clinic for the Visit 7/End-of-Trial visit assessments.  
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8.5.3.3 
Interval Evaluation Visit (Study Site/Clinic) - Week 3-4 
An in-person Interval Evaluation Visit during approximately Weeks 3-4 of the Treatment Period is 
recommended to assist the Investigator in the clinical management of the subject. The visit can be held at 
the discretion of the Investigator. The Interval Evaluation Visit may also be used to review the vaccination 
status of a study subject. 
At the Interval Evaluation Visit, the following parameters will be assessed: 
• A full physical examination will be performed, including assessment of pericardial rub. 
• Vital signs will be measured.  
• A 12-lead ECG and a full ECHO will be performed.  The Study Site/Clinic readings at the time of 
the examination will be made available to the Investigator for clinical decision-making. In addition 
both the ECG and ECHO will be sent to a core laboratory for additional analysis. 
• Changes in concomitant medication since the last Study Site/Clinic visit will be documented. 
• Samples for laboratory tests will be collected. 
o Local Lab Assessments: 
▪ 
Full hematology (including ESR), chemistry (including CRP), and urinalysis 
o Central Laboratory Assessments: 
▪ 
CRP/hsCRP  
▪ 
Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody 
testing will be collected, sent to the central laboratory, and stored for analysis.  
• Any AEs that have occurred since the last visit (Study Site/Clinic or outpatient) will be documented.  
• Medication diary compliance will be assessed by the Investigator/designated personnel and the 
subject reminded on the diary use. 
• Pericardial pain based on the 11-point NRS (Figure 3) will be assessed. 
• The subject's global overall well-being will be assessed using a validated Quality of Life 
Questionnaire (Appendix 3). 
8.5.3.4 
Unscheduled Visits (Study Site/Clinic) During the Treatment Period  
Subjects reporting worsening of pericarditis symptoms or AEs may be brought in at the discretion of the 
Investigator for an Unscheduled Visit at any time during the Treatment Period.  During the Unscheduled 
Visit, selected or comprehensive (see Interval Evaluation Visit) clinical and laboratory assessments may be 
performed.  
Any subject who is determined by the Investigator as not responding to treatment (e.g., no reduction in 
pericardial pain compared to baseline, no decrease in CRP levels, etc.) and who is therefore considered by 
the Investigator to be a “Treatment Failure” may be withdrawn from further Study Drug treatment at the 
discretion of the Investigator and receive rescue therapy for their pericarditis according to standard of care 
as per Investigator decision; these subjects will be followed for safety for the remainder of the 6-week 
Treatment Period.   
All study withdrawals must complete the Visit 7/End-of-trial Visit either at the Unscheduled Visit or at a 
separate Visit 7/End-of-trial Visit. 
8.5.3.5 
Visit 7/ End-of-Trial (Study Site/Clinic) - Week 6 
At Visit 7, “Treatment Responders” (defined by the Investigator as a clinically significant reduction in 
pericardial pain using the 11-point NRS, normal or near-normal CRP levels, and absent or decreasing 
echocardiographic effusion at the End-of-Trial Visit), will be offered participation in an optional 18-week 
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EP, at the discretion of the Investigator. During the EP, weekly open-label KPL-914 can be continued at the 
same dose as in the Treatment Period for a total duration of Study Drug treatment of up to 24 weeks.   
• Visit 7 will take place during Week 6 (or as soon as possible after study withdrawal if a subject has 
discontinued from Study Drug therapy).  
• A full physical examination will be performed, including assessment of pericardial rub. 
• Vital signs will be measured.  
• A 12-lead ECG and a full ECHO will be performed.  The Study Site/Clinic readings at the time of 
the examination will be made available to the Investigator for clinical decision-making.  In addition 
both the ECG and ECHO will be sent to a core laboratory for additional analysis. 
• Changes in concomitant medication since last Study Site visit will be documented. 
• Samples for laboratory tests will be collected. 
o Local Lab Assessments: 
▪ 
Full hematology (including ESR), chemistry (including CRP), and urinalysis 
o Central Laboratory Assessments: 
▪ 
CRP/hsCRP 
▪ 
Lipid panel  
▪ 
Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody 
testing will be collected, sent to the central laboratory, and stored for analysis. 
• Any AEs that have occurred since the last visit (Study Site/Clinic or outpatient) will be documented.  
• Medication diary compliance will be assessed by the Investigator/designated personnel. 
• Pericardial pain based on the 11-point NRS will be assessed (Figure 3). 
• The subject's global overall well-being will be assessed using a validated Quality of Life 
Questionnaire (Appendix 3). 
When all of these procedures have been performed, the next Study Site/Clinic visit should be scheduled for 
those who continue KPL-914 treatment during the EP (Treatment Responders).  Study Drug for outpatient 
administration will be provided to the subjects according to a process laid out in the pharmacy manual. 
Only subjects continuing treatment into the Extension Phase will receive Study Drug at Visit 7; Study Drug 
can be self-administered either as an outpatient or at the Clinic/Site (Site to provide Study Drug) depending 
on the logistics/timing of the EoT Visit 7. Continued weekly Study Drug treatment during the EP will be 
outpatient administration. 
8.5.4 
Extension Period 
Subjects will self-administer the Study Drug on a weekly basis and complete the medication diary during 
the Extension Period. Study nurse visits to the subject’s home will continue on a monthly basis. Investigator 
(or designee) phone calls/virtual visits will be performed monthly during the EP to perform NRS pain 
assessments, collect AE information, and document pericarditis/concomitant medication use. If scheduled, 
in-person Study Site/Clinic Visits (Unscheduled Visits or Evaluation Visits) can replace the phone 
calls/virtual visits. 
8.5.4.1 
Unscheduled Visits (Study Site/Clinic) during the EP 
Unscheduled Study Site/Clinic visits can take place during the Extension Period, as agreed upon by the 
Investigator and the subject or as needed.  
• A physical examination will be performed. 
• Vital signs will be measured.  
• Changes in concomitant medication since the last Study Site/Clinic visit will be documented. 
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• Samples for laboratory tests will be collected. 
o Local Lab Assessments: 
▪ 
Full hematology (including ESR), chemistry (including CRP), and urinalysis 
o Central Laboratory Assessments: 
▪ 
CRP/hsCRP  
▪ 
Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody 
testing will be collected, sent to the central laboratory, and stored for analysis.  
• A 12-lead ECG and a full ECHO will be performed as determined by the Investigator.  The Study 
Site/Clinic readings at the time of the examination will be made available to the Investigator for 
clinical decision-making. In addition, both the ECG and ECHO will be sent to a core laboratory for 
additional analysis. 
• Any AEs that have occurred since the last visit (Study Site/Clinic or outpatient) will be documented.  
• Pericardial pain based on the 11-point NRS will be assessed (Figure 3).  
8.5.4.2 
Interval Evaluation Visit During Extension Period (Study Site/Clinic) - Week 15-20 
An in-person Interval Evaluation Visit during approximately Weeks 15-20 of the Extension Period is 
recommended to assist the Investigator in the clinical management of the subject. The visit can be held at 
the discretion of the Investigator.  
At the Extension Period Interval Evaluation Visit, the following parameters will be assessed: 
• A physical examination will be performed. 
• Vital signs will be measured.  
• A 12-lead ECG and a full ECHO will be performed.  The Study Site/Clinic readings at the time of 
the examination will be made available to the Investigator for clinical decision-making. In addition, 
both the ECG and ECHO will be sent to a core laboratory for additional analysis. 
• Changes in concomitant medication since the last Study Site/Clinic visit will be documented. 
• Samples for laboratory tests will be collected. 
o Local Lab Assessments: 
▪ 
Full hematology (including ESR), chemistry (including CRP), and urinalysis 
o Central Laboratory Assessments: 
▪ 
CRP/hsCRP  
▪ 
Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody 
testing will be collected, sent to the central laboratory, and stored for analysis.  
• Any AEs that have occurred since the last visit (Study Site/Clinic or outpatient) will be documented.  
• Pericardial pain based on the 11-point NRS will be assessed (Figure 3). 
• The subject's global overall well-being will be assessed using a validated Quality of Life 
Questionnaire (Appendix 3). 
8.5.4.3 
Visit 8/Final Visit (Study Site/Clinic) - Week 25 
• Visit 8 will take place 18 weeks after Visit 7 (or as soon as possible after study withdrawal during the 
EP). 
• A full physical examination will be performed, including assessment of pericardial rub.  
• Body weight and height will be assessed. 
• Vital signs will be obtained in the seated position and include oral temperature, respiratory rate, blood 
pressure, and pulse. 
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• 12-lead ECG and ECHO will be performed.  Echocardiogram will include assessment of pericardial 
effusion.  In addition, both the ECG and ECHO will be sent to a core laboratory for additional 
analysis. 
• An MRI can be performed (optional).  
• Changes in concomitant medication since the last Study Site/Clinic visit will be documented. 
• Samples for laboratory tests will be collected. 
o Local Lab Assessments: 
▪ 
Full hematology (including ESR), chemistry (including CRP), and urinalysis 
o Central Laboratory Assessments: 
▪ 
CRP/hsCRP 
▪ 
Lipid panel  
▪ 
Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody 
testing will be collected, sent to the central laboratory, and stored for analysis.  
• Any AEs that have occurred since the last visit (Study Site/Clinic or outpatient) will be documented.  
• Pericardial pain based on the 11-point NRS will be assessed (Figure 3). 
• The subject's global overall well-being will be assessed using a validated Quality of Life 
Questionnaire (Appendix 3). 
8.5.5 
Duration of Treatment 
The overall study duration for subjects participating in the study until Visit 8 will be up to 171 days.  
The test product will be administered weekly for 6 weeks in the base study Treatment Period.  Treatment 
Responders will be offered participation in an optional 18-week EP at the discretion of the Investigator.  
During this EP the subject can receive 18 additional weekly doses of KPL-914.  
8.6 
Efficacy and Safety Variables 
The Schedule of Evaluations in Table 1 shows the planned study assessments. 
8.6.1 
Individual Efficacy Assessments 
8.6.1.1 
C-Reactive Protein, Biomarker, and PK Assessments 
CRP will be determined at Study Site/Clinic laboratory tests at Screening (SCV1 and SCV2) and during the 
Treatment Period (Visit 1 prior to dosing, if separate from SCV2, Interval Evaluation Visit [if applicable], 
and Visit 7/End-of-Trial).  Results from the Study Site/Clinic CRP testing will inform the Investigator on 
the subject's pericarditis status for clinical decision-making and support decisions on classifications of 
subjects as Treatment Responders or Treatment Failures and on subsequent disease management during the 
Extension Period.  
Central laboratory assessments of CRP will be performed at each Study Site/Clinic or outpatient study visit 
(samples collected by a visiting study nurse or at the Study Site/Clinic or a local laboratory).  Centrally 
determined CRP values will be used for statistical evaluations and report writing but will not be used as 
basis of the Investigator’s management of the subject. 
All subjects must present with elevated CRP values ≥1 mg/dL at the time of study enrollment.  CRP changes 
and the time course to decrease and resolution of CRP to normal values ≤0.5 mg/dL will be assessed. 
Samples from each study visit will be archived at the central laboratory for potential biomarker and/or PK 
analysis.  
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8.6.1.2 
Echocardiogram (Pericardial Effusion) 
Echocardiograms (ECHOs) including assessment of pericardial effusion will be performed at screening 
(SCV1), at Study Site/Clinic visits during the Treatment Period (Interval Evaluation Visit [if applicable] 
and Visit 7/End-of-Trial), at the Interval Evaluation Visit during the EP [if applicable], and at the Final 
Study Visit/Visit 8.  
Pericardial effusion is characterized by accumulation of excess fluid in the pericardial space surrounding 
the heart and is one of the common features of pericarditis.  Echocardiography is a sensitive tool and the 
most widely used imaging technique for the detection of pericardial effusion and/or thickening. 
For the purposes of the analysis of treatment response in all subjects at the end of the study, all ECHO 
images will be assessed by a central reader. The Study Site/Clinic reading of the ECHO at the time of the 
examination will be made available to the Investigator for clinical decision-making.  
8.6.1.3 
Electrocardiogram (Pericarditis Diagnostic Findings) 
Twelve-lead ECGs will be performed at screening (SCV1 and SCV2), at Study Site/Clinic visits during the 
Treatment Period (Interval Evaluation Visit [if applicable] and Visit 7/End-of-Trial), at the Interval 
Evaluation Visit during the EP [if applicable], and at the Final Study Visit/Visit 8.  
Pericarditis commonly involves changes in the electrophysiologic activity of the heart, resulting in typical 
ECG findings, namely widespread ST-elevation or PR depression.  Changes in ECG findings will help 
determine the pericarditis status of a subject.  
The Study Site/Clinic reading of the ECG at the time of the examination will be made available to the 
Investigator for clinical decision-making. For the purposes of the analysis of treatment response in all 
subjects at the end of the study, all ECG tracings will be assessed by a central reader.   
8.6.1.4 
Pericarditis Signs (Fever, Pericardial Rub) 
Common pericarditis signs include fever and pericardial rub.  These pericarditis signs will be assessed via 
documentation of vital signs and physical examinations.  
Physical examinations and vital signs assessments for pericarditis signs will be performed at screening 
(SCV1 and SCV2), at Study Site/Clinic visits during the Treatment Period (Interval Evaluation Visit [if 
applicable] and Visit 7/End-of-Trial), at the Interval Evaluation Visit during the EP [if applicable], and the 
Final Study Visit/Visit 8.  If applicable, assessment of pericarditis signs will also be performed at 
unscheduled visits.  
8.6.1.5 
Pericarditis Pain (Chest Pain) 
Common pericarditis symptoms include chest discomfort (pericarditis pain).  A validated 11-point NRS will 
be used to measure the subject's level of pericarditis (chest) pain intensity (Dworkin et al 2005; Mannion et 
al 2007; Hawker et al 2011).  The assessment will be performed at all study visits - on-site during Study 
Site/Clinic visits and as part of telephone calls/virtual visits during outpatient visits/treatment weeks (weekly 
during the Treatment Period and monthly during the EP).  
Subjects will be asked to select the score that best describes their average level of pain over the previous 24 
hours using a validated 11-point NRS instrument (Figure 3), where zero (0) indicates ‘no pain’ and ten (10) 
means indicates ‘pain as bad as it could be’.   
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On this scale of 0-10, zero (0) indicates ‘no pain’ and ten (10) indicates ‘pain as bad as it could be’, 
please rate your pain on average in the last 24 hours 
Figure 3: 
11-point Numerical Rating Scale (NRS) for Assessment of Pericarditis Pain 
 
8.6.1.6 
Magnetic Resonance Imaging 
Cardiac MRI is an optional assessment and may be performed at study entry (SCV1) and at the final study 
visit (Visit 8) to assess any changes in pericardial inflammation.  
For the purposes of the analysis of treatment response in all subjects at the end of the study, all cardiac MRI 
images will be assessed by a central reader. The Study Site/Clinic reading of the MRI at the time of the 
examination may be used by the Investigator for clinical decision-making.  
8.6.1.7 
Quality of Life Questionnaire 
A validated Quality of Life Questionnaires will be used to assess changes in the subject's overall well-being 
(Hays et al 2009).  The subject's global assessment will be performed at screening (SCV1), at Visit 1 (Day 
0), at the Interval Evaluation Visit (Week 3-4), at the end of the Treatment Period (Visit 7/End-of-Trial), at 
the Interval Evaluation Visit during the EP, and at the Final Visit (Visit 8).  
The Quality of Life Questionnaire to be used is presented in Appendix 3.  
8.6.1.8 
Dosing Procedure Questionnaire 
A questionnaire will be used to assess the dose preparation and administration procedure immediately after 
self-injecting the Study Drug in the presence of the Study Staff (either in person or via virtual visit) or of 
the visiting nurse. Each subject will complete a questionnaire after the third self-injection (third dose, Week 
3) and the sixth self-injection (sixth dose, Week 6), and once during the extension period. The Study 
Staff/visiting nurse observing the injection will also complete an observation checklist for observing 
subjects interacting with the system during self-injection. The checklist will list all key steps associated with 
proper system use, including setting up for an injection, reconstituting the medication, and administering 
the injection. Study Staff/visiting nurse will complete the checklists for the same injections for which the 
subjects will complete questionnaires.  
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8.6.2 
Safety Assessments 
8.6.2.1 
Adverse Events 
Adverse Event Definition 
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 and/or unintended 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. 
In this study, individual elements of pericarditis symptomatology (including pain) are captured as an 
efficacy parameter.  Pericarditis pain is not required to be reported as an AE.  However, if, in the opinion of 
the Investigator, the subject experiences new symptoms that had not been previously reported in the 
constellation of symptoms recorded at baseline, these new symptoms should be reported as an AE. 
The causal relationship between an AE and the Study Drug will be defined as below: 
• 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 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 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 drug, abates 
upon discontinuation of the drug, follows a known or hypothesized cause-effect relationship, and (if 
appropriate) reappears when the drug is reintroduced.   
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: medically significant event; daily activities limited or completely halted; hospitalization or 
prolongation of hospitalization indicated. 
Every reasonable effort will be made to follow subjects who have AEs.  Any subject who has an ongoing 
AE at study end or early withdrawal will be followed, where possible, until resolution.   
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Sponsor Reporting Responsibilities to Participating Investigators 
It is the responsibility of the Sponsor or designee to immediately notify all participating Investigators of any 
AE associated with the use of the drug that is both serious and unexpected, as well as any finding from tests 
in laboratory animals that suggest a significant risk for human subjects.   
8.6.2.3 
Adverse Reactions 
All noxious and unintended responses to an investigational medicinal product (IMP; i.e., where a causal 
relationship between an IMP and an AE is at least a reasonable possibility) related to any dose should be 
considered adverse drug reactions.   
Unexpected Adverse Reaction Definition 
An unexpected adverse drug reaction is defined as an adverse reaction, the nature or severity of which is 
not consistent with relevant product information for the IMP.  The current version of the ARCALYST® PI 
should be used as the Single Source Safety Reference Document when determining if an event is 
unexpected. Refer to the ARCALYST® PI (Appendix 2: ARCALYST® Prescribing Information) for a list 
of most frequent expected AEs.  All suspected adverse reactions related to an investigational medicinal 
product (the tested investigational medicinal products and comparators, if involved) which occur in the 
concerned trial, and that are both unexpected and serious are subject to expedited reporting. 
Warnings and Precautions 
Refer to the ARCALYST® PI (Appendix 2: ARCALYST® Prescribing Information) for Important Safety 
Information. 
IL-1 blockade may interfere with immune response to infections.  It is therefore recommended that prior to 
or shortly after initiation of therapy with KPL-914 subjects receive all recommended vaccinations, as 
appropriate, including pneumococcal vaccine and inactivated influenza vaccine. In case a subject needs 
vaccination after initiation of KPL-914 treatment, vaccination with inactive vaccine(s) may be performed 
during the active Treatment Period. However, to minimize the potential confounding of KPL-914-related 
AE reporting or CRP measurements during the KPL-914 Treatment Period, vaccination should not be 
performed during the Treatment Period (see Section 8.3.4).  It is recommended that all vaccinations be 
documented as up-to-date at or shortly after Visit 7, at which point subjects are being considered for longer-
term treatment with KPL-914.   
It is recommended that all vaccinations be documented as up-to-date at or shortly after Visit 7, at which 
point subjects are being considered for longer-term treatment with KPL-914.  
Taking KPL-914 with TNF inhibitors is not recommended because simultaneous inhibition of these two 
pathways may increase the risk of serious infections.   
It is also possible that taking drugs 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 KPL-914.   
8.6.2.4 
Clinical Laboratory Variables 
Clinical laboratory analyses will be performed at Study Site/Clinic or local laboratory near the subject and, 
for some parameters, at a central laboratory.  Laboratory analyses will be used at Study Site/Clinic visits for 
the Investigator to assess disease status and to determine treatment response and study (drug) continuation 
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or withdrawal.  Results for analyses performed by the Study Site/Clinic laboratory together with the 
laboratory reference ranges will be recorded in the eCRF and the Investigator must use clinical judgment to 
determine if any abnormal values are clinically significant or not. 
Central laboratory samples for CRP analysis will be collected at both Study Site/Clinic and outpatient (by a 
visiting study nurse or at local contract laboratories) visits and the results will be used for statistical analyses 
and study reporting. Study Site/Clinic and local laboratory results will be used for clinical decision-making 
and will be available in the source documents and listed in the CSR).  
The following analyses will be done at the central laboratory:  
• 
C-reactive protein (CRP)/hsCRP (The CRP analyzed by the central laboratory will not be available 
to the investigator in a timely manner to support the clinical management of the subject.  Results 
from the central laboratory will therefore not be transferred to the Investigator during the trial.) 
• 
Lipid Panel 
• 
Samples for biomarkers, PK, and anti-rilonacept (anti-KPL-914) antibody testing will be drawn and 
archived at all visits. 
The following laboratory analyses will be done at the Study Site/Clinic laboratories in accordance with 
local procedures and guidelines to support clinical management and decision-making: 
Hematology 
Hemoglobin, hematocrit, coagulation parameters (prothrombin [PT], prothrombin time [PTT], D-dimer), 
ESR, fibrinogen, WBC count (total and differential), red blood cell (RBC) count, ESR, platelet count, mean 
cell volume (MCV), mean cell hemoglobin (MCH), MCH concentration (MCHC). 
Clinical Chemistry 
CRP/hsCRP, troponin, creatinine, creatine kinase, urea, (or blood urea nitrogen [BUN]), aspartate 
aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), alkaline 
phosphatase, lactate dehydrogenase (LDH), total bilirubin, albumin, total protein, sodium, potassium, 
chloride, glucose, uric acid, total cholesterol*, triglycerides*, calcium, phosphorus. 
* Preferably fasting. 
Urinalysis 
pH, glucose, ketones, nitrites, leukocyte esterase, blood, protein and microscopy. Urine drug screen 
(alcohol, amphetamines, cocaine, or phencyclidine) at SCV1 only. Screening for pregnancy (urine β-HCG) 
at SCV1 only. 
Serology 
HCVAb, HBsAg, HBcAb, HBsAb and HIV tests (SCV 1 only). 
 
Other 
Screening for tuberculosis (QuantiFERON test) at SCV1 only (optional). 
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The amount of blood to be taken during screening will be approximately 37 mL at SCV1 and approximately 
17 mL at SCV2 (if done). The amount of blood to be taken at each Study Site/Clinic visit during the 
Treatment Period and EP will be approximately 31 mL.  The amount of blood to be taken at each outpatient 
visit will be approximately 21 mL. At the optional unscheduled visit, approximately 61 mL are planned. 
The total amount of blood to be taken during the study will be up to approximately 320 mL. 
8.6.2.5 
Vital Signs 
Vital signs will be recorded at Study Site/Clinic visits in a standardized manner, i.e., after the subject has 
rested in the sitting position for 5 minutes. 
The following measurements will be taken: oral temperature, respiratory rate, blood pressure, and pulse.  
Oral temperature (fever) will also be assessed as efficacy parameter (see Section 8.6.1.4). 
8.6.2.6 
Physical Examination 
At the Screening Visits 1 and 2, at the optional Evaluation Visit during the Treatment Period, at the End-of-
Trial Visit (Visit 7), at Unscheduled and Evaluation Visits during the EP and at the Final Visit (Visit 8) a 
full physical examination including the assessment of pericardial rub (efficacy parameter) will be performed 
(see also Section 8.6.1.4).   
8.6.2.7 
Body Weight and Height 
Body weight and height will be determined at SCV1 and at the final study visit.  
8.7 
Statistical Methods 
A full description of the statistical analyses to be performed together with the planned tables and figures 
will be given in a detailed document, the SAP, which will be developed and filed prior to data base lock.  
Any deviation(s) from the final SAP will be described and justified in the clinical study report. 
8.7.1 
Statistical and Analytical Plans 
8.7.1.1 
Datasets to be Analyzed 
The modified Intention to Treat (mITT) Population will consist of all subjects who received at least one 
dose of Study Drug.  The Per Protocol (PP) Population will consist of all subjects who received all 6 doses 
of Study Drug during the active Treatment Period and were maintained at stable dose levels of concomitant 
pericarditis medications (NSAIDs, colchicine, and/or corticosteroids, if used during screening) according to 
study protocol without a major protocol violation.  The Safety Population will be the same as the mITT 
Population. 
8.7.1.2 
General Statistical Methods 
Because of the small sample size, no inferential statistical analyses or hierarchical testing are planned. 
For analysis of continuous endpoints (e.g., change from baseline), summary statistics (n, mean, standard 
deviation, median, minimum, and maximum) will be calculated and presented for each treatment and/or 
analysis group.  For categorical endpoints (e.g., responder vs. non-responder), summary statistics will be 
calculated and presented for each treatment and/or analysis group.  
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8.7.2 
Determination of Sample Size 
Approximately 10 symptomatic subjects with RIP will be enrolled as study subjects.  Following review of 
the available data, the Sponsor, in collaboration with the Investigators, may increase the sample size to up 
to 20 subjects to address additional hypotheses. 
Subjects who discontinue the study (withdrawals and Treatment Early Failures) may be replaced at the 
Sponsor’s discretion. 
The sample size was chosen on an empirical basis, based on experience with other rilonacept trials and 
research in this patient population. 
8.8 
Quality Assurance and Quality Control 
8.8.1 
Audit and Inspection 
The study may be selected for audit originating from the Sponsor or external organizations acting on behalf 
of the Sponsor.  Audits will be followed by internal reports and corrective actions, if needed.  
The Investigator agrees to cooperate with the auditor to ensure that any problems detected in the course of 
these audit visits are resolved.  The anonymity of the subjects must be safeguarded and data checked during 
audits remain confidential. 
8.8.2 
Monitoring 
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.  
The Investigator will permit study-related monitoring, audits, ethics committee review and regulatory 
inspection(s), providing direct access to source data and documents.  
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 Good Clinical Practice (GCP) and International Conference on Harmonisation 
(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.   
8.8.3 
Data Management and Coding 
The Sponsor or Clinical Research Organization (CRO) 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 the 
Sponsor or CRO. 
Medical coding will use Medical Dictionary for Regulatory Activities (MedDRA) for concomitant diseases 
and AEs and World Health Organization (WHO) Drug for therapies. 
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8.8.4 
Record Keeping 
It is the responsibility of the Investigator to ensure all essential trial documentation and source records (e.g., 
signed ICFs, Study Site/Clinic files, patients’ hospital notes, copies of eCRFs, etc.) 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. 
9 Records and Supplies 
9.1 
Drug Accountability 
On receipt of the IMP (including rescue medication, if relevant), the Investigator (or deputy) will conduct 
an inventory of the supplies and verify that IMP supplies are received intact and in the correct amounts prior 
to completing a supplies receipt.  The Investigator will retain a copy of this receipt at the study site and 
return the original receipt to the drug depot.  The inventory of supplies at each study site will be reviewed 
by the study monitor. 
KPL-914 (rilonacept) will be provided by the Sponsor to the study sites and to the study subjects in its 
commercially-available formulation (ARCALYST®).  All vials of used and unused Study Drug during the 
active Treatment Period 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.   
10 
Ethics 
10.1 Institutional Review Board 
Before initiation of the study at each investigational site, the protocol, all protocol amendments, the ICF, 
and any other relevant study documentation will be submitted to the appropriate IRB.  Written approval of 
the study and all relevant study information must be obtained before the study site can be initiated or the 
IMP is released to the Investigator.  Any necessary extensions or renewals of IRB approval must be obtained, 
in particular, for changes to the study such as modification of the protocol, the informed consent form, the 
written information provided to subjects and/or other procedures. 
The Investigator will report promptly to the IRB any new information that may adversely affect the safety 
of the subjects or the conduct of the study.  The Investigator will submit written summaries of the study 
status to the IRB annually, or more frequently if requested by the IRB.  On completion of the study, the 
Sponsor will notify the IRB that the study has ended. 
10.2 Ethical Conduct of the Study 
This study will be conducted in compliance with the protocol, the ICH-GCP guideline, the Declaration of 
Helsinki and local regulations. 
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10.3 Subject Information and Consent 
The Investigator is responsible for ensuring that no subject undergoes any study related examination or 
activity before that subject and/or legal guardian has given written informed consent to participate in the 
study.  The written consent must be given by the subject and/or the legal guardian of the subject, after 
detailed information about the study has been given and in accordance with any national provisions on the 
protection of clinical study subjects.  The verbal explanation will cover all the elements specified in the 
written information provided for the subject. 
Subjects and/or legal guardians will be required to sign and date the ICF.  After signatures are obtained, the 
ICF will be kept and archived by the Investigator in the Investigator’s study file for possible inspection by 
regulatory authorities, the IRB, Sponsor and/or CRO personnel. 
It should be emphasized to the subject that he/she is at liberty to withdraw from the study at any time, 
without penalty or loss of benefits to which the subject is otherwise entitled.  Subjects who refuse to give or 
who withdraw written informed consent should not be included or continue in the study. 
10.4 Subject Confidentiality (US Studies) 
All personal data collected and processed for the purposes of this study should be managed by the 
Investigator and his/her staff with adequate precautions to ensure confidentiality of those data, and in 
accordance with the Health Insurance Portability and Accountability Act (HIPAA), applicable to national 
and/or local laws and regulations on personal data protection. 
Monitors, auditors, and other authorized agents of the Sponsor and/or its designee, the ethics committees 
approving this research, and the United States (US) FDA, as well as that of any other applicable agency(ies), 
will be granted direct access to the study subjects’ original medical records for verification of clinical study 
procedures and/or data, without violating the confidentiality of the subjects to the extent permitted by the 
law and regulations.  In any presentations of the results of this study or in publications, the subjects’ identity 
will remain confidential. 
11 Reporting and Publication 
All data generated in this study are the property of the Sponsor.  An integrated clinical and statistical report 
will be prepared at the completion of the study. 
Publication of the results by the Investigator(s) will be subject to mutual agreement between the Investigator 
and Kiniksa as outlined in the study agreement. 
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12 References 
Adler Y, Charron P, Imazio M, Badano L, Barón-Esquivias G, Bogaert J, Brucato A, 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 Nov 7;36(42):2921-64. 
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, Lazaros G, Maestroni S, Carraro M, Finetti M et al. Effect of Anakinra 
on Recurrent Pericarditis Among Patients With Colchicine Resistance and Corticosteroid 
Dependence: The AIRTRIP Randomized Clinical Trial. JAMA. 2016 Nov 8;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. Autoimmunity Reviews 2015;14:90–97. 
Doria A, Zen M, Bettio S et al. Autoinflammation and autoimmunity: bridging the divide. Autoimmunity 
Reviews 2012;12:22–30. 
Dworkin RH, Turk DC, Farrar JT et al. Core outcome measures for chronic pain clinical trials: IMMPACT 
recommendations. Pain. 2005 Jan;113(1-2): 9-19. 
Hays RD, Bjorner JB, Revicki DA, Spritzer KL, Cella D. Development of physical and mental health 
summary scores from the patient-reported outcomes measurement information system (PROMIS) 
global items. Qual Life Res (2009) 18:873–880. 
Hawker GA, Mian S, Kendzerska T, French M. 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 & Research. 2011; 63: S240–S252. 
Hoffman HM, Patel DD. Genomic-based therapy: targeting interleukin-1 for auto-inflammatory diseases. 
Arthritis and Rheum. 2004 Feb; 50(2): 345-349. 
Imazio M, Spodick DH, Brucato A, Trinchero R, Adler Y. Controversial issues in the management of 
pericardial diseases. Circulation. 2010;121:916-928. 
Imazio M, Bobbio M, Cecchi E, Demarie D, Demichelis B, Pomari F, Moratti M, Gaschino G, Giammaria 
M, Ghisio A, Belli R, Trinche-ro R. Colchicine in addition to conventional therapy for acute 
pericarditis: results of the COlchicine for acute PEricarditis (COPE) trial. Circulation. 
2005;112:2012-2016. 
Imazio M, Demichelis B, Parrini I et al. Management, risk factors, and outcomes in recurrent pericarditis. 
American Journal of Cardiology, 2005;96(5):736–739. 
Imazio M. Treatment of recurrent pericarditis. Revista Espanola de Cardiologia. 2014;67(5):345–348. 
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CONFIDENTIAL 
Khandaker MH, Espinosa RE, Nishimura RA, Sinak LJ, Hayes SN, Melduni RM, Oh JK. Pericardial 
disease: diagnosis and management. Mayo Clin Proc. 2010;85:572-593. 
Lazaros G, Imazio M, Brucato A, Vassilopoulus D, Vasileiou P, Gattorno M, Tousoulis D et al. Anakinra: 
an emerging option for refractory idiopathic recurrent pericarditis: a systematic review of published 
evidence. J Cardiovasc Med 2016;17(4):256-62. 
Lilly SL. Treatment of Acute and Recurrent Idiopathic Pericarditis. Circulation. 2013;127:1723-1726. 
Lotrionte M, Biondi-Zoccai G, Imazio M, Castagno D, Moretti C, Abbate A, Agostoni P, Brucato AL, Di 
Pasquale P, Raatikka M, Sangiorgi G, Laudito A, Sheiban I, Gaita F. International collaborative 
systematic review of controlled clinical trials on pharmacologic treatments for acute pericarditis and 
its recurrences. Am Heart J. 2010;160:662-670. 
Maisch B, Seferovic PM, Ristic AD, Erbel R, Rienmüller R, Adler Y, Tomkowski WZ, Thiene G, Yacoub 
MH; Task Force on the Di-agnosis and Management of Pericardial Diseases of the European Society 
of Cardiology. Guidelines on the diagnosis and management of pericardial diseases executive 
summary: the Task Force on the Diagnosis and Man-agement of Pericardia! Diseases of the 
Eu-ropean Society of Cardiology. Eur Heart J. 2004;25:587-610. 
Mannion AF, Balagué F, Pellisé F, Cedraschi C. Pain measurement in patients with low back pain. Nature 
Clinical Practice Rheumatology 2007; 3 (11): 610-18. 
Pankuweit S, Wädlich A, Meyer E, Portig I, Hufnagel G, and Maisch B. Cytokine activation in pericardial 
fluids in different forms of pericarditis. Herz 2000;25:748–754. 
Zayas R, Anguita M, Torres F, Gimenez D, Bergillos F, Ruiz M, Ciudad M, Gallardo A, Valles F. Incidence 
of specific etiology and role of methods for specific etiologic diagnosis of primary acute pericarditis. 
Am J Cardiol. 1995;75:378-382. 
 
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13 Appendices 
Appendix 1: Investigator Signature Page 
Protocol Title: 
An open-label pilot study of KPL-914 in symptomatic Recurrent 
Idiopathic Pericarditis. 
Protocol Number: 
KPL-914-C001 
Confidentiality and cGCP Compliance Statement 
I, the undersigned, have reviewed this protocol, including appendices and I will conduct the study as 
described in compliance with this protocol, GCP, and relevant ICH guidelines. 
Once the protocol has been approved by the IEC/IRB, I will not modify this protocol without obtaining prior 
approval of Kiniksa Pharmaceuticals Ltd. (Kinksa) and of the IEC/IRB. I will submit the protocol 
modifications and/or any ICF modifications to Kiniksa and IEC/IRB, and approval will be obtained before 
any modifications are implemented. 
I understand that all information obtained during the conduct of the study with regard to the subjects’ state 
of health will be regarded as confidential. No subjects’ names will be disclosed.  All subjects will be 
identified by assigned numbers on all Case Report Forms, laboratory samples or source documents 
forwarded to the Sponsor.  Clinical information may be reviewed by the Sponsor or its agents or regulatory 
agencies.  Agreement must be obtained from the subject before disclosure of subject information to a third 
party. 
Information developed in this clinical study may be disclosed by Kiniksa, to other clinical Investigators, 
regulatory agencies, or other health authority or government agencies as required. 
Investigator Signature 
Date 
Printed Name 
Institution 
 
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Appendix 2: ARCALYST® Prescribing Information 
 
KPL-914-C001 Protocol and Amendments 
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!		"'								!	91
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	'							+	5			"				
"	+										.			'
=5			"				+	+		5	'	+!		
"	!							.					03J		
														
	'	*				.	5"					
"			"			
-!	&-!	--		&--	"4"!		+		,				
					+	&--	"4"				+	
	"			5	0
	"			0-	"							'			
	"	"					/						'
7"	'					.	5"		+			+
.3/&3URWRFRODQG$PHQGPHQWV
3DJH

	+					"						&-!	--!	&--	"4"
			+	
	"			5	0	"			0-	"	
					'										
# 	"	"					'
3"9	)
	*

*			+	+			5			'	;		"		5		
!				5	+						"	+'
3":	
	/
5			+	 	+		"		&		0	+		+			
+!				&'&	"4"	
			5		0-	"		&3+	"		
	5	'			+	.								
/.				
'"'					.	 '		.	.
	/								+					
'
	"	"	.											+		.	

&-	"4!	"	,'0		,,	"4	+				.				+	 	

&3	"4!	"	2		80	"4'
		.				+		"		&	.			'
%			"	!				.					
			'	*			+			+			.			'
 			+			"		"		"+	
.'	G	'		
!(	%!	)H
3"@	$

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*							+	 			!	2-	
6			+		+	M	08			"!		0	+	M	28			"'	*	
 		!	!				+	"					
		"	F	+.!				M	08						'	*	
	5			 !		2			+	.		"			G
		H'	"					.		"				"
				'
3";				! 
 
7			.				5					
			+		'
3"8			#	! 
 
7			.				5					
			+		'
72	%6'4%$'
	.					.	+	'	$5	+					,&-	"
.							5	(							
+	 				0				+		.					+
.		"	5'	*	!		".	.					&---
"									5		+		+	"
5'		5											

.3/&3URWRFRODQG$PHQGPHQWV
3DJH

'
*			.!											"			
.			!						'
77	4'!!%)
						"			""				5
							
**		*			

* 					#				*"<'					+"	
5	&8	1'			5					.	
9A	'
				"!	&-	"	.	"		!	+		+!
6	+'	=	.							+	&',				%	
*/'		.				&				++!	+		"		.	0-	"	
		'		"			.!	!				+!	
			'	=	.		&&-	"	'		!		.
	(-	"4	!	30	$	!	8-	$	"!	,'-J	
+4.		"	,,8-!
&'-J	
+4.	!		'-J	
+4.	"			9		0'8	N	-','	7	..		'
71	!)!	#*%%$
71"7	* 		
 				"		"						7 ,	G7
"	!				
7!			"	,H	"	
	+		
*			G*
H'	 						
		+				"	B	'	#				
	.!		!	"!	"!	"!		/.'
*		!			 			+				7 ,	"	+	
		!						'		"		
				.				
*O'	$		7 ,			
..		"		5.			.	*O		.	'
		*O	""		"								*O		.
		+			'				*P		*		"	
*
	+		'		B					"		*O!	*P
	*	+	-'8	$!	'3	$		0'	$!	.'
71"1	
  
.	 	
 					
						.
		.			+	 '	=.					+		.	
				+	 '			!		+		
								 					.	"		
'			6				.	.'
71"9	
 B
	."	"	.			+	5	&3	"4			+"
+				0-	"				3(	+			+	 '		
					0	+'
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7		+			.				"!	"!			+"			5'
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				.			.			'	*			'
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		+							!			/				"	+
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'	 															/'	;			
						+						+	'
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'								"		'
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'					'
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'	1		.			.'			+				5		+	+	+'	A
	+				"		"			'	9					"	+
			+		&2""							"				"	+		
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0'	 9		"			.'	%			.				"			&',		!
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2'	 9		"			!									.	"	'	1		+
							.'	 			.	'	9		"				
	+			5	
		'	9			%	.					+
		'	+				"	"			'	1			
'	 		"				+							.	
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				"	"	'
K'	 $								.			B		+					"		
&',				++			%			.	
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-'	 S		.		+						"	+		"						
				"'
'	 	.			!	"				"										"
				'
&'	 	."		!			"						"				%	
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,'	 	.		"	+					%	.'	1				'
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		"	+	"							.'	 		"		
	+		/			%			.'
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8'	 9		.	"					+		/	+	
	"	+
				"								.!		B			.			

					
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	72
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2'	 			.							+	+	.		.'
('	 *		+				.!			.	B					,-	
'			.					'
K'	 		(			+			.					'
-'	 	5				!	!					+'	1				5
B						!								
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'	:0	
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Kiniksa Pharmaceuticals Ltd. 
 
17 January 2018 
KPL-914-C001 Amendment 1 
Final 
Page 62 of 64 
 
CONFIDENTIAL 
Appendix 3: Quality of Life Instrument 
 
 
 
 
 
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17 January 2018 
KPL-914-C001 Amendment 1 
Final 
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CONFIDENTIAL 
 
 
 
 
 
 
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KPL-914-C001 Amendment 1 
Final 
Page 64 of 64 
 
CONFIDENTIAL 
Appendix 4: 11-point Numerical Rating Scale (NRS) for Assessment of Pericarditis Pain 
Common pericarditis symptoms include chest discomfort (pericarditis pain).  A validated 11-point NRS will 
be used to measure the subject's level of pericarditis (chest) pain intensity (Dworkin et al 2005; Mannion et 
al 2007; Hawker et al 2011). 
Subjects will be asked to select the score that best describes their average level of 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’.   
On this scale of 0-10, zero (0) indicates ‘no pain’ and ten (10) indicates ‘pain as bad as it could be’, 
please rate your pain on average in the last 24 hours 
 
 
 
 
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Kiniksa Pharmaceuticals Ltd. 
14 February 2018 
KPL-914-C001 Amendment 2 
Final 
Page 4 of 85 
CONFIDENTIAL 
3 Synopsis 
Trial Number: 
KPL-914-C001 
Trial Title: 
An open-label, pilot study of KPL-914 in recurrent pericarditis 
Trial Centers: 
Approximately 15 sites 
Development Phase: 2 
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KPL-914-C001 Amendment 2 
Final 
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CONFIDENTIAL 
Objective(s): 
The study is comprised of 5 Parts. 
•
Part 1 enrolls symptomatic subjects with recurrent idiopathic pericarditis (RIP) with an elevated
marker of systemic inflammation (C-reactive protein [CRP] > 1mg/dL).
•
Part 2 enrolls symptomatic subjects with RIP with CRP ≤1 mg/dL which, in the opinion of the
investigator, can be attributed to concomitant medications (e.g., corticosteroids) and with
pericardial inflammation present on cardiac magnetic resonance imaging (MRI) confirmed by
the imaging core lab.
•
Part 3 enrolls subjects with corticosteroid-dependent RIP not experiencing symptoms which
would meet the diagnostic criteria for a flare of pericarditis.
•
Part 4 enrolls symptomatic subjects with recurrent post pericardiotomy syndrome (PPS) with an
elevated marker of systemic inflammation (CRP > 1mg/dL).
•
Part 5 enrolls subjects with corticosteroid-dependent recurrent PPS not experiencing symptoms
which would meet the diagnostic criteria for a flare of pericarditis.
Part 1: 
Primary Objective: 
To collect inter- and intra-subject variability data on CRP measurements and the 11-point NRS 
instrument for assessment of pericardial pain in subjects with RIP both at baseline and on treatment 
with KPL-914 in order to inform power calculations for future trials in pericarditis. 
Secondary Objectives: 
To explore the time course to improvement of pericarditis parameters in symptomatic subjects with RIP 
treated with KPL-914. 
To evaluate the effect of KPL-914 on pericardial inflammation based on cardiac MRI. 
To evaluate the safety of KPL-914 in symptomatic subjects with RIP. 
Part 2: 
Primary Objective: 
To collect inter- and intra-subject variability data on CRP measurements and the 11-point NRS 
instrument for assessment of pericardial pain in subjects with RIP both at baseline and on treatment 
with KPL-914 in order to inform power calculations for future trials in pericarditis. 
Secondary Objectives: 
To explore the time course to improvement of pericarditis parameters in symptomatic subjects with RIP 
treated with KPL-914 
To evaluate the effect of KPL-914 on pericardial inflammation based on cardiac MRI. 
To evaluate the safety of KPL-914 in symptomatic subjects with RIP. 
Part 3: 
Primary Objective: 
To evaluate feasibility of weaning from corticosteroids while receiving KPL-914 in subjects with 
corticosteroid-dependent RIP. 
Secondary Objectives: 
KPL-914-C001 Protocol and Amendments 
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14 February 2018 
KPL-914-C001 Amendment 2 
Final 
Page 6 of 85 
CONFIDENTIAL 
To evaluate the effect of KPL-914 on pericardial inflammation based on cardiac MRI. 
To evaluate the safety of KPL-914 in subjects with corticosteroid-dependent RIP. 
Part 4: 
Primary Objective: 
To collect inter- and intra-subject variability data on CRP measurements and the 11-point NRS 
instrument for assessment of pericardial pain in subjects with symptomatic recurrent PPS both at 
baseline and on treatment with KPL-914 in order to inform power calculations for future trials in 
pericarditis. 
Secondary Objectives: 
To explore the time course to improvement of pericarditis parameters in symptomatic subjects with 
recurrent PPS treated with KPL-914 
To evaluate the effect of KPL-914 on pericardial inflammation based on cardiac MRI. 
To evaluate the safety of KPL-914 in symptomatic subjects with recurrent PPS. 
Part 5: 
Primary Objective: 
To evaluate feasibility of weaning from corticosteroids while receiving KPL-914 in subjects with 
corticosteroid-dependent recurrent PPS. 
Secondary Objectives: 
To evaluate the effect of KPL-914 on pericardial inflammation based on cardiac MRI. 
To evaluate the safety of KPL-914 in subjects with corticosteroid-dependent recurrent PPS. 
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Page 7 of 85 
CONFIDENTIAL 
Methodology: 
This is an open-label, single-active-arm pilot study to explore clinical and biochemical endpoints of 
pericarditis symptomatology and to collect inter- and intra-subject variability data on both at-baseline 
and on-treatment parameters. This study consists of 5 distinct Parts, and all subjects will be treated with 
once-weekly subcutaneously (SC)-administered injections of KPL-914.   
Enrollment into Part 1: 
Subjects identified for participation in Part 1 of this trial will present during a symptomatic episode of 
RIP, having previously experienced a first (index) episode of acute pericarditis followed by at least 1 
recurrent episode before the current enrollment-qualifying episode, using the 2015 European 
Society of Cardiology (ESC) Guidelines for the Diagnosis and Management of Pericardial Diseases 
(Adler et al, 2015) as a frame of reference: 
-
The index episode of acute pericarditis would have been characterized by an inflammatory
pericardial syndrome with at least 2 of the 4 following criteria: pericarditic chest pain, pericardial
rub, new widespread ST-segment elevation or PR-segment depression on electrocardiogram
(ECG), and pericardial effusion (new or worsening).  Additional supportive findings would have
included elevations of markers of inflammation (i.e., CRP, ESR, or WBC count) or evidence of
pericardial inflammation by an imaging technique (e.g., MRI).
-
Recurrence of RIP would have been characterized as a subsequent episode of pericarditis
occurring after a symptom-free interval of 4-6 weeks or longer.
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14 February 2018 
KPL-914-C001 Amendment 2 
Final 
Page 8 of 85 
CONFIDENTIAL 
For the purposes of this study, the Investigator will determine, based on his/her judgement of the 
available data, if a subject has met these criteria for having previously experienced a first (index) 
episode of acute pericarditis followed by at least 1 recurrent episode of pericarditis prior to the 
current enrollment-qualifying episode of RIP and will record the criteria supporting this diagnosis in 
the electronic case report form (eCRF). 
Subjects with symptomatic RIP meeting the above diagnostic criteria may be enrolled into Part 1 only if 
the CRP value at screening is > 1 mg/dL. 
Enrollment into Part 2: 
Subjects identified for participation in Part 2 of this trial will present during a symptomatic episode of 
RIP, having previously experienced a first (index) episode of acute pericarditis followed by at least 1 
recurrent episode before the current enrollment-qualifying episode, using the 2015 European Society 
of Cardiology (ESC) Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 
2015) as a frame of reference: 
-
The index episode of acute pericarditis would have been characterized by an inflammatory
pericardial syndrome with at least 2 of the 4 following criteria: pericarditic chest pain, pericardial
rub, new widespread ST-segment elevation or PR-segment depression on electrocardiogram
(ECG), and pericardial effusion (new or worsening).  Additional supportive findings would have
included elevations of markers of inflammation (i.e., CRP, ESR, or WBC count) or evidence of
pericardial inflammation by an imaging technique (e.g., MRI).
-
Recurrence of RIP would have been characterized as a subsequent episode of pericarditis
occurring after a symptom-free interval of 4-6 weeks or longer.
For the purposes of this study, the Investigator will determine, based on his/her judgement of the 
available data, if a subject has met these criteria for having previously experienced a first (index) 
episode of acute pericarditis followed by at least 1 recurrent episode of pericarditis prior to the 
current enrollment-qualifying episode of RIP and will record the criteria supporting this diagnosis in 
the eCRF. 
Subjects with symptomatic RIP meeting the above diagnostic criteria but without an elevated CRP 
level (i.e., ≤1mg/dl) at screening may be enrolled into Part 2 only if, in the opinion of the investigator 
and in consultation with the Sponsor, the low CRP value can be attributed to concomitant 
medications (e.g., corticosteroids) AND if there is evidence of pericardial inflammation by cardiac 
MRI which has been confirmed by the MRI Core Laboratory. 
Enrollment into Part 3: 
Subjects identified for participation in Part 3 in this trial will present with corticosteroid-dependent 
RIP, having previously experienced a first (index) episode of acute pericarditis followed by at least 2 
recurrent episodes, using the 2015 European Society of Cardiology (ESC) Guidelines for the 
Diagnosis and Management of Pericardial Diseases (Adler et al, 2015) as a frame of reference: 
-
The index episode of acute pericarditis would have been characterized by an inflammatory
pericardial syndrome with at least 2 of the 4 following criteria: pericarditic chest pain, pericardial
rub, new widespread ST-segment elevation or PR-segment depression on electrocardiogram
(ECG), and pericardial effusion (new or worsening).  Additional supportive findings would have
included elevations of markers of inflammation (i.e., CRP, ESR, or WBC count) or evidence of
pericardial inflammation by an imaging technique (e.g., MRI).
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-
Recurrence of RIP would have been characterized as a subsequent episode of pericarditis
occurring after a symptom-free interval of 4-6 weeks or longer.
For the purposes of this study, the Investigator will determine, based on his/her judgement of the 
available data, if a subject has met these criteria for having previously experienced a first (index) 
episode of acute pericarditis followed by at least 2 recurrent episodes of pericarditis and will record 
the criteria supporting this diagnosis in the eCRF. 
Subjects who are taking corticosteroids for their RIP and who are not currently experiencing symptoms 
which, in the opinion of the Investigator, would meet the above diagnostic criteria for a flare may be 
enrolled into Part 3 only if, in the opinion of the Investigator and in consultation with the Sponsor, they 
are considered to be “corticosteroid- dependent” (i.e.; the signs and symptoms of pericarditis would 
return if the corticosteroids were withdrawn). 
Enrollment into Part 4: 
Subjects identified for participation in Part 4 in this trial will present during a symptomatic episode of 
recurrent PPS, having previously experienced a first (index) episode of acute PPS followed by at 
least 1 recurrent episode of PPS before the current enrollment-qualifying episode, using the 2015 
European Society of Cardiology (ESC) Guidelines for the Diagnosis and Management of Pericardial 
Diseases (Adler et al, 2015) as a frame of reference: 
-
The index episode of acute pericarditis would have been characterized by an inflammatory
pericardial syndrome with at least 2 of the following 5 clinical findings after cardiac surgery: fever
without alternative causes, pericardial chest pain, pericardial rub, evidence for pericardial effusion,
or elevated CRP.
-
Recurrence of PPS would have been characterized as a subsequent episode of pericarditis
occurring after a symptom-free interval of 4-6 weeks or longer.
For the purposes of this study, the Investigator will determine, based on his/her judgement of the 
available data, if a subject has met these criteria for having previously experienced a first (index) 
episode of acute PPS followed by at least 1 recurrent episode of PPS prior to the current 
enrollment-qualifying episode of recurrent PPS and will record the criteria supporting this diagnosis 
in the eCRF. 
In addition to meeting the above criteria for PPS, all subjects enrolled in Part 4 must have a CRP value 
> 1 mg/dL at screening.
Enrollment into Part 5: 
Subjects identified for participation in Part 5 in this trial will present with corticosteroid-dependent 
recurrent PPS, having previously experienced a first (index) episode of acute PPS followed by at least 
2 recurrent episodes, using the 2015 European Society of Cardiology (ESC) Guidelines for the 
Diagnosis and Management of Pericardial Diseases (Adler et al, 2015) as a frame of reference: 
-
The index episode of acute pericarditis would have been characterized by an inflammatory
pericardial syndrome with at least 2 of the following 5 clinical findings after cardiac surgery: fever
without alternative causes, pericardial chest pain, pericardial rub, evidence for pericardial effusion,
or elevated CRP.
-
Recurrence of PPS would have been characterized as a subsequent episode of pericarditis
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occurring after a symptom-free interval of 4-6 weeks or longer. 
For the purposes of this study, the Investigator will determine, based on his/her judgement of the 
available data, if a subject has met these criteria for having previously experienced a first (index) 
episode of acute PPS followed by at least 2 recurrent episodes of PPS and will record the criteria 
supporting this diagnosis in the eCRF. 
Subjects who are taking corticosteroids for the recurrent PPS and who are not currently experiencing 
symptoms which, in the opinion of the Investigator, would meet the above diagnostic criteria for a flare 
may be enrolled into Part 5 only if, in the opinion of the Investigator and in consultation with the 
Sponsor, they are considered to be “corticosteroid- dependent” (i.e.; the signs and symptoms of 
pericarditis would return if the corticosteroids were withdrawn). 
Enrollment Process for All Parts: 
Prior to enrollment, potential subjects may enter an optional Prescreening Period after signing a 
Prescreening ICF (or informed assent, if applicable) to confirm the diagnostic workup and to allow 
monitoring for symptoms and inflammatory markers (CRP, ESR, etc) while concomitant medications 
for pericarditis treatment may be managed by the Investigator or their clinician according to standard of 
care. 
Subjects included in Parts 1, 2 and 4 may be receiving concomitant nonsteroidal anti-inflammatory 
drugs (NSAIDs), and/or colchicine, and/or oral corticosteroid treatment in any combination, provided 
the dosages of these medications have been stable for at least 7 days, although stable doses for a shorter 
period will be acceptable if in the opinion of the Investigator, in consultation with the Sponsor, a shorter 
period of stability is not anticipated to alter the baseline CRP values.  
Subjects in Parts 3 and 5 must be receiving corticosteroids at the time of enrollment. 
Baseline therapy and disease characteristics will be determined during a Screening Period of up to 
72 hours, as needed, to confirm study eligibility.  At the SCV1, baseline subject and disease 
characteristics will be determined and captured in the eCRF.  At Screening Visit 2 (SCV2) during the 
24 - 72 hour period before subjects advance to the Treatment Period of the study, additional laboratory 
samples may be drawn to provide additional baseline reference data. Under special circumstances, the 
Investigator, in consultation with the Sponsor, can combine SCV1 and SCV2, and the subject can 
proceed directly to the Day 0 dosing visit. 
After having met all the entry criteria during the Screening Period, the adult subjects (18 years or older) 
entering the Treatment Period will receive a loading dose of 320 mg KPL-914 (2 x 160 mg) 
administered SC on Day 0, then 160 mg SC weekly for 5 additional doses. Subjects aged 6 years to <18 
years will receive a loading dose of 4.4 mg/kg KPL-914 (2x 2.2 mg/kg; maximum total 320 mg) 
administered SC on Day 0, then 2.2 mg/kg (maximum 160 mg) administered SC weekly for 5 
additional doses. 
The first Study Drug dose on Day 0 will be administered at the Study Site/Clinic (Visit 1).  Subsequent 
weekly Study Drug doses from Weeks 2 to 5 will be self-administered by the subject or will be 
administered to the subject by an adequately trained caregiver as an outpatient SC administration. Study 
center staff or a visiting study nurse will assess and record compliance with Study Drug administration 
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at the subject’s home as well as provide guidance and training on Study Drug administration as needed. 
At Week 6/End of Trial, Study Drug may be administered at home or other non-clinic location or 
administered at the study site.  Weekly assessments of safety and treatment response, including 
administration of the 11-point NRS instrument to assess pericardial pain, will be done at the Study 
Site/Clinic at Visit 1 (Day 0) and Visit 7 (Week 6/End-of-Trial), and via Investigator (or designee) 
phone calls/ virtual visits on Day 3 and at Weeks 2 to 5 (Visits 2 to 5). Weekly outpatient blood 
samples for central laboratory testing will be collected at the Study Site/Clinic, or at a qualified 
laboratory site in the vicinity of the subject, or by a visiting study nurse. 
Investigators are encouraged to schedule subjects at the Study Site/Clinic for an in-person Interval 
Evaluation Visit during approximately Weeks 3-4 to assist the Investigator in the clinical management 
of the subject.  During this visit a full assessment including physical examination, vital signs, ECG, 
echocardiogram, and laboratory testing can be performed as well as the recording of adverse events 
(AEs) and other study-related assessments as needed.   
At any time point during the Treatment Period, subjects reporting worsening of pericarditis symptoms 
or AEs may be brought into the Study Site/Clinic at the discretion of the Investigator for an 
Unscheduled Visit, in which select or comprehensive clinical assessments can be performed.  Any 
subject who is determined by the Investigator as not responding to treatment (e.g., no reduction in 
pericardial pain compared to baseline, no decrease in CRP levels [if applicable], etc.) and who is 
therefore considered by the Investigator to be a “Treatment Failure” may be withdrawn from further 
Study Drug treatment at the discretion of the Investigator and may receive rescue therapy for their 
pericarditis according to standard of care as per Investigator decision; these subjects will be followed 
for safety for the remainder of the 6-week Treatment Period.  Subjects identified as “Treatment 
Failures” may be replaced at the discretion of the Sponsor in order to provide an adequate sampling of 
subjects completing the active Treatment Period. 
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Subjects participating for the complete length of the active study Treatment Period will receive a total 
of 6 doses of KPL-914.  For the duration of the Treatment Period, concomitant NSAIDs and/or 
colchicine and/or corticosteroids, if present, should be continued at pre-study dose levels until after the 
6-dose Study Drug Treatment Period has concluded; however, should the Investigator determine that a
reduction/tapering of the NSAID, colchicine, and/or corticosteroid dose is medically indicated, the
NSAID, colchicine, and/or corticosteroid dose can be down-titrated in consultation with the Sponsor,
and the modification of dose should be recorded in the source records and the eCRF.
Opioid analgesics, non-narcotic analgesics (e.g., tramadol), and acetaminophen are allowed as rescue 
medication for ancillary pain control on an as-needed basis throughout the Treatment Period.  Although 
it is recommended that NSAID dose levels (if present) should remain constant during the active 
Treatment Period, the concomitant NSAID dose may be temporarily increased (or an NSAID initiated) 
for ancillary pain control if deemed necessary by the Investigator, after consultation with the Sponsor. 
Any rescue medication use must be recorded in source records, eCRF, and medication diary.  
At the discretion of the Investigator, “Treatment Responders” will be offered participation in an 
optional 18-week Extension Period (EP), in which weekly open-label KPL-914 administration can be 
continued at the same dose as in the Treatment Period for a total duration of Study Drug treatment of up 
to 24 weeks. 
Treatment response will be defined by the Investigator: 
•
Part 1: A clinically significant reduction in pericardial pain using the 11-point NRS, normal or
near normal CRP levels, and/or absent or decreasing echocardiographic effusion at the End-of-
Trial Visit.
•
Part 2: A clinically significant reduction in pericardial pain using the 11-point NRS, normal or
near normal levels CRP, and/or absent or decreasing echocardiographic effusion at the End-of-
Trial Visit
•
Part 3: Absence of pericarditis flare and feasibility to taper corticosteroids.
•
Part 4: A clinically significant reduction in pericardial pain using the 11-point NRS, normal or
near normal CRP levels, and/or absent or decreasing echocardiographic effusion at the End-of-
Trial Visit
•
Part 5: Absence of pericarditis flare and feasibility to taper corticosteroids.
Weekly Study Drug administrations during the EP are by self-administration or by an adequately-
trained caregiver, and study nurse visits to the subject’s home as well as Investigator (or designee) 
telephone calls/virtual visits are to continue on a monthly basis. 
During the EP, the Investigator is encouraged to wean concomitant NSAIDs and/or colchicine, and/or 
corticosteroids. It is encouraged that NSAIDs and colchicine be tapered and withdrawn within 15 days 
after entry into the EP. It is encouraged that corticosteroids be progressively taped (e.g., by 5 mg 
prednisone or equivalent every week in adults or 0.2mg/kg every week in subjects <18yo) and 
discontinued within 6 weeks after entering the EP (i.e., by Study Week 12) unless in the opinion of the 
Investigator, a different corticosteroid weaning schedule is required based on subject’s clinical status. 
All medication changes must be recorded in source records and the eCRF.  Investigators are encouraged 
to schedule subjects at the Study Site/Clinic for an in-person Interval Evaluation Visit between Weeks 
15 to 20 (8 to 13 weeks after Visit 7/End of Trial Visit) to assist the Investigator in the clinical 
management of the subject.  During this visit a physical examination, vital signs, ECG, echocardiogram 
(ECHO), and laboratory testing can be performed at the discretion of the Investigator. 
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Available safety, tolerability, and efficacy data for each subject will be reviewed by the Investigator as 
part of ongoing subject management.  A Safety Review Committee (SRC) including selected 
Investigator(s) and Sponsor representatives will review on a monthly basis (at a minimum) all available 
data for all subjects, considering trends across each subject and each Part.  
Given the following occurrences, dosing may be halted or reduced in any Part of the study, in 
accordance with an SRC recommendation, confirmed by the Sponsor: 
-
One or more subjects experience a serious and unexpected adverse event that is considered by
the Investigator to be related to Study Drug (SUSAR), or 2 or more subjects experience similar
severe (non-serious) and unexpected AEs that are considered by the Investigator to be related to
Study Drug.
After an initial group of subjects has been treated, depending on the safety profile observed as well as 
the magnitude and speed of treatment response (e.g., if an informative number of subjects achieve 
treatment response early in the Treatment Period), the Sponsor in collaboration with the Investigators 
may elect to decrease the KPL-914 dose administered to a subsequent consecutive group of subjects (in 
any Part of the Study): the adult subjects (18 years or older) entering the Treatment Period will receive 
a loading dose of 160 mg KPL-914 (2 x 80mg) SC on Day 0, then 80 mg administered SC weekly for 5 
additional doses. Subjects aged 6 years to <18 years will receive a loading dose of 2.2 mg/kg KPL-914 
(2 x 1.1 mg/kg; maximum total 160 mg) administered SC on Day 0, then 1.1 mg/kg (maximum 80 mg) 
administered SC weekly for 5 additional doses, in order to explore efficacy at a lower dose. 
Depending on treatment response observed with the 80 mg dose (or 1.1 mg/kg in subjects 6 years to 
<18years old), the weekly dose administered to either these subjects or subsequent subjects may be 
changed back to 160 mg (or 2.2 mg/kg in subjects 6 years to <18 years old) by the Investigator in 
collaboration with the Sponsor.  For any given subject, the KPL-914 dose level received at the end of 
the Treatment Period should be continued into the EP (if administration is continued); however, a 
change in the KPL-914 dose level during the EP for any individual subject can be made at the 
discretion of the Investigator in consultation with the Sponsor, and the modification of dose should be 
recorded in the source records and the eCRF. 
During the Screening and Treatment Periods, subjects will enter information concerning the use of 
pericarditis and rescue (pain) medication into a medication diary.  Such information will be entered by 
the subject immediately after dosing of study drug. 
Number of Subjects: 
Approximately up to a total of 40 subjects with RIP or recurrent PPS will be enrolled as study subjects 
across all Parts.   
Subjects who discontinue the study (withdrawals and Treatment Failures) may be replaced at the 
Sponsor’s discretion in order to provide an adequate sampling of subjects completing the active 
Treatment Period. 
Diagnosis and Main Criteria for Inclusion: 
Inclusion Criteria for All Parts 
To be eligible to participate in the trial, a subject must meet all of the following criteria: 
1.
Has given consent (or assent, if applicable) and signed an Informed Consent Form (ICF) (or
informed assent form, if applicable).
2.
Male or female, of any ethnic origin.
3.
6 to 75 years of age, inclusive.
4.
If used, has received NSAIDs, and/or colchicine and/or corticosteroids (in any combination) at
stable dose levels for at least 7 days (although stable doses for a shorter period will be acceptable
if in the opinion of the Investigator, in consultation with the Sponsor, a shorter period of stability
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is not anticipated to alter the baseline CRP values) and is anticipated to continue these 
concomitant medications at these dose levels for the duration of the active Treatment Period. 
5.
If female of child-bearing potential, must be nonpregnant and nonlactating and must agree to use
an effective method of contraception, e.g., hormonal contraception or double-barrier birth control.
6.
Is able to adequately maintain a medication diary.
7.
Agrees to refrain from making any new, major life-style changes that may affect pericarditis
symptoms (e.g., starting a new diet or changing exercise pattern) from the time of signature of the
ICF (or informed assent form, if applicable) to the End-of-Trial Visit (Week 6).
Inclusion Criteria for Part 1: 
8.
Has a diagnosis of RIP based on the judgement of the Investigator.
9.
Has previously had an index (first) episode of pericarditis which, in the judgement of the
Investigator based on the available data, met the criteria for an acute pericarditis event, using the
2015 ESC Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al,
2015) as a frame of reference --  i.e., met at least 2 of the 4 following criteria: pericarditic chest
pain, pericardial rub, new widespread ST-segment elevation or PR-segment depression on ECG,
and pericardial effusion (new or worsening).  Additional supportive findings could include
elevations of markers of inflammation (i.e., CRP, ESR or WBC count) or evidence of pericardial
inflammation by an imaging technique (e.g., MRI).
10. Has had at least one prior recurrent episode of pericarditis, in the judgement of the Investigator,
based upon the available diagnostic information.
11. Has an ongoing symptomatic episode of pericarditis at the time of study enrollment in the
judgement of the Investigator, based upon the available diagnostic information.
12. Has an elevated CRP value (i.e., >1 mg/dL) at the time of Screening.
Inclusion Criteria for Part 2: 
13. Has a diagnosis of RIP based on the judgement of the Investigator.
14. Has previously had an index (first) episode of pericarditis which, in the judgement of the
Investigator based on the available data, met the criteria for an acute pericarditis event, using the
2015 ESC Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al,
2015) as a frame of reference --  i.e., met at least 2 of the 4 following criteria: pericarditic chest
pain, pericardial rub, new widespread ST-segment elevation or PR-segment depression on ECG,
and pericardial effusion (new or worsening).  Additional supportive findings could include
elevations of markers of inflammation (i.e., CRP, ESR or WBC count) or evidence of pericardial
inflammation by an imaging technique (e.g., MRI).
15. Has had at least one prior recurrent episode of pericarditis, in the judgement of the Investigator,
based upon the available diagnostic information.
16. Has an ongoing symptomatic episode of pericarditis at the time of study enrollment in the
judgement of the Investigator, based upon the available diagnostic information.
17. Has CRP value < 1 mg/dL at Screening, which in the opinion of the Investigator in consultation
with the Sponsor, can be attributed to concomitant medications.
18. Has evidence of pericardial inflammation by cardiac MRI which has been confirmed by the
MRI core imaging lab.
Inclusion Criteria for Part 3: 
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19. Has a diagnosis of RIP based on the judgement of the Investigator. 
20. Has previously had an index (first) episode of pericarditis which, in the judgement of the 
Investigator based on the available data, met the criteria for an acute pericarditis event, using the 
2015 ESC Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 
2015) as a frame of reference --  i.e., met at least 2 of the 4 following criteria: pericarditic chest 
pain, pericardial rub, new widespread ST-segment elevation or PR-segment depression on ECG, 
and pericardial effusion (new or worsening).  Additional supportive findings could include 
elevations of markers of inflammation (i.e., CRP, ESR, or WBC count) or evidence of pericardial 
inflammation by an imaging technique (e.g., MRI). 
21. Has had at least two prior recurrent episodes of pericarditis, in the judgement of the 
Investigator, based upon the available diagnostic information. 
22. Is not currently (at Screening) experiencing symptoms which, in the judgment of the Investigator 
based on the available diagnostic information, would meet the diagnostic criteria for a flare of 
pericarditis. 
23. Is “corticosteroid-dependent,” in the judgement of the Investigator based on available data (i.e., 
the signs and symptoms of pericarditis would return if the corticosteroids were to be withdrawn). 
 
Inclusion Criteria for Part 4: 
24. Has a diagnosis of recurrent PPS based on the judgement of the Investigator. 
25. Has previously had an index (first) episode of PPS which, in the judgement of the Investigator 
based on the available data, met the criteria for an acute pericarditis event, using the 2015 ESC 
Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 2015) as a 
frame of reference,  i.e., met at least 2 of the 5 clinical findings after cardiac surgery: fever 
without alternative causes, pericardial chest pain, pericardial rub, evidence for pericardial 
effusion with elevated CRP  
26. Has had at least one prior recurrent episode of PPS, in the judgement of the Investigator, based 
upon the available diagnostic information. 
27. Has an ongoing symptomatic episode of recurrent PPS at the time of study enrollment in the 
judgement of the Investigator, based upon the available diagnostic information. 
28. Has an elevated CRP value (i.e., >1 mg/dL) at the time of Screening. 
 
Inclusion Criteria for Part 5: 
29. Has a diagnosis of recurrent PPS based on the judgement of the Investigator. 
30. Has previously had an index (first) episode of PPS which, in the judgement of the Investigator 
based on the available data, met the criteria for an acute pericarditis event, using the 2015 ESC 
Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 2015) as a 
frame of reference,  i.e., met at least 2 of the 5 clinical findings after cardiac surgery: fever 
without alternative causes, pericardial chest pain, pericardial rub, evidence for pericardial 
effusion with elevated CRP  
31. Has had at least two prior recurrent episodes of PPS, in the judgement of the Investigator, based 
upon the available diagnostic information. 
32. Is not currently (at Screening) experiencing symptoms which, in the judgment of the Investigator 
based on the available diagnostic information, would meet the diagnostic criteria for a flare of 
pericarditis. 
33. Is “corticosteroid-dependent,” in the judgement of the Investigator based on the available data, 
(i.e., the signs and symptoms of pericarditis would return if the corticosteroids were to be 
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withdrawn). 
 
Exclusion Criteria for all Parts: 
A subject who meets any of the following criteria will not be eligible to participate in the trial: 
1. Has a diagnosis of pericarditis that was secondary to specific excluded etiologies, including 
tuberculous, neoplastic, or purulent etiologies, post-myocardial infarction (early or late), thoracic 
trauma, myocarditis, or systemic diseases including autoinflammatory diseases, autoimmune 
diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, etc.). 
2. Has a history of immunodepression, including a positive human immunodeficiency virus test 
result. 
3. Has received treatment within the 6-month period before dosing with any systemic 
immunosuppressants (other than, for example, corticosteroids or mycophenolate) which, in the 
opinion of the Investigator (in consultation with the Sponsor), may interfere with the study 
endpoints.  
4. Currently receiving other interleukin (IL)-1 or IL-6 blockers, janus-activating kinase (JAK) or 
tumor necrosis factor (TNF) inhibitors. 
5. Has a history of myeloproliferative disorder, demyelinating disease, or symptoms suggestive of 
multiple sclerosis. 
6. Female subject who is pregnant or lactating or who does not agree to use an effective method of 
contraception, e.g., hormonal contraception or double-barrier birth control. 
7. Has a history of active or latent treated tuberculosis (TB), or had a positive QuantiFERON (QFT-
TB G In-Tube) test result, or a chest radiograph during the 3 months prior to Study Drug dosing 
suggestive of prior TB infection. A subject with a positive purified protein derivative (PPD) test 
result (≥5-mm induration) after the first attack of pericarditis is excluded unless he/she has had 
either a negative chest x-ray result or a negative QuantiFERON test result. 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, night sweats) upon review of medical history and/or 
physical exam.  Have recent close contact with a person with active TB.  
8. Chest radiograph (or historic results within 3 months of SCV1) that shows evidence of 
malignancy or any abnormalities suggestive of prior TB infection, including, but not limited to, 
apical scarring, apical fibrosis, or multiple calcified granulomata.  This does not include non-
caseating granulomata. 
9. Has received immunization with a live (attenuated) vaccine within 12 weeks before the start of 
the study. 
10. Has history of or positive or intermediate results for hepatitis B surface antigen (HBsAg), 
hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at SCV1. 
11. Has an estimated glomerular filtration rate (eGFR) <30 mL/min.  
12. Has a history of malignancy of any organ system within the past 5 years (other than a 
successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or 
localized carcinoma in situ of the cervix). 
13. 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. 
14. Has had a serious infection, has been hospitalized for an infection, has been treated with oral 
antibiotics within 2 weeks of Study Drug administration, or has been treated with intravenous 
(IV) antibiotics for an infection within 2 months of first Study Drug administration.  
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15. Has had an organ transplant.
16. In the Investigator's judgement, has a history of alcoholism or drug/chemical abuse within 2 years
prior to Study Drug administration.
17. Has a drug screen positive for amphetamines, cocaine, or phencyclidine or positive alcohol test at
SCV1.  Exceptions may be made if a subject is on an approved medication for a stable
concomitant condition that explains the positive screen.
18. Has taken commercially-available rilonacept (ARCALYST®) or participated in a rilonacept
clinical study during the 90 days before SCV1.  Has used anakinra within 14 days prior to Study
Drug administration. Rilonacept and anakinra could not have been discontinued due to lack of
efficacy or due to safety.
19. Has a history of hypersensitivity to rilonacept or to any of the excipients contained in the Study
Drug.
20. Has received an investigational drug during the 30 days (or 5 half-lives, whichever is longer)
before SCV1 or is planning to receive an investigational drug (other than that administered during
this trial) or use an investigational device at any time during the trial.
21. In the Investigator's judgement, has any other medical condition that could adversely affect the
subject's participation or interfere with study evaluations.
22. Subject who, in the opinion of the Investigator, is not likely to be compliant with the study
protocol.
23. Subject who, in the opinion of the Investigator in consultation with the Sponsor, should not
participate in this study.
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Test Products, Dosage, and Mode of Administration: 
KPL-914 (rilonacept) will be provided in its commercially-available formulation as a lyophilized 
powder to be reconstituted for SC administration. 
Subjects will receive a total of 6 doses of KPL-914 during the study active Treatment Period.  Subjects 
who are considered to be “Treatment Responders” will be offered, at the discretion of the Investigator, 
participation in an optional 18-week Extension Period (EP), in which weekly open-label KPL-914 can 
be continued for a total duration of KPL-914 treatment of up to 24 weeks. 
 
Adult subjects (≥ 18 years of age) 
KPL-914 will be administered as an initial loading dose of 320 mg SC, delivered as two subcutaneous 
injections of 160 mg SC each on Day 0, then 160 mg SC dosed once weekly for 5 subsequent weeks.   
 
Pediatric subjects (6 to <18 years of age) 
KPL-914 will be administered with an initial loading dose of 4.4 mg/kg, up to a maximum of 320 mg, 
delivered as two subcutaneous injections of 2.2 mg/kg each with a maximum single-injection volume of 
2 mL. Dosing will continue with a once-weekly injection of 2.2 mg/kg, up to a maximum of 160 mg, 
administered as a single subcutaneous injection of up to 2 mL as outpatient self-administration or 
administered by an adequately trained caregiver, for 5 subsequent weeks. 
 
After an initial group of subjects has been treated, depending on the safety profile observed as well as 
the magnitude and speed of treatment response (e.g., if an informative number of subjects achieve 
treatment response early in the Treatment Period), the Sponsor in collaboration with the Investigators 
may elect to decrease the KPL-914 dose administered to a subsequent consecutive group of subjects (in 
any Part of the Study):  the adult subjects (18 years or older) entering the Treatment Period will receive 
a loading dose of 160 mg KPL-914 (2 x 80mg) SC on Day 0, then 80 mg administered SC weekly for 5 
additional doses. Subjects aged 6 years to <18 years will receive a loading dose of 2.2 mg/kg KPL-914 
(2x 1.1 mg/kg; maximum total 160 mg) administered SC on Day 0, then 1.1 mg/kg (maximum 80 mg) 
administered SC weekly for 5 additional doses, in order to explore efficacy at a lower dose. 
 
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CONFIDENTIAL 
Concomitant Medication 
•
There is no wash-out of concomitant therapy (NSAIDs/colchicine/corticosteroids) during the
Screening Period of the study.
•
For the duration of the Treatment Period, concomitant pericarditis medications (e.g., NSAIDs,
colchicine and corticosteroids), if used, should be continued at pre-study dose levels until after the
6-dose Study Drug Treatment Period has concluded; however, should the Investigator determine
that a reduction/tapering of the NSAIDs, colchicine, and/or corticosteroid dose is medically
necessary, the NSAID, colchicine and/or corticosteroid dose can be down-titrated according to
standard of care paradigms in consultation with the Sponsor, and the modification of dose should be
recorded in the source records and the eCRF.
•
Opioid analgesics, non-narcotic (non-NSAID) analgesics (e.g., tramadol), and acetaminophen are
allowed as rescue medication for ancillary pain control on an as needed basis throughout the
Treatment Period.  Although it is recommended that NSAID dose levels (if present) should remain
constant during the active Treatment Period, the concomitant NSAID dose may be temporarily
increased (or an NSAID initiated) for ancillary pain control if deemed necessary by the
Investigator, after consultation with the Sponsor.  Any rescue medication use must be recorded in
source records, the medication diary and the eCRF.
•
Medical management of pericarditis during the EP is based on Investigator discretion. For example,
Investigators may continue subjects on KPL-914 at the same dosage level, wean-off or discontinue
Study Drug.  During the EP, the Investigator is encouraged to wean concomitant NSAIDs, and/or
colchicine, and/or corticosteroids.  It is encouraged that NSAIDs and colchicine be tapered and
withdrawn within 15 days after entry into the EP.  It is encouraged that corticosteroids be
progressively tapered  (e.g., by 5 mg prednisone or equivalent every week in adults or  0.2mg/kg
every week in subjects <18yo) and discontinued within 6 weeks after entering to EP (i.e., by Study
Week 12) unless in the opinion of Investigator, a different corticosteroid weaning schedule is
required based on subject’s clinical status
•
Other pericarditis medications may also be initiated at the discretion of the Investigator.  All
changes to pericarditis-related medications should be captured in the source records and eCRF.
•
Prohibited concomitant medicines: Other interleukin (IL)-1 or IL-6 blockers, janus-activating
kinase (JAK) or tumor necrosis factor (TNF) inhibitors.
Duration of Treatment: 
The Study Drug will be administered for 6 weeks in the base study Treatment Period. 
“Treatment Responders” will be offered participation in an optional 18-week EP at the discretion of the 
Investigator. 
Total subject participation is expected to last for up to 171 days for those that also participate in the 
18-week EP.
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CONFIDENTIAL 
Efficacy Measures: 
- Clinical laboratory analyses (e.g., CRP).
- Pericarditis symptoms (i.e., pain) using a 11-point NRS (Appendix 4: 11-point Numerical Rating
Scale (NRS) for Assessment of Pericarditis Pain)
- Echocardiogram (pericardial effusion)
- ECG (for pericarditis diagnostic findings)
- Pericarditis signs (e.g., fever, pericardial rub)
- Pericardial inflammation as determined by cardiac MRI (optional assessment for Parts 1, 3, 4, 5;
mandatory for Part 2)
- Quality of life (QoL) questionnaire (Appendix 3).
Safety Measure(s): 
Safety endpoints for this study include frequency and severity of AEs and SAEs, clinical laboratory 
analyses (including safety laboratory measurements, anti-drug antibodies, etc.), vital sign 
measurements, ECGs, and physical examination findings. 
Other Measure(s): 
 
Overview of Trial Design 
Trial Periods (all Parts) 
1.
Prescreening Period: Prior to enrollment, potential subjects may enter an optional prescreening
period after signing a Prescreening ICF (or prescreening informed assent, if applicable) to
confirm the diagnostic workup and to allow monitoring for symptoms and inflammatory
markers (CRP, ESR, etc) while concomitant pericarditis medications may be managed by the
Investigator or their clinician according to standard of care.
2.
Screening Period: The Screening Period starts with the signing of the full study ICF (or
informed assent form, if applicable) (SCV1) and may last for up to 3 days (72 hours) until
SCV2.  At SCV1, baseline subject and disease characteristics will be determined.  At Screening
Visit 2 [SCV2]), within the 24 – 72 hour period before subjects advance to the Treatment
Period of the study, additional laboratory samples may be drawn to provide additional baseline
reference data.  Under special circumstances, the Investigator in consultation with the Sponsor
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CONFIDENTIAL 
can combine SCV1 and SCV2.  The end of the Screening Period coincides with the start of the 
Treatment Period (Day 0 Visit).  
At the SCV1, subjects will be given a medication diary to record administration of pericarditis 
medications and rescue (pain) medication use during the Screening Period. 
Patient-reported pericardial pain evaluations will be performed on-site at SCV1 and SCV2 
using a validated 11-point NRS instrument.  A patient-reported QoL questionnaire will be 
administered as well. 
3. Treatment Period: The first dose of Study Drug will be administered to subjects at the Study 
site/Clinic at Visit 1 on Day 0.  During this visit, subjects and/or caregivers will be trained for 
outpatient drug administration.  At Day 3, the Investigator (or designee) telephone call/virtual 
visit will occur to evaluate safety (AE evaluations) and patient-reported pericardial pain using a 
validated 11-point NRS instrument. 
Subsequent weekly Study Drug administrations from Weeks 2 to 5 will be self-administered by 
the subject or administered by an adequately trained caregiver as an outpatient SC 
administration. A visiting study nurse will assess and record compliance with Study Drug 
administration at the subject’s home as well as provide guidance and training on Study Drug 
administration as needed. At Week 6/End-of-Trial, Study Drug may be self-administered or 
administered at the Study site/clinic.   
Investigators are encouraged to schedule subjects at the Study Site/Clinic for an in-person 
Interval Evaluation Visit during approximately Weeks 3-4 to assist the Investigator in the 
clinical management of the subject.   
Subjects reporting worsening of pericarditis symptoms or AEs may be brought in for an 
unscheduled visit at the Study Site/Clinic at any time during the Treatment Period, at the 
discretion of the Investigator.  Any subject who is considered by the Investigator to be a 
“Treatment Failure” may be withdrawn from further Study Drug treatment at the discretion of 
the Investigator and receive rescue therapy for their pericarditis according to standard of care as 
per Investigator decision; these subjects will be followed for safety for the remainder of the 6-
week Treatment Period.  Subjects identified as “Treatment Failures” may be replaced at the 
discretion of the Sponsor in order to provide an adequate sampling of subjects completing the 
active Treatment Period. 
During the Treatment Period, subjects will continue documentation of pericarditis treatment 
medication use as well as rescue (pain) medication use in the medication diary.  Patient-
reported pericardial pain evaluations will be performed on-site at the Study Site/Clinic and by 
weekly (and on Day 3) Investigator (or designee) telephone calls/virtual visits using a validated 
11-point NRS instrument.  A patient-reported QoL questionnaire will be administered at Visit 7 
(Study Site/Clinic).  Weekly blood samples for central laboratory testing will be collected at the 
Study Site/Clinic or at a qualified laboratory site in the vicinity of the subject or by a visiting 
study nurse. 
4. Extension Period (EP): The EP is defined as the 18 weeks following the Treatment Period.  
Subjects who are considered to be “Treatment Responders” will be, at the discretion of the 
Investigator, offered participation in an optional 18-week EP, in which weekly administration 
of open-label KPL-914 may be continued for a total duration of 24 weeks.  The weekly KPL-
914 doses will be by self-administration or administered by adequately trained caregiver, and 
study nurse visits to the subject’s home as well as Investigator (or designee) telephone 
calls/virtual visits will continue on a monthly basis. During the EP, the Investigator is 
encouraged to wean concomitant NSAIDs, and/or colchicine, and/or corticosteroids.  It is 
encouraged that NSAIDs and colchicine be tapered and withdrawn within 15 days after entry 
into the EP.  It is encouraged that corticosteroids be progressively tapered (e.g., by 5 mg 
prednisone or equivalent every week in adults or 0.2mg/kg every week in subjects <18yo) and 
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CONFIDENTIAL 
discontinued within 6 weeks after entering to EP (i.e., by Study Week 12) unless in the opinion 
of Investigator, a different corticosteroid weaning schedule is required based on subject’s 
clinical status. Other pericarditis medications may also be initiated at the discretion of the 
Investigator.  All changes to pericarditis-related medications should be captured in the source 
records and eCRF 
Unscheduled clinic visits can be scheduled any time as determined by the Investigator/upon 
subject request. In addition, Investigators are encouraged to schedule subjects at the Study 
Site/Clinic for an in-person Interval Evaluation Visit between Weeks 15 to 20 (8 to 13 weeks 
after Visit 7) to assist the Investigator in the clinical management of the subject.  During this 
visit a physical examination, vital signs, ECG, echocardiogram, and laboratory testing can be 
performed. 
Patient-reported pericardial pain evaluations using a validated 11-point NRS instrument as well 
as AE monitoring will be performed during the EP at on-site clinic visits and/or during monthly 
Investigator (or designee) phone calls/virtual visits.  A patient-reported QoL questionnaire will 
be administered at the Interval Evaluation Visit and the Final Visit of the EP.  At the end of the 
EP, subjects will complete the Week 25/Final Visit.  
Statistical Methods: 
Each Part will be analyzed separately and per the analysis populations below, to be finalized in the 
Statistical Analysis Plan to be provided separately.  
Analysis Populations (each Part) 
The modified Intention to Treat (mITT) Population will consist of all subjects who received at least one 
dose of Study Drug.  The Per Protocol (PP) Population will consist of all subjects who received all 6 
doses of Study Drug during the active Treatment Period and were maintained at stable dose levels of 
concomitant pericarditis medications (e.g., NSAIDs, colchicine, corticosteroids) according to study 
protocol without a major protocol violation.  The Safety Population will be the same as the mITT 
Population. 
General Methods 
Because of the small sample size no inferential statistical analyses or hierarchical testing are planned. 
For analysis of continuous endpoints (e.g., change from baseline), summary statistics (n, mean, standard 
deviation, median, minimum, and maximum) will be calculated and presented for each treatment and/or 
analysis group.  For categorical endpoints, summary statistics will be calculated and presented for each 
treatment and/or analysis group. Under certain circumstances, if appropriate in the context of statistical 
methodologies, the results of certain similar Parts might be pooled for greater statistical precision in 
determining therapeutic response or safety. 
Further details, including, for example, the process to be followed for reviewing individual pericarditis 
symptomatology endpoints to be used in the construction of a composite primary endpoint for 
subsequent trials, will be provided in the Statistical Analysis Plan (SAP). 
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CONFIDENTIAL 
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Table 1: 
Schedule of Evaluations 
Trial Period → 
Pre-
screening 
Period 
Run-In 
Period 
(Up to 3 
days) 
Treatment Period 
(6 weeks) 
Extension Period 
(18 weeks) 
Visit Days/Weeks → 
Day -3 to 
Day 0a 
Day 0b 
Day  
3 c 
Week  
2c 
Week  
3c 
W3-W4d 
Week 
4c 
Week 
5c 
Week 
6cc 
Week 
6/ 
End-
of-
Trial c 
W15-W20t 
Week 
25 
(Week 
7 +18 
weeks) 
Visit Number → 
SC 
Visit 
1 
SC 
Visit 
2 
Visit 1 
(Clinic) 
Day 3  
(Outpt) 
Visit 2 
(Outpt) 
Visit 3 
(Outpt)  
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 4 
(Outpt) 
Visit 5 
(Outpt) 
Visit 6 
(Outpt) 
Visit 7 
Clinic 
Monthly 
Visits 
(Outpt) 
Un-
scheduled 
Visits 
(Clinic) 
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 8 
(Final, 
Clinic) 
Dose Number → 
Dose 1 
N/A 
Dose 2 
Dose 3 
N/A 
Dose 4 
Dose 5 
Dose 6 
Trial Procedure ↓ 
Unscheduled Visitsu 
Signature of ICF (or 
informed assent, if 
applicable) 
X 
X 
Inclusion and 
exclusion criteria 
verification 
X 
X 
Demographics 
X 
X 
Medical history e 
X 
X 
Study Drug admin. – 
On site f 
X 
(Xf) 
Study Drug admin. - 
Outpatient f 
X 
X 
X 
X 
X 
Xf 
X w 
(weekly) 
Physical examination
g
X 
X 
X  
X 
X 
X 
X 
Body weight and 
height 
X 
X 
Vital Signs h 
X 
X 
X 
X 
X 
X 
X 
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CONFIDENTIAL 
Trial Period → 
Pre-
screening 
Period 
Run-In 
Period 
(Up to 3 
days) 
Treatment Period 
(6 weeks) 
Extension Period 
(18 weeks) 
Visit Days/Weeks → 
Day -3 to 
Day 0a 
Day 0b 
Day  
3 c 
Week  
2c 
Week  
3c 
W3-W4d 
Week 
4c 
Week 
5c 
Week 
6cc 
Week 
6/ 
End-
of-
Trial c 
W15-W20t 
Week 
25 
(Week 
7 +18 
weeks) 
Visit Number → 
SC 
Visit 
1 
SC 
Visit 
2 
Visit 1 
(Clinic) 
Day 3  
(Outpt) 
Visit 2 
(Outpt) 
Visit 3 
(Outpt)  
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 4 
(Outpt) 
Visit 5 
(Outpt) 
Visit 6 
(Outpt) 
Visit 7 
Clinic 
Monthly 
Visits 
(Outpt) 
Un-
scheduled 
Visits 
(Clinic) 
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 8 
(Final, 
Clinic) 
Dose Number → 
Dose 1 
N/A 
Dose 2 
Dose 3 
N/A 
Dose 4 
Dose 5 
Dose 6 
Trial Procedure ↓ 
Unscheduled Visitsu 
ECG/ECHO i 
X 
X 
(EC
G) 
X 
X 
X 
X 
MRI j 
X 
X 
X 
Prior and 
concomitant 
medicines k 
X 
X 
X 
X 
X 
X  
X 
X 
X 
Drug and alcohol test 
X 
QuantiFERON TB 
test   j 
X 
Clinical laboratory 
tests (incl CRP)– 
Central laboratory l 
X 
X 
(X)x 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical laboratory 
tests (lipid panel) – 
Central Laboratory 
X 
X aa 
X 
Clinical laboratory 
tests (incl CRP) – 
Study Site/Clinic 
laboratory m 
Xy
X 
X 
(X)x 
X 
X 
X 
X 
X 
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KPL-914-C001 Amendment 2                                                                             Final 
Page 27 of 85 
 
CONFIDENTIAL 
Trial Period → 
Pre-
screening 
Period 
Run-In 
Period 
(Up to 3 
days) 
 
Treatment Period 
(6 weeks) 
Extension Period 
(18 weeks) 
Visit Days/Weeks → 
Day -3 to 
Day 0a 
Day 0b 
 
 
Day  
3 c 
Week  
2c 
Week  
3c 
W3-W4d 
Week 
4c 
Week 
5c 
Week 
6cc 
Week 
6/ 
End-
of-
Trial c 
 
 
W15-W20t 
Week 
25 
(Week 
7 +18 
weeks) 
Visit Number → 
SC 
Visit 
1 
SC 
Visit 
2 
Visit 1 
(Clinic) 
 
 
Day 3  
(Outpt) 
Visit 2 
(Outpt) 
Visit 3 
(Outpt)  
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 4 
(Outpt) 
Visit 5 
(Outpt) 
Visit 6 
(Outpt) 
Visit 7 
Clinic 
 
Monthly 
Visits 
(Outpt) 
Un-
scheduled 
Visits 
(Clinic) 
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 8 
(Final, 
Clinic) 
Dose Number → 
 
 
Dose 1 
 
N/A 
Dose 2 
Dose 3 
N/A 
Dose 4 
Dose 5 
Dose 6 
 
 
 
 
 
Trial Procedure ↓ 
 
 
 
 
 
Unscheduled Visitsu 
 
 
 
 
Biomarker testing, 
PK, and anti-
rilonacept antibody – 
Central Laboratory l 
 
X 
 
(X) 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy test n 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE evaluations o 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medication diary 
dispensing p 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medication diary 
compliance 
verification and 
reminder q 
 
 
X 
(X)x 
 
 
 
X 
 
 
 
X 
 
 
 
X 
Pericardial pain (11-
pt Numerical Rating 
Scale) r 
X 
X 
X 
(X)x 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PGA (QoL 
questionnaire) s 
 
X 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
X 
Dosing Procedure 
Questionnaire z 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
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KPL-914-C001 Amendment 2                                                                             Final 
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CONFIDENTIAL 
Trial Period → 
Pre-
screening 
Period 
Run-In 
Period 
(Up to 3 
days) 
 
Treatment Period 
(6 weeks) 
Extension Period 
(18 weeks) 
Visit Days/Weeks → 
Day -3 to 
Day 0a 
Day 0b 
 
 
Day  
3 c 
Week  
2c 
Week  
3c 
W3-W4d 
Week 
4c 
Week 
5c 
Week 
6cc 
Week 
6/ 
End-
of-
Trial c 
 
 
W15-W20t 
Week 
25 
(Week 
7 +18 
weeks) 
Visit Number → 
SC 
Visit 
1 
SC 
Visit 
2 
Visit 1 
(Clinic) 
 
 
Day 3  
(Outpt) 
Visit 2 
(Outpt) 
Visit 3 
(Outpt)  
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 4 
(Outpt) 
Visit 5 
(Outpt) 
Visit 6 
(Outpt) 
Visit 7 
Clinic 
 
Monthly 
Visits 
(Outpt) 
Un-
scheduled 
Visits 
(Clinic) 
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 8 
(Final, 
Clinic) 
Dose Number → 
 
 
Dose 1 
 
N/A 
Dose 2 
Dose 3 
N/A 
Dose 4 
Dose 5 
Dose 6 
 
 
 
 
 
Trial Procedure ↓ 
 
 
 
 
 
Unscheduled Visitsu 
 
 
 
 
Investigator (or 
designee) phone 
call/virtual visit v 
 
 
 
 
 
X 
X 
X 
 
X 
X 
X 
 
X 
(monthly) 
 
 
 
ECHO = echocardiogram, ECG = electrocardiogram, ICF = informed consent form, MRI = magnetic resonance imaging, Outpt = outpatient, PGA = patient global 
assessment, pt = point, TB = tuberculosis, HBcAb = hepatitis B core antibody; HBsAb = hepatitis B surface antibody; HBsAg = hepatitis B surface antigen; HCVAb = 
hepatitis C virus antibody; HIV = human immunodeficiency virus 
a. 
A second Screening visit (SCV2) should be performed within ~24h to 72h.  Under special circumstances, the Investigator, in consultation with the Sponsor, can 
combine SCV1 and SCV2.  The last Screening and Day 0 procedures may be performed on the same day, but SCR procedures must be completed prior to Study 
Drug administration.  
b. Subjects who do not complete the Treatment Period (withdraw consent or are discontinued before they have completed 6 weeks treatment), must be asked to 
complete the procedures specified at the EoT Visit. 
c. 
Day 3 will occur ± 1 day after Day 0. Weekly intervals refer to 7 ± 1 days. The interval between Study Drug administrations must be at least 5 days.  
d. Subjects should return for an optional Interval Evaluation Visit at the clinic between approximately Week 3 and 4, as determined by the Investigator. 
e. 
Including age at first attack, number of previous attacks, and duration of attacks.  
f. 
Drug administration training of subjects is performed at Visit 1.  Study Drug will be administered in the Study Site/Clinic at Visit 1. Study Drug administrations are 
performed by the subjects (self-administration) or by an adequately trained caregiver on Visits (Outpatient) 2, 3, 4, 5, and 6. Participation in the Extension Phase 
(optional) is determined at the Week 6/EoT Visit 7 by the Investigator.  Subjects who are eligible and who are willing to participate will be consented during EoT 
Visit 7 at the Study Site/Clinic. Only subjects continuing treatment into the Extension Phase will receive Study Drug at Visit 7; Study Drug can be self-administered 
either as an outpatient or at the Study Site/Clinic (Site to provide Study Drug) depending on the logistics/timing of the EoT Visit 7 relative to the timing of weekly 
dosing. Timing for dose administration is per direction of the Investigator based upon the prescribing information and study-specified dosing intervals. Continued 
weekly Study Drug treatment during the EP will be outpatient administration.    
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CONFIDENTIAL 
g. Full physical examination including assessment of pericardial rub.    
h. Vital signs must be obtained in the seated position and include oral temperature, respiratory rate, blood pressure, and pulse. 
i. 
Central 12-lead ECG and echocardiogram reading (including assessment of pericardial effusion). At SCV2 only the ECG will be obtained. The Study Site/Clinic 
reading of the ECG and the ECHO at the time of the examination will be used by the Investigator for clinical decision-making. In addition, both the ECG and 
ECHO will be sent to a core laboratory for additional analysis. 
j. 
Optional in Parts 1, 3,4 and 5. Required for Part 2. 
k. At the SCV1, information related to concomitant medicine that subjects were taking during at least the 2 weeks prior to the visit will be captured. During the 
Treatment Period, changes in concomitant medication since the last Study Site/Clinic visit will be documented. During the EP, changes in pericarditis/concomitant 
medication will be assessed at Study Site/Clinic Visits and in monthly outpatient phone calls/virtual visits.  
l. 
Biomarker, pharmacokinetics (PK) and anti-rilonacept antibody analysis samples will be drawn in all subjects and archived for future testing. . During each Visit at 
the Study Site/Clinic a sample for CRP will be obtained and sent to the central laboratory (or designated qualified laboratory) for analysis; at each Outpatient Visit; 
blood for central laboratory measurement of CRP will be obtained as described in the Laboratory Manual. 
m. Hematology, chemistry, and urinalysis will be performed at the Study Site/Clinic laboratories, and results when available will be entered into the eCRF with 
appropriate reference values. Serology (HCVAb, HBsAg, HBcAb, HBsAb and HIV) and urine drug screen will be performed at SCV1 only. Hematology and 
urinalysis will not be performed at SCV2. 
n. To be eligible to continue in the trial, a negative urine pregnancy test must be documented at the SCV1. If the urine test is positive, additional Study Site/Clinic 
and/or central serum tests may be performed.  
o. All AEs occurring after the subject receives the first dose of Study Drug will be captured in source records and eCRF. 
p. At the SCV1, the Investigator or designee will instruct the subject about the use of the medication diary.  The subject will be asked to complete a entries   into the 
medication diary during the Screening Period and Treatment Period. Only information on pain/rescue medication will be collected. Other concomitant 
treatments/medications are not required to be captured. 
q. At the SCV2 and all subsequent visits at the Study Center, the Investigator or designee will review the Diary entry information to verify subject compliance.  If the 
last screening visit occurs at a different day than Visit 1, the review will also be performed at Visit 1.  Diary documentation will end at the End-of-Trial visit (Visit 
7).  
r. 
Subject assessment of pericardial pain using a validated 11-point Numerical Rating Scale.  The assessment will be performed on-site during clinic visits and as part 
of a telephone call/virtual visit during outpatient treatment weeks.  If the last screening visit occurs at a different day than Visit 1, the assessment will also be 
performed at Visit 1, prior to Study Drug treatment. All the assessments must occur prior to study drug injection. 
s. 
Adult subjects only. Subject global assessment of overall well-being will be assessed using a validated QoL Questionnaire (see Appendix 3). The assessment will be 
performed on-site during clinic visits.  If SCV2 occurs at a different day than Visit 1 (Day 0), the global assessment will also be performed at Visit 1, prior to Study 
Drug administration. 
t. 
Subjects may return for an optional EP Interval Evaluation Visit at the clinic between Week 15 and 20 (8 to 13 weeks after Visit 7), as determined by the 
Investigator.  
u. Subjects reporting worsening of pericarditis symptoms or AEs may be brought in at the discretion of the Investigator for an Unscheduled Visit at any time during 
the Treatment Period.  Any subject who is not responding to treatment (e.g., no reduction in pericardial pain compared to baseline, no decrease in CRP levels, etc.) 
and who is therefore considered by the Investigator to be a “Treatment Failure” may be withdrawn from further Study Drug treatment at the discretion of the 
Investigator and receive rescue therapy for their pericarditis according to standard of care as per Investigator decision; these subjects will be followed for safety for 
the remainder of the 6-week Treatment Period.  
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v. At weekly Investigator (or designee) phone calls/virtual visits during the Treatment Period, Study Drug compliance, medication diary compliance, and laboratory 
sample collection will be checked. The subjects will be asked using non-leading questions about any AEs occurring since the last contact (phone call/virtual visit or 
site visit), and NRS pain assessment will be performed.  Investigator (or designee) phone calls/virtual visits will be performed monthly during the during the EP to 
perform NRS pain assessments, collect AE information, and review pericarditis/concomitant medications. If scheduled, in-person Study Site/Clinic Visits 
(Unscheduled Visits or Evaluation Visits) can replace the phone calls/virtual visits. 
w. During the Extension Period, Study Drug treatment is weekly by self-administration, and the study nurse visits to the home and Investigator (or designee) phone 
calls/virtual visits are monthly. 
x. Visit 1 will coincide with SCV2.  In case Visit 1 is separated from SCV2, SCV2 clinical laboratory blood sampling and subject NRS pericardial pain rating must be 
repeated prior to Study Drug dosing. 
y. Per Standard of Care. 
z. 
Adult subjects only. The dosing preparation and administration questionnaire must be completed in the presence of Study Staff (via virtual visit) or visiting nurse. 
aa. This lab will be drawn only during the first monthly Extension Period visit. 
 
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4 Table of Contents 
1 
Protocol Approval Signatures ......................................................................................... 2 
1.1 
Sponsor Signature .......................................................................................................... 2 
2 
Investigator and Administrative Structure ...................................................................... 3 
3 
Synopsis ......................................................................................................................... 4 
4 
Table of Contents ......................................................................................................... 31 
5 
List of Abbreviations and Definition of Terms ............................................................... 34 
6 
Introduction ................................................................................................................. 36 
7 
Study Objectives ........................................................................................................... 38 
7.1 
Part 1 ........................................................................................................................... 39 
7.2 
Part 2 ........................................................................................................................... 39 
7.3 
Part 3 ........................................................................................................................... 39 
7.4 
Part 4: .......................................................................................................................... 39 
7.5 
Part 5: .......................................................................................................................... 40 
8 
Investigational Plan ...................................................................................................... 41 
8.1 
Overall Study Design and Plan ...................................................................................... 41 
8.2 
Discussion of Study Design ............................................................................................ 47 
8.3 
Selection of Study Population ........................................................................................ 47 
8.3.1 
Number of Planned Subjects ........................................................................... 47 
8.3.2 
Inclusion Criteria ........................................................................................... 48 
8.3.3 
Exclusion Criteria .......................................................................................... 50 
8.3.4 
Vaccination History and Immune status ............................................................ 51 
8.3.5 
Removal of Subjects from Therapy or Assessments ........................................... 52 
8.4 
Investigational Medicinal Products................................................................................ 53 
8.4.1 
Investigational Medicinal Products Administered .............................................. 53 
8.4.2 
Identity of Investigational Medicinal Products ................................................... 54 
8.4.3 
Method of Assigning Subjects to Treatment Groups ........................................... 54 
8.4.4 
Selection of Doses in the Study ....................................................................... 54 
8.4.5 
Selection and Timing of Dose for Each Subject ................................................. 55 
8.4.6 
Blinding........................................................................................................ 55 
8.4.7 
Prior and Concomitant Therapy ....................................................................... 56 
8.4.8 
Treatment Compliance ................................................................................... 57 
8.5 
Study Procedures ......................................................................................................... 57 
8.5.1 
Prescreening Period........................................................................................ 57 
8.5.2 
Screening Period ............................................................................................ 57 
8.5.2.1 
Screening Visit 1 (SCV1)................................................................................ 58 
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8.5.2.2 
Screening Visit 2 (SCV2)................................................................................ 58 
8.5.3 
Treatment Period ........................................................................................... 59 
8.5.3.1 
Visit 1 (Study Site/Clinic) - Day 0 ................................................................... 59 
8.5.3.2 
Day 3 (Outpatient) ......................................................................................... 59 
8.5.3.3 
Visits 2 to 6 (Outpatient) - Weeks 2, 3, 4, 5, 6 ................................................... 59 
8.5.3.4 
Interval Evaluation Visit (Study Site/Clinic) - Week 3-4 ..................................... 60 
8.5.3.5 
Unscheduled Visits (Study Site/Clinic) During the Treatment Period ................... 61 
8.5.3.6 
Visit 7/ End-of-Trial (Study Site/Clinic) - Week 6 ............................................. 61 
8.5.4 
Extension Period ............................................................................................ 62 
8.5.4.1 
Unscheduled Visits (Study Site/Clinic) during the EP ......................................... 62 
8.5.4.2 
Interval Evaluation Visit During Extension Period (Study Site/Clinic) - 
Week 15-20................................................................................................... 62 
8.5.4.3 
Visit 8/Final Visit (Study Site/Clinic) - Week 25 ............................................... 63 
8.5.5 
Duration of Treatment .................................................................................... 63 
8.6 
Efficacy and Safety Variables ........................................................................................ 64 
8.6.1 
Individual Efficacy Assessments ...................................................................... 64 
8.6.1.1 
C-Reactive Protein, Biomarker, and PK Assessments ......................................... 64 
8.6.1.2 
Echocardiogram (Pericardial Effusion) ............................................................. 64 
8.6.1.3 
Electrocardiogram (Pericarditis Diagnostic Findings) ......................................... 64 
8.6.1.4 
Pericarditis Signs (Fever, Pericardial Rub) ........................................................ 65 
8.6.1.5 
Pericarditis Pain (Chest Pain) .......................................................................... 65 
8.6.1.6 
Magnetic Resonance Imaging .......................................................................... 66 
8.6.1.7 
Quality of Life Questionnaire .......................................................................... 66 
8.6.1.8 
Dosing Procedure Questionnaire ...................................................................... 66 
8.6.2 
Safety Assessments ........................................................................................ 67 
8.6.2.1 
Adverse Events .............................................................................................. 67 
8.6.2.2 
Serious Adverse Events .................................................................................. 68 
8.6.2.3 
Adverse Reactions ......................................................................................... 70 
8.6.2.4 
Clinical Laboratory Variables .......................................................................... 70 
8.6.2.5 
Vital Signs .................................................................................................... 72 
8.6.2.6 
Physical Examination ..................................................................................... 72 
8.6.2.7 
Body Weight and Height................................................................................. 72 
8.7 
Statistical Methods ....................................................................................................... 72 
8.7.1 
Statistical and Analytical Plans ........................................................................ 72 
8.7.1.1 
Datasets to be Analyzed for Each Part .............................................................. 72 
8.7.1.2 
General Statistical Methods ............................................................................. 72 
8.7.1.3 
Efficacy Endpoints ......................................................................................... 73 
8.7.1.4 
Safety Variables ............................................................................................ 74 
8.7.2 
Determination of Sample Size ......................................................................... 74 
8.8 
Quality Assurance and Quality Control ......................................................................... 74 
8.8.1 
Audit and Inspection ...................................................................................... 74 
8.8.2 
Monitoring .................................................................................................... 74 
8.8.3 
Data Management and Coding ......................................................................... 75 
8.8.4 
Record Keeping ............................................................................................. 75 
9 
Records and Supplies .................................................................................................... 75 
9.1 
Drug Accountability ..................................................................................................... 75 
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10 
Ethics ........................................................................................................................... 76 
10.1 Institutional Review Board ........................................................................................... 76 
10.2 Ethical Conduct of the Study......................................................................................... 76 
10.3 Subject Information and Consent .................................................................................. 76 
10.4 Subject Confidentiality (US Studies) .............................................................................. 76 
11 
Reporting and Publication ............................................................................................ 77 
12 
References .................................................................................................................... 78 
13 
Appendices ................................................................................................................... 81 
Appendix 1: Investigator Signature Page ................................................................................ 81 
Appendix 2: ARCALYST® Prescribing Information ............................................................... 82 
Appendix 3: Quality of Life Instrument .................................................................................. 83 
Appendix 4: 11-point Numerical Rating Scale (NRS) for Assessment of Pericarditis Pain ......... 85 
 
List of In-text Tables 
Table 1: 
Schedule of Evaluations .................................................................................. 25 
 
List of In-text Figures 
Figure 1: 
Schematic of rilonacept (KPL-914) .................................................................. 37 
Figure 2: 
Overview of Trial Design................................................................................ 46 
Figure 3: 
11-point Numerical Rating Scale (NRS) for Assessment of Pericarditis Pain ......... 66 
 
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5 List of Abbreviations and Definition of Terms 
AcP 
accessory protein 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
BP 
blood pressure 
b.p.m. 
beats per minute 
BUN 
blood urea nitrogen 
CAPS 
Cryopyrin Associated Periodic Syndrome  
CDC 
Centers for Disease Control 
CHO 
Chinese hamster ovary 
CI 
confidence interval 
CRO 
contract research organization 
CRP 
C-reactive protein 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
CTAD 
citrate, theophylline, adenosine, dipyridamole 
EoT 
End-of-Trial 
EP 
Extension Period 
ESC 
European Society of Cardiology 
ESR 
erythrocyte sedimentation rate 
FCAS 
Familial Cold Auto-Inflammatory Syndrome 
GCP 
Good Clinical Practice 
GGT 
gamma glutamyltransferase 
HBcAb 
hepatitis B core antibody 
HBsAb  
hepatitis B surface antibody 
HBsAg 
hepatitis B surface antigen 
HCVAb 
hepatitis C virus antibody 
HIV 
human immunodeficiency virus 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IgG 
immunoglobulin G 
IL-1 
Interleukin-1 
IL-1RA 
IL-1 receptor antagonist 
IL-1RI 
IL-1 type I receptor 
IMP 
Investigational Medicinal Product 
IRB 
Institutional Review Board 
IV 
intravenous 
kDa 
kilo Dalton 
KPL-914 
Study Drug; nomenclature of rilonacept (ARCALYST®) in this protocol 
LDH 
lactate dehydrogenase 
MCH 
mean cell hemoglobin 
MCHC 
MCH concentration 
MCV 
mean cell volume  
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
magnetic resonance imaging 
mITT 
modified intent to treat 
MWS 
Muckle-Wells Syndrome 
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NRS 
Numerical Rating Scale 
NSAID 
nonsteroidal anti-inflammatory drugs 
PI 
Prescribing Information 
PP 
per protocol 
PPD 
purified protein derivative 
PPS 
post pericardiotomy syndrome 
PRO 
patient-reported outcome 
PT 
prothrombin 
PTT 
prothrombin time 
QoL 
quality of life 
RBC 
red blood cell 
RIP 
recurrent idiopathic pericarditis 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SC 
subcutaneous 
SCR 
Safety Review Committee 
SCV 
screening visit 
SD 
standard deviation 
SOP 
standard operating procedure 
SRC 
Safety Review Committee 
SUSAR 
serious and unexpected and related adverse reaction 
TB 
tuberculosis 
 
 
TNF 
tumor necrosis factor 
US 
United States of America 
WBC 
white blood cells 
WHO 
World Health Organization 
WFI 
water for injection 
 
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6 Introduction 
Pericarditis accounts for 5% of emergency department visits for chest pain in the absence of myocardial 
infarction (Khandaker et al, 2010).  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).  Diagnosis is based on the presence of typical chest pain (improved by sitting up and leaning 
forward) along with fever, pericardial friction rub, electrocardiographic (ECG) changes, pericardial 
effusion, or elevated markers of inflammation (white blood cell [WBC] count, C-reactive protein [CRP], or 
erythrocyte sedimentation rate [ESR]) (Imazio et al, 2014).  The European Society of Cardiology (ESC) 
Guidelines for the Diagnosis and Management of Pericardial Diseases define a pericarditis episode as the 
presence of at least 2 of the 4 following criteria: pericarditic chest pain, pericardial rub, new widespread ST-
elevation or PR depression on ECG, and pericardial effusion (new or worsening).  Elevations of 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 a common complication of acute pericarditis and affects 20–30% of patients 
(Imazio, 2014).  It is characterized by the recurrence of signs and symptoms of pericarditis after a symptom-
free interval of at least 4-6 weeks (Adler et al, 2015).  The underlying pathogenesis of recurrent idiopathic 
pericarditis (RIP) remains unclear, although immune-mediated mechanisms are believed to play a key role 
in the pathogenesis (Imazio et al, 2005).  A growing body of evidence suggests that these immune responses 
consist of both pathogenic autoimmune and auto-inflammatory processes (Cantarini et al, 2015; Doria et al, 
2012).  The presence of pro-inflammatory cytokines in the pericardial fluid of RIP patients lends direct 
support to both an autoimmune and/or auto-inflammatory etiopathogenesis (Pankuwait et al, 2000). 
Currently available treatments for RIP include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, 
and glucocorticoids (Lilly, 2013).  Aspirin and other NSAIDs are the first-line approach.  Because high 
doses are often required, consideration should be given to gastric protection therapy.  Colchicine is another 
mainstay therapy for RIP and is commonly used with NSAIDs, but a subset of patients has refractory 
symptoms and significant gastrointestinal side effects, including severe diarrhea, leading to discontinuation 
for intolerability.  Glucocorticoids should be prescribed only to patients with idiopathic pericarditis who are 
refractory or intolerant to treatment with NSAIDs plus colchicine, because of the side effects associated 
with long-term corticosteroid therapy and because of a high rate of relapse when the corticosteroid is tapered 
or stopped (Maisch et al, 2004; Imazio, 2005; Lotrionte et al, 2010), particularly in the absence of colchicine 
treatment.  Patients with refractory symptoms can be particularly challenging to manage, and multiple 
immunosuppressive medications have been used without consistent benefit (Baskar et al, 2016). In addition, 
a subset of corticosteroid dependent RIP subjects are also in need for new treatment options due to the side 
effects of high dose and/or long term corticosteroid use including osteoporosis, diabetes, weight gain and 
increased risk for infections. 
Post-pericardiotomy syndrome (PPS) is an inflammatory syndrome involving pericardium which occurs in 
a subgroup of patients who have undergone cardiothoracic surgery.  It is reported in approximately 9% of 
adult patients (Lehto el al 2015), and more commonly in pediatric/adolescent population where up to 28% 
of patients undergoing surgical closure of atrial septal defect were reported to develop PPS (Hechching et 
al, 2015). 
 PPS is characterized by fever, pericardial or pleuritic pain, pleural effusion or pericardial effusion with 
elevated serum CRP. It is associated with significant morbidity, and the leading complications include 
tamponade and constrictive pericarditis. Aspirin, NSAIDs, and colchicine are the mainstay of the current 
treatment for PPS. Although corticosteroids are used for refractory cases of PPS, they are associated with 
significant side effects when used for long-term treatment of this disease. Similar to RIP, there is an unmet 
need for new therapies, especially for the patients experiencing recurrent PPS episodes despite currently 
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Rilonacept was developed by Regeneron Pharmaceuticals, Inc. and is approved with the tradename 
ARCALYST® in the US for the treatment of Cryopyrin Associated Periodic Syndrome (CAPS), including 
Familial Cold Auto-Inflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and 
children 12 and older.   
Rilonacept is prepared as a lyophilized formulation containing histidine, polyethylene glycol 3350, glycine, 
arginine, and sucrose at pH 6.5.  For subcutaneous (SC) administration, rilonacept is manufactured in a 
dosage form containing 160 mg per vial.  The lyophilized powder is reconstituted with 2.3 mL of sterile 
Water for Injection (WFI) and drug is delivered in 2 mL at a concentration of 80 mg/mL.  Clinical dosing 
(e.g., in CAPS) initiates with a loading dose of 320 mg SC followed by 160 mg administered SC weekly.  
A lower dose of 80 mg weekly (initiated with a 160 mg loading dose) was also tested in Phase 3 clinical 
trials in gout. 
For a detailed review of the available rilonacept data, please refer to the Investigator Brochure and the 
ARCALYST® package insert.  
Kiniksa Pharmaceuticals Ltd. (Kiniksa) is now developing rilonacept for the treatment of RIP (Rilonacept 
will be referred to as KPL-914 in this investigational study protocol).  In this first pilot study in subjects 
with RIP, improvement of pericarditis symptomatology with KPL-914 administration as well as the safety 
and dose relationships will be assessed.  Commercially-available rilonacept (ARCALYST®) will be used in 
the study. 
The nonclinical development program for rilonacept (ARCALYST®) demonstrated biological activity and 
adequate safety across toxicity studies (Appendix 2: ARCALYST® Prescribing Information). 
The most common adverse reactions reported by patients with CAPS treated with ARCALYST® are 
injection-site reactions and upper respiratory tract infections.  Hypersensitivity reactions associated with 
rilonacept administration have been rare.  
Refer to the ARCALYST® PI for Important Safety Information regarding rilonacept (Appendix 2: 
ARCALYST® Prescribing Information).  
Based on its IL-1-antagonistic properties, its weekly-dosing pharmacokinetics, and its well-understood 
safety profile as shown in patients with CAPS, rilonacept (KPL-914) is a promising candidate for the 
treatment of RIP.  
 
7 Study Objectives 
The study is comprised of 5 Parts. 
• 
Part 1 enrolls symptomatic subjects with recurrent idiopathic pericarditis (RIP) with an elevated 
marker of systemic inflammation (C-reactive protein [CRP] > 1mg/dL). 
• 
Part 2 enrolls symptomatic subjects with RIP with CRP ≤1 mg/dL which, in the opinion of the 
investigator, can be attributed to concomitant medications (e.g., corticosteroids) and with 
pericardial inflammation present on cardiac magnetic resonance imaging (MRI) confirmed by the 
imaging core lab. 
• 
Part 3 enrolls subjects with corticosteroid-dependent RIP not experiencing symptoms which 
would meet the diagnostic criteria for a flare of pericarditis. 
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• 
Part 4 enrolls symptomatic subjects with recurrent post pericardiotomy syndrome (PPS) with an 
elevated marker of systemic inflammation (CRP > 1mg/dL). 
• 
Part 5 enrolls subjects with corticosteroid-dependent recurrent PPS not experiencing symptoms 
which would meet the diagnostic criteria for a flare of pericarditis. 
 
7.1 
Part 1 
Primary Objective: 
To collect inter- and intra-subject variability data on CRP measurements and the 11-point NRS instrument 
for assessment of pericardial pain in subjects with RIP both at baseline and on treatment with KPL-914 in 
order to inform power calculations for future trials in pericarditis. 
 
Secondary Objectives: 
To explore the time course to improvement of pericarditis parameters in symptomatic subjects with RIP 
treated with KPL-914. 
To evaluate the effect of KPL-914 on pericardial inflammation based on cardiac MRI. 
To evaluate the safety of KPL-914 in symptomatic subjects with RIP. 
 
7.2 
Part 2 
Primary Objective: 
To collect inter- and intra-subject variability data on CRP measurements and the 11-point NRS instrument 
for assessment of pericardial pain in subjects with RIP both at baseline and on treatment with KPL-914 in 
order to inform power calculations for future trials in pericarditis. 
 
Secondary Objectives: 
To explore the time course to improvement of pericarditis parameters in symptomatic subjects with RIP 
treated with KPL-914 
To evaluate the effect of KPL-914 on pericardial inflammation based on cardiac MRI. 
To evaluate the safety of KPL-914 in symptomatic subjects with RIP. 
 
7.3 
Part 3 
Primary Objective: 
To evaluate feasibility of weaning from corticosteroids while receiving KPL-914 in subjects with 
corticosteroid-dependent RIP. 
 
Secondary Objectives: 
To evaluate the effect of KPL-914 on pericardial inflammation based on cardiac MRI. 
To evaluate the safety of KPL-914 in subjects with corticosteroid-dependent RIP. 
 
7.4 
Part 4: 
Primary Objective: 
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To collect inter- and intra-subject variability data on CRP measurements and the 11-point NRS instrument 
for assessment of pericardial pain in subjects with symptomatic recurrent PPS both at baseline and on 
treatment with KPL-914 in order to inform power calculations for future trials in pericarditis. 
 
Secondary Objectives: 
To explore the time course to improvement of pericarditis parameters in symptomatic subjects with 
recurrent PPS treated with KPL-914 
To evaluate the effect of KPL-914 on pericardial inflammation based on cardiac MRI. 
To evaluate the safety of KPL-914 in symptomatic subjects with recurrent PPS. 
 
7.5 
Part 5: 
Primary Objective: 
To evaluate feasibility of weaning from corticosteroids while receiving KPL-914 in subjects with 
corticosteroid-dependent recurrent PPS. 
 
Secondary Objectives: 
To evaluate the effect of KPL-914 on pericardial inflammation based on cardiac MRI. 
To evaluate the safety of KPL-914 in subjects with corticosteroid-dependent recurrent PPS. 
 
 
 
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8 Investigational Plan 
8.1 
Overall Study Design and Plan 
This is an open-label single-active-arm pilot study to explore clinical and biochemical endpoints of 
improvement of pericarditis symptomatology and to collect inter- and intra-subject variability data on both 
at-baseline and on-treatment parameters. This study consists of 5 distinct Parts, and all subjects will be 
treated with once-weekly subcutaneously (SC)-administered injections of KPL-914.   
Enrollment into Part 1: 
Subjects identified for participation in Part 1 of this trial will present during a symptomatic episode of 
RIP, having previously experienced a first (index) episode of acute pericarditis followed by at least 1 
recurrent episode before the current enrollment-qualifying episode, using the 2015 European Society of 
Cardiology (ESC) Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 2015) 
as a frame of reference: 
- 
The index episode of acute pericarditis would have been characterized by an inflammatory 
pericardial syndrome with at least 2 of the 4 following criteria: pericarditic chest pain, pericardial 
rub, new widespread ST-segment elevation or PR-segment depression on electrocardiogram (ECG), 
and pericardial effusion (new or worsening).  Additional supportive findings would have included 
elevations of markers of inflammation (i.e., CRP, ESR, or WBC count) or evidence of pericardial 
inflammation by an imaging technique (e.g., magnetic resonance imaging [MRI]).   
- 
Recurrence of RIP would have been characterized as a subsequent episode of pericarditis occurring 
after a symptom-free interval of 4-6 weeks or longer.   
For the purposes of this study, the Investigator will determine, based on his/her judgement of the available 
data, if a subject has met these criteria for having experienced a first (index) episode of acute pericarditis 
followed by at least 1 recurrent episode of pericarditis prior to the current enrollment-qualifying 
episode of RIP and will record the criteria supporting this diagnosis in the electronic case report form 
(eCRF). 
Subjects with symptomatic RIP meeting the above diagnostic criteria may be enrolled into Part 1 only if 
the CRP value at screening is > 1 mg/dL. 
 
Enrollment into Part 2: 
Subjects identified for participation in Part 2 of this trial will present during a symptomatic episode of 
RIP, having previously experienced a first (index) episode of acute pericarditis followed by at least 1 
recurrent episode before the current enrollment-qualifying episode, using the 2015 European Society 
of Cardiology (ESC) Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 
2015) as a frame of reference: 
- 
The index episode of acute pericarditis would have been characterized by an inflammatory 
pericardial syndrome with at least 2 of the 4 following criteria: pericarditic chest pain, pericardial 
rub, new widespread ST-segment elevation or PR-segment depression on electrocardiogram (ECG), 
and pericardial effusion (new or worsening).  Additional supportive findings would have included 
elevations of markers of inflammation (i.e., CRP, ESR, or WBC count) or evidence of pericardial 
inflammation by an imaging technique (e.g., MRI).   
- 
Recurrence of RIP would have been characterized as a subsequent episode of pericarditis occurring 
after a symptom-free interval of 4-6 weeks or longer.   
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For the purposes of this study, the Investigator will determine, based on his/her judgement of the available 
data, if a subject has met these criteria for having previously experienced a first (index) episode of acute 
pericarditis followed by at least 1 recurrent episode of pericarditis prior to the current enrollment-
qualifying episode of RIP and will record the criteria supporting this diagnosis in the eCRF. 
 
Subjects with symptomatic RIP meeting the above diagnostic criteria but without an elevated CRP level 
(i.e., ≤1mg/dl) at screening may be enrolled into Part 2 only if, in the opinion of the investigator and in 
consultation with the Sponsor, the low CRP value can be attributed to concomitant medications (e.g., 
corticosteroids) AND if there is evidence of pericardial inflammation by cardiac MRI which has been 
confirmed by the MRI Core Laboratory. 
 
Enrollment into Part 3: 
Subjects identified for participation in Part 3 in this trial will present with corticosteroid-dependent RIP, 
having previously experienced a first (index) episode of acute pericarditis followed by at least 2 
recurrent episodes, using the 2015 European Society of Cardiology (ESC) Guidelines for the Diagnosis 
and Management of Pericardial Diseases (Adler et al, 2015) as a frame of reference: 
- 
The index episode of acute pericarditis would have been characterized by an inflammatory 
pericardial syndrome with at least 2 of the 4 following criteria: pericarditic chest pain, pericardial 
rub, new widespread ST-segment elevation or PR-segment depression on electrocardiogram (ECG), 
and pericardial effusion (new or worsening).  Additional supportive findings would have included 
elevations of markers of inflammation (i.e., CRP, ESR, or WBC count) or evidence of pericardial 
inflammation by an imaging technique (e.g., MRI).   
- 
Recurrence of RIP would have been characterized as a subsequent episode of pericarditis occurring 
after a symptom-free interval of 4-6 weeks or longer.   
 
For the purposes of this study, the Investigator will determine, based on his/her judgement of the available 
data, if a subject has met these criteria for having previously experienced a first (index) episode of acute 
pericarditis followed by at least 2 recurrent episodes of pericarditis and will record the criteria 
supporting this diagnosis in the eCRF. 
 
Subjects who are taking corticosteroids for their RIP and who are not currently experiencing symptoms 
which, in the opinion of the Investigator, would meet the above diagnostic criteria for a flare may be 
enrolled into Part 3 only if, in the opinion of the Investigator and in consultation with the Sponsor, they 
are considered to be “corticosteroid- dependent” (i.e.; the signs and symptoms of pericarditis would 
return if the corticosteroids were withdrawn). 
 
Enrollment into Part 4: 
Subjects identified for participation in Part 4 in this trial will present during a symptomatic episode of 
recurrent PPS, having previously experienced a first (index) episode of acute PPS followed by at least 1 
recurrent episode of PPS before the current enrollment-qualifying episode, using the 2015 European 
Society of Cardiology (ESC) Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler 
et al, 2015) as a frame of reference: 
- 
The index episode of acute pericarditis would have been characterized by an inflammatory 
pericardial syndrome with at least 2 of the following 5 clinical findings after cardiac surgery: fever 
without alternative causes, pericardial chest pain, pericardial rub, evidence for pericardial effusion, or 
elevated CRP.  
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- 
Recurrence of PPS would have been characterized as a subsequent episode of pericarditis occurring 
after a symptom-free interval of 4-6 weeks or longer.   
 
For the purposes of this study, the Investigator will determine, based on his/her judgement of the available 
data, if a subject has met these criteria for having previously experienced a first (index) episode of acute 
PPS followed by at least 1 recurrent episode of PPS prior to the current enrollment-qualifying episode 
of recurrent PPS and will record the criteria supporting this diagnosis in the eCRF. 
 
In addition to meeting the above criteria for PPS, all subjects enrolled in Part 4 must have a CRP value > 
1 mg/dL at screening. 
 
Enrollment into Part 5: 
Subjects identified for participation in Part 5 in this trial will present with corticosteroid-dependent 
recurrent PPS, having previously experienced a first (index) episode of acute PPS followed by at least 2 
recurrent episodes, using the 2015 European Society of Cardiology (ESC) Guidelines for the Diagnosis 
and Management of Pericardial Diseases (Adler et al, 2015) as a frame of reference: 
- 
The index episode of acute pericarditis would have been characterized by an inflammatory 
pericardial syndrome with at least 2 of the following 5 clinical findings after cardiac surgery: fever 
without alternative causes, pericardial chest pain, pericardial rub, evidence for pericardial effusion, or 
elevated CRP.  
- 
Recurrence of PPS would have been characterized as a subsequent episode of pericarditis occurring 
after a symptom-free interval of 4-6 weeks or longer.   
 
For the purposes of this study, the Investigator will determine, based on his/her judgement of the available 
data, if a subject has met these criteria for having previously experienced a first (index) episode of acute 
PPS followed by at least 2 recurrent episodes of PPS and will record the criteria supporting this 
diagnosis in the eCRF. 
 
Subjects who are taking corticosteroids for the recurrent PPS and who are not currently experiencing 
symptoms which, in the opinion of the Investigator, would meet the above diagnostic criteria for a flare 
may be enrolled into Part 5 only if, in the opinion of the Investigator and in consultation with the Sponsor, 
they are considered to be “corticosteroid- dependent” (i.e.; the signs and symptoms of pericarditis would 
return if the corticosteroids were withdrawn). 
 
Enrollment Process for All Parts: 
Prior to enrollment, potential subjects may enter an optional Prescreening Period, after signing a 
Prescreening ICF (or informed assent form, if applicable) to confirm the diagnostic workup and to allow 
monitoring for symptoms and inflammatory markers (CRP, ESR, etc) while concomitant medications for 
pericarditis treatment may be managed by the Investigator or their clinician according to standard of care. 
 
Subjects included in Parts 1, 2 and 4 may be receiving concomitant nonsteroidal anti-inflammatory drugs 
(NSAIDs), and/or colchicine, and/or oral corticosteroid treatment in any combination, provided the dosages 
of these medications have been stable for at least 7 days, although stable doses for a shorter period will be 
acceptable if in the opinion of the Investigator, in consultation with the Sponsor, a shorter period of stability 
is not anticipated to alter the baseline CRP values.  
Subjects in Parts 3 and 5 must be receiving corticosteroids at the time of enrollment. 
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Baseline therapy and disease characteristics will be determined during a Screening Period of up to 72 hours, 
as needed, to confirm study eligibility.  At the SCV1, baseline subject and disease characteristics will be 
determined and captured in the eCRF.  At Screening Visit 2 (SCV2) during the 24 - 72 hour period before 
subjects advance to the Treatment Period of the study, additional laboratory samples may be drawn to 
provide additional baseline reference data. Under special circumstances, the Investigator, in consultation 
with the Sponsor, can combine SCV1 and SCV2, and the subject can proceed directly to the Day 0 dosing 
visit. 
After having met all the entry criteria during the Screening Period, the adult subjects (18 years or older) 
entering the Treatment Period will receive a loading dose of 320 mg KPL-914 (2 x 160 mg) administered 
SC on Day 0, then 160 mg SC weekly for 5 additional doses. Subjects aged 6 years to <18 years will 
receive a loading dose of 4.4 mg/kg KPL-914 (2x 2.2 mg/kg; maximum total 320 mg) administered SC on 
Day 0, then 2.2 mg/kg (maximum 160 mg) administered SC weekly for 5 additional doses. 
 
The first Study Drug dose on Day 0 will be administered at the Study Site/Clinic (Visit 1).  Subsequent 
weekly Study Drug doses from Weeks 2 to 5 will be self-administered by the subject or will administered 
to the subject by an adequately trained caregiver as an outpatient SC administration. Study center staff or a 
visiting study nurse will assess and record compliance with Study Drug administration at the subject’s home 
as well as provide guidance and training on Study Drug administration as needed. At Week 6/End of Trial, 
Study Drug may be administered at home or other non-clinic location or administered at the study site.  
Weekly assessments of safety and treatment response, including administration of the 11-point NRS 
instrument to assess pericardial pain, will be done at the Study Site/Clinic at Visit 1 (Day 0) and Visit 7 
(Week 6/End-of-Trial), and via Investigator (or designee) phone calls/ virtual visits on Day 3 and at Weeks 
2 to 5 (Visits 2 to 5). Weekly outpatient blood samples for central laboratory testing will be collected at the 
Study Site/Clinic, or at a qualified laboratory site in the vicinity of the subject, or by a visiting study nurse. 
Investigators are encouraged to schedule subjects at the Study Site/Clinic for an in-person Interval 
Evaluation Visit during approximately Weeks 3-4 to assist the Investigator in the clinical management of 
the subject.  During this visit a full assessment including physical examination, vital signs, ECG, 
echocardiogram, and laboratory testing can be performed as well as the recording of adverse events (AEs) 
and other study related assessments as needed.   
At any time point during the Treatment Period, subjects reporting worsening of pericarditis symptoms or 
AEs may be brought into the Study Site/Clinic at the discretion of the Investigator for an Unscheduled Visit, 
in which select or comprehensive clinical assessments can be performed.  Any subject who is determined 
by the Investigator as not responding to treatment (e.g., no reduction in pericardial pain compared to 
baseline, no decrease in CRP levels [if applicable], etc.) and who is therefore considered by the Investigator 
to be a “Treatment Failure” may be withdrawn from further Study Drug treatment at the discretion of the 
Investigator and may receive rescue therapy for their pericarditis according to standard of care as per 
Investigator decision; these subjects will be followed for safety for the remainder of the 6-week Treatment 
Period.  Subjects identified as “Treatment Failures” may be replaced at the discretion of the Sponsor in order 
to provide an adequate sampling of subjects completing the active Treatment Period. 
Subjects participating for the complete length of the active study Treatment Period will receive a total of 6 
doses of KPL-914.  For the duration of the Treatment Period, concomitant NSAIDs and/or colchicine and/or 
corticosteroids, if present, should be continued at pre-study dose levels until after the 6-dose Study Drug 
Treatment Period has concluded; however, should the Investigator determine that a reduction/tapering of 
the NSAID, colchicine, and/or corticosteroid dose is medically indicated, the NSAID, colchicine, and/or 
corticosteroid dose can be down-titrated in consultation with the Sponsor, and the modification of dose 
should be recorded in the source records and the eCRF.  
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Opioid analgesics, non-narcotic analgesics (e.g., tramadol), and acetaminophen are allowed as rescue 
medication for ancillary pain control on an as-needed basis throughout the Treatment Period.  Although it 
is recommended that NSAID dose levels (if present) should remain constant during the active Treatment 
Period, the concomitant NSAID dose may be temporarily increased (or an NSAID initiated) for ancillary 
pain control if deemed necessary by the Investigator, after consultation with the Sponsor. Any rescue 
medication use must be recorded in source records, eCRF and medication diary.  
At the discretion of the Investigator, “Treatment Responders” will be offered participation in an optional 
18-week Extension Period (EP), in which weekly open-label KPL-914 can be continued at the same dose as 
in the Treatment Period for a total duration of Study Drug treatment of up to 24 weeks. 
Treatment response will be defined by the Investigator: 
• 
Part 1: A clinically significant reduction in pericardial pain using the 11-point NRS, normal or 
near normal CRP levels, and/or absent or decreasing echocardiographic effusion at the End-of-
Trial Visit. 
• 
Part 2: A clinically significant reduction in pericardial pain using the 11-point NRS, normal or 
near normal levels CRP, and/or absent or decreasing echocardiographic effusion at the End-of-
Trial Visit 
• 
Part 3: Absence of pericarditis flare and feasibility to taper corticosteroids.  
• 
Part 4: A clinically significant reduction in pericardial pain using the 11-point NRS, normal or 
near normal CRP levels, and/or absent or decreasing echocardiographic effusion at the End-of-
Trial Visit 
• 
Part 5: Absence of pericarditis flare and feasibility to taper corticosteroids.  
 
Weekly Study Drug administrations during the EP are by self-administration or by an adequately trained 
caregiver, and study nurse visits to the subject’s home as well as Investigator (or designee) telephone 
calls/virtual visits are to continue on a monthly basis. 
During the EP, the Investigator is encouraged to wean concomitant NSAIDs and/or colchicine, and/or 
corticosteroids. It is encouraged that NSAIDs and colchicine be tapered and withdrawn within 15 days after 
entry into the EP. It is encouraged that corticosteroids be progressively taped (e.g., by 5 mg prednisone or 
equivalent every week in adults or 0.2mg/kg every week in subjects <18yo) and discontinued within 6 weeks 
after entering the EP (i.e., by Study Week 12) unless in the opinion of the Investigator, a different 
corticosteroid weaning schedule is required based on subject’s clinical status. All medication changes must 
be recorded in source records and the eCRF. Investigators are encouraged to invite subjects to the Study 
Site/Clinic for an in-person Interval Evaluation Visit between Weeks 15 to 20 (8 to 13 weeks after the Visit 
7/End of Trial Visit) to assist the Investigator in the clinical management of the subject.  During this visit a 
physical examination, vital signs, ECG, echocardiogram (ECHO), and laboratory testing can be performed 
at the discretion of the Investigator. 
Available safety, tolerability, and efficacy data for each subject will be reviewed by the Investigator as part 
of ongoing subject management.  A Safety Review Committee (SRC) including selected Investigator(s) and 
Sponsor representatives will review on a monthly basis (at a minimum) all available data for all subjects, 
considering trends across each subject and each Part.  
Given the following occurrences, dosing may be halted or reduced in any Part of the study, in accordance 
with an SRC recommendation, confirmed by the Sponsor: 
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One or more subjects experience a serious and unexpected adverse event that is considered by the 
Investigator to be related to Study Drug (SUSAR), or 2 or more subjects experience similar severe 
(non-serious) and unexpected AEs that are considered by the Investigator to be related to Study 
Drug. 
After an initial group of subjects has been treated, depending on the safety profile observed as well as the 
magnitude and speed of treatment response (e.g., if an informative number of subjects achieve treatment 
response early in the Treatment Period), the Sponsor in collaboration with the Investigators may elect to 
decrease the KPL-914 dose administered to a subsequent consecutive group of subjects (in any Part of the 
Study): the adult subjects (18 years or older) entering the Treatment Period will receive a loading dose of 
160 mg KPL-914 (2 x 80mg) SC on Day 0, then 80 mg administered SC weekly for 5 additional doses. 
Subjects aged 6 years to <18 years will receive a loading dose of 2.2 mg/kg KPL-914 (2 x 1.1 mg/kg; 
maximum total 160 mg) administered SC on Day 0, then 1.1 mg/kg (maximum 80 mg) administered SC 
weekly for 5 additional doses, in order to explore efficacy at a lower dose. 
Depending on treatment response observed with the 80 mg dose (or 1.1 mg/kg in subjects 6 years to 
<18years old), the weekly dose administered to either these subjects or subsequent subjects may be 
changed back to 160 mg (or 2.2 mg/kg in subjects 6 years to <18 years old) by the Investigator in 
collaboration with the Sponsor. For any given subject, the KPL-914 dose level received at the end of the 
Treatment Period should be continued into the EP (if administration is continued); however, a change in 
the KPL-914 dose level during the EP for any individual subject can be made at the discretion of the 
Investigator in consultation with the Sponsor, and the modification of dose should be recorded in the 
source records and the eCRF. 
During the Screening and Treatment Periods, subjects will enter information concerning the use of 
pericarditis and rescue (pain) medication into a medication diary.  Such information will be entered by the 
subject immediately after dosing of study drug. 
 
Figure 2: 
Overview of Trial Design 
 
 
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The sample size was chosen on an empirical basis, based on experience with other rilonacept trials and other 
research in this patient population. 
8.3.2 
Inclusion Criteria 
Inclusion Criteria for All Parts 
To be eligible to participate in the trial, a subject must meet all of the following criteria: 
1. Has given consent (or assent, if applicable) and signed an Informed Consent Form (ICF) (or informed 
assent form, if applicable). 
2. Male or female, of any ethnic origin. 
3. 6 to 75 years of age, inclusive. 
4. If used, has received NSAIDs, and/or colchicine and/or corticosteroids (in any combination) at stable 
dose levels for at least 7 days prior to Study Drug dosing (although stable doses for a shorter period 
will be acceptable if, in the opinion of the Investigator in consultation with the Sponsor, a shorter 
period of stability is not anticipated to alter the baseline CRP values) and is anticipated to continue 
these concomitant medications at these dose levels for the duration of the active Treatment Period.   
5. If female of child-bearing potential, must be nonpregnant and nonlactating and must agree to use an 
effective method of contraception, e.g., hormonal contraception or double-barrier birth control.  
6. Is able to adequately maintain a medication diary. 
7. Agrees to refrain from making any new, major life-style changes that may affect pericarditis 
symptoms (e.g., starting a new diet or change in exercise pattern) from the time of signature of the 
ICF to the End-of-Trial Visit (Week 6). 
 
Inclusion Criteria for Part 1: 
8. Has a diagnosis of RIP based on the judgement of the Investigator. 
9. Has previously had an index (first) episode of pericarditis which, in the judgement of the Investigator 
based on the available data, met the criteria for an acute pericarditis event, using the 2015 ESC 
Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 2015) as a frame 
of reference --  i.e., met at least 2 of the 4 following criteria: pericarditic chest pain, pericardial rub, 
new widespread ST-segment elevation or PR-segment depression on ECG, and pericardial effusion 
(new or worsening).  Additional supportive findings could include elevations of markers of 
inflammation (i.e., CRP, ESR or WBC count) or evidence of pericardial inflammation by an imaging 
technique (e.g., MRI). 
10. Has had at least one prior recurrent episode of pericarditis, in the judgement of the Investigator, 
based upon the available diagnostic information. 
11. Has an ongoing symptomatic episode of pericarditis at the time of study enrollment in the judgement 
of the Investigator, based upon the available diagnostic information. 
12. Has an elevated CRP value (i.e., >1 mg/dL) at the time of Screening. 
 
Inclusion Criteria for Part 2: 
13. Has a diagnosis of RIP based on the judgement of the Investigator. 
14. Has previously had an index (first) episode of pericarditis which, in the judgement of the Investigator 
based on the available data, met the criteria for an acute pericarditis event, using the 2015 ESC 
Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 2015) as a frame 
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of reference --  i.e., met at least 2 of the 4 following criteria: pericarditic chest pain, pericardial rub, 
new widespread ST-segment elevation or PR-segment depression on ECG, and pericardial effusion 
(new or worsening).  Additional supportive findings could include elevations of markers of 
inflammation (i.e., CRP, ESR or WBC count) or evidence of pericardial inflammation by an imaging 
technique (e.g., MRI). 
15. Has had at least one prior recurrent episode of pericarditis, in the judgement of the Investigator, 
based upon the available diagnostic information. 
16. Has an ongoing symptomatic episode of pericarditis at the time of study enrollment in the judgement 
of the Investigator, based upon the available diagnostic information. 
17. Has CRP value < 1 mg/dL at Screening, which in the opinion of the Investigator in consultation with 
the Sponsor, can be attributed to concomitant medications. 
18. Has evidence of pericardial inflammation by cardiac MRI which has been confirmed by the MRI 
imaging core lab. 
 
Inclusion Criteria for Part 3: 
19. Has a diagnosis of RIP based on the judgement of the Investigator. 
20. Has previously had an index (first) episode of pericarditis which, in the judgement of the Investigator 
based on the available data, met the criteria for an acute pericarditis event, using the 2015 ESC 
Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 2015) as a frame 
of reference --  i.e., met at least 2 of the 4 following criteria: pericarditic chest pain, pericardial rub, 
new widespread ST-segment elevation or PR-segment depression on ECG, and pericardial effusion 
(new or worsening).  Additional supportive findings could include elevations of markers of 
inflammation (i.e., CRP, ESR, or WBC count) or evidence of pericardial inflammation by an imaging 
technique (e.g., MRI). 
21. Has had at least two prior recurrent episodes of pericarditis, in the judgement of the Investigator, 
based upon the available diagnostic information. 
22. Is not currently (at Screening) experiencing symptoms which, in the judgment of the Investigator 
based on the available diagnostic information, would meet the diagnostic criteria for a flare of 
pericarditis. 
23. Is “corticosteroid-dependent,” in the judgement of the Investigator based on available data (i.e., the 
signs and symptoms of pericarditis would return if the corticosteroids were to be withdrawn). 
 
Inclusion Criteria for Part 4: 
24. Has a diagnosis of recurrent PPS based on the judgement of the Investigator. 
25. Has previously had an index (first) episode of PPS which, in the judgement of the Investigator based 
on the available data, met the criteria for an acute pericarditis event, using the 2015 ESC Guidelines 
for the Diagnosis and Management of Pericardial Diseases (Adler et al, 2015) as a frame of reference,  
i.e., met at least 2 of the 5 clinical findings after cardiac surgery: fever without alternative causes, 
pericardial chest pain, pericardial rub, evidence for pericardial effusion with elevated CRP  
26. Has had at least one prior recurrent episode of PPS, in the judgement of the Investigator, based upon 
the available diagnostic information. 
27. Has an ongoing symptomatic episode of recurrent PPS at the time of study enrollment in the 
judgement of the Investigator, based upon the available diagnostic information. 
28. Has an elevated CRP value (i.e., >1 mg/dL) at the time of Screening. 
 
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29. Has a diagnosis of recurrent PPS based on the judgement of the Investigator. 
30. Has previously had an index (first) episode of PPS which, in the judgement of the Investigator based 
on the available data, met the criteria for an acute pericarditis event, using the 2015 ESC Guidelines 
for the Diagnosis and Management of Pericardial Diseases (Adler et al, 2015) as a frame of reference,  
i.e., met at least 2 of the 5 clinical findings after cardiac surgery: fever without alternative causes, 
pericardial chest pain, pericardial rub, evidence for pericardial effusion with elevated CRP  
31. Has had at least two prior recurrent episodes of PPS, in the judgement of the Investigator, based 
upon the available diagnostic information. 
32. Is not currently (at Screening) experiencing symptoms which, in the judgment of the Investigator 
based on the available diagnostic information, would meet the diagnostic criteria for a flare of 
pericarditis. 
33. Is “corticosteroid-dependent,” in the judgement of the Investigator based on the available data, (i.e., 
the signs and symptoms of pericarditis would return if the corticosteroids were to be withdrawn). 
8.3.3 
Exclusion Criteria 
Exclusion Criteria for All Parts 
A subject who meets any of the following criteria will not be eligible to participate in the trial: 
1. Has a diagnosis of pericarditis that was secondary to specific excluded etiologies, including 
tuberculous, neoplastic, or purulent etiologies, post-myocardial infarction (early or late), thoracic 
trauma, myocarditis, or systemic diseases including autoinflammatory diseases, autoimmune 
diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, etc.). 
2. Has a history of immunodepression, including a positive human immunodeficiency virus test result. 
3. Has received treatment within the 6-month period before dosing with any systemic 
immunosuppressants (other than, for example, corticosteroids or mycophenolate) which, in the 
opinion of the Investigator (in consultation with the Sponsor), may interfere with the study 
endpoints.  
4. Currently receiving other interleukin (IL)-1 or IL-6 blockers, janus-activating kinase (JAK) or tumor 
necrosis factor (TNF) inhibitors. 
5. Has a history of myeloproliferative disorder, demyelinating disease, or symptoms suggestive of 
multiple sclerosis. 
6. Female subject who is pregnant or lactating or who does not agree to use an effective method of 
contraception, e.g., hormonal contraception or double-barrier birth control. 
7. Has a history of active or latent treated tuberculosis (TB), or had a positive QuantiFERON (QFT-TB 
G In-Tube) test result, or a chest radiograph during the 3 months prior to Study Drug dosing 
suggestive of prior TB infection. A subject with a positive purified protein derivative (PPD) test 
result (≥5-mm induration) after the first attack of pericarditis is excluded unless he/she has had 
either a negative chest x-ray result or a negative QuantiFERON test result. 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, night sweats) upon review of medical history and/or 
physical exam.  Have recent close contact with a person with active TB.  
8. Chest radiograph (or historic results within 3 months of SCV1) that shows evidence of malignancy 
or any abnormalities suggestive of prior TB infection, including, but not limited to, apical scarring, 
apical fibrosis, or multiple calcified granulomata.  This does not include non-caseating granulomata. 
9. Has received immunization with a live (attenuated) vaccine within 12 weeks before the start of the 
study. 
10. Has history of or positive or intermediate results for hepatitis B surface antigen (HBsAg), hepatitis 
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B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at SCV1. 
11. Has an estimated glomerular filtration rate (eGFR) <30 mL/min.  
12. Has a history of malignancy of any organ system within the past 5 years (other than a successfully 
treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma 
in situ of the cervix). 
13. 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. 
14. Has had a serious infection, has been hospitalized for an infection, has been treated with oral 
antibiotics within 2 weeks, or has been treated with IV antibiotics for an infection within 2 months 
of first Study Drug administration.  
15. Has had an organ transplant.  
16. In the Investigator's judgement, has a history of alcoholism or drug/chemical abuse within 2 years 
prior to Study Drug administration. 
17. Has a drug screen positive for amphetamines, cocaine, or phencyclidine or positive alcohol test at 
SCV1.  Exceptions may be made if a subject is on an approved medication for a stable concomitant 
condition that explains the positive screen. 
18. Has taken commercially-available rilonacept (ARCALYST®) or participated in a rilonacept clinical 
study during the 90 days before SCV1.  Has used anakinra within 14 days (or 5 half-lives, 
whichever is longer) prior to Study Drug administration. Rilonacept and anakinra could not have 
been discontinued due to lack of efficacy or due to safety. 
19. Has a history of hypersensitivity to rilonacept or to any of the excipients contained in the Study 
Drug. 
20. Has received an investigational drug during the 30 days before SCV1 or is planning to receive an 
investigational drug (other than that administered during this trial) or use an investigational device 
at any time during the trial. 
21. In the Investigator's judgement, has any other medical condition that could adversely affect the 
subject's participation or interfere with study evaluations.  
22. Subject who, in the opinion of the Investigator, is not likely to be compliant with the study protocol. 
23. Subject who, in the opinion of the Investigator in consultation with the Sponsor, should not 
participate in this study. 
 
8.3.4 
Vaccination History and Immune status 
IL-1 blockade may interfere with immune response to infections. Therefore, the Investigator should review 
with the subject the subject's vaccination history relative to the current medical guidelines for vaccine use.  
A recommended immunization schedule is available at the website of the Centers for Disease Control (CDC) 
(www.cdc.gov/vaccines/recs/scheduled/default.htm). 
It is recommended that, prior to or shortly after initiation of therapy with KPL-914, subjects be brought up 
to date with all vaccinations, as appropriate, including pneumococcal vaccine and inactivated influenza 
vaccine. In case a subject needs vaccination after initiation of KPL-914 treatment, vaccination with inactive 
vaccine(s) may be performed (e.g., at the Study Site/Clinic) after the 6-week active Treatment Period.  
However, to minimize the potential confounding of KPL-914-related Adverse Experience reporting at 
initiation of KPL-914 dosing or measurements of CRP during the treatment period, vaccination should not 
be performed within the first 6 weeks after initiation of KPL-914 administration.   
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It is recommended that all vaccinations be documented as up-to-date at or shortly after Visit 7, at which 
point subjects are being considered for longer-term treatment with KPL-914.  
Administration of KPL-914 is prohibited within 12 weeks of having received a live (attenuated) vaccine.  It 
is also possible that taking drugs that block IL-1 increases the risk of TB.  Healthcare providers should 
follow current CDC guidelines both to evaluate for and to treat possible latent TB infections before initiating 
therapy with KPL-914. 
8.3.5 
Removal of Subjects from Therapy or Assessments 
Subjects reporting worsening of pericarditis symptoms or AEs may be brought into the Study Site/Clinic at 
the discretion of the Investigator for an Unscheduled Visit at any time during the Treatment Period.  Any 
subject who is not responding to treatment (e.g., no reduction in pericardial pain compared to baseline, no 
decrease in CRP levels, etc.) and who is therefore considered by the Investigator to be a “Treatment Failure” 
may be withdrawn from further Study Drug treatment at the discretion of the Investigator and receive rescue 
therapy for their pericarditis according to standard of care as per Investigator decision; these subjects will 
be followed for safety for the remainder of the 6-week Treatment Period.  Subjects identified as “Treatment 
Failures” may be replaced at the discretion of the Sponsor in order to provide an adequate sampling of 
subjects completing the active Treatment Period. 
Safety, tolerability, and efficacy data for each subject will be reviewed by the Investigator on an ongoing 
basis as part of subject management.  An SRC including selected Investigator(s) and Sponsor representatives 
will review on a monthly basis (at a minimum) all available data for all subjects in all Parts, considering 
trends across each.  
Given the following occurrences, dosing may be halted or the dose reduced, in accordance with an SRC 
recommendation, confirmed by the Sponsor: 
• 
One or more subjects experience a serious and unexpected adverse event that is considered by the 
Investigator to be related to Study Drug (SUSAR), or 2 or more subjects experience similar severe 
(non-serious) and unexpected AEs that are considered by the Investigator to be related to Study 
Drug. 
In addition, subjects may stop study treatment or may be withdrawn from treatment for any of the following 
reasons: 
• 
Subject request.  Subjects are free to withdraw from the study at any time without providing 
reason(s) for withdrawal and without prejudice to further treatment 
• 
Use of non-permitted concurrent therapy 
• 
Non-compliance 
• 
Investigator request. 
Treatment Failures or subjects who are withdrawn from the study for safety reasons will be replaced at the 
discretion of the Sponsor.  Similarly, subjects who do not comply with the protocol or who withdraw from 
the study for other reasons can be replaced.  The reason(s) for withdrawal will be documented in the source 
records and the eCRF. 
Subjects withdrawing from the study during the Treatment Period will be asked to complete the End-of-
Trial evaluations to document the status of their pericarditis disease progression at the time of withdrawal 
from treatment.  Subjects will continue to be followed for vital status for the duration of intended treatment 
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to address informative censoring.  Subjects withdrawing from the study during the EP will be asked to 
complete the Final Visit evaluations. 
All reasonable efforts will be made to contact subjects who are lost to follow-up.   
The Sponsor has the right to terminate the study at any time in case of safety concerns (e.g., SUSARs) or if 
special circumstances concerning the Investigational Medicinal Product (IMP) 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. 
Pregnancy 
Pregnant or lactating female subjects are excluded from study enrollment.  While not explicitly stated in the 
rilonacept (ARCALYST®) PI (Appendix 2: ARCALYST® Prescribing Information), for the purposes of this 
experimental protocol, females of child-bearing potential (i.e., not postmenopausal and not sterilized) must 
use an active method of birth control during the course of the study, e.g., oral, implanted or injected 
contraceptive hormones, an intrauterine device, or a barrier method (e.g., diaphragm, condoms, 
spermicides).  
Subjects will be instructed that known or suspected pregnancy occurring during the study should be 
confirmed and reported to the Investigator without delay.  If pregnancy is confirmed, the Investigator must 
notify the Sponsor within 24 hours and the subject must not receive (additional) Study Drug and must be 
discharged from the study.  The subject must be asked regarding their willingness to complete the End-of-
Trial Visit. 
In the event that a subject is found to be pregnant after having received at least one Study Drug dose, the 
pregnancy will be followed to term and the status of mother and child will be reported to the Sponsor after 
delivery. 
Instances of perinatal death or congenital abnormality, if brought to the attention of the Investigator at any 
time after cessation of the study treatment, will be reported to the Sponsor within 24 hours. 
Full details will be recorded on the pregnancy form. 
8.4 
Investigational Medicinal Products 
8.4.1 
Investigational Medicinal Products Administered 
During the Treatment Period, KPL-914 will be administered as an initial loading dose of 320 mg SC, 
delivered as two subcutaneous injections of 160 mg SC each on Day 0, then 160 mg SC dosed once 
weekly for 5 subsequent weeks  (18 years or older).  Subjects aged 6 years to <18 years will receive an 
initial loading dose of 4.4 mg/kg, up to a maximum of 320 mg, delivered as two subcutaneous injections 
of 2.2 mg/kg each with a maximum single-injection volume of 2 mL. Dosing will continue with a once-
weekly injection of 2.2 mg/kg, up to a maximum of 160 mg, administered as a single subcutaneous 
injection of up to 2 mL as outpatient administration or by an adequately trained caregiver, for 5 
subsequent weeks. 
 
Subjects will receive a total of 6 doses of KPL-914 during the study active Treatment Period.  Subjects 
who are considered to be “Treatment Responders” will be offered, at the discretion of the Investigator, 
participation in an optional 18-week Extension Period (EP), in which weekly open-label KPL-914 can be 
continued for a total duration of KPL-914 treatment of up to 24 weeks. 
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Sites for SC 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. 
No placebo or active comparator drug will be used.  
8.4.2 
Identity of Investigational Medicinal Products 
KPL-914 (rilonacept/ARCALYST®) is prepared as a lyophilized formulation containing histidine, 
polyethylene glycol 3350, glycine, arginine, and sucrose at pH 6.5.  It 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 WFI is required prior to SC 
administration of the drug.  The reconstituted drug product is a viscous, clear, colorless to pale yellow, 
essentially free from particulates, 80-mg/mL solution. 
After the addition of preservative-free sterile WFI, the vial contents should be reconstituted by gently 
shaking the vial for approximately 1 minute and then allowing it to sit for 1 minute.  A volume of up to 2 
mL can be withdrawn, which is designed to deliver 160 mg for SC administration only. 
KPL-914 (rilonacept) will be provided by the Sponsor to the study sites and to the study subjects in its 
commercially-available formulation (ARCALYST®) as a lyophilized powder to be reconstituted for SC 
administration.  The sites will receive Study Drug for on-site administration at Study Site/Clinic visits. Drug 
will be disseminated to the trial subjects for outpatient self-administration according to a supply chain 
described in the Pharmacy Manual.   
The lyophilized Study Drug (KPL-914 also called rilonacept, US tradename: ARCALYST®) is to be stored 
refrigerated at 2° to 8°C (36° to 46°F) inside the original carton to protect it from light.  After reconstitution, 
KPL-914 may be kept at room temperature, should be protected from light, and should be used within 3 
hours of reconstitution.  Unused portions of KPL-914 product must not be injected.  All vials of used and 
unused Study Drug during the active Treatment Period must be returned to the clinical site for cataloguing 
and documentation of compliance.   
The Sponsor through Regeneron Pharmaceuticals, Inc. will ensure that the Study Drug and certificates of 
analysis are available before the start of the study and at all times during the study. 
ARCALYST® is a registered trademark of Regeneron Pharmaceuticals, Inc. 
8.4.3 
Method of Assigning Subjects to Treatment Groups 
Subjects who meet all the inclusion criteria in a specific Part and none of the exclusion criteria will enter 
the Treatment Period at Visit 1 (Day 0). 
Since this is an open-label, single-active-arm study, all subjects will receive KPL-914 active treatment.  
Assignment to treatment groups is not applicable. 
8.4.4 
Selection of Doses in the Study 
This protocol is a pilot study intended to evaluate the safety, efficacy, and dose response of KPL-914 in the 
treatment of patients with RIP. 
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8.4.7 
Prior and Concomitant Therapy 
Subjects included in Parts 1, 2 and 4 may be using NSAIDs, colchicine, and/or corticosteroids in any 
combination at the time of study enrollment, but the dose levels must be stable for have been stable for at 
least 7 days, although stable doses for shorter period will be acceptable if in the opinion of the Investigator, 
in consultation with the Sponsor, a shorter period of stability is not anticipated to alter the baseline CRP 
values.   
Subjects in Parts 3 and 5 must be receiving corticosteroids at the time of enrollment. 
For the duration of the Treatment Period, pericarditis medications (e.g., concomitant NSAIDs, colchicine 
and/or corticosteroids, if used) should be continued at pre-study dose levels until after the 6-dose Study 
Drug Treatment Period has concluded; however, should the Investigator determine that a reduction/tapering 
of the NSAID, colchicine, and/or corticosteroid dose is medically indicated, the NSAID, colchicine and/or 
corticosteroid dose can be down-titrated in consultation with the Sponsor, and the modification of dose 
should be recorded in the source records and the eCRF. 
Subjects who received, within the 6-month period before dosing, immunomodulatory therapy other than, 
for example, corticosteroids or mycophenolate, which in the opinion of the Investigator (in consultation 
with the Sponsor) may interfere with the study endpoints, or subjects who used commercially-available 
rilonacept (ARCALYST®) within 90 days before the Screening Visit are excluded from participation.  
Throughout the Treatment Period opioid analgesics, non-narcotic analgesics (e.g., tramadol), and 
acetaminophen are allowed as rescue medication for ancillary pain control on an as-needed basis.  Although 
it is recommended that NSAID dose levels (if present) should remain constant during the active Treatment 
Period, the concomitant NSAID dose may be temporarily increased (or an NSAID initiated) for ancillary 
pain control if deemed necessary by the Investigator, after consultation with the Sponsor.  Any rescue 
medication use must be recorded in source records, the medication diary and the eCRF. Other interleukin 
(IL)-1 or IL-6 blockers, janus-activating kinase (JAK) and tumor necrosis factor (TNF) inhibitors are 
prohibited for the duration of the study.  
Medical management of pericarditis during the EP is based on Investigator discretion. For example, 
Investigators may continue subjects on KPL-914 at the same dosage level, wean-off or discontinue Study 
Drug.  During the EP, the Investigator is encouraged to wean concomitant NSAIDs, and/or   colchicine, 
and/or corticosteroids.  It is encouraged that NSAIDs and colchicine be tapered and withdrawn within 15 
days after entry into the EP.  It is encouraged that corticosteroids be progressively tapered (e.g., by 5 mg 
prednisone or equivalent every week in adults or 0.2mg/kg every week in subjects <18yo) and 
discontinued within 6 weeks after entering to EP (i.e., by Study Week 12) unless in the opinion of 
Investigator, a different corticosteroid weaning schedule is required based on subject’s clinical status 
 
Other pericarditis medications may also be initiated at the discretion of the Investigator.  All changes to 
pericarditis-related medications should be captured in the source records and the eCRF. 
 
During the Screening and Treatment Periods, subjects will enter information concerning the use of 
pericarditis and rescue (pain) medication into a medication diary.  Such information will be entered by the 
subject on a real-time basis. 
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8.4.8 
Treatment Compliance 
Study Drug will be administered to the subject by the Investigator or qualified study center staff at the Study 
Site/Clinic Visit 1 (Day 0).  Subsequent weekly Study Drug doses from Weeks 2 to 5 will be self-
administered by the subject or an adequately trained caregiver as an outpatient SC administration. The study 
center staff or a visiting study nurse will assess and record compliance with Study Drug administration at 
the subject’s home as well as provide guidance and training on Study Drug administration as needed. At 
Week 6/End-of-Trial, Study Drug may be self-administered or administered at the study site. All medication 
use (for pericarditis and use of rescue [pain] medication) will be documented by the subject in the medication 
diary during the Treatment Period.  
All vials of used and unused Study Drug during the active Treatment Period and the EP must be retained by 
the Study Site/Clinic and the subject to allow for cataloguing and documentation of compliance. Subjects 
must return all used and unused medication to the Study Site/Clinic.  Drug accountability and documentation 
thereof is described in the Pharmacy Manual. 
Study Drug compliance by the subject will be monitored during the Treatment Period by phone calls/virtual 
visits (made by qualified site staff).  Subjects will be reminded of recording all pericarditis and rescue pain 
medication information in the medication diary.  The medication diary will be returned to the site by the 
subject and reviewed by the Investigator/qualified staff.  During the EP, Study Drug use will be documented 
during monthly phone calls/virtual visits or Study Site/Clinic visits. 
8.5 
Study Procedures 
All data of Study Site/Clinic visit assessments as well as Investigator (or designee) phone calls/virtual visits 
will be documented in source records and in the eCRF. 
8.5.1 
Prescreening Period 
Prior to enrollment, potential subjects may enter an optional Prescreening Period, after signing of a 
Prescreening ICF (or prescreening assent form, if applicable), to confirm the diagnostic workup and to 
allow monitoring for symptoms, inflammatory markers (CRP, ESR, etc) while concomitant pericarditis 
medications may be managed by the Investigator or their clinician per standard of care. 
 
The Prescreening Period starts with the signing of the Prescreening ICF (or prescreening assent form, if 
applicable), and lasts until the subject enters the Screening Period by signing the ICF for the full study or is 
withdrawn (see section 8.3.5).  
8.5.2 
Screening Period 
The Screening Period starts with the signature of the ICF (or informed assent form, if applicable), and may 
last for up to 3 days.  During this period, subject eligibility for entry into the Treatment Period will be 
determined.  A rheumatology consultation during the Screening Period is optional. 
At SCV1, baseline subject and disease characteristics will be determined.  At Screening Visit 2 [SCV2]), 
within the 24 – 72 hour period before subjects advance to the Treatment Period of the study, additional 
laboratory samples may be drawn to provide additional baseline reference data Under special circumstances, 
the Investigator in consultation with the Sponsor, can combine SCV1 and SCV2. 
The end of the Screening Period may coincide with the start of the Treatment Period.   
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8.5.2.1 
Screening Visit 1 (SCV1) 
• At the SCV1, written informed consent (or assent, if applicable) will be obtained before any protocol-
specific assessments are made. 
• All subjects will be assessed for eligibility against the inclusion and exclusion criteria. 
• Demographic data, such as ethnic origin, date of birth and sex will be recorded. 
• The subject’s full medical history, including age at first attack, number of previous attacks, duration 
of attacks as well as concomitant illnesses/diseases will be documented. 
• Information related to concomitant medicine that subjects were taking during at least the 2 weeks 
prior to the visit will be captured. 
• A full physical examination will be performed, including assessment of pericardial rub. 
• Body weight and height will be assessed. 
• Vital signs will be obtained in the seated position and include oral temperature, respiratory rate, blood 
pressure, and pulse. 
• A pregnancy test (urine dip-stick) will be done. If the urine test is positive, additional Study 
Site/Clinic and/or central serum tests may be performed. 
• 12-lead ECG and full echocardiogram (ECHO) will be performed.  ECHO will include assessment 
of pericardial effusion.  The Study Site/Clinic readings at the time of the examination will be 
available to the Investigator for clinical decision-making. In addition, both the ECG and ECHO will 
be sent to a core laboratory for additional analysis. 
• A cardiac MRI may be performed (optional). If done, the images will be assessed by a central reader. 
The Study Site/Clinic reading at the time of the examination may be used by the Investigator for 
clinical decision-making. 
• Samples for laboratory tests will be collected. 
o Local Lab Assessments: 
▪ 
Full hematology (including ESR), chemistry (including CRP), and urinalysis 
▪ 
Serology (HCVAb, HBsAg, HBcAB, HBsAb and HIV)  
▪ 
A QuantiFERON® test for tuberculosis (TB) can be performed (optional).  
o Screening for drugs of abuse and alcohol abuse will be performed on urine samples 
collected at this visit.  
o Central Laboratory Assessments: 
▪ 
CRP/hsCRP  
• Samples for archive biomarker, pharmacokinetics (PK), and anti-rilonacept (anti-KPL-914) antibody 
testing will be collected, sent to the central laboratory, and stored for analysis. 
• A medication diary for documentation of pericarditis medication use and use of any rescue (pain) 
medication will be handed to the subject.  The study Investigator or designated personnel will 
instruct the subject about the use of the medication diary.  The subjects will be asked to complete 
entries immediately following administration. 
• The subjects will assess their pericardial pain based on a 11-point NRS. 
• The subject's global overall well-being will be assessed using a validated Quality of Life 
Questionnaire (Appendix 3). 
 
8.5.2.2 
Screening Visit 2 (SCV2) 
The end of the Screening Period (SCV2) coincides with the start of the Treatment Period (Day 0, Visit 1).  
All Screening assessments need to be completed prior to the first Study Drug administration.  
• SCV2 should take place when the laboratory test results from SCV1 are available. 
• Subjects will be reassessed for eligibility against the inclusion and exclusion criteria. 
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• Any changes in concomitant medications since SCV1 will be documented. 
• A full physical examination will be performed, including re-assessment of pericardial rub.  
• Vital signs will be measured.  
• 12-lead ECG will be performed.  The Study Site/Clinic reading at the time of the examination will be 
used by the Investigator for clinical decision-making. In addition, the ECG will be sent to a core 
laboratory for additional analysis. 
• Samples for laboratory tests will be collected. 
o Local Lab Assessments: 
▪ 
Full chemistry (including CRP) panel only 
o Central Laboratory Assessments: 
▪ 
CRP/hsCRP  
• Medication diary compliance will be assessed by the Investigator/designated personnel and the 
subject reminded on the diary use. 
• The subjects will assess their pericardial pain based on the 11-point NRS (Figure 3). 
 
When all screening procedures have been performed and the Investigator has confirmed the subject’s 
eligibility for the study, the Study Drug will be administered to the subject (see Study Site/Clinic Visit 1). 
 
8.5.3 
Treatment Period 
8.5.3.1 
Visit 1 (Study Site/Clinic) - Day 0 
Visit 1 will coincide with SCV2.  In case Visit 1 is separated from SCV2, SCV2 clinical laboratory blood 
sampling (including CRP), medication diary compliance verification and reminding, and subject NRS 
pericardial pain rating (see Figure 3) must be repeated prior to Study Drug dosing.  
• Sample for lipid panel to be sent to the Central Laboratory for analysis 
• Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody testing will be 
collected prior to Study Drug dosing, sent to the central laboratory, and stored for analysis.  
• The subject's global overall well-being will be assessed prior to Study Drug dosing using a validated 
Quality of Life Questionnaire (Appendix 3). 
• The initial dose of Study Drug will be administered at the Study Site/Clinic. 
• Subjects will be trained for outpatient Study Drug self-administration and reminded of completion of 
the daily medication diary. 
• Any AEs occurring during or after the subject receives the first dose of Study Drug will be captured. 
When all Visit 1 procedures have been performed, an appointment for the first weekly phone call/virtual 
visit will be scheduled. Study Drug for outpatient administration will be provided to the subjects according 
to a process laid out in the pharmacy manual. 
8.5.3.2 
Day 3 (Outpatient) 
• 
Day 3 will ± 1 day after Visit 1. 
• 
An Investigator (or designee) telephone call/virtual visit will occur to evaluate safety (AE 
evaluations) and patient-reported pericardial pain using a validated 11-point NRS instrument. 
 
8.5.3.3 
Visits 2 to 6 (Outpatient) - Weeks 2, 3, 4, 5, 6 
• Visits 2, 3, 4, 5, 6 will take place within intervals of 7 ± 1 days each after Visit 1. 
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• Subjects self-administer the Study Drug or be administered Study Drug by an adequately trained 
caregiver during Weeks 2 to 5. At Week 6/End-of-Trial, Study Drug may be self-administered or 
administered at the study site. 
•  Samples for laboratory tests will be collected. 
o Central Laboratory Assessments: 
▪ 
CRP/hsCRP  
▪ 
Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody 
testing will be collected (either by a visiting study nurse or at the Study Site or at a 
qualified local laboratory) and stored for analysis after shipment to the central 
laboratory.  
• After dosing at Week 3 and Week 6, a questionnaire to assess the dosing system will be completed 
by the subject and by the study center staff or visiting nurse observing the dosing 
• Any AEs that have occurred since the last contact will be assessed by non-leading questions as part 
of the weekly telephone call/virtual visit from the Study Site/Clinic.  
• Compliance with self-administration of drug, compliance with the medication diary, and compliance 
with laboratory blood sampling will be assessed as part of the weekly telephone call/virtual visit 
from the Study Site/Clinic. 
• Pericardial pain based on the 11-point NRS (Figure 3) will be assessed as part of the weekly telephone 
call/virtual visit from the Study Site/Clinic. 
Subjects withdrawing from the study any time during study weeks 2 to 6 will be asked to return to the Study 
Site/Clinic for the Visit 7/End-of-Trial visit assessments.  
8.5.3.4 
Interval Evaluation Visit (Study Site/Clinic) - Week 3-4 
An in-person Interval Evaluation Visit during approximately Weeks 3-4 of the Treatment Period is 
recommended to assist the Investigator in the clinical management of the subject. The visit can be held at 
the discretion of the Investigator. The Interval Evaluation Visit may also be used to review the vaccination 
status of a study subject. 
At the Interval Evaluation Visit, the following parameters will be assessed: 
• A full physical examination will be performed, including assessment of pericardial rub. 
• Vital signs will be measured.  
• A 12-lead ECG and a full ECHO will be performed.  The Study Site/Clinic readings at the time of 
the examination will be made available to the Investigator for clinical decision-making. In addition 
both the ECG and ECHO will be sent to a core laboratory for additional analysis. 
• Changes in concomitant medication since the last Study Site/Clinic visit will be documented. 
• Samples for laboratory tests will be collected. 
o Local Lab Assessments: 
▪ 
Full hematology (including ESR), chemistry (including CRP), and urinalysis 
o Central Laboratory Assessments: 
▪ 
CRP/hsCRP  
▪ 
Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody 
testing will be collected, sent to the central laboratory, and stored for analysis.  
• Any AEs that have occurred since the last visit (Study Site/Clinic or outpatient) will be documented.  
• Medication diary compliance will be assessed by the Investigator/designated personnel and the 
subject reminded on the diary use. 
• Pericardial pain based on the 11-point NRS (Figure 3) will be assessed. 
• The subject's global overall well-being will be assessed using a validated Quality of Life 
Questionnaire (Appendix 3). 
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8.5.3.5 
Unscheduled Visits (Study Site/Clinic) During the Treatment Period  
Subjects reporting worsening of pericarditis symptoms or AEs may be brought in at the discretion of the 
Investigator for an Unscheduled Visit at any time during the Treatment Period.  During the Unscheduled 
Visit, selected or comprehensive (see Interval Evaluation Visit) clinical and laboratory assessments may be 
performed.  
Any subject who is determined by the Investigator as not responding to treatment (e.g., no reduction in 
pericardial pain compared to baseline, no decrease in CRP levels, etc.) and who is therefore considered by 
the Investigator to be a “Treatment Failure” may be withdrawn from further Study Drug treatment at the 
discretion of the Investigator and receive rescue therapy for their pericarditis according to standard of care 
as per Investigator decision; these subjects will be followed for safety for the remainder of the 6-week 
Treatment Period.   
All study withdrawals must complete the Visit 7/End-of-trial Visit either at the Unscheduled Visit or at a 
separate Visit 7/End-of-trial Visit. 
8.5.3.6 
Visit 7/ End-of-Trial (Study Site/Clinic) - Week 6 
At Visit 7, “Treatment Responders” (defined by the Investigator as a clinically significant reduction in 
pericardial pain using the 11-point NRS, normal or near-normal CRP levels, and absent or decreasing 
echocardiographic effusion at the End-of-Trial Visit), will be offered participation in an optional 18-week 
EP, at the discretion of the Investigator. During the EP, weekly open-label KPL-914 can be continued at the 
same dose as in the Treatment Period for a total duration of Study Drug treatment of up to 24 weeks.   
• Visit 7 will take place during Week 6 (or as soon as possible after study withdrawal if a subject has 
discontinued from Study Drug therapy).  
• A full physical examination will be performed, including assessment of pericardial rub. 
• Vital signs will be measured.  
• A 12-lead ECG and a full ECHO will be performed.  The Study Site/Clinic readings at the time of 
the examination will be made available to the Investigator for clinical decision-making.  In addition 
both the ECG and ECHO will be sent to a core laboratory for additional analysis. 
• Changes in concomitant medication since last Study Site visit will be documented. 
• Samples for laboratory tests will be collected. 
o Local Lab Assessments: 
▪ 
Full hematology (including ESR), chemistry (including CRP), and urinalysis 
o Central Laboratory Assessments: 
▪ 
CRP/hsCRP 
▪ 
Lipid panel  
▪ 
Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody 
testing will be collected, sent to the central laboratory, and stored for analysis. 
• Any AEs that have occurred since the last visit (Study Site/Clinic or outpatient) will be documented.  
• Medication diary compliance will be assessed by the Investigator/designated personnel. 
• Pericardial pain based on the 11-point NRS will be assessed (Figure 3). 
• The subject's global overall well-being will be assessed using a validated Quality of Life 
Questionnaire (Appendix 3). 
When all of these procedures have been performed, the next Study Site/Clinic visit should be scheduled for 
those who continue KPL-914 treatment during the EP (Treatment Responders).  Study Drug for outpatient 
administration will be provided to the subjects according to a process laid out in the pharmacy manual. 
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Only subjects continuing treatment into the Extension Phase will receive Study Drug at Visit 7; Study Drug 
can be self-administered either as an outpatient or at the Clinic/Site (Site to provide Study Drug) depending 
on the logistics/timing of the EoT Visit 7. Continued weekly Study Drug treatment during the EP will be 
outpatient administration. 
8.5.4 
Extension Period 
Subjects will self-administer the Study Drug or be administered by an adequately trained caregiver weekly 
basis and complete the medication diary during the Extension Period. Study nurse visits to the subject’s 
home will continue on a monthly basis. Investigator (or designee) phone calls/virtual visits will be 
performed monthly during the EP to perform NRS pain assessments, collect AE information, and 
document pericarditis/concomitant medication use. If scheduled, in-person Study Site/Clinic Visits 
(Unscheduled Visits or Evaluation Visits) can replace the phone calls/virtual visits. During the EP, the 
Investigator is encouraged to wean concomitant NSAIDs, and/or colchicine, and/or corticosteroids.  It is 
encouraged that NSAIDs and colchicine be tapered and withdrawn within 15 days after entry into the EP.  
It is encouraged that corticosteroids be progressively tapered (e.g., by 5 mg prednisone or equivalent every 
week in adults or 0.2mg/kg every week in subjects <18yo) and discontinued within 6 weeks after entering 
to EP (i.e., by Study Week 12) unless in the opinion of Investigator, a different corticosteroid weaning 
schedule is required based on subject’s clinical status. Other pericarditis medications may also be initiated 
at the discretion of the Investigator.  All changes to pericarditis-related medications should be captured in 
the source records and eCRF 
 
8.5.4.1 
Unscheduled Visits (Study Site/Clinic) during the EP 
Unscheduled Study Site/Clinic visits can take place during the Extension Period, as agreed upon by the 
Investigator and the subject or as needed.  
• A physical examination will be performed. 
• Vital signs will be measured.  
• Changes in concomitant medication since the last Study Site/Clinic visit will be documented. 
• Samples for laboratory tests will be collected. 
o Local Lab Assessments: 
▪ 
Full hematology (including ESR), chemistry (including CRP), and urinalysis 
o Central Laboratory Assessments: 
▪ 
CRP/hsCRP  
▪ 
Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody 
testing will be collected, sent to the central laboratory, and stored for analysis.  
• A 12-lead ECG and a full ECHO will be performed as determined by the Investigator.  The Study 
Site/Clinic readings at the time of the examination will be made available to the Investigator for 
clinical decision-making. In addition, both the ECG and ECHO will be sent to a core laboratory for 
additional analysis. 
• Any AEs that have occurred since the last visit (Study Site/Clinic or outpatient) will be documented.  
• Pericardial pain based on the 11-point NRS will be assessed (Figure 3).  
8.5.4.2 
Interval Evaluation Visit During Extension Period (Study Site/Clinic) - Week 15-20 
An in-person Interval Evaluation Visit during approximately Weeks 15-20 of the Extension Period is 
recommended to assist the Investigator in the clinical management of the subject. The visit can be held at 
the discretion of the Investigator.  
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At the Extension Period Interval Evaluation Visit, the following parameters will be assessed: 
• A physical examination will be performed. 
• Vital signs will be measured.  
• A 12-lead ECG and a full ECHO will be performed.  The Study Site/Clinic readings at the time of 
the examination will be made available to the Investigator for clinical decision-making. In addition, 
both the ECG and ECHO will be sent to a core laboratory for additional analysis. 
• Changes in concomitant medication since the last Study Site/Clinic visit will be documented. 
• Samples for laboratory tests will be collected. 
o Local Lab Assessments: 
▪ 
Full hematology (including ESR), chemistry (including CRP), and urinalysis 
o Central Laboratory Assessments: 
▪ 
CRP/hsCRP  
▪ 
Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody 
testing will be collected, sent to the central laboratory, and stored for analysis.  
• Any AEs that have occurred since the last visit (Study Site/Clinic or outpatient) will be documented.  
• Pericardial pain based on the 11-point NRS will be assessed (Figure 3). 
• The subject's global overall well-being will be assessed using a validated Quality of Life 
Questionnaire (Appendix 3). 
8.5.4.3 
Visit 8/Final Visit (Study Site/Clinic) - Week 25 
• Visit 8 will take place 18 weeks after Visit 7 (or as soon as possible after study withdrawal during the 
EP). 
• A full physical examination will be performed, including assessment of pericardial rub.  
• Body weight and height will be assessed. 
• Vital signs will be obtained in the seated position and include oral temperature, respiratory rate, blood 
pressure, and pulse. 
• 12-lead ECG and ECHO will be performed.  Echocardiogram will include assessment of pericardial 
effusion.  In addition, both the ECG and ECHO will be sent to a core laboratory for additional 
analysis. 
• An MRI can be performed (optional).  
• Changes in concomitant medication since the last Study Site/Clinic visit will be documented. 
• Samples for laboratory tests will be collected. 
o Local Lab Assessments: 
▪ 
Full hematology (including ESR), chemistry (including CRP), and urinalysis 
o Central Laboratory Assessments: 
▪ 
CRP/hsCRP 
▪ 
Lipid panel  
▪ 
Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody 
testing will be collected, sent to the central laboratory, and stored for analysis.  
• Any AEs that have occurred since the last visit (Study Site/Clinic or outpatient) will be documented.  
• Pericardial pain based on the 11-point NRS will be assessed (Figure 3). 
• The subject's global overall well-being will be assessed using a validated Quality of Life 
Questionnaire (Appendix 3). 
8.5.5 
Duration of Treatment 
The overall study duration for subjects participating in the study until Visit 8 will be up to 171 days.  
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The test product will be administered weekly for 6 weeks in the base study Treatment Period.  Treatment 
Responders will be offered participation in an optional 18-week EP at the discretion of the Investigator.  
During this EP the subject can receive 18 additional weekly doses of KPL-914.  
8.6 
Efficacy and Safety Variables 
The Schedule of Evaluations in Table 1 shows the planned study assessments. 
8.6.1 
Individual Efficacy Assessments 
8.6.1.1 
C-Reactive Protein, Biomarker, and PK Assessments 
CRP will be determined at Study Site/Clinic laboratory tests at Screening (SCV1 and SCV2) and during the 
Treatment Period (Visit 1 prior to dosing, if separate from SCV2, Interval Evaluation Visit [if applicable], 
and Visit 7/End-of-Trial).  Results from the Study Site/Clinic CRP testing will inform the Investigator on 
the subject's pericarditis status for clinical decision-making and support decisions on classifications of 
subjects as Treatment Responders or Treatment Failures and on subsequent disease management during the 
Extension Period.  
Central laboratory assessments of CRP will be performed at each Study Site/Clinic or outpatient study visit 
(samples collected by a visiting study nurse or at the Study Site/Clinic or a local laboratory).  Centrally 
determined CRP values will be used for statistical evaluations and report writing but will not be used as 
basis of the Investigator’s management of the subject. 
All subjects must present with elevated CRP values ≥1 mg/dL at the time of study enrollment.  CRP changes 
and the time course to decrease and resolution of CRP to normal values ≤0.5 mg/dL will be assessed. 
Samples from each study visit will be archived at the central laboratory for potential biomarker and/or PK 
analysis.  
8.6.1.2 
Echocardiogram (Pericardial Effusion) 
Echocardiograms (ECHOs) including assessment of pericardial effusion will be performed at screening 
(SCV1), at Study Site/Clinic visits during the Treatment Period (Interval Evaluation Visit [if applicable] 
and Visit 7/End-of-Trial), at the Interval Evaluation Visit during the EP [if applicable], and at the Final 
Study Visit/Visit 8.  
Pericardial effusion is characterized by accumulation of excess fluid in the pericardial space surrounding 
the heart and is one of the common features of pericarditis.  Echocardiography is a sensitive tool and the 
most widely used imaging technique for the detection of pericardial effusion and/or thickening. 
For the purposes of the analysis of treatment response in all subjects at the end of the study, all ECHO 
images will be assessed by a central reader. The Study Site/Clinic reading of the ECHO at the time of the 
examination will be made available to the Investigator for clinical decision-making.  
8.6.1.3 
Electrocardiogram (Pericarditis Diagnostic Findings) 
Twelve-lead ECGs will be performed at screening (SCV1 and SCV2), at Study Site/Clinic visits during the 
Treatment Period (Interval Evaluation Visit [if applicable] and Visit 7/End-of-Trial), at the Interval 
Evaluation Visit during the EP [if applicable], and at the Final Study Visit/Visit 8.  
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Pericarditis commonly involves changes in the electrophysiologic activity of the heart, resulting in typical 
ECG findings, namely widespread ST-elevation or PR depression.  Changes in ECG findings will help 
determine the pericarditis status of a subject.  
The Study Site/Clinic reading of the ECG at the time of the examination will be made available to the 
Investigator for clinical decision-making. For the purposes of the analysis of treatment response in all 
subjects at the end of the study, all ECG tracings will be assessed by a central reader.   
8.6.1.4 
Pericarditis Signs (Fever, Pericardial Rub) 
Common pericarditis signs include fever and pericardial rub.  These pericarditis signs will be assessed via 
documentation of vital signs and physical examinations.  
Physical examinations and vital signs assessments for pericarditis signs will be performed at screening 
(SCV1 and SCV2), at Study Site/Clinic visits during the Treatment Period (Interval Evaluation Visit [if 
applicable] and Visit 7/End-of-Trial), at the Interval Evaluation Visit during the EP [if applicable], and the 
Final Study Visit/Visit 8.  If applicable, assessment of pericarditis signs will also be performed at 
unscheduled visits.  
8.6.1.5 
Pericarditis Pain (Chest Pain) 
Common pericarditis symptoms include chest discomfort (pericarditis pain).  A validated 11-point NRS will 
be used to measure the subject's level of pericarditis (chest) pain intensity (Dworkin et al 2005; Mannion et 
al 2007; Hawker et al 2011).  The assessment will be performed at all study visits - on-site during Study 
Site/Clinic visits and as part of telephone calls/virtual visits during outpatient visits/treatment weeks (weekly 
during the Treatment Period and monthly during the EP).  
Subjects will be asked to select the score that best describes their average level of pain over the previous 24 
hours using a validated 11-point NRS instrument (Figure 3), where zero (0) indicates ‘no pain’ and ten (10) 
means indicates ‘pain as bad as it could be’.   
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8.6.2 
Safety Assessments 
8.6.2.1 
Adverse Events 
Adverse Event Definition 
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 and/or unintended 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. 
In this study, individual elements of pericarditis symptomatology (including pain) are captured as an 
efficacy parameter.  Pericarditis pain is not required to be reported as an AE.  However, if, in the opinion of 
the Investigator, the subject experiences new symptoms that had not been previously reported in the 
constellation of symptoms recorded at baseline, these new symptoms should be reported as an AE. 
The causal relationship between an AE and the Study Drug will be defined as below: 
• 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 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 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 drug, abates 
upon discontinuation of the drug, follows a known or hypothesized cause-effect relationship, and (if 
appropriate) reappears when the drug is reintroduced.   
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: medically significant event; daily activities limited or completely halted; hospitalization or 
prolongation of hospitalization indicated. 
Every reasonable effort will be made to follow subjects who have AEs.  Any subject who has an ongoing 
AE at study end or early withdrawal will be followed, where possible, until resolution.   
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Sponsor Reporting Responsibilities to Participating Investigators 
It is the responsibility of the Sponsor or designee to immediately notify all participating Investigators of any 
AE associated with the use of the drug that is both serious and unexpected, as well as any finding from tests 
in laboratory animals that suggest a significant risk for human subjects.   
8.6.2.3 
Adverse Reactions 
All noxious and unintended responses to an investigational medicinal product (IMP; i.e., where a causal 
relationship between an IMP and an AE is at least a reasonable possibility) related to any dose should be 
considered adverse drug reactions.   
Unexpected Adverse Reaction Definition 
An unexpected adverse drug reaction is defined as an adverse reaction, the nature or severity of which is 
not consistent with relevant product information for the IMP.  The current version of the ARCALYST® PI 
should be used as the Single Source Safety Reference Document when determining if an event is 
unexpected. Refer to the ARCALYST® PI (Appendix 2: ARCALYST® Prescribing Information) for a list 
of most frequent expected AEs.  All suspected adverse reactions related to an investigational medicinal 
product (the tested investigational medicinal products and comparators, if involved) which occur in the 
concerned trial, and that are both unexpected and serious are subject to expedited reporting. 
Warnings and Precautions 
Refer to the ARCALYST® PI (Appendix 2: ARCALYST® Prescribing Information) for Important Safety 
Information. 
IL-1 blockade may interfere with immune response to infections.  It is therefore recommended that prior to 
or shortly after initiation of therapy with KPL-914 subjects receive all recommended vaccinations, as 
appropriate, including pneumococcal vaccine and inactivated influenza vaccine. In case a subject needs 
vaccination after initiation of KPL-914 treatment, vaccination with inactive vaccine(s) may be performed 
during the active Treatment Period. However, to minimize the potential confounding of KPL-914-related 
AE reporting or CRP measurements during the KPL-914 Treatment Period, vaccination should not be 
performed during the Treatment Period (see Section 8.3.4).  It is recommended that all vaccinations be 
documented as up-to-date at or shortly after Visit 7, at which point subjects are being considered for longer-
term treatment with KPL-914.   
It is recommended that all vaccinations be documented as up-to-date at or shortly after Visit 7, at which 
point subjects are being considered for longer-term treatment with KPL-914.  
Taking KPL-914 with TNF inhibitors is not recommended because simultaneous inhibition of these two 
pathways may increase the risk of serious infections.   
It is also possible that taking drugs 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 KPL-914.   
8.6.2.4 
Clinical Laboratory Variables 
Clinical laboratory analyses will be performed at Study Site/Clinic or local laboratory near the subject and, 
for some parameters, at a central laboratory.  Laboratory analyses will be used at Study Site/Clinic visits for 
the Investigator to assess disease status and to determine treatment response and study (drug) continuation 
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or withdrawal.  Results for analyses performed by the Study Site/Clinic laboratory together with the 
laboratory reference ranges will be recorded in the eCRF and the Investigator must use clinical judgment to 
determine if any abnormal values are clinically significant or not. 
Central laboratory samples for CRP analysis will be collected at both Study Site/Clinic and outpatient (by a 
visiting study nurse or at local contract laboratories) visits and the results will be used for statistical analyses 
and study reporting. Study Site/Clinic and local laboratory results will be used for clinical decision-making 
and will be available in the source documents and listed in the CSR).  
The following analyses will be done at the central laboratory:  
• 
C-reactive protein (CRP)/hsCRP (The CRP analyzed by the central laboratory will not be available 
to the investigator in a timely manner to support the clinical management of the subject.  Results 
from the central laboratory will therefore not be transferred to the Investigator during the trial.) 
• 
Lipid Panel 
• 
Samples for biomarkers, PK, and anti-rilonacept (anti-KPL-914) antibody testing will be drawn and 
archived at all visits. 
The following laboratory analyses will be done at the Study Site/Clinic laboratories in accordance with 
local procedures and guidelines to support clinical management and decision-making: 
Hematology 
Hemoglobin, hematocrit, coagulation parameters (prothrombin [PT], prothrombin time [PTT], D-dimer), 
ESR, fibrinogen, WBC count (total and differential), red blood cell (RBC) count, ESR, platelet count, mean 
cell volume (MCV), mean cell hemoglobin (MCH), MCH concentration (MCHC). 
Clinical Chemistry 
CRP/hsCRP, troponin, creatinine, creatine kinase, urea, (or blood urea nitrogen [BUN]), aspartate 
aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), alkaline 
phosphatase, lactate dehydrogenase (LDH), total bilirubin, albumin, total protein, sodium, potassium, 
chloride, glucose, uric acid, total cholesterol*, triglycerides*, calcium, phosphorus. 
* Preferably fasting. 
Urinalysis 
pH, glucose, ketones, nitrites, leukocyte esterase, blood, protein and microscopy. Urine drug screen 
(alcohol, amphetamines, cocaine, or phencyclidine) at SCV1 only. Screening for pregnancy (urine β-HCG) 
at SCV1 only. 
Serology 
HCVAb, HBsAg, HBcAb, HBsAb and HIV tests (SCV 1 only). 
 
Other 
Screening for tuberculosis (QuantiFERON test) at SCV1 only (optional). 
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The amount of blood to be taken during screening will be approximately 37 mL at SCV1 and approximately 
17 mL at SCV2 (if done). The amount of blood to be taken at each Study Site/Clinic visit during the 
Treatment Period and EP will be approximately 31 mL.  The amount of blood to be taken at each outpatient 
visit will be approximately 21 mL. At the optional unscheduled visit, approximately 61 mL are planned. 
The total amount of blood to be taken during the study will be up to approximately 320 mL. 
8.6.2.5 
Vital Signs 
Vital signs will be recorded at Study Site/Clinic visits in a standardized manner, i.e., after the subject has 
rested in the sitting position for 5 minutes. 
The following measurements will be taken: oral temperature, respiratory rate, blood pressure, and pulse.  
Oral temperature (fever) will also be assessed as efficacy parameter (see Section 8.6.1.4). 
8.6.2.6 
Physical Examination 
At the Screening Visits 1 and 2, at the optional Evaluation Visit during the Treatment Period, at the End-of-
Trial Visit (Visit 7), at Unscheduled and Evaluation Visits during the EP and at the Final Visit (Visit 8) a 
full physical examination including the assessment of pericardial rub (efficacy parameter) will be performed 
(see also Section 8.6.1.4).   
8.6.2.7 
Body Weight and Height 
Body weight and height will be determined at SCV1 and at the final study visit.  
8.7 
Statistical Methods 
Each Part will be analyzed separately and per the analysis populations below, to be finalized in the Statistical 
Analysis Plan (SAP) to be provided separately. A full description of the statistical analyses to be performed 
together with the planned tables and figures will be given in a detailed document, the SAP, which will be 
developed and filed prior to data base lock.  Any deviation(s) from the final SAP will be described and 
justified in the clinical study report. 
8.7.1 
Statistical and Analytical Plans 
8.7.1.1 
Datasets to be Analyzed for Each Part 
Each Part will be analyzed separately and per the analysis populations below. The modified Intention to 
Treat (mITT) Population will consist of all subjects who received at least one dose of Study Drug.  The Per 
Protocol (PP) Population will consist of all subjects who received all 6 doses of Study Drug during the active 
Treatment Period and were maintained at stable dose levels of concomitant pericarditis medications 
(NSAIDs, colchicine, and/or corticosteroids, if used during screening) according to study protocol without 
a major protocol violation.  The Safety Population will be the same as the mITT Population. 
8.7.1.2 
General Statistical Methods 
Because of the small sample size, no inferential statistical analyses or hierarchical testing are planned. 
For analysis of continuous endpoints (e.g., change from baseline), summary statistics (n, mean, standard 
deviation, median, minimum, and maximum) will be calculated and presented for each treatment and/or 
analysis group.  For categorical endpoints (e.g., responder vs. non-responder), summary statistics will be 
calculated and presented for each treatment and/or analysis group. Under certain circumstances, if 
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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 Good Clinical Practice (GCP) and International Conference on Harmonisation 
(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.   
8.8.3 
Data Management and Coding 
The Sponsor or Clinical Research Organization (CRO) 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 the 
Sponsor or CRO. 
Medical coding will use Medical Dictionary for Regulatory Activities (MedDRA) for concomitant diseases 
and AEs and World Health Organization (WHO) Drug for therapies. 
8.8.4 
Record Keeping 
It is the responsibility of the Investigator to ensure all essential trial documentation and source records (e.g., 
signed ICFs/assent forms, Study Site/Clinic files, patients’ hospital notes, copies of eCRFs, etc.) 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. 
9 Records and Supplies 
9.1 
Drug Accountability 
On receipt of the IMP (including rescue medication, if relevant), the Investigator (or deputy) will conduct 
an inventory of the supplies and verify that IMP supplies are received intact and in the correct amounts prior 
to completing a supplies receipt.  The Investigator will retain a copy of this receipt at the study site and 
return the original receipt to the drug depot.  The inventory of supplies at each study site will be reviewed 
by the study monitor. 
KPL-914 (rilonacept) will be provided by the Sponsor to the study sites and to the study subjects in its 
commercially-available formulation (ARCALYST®).  All vials of used and unused Study Drug during the 
active Treatment Period 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.   
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10 
Ethics 
10.1 Institutional Review Board 
Before initiation of the study at each investigational site, the protocol, all protocol amendments, the ICF, 
the informed assent form and any other relevant study documentation will be submitted to the appropriate 
IRB.  Written approval of the study and all relevant study information must be obtained before the study 
site can be initiated or the IMP is released to the Investigator.  Any necessary extensions or renewals of IRB 
approval must be obtained, in particular, for changes to the study such as modification of the protocol, the 
informed consent form (or assent, if applicable), the written information provided to subjects and/or other 
procedures. 
The Investigator will report promptly to the IRB any new information that may adversely affect the safety 
of the subjects or the conduct of the study.  The Investigator will submit written summaries of the study 
status to the IRB annually, or more frequently if requested by the IRB.  On completion of the study, the 
Sponsor will notify the IRB that the study has ended. 
10.2 Ethical Conduct of the Study 
This study will be conducted in compliance with the protocol, the ICH-GCP guideline, the Declaration of 
Helsinki and local regulations. 
10.3 Subject Information and Consent 
The Investigator is responsible for ensuring that no subject undergoes any study related examination or 
activity before that subject and/or legal guardian has given written informed consent (or informed assent, if 
applicable) to participate in the study.  The written consent (or informed assent, if applicable) must be given 
by the subject and/or the legal guardian of the subject, after detailed information about the study has been 
given and in accordance with any national provisions on the protection of clinical study subjects.  The verbal 
explanation will cover all the elements specified in the written information provided for the subject. 
Subjects and/or legal guardians will be required to sign and date the ICF.  After signatures are obtained, the 
ICF will be kept and archived by the Investigator in the Investigator’s study file for possible inspection by 
regulatory authorities, the IRB, Sponsor and/or CRO personnel. 
It should be emphasized to the subject that he/she is at liberty to withdraw from the study at any time, 
without penalty or loss of benefits to which the subject is otherwise entitled.  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 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 informed 
assent and the informed consent are required prior to participation in the trial.  
10.4 Subject Confidentiality (US Studies) 
All personal data collected and processed for the purposes of this study should be managed by the 
Investigator and his/her staff with adequate precautions to ensure confidentiality of those data, and in 
accordance with the Health Insurance Portability and Accountability Act (HIPAA), applicable to national 
and/or local laws and regulations on personal data protection. 
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Monitors, auditors, and other authorized agents of the Sponsor and/or its designee, the ethics committees 
approving this research, and the United States (US) FDA, as well as that of any other applicable agency(ies), 
will be granted direct access to the study subjects’ original medical records for verification of clinical study 
procedures and/or data, without violating the confidentiality of the subjects to the extent permitted by the 
law and regulations.  In any presentations of the results of this study or in publications, the subjects’ identity 
will remain confidential. 
11 Reporting and Publication 
All data generated in this study are the property of the Sponsor.  An integrated clinical and statistical report 
will be prepared at the completion of the study. 
Publication of the results by the Investigator(s) will be subject to mutual agreement between the Investigator 
and Kiniksa as outlined in the study agreement. 
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12 References 
Adler Y, Charron P, Imazio M, Badano L, Barón-Esquivias G, Bogaert J, Brucato A, 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 Nov 7;36(42):2921-64. 
Amizguine J, Cohen-Wolkowiez M, Ilowite N. Rilonacept pharmacokinetics in children with Systemic  
Juvenile Idiopathic Arthritis. J Clin Pharmacol 2015, 55(1); 39-44. 
 
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, Lazaros G, Maestroni S, Carraro M, Finetti M et al. Effect of Anakinra 
on Recurrent Pericarditis Among Patients With Colchicine Resistance and Corticosteroid 
Dependence: The AIRTRIP Randomized Clinical Trial. JAMA. 2016 Nov 8;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. Autoimmunity Reviews 2015;14:90–97. 
Doria A, Zen M, Bettio S et al. Autoinflammation and autoimmunity: bridging the divide. Autoimmunity 
Reviews 2012;12:22–30. 
Dworkin RH, Turk DC, Farrar JT et al. Core outcome measures for chronic pain clinical trials: IMMPACT 
recommendations. Pain. 2005 Jan;113(1-2): 9-19. 
Garg M, de Jesus AA, Chapelle D, Dancey P, Herzog R, Rivas-Chacon R, Wampler Muskardin TL, Reed  
A, Reynolds JC, Goldbach-Mansky R, Montealegre Sanchez GA. Rilonacept maintains long-term  
inflammatory remission in patients with deficiency of the IL-1 receptor antagonist. JCI Insight, 2017;  
2(16); e94838. 
 
Hays RD, Bjorner JB, Revicki DA, Spritzer KL, Cella D. Development of physical and mental health 
summary scores from the patient-reported outcomes measurement information system (PROMIS) 
global items. Qual Life Res (2009) 18:873–880. 
Hawker GA, Mian S, Kendzerska T, French M. 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 & Research. 2011; 63: S240–S252. 
Heching HJ, Bacha EA,  Liberman L. Post-pericardiotomy syndrome in pediatric patients following surgical  
closure of secundum atrial septal defects: incidence and risk factors.  Pediatr Cardiol 2015;36 (3);  
498-502. 
 
Hoffman HM, Patel DD. Genomic-based therapy: targeting interleukin-1 for auto-inflammatory diseases. 
Arthritis and Rheum. 2004 Feb; 50(2): 345-349. 
Ilowite NT, Prather K, Lokhnygina Y, Schanberg LE, Elder M, Milojevic D, Verbsky JW, Spalding AJ,  
 
KPL-914-C001 Protocol and Amendments 
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14 February 2018 
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CONFIDENTIAL 
Kimura Y, Imundo LF, Punaro MG, Sherry DD, Tarvin SE, Zemel LS. Randomized, double-blind,  
placebo-controlled trial of the efficacy and safety of rilonacept in the treatment of Systemic Juvenile  
Idiopathic Arthritis (RAPPORT). Arthr and Rheum 2014;66 (9);2570-2579. 
 
Imazio M, Spodick DH, Brucato A, Trinchero R, Adler Y. Controversial issues in the management of 
pericardial diseases. Circulation. 2010;121:916-928. 
Imazio M, Bobbio M, Cecchi E, Demarie D, Demichelis B, Pomari F, Moratti M, Gaschino G, Giammaria 
M, Ghisio A, Belli R, Trinche-ro R. Colchicine in addition to conventional therapy for acute 
pericarditis: results of the COlchicine for acute PEricarditis (COPE) trial. Circulation. 
2005;112:2012-2016. 
Imazio M, Demichelis B, Parrini I et al. Management, risk factors, and outcomes in recurrent pericarditis. 
American Journal of Cardiology, 2005;96(5):736–739. 
Imazio M. Treatment of recurrent pericarditis. Revista Espanola de Cardiologia. 2014;67(5):345–348. 
Imazio M, Brucato A, Pluymaekers N, Breda L, Calabri G, Cantarini L, Cimaz R, Colimodio F, Corona F,  
Cumetti D, Di Blasi Lo Cuccio C, Gattorno M, Insalaco A, Limongelli G, Russo MG, Valenti A,  
Finkelstein Y, Martini A. Recurrent pericarditis in children and adolescents:a multicenter cohort  
study. J Cardiovasc Med 2016;17; 707-712. 
 
Khandaker MH, Espinosa RE, Nishimura RA, Sinak LJ, Hayes SN, Melduni RM, Oh JK. Pericardial 
disease: diagnosis and management. Mayo Clin Proc. 2010;85:572-593. 
Lazaros G, Imazio M, Brucato A, Vassilopoulus D, Vasileiou P, Gattorno M, Tousoulis D et al. Anakinra: 
an emerging option for refractory idiopathic recurrent pericarditis: a systematic review of published 
evidence. J Cardiovasc Med 2016;17(4):256-62. 
Lehto J, Gunn J, Karjalainen P, Airaksinen J, Kiviniemi T. Incidence and risk factors of postpericardiotomy  
syndrome requiring medical attention:The Finland Postpericardiotomy syndrome study. J Thorac   
Cardiovasc Surg 2015; 149(5); 1324-9. 
 
Lilly SL. Treatment of Acute and Recurrent Idiopathic Pericarditis. Circulation. 2013;127:1723-1726. 
Lotrionte M, Biondi-Zoccai G, Imazio M, Castagno D, Moretti C, Abbate A, Agostoni P, Brucato AL, Di 
Pasquale P, Raatikka M, Sangiorgi G, Laudito A, Sheiban I, Gaita F. International collaborative 
systematic review of controlled clinical trials on pharmacologic treatments for acute pericarditis and 
its recurrences. Am Heart J. 2010;160:662-670. 
Lovell DJ, Giannini EH, Reiff AO, Kimura Y, Li S, Hashkes PJ, Wallace CA, Onel KB, Foell D, Wu R,  
Biedermann S, Hamilton JD, Radin AR.  Long-term safety and efficacyof rilonacept in patients with  
Systemic Idiopathic Juvenile Arthritis. Arthr and Rheum 2013; 65(9); 2486-2496. 
 
Maisch B, Seferovic PM, Ristic AD, Erbel R, Rienmüller R, Adler Y, Tomkowski WZ, Thiene G, Yacoub 
MH; Task Force on the Di-agnosis and Management of Pericardial Diseases of the European Society 
of Cardiology. Guidelines on the diagnosis and management of pericardial diseases executive 
summary: the Task Force on the Diagnosis and Man-agement of Pericardia! Diseases of the 
Eu-ropean Society of Cardiology. Eur Heart J. 2004;25:587-610. 
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KPL-914-C001 Amendment 2 
Final 
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CONFIDENTIAL 
Mannion AF, Balagué F, Pellisé F, Cedraschi C. Pain measurement in patients with low back pain. Nature 
Clinical Practice Rheumatology 2007; 3 (11): 610-18. 
Pankuweit S, Wädlich A, Meyer E, Portig I, Hufnagel G, and Maisch B. Cytokine activation in pericardial 
fluids in different forms of pericarditis. Herz 2000;25:748–754. 
Tamarappoo BK, Klein AL. Post-pericardiotomy syndrome.  Curr Cardiol Rep 2016; 18(11);116. 
Zayas R, Anguita M, Torres F, Gimenez D, Bergillos F, Ruiz M, Ciudad M, Gallardo A, Valles F. Incidence 
of specific etiology and role of methods for specific etiologic diagnosis of primary acute pericarditis. 
Am J Cardiol. 1995;75:378-382. 
 
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KPL-914-C001 Amendment 2 
Final 
Page 81 of 85 
 
CONFIDENTIAL 
13 Appendices 
Appendix 1: Investigator Signature Page 
Protocol Title: 
An open-label pilot study of KPL-914 in symptomatic Recurrent 
Idiopathic Pericarditis. 
Protocol Number: 
KPL-914-C001 
Confidentiality and cGCP Compliance Statement 
I, the undersigned, have reviewed this protocol, including appendices and I will conduct the study as 
described in compliance with this protocol, GCP, and relevant ICH guidelines. 
Once the protocol has been approved by the IEC/IRB, I will not modify this protocol without obtaining prior 
approval of Kiniksa Pharmaceuticals Ltd. (Kinksa) and of the IEC/IRB. I will submit the protocol 
modifications and/or any ICF/assent modifications to Kiniksa and IEC/IRB, and approval will be obtained 
before any modifications are implemented. 
I understand that all information obtained during the conduct of the study with regard to the subjects’ state 
of health will be regarded as confidential. No subjects’ names will be disclosed.  All subjects will be 
identified by assigned numbers on all Case Report Forms, laboratory samples or source documents 
forwarded to the Sponsor.  Clinical information may be reviewed by the Sponsor or its agents or regulatory 
agencies.  Agreement must be obtained from the subject before disclosure of subject information to a third 
party. 
Information developed in this clinical study may be disclosed by Kiniksa, to other clinical Investigators, 
regulatory agencies, or other health authority or government agencies as required. 
 
 
Investigator Signature 
 
Date 
 
 
Printed Name 
 
 
 
Institution 
 
 
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14 February 2018 
KPL-914-C001 Amendment 2 
Final 
Page 82 of 85 
 
CONFIDENTIAL 
Appendix 2: ARCALYST® Prescribing Information 
 
KPL-914-C001 Protocol and Amendments 
Page 262

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+		
2J'	*	 	;!	6	++!					+			
	
(J					
&&J'	 					+				+	!
+	 	;	+						'
*					.				"	,0-		
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5			'(		5	!	.!				'
	*)	A		."				.				
.							+	 	'			+	
	"	'							"	/
			+	B		5						'		
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							 		
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A							.		.			
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			+		'
;";	!  
		"						+				=*		
	+	 			+	'	7		88		
,8J	+		.
				0	+		.		"	"				
	'	A		K!	.		.					
%	(		&3			
5	!		.			.		6"						'
	+					.				.		'
				"			+			+	.				
					!			"				.	
			'		.				
"	6"	
.					"			.		"		.		!
	"!		"!	"			!		!	
"	'	#		!									+	
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3DJH

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;"8		

			.						+		'	 	+	 
	+		5						!	91	!	1
!		"'								!	91
!	1	!		"	+	K	"4!	&	"4!	-	"4!		82	"4
.		0	+			'	 							
	
	5		&,				+"					
.					"'
8	4/$	!)'!%)
8"7	)&(B			!7	(B	
	"			.				+	'	
			"			*	+		7#"	"				
			+												'
					+	7#"	"					
5					G	#$		%	&H'			
		+		"			*				'	;				
"		+					*!			
			"			*						'
8"1	
 	:@2	,

			 38-	6					.			
'"'!	*	"
	'				5								*!			!	
		 38-	6			6'				.		 38-	
+		+		5!	+				.	/	
'"'!	+'	>	
	!			"		+					!		"
				"							.				
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3"7	

 "	"	'				B		+					"
+'	;			!					'			.
5		+			"			+	-!	8!	8		,-	"4"	".	+	
+	
"			5	,'2	"						0-	"			
	'							+	5			"				
"	+										.			'
=5			"				+	+		5	'	+!		
"	!							.					03J		
														
	'	*				.	5"					
"			"			
-!	&-!	--		&--	"4"!		+		,				
					+	&--	"4"				+	
	"			5	0
	"			0-	"							'			
	"	"					/						'
7"	'					.	5"		+			+
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3DJH

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			+	
	"			5	0	"			0-	"	
					'										
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3"9	)
	*

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!				5	+						"	+'
3":	
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5			+	 	+		"		&		0	+		+			
+!				&'&	"4"	
			5		0-	"		&3+	"		
	5	'			+	.								
/.				
'"'					.	 '		.	.
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'
	"	"	.											+		.	
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		.				+		"		&	.			'
%			"	!				.					
			'	*			+			+			.			'
 			+			"		"		"+	
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6			+		+	M	08			"!		0	+	M	28			"'	*	
 		!	!				+	"					
		"	F	+.!				M	08						'	*	
	5			 !		2			+	.		"			G
		H'	"					.		"				"
				'
3";				! 
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7			.				5					
			+		'
3"8			#	! 
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7			.				5					
			+		'
72	%6'4%$'
	.					.	+	'	$5	+					,&-	"
.							5	(							
+	 				0				+		.					+
.		"	5'	*	!		".	.					&---
"									5		+		+	"
5'		5											
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*			.!											"			
.			!						'
77	4'!!%)
						"			""				5
							
**		*			

* 					#				*"<'					+"	
5	&8	1'			5					.	
9A	'
				"!	&-	"	.	"		!	+		+!
6	+'	=	.							+	&',				%	
*/'		.				&				++!	+		"		.	0-	"	
		'		"			.!	!				+!	
			'	=	.		&&-	"	'		!		.
	(-	"4	!	30	$	!	8-	$	"!	,'-J	
+4.		"	,,8-!
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+4.	"			9		0'8	N	-','	7	..		'
71	!)!	#*%%$
71"7	* 		
 				"		"						7 ,	G7
"	!				
7!			"	,H	"	
	+		
*			G*
H'	 						
		+				"	B	'	#				
	.!		!	"!	"!	"!		/.'
*		!			 			+				7 ,	"	+	
		!						'		"		
				.				
*O'	$		7 ,			
..		"		5.			.	*O		.	'
		*O	""		"								*O		.
		+			'				*P		*		"	
*
	+		'		B					"		*O!	*P
	*	+	-'8	$!	'3	$		0'	$!	.'
71"1	
  
.	 	
 					
						.
		.			+	 '	=.					+		.	
				+	 '			!		+		
								 					.	"		
'			6				.	.'
71"9	
 B
	."	"	.			+	5	&3	"4			+"
+				0-	"				3(	+			+	 '		
					0	+'
7				.			+				'
7		+			.				"!	"!			+"			5'
;								!			"		+	
.3/&3URWRFRODQG$PHQGPHQWV
3DJH

+				'	"	
&02(					+"	
8-&-	"				
.		"			"		'								
								!	"		"		
'
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79"7	
	*	! 
 		&

"			.					.		"			'
	"				+		.'
$				+	.				"		"			"		'
$		+		""	(	+			"		"	"		"	
8'	#		+			&	+			"			"		-!	,!		0'		
"																&--	"4"

			5	0	"			0-	"						
'
7:	!)!	/4!'
										 	+				6!
!			+	+		
		;		B			
	+	#		$%'
 		+		0+!	6!	!	"		"			
		0-	"	+				"			,&-	"		'	 	;	+	
	 						K+!			"	+			.
	0-	"	+!	+			K+!	!	6	++		
+		+		"						0-	"	+			.
'	 	+		".							&3+!			5
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	.		..		%		*/
							!	"!		.
7)
1				%		*/!	"						.		
'								"		'
1											.	+		'	*				
!			+				+'
*										!	+	+			"		
				.	+		+	"'
4		
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	
"
								!			.			+	+
.	"!	+			!						"		'		



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'	10	
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	6
'	 		5						'	1				.			5		
'					'
&'	 		5				.			%		*/'	1				.		
5			'					'
,'	 .		.					.'
3'	 					.	+			+'	>		+			.		+		
						.	
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	9
8'	 A		+				&2""			"									
'	1		.			.'			+				5		+	+	+'	A
	+				"		"			'	9					"	+
			+		&2""							"				"	+		
	
	#"	3'
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3DJH

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	:
0'	 9		"			.'	%			.				"			&',		!
"		"	+		
	#"	8'
&
	@
2'	 9		"			!									.	"	'	1		+
							.'	 			.	'	9		"				
	+			5	
		'	9			%	.					+
		'	+				"	"			'	1			
'	 		"				+							.	
	#"	0'
&
	;
('	 9		.						"									.		+	
				"	"	'
K'	 $								.			B		+					"		
&',				++			%			.	
	#"	2'
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	8
-'	 S		.		+						"	+		"						
				"'
'	 	.			!	"				"										"
				'
&'	 	."		!			"						"				%	
	+			"	
	#"	('
&
	3
,'	 	.		"	+					%	.'	1				'
'	90	*C	-.	
'	 %		!				.				'
&'	 %			!			"	+			%				!		+	
		"	+	"							.'	 		"		
	+		/			%			.'
,'	 1		+			"	"	+					.			+	
	#"	K'
&
	=
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3DJH

3'	 .		"							+	+		!	"!		
%	.				'	1							.				'
8'	 9		.	"					+		/	+	
	"	+
				"								.!		B			.			

					
	#"	-'
&
	72
0'	  		.								.					'
2'	 			.							+	+	.		.'
('	 *		+				.!			.	B					,-	
'			.					'
K'	 		(			+			.					'
-'	 	5				!	!					+'	1				5
B						!								
	#"	'
7A=)							5						
'
&
	77
'	 								5"'					+

	
		5"'	S		+		"'
'	:0	

		
'	 9			.						+						.	+		+
	+	
	#"	&'
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	71
&'	 		+	!								+	"	+	."	
	.	
	#"	,'
&
	79
,'	 					+			"		B				5		
		.						/'
3'	 	+				"!			"			.'	1		.			.'	 
		"			"						B					5		
		.						/	
	#"	3'
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	7:
8'	 .			.								'	S			.			
		+				"	+	"		'	 		"	+	
/						.	
	#"	8'
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3DJH

&
	7@
0'	 9		.						"									.		+	
				"	"	'	9		.			.'
2'	 S								B		+					"						"
										.	
	#"	0'
&
	7;
7A=)		5						&	'
('	 S		.		+	+			"	!		"			"			
							"	
	#"	2'
*				.						++			"					
.'
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	78
K'	 	.			!	+		"				"							"
	'
-'	 						.									.	
	"'
'	 +	+			.					.					
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3DJH

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	#"	('	1				.						'
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	73
'	@0	$+		!
'	 		".			/!		/			".				
+				'	*					"			!	.!		'
	

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		
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	
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
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Kiniksa Pharmaceuticals Ltd. 
 
19 February 2019 
KPL-914-C001 Amendment 3 
Final 
Page 4 of 85 
 
CONFIDENTIAL 
3 Synopsis 
Trial Number: 
KPL-914-C001 
Trial Title: 
An open-label, pilot study of KPL-914 in recurrent pericarditis 
Trial Centers: 
Approximately 15 sites 
Development Phase: 2 
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CONFIDENTIAL 
Objective(s): 
 
The study is comprised of 5 Parts.  
• 
Part 1 enrolls symptomatic subjects with recurrent idiopathic pericarditis (RIP) with an elevated 
marker of systemic inflammation (C-reactive protein [CRP] > 1mg/dL). 
• 
Part 2 enrolls symptomatic subjects with RIP with CRP ≤1 mg/dL which, in the opinion of the 
investigator, can be attributed to concomitant medications (e.g., corticosteroids) and with 
pericardial inflammation present on cardiac magnetic resonance imaging (MRI) confirmed by 
the imaging core lab. 
• 
Part 3 enrolls subjects with corticosteroid-dependent RIP not experiencing symptoms which 
would meet the diagnostic criteria for a flare of pericarditis. 
• 
Part 4 enrolls symptomatic subjects with recurrent post pericardiotomy syndrome (PPS) with an 
elevated marker of systemic inflammation (CRP > 1mg/dL). 
• 
Part 5 enrolls subjects with corticosteroid-dependent recurrent PPS not experiencing symptoms 
which would meet the diagnostic criteria for a flare of pericarditis. 
 
Part 1: 
Primary Objective: 
To collect inter- and intra-subject variability data on CRP measurements and the 11-point NRS 
instrument for assessment of pericardial pain in subjects with RIP both at baseline and on treatment 
with KPL-914 in order to inform power calculations for future trials in pericarditis. 
Secondary Objectives: 
To explore the time course to improvement of pericarditis parameters in symptomatic subjects with RIP 
treated with KPL-914. 
To evaluate the effect of KPL-914 on pericardial inflammation based on cardiac MRI. 
To evaluate the safety of KPL-914 in symptomatic subjects with RIP. 
 
Part 2: 
Primary Objective: 
To collect inter- and intra-subject variability data on CRP measurements and the 11-point NRS 
instrument for assessment of pericardial pain in subjects with RIP both at baseline and on treatment 
with KPL-914 in order to inform power calculations for future trials in pericarditis. 
Secondary Objectives: 
To explore the time course to improvement of pericarditis parameters in symptomatic subjects with RIP 
treated with KPL-914 
To evaluate the effect of KPL-914 on pericardial inflammation based on cardiac MRI. 
To evaluate the safety of KPL-914 in symptomatic subjects with RIP. 
 
Part 3: 
Primary Objective: 
To evaluate feasibility of weaning from corticosteroids while receiving KPL-914 in subjects with 
corticosteroid-dependent RIP. 
Secondary Objectives: 
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19 February 2019 
KPL-914-C001 Amendment 3 
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Page 6 of 85 
 
CONFIDENTIAL 
To evaluate the effect of KPL-914 on pericardial inflammation based on cardiac MRI. 
To evaluate the safety of KPL-914 in subjects with corticosteroid-dependent RIP. 
 
Part 4: 
Primary Objective: 
To collect inter- and intra-subject variability data on CRP measurements and the 11-point NRS 
instrument for assessment of pericardial pain in subjects with symptomatic recurrent PPS both at 
baseline and on treatment with KPL-914 in order to inform power calculations for future trials in 
pericarditis. 
Secondary Objectives: 
To explore the time course to improvement of pericarditis parameters in symptomatic subjects with 
recurrent PPS treated with KPL-914 
To evaluate the effect of KPL-914 on pericardial inflammation based on cardiac MRI. 
To evaluate the safety of KPL-914 in symptomatic subjects with recurrent PPS. 
 
Part 5: 
Primary Objective: 
To evaluate feasibility of weaning from corticosteroids while receiving KPL-914 in subjects with 
corticosteroid-dependent recurrent PPS. 
Secondary Objectives: 
To evaluate the effect of KPL-914 on pericardial inflammation based on cardiac MRI. 
To evaluate the safety of KPL-914 in subjects with corticosteroid-dependent recurrent PPS. 
 
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KPL-914-C001 Amendment 3 
Final 
Page 7 of 85 
 
CONFIDENTIAL 
Methodology: 
 
This is an open-label, single-active-arm pilot study to explore clinical and biochemical endpoints of 
pericarditis symptomatology and to collect inter- and intra-subject variability data on both at-baseline 
and on-treatment parameters. This study consists of 5 distinct Parts, and all subjects will be treated with 
once-weekly subcutaneously (SC)-administered injections of KPL-914.   
 
Enrollment into Part 1: 
Subjects identified for participation in Part 1 of this trial will present during a symptomatic episode of 
RIP, having previously experienced a first (index) episode of acute pericarditis followed by at least 1 
recurrent episode before the current enrollment-qualifying episode, using the 2015 European 
Society of Cardiology (ESC) Guidelines for the Diagnosis and Management of Pericardial Diseases 
(Adler et al, 2015) as a frame of reference: 
- 
The index episode of acute pericarditis would have been characterized by an inflammatory 
pericardial syndrome with at least 2 of the 4 following criteria: pericarditic chest pain, pericardial 
rub, new widespread ST-segment elevation or PR-segment depression on electrocardiogram 
(ECG), and pericardial effusion (new or worsening).  Additional supportive findings would have 
included elevations of markers of inflammation (i.e., CRP, ESR, or WBC count) or evidence of 
pericardial inflammation by an imaging technique (e.g., MRI).   
- 
Recurrence of RIP would have been characterized as a subsequent episode of pericarditis 
occurring after a symptom-free interval of 4-6 weeks or longer.   
 
 
 
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CONFIDENTIAL 
For the purposes of this study, the Investigator will determine, based on his/her judgement of the 
available data, if a subject has met these criteria for having previously experienced a first (index) 
episode of acute pericarditis followed by at least 1 recurrent episode of pericarditis prior to the 
current enrollment-qualifying episode of RIP and will record the criteria supporting this diagnosis in 
the electronic case report form (eCRF). 
 
Subjects with symptomatic RIP meeting the above diagnostic criteria may be enrolled into Part 1 only if 
the CRP value at screening is > 1 mg/dL. 
 
Enrollment into Part 2: 
Subjects identified for participation in Part 2 of this trial will present during a symptomatic episode of 
RIP, having previously experienced a first (index) episode of acute pericarditis followed by at least 1 
recurrent episode before the current enrollment-qualifying episode, using the 2015 European Society 
of Cardiology (ESC) Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 
2015) as a frame of reference: 
- 
The index episode of acute pericarditis would have been characterized by an inflammatory 
pericardial syndrome with at least 2 of the 4 following criteria: pericarditic chest pain, pericardial 
rub, new widespread ST-segment elevation or PR-segment depression on electrocardiogram 
(ECG), and pericardial effusion (new or worsening).  Additional supportive findings would have 
included elevations of markers of inflammation (i.e., CRP, ESR, or WBC count) or evidence of 
pericardial inflammation by an imaging technique (e.g., MRI).   
- 
Recurrence of RIP would have been characterized as a subsequent episode of pericarditis 
occurring after a symptom-free interval of 4-6 weeks or longer.   
 
For the purposes of this study, the Investigator will determine, based on his/her judgement of the 
available data, if a subject has met these criteria for having previously experienced a first (index) 
episode of acute pericarditis followed by at least 1 recurrent episode of pericarditis prior to the 
current enrollment-qualifying episode of RIP and will record the criteria supporting this diagnosis in 
the eCRF. 
 
Subjects with symptomatic RIP meeting the above diagnostic criteria but without an elevated CRP 
level (i.e., ≤1mg/dl) at screening may be enrolled into Part 2 only if, in the opinion of the investigator 
and in consultation with the Sponsor, the low CRP value can be attributed to concomitant 
medications (e.g., corticosteroids) AND if there is evidence of pericardial inflammation by cardiac 
MRI which has been confirmed by the MRI Core Laboratory. 
 
Enrollment into Part 3: 
Subjects identified for participation in Part 3 in this trial will present with corticosteroid-dependent 
RIP, having previously experienced a first (index) episode of acute pericarditis followed by at least 2 
recurrent episodes, using the 2015 European Society of Cardiology (ESC) Guidelines for the 
Diagnosis and Management of Pericardial Diseases (Adler et al, 2015) as a frame of reference: 
- 
The index episode of acute pericarditis would have been characterized by an inflammatory 
pericardial syndrome with at least 2 of the 4 following criteria: pericarditic chest pain, pericardial 
rub, new widespread ST-segment elevation or PR-segment depression on electrocardiogram 
(ECG), and pericardial effusion (new or worsening).  Additional supportive findings would have 
included elevations of markers of inflammation (i.e., CRP, ESR, or WBC count) or evidence of 
pericardial inflammation by an imaging technique (e.g., MRI).   
KPL-914-C001 Protocol and Amendments 
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19 February 2019 
KPL-914-C001 Amendment 3 
Final 
Page 9 of 85 
 
CONFIDENTIAL 
- 
Recurrence of RIP would have been characterized as a subsequent episode of pericarditis 
occurring after a symptom-free interval of 4-6 weeks or longer.   
 
For the purposes of this study, the Investigator will determine, based on his/her judgement of the 
available data, if a subject has met these criteria for having previously experienced a first (index) 
episode of acute pericarditis followed by at least 2 recurrent episodes of pericarditis and will record 
the criteria supporting this diagnosis in the eCRF. 
 
Subjects who are taking corticosteroids for their RIP and who are not currently experiencing symptoms 
which, in the opinion of the Investigator, would meet the above diagnostic criteria for a flare may be 
enrolled into Part 3 only if, in the opinion of the Investigator and in consultation with the Sponsor, they 
are considered to be “corticosteroid- dependent” (i.e.; the signs and symptoms of pericarditis would 
return if the corticosteroids were withdrawn). 
 
Enrollment into Part 4: 
Subjects identified for participation in Part 4 in this trial will present during a symptomatic episode of 
recurrent PPS, having previously experienced a first (index) episode of acute PPS followed by at 
least 1 recurrent episode of PPS before the current enrollment-qualifying episode, using the 2015 
European Society of Cardiology (ESC) Guidelines for the Diagnosis and Management of Pericardial 
Diseases (Adler et al, 2015) as a frame of reference: 
- 
The index episode of acute pericarditis would have been characterized by an inflammatory 
pericardial syndrome with at least 2 of the following 5 clinical findings after cardiac surgery: fever 
without alternative causes, pericardial chest pain, pericardial rub, evidence for pericardial effusion, 
or elevated CRP.  
- 
Recurrence of PPS would have been characterized as a subsequent episode of pericarditis 
occurring after a symptom-free interval of 4-6 weeks or longer.   
 
For the purposes of this study, the Investigator will determine, based on his/her judgement of the 
available data, if a subject has met these criteria for having previously experienced a first (index) 
episode of acute PPS followed by at least 1 recurrent episode of PPS prior to the current 
enrollment-qualifying episode of recurrent PPS and will record the criteria supporting this diagnosis 
in the eCRF. 
 
In addition to meeting the above criteria for PPS, all subjects enrolled in Part 4 must have a CRP value 
> 1 mg/dL at screening. 
 
Enrollment into Part 5: 
Subjects identified for participation in Part 5 in this trial will present with corticosteroid-dependent 
recurrent PPS, having previously experienced a first (index) episode of acute PPS followed by at least 
2 recurrent episodes, using the 2015 European Society of Cardiology (ESC) Guidelines for the 
Diagnosis and Management of Pericardial Diseases (Adler et al, 2015) as a frame of reference: 
- 
The index episode of acute pericarditis would have been characterized by an inflammatory 
pericardial syndrome with at least 2 of the following 5 clinical findings after cardiac surgery: fever 
without alternative causes, pericardial chest pain, pericardial rub, evidence for pericardial effusion, 
or elevated CRP.  
- 
Recurrence of PPS would have been characterized as a subsequent episode of pericarditis 
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19 February 2019 
KPL-914-C001 Amendment 3 
Final 
Page 10 of 85 
 
CONFIDENTIAL 
occurring after a symptom-free interval of 4-6 weeks or longer.   
 
For the purposes of this study, the Investigator will determine, based on his/her judgement of the 
available data, if a subject has met these criteria for having previously experienced a first (index) 
episode of acute PPS followed by at least 2 recurrent episodes of PPS and will record the criteria 
supporting this diagnosis in the eCRF. 
 
Subjects who are taking corticosteroids for the recurrent PPS and who are not currently experiencing 
symptoms which, in the opinion of the Investigator, would meet the above diagnostic criteria for a flare 
may be enrolled into Part 5 only if, in the opinion of the Investigator and in consultation with the 
Sponsor, they are considered to be “corticosteroid- dependent” (i.e.; the signs and symptoms of 
pericarditis would return if the corticosteroids were withdrawn). 
 
Enrollment Process for All Parts: 
Prior to enrollment, potential subjects may enter an optional Prescreening Period after signing a 
Prescreening ICF (or informed assent, if applicable) to confirm the diagnostic workup and to allow 
monitoring for symptoms and inflammatory markers (CRP, ESR, etc) while concomitant medications 
for pericarditis treatment may be managed by the Investigator or their clinician according to standard of 
care. 
 
Subjects included in Parts 1, 2 and 4 may be receiving concomitant nonsteroidal anti-inflammatory 
drugs (NSAIDs), and/or colchicine, and/or oral corticosteroid treatment in any combination, provided 
the dosages of these medications have been stable for at least 7 days, although stable doses for a shorter 
period will be acceptable if in the opinion of the Investigator, in consultation with the Sponsor, a shorter 
period of stability is not anticipated to alter the baseline CRP values.  
 
Subjects in Parts 3 and 5 must be receiving corticosteroids at the time of enrollment. 
 
Baseline therapy and disease characteristics will be determined during a Screening Period of up to 
72 hours, as needed, to confirm study eligibility.  At the SCV1, baseline subject and disease 
characteristics will be determined and captured in the eCRF.  At Screening Visit 2 (SCV2) during the 
24 - 72 hour period before subjects advance to the Treatment Period of the study, additional laboratory 
samples may be drawn to provide additional baseline reference data. Under special circumstances, the 
Investigator, in consultation with the Sponsor, can combine SCV1 and SCV2, and the subject can 
proceed directly to the Day 0 dosing visit. 
 
After having met all the entry criteria during the Screening Period, the adult subjects (18 years or older) 
entering the Treatment Period will receive a loading dose of 320 mg KPL-914 (2 x 160 mg) 
administered SC on Day 0, then 160 mg SC weekly for 5 additional doses. Subjects aged 6 years to <18 
years will receive a loading dose of 4.4 mg/kg KPL-914 (2x 2.2 mg/kg; maximum total 320 mg) 
administered SC on Day 0, then 2.2 mg/kg (maximum 160 mg) administered SC weekly for 5 
additional doses. 
 
The first Study Drug dose on Day 0 will be administered at the Study Site/Clinic (Visit 1).  Subsequent 
weekly Study Drug doses from Weeks 2 to 5 will be self-administered by the subject or will be 
administered to the subject by an adequately trained caregiver as an outpatient SC administration. Study 
center staff or a visiting study nurse will assess and record compliance with Study Drug administration 
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19 February 2019 
KPL-914-C001 Amendment 3 
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Page 11 of 85 
 
CONFIDENTIAL 
at the subject’s home as well as provide guidance and training on Study Drug administration as needed. 
At Week 6/End of Trial, Study Drug may be administered at home or other non-clinic location or 
administered at the study site.  Weekly assessments of safety and treatment response, including 
administration of the 11-point NRS instrument to assess pericardial pain, will be done at the Study 
Site/Clinic at Visit 1 (Day 0) and Visit 7 (Week 6/End-of-Trial), and via Investigator (or designee) 
phone calls/ virtual visits on Day 3 and at Weeks 2 to 5 (Visits 2 to 5). Weekly outpatient blood 
samples for central laboratory testing will be collected at the Study Site/Clinic, or at a qualified 
laboratory site in the vicinity of the subject, or by a visiting study nurse. 
 
Investigators are encouraged to schedule subjects at the Study Site/Clinic for an in-person Interval 
Evaluation Visit during approximately Weeks 3-4 to assist the Investigator in the clinical management 
of the subject.  During this visit a full assessment including physical examination, vital signs, ECG, 
echocardiogram, and laboratory testing can be performed as well as the recording of adverse events 
(AEs) and other study-related assessments as needed.   
 
 
At any time point during the Treatment Period, subjects reporting worsening of pericarditis symptoms 
or AEs may be brought into the Study Site/Clinic at the discretion of the Investigator for an 
Unscheduled Visit, in which select or comprehensive clinical assessments can be performed.  Any 
subject who is determined by the Investigator as not responding to treatment (e.g., no reduction in 
pericardial pain compared to baseline, no decrease in CRP levels [if applicable], etc.) and who is 
therefore considered by the Investigator to be a “Treatment Failure” may be withdrawn from further 
Study Drug treatment at the discretion of the Investigator and may receive rescue therapy for their 
pericarditis according to standard of care as per Investigator decision; these subjects will be followed 
for safety for the remainder of the 6-week Treatment Period.  Subjects identified as “Treatment 
Failures” may be replaced at the discretion of the Sponsor in order to provide an adequate sampling of 
subjects completing the active Treatment Period. 
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Subjects participating for the complete length of the active study Treatment Period will receive a total 
of 6 doses of KPL-914.  For the duration of the Treatment Period, concomitant NSAIDs and/or 
colchicine and/or corticosteroids, if present, should be continued at pre-study dose levels until after the 
6-dose Study Drug Treatment Period has concluded; however, should the Investigator determine that a 
reduction/tapering of the NSAID, colchicine, and/or corticosteroid dose is medically indicated, the 
NSAID, colchicine, and/or corticosteroid dose can be down-titrated in consultation with the Sponsor, 
and the modification of dose should be recorded in the source records and the eCRF.  
Opioid analgesics, non-narcotic analgesics (e.g., tramadol), and acetaminophen are allowed as rescue 
medication for ancillary pain control on an as-needed basis throughout the Treatment Period.  Although 
it is recommended that NSAID dose levels (if present) should remain constant during the active 
Treatment Period, the concomitant NSAID dose may be temporarily increased (or an NSAID initiated) 
for ancillary pain control if deemed necessary by the Investigator, after consultation with the Sponsor. 
Any rescue medication use must be recorded in source records, eCRF, and medication diary.  
At the discretion of the Investigator, “Treatment Responders” will be offered participation in an 
optional 18-week Extension Period (EP), in which weekly open-label KPL-914 administration can be 
continued at the same dose as in the Treatment Period for a total duration of Study Drug treatment of up 
to 24 weeks. 
Treatment response will be defined by the Investigator: 
• 
Part 1: A clinically significant reduction in pericardial pain using the 11-point NRS, normal or 
near normal CRP levels, and/or absent or decreasing echocardiographic effusion at the End-of-
Trial Visit. 
• 
Part 2: A clinically significant reduction in pericardial pain using the 11-point NRS, normal or 
near normal levels CRP, and/or absent or decreasing echocardiographic effusion at the End-of-
Trial Visit 
• 
Part 3: Absence of pericarditis flare and feasibility to taper corticosteroids.  
• 
Part 4: A clinically significant reduction in pericardial pain using the 11-point NRS, normal or 
near normal CRP levels, and/or absent or decreasing echocardiographic effusion at the End-of-
Trial Visit 
• 
Part 5: Absence of pericarditis flare and feasibility to taper corticosteroids.  
Weekly Study Drug administrations during the EP are by self-administration or by an adequately-
trained caregiver, and study nurse visits to the subject’s home as well as Investigator (or designee) 
telephone calls/virtual visits are to continue on a monthly basis. 
During the EP, the Investigator is encouraged to wean concomitant NSAIDs and/or colchicine, and/or 
corticosteroids. It is encouraged that NSAIDs and colchicine be tapered and withdrawn within 15 days 
after entry into the EP. It is encouraged that corticosteroids be progressively taped (e.g., by 5 mg 
prednisone or equivalent every week in adults or 0.2mg/kg every week in subjects <18yo) and 
discontinued within 6 weeks after entering the EP (i.e., by Study Week 12) unless in the opinion of the 
Investigator, a different corticosteroid weaning schedule is required based on subject’s clinical status. 
All medication changes must be recorded in source records and the eCRF.  Investigators are encouraged 
to schedule subjects at the Study Site/Clinic for an in-person Interval Evaluation Visit between Weeks 
15 to 20 (8 to 13 weeks after Visit 7/End of Trial Visit) to assist the Investigator in the clinical 
management of the subject.  During this visit a physical examination, vital signs, ECG, echocardiogram 
(ECHO), and laboratory testing can be performed at the discretion of the Investigator. 
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Available safety, tolerability, and efficacy data for each subject will be reviewed by the Investigator as 
part of ongoing subject management.  A Safety Review Committee (SRC) including selected 
Investigator(s) and Sponsor representatives will review on a monthly basis (at a minimum) all available 
data for all subjects, considering trends across each subject and each Part.  
Given the following occurrences, dosing may be halted or reduced in any Part of the study, in 
accordance with an SRC recommendation, confirmed by the Sponsor: 
- 
One or more subjects experience a serious and unexpected adverse event that is considered by 
the Investigator to be related to Study Drug (SUSAR), or 2 or more subjects experience similar 
severe (non-serious) and unexpected AEs that are considered by the Investigator to be related to 
Study Drug. 
After an initial group of subjects has been treated, depending on the safety profile observed as well as 
the magnitude and speed of treatment response (e.g., if an informative number of subjects achieve 
treatment response early in the Treatment Period), the Sponsor in collaboration with the Investigators 
may elect to decrease the KPL-914 dose administered to a subsequent consecutive group of subjects (in 
any Part of the Study): the adult subjects (18 years or older) entering the Treatment Period will receive 
a loading dose of 160 mg KPL-914 (2 x 80mg) SC on Day 0, then 80 mg administered SC weekly for 5 
additional doses. Subjects aged 6 years to <18 years will receive a loading dose of 2.2 mg/kg KPL-914 
(2 x 1.1 mg/kg; maximum total 160 mg) administered SC on Day 0, then 1.1 mg/kg (maximum 80 mg) 
administered SC weekly for 5 additional doses, in order to explore efficacy at a lower dose. 
Depending on treatment response observed with the 80 mg dose (or 1.1 mg/kg in subjects 6 years to 
<18years old), the weekly dose administered to either these subjects or subsequent subjects may be 
changed back to 160 mg (or 2.2 mg/kg in subjects 6 years to <18 years old) by the Investigator in 
collaboration with the Sponsor.  For any given subject, the KPL-914 dose level received at the end of 
the Treatment Period should be continued into the EP (if administration is continued); however, a 
change in the KPL-914 dose level during the EP for any individual subject can be made at the 
discretion of the Investigator in consultation with the Sponsor, and the modification of dose should be 
recorded in the source records and the eCRF. 
During the Screening and Treatment Periods, subjects will enter information concerning the use of 
pericarditis and rescue (pain) medication into a medication diary.  Such information will be entered by 
the subject immediately after dosing of study drug. 
Number of Subjects: 
Approximately up to a total of 40 subjects with RIP or recurrent PPS will be enrolled as study subjects 
across all Parts.   
Subjects who discontinue the study (withdrawals and Treatment Failures) may be replaced at the 
Sponsor’s discretion in order to provide an adequate sampling of subjects completing the active 
Treatment Period. 
 
Diagnosis and Main Criteria for Inclusion: 
Inclusion Criteria for All Parts 
To be eligible to participate in the trial, a subject must meet all of the following criteria: 
1. Has given consent (or assent, if applicable) and signed an Informed Consent Form (ICF) (or 
informed assent form, if applicable). 
2. Male or female, of any ethnic origin. 
3. 6 to 75 years of age, inclusive. 
4. If used, has received NSAIDs, and/or colchicine and/or corticosteroids (in any combination) at 
stable dose levels for at least 7 days (although stable doses for a shorter period will be acceptable 
if in the opinion of the Investigator, in consultation with the Sponsor, a shorter period of stability 
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is not anticipated to alter the baseline CRP values) and is anticipated to continue these 
concomitant medications at these dose levels for the duration of the active Treatment Period.  
5. If female of child-bearing potential, must be nonpregnant and nonlactating and must agree to use 
an effective method of contraception, e.g., hormonal contraception or double-barrier birth control.  
6. Is able to adequately maintain a medication diary. 
7. Agrees to refrain from making any new, major life-style changes that may affect pericarditis 
symptoms (e.g., starting a new diet or changing exercise pattern) from the time of signature of the 
ICF (or informed assent form, if applicable) to the End-of-Trial Visit (Week 6). 
 
Inclusion Criteria for Part 1: 
8. Has a diagnosis of RIP based on the judgement of the Investigator. 
9. Has previously had an index (first) episode of pericarditis which, in the judgement of the 
Investigator based on the available data, met the criteria for an acute pericarditis event, using the 
2015 ESC Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 
2015) as a frame of reference --  i.e., met at least 2 of the 4 following criteria: pericarditic chest 
pain, pericardial rub, new widespread ST-segment elevation or PR-segment depression on ECG, 
and pericardial effusion (new or worsening).  Additional supportive findings could include 
elevations of markers of inflammation (i.e., CRP, ESR or WBC count) or evidence of pericardial 
inflammation by an imaging technique (e.g., MRI). 
10. Has had at least one prior recurrent episode of pericarditis, in the judgement of the Investigator, 
based upon the available diagnostic information. 
11. Has an ongoing symptomatic episode of pericarditis at the time of study enrollment in the 
judgement of the Investigator, based upon the available diagnostic information. 
12. Has an elevated CRP value (i.e., >1 mg/dL) at the time of Screening. 
 
Inclusion Criteria for Part 2: 
13. Has a diagnosis of RIP based on the judgement of the Investigator. 
14. Has previously had an index (first) episode of pericarditis which, in the judgement of the 
Investigator based on the available data, met the criteria for an acute pericarditis event, using the 
2015 ESC Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 
2015) as a frame of reference --  i.e., met at least 2 of the 4 following criteria: pericarditic chest 
pain, pericardial rub, new widespread ST-segment elevation or PR-segment depression on ECG, 
and pericardial effusion (new or worsening).  Additional supportive findings could include 
elevations of markers of inflammation (i.e., CRP, ESR or WBC count) or evidence of pericardial 
inflammation by an imaging technique (e.g., MRI). 
15. Has had at least one prior recurrent episode of pericarditis, in the judgement of the Investigator, 
based upon the available diagnostic information. 
16. Has an ongoing symptomatic episode of pericarditis at the time of study enrollment in the 
judgement of the Investigator, based upon the available diagnostic information. 
17. Has CRP value < 1 mg/dL at Screening, which in the opinion of the Investigator in consultation 
with the Sponsor, can be attributed to concomitant medications. 
18. Has evidence of pericardial inflammation by cardiac MRI which has been confirmed by the 
MRI core imaging lab. 
 
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19. Has a diagnosis of RIP based on the judgement of the Investigator. 
20. Has previously had an index (first) episode of pericarditis which, in the judgement of the 
Investigator based on the available data, met the criteria for an acute pericarditis event, using the 
2015 ESC Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 
2015) as a frame of reference --  i.e., met at least 2 of the 4 following criteria: pericarditic chest 
pain, pericardial rub, new widespread ST-segment elevation or PR-segment depression on ECG, 
and pericardial effusion (new or worsening).  Additional supportive findings could include 
elevations of markers of inflammation (i.e., CRP, ESR, or WBC count) or evidence of pericardial 
inflammation by an imaging technique (e.g., MRI). 
21. Has had at least two prior recurrent episodes of pericarditis, in the judgement of the 
Investigator, based upon the available diagnostic information. 
22. Is not currently (at Screening) experiencing symptoms which, in the judgment of the Investigator 
based on the available diagnostic information, would meet the diagnostic criteria for a flare of 
pericarditis. 
23. Is “corticosteroid-dependent,” in the judgement of the Investigator based on available data (i.e., 
the signs and symptoms of pericarditis would return if the corticosteroids were to be withdrawn). 
 
Inclusion Criteria for Part 4: 
24. Has a diagnosis of recurrent PPS based on the judgement of the Investigator. 
25. Has previously had an index (first) episode of PPS which, in the judgement of the Investigator 
based on the available data, met the criteria for an acute pericarditis event, using the 2015 ESC 
Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 2015) as a 
frame of reference,  i.e., met at least 2 of the 5 clinical findings after cardiac surgery: fever 
without alternative causes, pericardial chest pain, pericardial rub, evidence for pericardial 
effusion with elevated CRP  
26. Has had at least one prior recurrent episode of PPS, in the judgement of the Investigator, based 
upon the available diagnostic information. 
27. Has an ongoing symptomatic episode of recurrent PPS at the time of study enrollment in the 
judgement of the Investigator, based upon the available diagnostic information. 
28. Has an elevated CRP value (i.e., >1 mg/dL) at the time of Screening. 
 
Inclusion Criteria for Part 5: 
29. Has a diagnosis of recurrent PPS based on the judgement of the Investigator. 
30. Has previously had an index (first) episode of PPS which, in the judgement of the Investigator 
based on the available data, met the criteria for an acute pericarditis event, using the 2015 ESC 
Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 2015) as a 
frame of reference,  i.e., met at least 2 of the 5 clinical findings after cardiac surgery: fever 
without alternative causes, pericardial chest pain, pericardial rub, evidence for pericardial 
effusion with elevated CRP  
31. Has had at least two prior recurrent episodes of PPS, in the judgement of the Investigator, based 
upon the available diagnostic information. 
32. Is not currently (at Screening) experiencing symptoms which, in the judgment of the Investigator 
based on the available diagnostic information, would meet the diagnostic criteria for a flare of 
pericarditis. 
33. Is “corticosteroid-dependent,” in the judgement of the Investigator based on the available data, 
(i.e., the signs and symptoms of pericarditis would return if the corticosteroids were to be 
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withdrawn). 
 
Exclusion Criteria for all Parts: 
A subject who meets any of the following criteria will not be eligible to participate in the trial: 
1. Has a diagnosis of pericarditis that was secondary to specific excluded etiologies, including 
tuberculous, neoplastic, or purulent etiologies, post-myocardial infarction (early or late), thoracic 
trauma, myocarditis, or systemic diseases including autoinflammatory diseases, autoimmune 
diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, etc.). 
2. Has a history of immunodepression, including a positive human immunodeficiency virus test 
result. 
3. Has received treatment within the 6-month period before dosing with any systemic 
immunosuppressants (other than, for example, corticosteroids or mycophenolate) which, in the 
opinion of the Investigator (in consultation with the Sponsor), may interfere with the study 
endpoints.  
4. Currently receiving other interleukin (IL)-1 or IL-6 blockers, janus-activating kinase (JAK) or 
tumor necrosis factor (TNF) inhibitors. 
5. Has a history of myeloproliferative disorder, demyelinating disease, or symptoms suggestive of 
multiple sclerosis. 
6. Female subject who is pregnant or lactating or who does not agree to use an effective method of 
contraception, e.g., hormonal contraception or double-barrier birth control. 
7. Has a history of active or latent treated tuberculosis (TB), or had a positive QuantiFERON (QFT-
TB G In-Tube) test result, or a chest radiograph during the 3 months prior to Study Drug dosing 
suggestive of prior TB infection. A subject with a positive purified protein derivative (PPD) test 
result (≥5-mm induration) after the first attack of pericarditis is excluded unless he/she has had 
either a negative chest x-ray result or a negative QuantiFERON test result. 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, night sweats) upon review of medical history and/or 
physical exam.  Have recent close contact with a person with active TB.  
8. Chest radiograph (or historic results within 3 months of SCV1) that shows evidence of 
malignancy or any abnormalities suggestive of prior TB infection, including, but not limited to, 
apical scarring, apical fibrosis, or multiple calcified granulomata.  This does not include non-
caseating granulomata. 
9. Has received immunization with a live (attenuated) vaccine within 12 weeks before the start of 
the study. 
10. Has history of or positive or intermediate results for hepatitis B surface antigen (HBsAg), 
hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at SCV1. 
11. Has an estimated glomerular filtration rate (eGFR) <30 mL/min.  
12. Has a history of malignancy of any organ system within the past 5 years (other than a 
successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or 
localized carcinoma in situ of the cervix). 
13. 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. 
14. Has had a serious infection, has been hospitalized for an infection, has been treated with oral 
antibiotics within 2 weeks of Study Drug administration, or has been treated with intravenous 
(IV) antibiotics for an infection within 2 months of first Study Drug administration.  
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15. Has had an organ transplant.  
16. In the Investigator's judgement, has a history of alcoholism or drug/chemical abuse within 2 years 
prior to Study Drug administration. 
17. Has a drug screen positive for amphetamines, cocaine, or phencyclidine or positive alcohol test at 
SCV1.  Exceptions may be made if a subject is on an approved medication for a stable 
concomitant condition that explains the positive screen. 
18. Has taken commercially-available rilonacept (ARCALYST®) or participated in a rilonacept 
clinical study during the 90 days before SCV1.  Has used anakinra within 14 days prior to Study 
Drug administration. Rilonacept and anakinra could not have been discontinued due to lack of 
efficacy or due to safety. 
19. Has a history of hypersensitivity to rilonacept or to any of the excipients contained in the Study 
Drug. 
20. Has received an investigational drug during the 30 days (or 5 half-lives, whichever is longer) 
before SCV1 or is planning to receive an investigational drug (other than that administered during 
this trial) or use an investigational device at any time during the trial. 
21. In the Investigator's judgement, has any other medical condition that could adversely affect the 
subject's participation or interfere with study evaluations.  
22. Subject who, in the opinion of the Investigator, is not likely to be compliant with the study 
protocol. 
23. Subject who, in the opinion of the Investigator in consultation with the Sponsor, should not 
participate in this study. 
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Test Products, Dosage, and Mode of Administration: 
KPL-914 (rilonacept) will be provided in its commercially-available formulation as a lyophilized 
powder to be reconstituted for SC administration. 
Subjects will receive a total of 6 doses of KPL-914 during the study active Treatment Period.  Subjects 
who are considered to be “Treatment Responders” will be offered, at the discretion of the Investigator, 
participation in an optional 18-week Extension Period (EP), in which weekly open-label KPL-914 can 
be continued for a total duration of KPL-914 treatment of up to 24 weeks. 
 
Adult subjects (≥ 18 years of age) 
KPL-914 will be administered as an initial loading dose of 320 mg SC, delivered as two subcutaneous 
injections of 160 mg SC each on Day 0, then 160 mg SC dosed once weekly for 5 subsequent weeks.   
 
Pediatric subjects (6 to <18 years of age) 
KPL-914 will be administered with an initial loading dose of 4.4 mg/kg, up to a maximum of 320 mg, 
delivered as two subcutaneous injections of 2.2 mg/kg each with a maximum single-injection volume of 
2 mL. Dosing will continue with a once-weekly injection of 2.2 mg/kg, up to a maximum of 160 mg, 
administered as a single subcutaneous injection of up to 2 mL as outpatient self-administration or 
administered by an adequately trained caregiver, for 5 subsequent weeks. 
 
After an initial group of subjects has been treated, depending on the safety profile observed as well as 
the magnitude and speed of treatment response (e.g., if an informative number of subjects achieve 
treatment response early in the Treatment Period), the Sponsor in collaboration with the Investigators 
may elect to decrease the KPL-914 dose administered to a subsequent consecutive group of subjects (in 
any Part of the Study):  the adult subjects (18 years or older) entering the Treatment Period will receive 
a loading dose of 160 mg KPL-914 (2 x 80mg) SC on Day 0, then 80 mg administered SC weekly for 5 
additional doses. Subjects aged 6 years to <18 years will receive a loading dose of 2.2 mg/kg KPL-914 
(2x 1.1 mg/kg; maximum total 160 mg) administered SC on Day 0, then 1.1 mg/kg (maximum 80 mg) 
administered SC weekly for 5 additional doses, in order to explore efficacy at a lower dose. 
 
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Concomitant Medication 
• There is no wash-out of concomitant therapy (NSAIDs/colchicine/corticosteroids) during the 
Screening Period of the study. 
• For the duration of the Treatment Period, concomitant pericarditis medications (e.g., NSAIDs, 
colchicine and corticosteroids), if used, should be continued at pre-study dose levels until after the 
6-dose Study Drug Treatment Period has concluded; however, should the Investigator determine 
that a reduction/tapering of the NSAIDs, colchicine, and/or corticosteroid dose is medically 
necessary, the NSAID, colchicine and/or corticosteroid dose can be down-titrated according to 
standard of care paradigms in consultation with the Sponsor, and the modification of dose should be 
recorded in the source records and the eCRF.  
• Opioid analgesics, non-narcotic (non-NSAID) analgesics (e.g., tramadol), and acetaminophen are 
allowed as rescue medication for ancillary pain control on an as needed basis throughout the 
Treatment Period.  Although it is recommended that NSAID dose levels (if present) should remain 
constant during the active Treatment Period, the concomitant NSAID dose may be temporarily 
increased (or an NSAID initiated) for ancillary pain control if deemed necessary by the 
Investigator, after consultation with the Sponsor.  Any rescue medication use must be recorded in 
source records, the medication diary and the eCRF. 
• Medical management of pericarditis during the EP is based on Investigator discretion. For example, 
Investigators may continue subjects on KPL-914 at the same dosage level, wean-off or discontinue 
Study Drug.  During the EP, the Investigator is encouraged to wean concomitant NSAIDs, and/or   
colchicine, and/or corticosteroids.  It is encouraged that NSAIDs and colchicine be tapered and 
withdrawn within 15 days after entry into the EP.  It is encouraged that corticosteroids be 
progressively tapered  (e.g., by 5 mg prednisone or equivalent every week in adults or  0.2mg/kg 
every week in subjects <18yo) and discontinued within 6 weeks after entering to EP (i.e., by Study 
Week 12) unless in the opinion of Investigator, a different corticosteroid weaning schedule is 
required based on subject’s clinical status 
• Other pericarditis medications may also be initiated at the discretion of the Investigator.  All 
changes to pericarditis-related medications should be captured in the source records and eCRF. 
• Prohibited concomitant medicines: Other interleukin (IL)-1 or IL-6 blockers, janus-activating 
kinase (JAK) or tumor necrosis factor (TNF) inhibitors. 
Duration of Treatment: 
The Study Drug will be administered for 6 weeks in the base study Treatment Period.  
“Treatment Responders” will be offered participation in an optional 18-week EP at the discretion of the 
Investigator. 
Total subject participation is expected to last for up to 171 days for those that also participate in the 
18-week EP. 
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Efficacy Measures: 
- Clinical laboratory analyses (e.g., CRP).  
- Pericarditis symptoms (i.e., pain) using a 11-point NRS (Appendix 4: 11-point Numerical Rating 
Scale (NRS) for Assessment of Pericarditis Pain) 
- Echocardiogram (pericardial effusion) 
- ECG (for pericarditis diagnostic findings) 
- Pericarditis signs (e.g., fever, pericardial rub) 
- Pericardial inflammation as determined by cardiac MRI (optional assessment for Parts 1, 3, 4, 5; 
mandatory for Part 2) 
- Quality of life (QoL) questionnaire (Appendix 3). 
Safety Measure(s): 
Safety endpoints for this study include frequency and severity of AEs and SAEs, clinical laboratory 
analyses (including safety laboratory measurements, anti-drug antibodies, etc.), vital sign 
measurements, ECGs, and physical examination findings. 
Other Measure(s): 
 
Overview of Trial Design  
 
Trial Periods (all Parts) 
1. Prescreening Period: Prior to enrollment, potential subjects may enter an optional prescreening 
period after signing a Prescreening ICF (or prescreening informed assent, if applicable) to 
confirm the diagnostic workup and to allow monitoring for symptoms and inflammatory 
markers (CRP, ESR, etc) while concomitant pericarditis medications may be managed by the 
Investigator or their clinician according to standard of care. 
2. Screening Period: The Screening Period starts with the signing of the full study ICF (or 
informed assent form, if applicable) (SCV1) and may last for up to 3 days (72 hours) until 
SCV2.  At SCV1, baseline subject and disease characteristics will be determined.  At Screening 
Visit 2 [SCV2]), within the 24 – 72 hour period before subjects advance to the Treatment 
Period of the study, additional laboratory samples may be drawn to provide additional baseline 
reference data.  Under special circumstances, the Investigator in consultation with the Sponsor 
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can combine SCV1 and SCV2.  The end of the Screening Period coincides with the start of the 
Treatment Period (Day 0 Visit).  
At the SCV1, subjects will be given a medication diary to record administration of pericarditis 
medications and rescue (pain) medication use during the Screening Period. 
Patient-reported pericardial pain evaluations will be performed on-site at SCV1 and SCV2 
using a validated 11-point NRS instrument.  A patient-reported QoL questionnaire will be 
administered as well. 
3. Treatment Period: The first dose of Study Drug will be administered to subjects at the Study 
site/Clinic at Visit 1 on Day 0.  During this visit, subjects and/or caregivers will be trained for 
outpatient drug administration.  At Day 3, the Investigator (or designee) telephone call/virtual 
visit will occur to evaluate safety (AE evaluations) and patient-reported pericardial pain using a 
validated 11-point NRS instrument. 
Subsequent weekly Study Drug administrations from Weeks 2 to 5 will be self-administered by 
the subject or administered by an adequately trained caregiver as an outpatient SC 
administration. A visiting study nurse will assess and record compliance with Study Drug 
administration at the subject’s home as well as provide guidance and training on Study Drug 
administration as needed. At Week 6/End-of-Trial, Study Drug may be self-administered or 
administered at the Study site/clinic.   
Investigators are encouraged to schedule subjects at the Study Site/Clinic for an in-person 
Interval Evaluation Visit during approximately Weeks 3-4 to assist the Investigator in the 
clinical management of the subject.   
Subjects reporting worsening of pericarditis symptoms or AEs may be brought in for an 
unscheduled visit at the Study Site/Clinic at any time during the Treatment Period, at the 
discretion of the Investigator.  Any subject who is considered by the Investigator to be a 
“Treatment Failure” may be withdrawn from further Study Drug treatment at the discretion of 
the Investigator and receive rescue therapy for their pericarditis according to standard of care as 
per Investigator decision; these subjects will be followed for safety for the remainder of the 6-
week Treatment Period.  Subjects identified as “Treatment Failures” may be replaced at the 
discretion of the Sponsor in order to provide an adequate sampling of subjects completing the 
active Treatment Period. 
During the Treatment Period, subjects will continue documentation of pericarditis treatment 
medication use as well as rescue (pain) medication use in the medication diary.  Patient-
reported pericardial pain evaluations will be performed on-site at the Study Site/Clinic and by 
weekly (and on Day 3) Investigator (or designee) telephone calls/virtual visits using a validated 
11-point NRS instrument.  A patient-reported QoL questionnaire will be administered at Visit 7 
(Study Site/Clinic).  Weekly blood samples for central laboratory testing will be collected at the 
Study Site/Clinic or at a qualified laboratory site in the vicinity of the subject or by a visiting 
study nurse. 
4. Extension Period (EP): The EP is defined as the 18 weeks following the Treatment Period.  
Subjects who are considered to be “Treatment Responders” will be, at the discretion of the 
Investigator, offered participation in an optional 18-week EP, in which weekly administration 
of open-label KPL-914 may be continued for a total duration of 24 weeks.  The weekly KPL-
914 doses will be by self-administration or administered by adequately trained caregiver, and 
study nurse visits to the subject’s home as well as Investigator (or designee) telephone 
calls/virtual visits will continue on a monthly basis. During the EP, the Investigator is 
encouraged to wean concomitant NSAIDs, and/or colchicine, and/or corticosteroids.  It is 
encouraged that NSAIDs and colchicine be tapered and withdrawn within 15 days after entry 
into the EP.  It is encouraged that corticosteroids be progressively tapered (e.g., by 5 mg 
prednisone or equivalent every week in adults or 0.2mg/kg every week in subjects <18yo) and 
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discontinued within 6 weeks after entering to EP (i.e., by Study Week 12) unless in the opinion 
of Investigator, a different corticosteroid weaning schedule is required based on subject’s 
clinical status. Other pericarditis medications may also be initiated at the discretion of the 
Investigator.  All changes to pericarditis-related medications should be captured in the source 
records and eCRF 
Unscheduled clinic visits can be scheduled any time as determined by the Investigator/upon 
subject request. In addition, Investigators are encouraged to schedule subjects at the Study 
Site/Clinic for an in-person Interval Evaluation Visit between Weeks 15 to 20 (8 to 13 weeks 
after Visit 7) to assist the Investigator in the clinical management of the subject.  During this 
visit a physical examination, vital signs, ECG, echocardiogram, and laboratory testing can be 
performed. 
Patient-reported pericardial pain evaluations using a validated 11-point NRS instrument as well 
as AE monitoring will be performed during the EP at on-site clinic visits and/or during monthly 
Investigator (or designee) phone calls/virtual visits.  A patient-reported QoL questionnaire will 
be administered at the Interval Evaluation Visit and the Final Visit of the EP.  At the end of the 
EP, subjects will complete the Week 25/Final Visit.  
Statistical Methods: 
Each Part will be analyzed separately and per the analysis populations below, to be finalized in the 
Statistical Analysis Plan to be provided separately.  
Analysis Populations (each Part) 
The modified Intention to Treat (mITT) Population will consist of all subjects who received at least one 
dose of Study Drug.  The Per Protocol (PP) Population will consist of all subjects who received all 6 
doses of Study Drug during the active Treatment Period and were maintained at stable dose levels of 
concomitant pericarditis medications (e.g., NSAIDs, colchicine, corticosteroids) according to study 
protocol without a major protocol violation.  The Safety Population will be the same as the mITT 
Population. 
General Methods 
Because of the small sample size no inferential statistical analyses or hierarchical testing are planned. 
For analysis of continuous endpoints (e.g., change from baseline), summary statistics (n, mean, standard 
deviation, median, minimum, and maximum) will be calculated and presented for each treatment and/or 
analysis group.  For categorical endpoints, summary statistics will be calculated and presented for each 
treatment and/or analysis group. Under certain circumstances, if appropriate in the context of statistical 
methodologies, the results of certain similar Parts might be pooled for greater statistical precision in 
determining therapeutic response or safety. 
Further details, including, for example, the process to be followed for reviewing individual pericarditis 
symptomatology endpoints to be used in the construction of a composite primary endpoint for 
subsequent trials, will be provided in the Statistical Analysis Plan (SAP). 
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Table 1: 
Schedule of Evaluations 
Trial Period → 
Pre-
screening 
Period 
Run-In 
Period 
(Up to 3 
days) 
 
Treatment Period 
(6 weeks) 
Extension Period 
(18 weeks) 
Visit Days/Weeks → 
Day -3 to 
Day 0a 
Day 0b 
 
 
Day  
3 c 
Week  
2c 
Week  
3c 
W3-W4d 
Week 
4c 
Week 
5c 
Week 
6cc 
Week 
6/ 
End-
of-
Trial c 
 
 
W15-W20t 
Week 
25 
(Week 
7 +18 
weeks) 
Visit Number → 
SC 
Visit 
1 
SC 
Visit 
2 
Visit 1 
(Clinic) 
 
 
Day 3  
(Outpt) 
Visit 2 
(Outpt) 
Visit 3 
(Outpt)  
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 4 
(Outpt) 
Visit 5 
(Outpt) 
Visit 6 
(Outpt) 
Visit 7 
Clinic 
 
Monthly 
Visits 
(Outpt) 
Un-
scheduled 
Visits 
(Clinic) 
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 8 
(Final, 
Clinic) 
Dose Number → 
 
 
Dose 1 
 
N/A 
Dose 2 
Dose 3 
N/A 
Dose 4 
Dose 5 
Dose 6 
 
 
 
 
 
Trial Procedure ↓ 
 
 
 
 
 
Unscheduled Visitsu 
 
 
 
 
Signature of ICF (or 
informed assent, if 
applicable) 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion and 
exclusion criteria 
verification 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history e 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Drug admin. – 
On site f 
 
 
 
X 
 
 
 
 
 
 
 
(Xf) 
 
 
 
 
Study Drug admin. - 
Outpatient f 
 
 
 
 
 
X 
X 
 
X 
X 
X 
Xf 
X w 
(weekly) 
 
 
 
Physical examination 
g 
 
X 
X 
 
 
 
 
X  
 
 
 
X 
 
X 
X 
X 
Body weight and 
height 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Vital Signs h 
 
X 
X 
 
 
 
 
X 
 
 
 
X 
 
X 
X 
X 
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Trial Period → 
Pre-
screening 
Period 
Run-In 
Period 
(Up to 3 
days) 
 
Treatment Period 
(6 weeks) 
Extension Period 
(18 weeks) 
Visit Days/Weeks → 
Day -3 to 
Day 0a 
Day 0b 
 
 
Day  
3 c 
Week  
2c 
Week  
3c 
W3-W4d 
Week 
4c 
Week 
5c 
Week 
6cc 
Week 
6/ 
End-
of-
Trial c 
 
 
W15-W20t 
Week 
25 
(Week 
7 +18 
weeks) 
Visit Number → 
SC 
Visit 
1 
SC 
Visit 
2 
Visit 1 
(Clinic) 
 
 
Day 3  
(Outpt) 
Visit 2 
(Outpt) 
Visit 3 
(Outpt)  
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 4 
(Outpt) 
Visit 5 
(Outpt) 
Visit 6 
(Outpt) 
Visit 7 
Clinic 
 
Monthly 
Visits 
(Outpt) 
Un-
scheduled 
Visits 
(Clinic) 
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 8 
(Final, 
Clinic) 
Dose Number → 
 
 
Dose 1 
 
N/A 
Dose 2 
Dose 3 
N/A 
Dose 4 
Dose 5 
Dose 6 
 
 
 
 
 
Trial Procedure ↓ 
 
 
 
 
 
Unscheduled Visitsu 
 
 
 
 
ECG/ECHO i 
 
X 
X 
(EC
G) 
 
 
 
 
X 
 
 
 
X 
 
 
X 
X 
MRI j 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Prior and 
concomitant 
medicines k 
X 
X 
X 
 
 
 
 
X 
 
 
 
X 
X  
X 
X 
X 
Drug and alcohol test 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
QuantiFERON TB 
test   j 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical laboratory 
tests (incl CRP)– 
Central laboratory l 
 
 
X 
X 
(X)x 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical laboratory 
tests (lipid panel) – 
Central Laboratory 
 
 
 
X 
 
 
 
 
 
 
 
 
X aa 
 
 
X 
Clinical laboratory 
tests (incl CRP) – 
Study Site/Clinic 
laboratory m 
 
Xy 
X 
X 
(X)x 
 
 
 
X 
 
 
 
X 
 
X 
X 
X 
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Trial Period → 
Pre-
screening 
Period 
Run-In 
Period 
(Up to 3 
days) 
 
Treatment Period 
(6 weeks) 
Extension Period 
(18 weeks) 
Visit Days/Weeks → 
Day -3 to 
Day 0a 
Day 0b 
 
 
Day  
3 c 
Week  
2c 
Week  
3c 
W3-W4d 
Week 
4c 
Week 
5c 
Week 
6cc 
Week 
6/ 
End-
of-
Trial c 
 
 
W15-W20t 
Week 
25 
(Week 
7 +18 
weeks) 
Visit Number → 
SC 
Visit 
1 
SC 
Visit 
2 
Visit 1 
(Clinic) 
 
 
Day 3  
(Outpt) 
Visit 2 
(Outpt) 
Visit 3 
(Outpt)  
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 4 
(Outpt) 
Visit 5 
(Outpt) 
Visit 6 
(Outpt) 
Visit 7 
Clinic 
 
Monthly 
Visits 
(Outpt) 
Un-
scheduled 
Visits 
(Clinic) 
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 8 
(Final, 
Clinic) 
Dose Number → 
 
 
Dose 1 
 
N/A 
Dose 2 
Dose 3 
N/A 
Dose 4 
Dose 5 
Dose 6 
 
 
 
 
 
Trial Procedure ↓ 
 
 
 
 
 
Unscheduled Visitsu 
 
 
 
 
Biomarker testing, 
PK, and anti-
rilonacept antibody – 
Central Laboratory l 
 
X 
 
(X) 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy test n 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE evaluations o 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medication diary 
dispensing p 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medication diary 
compliance 
verification and 
reminder q 
 
 
X 
(X)x 
 
 
 
X 
 
 
 
X 
 
 
 
X 
Pericardial pain (11-
pt Numerical Rating 
Scale) r 
X 
X 
X 
(X)x 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PGA (QoL 
questionnaire) s 
 
X 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
X 
Dosing Procedure 
Questionnaire z 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
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Trial Period → 
Pre-
screening 
Period 
Run-In 
Period 
(Up to 3 
days) 
 
Treatment Period 
(6 weeks) 
Extension Period 
(18 weeks) 
Visit Days/Weeks → 
Day -3 to 
Day 0a 
Day 0b 
 
 
Day  
3 c 
Week  
2c 
Week  
3c 
W3-W4d 
Week 
4c 
Week 
5c 
Week 
6cc 
Week 
6/ 
End-
of-
Trial c 
 
 
W15-W20t 
Week 
25 
(Week 
7 +18 
weeks) 
Visit Number → 
SC 
Visit 
1 
SC 
Visit 
2 
Visit 1 
(Clinic) 
 
 
Day 3  
(Outpt) 
Visit 2 
(Outpt) 
Visit 3 
(Outpt)  
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 4 
(Outpt) 
Visit 5 
(Outpt) 
Visit 6 
(Outpt) 
Visit 7 
Clinic 
 
Monthly 
Visits 
(Outpt) 
Un-
scheduled 
Visits 
(Clinic) 
Optional 
Interval 
Evaluation 
Visit 
(Clinic) 
Visit 8 
(Final, 
Clinic) 
Dose Number → 
 
 
Dose 1 
 
N/A 
Dose 2 
Dose 3 
N/A 
Dose 4 
Dose 5 
Dose 6 
 
 
 
 
 
Trial Procedure ↓ 
 
 
 
 
 
Unscheduled Visitsu 
 
 
 
 
Investigator (or 
designee) phone 
call/virtual visit v 
 
 
 
 
 
X 
X 
X 
 
X 
X 
X 
 
X 
(monthly) 
 
 
 
ECHO = echocardiogram, ECG = electrocardiogram, ICF = informed consent form, MRI = magnetic resonance imaging, Outpt = outpatient, PGA (Quality of Life) = 
patient global assessment, pt = point, TB = tuberculosis, HBcAb = hepatitis B core antibody; HBsAb = hepatitis B surface antibody; HBsAg = hepatitis B surface 
antigen; HCVAb = hepatitis C virus antibody; HIV = human immunodeficiency virus 
a. 
A second Screening visit (SCV2) should be performed within ~24h to 72h.  Under special circumstances, the Investigator, in consultation with the Sponsor, can 
combine SCV1 and SCV2.  The last Screening and Day 0 procedures may be performed on the same day, but SCR procedures must be completed prior to Study 
Drug administration.  
b. Subjects who do not complete the Treatment Period (withdraw consent or are discontinued before they have completed 6 weeks treatment), must be asked to 
complete the procedures specified at the EoT Visit. 
c. 
Day 3 will occur ± 1 day after Day 0. Weekly intervals refer to 7 ± 1 days. The interval between Study Drug administrations must be at least 5 days.  
d. Subjects should return for an optional Interval Evaluation Visit at the clinic between approximately Week 3 and 4, as determined by the Investigator. 
e. 
Including age at first attack, number of previous attacks, and duration of attacks.  
f. 
Drug administration training of subjects is performed at Visit 1.  Study Drug will be administered in the Study Site/Clinic at Visit 1. Study Drug administrations are 
performed by the subjects (self-administration) or by an adequately trained caregiver on Visits (Outpatient) 2, 3, 4, 5, and 6. Participation in the Extension Phase 
(optional) is determined at the Week 6/EoT Visit 7 by the Investigator.  Subjects who are eligible and who are willing to participate will be consented during EoT 
Visit 7 at the Study Site/Clinic. Only subjects continuing treatment into the Extension Phase will receive Study Drug at Visit 7; Study Drug can be self-administered 
either as an outpatient or at the Study Site/Clinic (Site to provide Study Drug) depending on the logistics/timing of the EoT Visit 7 relative to the timing of weekly 
dosing. Timing for dose administration is per direction of the Investigator based upon the prescribing information and study-specified dosing intervals. Continued 
weekly Study Drug treatment during the EP will be outpatient administration.    
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g. Full physical examination including assessment of pericardial rub.    
h. Vital signs must be obtained in the seated position and include oral temperature, respiratory rate, blood pressure, and pulse. 
i. 
Central 12-lead ECG and echocardiogram reading (including assessment of pericardial effusion). At SCV2 only the ECG will be obtained. The Study Site/Clinic 
reading of the ECG and the ECHO at the time of the examination will be used by the Investigator for clinical decision-making. In addition, both the ECG and 
ECHO will be sent to a core laboratory. 
j. 
Optional in Parts 1, 3,4 and 5. Required for Part 2. 
k. At the SCV1, information related to concomitant medicine that subjects were taking during at least the 2 weeks prior to the visit will be captured. During the 
Treatment Period, changes in concomitant medication since the last Study Site/Clinic visit will be documented. During the EP, changes in pericarditis/concomitant 
medication will be assessed at Study Site/Clinic Visits and in monthly outpatient phone calls/virtual visits.  
l. 
Biomarker, pharmacokinetics (PK) and anti-rilonacept antibody analysis samples will be drawn in all subjects and archived for future testing. . During each Visit at 
the Study Site/Clinic a sample for CRP will be obtained and sent to the central laboratory (or designated qualified laboratory) for analysis; at each Outpatient Visit; 
blood for central laboratory measurement of CRP will be obtained as described in the Laboratory Manual. 
m. Hematology, chemistry, and urinalysis will be performed at the Study Site/Clinic laboratories, and results when available will be entered into the eCRF with 
appropriate reference values. Serology (HCVAb, HBsAg, HBcAb, HBsAb and HIV) and urine drug screen will be performed at SCV1 only. Hematology and 
urinalysis will not be performed at SCV2. 
n. To be eligible to continue in the trial, a negative urine pregnancy test must be documented at the SCV1. If the urine test is positive, additional Study Site/Clinic 
and/or central serum tests may be performed.  
o. All AEs occurring after the subject receives the first dose of Study Drug will be captured in source records and eCRF. 
p. At the SCV1, the Investigator or designee will instruct the subject about the use of the medication diary.  The subject will be asked to complete  entries   into the 
medication diary during the Screening Period and Treatment Period. Only information on pain/rescue medication will be collected. Other concomitant 
treatments/medications are not required to be captured. 
q. At the SCV2 and all subsequent visits at the Study Center, the Investigator or designee will review the Diary entry information to verify subject compliance.  If the 
last screening visit occurs at a different day than Visit 1, the review will also be performed at Visit 1.  Diary documentation will end at the End-of-Trial visit (Visit 
7).  
r. 
Subject assessment of pericardial pain using a validated 11-point Numerical Rating Scale.  The assessment will be performed on-site during clinic visits and as part 
of a telephone call/virtual visit during outpatient treatment weeks.  If the last screening visit occurs at a different day than Visit 1, the assessment will also be 
performed at Visit 1, prior to Study Drug treatment. All the assessments must occur prior to study drug injection. 
s. 
Adult subjects only. Subject global assessment of overall well-being will be assessed using a validated QoL Questionnaire (see Appendix 3). The assessment will be 
performed on-site during clinic visits.  If SCV2 occurs at a different day than Visit 1 (Day 0), the global assessment will also be performed at Visit 1, prior to Study 
Drug administration. 
t. 
Subjects may return for an optional EP Interval Evaluation Visit at the clinic between Week 15 and 20 (8 to 13 weeks after Visit 7), as determined by the 
Investigator.  
u. Subjects reporting worsening of pericarditis symptoms or AEs may be brought in at the discretion of the Investigator for an Unscheduled Visit at any time during 
the Treatment Period.  Any subject who is not responding to treatment (e.g., no reduction in pericardial pain compared to baseline, no decrease in CRP levels, etc.) 
and who is therefore considered by the Investigator to be a “Treatment Failure” may be withdrawn from further Study Drug treatment at the discretion of the 
Investigator and receive rescue therapy for their pericarditis according to standard of care as per Investigator decision; these subjects will be followed for safety for 
the remainder of the 6-week Treatment Period.  
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v. At weekly Investigator (or designee) phone calls/virtual visits during the Treatment Period, Study Drug compliance, medication diary compliance, and laboratory 
sample collection will be checked. The subjects will be asked using non-leading questions about any AEs occurring since the last contact (phone call/virtual visit or 
site visit), and NRS pain assessment will be performed.  Investigator (or designee) phone calls/virtual visits will be performed monthly during the during the EP to 
perform NRS pain assessments, collect AE information, and review pericarditis/concomitant medications. If scheduled, in-person Study Site/Clinic Visits 
(Unscheduled Visits or Evaluation Visits) can replace the phone calls/virtual visits. 
w. During the Extension Period, Study Drug treatment is weekly by self-administration, and the study nurse visits to the home and Investigator (or designee) phone 
calls/virtual visits are monthly. 
x. Visit 1 will coincide with SCV2.  In case Visit 1 is separated from SCV2, SCV2 clinical laboratory blood sampling and subject NRS pericardial pain rating must be 
repeated prior to Study Drug dosing. 
y. Per Standard of Care. 
z. 
Adult subjects only. The dosing preparation and administration questionnaire must be completed in the presence of Study Staff (via virtual visit) or visiting nurse. 
aa. This lab will be drawn only during the first monthly Extension Period visit. 
 
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4 Table of Contents 
 
 
 
 
  
 
 
 
  
2 
Investigator and Administrative Structure ...................................................................... 3 
3 
Synopsis ......................................................................................................................... 4 
4 
Table of Contents ......................................................................................................... 31 
5 
List of Abbreviations and Definition of Terms ............................................................... 34 
6 
Introduction ................................................................................................................. 36 
7 
Study Objectives ........................................................................................................... 38 
7.1 
Part 1 ........................................................................................................................... 39 
7.2 
Part 2 ........................................................................................................................... 39 
7.3 
Part 3 ........................................................................................................................... 39 
7.4 
Part 4: .......................................................................................................................... 39 
7.5 
Part 5: .......................................................................................................................... 40 
8 
Investigational Plan ...................................................................................................... 41 
8.1 
Overall Study Design and Plan ...................................................................................... 41 
8.2 
Discussion of Study Design ............................................................................................ 47 
8.3 
Selection of Study Population ........................................................................................ 47 
8.3.1 
Number of Planned Subjects ........................................................................... 47 
8.3.2 
Inclusion Criteria ........................................................................................... 48 
8.3.3 
Exclusion Criteria .......................................................................................... 50 
8.3.4 
Vaccination History and Immune status ............................................................ 51 
8.3.5 
Removal of Subjects from Therapy or Assessments ........................................... 52 
8.4 
Investigational Medicinal Products................................................................................ 53 
8.4.1 
Investigational Medicinal Products Administered .............................................. 53 
8.4.2 
Identity of Investigational Medicinal Products ................................................... 54 
8.4.3 
Method of Assigning Subjects to Treatment Groups ........................................... 54 
8.4.4 
Selection of Doses in the Study ....................................................................... 54 
8.4.5 
Selection and Timing of Dose for Each Subject ................................................. 55 
8.4.6 
Blinding........................................................................................................ 55 
8.4.7 
Prior and Concomitant Therapy ....................................................................... 56 
8.4.8 
Treatment Compliance ................................................................................... 57 
8.5 
Study Procedures ......................................................................................................... 57 
8.5.1 
Prescreening Period........................................................................................ 57 
8.5.2 
Screening Period ............................................................................................ 57 
8.5.2.1 
Screening Visit 1 (SCV1)................................................................................ 58 
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8.5.2.2 
Screening Visit 2 (SCV2)................................................................................ 58 
8.5.3 
Treatment Period ........................................................................................... 59 
8.5.3.1 
Visit 1 (Study Site/Clinic) - Day 0 ................................................................... 59 
8.5.3.2 
Day 3 (Outpatient) ......................................................................................... 59 
8.5.3.3 
Visits 2 to 6 (Outpatient) - Weeks 2, 3, 4, 5, 6 ................................................... 59 
8.5.3.4 
Interval Evaluation Visit (Study Site/Clinic) - Week 3-4 ..................................... 60 
8.5.3.5 
Unscheduled Visits (Study Site/Clinic) During the Treatment Period ................... 61 
8.5.3.6 
Visit 7/ End-of-Trial (Study Site/Clinic) - Week 6 ............................................. 61 
8.5.4 
Extension Period ............................................................................................ 62 
8.5.4.1 
Unscheduled Visits (Study Site/Clinic) during the EP ......................................... 62 
8.5.4.2 
Interval Evaluation Visit During Extension Period (Study Site/Clinic) - 
Week 15-20................................................................................................... 62 
8.5.4.3 
Visit 8/Final Visit (Study Site/Clinic) - Week 25 ............................................... 63 
8.5.5 
Duration of Treatment .................................................................................... 63 
8.6 
Efficacy and Safety Variables ........................................................................................ 64 
8.6.1 
Individual Efficacy Assessments ...................................................................... 64 
8.6.1.1 
C-Reactive Protein, Biomarker, and PK Assessments ......................................... 64 
8.6.1.2 
Echocardiogram (Pericardial Effusion) ............................................................. 64 
8.6.1.3 
Electrocardiogram (Pericarditis Diagnostic Findings) ......................................... 64 
8.6.1.4 
Pericarditis Signs (Fever, Pericardial Rub) ........................................................ 65 
8.6.1.5 
Pericarditis Pain (Chest Pain) .......................................................................... 65 
8.6.1.6 
Magnetic Resonance Imaging .......................................................................... 66 
8.6.1.7 
Quality of Life Questionnaire .......................................................................... 66 
8.6.1.8 
Dosing Procedure Questionnaire ...................................................................... 66 
8.6.2 
Safety Assessments ........................................................................................ 67 
8.6.2.1 
Adverse Events .............................................................................................. 67 
8.6.2.2 
Serious Adverse Events .................................................................................. 68 
8.6.2.3 
Adverse Reactions ......................................................................................... 70 
8.6.2.4 
Clinical Laboratory Variables .......................................................................... 70 
8.6.2.5 
Vital Signs .................................................................................................... 72 
8.6.2.6 
Physical Examination ..................................................................................... 72 
8.6.2.7 
Body Weight and Height................................................................................. 72 
8.7 
Statistical Methods ....................................................................................................... 72 
8.7.1 
Statistical and Analytical Plans ........................................................................ 72 
8.7.1.1 
Datasets to be Analyzed for Each Part .............................................................. 72 
8.7.1.2 
General Statistical Methods ............................................................................. 72 
8.7.1.3 
Efficacy Endpoints ......................................................................................... 73 
8.7.1.4 
Safety Variables ............................................................................................ 74 
8.7.2 
Determination of Sample Size ......................................................................... 74 
8.8 
Quality Assurance and Quality Control ......................................................................... 74 
8.8.1 
Audit and Inspection ...................................................................................... 74 
8.8.2 
Monitoring .................................................................................................... 74 
8.8.3 
Data Management and Coding ......................................................................... 75 
8.8.4 
Record Keeping ............................................................................................. 75 
9 
Records and Supplies .................................................................................................... 75 
9.1 
Drug Accountability ..................................................................................................... 75 
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10 
Ethics ........................................................................................................................... 75 
10.1 Institutional Review Board ........................................................................................... 75 
10.2 Ethical Conduct of the Study......................................................................................... 76 
10.3 Subject Information and Consent .................................................................................. 76 
10.4 Subject Confidentiality (US Studies) .............................................................................. 76 
11 
Reporting and Publication ............................................................................................ 77 
12 
References .................................................................................................................... 78 
13 
Appendices ................................................................................................................... 81 
Appendix 1: Investigator Signature Page ................................................................................ 81 
Appendix 2: ARCALYST® Prescribing Information ............................................................... 82 
Appendix 3: Quality of Life Instrument .................................................................................. 83 
Appendix 4: 11-point Numerical Rating Scale (NRS) for Assessment of Pericarditis Pain ......... 85 
 
List of In-text Tables 
Table 1: 
Schedule of Evaluations .................................................................................. 25 
 
List of In-text Figures 
Figure 1: 
Schematic of rilonacept (KPL-914) .................................................................. 37 
Figure 2: 
Overview of Trial Design................................................................................ 46 
Figure 3: 
11-point Numerical Rating Scale (NRS) for Assessment of Pericarditis Pain ......... 66 
 
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5 List of Abbreviations and Definition of Terms 
AcP 
accessory protein 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
BP 
blood pressure 
b.p.m. 
beats per minute 
BUN 
blood urea nitrogen 
CAPS 
Cryopyrin Associated Periodic Syndrome  
CDC 
Centers for Disease Control 
CHO 
Chinese hamster ovary 
CI 
confidence interval 
CRO 
contract research organization 
CRP 
C-reactive protein 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
CTAD 
citrate, theophylline, adenosine, dipyridamole 
EoT 
End-of-Trial 
EP 
Extension Period 
ESC 
European Society of Cardiology 
ESR 
erythrocyte sedimentation rate 
FCAS 
Familial Cold Auto-Inflammatory Syndrome 
GCP 
Good Clinical Practice 
GGT 
gamma glutamyltransferase 
HBcAb 
hepatitis B core antibody 
HBsAb  
hepatitis B surface antibody 
HBsAg 
hepatitis B surface antigen 
HCVAb 
hepatitis C virus antibody 
HIV 
human immunodeficiency virus 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IgG 
immunoglobulin G 
IL-1 
Interleukin-1 
IL-1RA 
IL-1 receptor antagonist 
IL-1RI 
IL-1 type I receptor 
IMP 
Investigational Medicinal Product 
IRB 
Institutional Review Board 
IV 
intravenous 
kDa 
kilo Dalton 
KPL-914 
Study Drug; nomenclature of rilonacept (ARCALYST®) in this protocol 
LDH 
lactate dehydrogenase 
MCH 
mean cell hemoglobin 
MCHC 
MCH concentration 
MCV 
mean cell volume  
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
magnetic resonance imaging 
mITT 
modified intent to treat 
MWS 
Muckle-Wells Syndrome 
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NRS 
Numerical Rating Scale 
NSAID 
nonsteroidal anti-inflammatory drugs 
PI 
Prescribing Information 
PP 
per protocol 
PPD 
purified protein derivative 
PPS 
post pericardiotomy syndrome 
PRO 
patient-reported outcome 
PT 
prothrombin 
PTT 
prothrombin time 
QoL 
quality of life 
RBC 
red blood cell 
RIP 
recurrent idiopathic pericarditis 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SC 
subcutaneous 
SCR 
Safety Review Committee 
SCV 
screening visit 
SD 
standard deviation 
SOP 
standard operating procedure 
SRC 
Safety Review Committee 
SUSAR 
serious and unexpected and related adverse reaction 
TB 
tuberculosis 
 
 
TNF 
tumor necrosis factor 
US 
United States of America 
WBC 
white blood cells 
WHO 
World Health Organization 
WFI 
water for injection 
 
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6 Introduction 
Pericarditis accounts for 5% of emergency department visits for chest pain in the absence of myocardial 
infarction (Khandaker et al, 2010).  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).  Diagnosis is based on the presence of typical chest pain (improved by sitting up and leaning 
forward) along with fever, pericardial friction rub, electrocardiographic (ECG) changes, pericardial 
effusion, or elevated markers of inflammation (white blood cell [WBC] count, C-reactive protein [CRP], or 
erythrocyte sedimentation rate [ESR]) (Imazio et al, 2014).  The European Society of Cardiology (ESC) 
Guidelines for the Diagnosis and Management of Pericardial Diseases define a pericarditis episode as the 
presence of at least 2 of the 4 following criteria: pericarditic chest pain, pericardial rub, new widespread ST-
elevation or PR depression on ECG, and pericardial effusion (new or worsening).  Elevations of 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 a common complication of acute pericarditis and affects 20–30% of patients 
(Imazio, 2014).  It is characterized by the recurrence of signs and symptoms of pericarditis after a symptom-
free interval of at least 4-6 weeks (Adler et al, 2015).  The underlying pathogenesis of recurrent idiopathic 
pericarditis (RIP) remains unclear, although immune-mediated mechanisms are believed to play a key role 
in the pathogenesis (Imazio et al, 2005).  A growing body of evidence suggests that these immune responses 
consist of both pathogenic autoimmune and auto-inflammatory processes (Cantarini et al, 2015; Doria et al, 
2012).  The presence of pro-inflammatory cytokines in the pericardial fluid of RIP patients lends direct 
support to both an autoimmune and/or auto-inflammatory etiopathogenesis (Pankuwait et al, 2000). 
Currently available treatments for RIP include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, 
and glucocorticoids (Lilly, 2013).  Aspirin and other NSAIDs are the first-line approach.  Because high 
doses are often required, consideration should be given to gastric protection therapy.  Colchicine is another 
mainstay therapy for RIP and is commonly used with NSAIDs, but a subset of patients has refractory 
symptoms and significant gastrointestinal side effects, including severe diarrhea, leading to discontinuation 
for intolerability.  Glucocorticoids should be prescribed only to patients with idiopathic pericarditis who are 
refractory or intolerant to treatment with NSAIDs plus colchicine, because of the side effects associated 
with long-term corticosteroid therapy and because of a high rate of relapse when the corticosteroid is tapered 
or stopped (Maisch et al, 2004; Imazio, 2005; Lotrionte et al, 2010), particularly in the absence of colchicine 
treatment.  Patients with refractory symptoms can be particularly challenging to manage, and multiple 
immunosuppressive medications have been used without consistent benefit (Baskar et al, 2016). In addition, 
a subset of corticosteroid dependent RIP subjects are also in need for new treatment options due to the side 
effects of high dose and/or long term corticosteroid use including osteoporosis, diabetes, weight gain and 
increased risk for infections. 
Post-pericardiotomy syndrome (PPS) is an inflammatory syndrome involving pericardium which occurs in 
a subgroup of patients who have undergone cardiothoracic surgery.  It is reported in approximately 9% of 
adult patients (Lehto el al 2015), and more commonly in pediatric/adolescent population where up to 28% 
of patients undergoing surgical closure of atrial septal defect were reported to develop PPS (Hechching et 
al, 2015). 
 PPS is characterized by fever, pericardial or pleuritic pain, pleural effusion or pericardial effusion with 
elevated serum CRP. It is associated with significant morbidity, and the leading complications include 
tamponade and constrictive pericarditis. Aspirin, NSAIDs, and colchicine are the mainstay of the current 
treatment for PPS. Although corticosteroids are used for refractory cases of PPS, they are associated with 
significant side effects when used for long-term treatment of this disease. Similar to RIP, there is an unmet 
need for new therapies, especially for the patients experiencing recurrent PPS episodes despite currently 
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Rilonacept was developed by Regeneron Pharmaceuticals, Inc. and is approved with the tradename 
ARCALYST® in the US for the treatment of Cryopyrin Associated Periodic Syndrome (CAPS), including 
Familial Cold Auto-Inflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and 
children 12 and older.   
Rilonacept is prepared as a lyophilized formulation containing histidine, polyethylene glycol 3350, glycine, 
arginine, and sucrose at pH 6.5.  For subcutaneous (SC) administration, rilonacept is manufactured in a 
dosage form containing 160 mg per vial.  The lyophilized powder is reconstituted with 2.3 mL of sterile 
Water for Injection (WFI) and drug is delivered in 2 mL at a concentration of 80 mg/mL.  Clinical dosing 
(e.g., in CAPS) initiates with a loading dose of 320 mg SC followed by 160 mg administered SC weekly.  
A lower dose of 80 mg weekly (initiated with a 160 mg loading dose) was also tested in Phase 3 clinical 
trials in gout. 
For a detailed review of the available rilonacept data, please refer to the Investigator Brochure and the 
ARCALYST® package insert.  
Kiniksa Pharmaceuticals Ltd. (Kiniksa) is now developing rilonacept for the treatment of RIP (Rilonacept 
will be referred to as KPL-914 in this investigational study protocol).  In this first pilot study in subjects 
with RIP, improvement of pericarditis symptomatology with KPL-914 administration as well as the safety 
and dose relationships will be assessed.  Commercially-available rilonacept (ARCALYST®) will be used in 
the study. 
The nonclinical development program for rilonacept (ARCALYST®) demonstrated biological activity and 
adequate safety across toxicity studies (Appendix 2: ARCALYST® Prescribing Information). 
The most common adverse reactions reported by patients with CAPS treated with ARCALYST® are 
injection-site reactions and upper respiratory tract infections.  Hypersensitivity reactions associated with 
rilonacept administration have been rare.  
Refer to the ARCALYST® PI for Important Safety Information regarding rilonacept (Appendix 2: 
ARCALYST® Prescribing Information).  
Based on its IL-1-antagonistic properties, its weekly-dosing pharmacokinetics, and its well-understood 
safety profile as shown in patients with CAPS, rilonacept (KPL-914) is a promising candidate for the 
treatment of RIP.  
 
7 Study Objectives 
The study is comprised of 5 Parts. 
• 
Part 1 enrolls symptomatic subjects with recurrent idiopathic pericarditis (RIP) with an elevated 
marker of systemic inflammation (C-reactive protein [CRP] > 1mg/dL). 
• 
Part 2 enrolls symptomatic subjects with RIP with CRP ≤1 mg/dL which, in the opinion of the 
investigator, can be attributed to concomitant medications (e.g., corticosteroids) and with 
pericardial inflammation present on cardiac magnetic resonance imaging (MRI) confirmed by the 
imaging core lab. 
• 
Part 3 enrolls subjects with corticosteroid-dependent RIP not experiencing symptoms which 
would meet the diagnostic criteria for a flare of pericarditis. 
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• 
Part 4 enrolls symptomatic subjects with recurrent post pericardiotomy syndrome (PPS) with an 
elevated marker of systemic inflammation (CRP > 1mg/dL). 
• 
Part 5 enrolls subjects with corticosteroid-dependent recurrent PPS not experiencing symptoms 
which would meet the diagnostic criteria for a flare of pericarditis. 
 
7.1 
Part 1 
Primary Objective: 
To collect inter- and intra-subject variability data on CRP measurements and the 11-point NRS instrument 
for assessment of pericardial pain in subjects with RIP both at baseline and on treatment with KPL-914 in 
order to inform power calculations for future trials in pericarditis. 
 
Secondary Objectives: 
To explore the time course to improvement of pericarditis parameters in symptomatic subjects with RIP 
treated with KPL-914. 
To evaluate the effect of KPL-914 on pericardial inflammation based on cardiac MRI. 
To evaluate the safety of KPL-914 in symptomatic subjects with RIP. 
 
7.2 
Part 2 
Primary Objective: 
To collect inter- and intra-subject variability data on CRP measurements and the 11-point NRS instrument 
for assessment of pericardial pain in subjects with RIP both at baseline and on treatment with KPL-914 in 
order to inform power calculations for future trials in pericarditis. 
 
Secondary Objectives: 
To explore the time course to improvement of pericarditis parameters in symptomatic subjects with RIP 
treated with KPL-914 
To evaluate the effect of KPL-914 on pericardial inflammation based on cardiac MRI. 
To evaluate the safety of KPL-914 in symptomatic subjects with RIP. 
 
7.3 
Part 3 
Primary Objective: 
To evaluate feasibility of weaning from corticosteroids while receiving KPL-914 in subjects with 
corticosteroid-dependent RIP. 
 
Secondary Objectives: 
To evaluate the effect of KPL-914 on pericardial inflammation based on cardiac MRI. 
To evaluate the safety of KPL-914 in subjects with corticosteroid-dependent RIP. 
 
7.4 
Part 4: 
Primary Objective: 
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To collect inter- and intra-subject variability data on CRP measurements and the 11-point NRS instrument 
for assessment of pericardial pain in subjects with symptomatic recurrent PPS both at baseline and on 
treatment with KPL-914 in order to inform power calculations for future trials in pericarditis. 
 
Secondary Objectives: 
To explore the time course to improvement of pericarditis parameters in symptomatic subjects with 
recurrent PPS treated with KPL-914 
To evaluate the effect of KPL-914 on pericardial inflammation based on cardiac MRI. 
To evaluate the safety of KPL-914 in symptomatic subjects with recurrent PPS. 
 
7.5 
Part 5: 
Primary Objective: 
To evaluate feasibility of weaning from corticosteroids while receiving KPL-914 in subjects with 
corticosteroid-dependent recurrent PPS. 
 
Secondary Objectives: 
To evaluate the effect of KPL-914 on pericardial inflammation based on cardiac MRI. 
To evaluate the safety of KPL-914 in subjects with corticosteroid-dependent recurrent PPS. 
 
 
 
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8 Investigational Plan 
8.1 
Overall Study Design and Plan 
This is an open-label single-active-arm pilot study to explore clinical and biochemical endpoints of 
improvement of pericarditis symptomatology and to collect inter- and intra-subject variability data on both 
at-baseline and on-treatment parameters. This study consists of 5 distinct Parts, and all subjects will be 
treated with once-weekly subcutaneously (SC)-administered injections of KPL-914.   
Enrollment into Part 1: 
Subjects identified for participation in Part 1 of this trial will present during a symptomatic episode of 
RIP, having previously experienced a first (index) episode of acute pericarditis followed by at least 1 
recurrent episode before the current enrollment-qualifying episode, using the 2015 European Society of 
Cardiology (ESC) Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 2015) 
as a frame of reference: 
- 
The index episode of acute pericarditis would have been characterized by an inflammatory 
pericardial syndrome with at least 2 of the 4 following criteria: pericarditic chest pain, pericardial 
rub, new widespread ST-segment elevation or PR-segment depression on electrocardiogram (ECG), 
and pericardial effusion (new or worsening).  Additional supportive findings would have included 
elevations of markers of inflammation (i.e., CRP, ESR, or WBC count) or evidence of pericardial 
inflammation by an imaging technique (e.g., magnetic resonance imaging [MRI]).   
- 
Recurrence of RIP would have been characterized as a subsequent episode of pericarditis occurring 
after a symptom-free interval of 4-6 weeks or longer.   
For the purposes of this study, the Investigator will determine, based on his/her judgement of the available 
data, if a subject has met these criteria for having experienced a first (index) episode of acute pericarditis 
followed by at least 1 recurrent episode of pericarditis prior to the current enrollment-qualifying 
episode of RIP and will record the criteria supporting this diagnosis in the electronic case report form 
(eCRF). 
Subjects with symptomatic RIP meeting the above diagnostic criteria may be enrolled into Part 1 only if 
the CRP value at screening is > 1 mg/dL. 
 
Enrollment into Part 2: 
Subjects identified for participation in Part 2 of this trial will present during a symptomatic episode of 
RIP, having previously experienced a first (index) episode of acute pericarditis followed by at least 1 
recurrent episode before the current enrollment-qualifying episode, using the 2015 European Society 
of Cardiology (ESC) Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 
2015) as a frame of reference: 
- 
The index episode of acute pericarditis would have been characterized by an inflammatory 
pericardial syndrome with at least 2 of the 4 following criteria: pericarditic chest pain, pericardial 
rub, new widespread ST-segment elevation or PR-segment depression on electrocardiogram (ECG), 
and pericardial effusion (new or worsening).  Additional supportive findings would have included 
elevations of markers of inflammation (i.e., CRP, ESR, or WBC count) or evidence of pericardial 
inflammation by an imaging technique (e.g., MRI).   
- 
Recurrence of RIP would have been characterized as a subsequent episode of pericarditis occurring 
after a symptom-free interval of 4-6 weeks or longer.   
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For the purposes of this study, the Investigator will determine, based on his/her judgement of the available 
data, if a subject has met these criteria for having previously experienced a first (index) episode of acute 
pericarditis followed by at least 1 recurrent episode of pericarditis prior to the current enrollment-
qualifying episode of RIP and will record the criteria supporting this diagnosis in the eCRF. 
 
Subjects with symptomatic RIP meeting the above diagnostic criteria but without an elevated CRP level 
(i.e., ≤1mg/dl) at screening may be enrolled into Part 2 only if, in the opinion of the investigator and in 
consultation with the Sponsor, the low CRP value can be attributed to concomitant medications (e.g., 
corticosteroids) AND if there is evidence of pericardial inflammation by cardiac MRI which has been 
confirmed by the MRI Core Laboratory. 
 
Enrollment into Part 3: 
Subjects identified for participation in Part 3 in this trial will present with corticosteroid-dependent RIP, 
having previously experienced a first (index) episode of acute pericarditis followed by at least 2 
recurrent episodes, using the 2015 European Society of Cardiology (ESC) Guidelines for the Diagnosis 
and Management of Pericardial Diseases (Adler et al, 2015) as a frame of reference: 
- 
The index episode of acute pericarditis would have been characterized by an inflammatory 
pericardial syndrome with at least 2 of the 4 following criteria: pericarditic chest pain, pericardial 
rub, new widespread ST-segment elevation or PR-segment depression on electrocardiogram (ECG), 
and pericardial effusion (new or worsening).  Additional supportive findings would have included 
elevations of markers of inflammation (i.e., CRP, ESR, or WBC count) or evidence of pericardial 
inflammation by an imaging technique (e.g., MRI).   
- 
Recurrence of RIP would have been characterized as a subsequent episode of pericarditis occurring 
after a symptom-free interval of 4-6 weeks or longer.   
 
For the purposes of this study, the Investigator will determine, based on his/her judgement of the available 
data, if a subject has met these criteria for having previously experienced a first (index) episode of acute 
pericarditis followed by at least 2 recurrent episodes of pericarditis and will record the criteria 
supporting this diagnosis in the eCRF. 
 
Subjects who are taking corticosteroids for their RIP and who are not currently experiencing symptoms 
which, in the opinion of the Investigator, would meet the above diagnostic criteria for a flare may be 
enrolled into Part 3 only if, in the opinion of the Investigator and in consultation with the Sponsor, they 
are considered to be “corticosteroid- dependent” (i.e.; the signs and symptoms of pericarditis would 
return if the corticosteroids were withdrawn). 
 
Enrollment into Part 4: 
Subjects identified for participation in Part 4 in this trial will present during a symptomatic episode of 
recurrent PPS, having previously experienced a first (index) episode of acute PPS followed by at least 1 
recurrent episode of PPS before the current enrollment-qualifying episode, using the 2015 European 
Society of Cardiology (ESC) Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler 
et al, 2015) as a frame of reference: 
- 
The index episode of acute pericarditis would have been characterized by an inflammatory 
pericardial syndrome with at least 2 of the following 5 clinical findings after cardiac surgery: fever 
without alternative causes, pericardial chest pain, pericardial rub, evidence for pericardial effusion, or 
elevated CRP.  
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- 
Recurrence of PPS would have been characterized as a subsequent episode of pericarditis occurring 
after a symptom-free interval of 4-6 weeks or longer.   
 
For the purposes of this study, the Investigator will determine, based on his/her judgement of the available 
data, if a subject has met these criteria for having previously experienced a first (index) episode of acute 
PPS followed by at least 1 recurrent episode of PPS prior to the current enrollment-qualifying episode 
of recurrent PPS and will record the criteria supporting this diagnosis in the eCRF. 
 
In addition to meeting the above criteria for PPS, all subjects enrolled in Part 4 must have a CRP value > 
1 mg/dL at screening. 
 
Enrollment into Part 5: 
Subjects identified for participation in Part 5 in this trial will present with corticosteroid-dependent 
recurrent PPS, having previously experienced a first (index) episode of acute PPS followed by at least 2 
recurrent episodes, using the 2015 European Society of Cardiology (ESC) Guidelines for the Diagnosis 
and Management of Pericardial Diseases (Adler et al, 2015) as a frame of reference: 
- 
The index episode of acute pericarditis would have been characterized by an inflammatory 
pericardial syndrome with at least 2 of the following 5 clinical findings after cardiac surgery: fever 
without alternative causes, pericardial chest pain, pericardial rub, evidence for pericardial effusion, or 
elevated CRP.  
- 
Recurrence of PPS would have been characterized as a subsequent episode of pericarditis occurring 
after a symptom-free interval of 4-6 weeks or longer.   
 
For the purposes of this study, the Investigator will determine, based on his/her judgement of the available 
data, if a subject has met these criteria for having previously experienced a first (index) episode of acute 
PPS followed by at least 2 recurrent episodes of PPS and will record the criteria supporting this 
diagnosis in the eCRF. 
 
Subjects who are taking corticosteroids for the recurrent PPS and who are not currently experiencing 
symptoms which, in the opinion of the Investigator, would meet the above diagnostic criteria for a flare 
may be enrolled into Part 5 only if, in the opinion of the Investigator and in consultation with the Sponsor, 
they are considered to be “corticosteroid- dependent” (i.e.; the signs and symptoms of pericarditis would 
return if the corticosteroids were withdrawn). 
 
Enrollment Process for All Parts: 
Prior to enrollment, potential subjects may enter an optional Prescreening Period, after signing a 
Prescreening ICF (or informed assent form, if applicable) to confirm the diagnostic workup and to allow 
monitoring for symptoms and inflammatory markers (CRP, ESR, etc) while concomitant medications for 
pericarditis treatment may be managed by the Investigator or their clinician according to standard of care. 
 
Subjects included in Parts 1, 2 and 4 may be receiving concomitant nonsteroidal anti-inflammatory drugs 
(NSAIDs), and/or colchicine, and/or oral corticosteroid treatment in any combination, provided the dosages 
of these medications have been stable for at least 7 days, although stable doses for a shorter period will be 
acceptable if in the opinion of the Investigator, in consultation with the Sponsor, a shorter period of stability 
is not anticipated to alter the baseline CRP values.  
Subjects in Parts 3 and 5 must be receiving corticosteroids at the time of enrollment. 
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Baseline therapy and disease characteristics will be determined during a Screening Period of up to 72 hours, 
as needed, to confirm study eligibility.  At the SCV1, baseline subject and disease characteristics will be 
determined and captured in the eCRF.  At Screening Visit 2 (SCV2) during the 24 - 72 hour period before 
subjects advance to the Treatment Period of the study, additional laboratory samples may be drawn to 
provide additional baseline reference data. Under special circumstances, the Investigator, in consultation 
with the Sponsor, can combine SCV1 and SCV2, and the subject can proceed directly to the Day 0 dosing 
visit. 
After having met all the entry criteria during the Screening Period, the adult subjects (18 years or older) 
entering the Treatment Period will receive a loading dose of 320 mg KPL-914 (2 x 160 mg) administered 
SC on Day 0, then 160 mg SC weekly for 5 additional doses. Subjects aged 6 years to <18 years will 
receive a loading dose of 4.4 mg/kg KPL-914 (2x 2.2 mg/kg; maximum total 320 mg) administered SC on 
Day 0, then 2.2 mg/kg (maximum 160 mg) administered SC weekly for 5 additional doses. 
 
The first Study Drug dose on Day 0 will be administered at the Study Site/Clinic (Visit 1).  Subsequent 
weekly Study Drug doses from Weeks 2 to 5 will be self-administered by the subject or will administered 
to the subject by an adequately trained caregiver as an outpatient SC administration. Study center staff or a 
visiting study nurse will assess and record compliance with Study Drug administration at the subject’s home 
as well as provide guidance and training on Study Drug administration as needed. At Week 6/End of Trial, 
Study Drug may be administered at home or other non-clinic location or administered at the study site.  
Weekly assessments of safety and treatment response, including administration of the 11-point NRS 
instrument to assess pericardial pain, will be done at the Study Site/Clinic at Visit 1 (Day 0) and Visit 7 
(Week 6/End-of-Trial), and via Investigator (or designee) phone calls/ virtual visits on Day 3 and at Weeks 
2 to 5 (Visits 2 to 5). Weekly outpatient blood samples for central laboratory testing will be collected at the 
Study Site/Clinic, or at a qualified laboratory site in the vicinity of the subject, or by a visiting study nurse. 
Investigators are encouraged to schedule subjects at the Study Site/Clinic for an in-person Interval 
Evaluation Visit during approximately Weeks 3-4 to assist the Investigator in the clinical management of 
the subject.  During this visit a full assessment including physical examination, vital signs, ECG, 
echocardiogram, and laboratory testing can be performed as well as the recording of adverse events (AEs) 
and other study related assessments as needed.   
At any time point during the Treatment Period, subjects reporting worsening of pericarditis symptoms or 
AEs may be brought into the Study Site/Clinic at the discretion of the Investigator for an Unscheduled Visit, 
in which select or comprehensive clinical assessments can be performed.  Any subject who is determined 
by the Investigator as not responding to treatment (e.g., no reduction in pericardial pain compared to 
baseline, no decrease in CRP levels [if applicable], etc.) and who is therefore considered by the Investigator 
to be a “Treatment Failure” may be withdrawn from further Study Drug treatment at the discretion of the 
Investigator and may receive rescue therapy for their pericarditis according to standard of care as per 
Investigator decision; these subjects will be followed for safety for the remainder of the 6-week Treatment 
Period.  Subjects identified as “Treatment Failures” may be replaced at the discretion of the Sponsor in order 
to provide an adequate sampling of subjects completing the active Treatment Period. 
Subjects participating for the complete length of the active study Treatment Period will receive a total of 6 
doses of KPL-914.  For the duration of the Treatment Period, concomitant NSAIDs and/or colchicine and/or 
corticosteroids, if present, should be continued at pre-study dose levels until after the 6-dose Study Drug 
Treatment Period has concluded; however, should the Investigator determine that a reduction/tapering of 
the NSAID, colchicine, and/or corticosteroid dose is medically indicated, the NSAID, colchicine, and/or 
corticosteroid dose can be down-titrated in consultation with the Sponsor, and the modification of dose 
should be recorded in the source records and the eCRF.  
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Opioid analgesics, non-narcotic analgesics (e.g., tramadol), and acetaminophen are allowed as rescue 
medication for ancillary pain control on an as-needed basis throughout the Treatment Period.  Although it 
is recommended that NSAID dose levels (if present) should remain constant during the active Treatment 
Period, the concomitant NSAID dose may be temporarily increased (or an NSAID initiated) for ancillary 
pain control if deemed necessary by the Investigator, after consultation with the Sponsor. Any rescue 
medication use must be recorded in source records, eCRF and medication diary.  
At the discretion of the Investigator, “Treatment Responders” will be offered participation in an optional 
18-week Extension Period (EP), in which weekly open-label KPL-914 can be continued at the same dose as 
in the Treatment Period for a total duration of Study Drug treatment of up to 24 weeks. 
Treatment response will be defined by the Investigator: 
• 
Part 1: A clinically significant reduction in pericardial pain using the 11-point NRS, normal or 
near normal CRP levels, and/or absent or decreasing echocardiographic effusion at the End-of-
Trial Visit. 
• 
Part 2: A clinically significant reduction in pericardial pain using the 11-point NRS, normal or 
near normal levels CRP, and/or absent or decreasing echocardiographic effusion at the End-of-
Trial Visit 
• 
Part 3: Absence of pericarditis flare and feasibility to taper corticosteroids.  
• 
Part 4: A clinically significant reduction in pericardial pain using the 11-point NRS, normal or 
near normal CRP levels, and/or absent or decreasing echocardiographic effusion at the End-of-
Trial Visit 
• 
Part 5: Absence of pericarditis flare and feasibility to taper corticosteroids.  
 
Weekly Study Drug administrations during the EP are by self-administration or by an adequately trained 
caregiver, and study nurse visits to the subject’s home as well as Investigator (or designee) telephone 
calls/virtual visits are to continue on a monthly basis. 
During the EP, the Investigator is encouraged to wean concomitant NSAIDs and/or colchicine, and/or 
corticosteroids. It is encouraged that NSAIDs and colchicine be tapered and withdrawn within 15 days after 
entry into the EP. It is encouraged that corticosteroids be progressively taped (e.g., by 5 mg prednisone or 
equivalent every week in adults or 0.2mg/kg every week in subjects <18yo) and discontinued within 6 weeks 
after entering the EP (i.e., by Study Week 12) unless in the opinion of the Investigator, a different 
corticosteroid weaning schedule is required based on subject’s clinical status. All medication changes must 
be recorded in source records and the eCRF. Investigators are encouraged to invite subjects to the Study 
Site/Clinic for an in-person Interval Evaluation Visit between Weeks 15 to 20 (8 to 13 weeks after the Visit 
7/End of Trial Visit) to assist the Investigator in the clinical management of the subject.  During this visit a 
physical examination, vital signs, ECG, echocardiogram (ECHO), and laboratory testing can be performed 
at the discretion of the Investigator. 
Available safety, tolerability, and efficacy data for each subject will be reviewed by the Investigator as part 
of ongoing subject management.  A Safety Review Committee (SRC) including selected Investigator(s) and 
Sponsor representatives will review on a monthly basis (at a minimum) all available data for all subjects, 
considering trends across each subject and each Part.  
Given the following occurrences, dosing may be halted or reduced in any Part of the study, in accordance 
with an SRC recommendation, confirmed by the Sponsor: 
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- 
One or more subjects experience a serious and unexpected adverse event that is considered by the 
Investigator to be related to Study Drug (SUSAR), or 2 or more subjects experience similar severe 
(non-serious) and unexpected AEs that are considered by the Investigator to be related to Study 
Drug. 
After an initial group of subjects has been treated, depending on the safety profile observed as well as the 
magnitude and speed of treatment response (e.g., if an informative number of subjects achieve treatment 
response early in the Treatment Period), the Sponsor in collaboration with the Investigators may elect to 
decrease the KPL-914 dose administered to a subsequent consecutive group of subjects (in any Part of the 
Study): the adult subjects (18 years or older) entering the Treatment Period will receive a loading dose of 
160 mg KPL-914 (2 x 80mg) SC on Day 0, then 80 mg administered SC weekly for 5 additional doses. 
Subjects aged 6 years to <18 years will receive a loading dose of 2.2 mg/kg KPL-914 (2 x 1.1 mg/kg; 
maximum total 160 mg) administered SC on Day 0, then 1.1 mg/kg (maximum 80 mg) administered SC 
weekly for 5 additional doses, in order to explore efficacy at a lower dose. 
Depending on treatment response observed with the 80 mg dose (or 1.1 mg/kg in subjects 6 years to 
<18years old), the weekly dose administered to either these subjects or subsequent subjects may be 
changed back to 160 mg (or 2.2 mg/kg in subjects 6 years to <18 years old) by the Investigator in 
collaboration with the Sponsor. For any given subject, the KPL-914 dose level received at the end of the 
Treatment Period should be continued into the EP (if administration is continued); however, a change in 
the KPL-914 dose level during the EP for any individual subject can be made at the discretion of the 
Investigator in consultation with the Sponsor, and the modification of dose should be recorded in the 
source records and the eCRF. 
During the Screening and Treatment Periods, subjects will enter information concerning the use of 
pericarditis and rescue (pain) medication into a medication diary.  Such information will be entered by the 
subject immediately after dosing of study drug. 
 
Figure 2: 
Overview of Trial Design 
 
 
The study will be conducted in compliance with Good Clinical Practice regulations and other regulatory 
requirements.  
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8.3.2 
Inclusion Criteria 
Inclusion Criteria for All Parts 
To be eligible to participate in the trial, a subject must meet all of the following criteria: 
1. Has given consent (or assent, if applicable) and signed an Informed Consent Form (ICF) (or informed 
assent form, if applicable). 
2. Male or female, of any ethnic origin. 
3. 6 to 75 years of age, inclusive. 
4. If used, has received NSAIDs, and/or colchicine and/or corticosteroids (in any combination) at 
stable dose levels for at least 7 days prior to Study Drug dosing (although stable doses for a 
shorter period will be acceptable if, in the opinion of the Investigator in consultation with the 
Sponsor, a shorter period of stability is not anticipated to alter the baseline CRP values) and is 
anticipated to continue these concomitant medications at these dose levels for the duration of the 
active Treatment Period.   
5. If female of child-bearing potential, must be nonpregnant and nonlactating and must agree to use an 
effective method of contraception, e.g., hormonal contraception or double-barrier birth control.  
6. Is able to adequately maintain a medication diary. 
7. Agrees to refrain from making any new, major life-style changes that may affect pericarditis 
symptoms (e.g., starting a new diet or change in exercise pattern) from the time of signature of 
the ICF to the End-of-Trial Visit (Week 6). 
 
Inclusion Criteria for Part 1: 
8. Has a diagnosis of RIP based on the judgement of the Investigator. 
9. Has previously had an index (first) episode of pericarditis which, in the judgement of the 
Investigator based on the available data, met the criteria for an acute pericarditis event, using the 
2015 ESC Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 
2015) as a frame of reference --  i.e., met at least 2 of the 4 following criteria: pericarditic chest 
pain, pericardial rub, new widespread ST-segment elevation or PR-segment depression on ECG, 
and pericardial effusion (new or worsening).  Additional supportive findings could include 
elevations of markers of inflammation (i.e., CRP, ESR or WBC count) or evidence of pericardial 
inflammation by an imaging technique (e.g., MRI). 
10. Has had at least one prior recurrent episode of pericarditis, in the judgement of the 
Investigator, based upon the available diagnostic information. 
11. Has an ongoing symptomatic episode of pericarditis at the time of study enrollment in the 
judgement of the Investigator, based upon the available diagnostic information. 
12. Has an elevated CRP value (i.e., >1 mg/dL) at the time of Screening. 
 
Inclusion Criteria for Part 2: 
13. Has a diagnosis of RIP based on the judgement of the Investigator. 
14. Has previously had an index (first) episode of pericarditis which, in the judgement of the 
Investigator based on the available data, met the criteria for an acute pericarditis event, using the 
2015 ESC Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 
2015) as a frame of reference --  i.e., met at least 2 of the 4 following criteria: pericarditic chest 
pain, pericardial rub, new widespread ST-segment elevation or PR-segment depression on ECG, 
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and pericardial effusion (new or worsening).  Additional supportive findings could include 
elevations of markers of inflammation (i.e., CRP, ESR or WBC count) or evidence of pericardial 
inflammation by an imaging technique (e.g., MRI). 
15. Has had at least one prior recurrent episode of pericarditis, in the judgement of the Investigator, 
based upon the available diagnostic information. 
16. Has an ongoing symptomatic episode of pericarditis at the time of study enrollment in the 
judgement of the Investigator, based upon the available diagnostic information. 
17. Has CRP value < 1 mg/dL at Screening, which in the opinion of the Investigator in consultation 
with the Sponsor, can be attributed to concomitant medications. 
18. Has evidence of pericardial inflammation by cardiac MRI which has been confirmed by the 
MRI imaging core lab. 
 
Inclusion Criteria for Part 3: 
19. Has a diagnosis of RIP based on the judgement of the Investigator. 
20. Has previously had an index (first) episode of pericarditis which, in the judgement of the 
Investigator based on the available data, met the criteria for an acute pericarditis event, using the 
2015 ESC Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 
2015) as a frame of reference --  i.e., met at least 2 of the 4 following criteria: pericarditic chest 
pain, pericardial rub, new widespread ST-segment elevation or PR-segment depression on ECG, 
and pericardial effusion (new or worsening).  Additional supportive findings could include 
elevations of markers of inflammation (i.e., CRP, ESR, or WBC count) or evidence of pericardial 
inflammation by an imaging technique (e.g., MRI). 
21. Has had at least two prior recurrent episodes of pericarditis, in the judgement of the 
Investigator, based upon the available diagnostic information. 
22. Is not currently (at Screening) experiencing symptoms which, in the judgment of the Investigator 
based on the available diagnostic information, would meet the diagnostic criteria for a flare of 
pericarditis. 
23. Is “corticosteroid-dependent,” in the judgement of the Investigator based on available data (i.e., 
the signs and symptoms of pericarditis would return if the corticosteroids were to be withdrawn). 
 
Inclusion Criteria for Part 4: 
24. Has a diagnosis of recurrent PPS based on the judgement of the Investigator. 
25. Has previously had an index (first) episode of PPS which, in the judgement of the Investigator 
based on the available data, met the criteria for an acute pericarditis event, using the 2015 ESC 
Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 2015) as a 
frame of reference,  i.e., met at least 2 of the 5 clinical findings after cardiac surgery: fever 
without alternative causes, pericardial chest pain, pericardial rub, evidence for pericardial 
effusion with elevated CRP  
26. Has had at least one prior recurrent episode of PPS, in the judgement of the Investigator, based 
upon the available diagnostic information. 
27. Has an ongoing symptomatic episode of recurrent PPS at the time of study enrollment in the 
judgement of the Investigator, based upon the available diagnostic information. 
28. Has an elevated CRP value (i.e., >1 mg/dL) at the time of Screening. 
 
Inclusion Criteria for Part 5: 
29. Has a diagnosis of recurrent PPS based on the judgement of the Investigator. 
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30. Has previously had an index (first) episode of PPS which, in the judgement of the Investigator 
based on the available data, met the criteria for an acute pericarditis event, using the 2015 ESC 
Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al, 2015) as a 
frame of reference,  i.e., met at least 2 of the 5 clinical findings after cardiac surgery: fever 
without alternative causes, pericardial chest pain, pericardial rub, evidence for pericardial 
effusion with elevated CRP  
31. Has had at least two prior recurrent episodes of PPS, in the judgement of the Investigator, 
based upon the available diagnostic information. 
32. Is not currently (at Screening) experiencing symptoms which, in the judgment of the Investigator 
based on the available diagnostic information, would meet the diagnostic criteria for a flare of 
pericarditis. 
33. Is “corticosteroid-dependent,” in the judgement of the Investigator based on the available data, 
(i.e., the signs and symptoms of pericarditis would return if the corticosteroids were to be 
withdrawn). 
8.3.3 
Exclusion Criteria 
Exclusion Criteria for All Parts 
A subject who meets any of the following criteria will not be eligible to participate in the trial: 
1.  
Has a diagnosis of pericarditis that was secondary to specific excluded etiologies, including 
tuberculous, neoplastic, or purulent etiologies, post-myocardial infarction (early or late), thoracic 
trauma, myocarditis, or systemic diseases including autoinflammatory diseases, autoimmune 
diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, etc.). 
2. Has a history of immunodepression, including a positive human immunodeficiency virus test result. 
3. Has received treatment within the 6-month period before dosing with any systemic 
immunosuppressants (other than, for example, corticosteroids or mycophenolate) which, in the 
opinion of the Investigator (in consultation with the Sponsor), may interfere with the study 
endpoints.  
4. Currently receiving other interleukin (IL)-1 or IL-6 blockers, janus-activating kinase (JAK) or tumor 
necrosis factor (TNF) inhibitors. 
5. Has a history of myeloproliferative disorder, demyelinating disease, or symptoms suggestive of 
multiple sclerosis. 
6. Female subject who is pregnant or lactating or who does not agree to use an effective method of 
contraception, e.g., hormonal contraception or double-barrier birth control. 
7. Has a history of active or latent treated tuberculosis (TB), or had a positive QuantiFERON (QFT-TB 
G In-Tube) test result, or a chest radiograph during the 3 months prior to Study Drug dosing 
suggestive of prior TB infection. A subject with a positive purified protein derivative (PPD) test 
result (≥5-mm induration) after the first attack of pericarditis is excluded unless he/she has had 
either a negative chest x-ray result or a negative QuantiFERON test result. 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, night sweats) upon review of medical history and/or 
physical exam.  Have recent close contact with a person with active TB.  
8. Chest radiograph (or historic results within 3 months of SCV1) that shows evidence of malignancy 
or any abnormalities suggestive of prior TB infection, including, but not limited to, apical scarring, 
apical fibrosis, or multiple calcified granulomata.  This does not include non-caseating granulomata. 
9. Has received immunization with a live (attenuated) vaccine within 12 weeks before the start of the 
study. 
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10. Has history of or positive or intermediate results for hepatitis B surface antigen (HBsAg), hepatitis 
B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at SCV1. 
11. Has an estimated glomerular filtration rate (eGFR) <30 mL/min.  
12. Has a history of malignancy of any organ system within the past 5 years (other than a successfully 
treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma 
in situ of the cervix). 
13. 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. 
14. Has had a serious infection, has been hospitalized for an infection, has been treated with oral 
antibiotics within 2 weeks, or has been treated with IV antibiotics for an infection within 2 months 
of first Study Drug administration.  
15. Has had an organ transplant.  
16. In the Investigator's judgement, has a history of alcoholism or drug/chemical abuse within 2 years 
prior to Study Drug administration. 
17. Has a drug screen positive for amphetamines, cocaine, or phencyclidine or positive alcohol test at 
SCV1.  Exceptions may be made if a subject is on an approved medication for a stable concomitant 
condition that explains the positive screen. 
18. Has taken commercially-available rilonacept (ARCALYST®) or participated in a rilonacept clinical 
study during the 90 days before SCV1.  Has used anakinra within 14 days (or 5 half-lives, 
whichever is longer) prior to Study Drug administration. Rilonacept and anakinra could not have 
been discontinued due to lack of efficacy or due to safety. 
19. Has a history of hypersensitivity to rilonacept or to any of the excipients contained in the Study 
Drug. 
20. Has received an investigational drug during the 30 days before SCV1 or is planning to receive an 
investigational drug (other than that administered during this trial) or use an investigational device 
at any time during the trial. 
21. In the Investigator's judgement, has any other medical condition that could adversely affect the 
subject's participation or interfere with study evaluations.  
22. Subject who, in the opinion of the Investigator, is not likely to be compliant with the study protocol. 
23. Subject who, in the opinion of the Investigator in consultation with the Sponsor, should not 
participate in this study. 
 
8.3.4 
Vaccination History and Immune status 
IL-1 blockade may interfere with immune response to infections. Therefore, the Investigator should review  
the subject's vaccination history relative to the current medical guidelines for vaccine use.  A recommended 
immunization schedule is available at the website of the Centers for Disease Control (CDC) 
(www.cdc.gov/vaccines/recs/scheduled/default.htm). 
It is recommended that, prior to or shortly after initiation of therapy with KPL-914, subjects be brought up 
to date with all vaccinations, as appropriate, including pneumococcal vaccine and inactivated influenza 
vaccine. In case a subject needs vaccination after initiation of KPL-914 treatment, vaccination with inactive 
vaccine(s) may be performed (e.g., at the Study Site/Clinic) after the 6-week active Treatment Period.  
However, to minimize the potential confounding of KPL-914-related Adverse Experience reporting at 
initiation of KPL-914 dosing or measurements of CRP during the treatment period, vaccination should not 
be performed within the first 6 weeks after initiation of KPL-914 administration.   
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It is recommended that all vaccinations be documented as up-to-date at or shortly after Visit 7, at which 
point subjects are being considered for longer-term treatment with KPL-914.  
Administration of KPL-914 is prohibited within 12 weeks of having received a live (attenuated) vaccine.  It 
is also possible that taking drugs that block IL-1 increases the risk of TB.  Healthcare providers should 
follow current CDC guidelines both to evaluate for and to treat possible latent TB infections before initiating 
therapy with KPL-914. 
8.3.5 
Removal of Subjects from Therapy or Assessments 
Subjects reporting worsening of pericarditis symptoms or AEs may be brought into the Study Site/Clinic at 
the discretion of the Investigator for an Unscheduled Visit at any time during the Treatment Period.  Any 
subject who is not responding to treatment (e.g., no reduction in pericardial pain compared to baseline, no 
decrease in CRP levels, etc.) and who is therefore considered by the Investigator to be a “Treatment Failure” 
may be withdrawn from further Study Drug treatment at the discretion of the Investigator and receive rescue 
therapy for their pericarditis according to standard of care as per Investigator decision; these subjects will 
be followed for safety for the remainder of the 6-week Treatment Period.  Subjects identified as “Treatment 
Failures” may be replaced at the discretion of the Sponsor in order to provide an adequate sampling of 
subjects completing the active Treatment Period. 
Safety, tolerability, and efficacy data for each subject will be reviewed by the Investigator on an ongoing 
basis as part of subject management.  An SRC including selected Investigator(s) and Sponsor representatives 
will review on a monthly basis (at a minimum) all available data for all subjects in all Parts, considering 
trends across each.  
Given the following occurrences, dosing may be halted or the dose reduced, in accordance with an SRC 
recommendation, confirmed by the Sponsor: 
• 
One or more subjects experience a serious and unexpected adverse event that is considered by the 
Investigator to be related to Study Drug (SUSAR), or 2 or more subjects experience similar severe 
(non-serious) and unexpected AEs that are considered by the Investigator to be related to Study 
Drug. 
In addition, subjects may stop study treatment or may be withdrawn from treatment for any of the following 
reasons: 
• 
Subject request.  Subjects are free to withdraw from the study at any time without providing 
reason(s) for withdrawal and without prejudice to further treatment 
• 
Use of non-permitted concurrent therapy 
• 
Non-compliance 
• 
Investigator request. 
Treatment Failures or subjects who are withdrawn from the study for safety reasons will be replaced at the 
discretion of the Sponsor.  Similarly, subjects who do not comply with the protocol or who withdraw from 
the study for other reasons can be replaced.  The reason(s) for withdrawal will be documented in the source 
records and the eCRF. 
Subjects withdrawing from the study during the Treatment Period will be asked to complete the End-of-
Trial evaluations to document the status of their pericarditis disease progression at the time of withdrawal 
from treatment.  Subjects will continue to be followed for vital status for the duration of intended treatment 
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to address informative censoring.  Subjects withdrawing from the study during the EP will be asked to 
complete the Final Visit evaluations. 
All reasonable efforts will be made to contact subjects who are lost to follow-up.   
The Sponsor has the right to terminate the study at any time in case of safety concerns (e.g., SUSARs) or if 
special circumstances concerning the Investigational Medicinal Product (IMP) 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. 
Pregnancy 
Pregnant or lactating female subjects are excluded from study enrollment.  While not explicitly stated in the 
rilonacept (ARCALYST®) PI (Appendix 2: ARCALYST® Prescribing Information), for the purposes of this 
experimental protocol, females of child-bearing potential (i.e., not postmenopausal and not sterilized) must 
use an active method of birth control during the course of the study, e.g., oral, implanted or injected 
contraceptive hormones, an intrauterine device, or a barrier method (e.g., diaphragm, condoms, 
spermicides).  
Subjects will be instructed that known or suspected pregnancy occurring during the study should be 
confirmed and reported to the Investigator without delay.  If pregnancy is confirmed, the Investigator must 
notify the Sponsor within 24 hours and the subject must not receive (additional) Study Drug and must be 
discharged from the study.  The subject must be asked regarding their willingness to complete the End-of-
Trial Visit. 
In the event that a subject is found to be pregnant after having received at least one Study Drug dose, the 
pregnancy will be followed to term and the status of mother and child will be reported to the Sponsor after 
delivery. 
Instances of perinatal death or congenital abnormality, if brought to the attention of the Investigator at any 
time after cessation of the study treatment, will be reported to the Sponsor within 24 hours. 
Full details will be recorded on the pregnancy form. 
8.4 
Investigational Medicinal Products 
8.4.1 
Investigational Medicinal Products Administered 
During the Treatment Period, KPL-914 will be administered as an initial loading dose of 320 mg SC, 
delivered as two subcutaneous injections of 160 mg SC each on Day 0, then 160 mg SC dosed once 
weekly for 5 subsequent weeks  (18 years or older).  Subjects aged 6 years to <18 years will receive an 
initial loading dose of 4.4 mg/kg, up to a maximum of 320 mg, delivered as two subcutaneous injections 
of 2.2 mg/kg each with a maximum single-injection volume of 2 mL. Dosing will continue with a once-
weekly injection of 2.2 mg/kg, up to a maximum of 160 mg, administered as a single subcutaneous 
injection of up to 2 mL as outpatient administration or by an adequately trained caregiver, for 5 
subsequent weeks. 
 
Subjects will receive a total of 6 doses of KPL-914 during the study active Treatment Period.  Subjects 
who are considered to be “Treatment Responders” will be offered, at the discretion of the Investigator, 
participation in an optional 18-week Extension Period (EP), in which weekly open-label KPL-914 can be 
continued for a total duration of KPL-914 treatment of up to 24 weeks. 
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Sites for SC 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. 
No placebo or active comparator drug will be used.  
8.4.2 
Identity of Investigational Medicinal Products 
KPL-914 (rilonacept/ARCALYST®) is prepared as a lyophilized formulation containing histidine, 
polyethylene glycol 3350, glycine, arginine, and sucrose at pH 6.5.  It 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 WFI is required prior to SC 
administration of the drug.  The reconstituted drug product is a viscous, clear, colorless to pale yellow, 
essentially free from particulates, 80-mg/mL solution. 
After the addition of preservative-free sterile WFI, the vial contents should be reconstituted by gently 
shaking the vial for approximately 1 minute and then allowing it to sit for 1 minute.  A volume of up to 2 
mL can be withdrawn, which is designed to deliver 160 mg for SC administration only. 
KPL-914 (rilonacept) will be provided by the Sponsor to the study sites and to the study subjects in its 
commercially-available formulation (ARCALYST®) as a lyophilized powder to be reconstituted for SC 
administration.  The sites will receive Study Drug for on-site administration at Study Site/Clinic visits. Drug 
will be disseminated to the trial subjects for outpatient self-administration according to a supply chain 
described in the Pharmacy Manual.   
The lyophilized Study Drug (KPL-914 also called rilonacept, US tradename: ARCALYST®) is to be stored 
refrigerated at 2° to 8°C (36° to 46°F) inside the original carton to protect it from light.  After reconstitution, 
KPL-914 may be kept at room temperature, should be protected from light, and should be used within 3 
hours of reconstitution.  Unused portions of KPL-914 product must not be injected.  All vials of used and 
unused Study Drug during the active Treatment Period must be returned to the clinical site for cataloguing 
and documentation of compliance.   
The Sponsor through Regeneron Pharmaceuticals, Inc. will ensure that the Study Drug and certificates of 
analysis are available before the start of the study and at all times during the study. 
ARCALYST® is a registered trademark of Regeneron Pharmaceuticals, Inc. 
8.4.3 
Method of Assigning Subjects to Treatment Groups 
Subjects who meet all the inclusion criteria in a specific Part and none of the exclusion criteria will enter 
the Treatment Period at Visit 1 (Day 0). 
Since this is an open-label, single-active-arm study, all subjects will receive KPL-914 active treatment.  
Assignment to treatment groups is not applicable. 
8.4.4 
Selection of Doses in the Study 
This protocol is a pilot study intended to evaluate the safety, efficacy, and dose response of KPL-914 in the 
treatment of patients with RIP. 
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8.4.7 
Prior and Concomitant Therapy 
Subjects included in Parts 1, 2 and 4 may be using NSAIDs, colchicine, and/or corticosteroids in any 
combination at the time of study enrollment, but the dose levels must be stable for have been stable for at 
least 7 days, although stable doses for shorter period will be acceptable if in the opinion of the Investigator, 
in consultation with the Sponsor, a shorter period of stability is not anticipated to alter the baseline CRP 
values.   
Subjects in Parts 3 and 5 must be receiving corticosteroids at the time of enrollment. 
For the duration of the Treatment Period, pericarditis medications (e.g., concomitant NSAIDs, colchicine 
and/or corticosteroids, if used) should be continued at pre-study dose levels until after the 6-dose Study 
Drug Treatment Period has concluded; however, should the Investigator determine that a reduction/tapering 
of the NSAID, colchicine, and/or corticosteroid dose is medically indicated, the NSAID, colchicine and/or 
corticosteroid dose can be down-titrated in consultation with the Sponsor, and the modification of dose 
should be recorded in the source records and the eCRF. 
Subjects who received, within the 6-month period before dosing, immunomodulatory therapy other than, 
for example, corticosteroids or mycophenolate, which in the opinion of the Investigator (in consultation 
with the Sponsor) may interfere with the study endpoints, or subjects who used commercially-available 
rilonacept (ARCALYST®) within 90 days before the Screening Visit are excluded from participation.  
Throughout the Treatment Period opioid analgesics, non-narcotic analgesics (e.g., tramadol), and 
acetaminophen are allowed as rescue medication for ancillary pain control on an as-needed basis.  Although 
it is recommended that NSAID dose levels (if present) should remain constant during the active Treatment 
Period, the concomitant NSAID dose may be temporarily increased (or an NSAID initiated) for ancillary 
pain control if deemed necessary by the Investigator, after consultation with the Sponsor.  Any rescue 
medication use must be recorded in source records, the medication diary and the eCRF. Other interleukin 
(IL)-1 or IL-6 blockers, janus-activating kinase (JAK) and tumor necrosis factor (TNF) inhibitors are 
prohibited for the duration of the study.  
Medical management of pericarditis during the EP is based on Investigator discretion. For example, 
Investigators may continue subjects on KPL-914 at the same dosage level, wean-off or discontinue Study 
Drug.  During the EP, the Investigator is encouraged to wean concomitant NSAIDs, and/or   colchicine, 
and/or corticosteroids.  It is encouraged that NSAIDs and colchicine be tapered and withdrawn within 15 
days after entry into the EP.  It is encouraged that corticosteroids be progressively tapered (e.g., by 5 mg 
prednisone or equivalent every week in adults or 0.2mg/kg every week in subjects <18yo) and 
discontinued within 6 weeks after entering to EP (i.e., by Study Week 12) unless in the opinion of 
Investigator, a different corticosteroid weaning schedule is required based on subject’s clinical status 
 
Other pericarditis medications may also be initiated at the discretion of the Investigator.  All changes to 
pericarditis-related medications should be captured in the source records and the eCRF. 
 
During the Screening and Treatment Periods, subjects will enter information concerning the use of 
pericarditis and rescue (pain) medication into a medication diary.  Such information will be entered by the 
subject on a real-time basis. 
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8.4.8 
Treatment Compliance 
Study Drug will be administered to the subject by the Investigator or qualified study center staff at the Study 
Site/Clinic Visit 1 (Day 0).  Subsequent weekly Study Drug doses from Weeks 2 to 5 will be self-
administered by the subject or an adequately trained caregiver as an outpatient SC administration. The study 
center staff or a visiting study nurse will assess and record compliance with Study Drug administration at 
the subject’s home as well as provide guidance and training on Study Drug administration as needed. At 
Week 6/End-of-Trial, Study Drug may be self-administered or administered at the study site. All medication 
use (for pericarditis and use of rescue [pain] medication) will be documented by the subject in the medication 
diary during the Treatment Period.  
All vials of used and unused Study Drug during the active Treatment Period and the EP must be retained by 
the Study Site/Clinic and the subject to allow for cataloguing and documentation of compliance. Subjects 
must return all used and unused medication to the Study Site/Clinic.  Drug accountability and documentation 
thereof is described in the Pharmacy Manual. 
Study Drug compliance by the subject will be monitored during the Treatment Period by phone calls/virtual 
visits (made by qualified site staff).  Subjects will be reminded of recording all pericarditis and rescue pain 
medication information in the medication diary.  The medication diary will be returned to the site by the 
subject and reviewed by the Investigator/qualified staff.  During the EP, Study Drug use will be documented 
during monthly phone calls/virtual visits or Study Site/Clinic visits. 
8.5 
Study Procedures 
All data of Study Site/Clinic visit assessments as well as Investigator (or designee) phone calls/virtual visits 
will be documented in source records and in the eCRF. 
8.5.1 
Prescreening Period 
Prior to enrollment, potential subjects may enter an optional Prescreening Period, after signing of a 
Prescreening ICF (or prescreening assent form, if applicable), to confirm the diagnostic workup and to 
allow monitoring for symptoms, inflammatory markers (CRP, ESR, etc) while concomitant pericarditis 
medications may be managed by the Investigator or their clinician per standard of care. 
 
The Prescreening Period starts with the signing of the Prescreening ICF (or prescreening assent form, if 
applicable), and lasts until the subject enters the Screening Period by signing the ICF for the full study or is 
withdrawn (see section 8.3.5).  
8.5.2 
Screening Period 
The Screening Period starts with the signature of the ICF (or informed assent form, if applicable), and may 
last for up to 3 days.  During this period, subject eligibility for entry into the Treatment Period will be 
determined.  A rheumatology consultation during the Screening Period is optional. 
At SCV1, baseline subject and disease characteristics will be determined.  At Screening Visit 2 [SCV2]), 
within the 24 – 72 hour period before subjects advance to the Treatment Period of the study, additional 
laboratory samples may be drawn to provide additional baseline reference data under special circumstances, 
the Investigator in consultation with the Sponsor, can combine SCV1 and SCV2. 
The end of the Screening Period may coincide with the start of the Treatment Period.   
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8.5.2.1 
Screening Visit 1 (SCV1) 
• At the SCV1, written informed consent (or assent, if applicable) will be obtained before any protocol-
specific assessments are made. 
• All subjects will be assessed for eligibility against the inclusion and exclusion criteria. 
• Demographic data, such as ethnic origin, date of birth and sex will be recorded. 
• The subject’s full medical history, including age at first attack, number of previous attacks, duration 
of attacks as well as concomitant illnesses/diseases will be documented. 
• Information related to concomitant medicine that subjects were taking during at least the 2 weeks 
prior to the visit will be captured. 
• A full physical examination will be performed, including assessment of pericardial rub. 
• Body weight and height will be assessed. 
• Vital signs will be obtained in the seated position and include oral temperature, respiratory rate, blood 
pressure, and pulse. 
• A pregnancy test (urine dip-stick) will be done. If the urine test is positive, additional Study 
Site/Clinic and/or central serum tests may be performed. 
• 12-lead ECG and full echocardiogram (ECHO) will be performed.  ECHO will include assessment 
of pericardial effusion.  The Study Site/Clinic readings at the time of the examination will be 
available to the Investigator for clinical decision-making. In addition, both the ECG and ECHO will 
be sent to a core laboratory. 
• A cardiac MRI may be performed (optional). If done, the images will be assessed by a central reader. 
The Study Site/Clinic reading at the time of the examination may be used by the Investigator for 
clinical decision-making. 
• Samples for laboratory tests will be collected. 
o Local Lab Assessments: 
 
Full hematology (including ESR), chemistry (including CRP), and urinalysis 
 
Serology (HCVAb, HBsAg, HBcAB, HBsAb and HIV)  
 
A QuantiFERON® test for tuberculosis (TB) can be performed (optional).  
o Screening for drugs of abuse and alcohol abuse will be performed on urine samples 
collected at this visit.  
o Central Laboratory Assessments: 
 
CRP/hsCRP  
• Samples for archive biomarker, pharmacokinetics (PK), and anti-rilonacept (anti-KPL-914) antibody 
testing will be collected, sent to the central laboratory, and stored for analysis. 
• A medication diary for documentation of pericarditis medication use and use of any rescue (pain) 
medication will be handed to the subject.  The study Investigator or designated personnel will 
instruct the subject about the use of the medication diary.  The subjects will be asked to complete 
entries immediately following administration. 
• The subjects will assess their pericardial pain based on a 11-point NRS. 
• The subject's global overall well-being will be assessed using a validated Quality of Life 
Questionnaire (Appendix 3). 
 
8.5.2.2 
Screening Visit 2 (SCV2) 
The end of the Screening Period (SCV2) coincides with the start of the Treatment Period (Day 0, Visit 1).  
All Screening assessments need to be completed prior to the first Study Drug administration.  
• SCV2 should take place when the laboratory test results from SCV1 are available. 
• Subjects will be reassessed for eligibility against the inclusion and exclusion criteria. 
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• Any changes in concomitant medications since SCV1 will be documented. 
• A full physical examination will be performed, including re-assessment of pericardial rub.  
• Vital signs will be measured.  
• 12-lead ECG will be performed.  The Study Site/Clinic reading at the time of the examination will be 
used by the Investigator for clinical decision-making. In addition, the ECG will be sent to a core 
laboratory for additional analysis. 
• Samples for laboratory tests will be collected. 
o Local Lab Assessments: 
 
Full chemistry (including CRP) panel only 
o Central Laboratory Assessments: 
 
CRP/hsCRP  
• Medication diary compliance will be assessed by the Investigator/designated personnel and the 
subject reminded on the diary use. 
• The subjects will assess their pericardial pain based on the 11-point NRS (Figure 3). 
 
When all screening procedures have been performed and the Investigator has confirmed the subject’s 
eligibility for the study, the Study Drug will be administered to the subject (see Study Site/Clinic Visit 1). 
 
8.5.3 
Treatment Period 
8.5.3.1 
Visit 1 (Study Site/Clinic) - Day 0 
Visit 1 will coincide with SCV2.  In case Visit 1 is separated from SCV2, SCV2 clinical laboratory blood 
sampling (including CRP), medication diary compliance verification and reminding, and subject NRS 
pericardial pain rating (see Figure 3) must be repeated prior to Study Drug dosing.  
• Sample for lipid panel to be sent to the Central Laboratory for analysis 
• Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody testing will be 
collected prior to Study Drug dosing, sent to the central laboratory, and stored for analysis.  
• The subject's global overall well-being will be assessed prior to Study Drug dosing using a validated 
Quality of Life Questionnaire (Appendix 3). 
• The initial dose of Study Drug will be administered at the Study Site/Clinic. 
• Subjects will be trained for outpatient Study Drug self-administration and reminded of completion of 
the daily medication diary. 
• Any AEs occurring during or after the subject receives the first dose of Study Drug will be captured. 
When all Visit 1 procedures have been performed, an appointment for the first weekly phone call/virtual 
visit will be scheduled. Study Drug for outpatient administration will be provided to the subjects according 
to a process laid out in the pharmacy manual. 
8.5.3.2 
Day 3 (Outpatient) 
• 
Day 3 will ± 1 day after Visit 1. 
• 
An Investigator (or designee) telephone call/virtual visit will occur to evaluate safety (AE 
evaluations) and patient-reported pericardial pain using a validated 11-point NRS instrument. 
 
8.5.3.3 
Visits 2 to 6 (Outpatient) - Weeks 2, 3, 4, 5, 6 
• Visits 2, 3, 4, 5, 6 will take place within intervals of 7 ± 1 days each after Visit 1. 
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• Subjects self-administer the Study Drug or be administered Study Drug by an adequately trained 
caregiver during Weeks 2 to 5. At Week 6/End-of-Trial, Study Drug may be self-administered or 
administered at the study site. 
•  Samples for laboratory tests will be collected. 
o Central Laboratory Assessments: 
 
CRP/hsCRP  
 
Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody 
testing will be collected (either by a visiting study nurse or at the Study Site or at a 
qualified local laboratory) and stored for analysis after shipment to the central 
laboratory.  
• After dosing at Week 3 and Week 6, a questionnaire to assess the dosing system will be completed 
by the subject and by the study center staff or visiting nurse observing the dosing 
• Any AEs that have occurred since the last contact will be assessed by non-leading questions as part 
of the weekly telephone call/virtual visit from the Study Site/Clinic.  
• Compliance with self-administration of drug, compliance with the medication diary, and compliance 
with laboratory blood sampling will be assessed as part of the weekly telephone call/virtual visit 
from the Study Site/Clinic. 
• Pericardial pain based on the 11-point NRS (Figure 3) will be assessed as part of the weekly telephone 
call/virtual visit from the Study Site/Clinic. 
Subjects withdrawing from the study any time during study weeks 2 to 6 will be asked to return to the Study 
Site/Clinic for the Visit 7/End-of-Trial visit assessments.  
8.5.3.4 
Interval Evaluation Visit (Study Site/Clinic) - Week 3-4 
An in-person Interval Evaluation Visit during approximately Weeks 3-4 of the Treatment Period is 
recommended to assist the Investigator in the clinical management of the subject. The visit can be held at 
the discretion of the Investigator. The Interval Evaluation Visit may also be used to review the vaccination 
status of a study subject. 
At the Interval Evaluation Visit, the following parameters will be assessed: 
• A full physical examination will be performed, including assessment of pericardial rub. 
• Vital signs will be measured.  
• A 12-lead ECG and a full ECHO will be performed.  The Study Site/Clinic readings at the time of 
the examination will be made available to the Investigator for clinical decision-making. In addition, 
both the ECG and ECHO will be sent to a core laboratory. 
• Changes in concomitant medication since the last Study Site/Clinic visit will be documented. 
• Samples for laboratory tests will be collected. 
o Local Lab Assessments: 
 
Full hematology (including ESR), chemistry (including CRP), and urinalysis 
o Central Laboratory Assessments: 
 
CRP/hsCRP  
 
Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody 
testing will be collected, sent to the central laboratory, and stored for analysis.  
• Any AEs that have occurred since the last visit (Study Site/Clinic or outpatient) will be documented.  
• Medication diary compliance will be assessed by the Investigator/designated personnel and the 
subject reminded on the diary use. 
• Pericardial pain based on the 11-point NRS (Figure 3) will be assessed. 
• The subject's global overall well-being will be assessed using a validated Quality of Life 
Questionnaire (Appendix 3). 
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8.5.3.5 
Unscheduled Visits (Study Site/Clinic) During the Treatment Period  
Subjects reporting worsening of pericarditis symptoms or AEs may be brought in at the discretion of the 
Investigator for an Unscheduled Visit at any time during the Treatment Period.  During the Unscheduled 
Visit, selected or comprehensive (see Interval Evaluation Visit) clinical and laboratory assessments may be 
performed.  
Any subject who is determined by the Investigator as not responding to treatment (e.g., no reduction in 
pericardial pain compared to baseline, no decrease in CRP levels, etc.) and who is therefore considered by 
the Investigator to be a “Treatment Failure” may be withdrawn from further Study Drug treatment at the 
discretion of the Investigator and receive rescue therapy for their pericarditis according to standard of care 
as per Investigator decision; these subjects will be followed for safety for the remainder of the 6-week 
Treatment Period.   
All study withdrawals must complete the Visit 7/End-of-trial Visit either at the Unscheduled Visit or at a 
separate Visit 7/End-of-trial Visit. 
8.5.3.6 
Visit 7/ End-of-Trial (Study Site/Clinic) - Week 6 
At Visit 7, “Treatment Responders” (defined by the Investigator as a clinically significant reduction in 
pericardial pain using the 11-point NRS, normal or near-normal CRP levels, and absent or decreasing 
echocardiographic effusion at the End-of-Trial Visit), will be offered participation in an optional 18-week 
EP, at the discretion of the Investigator. During the EP, weekly open-label KPL-914 can be continued at the 
same dose as in the Treatment Period for a total duration of Study Drug treatment of up to 24 weeks.   
• Visit 7 will take place during Week 6 (or as soon as possible after study withdrawal if a subject has 
discontinued from Study Drug therapy).  
• A full physical examination will be performed, including assessment of pericardial rub. 
• Vital signs will be measured.  
• A 12-lead ECG and a full ECHO will be performed.  The Study Site/Clinic readings at the time of 
the examination will be made available to the Investigator for clinical decision-making.  In addition, 
both the ECG and ECHO will be sent to a core laboratory. 
• Changes in concomitant medication since last Study Site visit will be documented. 
• Samples for laboratory tests will be collected. 
o Local Lab Assessments: 
 
Full hematology (including ESR), chemistry (including CRP), and urinalysis 
o Central Laboratory Assessments: 
 
CRP/hsCRP 
 
Lipid panel  
 
Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody 
testing will be collected, sent to the central laboratory, and stored for analysis. 
• Any AEs that have occurred since the last visit (Study Site/Clinic or outpatient) will be documented.  
• Medication diary compliance will be assessed by the Investigator/designated personnel. 
• Pericardial pain based on the 11-point NRS will be assessed (Figure 3). 
• The subject's global overall well-being will be assessed using a validated Quality of Life 
Questionnaire (Appendix 3). 
When all of these procedures have been performed, the next Study Site/Clinic visit should be scheduled for 
those who continue KPL-914 treatment during the EP (Treatment Responders).  Study Drug for outpatient 
administration will be provided to the subjects according to a process laid out in the pharmacy manual. 
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Only subjects continuing treatment into the Extension Phase will receive Study Drug at Visit 7; Study Drug 
can be self-administered either as an outpatient or at the Clinic/Site (Site to provide Study Drug) depending 
on the logistics/timing of the EoT Visit 7. Continued weekly Study Drug treatment during the EP will be 
outpatient administration. 
8.5.4 
Extension Period 
Subjects will self-administer the Study Drug or be administered by an adequately trained caregiver on a 
weekly basis and complete the medication diary during the Extension Period. Study nurse visits to the 
subject’s home will continue on a monthly basis. Investigator (or designee) phone calls/virtual visits will 
be performed monthly during the EP to perform NRS pain assessments, collect AE information, and 
document pericarditis/concomitant medication use. If scheduled, in-person Study Site/Clinic Visits 
(Unscheduled Visits or Evaluation Visits) can replace the phone calls/virtual visits. During the EP, the 
Investigator is encouraged to wean concomitant NSAIDs, and/or colchicine, and/or corticosteroids.  It is 
encouraged that NSAIDs and colchicine be tapered and withdrawn within 15 days after entry into the EP.  
It is encouraged that corticosteroids be progressively tapered (e.g., by 5 mg prednisone or equivalent every 
week in adults or 0.2mg/kg every week in subjects <18yo) and discontinued within 6 weeks after entering 
to EP (i.e., by Study Week 12) unless in the opinion of Investigator, a different corticosteroid weaning 
schedule is required based on subject’s clinical status. Other pericarditis medications may also be initiated 
at the discretion of the Investigator.  All changes to pericarditis-related medications should be captured in 
the source records and eCRF 
 
8.5.4.1 
Unscheduled Visits (Study Site/Clinic) during the EP 
Unscheduled Study Site/Clinic visits can take place during the Extension Period, as agreed upon by the 
Investigator and the subject or as needed.  
• A physical examination will be performed. 
• Vital signs will be measured.  
• Changes in concomitant medication since the last Study Site/Clinic visit will be documented. 
• Samples for laboratory tests will be collected. 
o Local Lab Assessments: 
 
Full hematology (including ESR), chemistry (including CRP), and urinalysis 
o Central Laboratory Assessments: 
 
CRP/hsCRP  
 
Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody 
testing will be collected, sent to the central laboratory, and stored for analysis.  
• A 12-lead ECG and a full ECHO will be performed as determined by the Investigator.  The Study 
Site/Clinic readings at the time of the examination will be made available to the Investigator for 
clinical decision-making. In addition, both the ECG and ECHO will be sent to a core laboratory.  
• Any AEs that have occurred since the last visit (Study Site/Clinic or outpatient) will be documented.  
• Pericardial pain based on the 11-point NRS will be assessed (Figure 3).  
8.5.4.2 
Interval Evaluation Visit During Extension Period (Study Site/Clinic) - Week 15-20 
An in-person Interval Evaluation Visit during approximately Weeks 15-20 of the Extension Period is 
recommended to assist the Investigator in the clinical management of the subject. The visit can be held at 
the discretion of the Investigator.  
At the Extension Period Interval Evaluation Visit, the following parameters will be assessed: 
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• A physical examination will be performed. 
• Vital signs will be measured.  
• A 12-lead ECG and a full ECHO will be performed.  The Study Site/Clinic readings at the time of 
the examination will be made available to the Investigator for clinical decision-making. In addition, 
both the ECG and ECHO will be sent to a core laboratory. 
• Changes in concomitant medication since the last Study Site/Clinic visit will be documented. 
• Samples for laboratory tests will be collected. 
o Local Lab Assessments: 
 
Full hematology (including ESR), chemistry (including CRP), and urinalysis 
o Central Laboratory Assessments: 
 
CRP/hsCRP  
 
Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody 
testing will be collected, sent to the central laboratory, and stored for analysis.  
• Any AEs that have occurred since the last visit (Study Site/Clinic or outpatient) will be documented.  
• Pericardial pain based on the 11-point NRS will be assessed (Figure 3). 
• The subject's global overall well-being will be assessed using a validated Quality of Life 
Questionnaire (Appendix 3). 
  
8.5.4.3 
Visit 8/Final Visit (Study Site/Clinic) - Week 25 
• Visit 8 will take place 18 weeks after Visit 7 (or as soon as possible after study withdrawal during the 
EP). 
• A full physical examination will be performed, including assessment of pericardial rub.  
• Body weight and height will be assessed. 
• Vital signs will be obtained in the seated position and include oral temperature, respiratory rate, blood 
pressure, and pulse. 
• 12-lead ECG and ECHO will be performed.  Echocardiogram will include assessment of pericardial 
effusion.  In addition, both the ECG and ECHO will be sent to a core laboratory. 
• An MRI can be performed (optional).  
• Changes in concomitant medication since the last Study Site/Clinic visit will be documented. 
• Samples for laboratory tests will be collected. 
o Local Lab Assessments: 
 
Full hematology (including ESR), chemistry (including CRP), and urinalysis 
o Central Laboratory Assessments: 
 
CRP/hsCRP 
 
Lipid panel  
 
Samples for archive biomarker, PK and anti-rilonacept (anti-KPL-914) antibody 
testing will be collected, sent to the central laboratory, and stored for analysis.  
• Any AEs that have occurred since the last visit (Study Site/Clinic or outpatient) will be documented.  
• Pericardial pain based on the 11-point NRS will be assessed (Figure 3). 
• The subject's global overall well-being will be assessed using a validated Quality of Life 
Questionnaire (Appendix 3). 
  
8.5.5 
Duration of Treatment 
The overall study duration for subjects participating in the study until Visit 8 will be up to 171 days.  
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The test product will be administered weekly for 6 weeks in the base study Treatment Period.  Treatment 
Responders will be offered participation in an optional 18-week EP at the discretion of the Investigator.  
During this EP the subject can receive 18 additional weekly doses of KPL-914.  
8.6 
Efficacy and Safety Variables 
The Schedule of Evaluations in Table 1 shows the planned study assessments. 
8.6.1 
Individual Efficacy Assessments 
8.6.1.1 
C-Reactive Protein, Biomarker, and PK Assessments 
CRP will be determined at Study Site/Clinic laboratory tests at Screening (SCV1 and SCV2) and during the 
Treatment Period (Visit 1 prior to dosing, if separate from SCV2, Interval Evaluation Visit [if applicable], 
and Visit 7/End-of-Trial).  Results from the Study Site/Clinic CRP testing will inform the Investigator on 
the subject's pericarditis status for clinical decision-making and support decisions on classifications of 
subjects as Treatment Responders or Treatment Failures and on subsequent disease management during the 
Extension Period.  
Central laboratory assessments of CRP will be performed at each Study Site/Clinic or outpatient study visit 
(samples collected by a visiting study nurse or at the Study Site/Clinic or a local laboratory).  Centrally 
determined CRP values will be used for statistical evaluations and report writing but will not be used as 
basis of the Investigator’s management of the subject. 
All subjects must present with elevated CRP values ≥1 mg/dL at the time of study enrollment.  CRP changes 
and the time course to decrease and resolution of CRP to normal values ≤0.5 mg/dL will be assessed. 
Samples from each study visit will be archived at the central laboratory for potential biomarker and/or PK 
analysis.  
8.6.1.2 
Echocardiogram (Pericardial Effusion) 
Echocardiograms (ECHOs) including assessment of pericardial effusion will be performed at screening 
(SCV1), at Study Site/Clinic visits during the Treatment Period (Interval Evaluation Visit [if applicable] 
and Visit 7/End-of-Trial), at the Interval Evaluation Visit during the EP [if applicable], and at the Final 
Study Visit/Visit 8.  
Pericardial effusion is characterized by accumulation of excess fluid in the pericardial space surrounding 
the heart and is one of the common features of pericarditis.  Echocardiography is a sensitive tool and the 
most widely used imaging technique for the detection of pericardial effusion and/or thickening. 
ECHO images may be assessed by a central reader after the study end. The Study Site/Clinic reading of the 
ECHO at the time of the examination will be made available to the Investigator for clinical decision-making, 
and will be used for analysis of treatment response.  
8.6.1.3 
Electrocardiogram (Pericarditis Diagnostic Findings) 
Twelve-lead ECGs will be performed at screening (SCV1 and SCV2), at Study Site/Clinic visits during the 
Treatment Period (Interval Evaluation Visit [if applicable] and Visit 7/End-of-Trial), at the Interval 
Evaluation Visit during the EP [if applicable], and at the Final Study Visit/Visit 8.  
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Pericarditis commonly involves changes in the electrophysiologic activity of the heart, resulting in typical 
ECG findings, namely widespread ST-elevation or PR depression.  Changes in ECG findings will help 
determine the pericarditis status of a subject.  
The Study Site/Clinic reading of the ECG at the time of the examination will be made available to the 
Investigator for clinical decision-making and will be used for analyses of treatment response. In all subjects 
ECG tracings will be assessed by a central reader and used for central read ECG analysis.   
8.6.1.4 
Pericarditis Signs (Fever, Pericardial Rub) 
Common pericarditis signs include fever and pericardial rub.  These pericarditis signs will be assessed via 
documentation of vital signs and physical examinations.  
Physical examinations and vital sign assessments for pericarditis signs will be performed at screening 
(SCV1 and SCV2), at Study Site/Clinic visits during the Treatment Period (Interval Evaluation Visit [if 
applicable] and Visit 7/End-of-Trial), at the Interval Evaluation Visit during the EP [if applicable], and the 
Final Study Visit/Visit 8.  If applicable, assessment of pericarditis signs will also be performed at 
unscheduled visits.  
8.6.1.5 
Pericarditis Pain (Chest Pain) 
Common pericarditis symptoms include chest discomfort (pericarditis pain).  A validated 11-point NRS will 
be used to measure the subject's level of pericarditis (chest) pain intensity (Dworkin et al 2005; Mannion et 
al 2007; Hawker et al 2011).  The assessment will be performed at all study visits - on-site during Study 
Site/Clinic visits and as part of telephone calls/virtual visits during outpatient visits/treatment weeks (weekly 
during the Treatment Period and monthly during the EP).  
Subjects will be asked to select the score that best describes their average level of pain over the previous 24 
hours using a validated 11-point NRS instrument (Figure 3), where zero (0) indicates ‘no pain’ and ten (10) 
means indicates ‘pain as bad as it could be’.   
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8.6.2 
Safety Assessments 
8.6.2.1 
Adverse Events 
Adverse Event Definition 
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 and/or unintended 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. 
In this study, individual elements of pericarditis symptomatology (including pain) are captured as an 
efficacy parameter.  Pericarditis pain is not required to be reported as an AE.  However, if, in the opinion of 
the Investigator, the subject experiences new symptoms that had not been previously reported in the 
constellation of symptoms recorded at baseline, these new symptoms should be reported as an AE. 
The causal relationship between an AE and the Study Drug will be defined as below: 
• 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 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 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 drug, abates 
upon discontinuation of the drug, follows a known or hypothesized cause-effect relationship, and (if 
appropriate) reappears when the drug is reintroduced.   
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: medically significant event; daily activities limited or completely halted; hospitalization or 
prolongation of hospitalization indicated. 
Every reasonable effort will be made to follow subjects who have AEs.  Any subject who has an ongoing 
AE at study end or early withdrawal will be followed, where possible, until resolution.   
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Sponsor Reporting Responsibilities to Participating Investigators 
It is the responsibility of the Sponsor or designee to immediately notify all participating Investigators of any 
AE associated with the use of the drug that is both serious and unexpected, as well as any finding from tests 
in laboratory animals that suggest a significant risk for human subjects.   
8.6.2.3 
Adverse Reactions 
All noxious and unintended responses to an investigational medicinal product (IMP; i.e., where a causal 
relationship between an IMP and an AE is at least a reasonable possibility) related to any dose should be 
considered adverse drug reactions.   
Unexpected Adverse Reaction Definition 
An unexpected adverse drug reaction is defined as an adverse reaction, the nature or severity of which is 
not consistent with relevant product information for the IMP.  The current version of the ARCALYST® PI 
should be used as the Single Source Safety Reference Document when determining if an event is 
unexpected. Refer to the ARCALYST® PI (Appendix 2: ARCALYST® Prescribing Information) for a list 
of most frequent expected AEs.  All suspected adverse reactions related to an investigational medicinal 
product (the tested investigational medicinal products and comparators, if involved) which occur in the 
concerned trial, and that are both unexpected and serious are subject to expedited reporting. 
Warnings and Precautions 
Refer to the ARCALYST® PI (Appendix 2: ARCALYST® Prescribing Information) for Important Safety 
Information. 
IL-1 blockade may interfere with immune response to infections.  It is therefore recommended that prior to 
or shortly after initiation of therapy with KPL-914 subjects receive all recommended vaccinations, as 
appropriate, including pneumococcal vaccine and inactivated influenza vaccine. In case a subject needs 
vaccination after initiation of KPL-914 treatment, vaccination with inactive vaccine(s) may be performed 
during the active Treatment Period. However, to minimize the potential confounding of KPL-914-related 
AE reporting or CRP measurements during the KPL-914 Treatment Period, vaccination should not be 
performed during the Treatment Period (see Section 8.3.4).  It is recommended that all vaccinations be 
documented as up-to-date at or shortly after Visit 7, at which point subjects are being considered for longer-
term treatment with KPL-914.   
Taking KPL-914 with TNF inhibitors is not recommended because simultaneous inhibition of these two 
pathways may increase the risk of serious infections.   
It is also possible that taking drugs 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 KPL-914.   
8.6.2.4 
Clinical Laboratory Variables 
Clinical laboratory analyses will be performed at Study Site/Clinic or local laboratory near the subject and, 
for some parameters, at a central laboratory.  Laboratory analyses will be used at Study Site/Clinic visits for 
the Investigator to assess disease status and to determine treatment response and study (drug) continuation 
or withdrawal.  Results for analyses performed by the Study Site/Clinic laboratory together with the 
laboratory reference ranges will be recorded in the eCRF and the Investigator must use clinical judgment to 
determine if any abnormal values are clinically significant or not. 
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Central laboratory samples for CRP analysis will be collected at both Study Site/Clinic and outpatient (by a 
visiting study nurse or at local contract laboratories) visits and the results will be used for statistical analyses 
and study reporting. Study Site/Clinic and local laboratory results will be used for clinical decision-making 
and will be available in the source documents and listed in the CSR).  
The following analyses will be done at the central laboratory:  
• 
C-reactive protein (CRP)/hsCRP (The CRP analyzed by the central laboratory will not be available 
to the investigator in a timely manner to support the clinical management of the subject.  Results 
from the central laboratory will therefore not be transferred to the Investigator during the trial.) 
• 
Lipid Panel 
• 
Samples for biomarkers, PK, and anti-rilonacept (anti-KPL-914) antibody testing will be drawn and 
archived at all visits. 
The following laboratory analyses will be done at the Study Site/Clinic laboratories in accordance with 
local procedures and guidelines to support clinical management and decision-making: 
Hematology 
Hemoglobin, hematocrit, coagulation parameters (prothrombin [PT], prothrombin time [PTT], D-dimer), 
ESR, fibrinogen, WBC count (total and differential), red blood cell (RBC) count, ESR, platelet count, mean 
cell volume (MCV), mean cell hemoglobin (MCH), MCH concentration (MCHC). 
Clinical Chemistry 
CRP/hsCRP, troponin, creatinine, creatine kinase, urea, (or blood urea nitrogen [BUN]), aspartate 
aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), alkaline 
phosphatase, lactate dehydrogenase (LDH), total bilirubin, albumin, total protein, sodium, potassium, 
chloride, glucose, uric acid, total cholesterol*, triglycerides*, calcium, phosphorus. 
* Preferably fasting. 
Urinalysis 
pH, glucose, ketones, nitrites, leukocyte esterase, blood, protein and microscopy. Urine drug screen 
(alcohol, amphetamines, cocaine, or phencyclidine) at SCV1 only. Screening for pregnancy (urine β-HCG) 
at SCV1 only. 
Serology 
HCVAb, HBsAg, HBcAb, HBsAb and HIV tests (SCV 1 only). 
 
Other 
Screening for tuberculosis (QuantiFERON test) at SCV1 only (optional). 
The amount of blood to be taken during screening will be approximately 37 mL at SCV1 and approximately 
17 mL at SCV2 (if done). The amount of blood to be taken at each Study Site/Clinic visit during the 
Treatment Period and EP will be approximately 31 mL.  The amount of blood to be taken at each outpatient 
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visit will be approximately 21 mL. At the optional unscheduled visit, approximately 61 mL are planned. 
The total amount of blood to be taken during the study will be up to approximately 320 mL. 
8.6.2.5 
Vital Signs 
Vital signs will be recorded at Study Site/Clinic visits in a standardized manner, i.e., after the subject has 
rested in the sitting position for 5 minutes. 
The following measurements will be taken: oral temperature, respiratory rate, blood pressure, and pulse.  
Oral temperature (fever) will also be assessed as efficacy parameter (see Section 8.6.1.4). 
8.6.2.6 
Physical Examination 
At the Screening Visits 1 and 2, at the optional Evaluation Visit during the Treatment Period, at the End-of-
Trial Visit (Visit 7), at Unscheduled and Evaluation Visits during the EP and at the Final Visit (Visit 8) a 
full physical examination including the assessment of pericardial rub (efficacy parameter) will be performed 
(see also Section 8.6.1.4).   
8.6.2.7 
Body Weight and Height 
Body weight and height will be determined at SCV1 and at the final study visit.  
8.7 
Statistical Methods 
Each Part will be analyzed separately and per the analysis populations below, to be finalized in the Statistical 
Analysis Plan (SAP) to be provided separately. A full description of the statistical analyses to be performed 
together with the planned tables and figures will be given in a detailed document, the SAP, which will be 
developed and filed prior to data base lock.  Any deviation(s) from the final SAP will be described and 
justified in the clinical study report. 
8.7.1 
Statistical and Analytical Plans 
8.7.1.1 
Datasets to be Analyzed for Each Part 
Each Part will be analyzed separately and per the analysis populations below. The modified Intention to 
Treat (mITT) Population will consist of all subjects who received at least one dose of Study Drug.  The Per 
Protocol (PP) Population will consist of all subjects who received all 6 doses of Study Drug during the active 
Treatment Period and were maintained at stable dose levels of concomitant pericarditis medications 
(NSAIDs, colchicine, and/or corticosteroids, if used during screening) according to study protocol without 
a major protocol violation.  The Safety Population will be the same as the mITT Population. 
8.7.1.2 
General Statistical Methods 
Because of the small sample size, no inferential statistical analyses or hierarchical testing are planned. 
For analysis of continuous endpoints (e.g., change from baseline), summary statistics (n, mean, standard 
deviation, median, minimum, and maximum) will be calculated and presented for each treatment and/or 
analysis group.  For categorical endpoints (e.g., responder vs. non-responder), summary statistics will be 
calculated and presented for each treatment and/or analysis group. Under certain circumstances, if 
appropriate in the context of statistical methodologies, the results of certain similar Parts might be pooled 
for greater statistical precision in determining therapeutic response or safety. 
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In accordance with current Good Clinical Practice (GCP) and International Conference on Harmonisation 
(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.   
8.8.3 
Data Management and Coding 
The Sponsor or Clinical Research Organization (CRO) 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 the 
Sponsor or CRO. 
Medical coding will use Medical Dictionary for Regulatory Activities (MedDRA) for concomitant diseases 
and AEs and World Health Organization (WHO) Drug for therapies. 
8.8.4 
Record Keeping 
It is the responsibility of the Investigator to ensure all essential trial documentation and source records (e.g., 
signed ICFs/assent forms, Study Site/Clinic files, patients’ hospital notes, copies of eCRFs, etc.) 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. 
9 Records and Supplies 
9.1 
Drug Accountability 
On receipt of the IMP (including rescue medication, if relevant), the Investigator (or deputy) will conduct 
an inventory of the supplies and verify that IMP supplies are received intact and in the correct amounts prior 
to completing a supplies receipt.  The Investigator will retain a copy of this receipt at the study site and 
return the original receipt to the drug depot.  The inventory of supplies at each study site will be reviewed 
by the study monitor. 
KPL-914 (rilonacept) will be provided by the Sponsor to the study sites and to the study subjects in its 
commercially-available formulation (ARCALYST®).  All vials of used and unused Study Drug during the 
active Treatment Period 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.   
10 
Ethics 
10.1 Institutional Review Board 
Before initiation of the study at each investigational site, the protocol, all protocol amendments, the ICF, 
the informed assent form and any other relevant study documentation will be submitted to the appropriate 
IRB.  Written approval of the study and all relevant study information must be obtained before the study 
site can be initiated or the IMP is released to the Investigator.  Any necessary extensions or renewals of IRB 
approval must be obtained, in particular, for changes to the study such as modification of the protocol, the 
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informed consent form (or assent, if applicable), the written information provided to subjects and/or other 
procedures. 
The Investigator will report promptly to the IRB any new information that may adversely affect the safety 
of the subjects or the conduct of the study.  The Investigator will submit written summaries of the study 
status to the IRB annually, or more frequently if requested by the IRB.  On completion of the study, the 
Sponsor will notify the IRB that the study has ended. 
10.2 Ethical Conduct of the Study 
This study will be conducted in compliance with the protocol, the ICH-GCP guideline, the Declaration of 
Helsinki and local regulations. 
10.3 Subject Information and Consent 
The Investigator is responsible for ensuring that no subject undergoes any study related examination or 
activity before that subject and/or legal guardian has given written informed consent (or informed assent, if 
applicable) to participate in the study.  The written consent (or informed assent, if applicable) must be given 
by the subject and/or the legal guardian of the subject, after detailed information about the study has been 
given and in accordance with any national provisions on the protection of clinical study subjects.  The verbal 
explanation will cover all the elements specified in the written information provided for the subject. 
Subjects and/or legal guardians will be required to sign and date the ICF.  After signatures are obtained, the 
ICF will be kept and archived by the Investigator in the Investigator’s study file for possible inspection by 
regulatory authorities, the IRB, Sponsor and/or CRO personnel. 
It should be emphasized to the subject that he/she is at liberty to withdraw from the study at any time, 
without penalty or loss of benefits to which the subject is otherwise entitled.  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 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 informed 
assent and the informed consent are required prior to participation in the trial.  
10.4 Subject Confidentiality (US Studies) 
All personal data collected and processed for the purposes of this study should be managed by the 
Investigator and his/her staff with adequate precautions to ensure confidentiality of those data, and in 
accordance with the Health Insurance Portability and Accountability Act (HIPAA), applicable to national 
and/or local laws and regulations on personal data protection. 
Monitors, auditors, and other authorized agents of the Sponsor and/or its designee, the ethics committees 
approving this research, and the United States (US) FDA, as well as that of any other applicable agency(ies), 
will be granted direct access to the study subjects’ original medical records for verification of clinical study 
procedures and/or data, without violating the confidentiality of the subjects to the extent permitted by the 
law and regulations.  In any presentations of the results of this study or in publications, the subjects’ identity 
will remain confidential. 
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11 Reporting and Publication 
All data generated in this study are the property of the Sponsor.  An integrated clinical and statistical report 
will be prepared at the completion of the study.  
Publication of the results by the Investigator(s) will be subject to mutual agreement between the Investigator 
and Kiniksa as outlined in the study agreement. 
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12 References 
Adler Y, Charron P, Imazio M, Badano L, Barón-Esquivias G, Bogaert J, Brucato A, 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 Nov 7;36(42):2921-64. 
Amizguine J, Cohen-Wolkowiez M, Ilowite N. Rilonacept pharmacokinetics in children with Systemic 
Juvenile Idiopathic Arthritis. J Clin Pharmacol 2015, 55(1); 39-44. 
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, Lazaros G, Maestroni S, Carraro M, Finetti M et al. Effect of Anakinra 
on Recurrent Pericarditis Among Patients With Colchicine Resistance and Corticosteroid 
Dependence: The AIRTRIP Randomized Clinical Trial. JAMA. 2016 Nov 8;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. Autoimmunity Reviews 2015;14:90–97. 
Doria A, Zen M, Bettio S et al. Autoinflammation and autoimmunity: bridging the divide. Autoimmunity 
Reviews 2012;12:22–30. 
Dworkin RH, Turk DC, Farrar JT et al. Core outcome measures for chronic pain clinical trials: IMMPACT 
recommendations. Pain. 2005 Jan;113(1-2): 9-19. 
Garg M, de Jesus AA, Chapelle D, Dancey P, Herzog R, Rivas-Chacon R, Wampler Muskardin TL, Reed 
A, Reynolds JC, Goldbach-Mansky R, Montealegre Sanchez GA. Rilonacept maintains long-term  
inflammatory remission in patients with deficiency of the IL-1 receptor antagonist. JCI Insight, 2017; 
2(16); e94838. 
Hays RD, Bjorner JB, Revicki DA, Spritzer KL, Cella D. Development of physical and mental health 
summary scores from the patient-reported outcomes measurement information system (PROMIS) 
global items. Qual Life Res (2009) 18:873–880. 
Hawker GA, Mian S, Kendzerska T, French M. 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 & Research. 2011; 63: S240–S252. 
Heching HJ, Bacha EA,  Liberman L. Post-pericardiotomy syndrome in pediatric patients following surgical 
closure of secundum atrial septal defects: incidence and risk factors.  Pediatr Cardiol 2015;36 (3); 
498-502.
Hoffman HM, Patel DD. Genomic-based therapy: targeting interleukin-1 for auto-inflammatory diseases. 
Arthritis and Rheum. 2004 Feb; 50(2): 345-349. 
Ilowite NT, Prather K, Lokhnygina Y, Schanberg LE, Elder M, Milojevic D, Verbsky JW, Spalding AJ, 
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19 February 2019 
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Kimura Y, Imundo LF, Punaro MG, Sherry DD, Tarvin SE, Zemel LS. Randomized, double-blind,  
placebo-controlled trial of the efficacy and safety of rilonacept in the treatment of Systemic Juvenile  
Idiopathic Arthritis (RAPPORT). Arthr and Rheum 2014;66 (9);2570-2579. 
 
Imazio M, Spodick DH, Brucato A, Trinchero R, Adler Y. Controversial issues in the management of 
pericardial diseases. Circulation. 2010;121:916-928. 
Imazio M, Bobbio M, Cecchi E, Demarie D, Demichelis B, Pomari F, Moratti M, Gaschino G, Giammaria 
M, Ghisio A, Belli R, Trinche­ro R. Colchicine in addition to conventional therapy for acute 
pericarditis: results of the COlchicine for acute PEricarditis (COPE) trial. Circulation. 
2005;112:2012-2016. 
Imazio M, Demichelis B, Parrini I et al. Management, risk factors, and outcomes in recurrent pericarditis. 
American Journal of Cardiology, 2005;96(5):736–739. 
Imazio M. Treatment of recurrent pericarditis. Revista Espanola de Cardiologia. 2014;67(5):345–348. 
Imazio M, Brucato A, Pluymaekers N, Breda L, Calabri G, Cantarini L, Cimaz R, Colimodio F, Corona F,  
Cumetti D, Di Blasi Lo Cuccio C, Gattorno M, Insalaco A, Limongelli G, Russo MG, Valenti A,  
Finkelstein Y, Martini A. Recurrent pericarditis in children and adolescents:a multicenter cohort  
study. J Cardiovasc Med 2016;17; 707-712. 
 
Khandaker MH, Espinosa RE, Nishimura RA, Sinak LJ, Hayes SN, Melduni RM, Oh JK. Pericardial 
disease: diagnosis and management. Mayo Clin Proc. 2010;85:572-593. 
Lazaros G, Imazio M, Brucato A, Vassilopoulus D, Vasileiou P, Gattorno M, Tousoulis D et al. Anakinra: 
an emerging option for refractory idiopathic recurrent pericarditis: a systematic review of published 
evidence. J Cardiovasc Med 2016;17(4):256-62. 
Lehto J, Gunn J, Karjalainen P, Airaksinen J, Kiviniemi T. Incidence and risk factors of postpericardiotomy  
syndrome requiring medical attention:The Finland Postpericardiotomy syndrome study. J Thorac   
Cardiovasc Surg 2015; 149(5); 1324-9. 
 
Lilly SL. Treatment of Acute and Recurrent Idiopathic Pericarditis. Circulation. 2013;127:1723-1726. 
Lotrionte M, Biondi-Zoccai G, Imazio M, Castagno D, Moretti C, Abbate A, Agostoni P, Brucato AL, Di 
Pasquale P, Raatikka M, Sangiorgi G, Laudito A, Sheiban I, Gaita F. International collaborative 
systematic review of controlled clinical trials on pharmacologic treatments for acute pericarditis and 
its recurrences. Am Heart J. 2010;160:662-670. 
Lovell DJ, Giannini EH, Reiff AO, Kimura Y, Li S, Hashkes PJ, Wallace CA, Onel KB, Foell D, Wu R,  
Biedermann S, Hamilton JD, Radin AR.  Long-term safety and efficacyof rilonacept in patients with  
Systemic Idiopathic Juvenile Arthritis. Arthr and Rheum 2013; 65(9); 2486-2496. 
 
Maisch B, Seferovic PM, Ristic AD, Erbel R, Rienmüller R, Adler Y, Tomkowski WZ, Thiene G, Yacoub 
MH; Task Force on the Di­agnosis and Management of Pericardial Diseases of the European Society 
of Cardiology. Guidelines on the diagnosis and management of pericardial diseases executive 
summary: the Task Force on the Diagnosis and Man­agement of Pericardia! Diseases of the 
Eu­ropean Society of Cardiology. Eur Heart J. 2004;25:587-610. 
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Mannion AF, Balagué F, Pellisé F, Cedraschi C. Pain measurement in patients with low back pain. Nature 
Clinical Practice Rheumatology 2007; 3 (11): 610-18. 
Pankuweit S, Wädlich A, Meyer E, Portig I, Hufnagel G, and Maisch B. Cytokine activation in pericardial 
fluids in different forms of pericarditis. Herz 2000;25:748–754. 
Tamarappoo BK, Klein AL. Post-pericardiotomy syndrome.  Curr Cardiol Rep 2016; 18(11);116. 
Zayas R, Anguita M, Torres F, Gimenez D, Bergillos F, Ruiz M, Ciudad M, Gallardo A, Valles F. Incidence 
of specific etiology and role of methods for specific etiologic diagnosis of primary acute pericarditis. 
Am J Cardiol. 1995;75:378-382. 
 
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13 Appendices 
Appendix 1: Investigator Signature Page 
Protocol Title: 
An Open-Label Pilot Study of KPL-914 in Recurrent Pericarditis 
Protocol Number: 
KPL-914-C001 
Confidentiality and cGCP Compliance Statement 
I, the undersigned, have reviewed this protocol, including appendices and I will conduct the study as 
described in compliance with this protocol, GCP, and relevant ICH guidelines. 
Once the protocol has been approved by the IEC/IRB, I will not modify this protocol without obtaining prior 
approval of Kiniksa Pharmaceuticals Ltd. (Kinksa) and of the IEC/IRB. I will submit the protocol 
modifications and/or any ICF/assent modifications to Kiniksa and IEC/IRB, and approval will be obtained 
before any modifications are implemented. 
I understand that all information obtained during the conduct of the study with regard to the subjects’ state 
of health will be regarded as confidential. No subjects’ names will be disclosed.  All subjects will be 
identified by assigned numbers on all Case Report Forms, laboratory samples or source documents 
forwarded to the Sponsor.  Clinical information may be reviewed by the Sponsor or its agents or regulatory 
agencies.  Agreement must be obtained from the subject before disclosure of subject information to a third 
party. 
Information developed in this clinical study may be disclosed by Kiniksa, to other clinical Investigators, 
regulatory agencies, or other health authority or government agencies as required. 
Investigator Signature 
Date 
Printed Name 
Institution 
 
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Appendix 2: ARCALYST® Prescribing Information 
 
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	H'								.			'
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		*				+	7#	'	B			)&	,
	
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				"			+			+	.				
					!			"				.	
			'		.				
"	6"	
.					"			.		"		.		!
	"!		"!	"			!		!	
"	'	#		!									+	
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3DJH

								"'
;"8		
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			.						+		'	 	+	 
	+		5						!	91	!	1
!		"'								!	91
!	1	!		"	+	K	"4!	&	"4!	-	"4!		82	"4
.		0	+			'	 							
	
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.					"'
8	4/$	!)'!%)
8"7	)&(B			!7	(B	
	"			.				+	'	
			"			*	+		7#"	"				
			+												'
					+	7#"	"					
5					G	#$		%	&H'			
		+		"			*				'	;				
"		+					*!			
			"			*						'
8"1	
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
			 38-	6					.			
'"'!	*	"
	'				5								*!			!	
		 38-	6			6'				.		 38-	
+		+		5!	+				.	/	
'"'!	+'	>	
	!			"		+					!		"
				"							.				
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3"7	
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 "	"	'				B		+					"
+'	;			!					'			.
5		+			"			+	-!	8!	8		,-	"4"	".	+	
+	
"			5	,'2	"						0-	"			
	'							+	5			"				
"	+										.			'
=5			"				+	+		5	'	+!		
"	!							.					03J		
														
	'	*				.	5"					
"			"			
-!	&-!	--		&--	"4"!		+		,				
					+	&--	"4"				+	
	"			5	0
	"			0-	"							'			
	"	"					/						'
7"	'					.	5"		+			+
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3DJH

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			+	
	"			5	0	"			0-	"	
					'										
# 	"	"					'
3"9	)
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!				5	+						"	+'
3":	
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+!				&'&	"4"	
			5		0-	"		&3+	"		
	5	'			+	.								
/.				
'"'					.	 '		.	.
	/								+					
'
	"	"	.											+		.	

&-	"4!	"	,'0		,,	"4	+				.				+	 	

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		.				+		"		&	.			'
%			"	!				.					
			'	*			+			+			.			'
 			+			"		"		"+	
.'	G	'		
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6			+		+	M	08			"!		0	+	M	28			"'	*	
 		!	!				+	"					
		"	F	+.!				M	08						'	*	
	5			 !		2			+	.		"			G
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				'
3";				! 
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7			.				5					
			+		'
3"8			#	! 
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7			.				5					
			+		'
72	%6'4%$'
	.					.	+	'	$5	+					,&-	"
.							5	(							
+	 				0				+		.					+
.		"	5'	*	!		".	.					&---
"									5		+		+	"
5'		5											
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.			!						'
77	4'!!%)
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							
**		*			

* 					#				*"<'					+"	
5	&8	1'			5					.	
9A	'
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6	+'	=	.							+	&',				%	
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		'		"			.!	!				+!	
			'	=	.		&&-	"	'		!		.
	(-	"4	!	30	$	!	8-	$	"!	,'-J	
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71	!)!	#*%%$
71"7	* 		
 				"		"						7 ,	G7
"	!				
7!			"	,H	"	
	+		
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		+				"	B	'	#				
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		!						'		"		
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..		"		5.			.	*O		.	'
		*O	""		"								*O		.
		+			'				*P		*		"	
*
	+		'		B					"		*O!	*P
	*	+	-'8	$!	'3	$		0'	$!	.'
71"1	
  
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						.
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				+	 '			!		+		
								 					.	"		
'			6				.	.'
71"9	
 B
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+				0-	"				3(	+			+	 '		
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7				.			+				'
7		+			.				"!	"!			+"			5'
;								!			"		+	
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								!	"		"		
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"																&--	"4"

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B		"		/"		!						".	+		
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	+			5	
		'	9			%	.					+
		'	+				"	"			'	1			
'	 		"				+							.	
	#"	0'
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	;
('	 9		.						"									.		+	
				"	"	'
K'	 $								.			B		+					"		
&',				++			%			.	
	#"	2'
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	8
-'	 S		.		+						"	+		"						
				"'
'	 	.			!	"				"										"
				'
&'	 	."		!			"						"				%	
	+			"	
	#"	('
&
	3
,'	 	.		"	+					%	.'	1				'
'	90	*C	-.	
'	 %		!				.				'
&'	 %			!			"	+			%				!		+	
		"	+	"							.'	 		"		
	+		/			%			.'
,'	 1		+			"	"	+					.			+	
	#"	K'
&
	=
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3'	 .		"							+	+		!	"!		
%	.				'	1							.				'
8'	 9		.	"					+		/	+	
	"	+
				"								.!		B			.			

					
	#"	-'
&
	72
0'	  		.								.					'
2'	 			.							+	+	.		.'
('	 *		+				.!			.	B					,-	
'			.					'
K'	 		(			+			.					'
-'	 	5				!	!					+'	1				5
B						!								
	#"	'
7A=)							5						
'
&
	77
'	 								5"'					+

	
		5"'	S		+		"'
'	:0	

		
'	 9			.						+						.	+		+
	+	
	#"	&'
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	71
&'	 		+	!								+	"	+	."	
	.	
	#"	,'
&
	79
,'	 					+			"		B				5		
		.						/'
3'	 	+				"!			"			.'	1		.			.'	 
		"			"						B					5		
		.						/	
	#"	3'
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	7:
8'	 .			.								'	S			.			
		+				"	+	"		'	 		"	+	
/						.	
	#"	8'
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3DJH

&
	7@
0'	 9		.						"									.		+	
				"	"	'	9		.			.'
2'	 S								B		+					"						"
										.	
	#"	0'
&
	7;
7A=)		5						&	'
('	 S		.		+	+			"	!		"			"			
							"	
	#"	2'
*				.						++			"					
.'
&
	78
K'	 	.			!	+		"				"							"
	'
-'	 						.									.	
	"'
'	 +	+			.					.					
.3/&3URWRFRODQG$PHQGPHQWV
3DJH

			.	
	#"	('	1				.						'
&
	73
'	@0	$+		!
'	 		".			/!		/			".				
+				'	*					"			!	.!		'
	



		
		

	
	


"	/				.			+					
'				.		B			.		"	/	'
1		/					!	!		'	*							!	
			/					T"T	"	+'
			.					"	!	+"!		"
		'
	+			/						"				!		
	"	"'	*				"."		/!					"				
		/	
	#"	K)
	
	
 
	!"		
	#
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	7=
&'	 					/'								+		+		+'
;"								.	+'						'
,'	 		.											'
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3DJH

3'	 9		"						+			'
8'	 %				"											/	
	#"	&-'
&
	12
0'	 >		B	U	V						"				
K-	"	"	

#"	&'	1			+			"	+	"					'
#					+					!							"	
			38	"	"	
	#"	&'
&
	17
2'	 							!		"							"'
('	 %						"			'	<				"'	*			
	"!							.'	.		!			"	
'		.	+	U= 	)	"				/V	"	+		
"!	!
.!		+		"6	'
K'	 *			!	/						"			+!		!	"		"
		+	+'	*					,-			/			'
-'	  						!							"6	.		/			.
	
	#"	&&'
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	11
'	 1					.'	+	+		.!		"					
		
	#"	&,'	1				'	1A	7A	+	+	.!
!		"						'
&
	19
&'	 S								'	%					+
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			.	"	+	+		B				'
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!	D	;"	'!	"	*'!		W	;!	*'!	.'

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"	 !	*'
222	A	+	$	.	
+!	7	-8K02-2
>''		7	20-
71	0288---
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	"	.'	
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