Conditions: Psoriasis
Keywords: BI 655066 risankizumab
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 110
Healthy volunteers: no

Brief summary:
The primary objective of Study M16-009 was to investigate the safety of risankizumab in participants with moderate to severe chronic plaque psoriasis who were receiving long-term treatment. Additional study objectives were to further investigate the long-term efficacy, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of risankizumab.

Detailed description:
Participants who had successfully completed Study 1311.2 (NCT02054481; the lead-in study) and met the eligibility criteria for Study M16-009 (extension study) had the option to enter the extension study. Participants were allowed to have the End of Study Visit in the lead in study combined with the Week 0 Visit for the extension study. At the Week 12 visit, participants were assigned to treatment based on 90% improvement in Psoriasis Area and Severity Index (PASI90) Score: participants with ≥PASI90 Score at Week 12 continued to receive risankizumab 90 mg by subcutaneous (SC) injection; participants with \<PASI90 Score at Week 12 switched to risankizumab 180 mg by SC injection.

Efficacy results are summarized by the 4 treatment groups from the lead-in study, which included the following: Participants who received risankizumab 18 mg in the lead-in study and risankizumab in the extension study (Risankizumab 18 mg/Risankizumab); participants who received risankizumab 90 mg in the lead-in study and risankizumab in the extension study (Risankizumab 90 mg/Risankizumab); participants who received risankizumab 180 mg in the lead-in study and risankizumab in the extension study (Risankizumab 180 mg/Risankizumab); and participants who received ustekinumab (Stelara) 45 or 90 mg in the lead-in study and risankizumab in the extension study (Ustekinumab/Risankizumab).

Arms:
arm 1: Participants entered the study receiving risankizumab 90 mg by subcutaneous (SC) injection and had achieved ≥90% improvement in Psoriasis Area and Severity Index (PASI90) Score at Week 12 continued to receive open-label (OL) risankizumab 90 mg by SC injection at Week 12 and every 12 weeks for approximately 4 years from the first dose in either the lead-in or extension study. arm 2: Participants entered the study receiving risankizumab 90 mg by subcutaneous (SC) injection and had achieved \<90% improvement in Psoriasis Area and Severity Index (PASI90) Score at Week 12 switched to open-label (OL) risankizumab 180 mg by SC injection at Week 12 and every 12 weeks for approximately 4 years from the first dose in either the lead-in or extension study.

Interventions: intervention 1: Risankizumab
Intervention descriptions: intervention 1: Risankizumab administered by subcutaneous (SC) injection

Protocol document:
Prot_000.pdf: 
Clinical Trial Protocol
Doc. No.: c02318676-08
EudraCT No.:
   BI Trial No.:  
2014-001687-36
1311.13
BI Investigational
Product(s):
BI 655066
Title:
  An open label extension trial assessing the safety and
Efficacy of BI 655066/ ABBV-066/risankizumab administered 
subcutaneously in patients with moderate to severe chronic plaque 
psoriasis.
Clinical Phase:
IIb
Trial Clinical 
Monitor:
 
 
 
 
Co-ordinating 
Investigator:
Status:
Final Protocol (Revised Protocol (based on global amendment 5)
Version and Date:
Version: 6.0         
Date: 30-Jan-2018
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TITLE PAGE
NCT02203851


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CLINICAL TRIAL PROTOCOL SYNOPSIS
Name of company:
Tabulated
Trial Protocol
Boehringer Ingelheim
Name of finished product:
NA 
Name of active ingredient:
BI 655066
Protocol date:
Trial number:
Revision date:
30-Jan-2018
13 June 2014
1311.13
Title of trial:
An open label extension trial assessing the safety and efficacy of BI 655066/ 
ABBV-066/risankizumab administered subcutaneously in patients with 
moderate to severe chronic plaque psoriasis.
Co-ordinating 
Investigator:
Trial site(s):
Multicenter, multinational
Clinical phase:
IIb
Objective(s):
Long term safety and efficacy of BI 655066/ ABBV-066/risankizumab during 
open-label treatment in patients with moderate to severe chronic plaque 
psoriasis.
Methodology:                  Open label extension. 
No. of patients: 
100 (estimated)
total entered:
100 (estimated)
each treatment:
All patients will receive 90 mg BI 655066/ ABBV-066/risankizumab for 12 
weeks, followed by 90 or 180 mg every 12 weeks depending on efficacy
Diagnosis :
Moderate to severe chronic plaque psoriasis.
Main criteria
for inclusion:
Patients with moderate to severe chronic plaque psoriasis, who have 
successfully completed the preceding trial 1311.2. Successful completion of 
preceding trial is defined as either of the following: 
a. Completion of the entire follow up period, thus reaching EOS visit. 
b. Loss of response, defined as decrease in response to <PASI50 at any 
time from week 24.
Test product(s):
BI 655066
dose:
90 mg every 12 weeks, or 180 mg every 12 weeks
mode of admin.:
Subcutaneous injection 
Comparator products: NA 
dose:
NA


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Name of company:
Tabulated
Trial Protocol
Boehringer Ingelheim
Name of finished product:
NA 
Name of active ingredient:
BI 655066
Protocol date:
Trial number:
Revision date:
30-Jan-2018
13 June 2014
1311.13
mode of admin.:
NA
Duration of treatment:
Approximately four years of administration to patient after receiving first BI 
655066/ ABBV-066/risankizumab dose in either trial 1311.2 or trial 1311.13
Criteria for efficacy:
The achievement of PASI90 at week 48 in the Extended dosing period (i.e. a ≥ 
90% reduction in PASI score from baseline), is the primary efficacy 
endpoint.  
Criteria for safety:
Occurrence of AEs, drug related AEs and SAEs are primary endpoints of 
safety.
Safety analyses will focus on adverse events related to early discontinuation, 
immune suppression and injection site reactions. 
Analysis of laboratory measures will similarly focus on hematologic measures 
of immune suppression. 
Safety will also be assessed by evaluation of vital signs (BP, PR, RR, oral or 
tympanic body temperature) and local tolerability.
Additionally, time to antibody development formation will be examined using 
Kaplan Meier empirical survival curves.
Statistical methods:
There is no statistical model; the analyses are descriptive.  Statistical analyses 
will include a responder analysis, time to loss of response, and time to AESI.  
The analyses will be based on proportions of patients achieving a response, 
Kaplan Meier empirical survival curves to describe patterns of event 
incidence, and as well as cumulative event rates at critical time-points.






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Footnotes:
1.
Extended Visit 1 of this OLE study should preferably be performed in one visit combined with EOS visit in preceding trial 1311.2, or within an interim period of maximum 6 weeks
thereafter. If not performed as combined visits, informed consent must be signed before the roll-over visit due to lab sampling fasting at EV1 in trial 1311.13. Informed consent must not be 
signed before the 1311.2 date of last visit. 
2.
Assessments performed at EOS in the previous trial do not have to be repeated at EV1 in this trial, if performed as combined visits. If EV1 is performed as a separate visit to 1311.2 EOS, all 
EV1 assessments should be performed.
3.
After the approval of this protocol amendment in each respective country, all patients will follow Flow Chart (Extended dosing period) and receive 90mg BI 655066 subcutaneously at their 
EV1. After 12 weeks, at EV2, the dose can be increased to 180 mg BI 655066 based on evaluation of the PASI90 achievement (see section 4.1.2 and 6.2.2). For ongoing patients under the 
previous protocol amendment, EV1 should be conducted at the following time points:
a.
For ongoing patients with ≥12 weeks since the EOT visit: Conduct EV1 as soon as possible 
b.
For ongoing patients still undergoing treatment or with <12 weeks since the EOT visit: Conduct EV1 at the time of the next scheduled treatment or follow up visit (note: EV1 
should not be conducted at the time point of Visit 2 under the previous protocol, patients with Visit 2 as their next scheduled visit should have their EV1 replacing their Visit 3 
instead)
4.
For patients who prematurely discontinue the treatment period before study end (for any reason), an early Extended EOT visit is required. If the decision to discontinue study participation is 
taken at a regular study visit, the visit should be turned into an Extended EOT visit, i.e. an Extended EOT visit is to be performed instead of the scheduled visit. If the decision to discontinue 
study participation is taken in between study visits, an Extended EOT visit is to be scheduled at the earliest convenience and by the latest at the next upcoming visit according to the Flow 
Chart. This early Extended EOT visit will include the same procedures as the normal Extended EOT visit and the patient will subsequently enter a follow up period of 12 weeks, until a final 
Extended EOS is performed.
5.
The Psoriatic Arthritis status assessment (PSOA: Psoriatic arthritis diagnosed, suspected, or not present) will be performed at roll-over visit only. Psoriatic arthritis screening and evaluation 
tool (PASE) to be completed by the patient if psoriatic arthritis is suspected or confirmed. To be repeated once per year until study end, i.e at EV1, EV5, EV10…
6.
“xC” is a complete physical examination including assessment of vital sign measurements, general appearance, and evaluation of all organ systems
7.
”xT” is a targeted physical examination including assessment of vital sign measurements, and evaluation of organ systems associated with AE(s) symptoms or laboratory abnormalities.
8.
Measured after 5 minutes of rest in the supine position. Measurements of vital signs should, if possible, always precede blood sampling. 
a.
Extended visit 1: Vital signs will be taken ~ 30 min predose, 5 minutes, and 1 hour after the dose is administered
b.
Following dosing visits: Vital signs will be taken ~ 30 min predose, 5 minutes and 30 minutes after the dose is administered
c.
Non-dosing visit (Extended EOS): Vital signs will be measured once per visit
9.
ECG to be performed after 5 minutes of rest in the supine position, at every 24 weeks, starting from EV1 (EV1, EV3, EV5…). Should, if possible, be performed prior to blood sampling.
10.
Not to be performed for patients who prematurely discontinue the treatment period.
11.
All new AEs as well as unresolved AE from the preceding trial 1311.2 should be followed up within this study.
12.
Only for patients with psoriatic arthritis.
13.
For details of laboratory tests cf. Section5.2.3, Table 5.2.3:1 and 5.2.3:2
14.
Patients must be fasting for at least 8 hours prior to collection of the safety laboratory samples.
15.
Only applicable for women of childbearing potential.
16.
In women of childbearing potential urine pregnancy test has to be performed before each administration of study drug. 
17.
Blood samples for protein biomarker, PK and ADA will be drawn ~ 30 min before the subcutaneous injection (PreD) at every 24 weeks, starting from EV1 (EV1, EV3, EV5…).
18.
For patients who prematurely discontinue the follow up period before study end (for any reason), an early Extended EOS visit is required. This early Extended EOS visit will include the same 
procedures as the normal Extended EOS visit.
19.
Patients will be asked to give consent to be contacted (or for their primary care physician to be contacted) by the study team to obtain vital status information preferably at the time of study 
entry
20.
Only required at EV1 for patients who are having EV1 as their first 1311.13 visit
21.
All efficacy assessments should be performed pre-dose (PreD)
22.
To be repeated once per year until study end (EV1, EV5, EV10…)


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23.
After 01-May-2018 and approval of this protocol amendment in each respective country patients who have completed the study without early treatment discontinuation will be offered to roll 
over to M15-997 open label extension (OLE) trial if they fulfill the in- and exclusion criteria for the M15-997 trial. Refer to section 6.2.3.
The next visit and also the last visit after 1st May and approval of this amendment will be Extended EOS visit. Termination of trial medication page should be completed in the eCRF and 
treatment completed registered in IRT.
24.
For patients not prematurely discontinued.
Abbreviations: PreD = Prior to dose


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TABLE OF CONTENTS
TITLE PAGE ......................................................................................................1
CLINICAL TRIAL PROTOCOL SYNOPSIS ................................................2
FLOW CHART – EXTENDED DOSING PERIOD.......................................4
TABLE OF CONTENTS ...................................................................................8
ABBREVIATIONS.......................................................................................... 12
1.
INTRODUCTION.................................................................................... 15
1.1
MEDICAL BACKGROUND............................................................................15
1.2
DRUG PROFILE...............................................................................................16
2.
RATIONALE, OBJECTIVES, AND BENEFIT - RISK 
ASSESSMENT ......................................................................................... 18
2.1
RATIONALE FOR PERFORMING THE TRIAL........................................18
2.2
TRIAL OBJECTIVES.......................................................................................18
2.3
BENEFIT - RISK ASSESSMENT ...................................................................18
3.
DESCRIPTION OF DESIGN AND TRIAL POPULATION.............. 20
3.1
OVERALL TRIAL DESIGN AND PLAN ......................................................20
3.1.1
Administrative structure of the trial...................................................22
3.1.2
Data Monitoring Committee (DMC)...................................................23
3.2
DISCUSSION OF TRIAL DESIGN, INCLUDING THE CHOICE OF 
CONTROL GROUP(S).....................................................................................23
3.3
SELECTION OF TRIAL POPULATION ......................................................24
3.3.1
Main diagnosis for study entry............................................................24
3.3.2
Inclusion criteria...................................................................................24
3.3.3
Exclusion criteria ..................................................................................25
3.3.4
Removal of patients from therapy or assessments.............................26
3.3.4.1
Removal of individual patients................................................26
3.3.4.2
Discontinuation of the trial by the sponsor..............................27
4.
TREATMENTS........................................................................................ 28
4.1
TREATMENTS TO BE ADMINISTERED....................................................28
4.1.1
Identity of BI 655066 and comparator product(s).............................28
4.1.2
Method of assigning patients to treatment groups ............................28
4.1.3
Selection of doses in the trial................................................................28
4.1.4
Drug assignment and administration of doses for each patient .......29
4.1.5
Blinding and procedures for unblinding ............................................29
4.1.6
Packaging, labelling, and re-supply ....................................................30


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4.1.7
Storage conditions.................................................................................30
4.1.8
Drug accountability ..............................................................................30
4.2
CONCOMITANT THERAPY, RESTRICTIONS, AND RESCUE 
TREATMENT....................................................................................................31
4.2.1
Rescue medication, emergency procedures, and additional 
treatment(s) ...........................................................................................31
4.2.2
Restrictions............................................................................................31
4.2.2.1 Restrictions regarding concomitant treatment .........................31
4.2.2.2
Restrictions regarding vaccination...........................................32
4.2.2.3
Restrictions on diet and life style.............................................32
4.3
TREATMENT COMPLIANCE.......................................................................33
5.
VARIABLES AND THEIR ASSESSMENT ......................................... 34
5.1
EFFICACY - PHARMACODYNAMICS........................................................34
5.1.1
Endpoints of efficacy.............................................................................34
5.1.1.1
Primary endpoint of efficacy ...................................................34
5.1.1.2
Secondary endpoints of efficacy..............................................34
5.1.1.3
Further endpoints of efficacy...................................................34
5.1.2
Assessment of efficacy...........................................................................34
5.2
SAFETY..............................................................................................................35
5.2.1
Endpoint(s) of safety.............................................................................35
5.2.1.1
Primary endpoints of safety .....................................................35
5.2.1.2
Secondary endpoints of safety .................................................35
5.2.1.3
Further endpoints of safety ......................................................35
5.2.2
Assessment of adverse events...............................................................35
5.2.2.1
Definitions of adverse events...................................................35
5.2.2.2
Adverse event and serious adverse event reporting.................37
5.2.3
Assessment of safety laboratory parameters......................................38
5.2.4
Electrocardiogram................................................................................41
5.2.5
Assessment of other safety parameters...............................................41
5.3
OTHER...............................................................................................................42
5.3.1
Other endpoint(s)..................................................................................42
5.3.2
Other assessment(s) ..............................................................................42
5.3.3
Pharmacogenomic evaluation..............................................................42
5.4
APPROPRIATENESS OF MEASUREMENTS.............................................42
5.5
DRUG CONCENTRATION MEASUREMENTS AND 
PHARMACOKINETICS..................................................................................43
5.5.1
Pharmacokinetic endpoint(s)...............................................................43
5.5.2
Methods of sample collection...............................................................43
5.5.2.1
Plasma sampling for pharmacokinetic analysis.......................43
5.5.2.2
Plasma sampling for assessment of anti-drug antibody...........44


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5.5.3
Analytical determinations ....................................................................44
5.6
BIOMARKER(S) ...............................................................................................44
5.6.1
Endpoints based on biomarker(s) .......................................................45
5.6.2
Methods of sample collection...............................................................45
5.6.3
Analytical determinations ....................................................................45
5.7
PHARMACODYNAMICS................................................................................45
5.7.1
Pharmacodynamic endpoints...............................................................45
5.7.2 Methods of sample collection...............................................................46
5.8
PHARMACOKINETIC - PHARMACODYNAMIC RELATIONSHIP .....46
6.
INVESTIGATIONAL PLAN.................................................................. 47
6.1
VISIT SCHEDULE............................................................................................47
6.2
DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS ................47
6.2.1
Screening and run-in period(s)............................................................47
6.2.2
Treatment period(s)..............................................................................47
6.2.2.1 Rollover visit - Extended visit 1.................................................47
6.2.2.2 Extended Dosing Period.............................................................48
6.2.3
End of trial and Extended follow-up period.......................................49
6.2.3.1 Vital status..................................................................................49
7.
STATISTICAL METHODS AND DETERMINATION OF
SAMPLE SIZE......................................................................................... 50
7.1
STATISTICAL DESIGN - MODEL................................................................50
7.2
NULL AND ALTERNATIVE HYPOTHESES ..............................................50
7.3
PLANNED ANALYSES....................................................................................50
7.3.1
Primary analyses...................................................................................50
7.3.2
Secondary analyses ...............................................................................50
7.3.3
Safety analyses.......................................................................................51
7.3.4
Interim analyses ....................................................................................51
7.3.5
Pharmacokinetic analyses ....................................................................51
7.3.6
Pharmacodynamic analyses.................................................................52
7.3.7
Pharmacogenomic analyses..................................................................52
7.4
HANDLING OF MISSING DATA ..................................................................52
7.5
RANDOMISATION ..........................................................................................52
7.6
DETERMINATION OF SAMPLE SIZE ........................................................52
8.
INFORMED CONSENT, DATA PROTECTION, TRIAL
RECORDS ................................................................................................ 53
8.1
STUDY APPROVAL, PATIENT INFORMATION, AND INFORMED 
CONSENT ..........................................................................................................53
8.2
DATA QUALITY ASSURANCE .....................................................................53


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8.3
RECORDS..........................................................................................................54
8.3.1
Source documents .................................................................................54
8.3.2
Direct access to source data and documents.......................................54
8.4
LISTEDNESS AND EXPEDITED REPORTING OF ADVERSE 
EVENTS..............................................................................................................54
8.4.1
Listedness...............................................................................................54
8.4.2
Expedited reporting to health authorities and IECs/IRBs................54
8.5
STATEMENT OF CONFIDENTIALITY.......................................................55
8.6
COMPLETION OF TRIAL..............................................................................55
9.
REFERENCES......................................................................................... 56
9.1
PUBLISHED REFERENCES...........................................................................56
9.2
UNPUBLISHED REFERENCES.....................................................................57
10. APPENDICES .......................................................................................... 58
10.1
PASI SCORE DEFINITION AND INSTRUCTIONS ...................................58
10.2 STATIC PHYSICIAN'S GLOBAL ASSESSMENT (SPGA) OF THE NPF 
PSORIASIS SCORE (NPFPS)..........................................................................59
10.3
PAIN VISUAL ANALOG SCALE (VAS) .......................................................60
10.4
DERMATOLOGY LIFE QUALITY INDEX.................................................61
10.5
PSORIATIC ARTHRITIS SCREENING AND EVALUATION TOOL.....61
10.6
CLINICAL EVALUATION OF LIVER INJURY .........................................63
10.6.1 Introduction...........................................................................................63
10.6.2 Procedures .............................................................................................63
10.7  SEVERITY OF AE AS DESCRIBED IN THE RHEUMATOLOGY 
COMMON TOXICITY CRITERIA V. 2.0.....................................................65
11. DESCRIPTION OF GLOBAL AMENDMENT(S).............................. 90


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ABBREVIATIONS
ADA
Anti-drug antibodies
ADL
Activities of daily living
AE(s)
Adverse event(s)
AESI
Adverse event of special interest
ALT [U/L]
aPTT
AP/ALP 
Alanine transaminase (SGPT)
Partial Thromboplastin Time
Alkaline Phosphatase
AST [U/L]
Aspartate transaminase (SGOT)
β
Slope parameter associated with the power model used
to evaluate dose proportionality
BCG
Bacille Calmette-Guérin vaccine
BI
Boehringer Ingelheim
BP [mmHg] 
Blood pressure
BSA 
Body surface area
CA
Competent Authority
Cf.
Confer (compare)
CHF
Congestive heart failure
CML
Local clinical monitor
CRA
CRO 
Clinical research associate
Clinical research organisation
CRF(s)
Case report form(s)
CRP
C-reactive protein
CTP
Clinical Trial Protocol
DILI
DLQI
Drug-induced liver injury
Dermatology Life Quality Index
DMC
Data monitoring committee
e.g.
Example given
ECG
Electrocardiogram
eCRF(s)
Electronic case report form(s)
EDTA
Ethylendiaminetetraacetic acid
ELISA
Enzyme-linked immunosorbent assay
EOS
EOT
Etc.
EV
FDA 
End of study
End of treatment
Etcetera
Extended Visit
Food and drug administration
FVC
Forced vital capacity
g 
gram(s) (for description of mass);
gravity (description of centrifugation)
GCP 
Good clinical practice


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Hb
Haemoglobin
HbA1c 
Haemoglobin (glycated Hb of A1c subtype)
HCG 
Hct
Human chorionic gonadotropin
Haematocrit
HDL 
HIV
High density lipoprotein
Human immunodeficiency virus
i.e.
Id est, that is
ICH 
International conference on harmonisation
IEC 
Independent ethics committee
IFN
IgG
Interferon
Immuneglobuline
IGRA
Interferon gamma release assay
IL 
Interleukin
INR 
International normalised ratio
IRB 
IRT
ISF
Institutional review board
Interactive Response Technology
Investigator site file
i.v. 
Intravenous
LLN
Lower limit of normal
mAb 
Monoclonal antibody
MACE 
Major Adverse Cardiovascular Events
MedDRA
mg
ml
mM
Medical dictionary for drug regulatory affairs
Milligrams
Millilitre
Millimole/Millimolar 
MRI
Magnetic resonance imaging
NGAL
nM
Neutrophil gelatinase associated lipocalin
Nanomole/nanomolar 
NPFPS
National Psoriasis Foundation Psoriasis Score
OLE
OPU
Open label extension
Operation Unit
OTC
PASE
Over the counter medication 
Psoriatric Arthritis Screening and Evaluation Tool
PASI
Psoriasis Area and Severity Index
PD
pH
Pharmacodynamic(s)
Power of hydrogen
PK
PMN
Pharmacokinetic(s)
Polymorphonuclear
PR [1/min] 
PT
PUVA
RBC
Pulse rate
Prothrombin time
Psoralen + UVA
Red blood  cell count 
RCTC
Rheumatology Common Toxicity Criteria
RDC
Remote data capture


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REP
Residual effect period
RR 
Respiratory rate
SAE 
Serious adverse event
s.c. 
Subcutaneous
SOP 
Standard operating procedure
sPGA 
Static Physician Global Assessment
SUSARs 
Suspected unexpected serious adverse reactions
TB
TCM
Th
Tuberculosis
Trial Clinical Monitor
T helper (cell)
TMF
Trial Master File
TNF  
Tumor necrosis factor
ULN
US
UVA
UVB
Upper limit of normal
United States
Ultraviolet-A rays
Ultraviolet-B rays
VAS
Visual Analogue Scale
WBC
White blood cells


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1.
INTRODUCTION
1.1
MEDICAL BACKGROUND
Psoriasis is a common skin disease characterized by raised, well-demarcated erythematous 
oval plaques with adherent silvery scales (R11-1257). It affects approximately 2% of the 
world population including 25 million people in North America and Europe making it the 
most prevalent immune mediated skin disease (R08-1089). It usually begins in late 
adolescence and early adulthood and then usually persists for life with remissions and 
relapses. The latter can be triggered by infections, medications and stress.
Disease severity can be characterized by body surface area (BSA) involvement with <5% 
being considered mild, 5-10% moderate and >10% severe (R11-1259). Disease status has 
been measured using the Psoriasis Area and Severity Index (PASI), a composite measure of 
erythema, induration, desquamation and BSA affected by psoriasis with a range of scores 
from 0 to 72 (R96-3541). The percentage of patients reaching PASI75, a 75% reduction in 
score from baseline to 12 or 16 weeks is traditionally used as a primary endpoint in psoriasis 
treatment trials.
Topical agents, including corticosteroids, are the mainstay for mild disease. Treatments for 
more advanced conditions can be classified into phototherapy, immunosuppressants, other 
systemic agents, and more recently, biologics (R11-1261).
Many of the agents may be used in combination or on a rotational basis to limit toxicity. 
Phototherapy may be used alone or with topical tar and dithranol products or with systemic 
and biologic agents. Although effective, the frequency and nature of this treatment reduces 
adherence. Adverse events (AEs) of phototoxicity, skin aging and concerns of development 
of skin cancers, also reduce acceptance of this therapy (R11-1261). Immunosuppressants, 
such as methotrexate or cyclosporine, are also effective for the management of moderate to 
severe psoriasis and relapses, but cumulative hepatotoxicity, bone marrow suppression and 
rarely pulmonary toxicity with methotrexate and nephrotoxicity with cyclosporine, requires 
careful monitoring and prevents the use of these agents long term.
Biologic agents such as tumor necrosis factor (TNF) blockers were first found efficacious in 
Crohn’s disease, ulcerative colitis and rheumatoid arthritis prior to their use in psoriasis. 
Although not studied in head-to-head comparisons, different agents in this class have varying 
efficacy in psoriasis: infliximab and adalimumab are more efficacious especially in short term 
with PASI75 of 70-87% vs. etanercept (PASI75 of 50%) (R11-1261). These agents have been 
used for treating relapses and maintenance as well as the management of psoriatic arthritis, 
which occurs in approximately a third of all patients with psoriasis. However, TNF has 
myriad effects on immune function and TNF blockers have been associated with an increased 
risk of serious infections, in particular, tuberculosis and other opportunistic infections, 
cancers, including lymphomas, and demyelinating disorders.
BI 655066 is a humanized antagonistic monoclonal antibody (mAb) directed against the p19 
subunit of the human cytokine interleukin-23 (IL-23). IL-23 plays a critical role in the 


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differentiation and function of Th17 cells, which have emerged as an important T-cell 
subpopulation involved in the pathogenesis of immune mediated disorders (R12-1008)
The therapeutic rationale for an IL-23 antagonist in inflammatory diseases such as psoriasis, 
Crohn’s disease, and ankylosing spondylitis, is supported by several lines of evidence 
including mouse models, genome-wide association studies and histological findings in 
humans.
Although previous experience with selective IL-23 antagonists is limited, a mAb targeting the 
common p40 subunit of the IL-12 and IL-23 cytokines, ustekinumab (Stelara®), has been 
approved for the treatment of psoriasis, and a second (briakinumab) reached Phase III clinical 
trials before development was stopped. Both ustekinumab and briakinumab showed efficacy 
in the treatment of psoriasis.
The critical role of IL-12 in adaptive immunity raised concerns that mAbs directed against 
the IL-12 p40 subunit could increase the risk of infections or cancer, due to inhibition of IL-
12-dependent immune surveillance mechanisms (P06-11555, R11-1236). Indeed, higher rates 
of these events were noted in pivotal Phase III randomised controlled trials of briakinumab 
(R11-1529, R12-1010), although not in trials of ustekinumab. However, complete IL-23 
deficiency is not associated with a predisposition to mycobacterial infections (R12-1011) 
although it is associated with significant defects in humoral and delayed-type hypersensitivity 
responses in mice (R11-1204).
Observations of Major Adverse Cardiovascular Events (MACE) during the clinical 
development of both briakinumab and ustekinumab raised concerns that inhibition of either 
IL-12, IL-23, or both could pose cardiovascular safety risks (R11-4193). However, such a 
risk has not been confirmed among patients receiving ustekinumab for up to five years (R13-
3518). No additional data has emerged to suggest a specific cardiovascular risk associated 
with inhibition of IL-23; nevertheless, particular attention will be given to cardiovascular 
AEs in clinical trials of BI 655066.
1.2
DRUG PROFILE
BI 655066 is a humanized monoclonal antibody (mAb) of the IgG1 subclass that is directed 
towards IL-23p19. The framework of the antibody has been engineered with two mutations in 
the Fc region to reduce Fcγ receptor and complement binding. The C-terminal lysine of the 
heavy chain has also been deleted to reduce potential charge heterogeneity.
In Study 1311.1, a Phase I single rising dose trial in psoriasis patients, administration of BI 
655066 either intravenously or subcutaneously appeared to be well tolerated.  A total of 39 
patients received a single dose of either BI 655066 i.v. (n=18), s.c. (n= 13), or placebo (n=8). 
All patients who received 0·01, 0·25, 3, or 5 mg/kg i.v., or 0·25 or 1 mg/kg s.c. doses of BI 
655066 (n=27) achieved PASI75 responses by Week 12 vs. 33% (1/3) and 67% (2/3) in 0·05 
and 1 mg/kg i.v. dose groups, respectively vs. 13% (1/8) in the combined placebo group. 
PASI90 rates by Week 12 were up to 100% (0·01 mg/kg i.v. group [3/3] and in both s.c. dose 
groups [13/13]) vs. 0% (0/8) in placebo group. Efficacy was well maintained at Week 24 and 
beyond. Treatment with BI 655066 resulted in significant changes in select psoriasis related 


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biomarkers in the skin and plasma through Week 12 and correlated with improvement in 
PASI scores. There were no clear relationships between the overall frequency of AEs and 
treatment; nor were there clear relationships between the occurrence of AEs in specific organ 
classes, individual AEs, their severity or relatedness, and treatment. Exposure increased in an 
approximately dose-proportional manner, with absolute bioavailability of 59%, providing a 
rationale for conducting further clinical studies of BI 655066 in patients with psoriasis. (M14-
0004)


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2.
RATIONALE, OBJECTIVES, AND BENEFIT - RISK 
ASSESSMENT
2.1
RATIONALE FOR PERFORMING THE TRIAL
The phase I, single rising dose study (1311.1) has shown proof of concept and proof of 
efficacy for BI 655066 in patients with moderate to severe psoriasis. 
The preceding phase II study (1311.2) will allow for the evaluation of the efficacy, safety, 
tolerability, pharmacokinetics and pharmacodynamics of three different dose regimens (18 
mg, 90 mg and 180 mg) of BI 655066, as well as dose-finding of BI 655066 for further 
studies. In addition the 1311.2 trial will compare the efficacy of BI 655066 with Stelara®, an 
approved therapy for patients with moderate to severe psoriasis.
The data generated from this extension study is anticipated to provide additional safety data 
of up to approximately four years treatment in approximately 100 patients treated with BI 
655066. Furthermore the study is being performed in order to allow extended access to a 
potential beneficial intervention, according to the principles laid down in the Declaration of 
Helsinki.
2.2
TRIAL OBJECTIVES
The overall purpose of this open label extension (OLE) trial is to assess long-term safety and 
efficacy (durability of response) of BI 655066 in patients with moderate to severe chronic 
plaque psoriasis. In addition, this study will provide an opportunity for subjects to have 
extended access to a proven active therapy for approximately four years administration.
The primary objective of the study is to investigate safety of BI 655066, in patients with 
moderate to severe chronic plaque psoriasis, receiving long-term treatment. 
Additional objectives of this study are to further investigate long-term efficacy, tolerability, 
pharmacokinetics, pharmacodynamics and immunogenicity of BI 655066. 
Study endpoints are listed in Section 5.
2.3
BENEFIT - RISK ASSESSMENT
Results of the Phase I study with BI 655066 (study 1311.1) suggest that a single injection 
intravenously or subcutaneously (i.v. or s.c.) of BI 655066 is associated with substantial and 
durable improvements in the cutaneous manifestations of psoriasis. At doses of 0.25 mg/kg 
intravenously and above, all active dose groups showed improvement in mean PASI scores of 
at least 75% from baseline by week 12, which lasted at least until week 24. Similar 
improvements were observed in both of the active BI 655066 subcutaneous dose groups
(M14-0004). 
Patients rolling over in this OLE will have completed the single blind 1311.2 study where 
75% of all patients will have received BI 655066 at different dose levels.  Based on the 
preliminary data from study 1311.1 described in Section 1.2, where good tolerability was 


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shown, and no drug related serious adverse events (SAE), patients are likely to benefit from 
participation in this study.
Risks of participating in this study include risks related to the trial specific procedures such as 
blood sampling, subcutaneous injection of study medication. Blood sampling and 
subcutaneous injections can cause local bruising, inflammation, and pain. 
As with any immune modulating agent, BI 655066 has the potential to impair immune 
function resulting in a risk of infection. This will be addressed by clinical monitoring for AEs 
during the treatment and follow up periods. Interferon gamma (IFN-γ) release assay to M. 
tuberculosis will be obtained at the initial roll-over visit, in order to exclude or discontinue 
documented untreated patients with active or latent tuberculosis infection (TB). All patients 
will be re-tested at the Extended end of treatment visit in order to assess long-term impact of 
BI 655066 on M. tuberculosis exposure. Patients having current signs or symptoms of 
infection or history of serious infection will not be included in the study. 
The role of IL-23 in tumour immunity is not well established at this time, but an increased 
risk of cancer from an IL-23 antagonist, though considered small, cannot be excluded.
Major adverse cardiovascular events (MACE), including myocardial infarction, 
cerebrovascular accident, and cardiovascular death, have been initially reported in association 
with the anti-IL-12/23 agents, ustekinumab and briakinumab, in patients with psoriasis. 
However, such a risk has not been confirmed among patients receiving ustekinumab for up to 
five years (R13-3518). The overall risk of MACE in the present study is considered to be 
low.
Local reactions to i.v. and s.c. administered biologic agents are uncommon, and are usually 
limited to redness, swelling or induration at the injection site. Manifestations of systemic 
hypersensitivity reactions include anaphylaxis, pruritus, hypotension, and respiratory distress. 
Both local and systemic hypersensitivity reactions are readily detectable, transient in nature, 
and manageable with standard medical treatment. No systemic hypersensitivity reactions 
have been reported with BI 655066 to date. Patients will be closely monitored 30 minutes to 
1 hour after drug administration for signs of redness, swelling or hardness at the injection site 
or generalized itching, dizziness or difficulty breathing.
Although rare, a potential for drug-induced liver injury is under constant surveillance by 
sponsors and regulators. Therefore, this study requires timely detection, evaluation, and 
follow-up of laboratory alterations of selected liver laboratory parameters to ensure patients´ 
safety (cf. section 10.4).
The study has been designed, and will be conducted in such a manner as to limit these risks 
as much as possible. In order to mitigate any safety signals as early as possible, an 
independent Data Monitoring Committee (DMC) will oversee this study. Since all patients 
will receive active treatment at a dose of, or greater than the projected marketed dose, most 
patients will likely have a benefit from participating in this study. Therefore, the benefit-risk 
assessment is considered appropriate for a clinical trial of an experimental therapy at this 
stage of development.


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3.
DESCRIPTION OF DESIGN AND TRIAL POPULATION
3.1
OVERALL TRIAL DESIGN AND PLAN
This open label extension trial (OLE), investigates the additional safety and efficacy of the 90 
mg dose of BI 655066.  Approximately 100 patients who meet the entry criteria are planned 
for inclusion in this trial, rolling over from the preceding 1311.2 trial. The treatment will be 
open label. 
The treatment period will be approximately four years of administration starting with first 
administration of BI 655066 in either trial 1311.2 or 1311.13, followed by a 12 week follow 
up period. After 01-May-2018 and approval of this protocol amendment in each respective 
country, the next study visit will be the Extended EOS visit and therewith the last visit in this 
study. Patients who have completed the study without early treatment discontinuation will be 
offered to roll over to M15-997 open label extension (OLE) trial if they fulfill the in- and 
exclusion criteria for the M15-997 trial. Refer to section 6.2.3.
Patients rolling over from the preceding trial 1311.2 will have to complete the treatment 
period in that trial, or complete the entire trial including the follow up period, reaching end of 
study. If, during the follow up period of the preceding trial (at any visit from week 24 and 
onwards in trial 1311.2) loss of response is detected, the patient can roll over in this extension 
trial. For this, loss of response is defined as < PASI50. 
Extended visit 1of this trial should preferably be performed as a combined visit the same day 
as End of Study visit of 1311.2, or within an interim period of maximum 6 weeks thereafter. 
Figure 3.1:1 Guideline for roll over of patients from 1311.2 to OLE study 1311.13


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After the approval of this protocol amendment in each respective country, all patients will 
follow Flow Chart (Extended Dosing Period) and receive 90mg BI 655066 subcutaneously at 
their Extended visit 1 (EV1). From EV1 onwards, BI655066 will be administered 
subcutaneously every 12 weeks during the trial. At EV2, if there is a lack of response, 
defined as <PASI90, the dose should be increased to 180mg for the remainder of the trial (see 
Fig 3.1.2).
For ongoing patients under the previous protocol amendment (Pre-Extended Dosing Period, 
see Fig 3.1.3), EV1 should be conducted at the following time points:
1. For ongoing patients with ≥12 weeks since the EOT visit: Conduct EV1 as soon as 
possible 
2. For ongoing patients still undergoing treatment or with <12 weeks since the EOT 
visit: Conduct EV1 at the time of the next scheduled treatment or follow up visit 
(note: EV1 should not be conducted at the time point of Visit 2 under the previous 
protocol, patients with Visit 2 as their next scheduled visit should have their EV1 
replacing their Visit 3 instead)
Figure 3.1:2 Guideline for assessment of dose adjustment


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Figure 3.1:3 Visit schedule Pre-Extended Dosing Period
If there are any tolerability issues, as assessed by the investigator, the patient will be 
discontinued. 
The plaque psoriasis will be evaluated by PASI score at each visit. The standard clinical 
endpoints of PASI50, PASI75, PASI90 and PASI100 will be assessed at each visit based on 
the baseline PASI from 1311.2.  
The end of study is defined as the date the last subject completes the Extended End-of-study 
visit. 
3.1.1
Administrative structure of the trial
The trial is sponsored by AbbVie in the US and Boehringer Ingelheim (BI) ex-US.
The trial is planned to be conducted at sites participating in the 1311.2 trial, i.e. it will be 
conducted at approximately 24 sites in 4 different countries. 
Boehringer Ingelheim has appointed a Trial Clinical Monitor (TCM), responsible for 
coordinating the activities required in order to manage the trial in accordance with applicable 
regulations and internal standard operating procedures (SOPs), directing the clinical trial 
team in the preparation, conduct and reporting of the trial and ensuring appropriate training 
and information for Local Clinical Monitors (CML), Clinical Research Associates (CRAs) 
and investigators of participating countries.
Data management will be done by BI according to BI SOPs and the Statistical Evaluation
will be done by AbbVie according to their SOPs. For these activities a Trial Data Manager 
and a Trial Statistician have been appointed. A list of responsible persons will be available in 
the Trial Master File (TMF).
The organisation of the trial in the participating countries will be performed by the respective 
local BI-organisation (Operation Unit (OPU)) or by a Contract Research Organisation (CRO) 
with which the responsibilities and tasks have been agreed and a written contract filed before 
initiation of the clinical trial. In each OPU participating in this study, a CML will be 
appointed responsible for coordinating the activities required, in order to manage the trial in 
accordance with applicable regulations and internal SOPs in the countries covered by the 
respective BI OPU.


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A Co-ordinating Investigator has been nominated to coordinate investigators at different sites 
participating in this multicentre, multinational trial. Tasks and responsibilities for the 
Coordinating Investigator will be defined in a written contract filed before initiation of the 
trial.
Details of the trial supplies including responsible institutions are given in Section 4 of this 
protocol.
The Investigator Site File (ISF) will be maintained at the sites as required by local regulation 
and BI-SOPs. A copy of the essential ISF documents will also be kept as an electronic TMF 
document according to BI SOPs.
A central laboratory service and an Interactive Response Technology (IRT) vendor will be 
used in this trial. Details will be provided in IRT Manual and Central Laboratory Manual, 
available in ISF.
Safety will be monitored by an independent Data Monitoring Committee (DMC).
3.1.2
Data Monitoring Committee (DMC)
The trial will include the review of data by an external, independent DMC, including an 
independent statistician. The purpose of the DMC is to ensure the welfare of subjects 
participating in this trial is maintained by monitoring the trial for possible, untoward harmful 
effects or inappropriate frequency of adverse events for this class of medication. The DMC 
will evaluate and analyse accrued, unblinded safety and efficacy data in order to recommend 
whether the trial should continue, be modified or stopped due to safety or lack of efficacy 
concerns. For details regarding DMC structure and scheduled meetings, please consult the 
DMC charter.
Sponsor will agree with the DMC a set of strictly defined stopping criteria for the study level, 
to be included into the DMC Charter.
The final DMC Charter will be available before study initiation.
3.2
DISCUSSION OF TRIAL DESIGN, INCLUDING THE CHOICE OF 
CONTROL GROUP(S)
Study 1311.13 is designed as an open label extension clinical trial, and is expected to 
generate additional safety information to support the registration submission. As noted in 
section 4.1.3 below, the intermediate dose (90 mg) from the 1311.2 study will be used, with 
the option of moving to a higher dose (180 mg) if inadequate clinical activity is noted. Our 
goal in this study is to obtain safety and efficacy data following long-term drug 
administration. As an open-label study, we realize that no powered or controlled analysis can 
be obtained. However, we will be able to evaluate initial tendencies and at the same time 
permit our early study participants an opportunity to maintain access to a therapy that initially 
has shown the potential to have significant clinical benefit. 


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3.3
SELECTION OF TRIAL POPULATION
Eligible patients from trial 1311.2 will be offered participation in this OLE trial. The check 
for patient eligibility will be based upon a successful completion (cf. Section 3.3.2) of the 
previous trial and on signing the Informed Consent for the OLE. 
A 40 % dropout rate from preceding trial is expected, leaving approximately 100 patients to 
be entered in this trial. 
A log of all patients included into the study (i.e. having given informed consent) will be 
maintained in the ISF at the investigational site. 
3.3.1
Main diagnosis for study entry
Moderate to severe chronic plaque psoriasis.
3.3.2
Inclusion criteria
1. Patients with moderate to severe chronic plaque psoriasis, who have successfully 
completed the preceding trial, 1311.2. Successful completion of preceding trial is 
defined as either of the following:
a. Completion of the entire follow up period, thus reaching End-of-study (EOS)
visit.
b. Loss of response, defined as decrease in response to <PASI50 at any time 
from week 24.
2. Patient must give informed consent and sign an approved consent form prior to 
any study procedures in accordance with Good Clinical Practice (GCP) and local 
legislation
3. Applicable only for female patients:
Negative urine pregnancy dip stick test at the roll-over visit, and if available at roll-
over visit, negative
Serum ß-Human Chorionic Gonadotropin (ß-HCG) test (cf.Section3.3.4.1).
In addition:
Women of childbearing potential (not surgically sterilized and between menarche and
1 year postmenopausal), that, if sexually active agree to use one of the appropriate 
medically accepted methods of birth control in addition to the consistent and correct 
use of a condom from date of the roll-over visit until 12 weeks after last treatment in 
this trial. Medically accepted methods of contraception’s are: ethinyl estradiol 
containing contraceptives, diaphragm with spermicide substance, and intra-uterine-
device.
OR


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Female patients which have vasectomized sexual partner(s) (vasectomy at least 1 year 
prior to enrolment).
OR
Surgically sterilized female patients with documentation of prior hysterectomy, tubal 
ligation or complete bilateral oophorectomy.
OR
Postmenopausal women with postmenopausal is defined as permanent cessation ≥ 1 
year of previously occurring menses.
3.3.3
Exclusion criteria
1. Patients who experienced any drug related Serious Adverse Event in the preceding 
trial
2. Patients who have developed guttate, erythrodermic or pustular psoriasis or drug-
induced psoriasis (as diagnosed by the investigator), during the preceding trial 1311.2. 
3. Evidence of current or previous clinically significant disease, medical condition other 
than psoriasis, or finding of the medical examination (including vital signs and 
(electrocardiography (ECG)), that in the opinion of the investigator, would 
compromise the safety of the patient or the quality of the data. 
4. Known clinically important acute or chronic infections including hepatitis, HIV. In 
regards to Tuberculosis the following applies: 
#
Signs or symptoms suggestive of current active or latent tuberculosis upon 
medical history, physical examination and/or a chest radiograph (both 
posterior-anterior and lateral views, taken within 3 months prior to the first 
administration of study drug and read by a qualified radiologist).
#
History of latent or active TB prior to screening, except for patients with 
documented completion of an adequate treatment regimen, at least 6 
months prior to the first administration of study agent. 
#
Positive QuantiFERON-TB Gold In-Tube test (IGRA) within 2 months 
prior to the roll-over visit (if available) (cf. Section 3.3.4.1), in which 
active tuberculosis has not been ruled out. This does not apply to patients 
with history of latent tuberculosis with documented completion of an 
adequate treatment regimen, at least 6 months prior to the first 
administration of study agent. 
5. Patients who have developed malignancy, or suspicion of active malignant disease 
during the preceding trial 1311.2 (except treated cutaneous squamous cell or basal cell 
carcinoma or carcinoma in situ of the cervix that have been adequately treated). 


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6. Intake of restricted medications (cf. Section 4.2.2.1) or other drugs considered likely 
to interfere with the safe conduct of the study, as assessed by the investigator.
7. Alcohol or drug abuse within 3 months prior to the roll-over visit that would interfere 
with trial participation or any ongoing condition leading to a decreased compliance to 
study procedures in the opinion of the investigator.
8. Any clinically significant laboratory abnormalities based on the last available lab 
results received during the preceding trial (according to the investigator’s medical 
assessment) (cf. Section 6.2.2.1).
9. Pre-menopausal woman who is pregnant or nursing
Note: 
As there might be other medical and social issues, not covered by the above criteria it is left 
to the discretion of the investigator to exclude patients based on clinical judgment, even if 
other eligibility criteria are satisfied. 
3.3.4
Removal of patients from therapy or assessments
3.3.4.1
Removal of individual patients
An individual patient is to be withdrawn from the trial if:
#
The patient withdraws consent, without the need to justify the decision.
#
Clinically important acute or chronic infections including hepatitis, HIV and tuberculosis 
(including latent tuberculosis), or a positive interferon gamma release assay (IGRA) 
testing for tuberculosis (cf. Table 5.2.3: 1) according to test at the roll-over visit. 
#
The patient is no longer able to participate for other medical reasons (e.g. pregnancy, 
surgery, AEs or other diseases).
A patient can be withdrawn after discussion between sponsor and investigator if eligibility 
criteria are being violated or if the patient fails to comply with the protocol (e.g. non-
attendance at study assessments). Note: Patients using restricted medications (cf. Section 
4.2.2), will continue to be followed up to collect safety data but their efficacy and PD 
endpoints assessed after administration of restricted medications will not be considered for 
analysis.
If a patient withdraws from the study after informed consent, this will be documented and the 
reason for withdrawal will be recorded in the case report form (CRF). This data will be 
included in the trial database and will be reported. At the time of discontinuation a complete 
end of treatment (Extended EOT) evaluation should be performed according to Flow Chart
and the patient will subsequently enter a follow up period of 12 weeks, until a final Extended 
EOS visit is performed. If the decision to discontinue study participation is taken in between 
study visits in the treatment period, an Extended EOT visit is to be scheduled at the earliest 
convenience and by the latest at the next upcoming visit according to Flow Chart and the 
information will be recorded in the CRFs.


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If the decision to discontinue is taken in the 12 week follow up period, an early Extended 
EOS visit is to be scheduled at the earliest convenience. The procedures described at 
Extended EOS will be performed and the information will be recorded in the CRFs. The 
withdrawals will be discussed in the final report of the study.
If a patient becomes pregnant during the trial, the investigational product needs to be stopped. 
The patient will be followed up until birth or otherwise termination of the pregnancy. The 
data of the patient will be collected and reported in the clinical trial report until last patient 
last visit and any events thereafter will be reported in the BI 655066 safety database. 
3.3.4.2
Discontinuation of the trial by the sponsor
AbbVie/ Boehringer Ingelheim reserves the right to discontinue the trial overall or at a 
particular trial site at any time for the following reasons:
a. Emergence of any efficacy/safety information that could significantly affect 
continuation of the trial or any other administrative reasons. 
b. Violation of GCP, the clinical trial protocol (CTP), or the contract by a trial 
site or investigator, disturbing the appropriate conduct of the trial.
The investigator / the trial site will be reimbursed for reasonable expenses incurred in case of 
trial termination according to option a.


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4.
TREATMENTS
4.1
TREATMENTS TO BE ADMINISTERED
BI 655066 is supplied by Boehringer Ingelheim, and will be administered subcutaneously. 
4.1.1
Identity of BI 655066 and comparator product(s)
The characteristics of the test product for s.c. administration are below.
Substance:
BI 655066: Anti-human IL23p19 mAb
Pharmaceutical formulation:
Chemical name:
Anti-human IL-23p19 mAb
Molecular weight:
Approximately 148 kDa
Source:
Boehringer Ingelheim Pharma GmbH & Co. KG
Unit strength:
90 mg BI 655066 in a pre-filled syringe with 1 ml 
(concentration 90 mg/ml)
Posology
Multiple doses
Route of administration:
s.c.
4.1.2
Method of assigning patients to treatment groups
Patients will receive a single dose of open label BI 655066 every 12 weeks. The initial dose 
for all patients moving into the open label extension study will be 90 mg. 
If response is maintained, i.e. achievement of PASI90 at Extended visit 2, 90 mg dosing will 
occur every 12 weeks until Extended EOT. 
If there is a lack of response, defined as response below PASI90 at Extended visit 2, the dose 
should be increased to 180 mg, and the 180 mg dosing will occur every 12 weeks until 
Extended EOT.
Detailed instructions for preparation of BI 655066 for administration of each dose will be 
given in the ISF.
4.1.3
Selection of doses in the trial
The treatment is derived from the treatment groups in the preceding phase II trial, where the 
dose selection is based on the completed phase I trial in which clinical improvement in 
patients with psoriasis was observed across a wide dose range (~18 mg -375 mg). 
The choice of the “90 mg/dose” was based on several pieces of data obtained in the initial 
1311.1 single-dose, dose-escalation study:  an analysis of dose given (and the subsequent 
“area under the curve” exposure data) plotted against the clinical response based on the PASI 


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score noted that the stable effective dose was likely to be greater than 1.0 mg/kg 
(approximately 90 mg) 
Subsequent to selection of the starting dose for 1311.13, an interim analysis of 1311.2 
indicated that the 180 mg dose resulted in a numerically higher proportion of patients who 
achieved PASI90. Since the higher dose was not associated with a higher incidence of any 
specific adverse events, patients who do not achieve PASI90 on the 90 mg dose are eligible 
to receive the higher dose of 180 mg. This dose is also consistent with the objective of 
obtaining safety data on a dose equal to or greater than the proposed “to be marketed” dose of 
150 mg, allowing us to obtain additional safety information appropriate for inclusion in future 
discussion with health authorities.
4.1.4
Drug assignment and administration of doses for each patient
The study drug will be administered by the physician investigator or by authorised study 
personnel (e.g. study nurse). The study drug will be administered as a subcutaneous injection 
in the abdomen, thighs, gluteal regions, or upper arms. Injections being given in the same 
area should be at least 2 cm apart and should not be close to a vein. The injection site should 
avoid sites of psoriasis involvement as well as sites where the skin is tender, bruised, 
erythematous, or indurated, and should be alternated to other areas for subsequent doses.
Further information regarding technique of injection and injection materials (syringes, 
needles) will be provided in the ISF. For 180 mg doses, two syringes of 1 ml BI 655066, each 
of 90 mg, will be allocated and injected. Dilution of the study medication is not allowed and 
no dose modification, apart from the protocol specified doses, is permitted.
Administration of biologic agents involves the risk of local (injection site) or systemic 
hypersensitivity reactions. Therefore the patients should be closely monitored for signs and 
symptoms of hypersensitivity reactions for approximately 1 hour after the first dose 
administered, and 30 minutes following all other doses of study drug. Study personnel should 
observe the injection site for signs of redness, swelling or hardness. They should also ask 
subjects about itching, dizziness or shortness of breath. Patients should be advised that if they 
experience redness, swelling or other changes at the injection site, they should notify site 
personnel. They should further be advised that if they experience itching all over or a feeling 
of being swollen, dizzy or short of breath, they should notify site personnel or their own 
healthcare provider immediately. 
Vital signs will be taken pre-dose, 5 minutes, and 1 hour (at roll-over visit) or 30 minutes (at 
following visits) after the dose is administered (cf. Flow Chart). Hypersensitivity reactions 
should be treated according to medical standards. Pre-medications for further injections might 
be considered and will be agreed on between investigator and BI clinical monitor. 
4.1.5
Blinding and procedures for unblinding
Not applicable.
In this open-label trial, treatment allocation will not be concealed throughout the study. The 
CRF will contain information on treatment. 


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4.1.6
Packaging, labelling, and re-supply
BI 655066 supplies will be provided by Boehringer Ingelheim (cf. Section 4.1.1 for more 
details regarding the supplies). Pre-filled syringes of study medication will be provided in 
individual boxes identified with the trial number, batch and medication number. Supply of 
study medication will be managed by the IRT.
For details of packaging and the description of the label, refer to the ISF.
4.1.7
Storage conditions
The trial medication must be stored securely, e.g. in a locked refrigerator or at a pharmacy, in 
their original packaging. It may only be dispensed to trial patients according to the clinical 
trial protocol, by authorised personnel as documented in “Trial Staff List”.
Drug supplies should be stored as indicated on the country specific booklet page. A 
temperature log must be maintained. If the storage conditions are found to be outside the 
specified range, immediately contact the local clinical monitor as provided in the lists of 
contacts.
Further details are provided in the Investigator´s Brochure and on the country specific labels 
of which a sample will be maintained in the ISF. 
4.1.8
Drug accountability
The investigator/ pharmacist/ investigational drug storage manager will receive the 
investigational drugs delivered by the sponsor when the following requirements are fulfilled:
#
approval of the study protocol by the Institutional Review Board (IRB) / ethics 
committee,
#
availability of a signed and dated clinical trial contract between the sponsor and the 
Head of Trial Centre,
#
approval/notification of the regulatory authority, e.g. competent authority,
#
availability of the curriculum vitae of the principal investigator,
#
availability of a signed and dated clinical trial protocol or immediately imminent 
signing of the clinical trial protocol,
#
availability of the proof of a medical licence for the principal investigator, 
#
availability of the Form 1572 (only applicable for (United States (US)).
The investigator/ pharmacist/ investigational drug storage manager must maintain records of 
the product’s delivery to the trial site, the inventory at the site, the use by each patient, and 
the return to the sponsor or alternative disposition of unused product(s), on the respective 
forms in the ISF. 
These records will include dates, quantities, batch/serial numbers, expiry (‘use by’) dates, and 
the unique code numbers assigned to the investigational product(s) and trial patients. The 


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investigator / pharmacist / investigational drug storage manager will maintain records that 
document adequately that the patients were provided the doses specified by the CTP and 
reconcile all investigational product(s) received from the sponsor. At the time of return to the 
sponsor or designee, the investigator / pharmacist / investigational drug storage manager must 
verify that all unused or partially used drug supplies have been returned and that no 
remaining supplies are in the investigator’s possession. Account must be given for any 
discrepancies.
4.2
CONCOMITANT THERAPY, RESTRICTIONS, AND RESCUE 
TREATMENT
4.2.1
Rescue medication, emergency procedures, and additional treatment(s)
In principle, any additional concomitant therapy considered necessary for the patient’s 
welfare may be given at the discretion of the investigator. Stable doses of concomitant 
therapies for chronic conditions, for which neither the condition nor the treatment are judged 
to exclude the patient from participation (cf. Section 3.3.3), are permissible. However, all 
concomitant medications being taken by eligible patients must be carefully evaluated, and 
questions on the use of concomitant medications should be discussed with the BI clinical 
monitor.
In the event that a patient experiences an intolerable increase of psoriasis during the course of 
the trial, topical steroids of US class 6 (mild, such as desonide) or US class 7 (least potent, 
such as hydrocortisone) will be permitted for use limited to the face, axilla, and/or genitalia. 
Details of the drug used and the reason must be recorded in the electronic case report forms 
(eCRF). These topical medications should not be used within approximately 24 hours prior to 
visits requiring the PASI.
Investigational products are not allowed during the course of the trial.
In case of adverse events in need of treatment, symptomatic therapy according to the 
judgment of the investigator will be permitted. All concomitant and/or rescue therapies will 
be recorded on the appropriate pages of the eCRF.
There are no special emergency procedures to be followed.
Patients with a positive IGRA testing (Tb screening) at the roll-over visit should be followed-
up according to local guidelines.
4.2.2
Restrictions
4.2.2.1 Restrictions regarding concomitant treatment
The medications (or classes of medication) listed in Table 4.2.2.1:1 must not be taken for the 
specified times before the roll-over l visit and for the whole duration of the study including 
the Extended Follow-up Period.


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Table 4.2.2.1: 1 Restricted medications
Investigational products not otherwise 
described below (except 1311.2 study drug) 
Throughout the duration of preceding trial 
1311.2, and for the whole duration of this 
trial, including any interim period between 
the trials and the Extended Follow-up Period.
Any biological agents, including but not 
limited to infliximab, etanercept, 
adalimumab
Throughout the duration of preceding trial 
1311.2, and for the whole duration of this 
trial, including any interim period between 
the trials and the Extended Follow-up Period
Oral or injectable psoriasis medications (not 
biologicals) including but not limited to 
retinoids, methotrexate, cyclosporine, 
fumarates, or any other drugs known to 
possibly benefit psoriasis.
Systemic corticosteroids in any dosage form.
Any drug known to interfere with or to 
aggravate psoriasis including but not limited 
to lithium and interferons, or 
Phototherapy (UVB, PUVA, UVA).
Throughout the duration of preceding trial 
1311.2, and for the whole duration of this 
trial, including any interim period between 
the trials and the Extended Follow-up Period
Steroids, retinoids, vitamin D analogs, 
vitamin A analogs and anthralin in any 
formulation (i.v., s.c., topicals, oral).
Throughout the duration of preceding trial 
1311.2, and for the whole duration of this 
trial, including any interim period between 
the trials and the Extended Follow-up Period. 
(for exceptions cf. Section 4.2.1)
4.2.2.2
Restrictions regarding vaccination
Live vaccinations during the study are not allowed. Bacille Calmette-Guérin vaccines (BCG)
are not allowed throughout the duration of preceding trial 1311.2, and for the whole duration 
of this trial, including any interim period between the trials. It is recommended that patients 
are advised not to take any live vaccines or BCG vaccines for up to 1 year after the last 
administration of study drug. 
4.2.2.3
Restrictions on diet and life style
Patients must be fasted for at least 8 hours prior to collection of the safety laboratory samples, 
starting from the initial roll-over visit.
Patients should refrain from excessive physical activity at least 24 hours prior to study visits, 
during the course of the study (competitive sport etc.).
Use of tanning beds is not allowed during the course of the study.


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4.3
TREATMENT COMPLIANCE
Dose administration compliance will be assured by administration of all study medication 
under supervision of the investigating physician or a designee at the research site. The 
measured plasma concentrations will provide additional information about compliance.


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5.
VARIABLES AND THEIR ASSESSMENT
5.1
EFFICACY - PHARMACODYNAMICS
5.1.1
Endpoints of efficacy
5.1.1.1
Primary endpoint of efficacy
The primary efficacy endpoint is achievement of a ≥ 90% reduction in PASI score from 
baseline (i.e., achieving PASI90) at week 48 in the Extended dosing period.  Baseline PASI 
for this study is defined as the baseline PASI for the 1311.2 study. 
5.1.1.2
Secondary endpoints of efficacy
The following secondary endpoints will all be evaluated at week 48in the Extended dosing 
period:
#
achievement of PASI50
#
achievement of PASI75
#
achievement of PASI100
#
achievement of sPGA of clear or almost clear
5.1.1.3
Further endpoints of efficacy
Additional efficacy analyses will include, but are not limited to, the following:
#
achievement of PASI50 at all Extended dosing period visits where PASI is collected
#
achievement of PASI75 at all Extended dosing period visits where PASI is collected
#
achievement of PASI90 at all Extended dosing period visits where PASI is collected 
#
achievement of PASI100 at all Extended dosing period visits where PASI is collected 
#
achievement of sPGA of clear or almost clear at all visits where sPGA is collected
#
time to loss of PASI50, which is a time to failure endpoint.  This will be repeated using 
PASI75, PASI90, and PASI100 as the endpoint.
#
sPGA will be evaluated in terms of time to loss of response which is defined as a 
score exceeding 1, and will be evaluated as a time to failure endpoint
#
change from baseline in Pain-VAS (in subgroup of patients with psoriatic arthritis 
only where baseline VAS is from 1311.2)
#
mean DLQI scores at all Extended dosing period visits where PASI is collected
5.1.2
Assessment of efficacy
The PASI measures the severity of a patient’s psoriasis and the percent of the patient’s skin 
that is affected. See Section 10.1 for a detailed description of the PASI.
The Static Physician Global Assessment (sPGA) is a 6 point scale used by physicians to 
describe the severity of a patient’s psoriasis. See Section 10.2 for a detailed description of the 
sPGA.


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The Pain-VAS is a Visual Analogue Scale used to assess a patient’s psoriatic arthritis. See
Section 10.3 for a detailed description of the Pain-VAS.
Immunogenicity testing (Anti-Drug Antibodies (ADA)) will be performed at the visits 
specified in the Flow Chart in order to detect the emergence of antibodies.  
The Dermatology Life Quality Index (DLQI) is a questionnaire that determines a patient’s 
quality of life. See Section 10.4 for a detailed description of the DLQI.
5.2
SAFETY
5.2.1
Endpoint(s) of safety
5.2.1.1
Primary endpoints of safety
The primary endpoints of safety are as follows:
#
the occurrence of AEs
#
the occurrence of drug related AEs
#
the occurrence of SAEs
5.2.1.2
Secondary endpoints of safety
Not applicable as there are no secondary endpoints of safety.
5.2.1.3
Further endpoints of safety
Safety and tolerability will be assessed in a descriptive way based on:
#
Changes in vital signs and physical examination
#
Adverse events (AEs)
#
The occurrence of Adverse events of special interest (AESIs)
#
Discontinuation of therapy due to AEs, SAE
#
Changes in safety laboratory analysis
Immunogenicity testing (ADA) will be performed at the visits specified in Flow Chart in 
order to detect the emergence of antibodies.  Immunogenicity will be evaluated in terms of 
time to antibody emergence starting from the time of first exposure to BI 655066 in either 
1311.2 or 1311.13.
5.2.2
Assessment of adverse events
5.2.2.1
Definitions of adverse events
Adverse event
An adverse event (AE) is defined as any untoward medical occurrence, including an 
exacerbation of a pre-existing condition, in a patient in a clinical investigation who received a 


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pharmaceutical product. The event does not necessarily have to have a causal relationship 
with this treatment.
Serious adverse event
A serious adverse event (SAE) is defined as any AE which results in death, is immediately 
life-threatening, results in persistent or significant disability / incapacity, requires or prolongs 
patient hospitalisation, is a congenital anomaly / birth defect, or is to be deemed serious for 
any other reason if it is an important medical event when based upon appropriate medical 
judgement which may jeopardise the patient and may require medical or surgical intervention 
to prevent one of the other outcomes listed in the above definitions.
Intensity of adverse event
The intensity grading of AEs will be performed according to Rheumatology Common 
Toxicity Criteria (RCTC) Version 2.0 developed by Outcome Measures in Rheumatology
(OMERACT) (R13-3515). Cf. Appendix 10.7 and ISF for intensity/severity classification.
Causal relationship of adverse event
Medical judgment should be used to determine the relationship, considering all relevant 
factors, including pattern of reaction, temporal relationship, de-challenge or re-challenge, 
confounding factors such as concomitant medication, concomitant diseases and relevant 
history. Assessment of causal relationship should be recorded in the case report forms. 
Yes:
There is a reasonable causal relationship between the investigational product 
administered and the AE. 
No:
There is no reasonable causal relationship between the investigational product 
administered and the AE. 
Worsening of the underlying disease or other pre-existing conditions
Worsening of the underlying disease or of other pre-existing conditions will be recorded as an 
(S)AE in the (e)CRF.
Changes in vital signs, ECG, physical examination, and laboratory test results
Changes in vital signs, ECG, physical examination and laboratory test results will be
recorded as an (S)AE in the (e) CRF, if they are judged clinically relevant by the investigator.
Adverse Events of Special Interest (AESI)
The following are considered as Adverse events of Special Interest (AESI):
Hepatic injury defined by the following alterations of liver parameters (for patients with 
normal liver function at baseline): an elevation of AST and/or ALT >3 fold upper limit of 
normal (ULN) combined with an elevation of total bilirubin >2 fold ULN measured in the 


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same blood draw sample. 
Patients showing these lab abnormalities need to be followed up according to section 10.6 of 
this clinical trial protocol and the “Drug induced liver injury (DILI) checklist” provided in 
ISF.
#
Major adverse cardiovascular events (MACE).
Including, but not limited to the following preferred terms: Atherosclerosis, Coronary 
artery disease, Myocardial infarction, Angina Pectoris, Transient ischemic attack, 
Cerebrovascular accident (including Stroke), Cardiac failure congestive, Peripheral 
arterial occlusive disease.
ASEIs are to be reported in an expedited manner similar to Serious Adverse Events, even if 
they do not meet any of the seriousness criteria – for details please see section 5.2.2.2.
5.2.2.2
Adverse event and serious adverse event reporting
All adverse events, serious and non-serious, occurring during the course of the clinical trial 
(i.e., from signing the informed consent onwards through the Residual Effect Period (REP) 
/Extended follow-up period) will be collected, documented and reported to the sponsor by the 
investigator on the appropriate CRF(s) / eCRFs / SAE reporting forms. Reporting will be 
done according to the specific definitions and instructions detailed in the ‘Adverse Event 
Reporting’ section of the Investigator Site File. 
Reporting of Adverse Events in Remote Data Capture system (RDC):
AEs that are ongoing at the end of the previous trial (1311.2) will have to be re-entered, and 
any adverse events that have started between the two trials (in the event that the 6 weeks
time-window is used), will also be entered into the 1311.13 RDC system.
Reporting of Adverse Events on the SAE form: 
Specific instructions for the SAE reporting process concerning SAE forms in previous and 
roll-over studies will be provided in the ISF.
The REP for BI 655066 is 12 weeks. Therefore, all events reported within 12 weeks of the 
last trial medication will be considered on treatment. All adverse events will be reported up 
until the last per protocol visit (Extended EOS visit), which is 84 (+7 days) days after the last 
dose of trial medication.
The investigator does not need to actively monitor patients for AEs once the clinical trial has 
ended. However, if the investigator becomes aware of an SAE(s) that occurred after the 
patient has completed the clinical trial (including any protocol required REP and / or follow-
up), it should be reported by the investigator to the sponsor if considered relevant by the 
investigator.
For each adverse event, the investigator will provide the onset date, end date, intensity, 
treatment required, outcome, seriousness, and action taken with the investigational drug. The 


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investigator will determine the relationship of the investigational drug to all AEs as defined in 
Section 5.2.2.1. 
The investigator must report the following events using paper process SAE form via 
telephone/fax immediately (within 24 hours) to the sponsor: SAEs and non-serious AEs 
relevant to the SAE(s), and AESIs.
Boehringer Ingelheim has set up a list of AEs which are defined to be always serious. In 
order to support the investigator with the identification of these “always serious adverse 
events”, if a non-serious AE is identified to be serious per Boehringer Ingelheim definition, a 
query will be raised. The investigator must verify the description and seriousness of the 
event.  If the event description is correct, the item “serious” needs to be ticked and an SAE 
has to be reported in expedited fashion following the same procedure as above.
The list of these adverse events can be found via the RDC-system.
With receipt of any further information to these events, a follow-up SAE report has to be 
provided. SAEs and non-serious AEs must include a causal relationship assessment made by 
the investigator.
The SAE form is to be forwarded to the defined unique entry point identified for the BI OPU 
(country-specific contact details will be provided in the Investigator Site File) or by using the 
electronic submission process. This immediate report is required irrespective of whether the 
investigational product has been administered or not and irrespective of causal relationship. It 
also applies if new information to existing SAEs or AESIs becomes available. 
Pregnancy
In rare cases, pregnancy might occur in clinical trials. Once a female subject has been 
enrolled into the clinical trial, after having taken study medication, the investigator must 
report immediately any drug exposure during pregnancy to the sponsor. Drug exposure 
during pregnancy has to be reported immediately (within 24 hours or next business day 
whichever is shorter) to the defined unique entry point for SAE forms of the respective BI 
OPU (country-specific contact details will be provided in the Investigator Site File). The 
outcome of the pregnancy associated with the drug exposure during pregnancy must be 
followed up. In the absence of an (S)AE, only the Pregnancy Monitoring Form for Clinical 
Trials and not the SAE form is to be completed. The ISF will contain the Pregnancy 
Monitoring Form for Clinical Trials (Part A and Part B).
5.2.3
Assessment of safety laboratory parameters
The laboratory parameters that will be determined are listed in Tables 5.2.3: 1 and 5.2.3: 2 at
the time points provided in Flow Chart. The respective reference ranges will be provided in 
the ISF. The laboratory tests will be performed at a designated central laboratory, and if 
necessary by additional specialist laboratories.
Laboratory results of the patients will be available in real time to the respective investigator 
and to the clinical monitor of each country (central laboratory website), and selected 


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abnormal laboratory alerts will be sent automatically to the sites and to the sponsor in real 
time. PK, PD and biomarker data will not be available to the investigators or local clinical 
monitors, but only to the Trial Team (sponsor) and to the DMC.
Clinically relevant laboratory values will be commented on in the eCRF. A clinically relevant 
value may be either in- or outside the reference range. Clinically relevant abnormal 
laboratory test results must be repeated using an unscheduled visit lab kit and must be 
repeated until normalisation or stabilisation or until an alternative explanation has been 
found. Clinically relevant abnormal laboratory values will be also graded for intensity by 
using RCTC Version 2.0 criteria.
The tests listed in Table 5.2.3: 1 constitute laboratory tests and hormones (assessed in female 
patients only) that will be done only at the initial roll-over visit and at Extended EOT or 
Extended EOS after approval of amendment # 5 and start of the rollover of patients to the 
M15-997 study from 01-May-2018, i.e. these tests are only required at EV1 for patients that 
are having EV1 as their first 1311.13 visit. The results will not be included into the report.  
Samples will be archived and run as clinically necessary.
Table 5.2.3: 1
Exclusionary Testing
Category
Test name 
Tb screening
Serum pregnancy test (only 
female patients of childbearing 
potential)
Interferon-gamma release assay (IGRA)
Serum β-Human Chorionic Gonadotropin
Table 5.2.3: 2
Safety laboratory tests
Category
Test name 
Haematology
Haematocrit (Hct)
Haemoglobin (Hb)
Red Blood Cell Count / Erythrocytes
Reticulocyte Count
White Blood Cells / Leucocytes
Platelet Count / Thrombocytes
HbA1c (Haemoglobin (glycated Hb of A1c subtype)) 
Roll-over and final visits only


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Table 5.2.3: 2
Safety laboratory tests (cont’d)
Category
Test name 
Diff Automatic
Neutrophils (relative and absolute count)
Eosinophils (relative and absolute count)
Basophils (relative and absolute count)
Monocytes (relative and absolute count)
Lymphocytes (relative and absolute count)
Diff Manual
(if Diff Automatic is abnormal)
Neutrophils, Bands (Stabs) 
Neutrophils, Polymorphonuclear (PMN)
Eosinophils 
Basophils 
Monocytes 
Lymphocytes 
Coagulation
Partial Thromboplastin Time (=aPTT)
Prothrombin Time (Quick and International normalised ratio (INR))
Enzymes
Aspartate Aminotransferase/ Glutamate-Oxaloacetate Transaminase 
(AST/GOT )
Alanine transaminase(Glutamic Pyruvate Transaminase (ALT/GPT)
Alkaline Phosphatase (AP/ALP)
Creatine Kinase (CK)
CK-MB if CK is elevated
Lactic Dehydrogenase (LDH)
Substrates
Glucose
Creatinine
Blood urea nitrogen
Bilirubin Total 
Bilirubin Direct
Protein, Total
C-Reactive Protein (CRP)
Uric Acid 
Cholesterol, total
High density lipoprotein (HDL) Cholesterol
Calculated low density lipoprotein (LDL) Cholesterol
Triglycerides
Electrolytes
Calcium
Sodium
Potassium


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Table 5.2.3: 2
Safety laboratory tests (cont’d)
Category
Test name 
Urinalysis (Stix)
Urine Nitrite
Urine Protein
Urine Glucose
Urine Ketone
Urobilinogen
Urine Bilirubin
Urine RBC/Erythrocyte
Urine WBC/Leukocytes
Urine pH
Urine albumin (microalbumin urine test) (roll-over visit only)
Urine-Sediment
(microscopic examination)
(if urine analysis abnormal)
Urine Sediment Bacteria 
Urine Cast in Sediment 
Urine Squamous Epith Cells
Urine Sediment Crystals, Unspecified
Urine Sediment red blood cell count (RBC)/Erythrocytes
Urine Sediment white blood cell count (WBC)/Leucocytes
5.2.4
Electrocardiogram
The 12-lead ECGs (I, II, III, aVR, aVL, aVF, V1-V6) will be recorded after the patients have 
rested for at least 5 minutes in a supine position. Electrode placement will be performed 
according to the method of Wilson, Goldberger and Einthoven. The ECGs will be evaluated 
by the study physician investigator or designee. ECGs may be repeated for quality reasons 
and the repeat tracing may be used for analysis. Additional ECGs may be collected by the 
investigator for safety reasons. Abnormal ECG recordings will be noted, and clinically 
relevant abnormal findings will be reported as AEs by the investigator. Any ECG 
abnormalities will be carefully monitored and if necessary medically treated.
ECG recordings will be obtained from roll-over visit and every 24 weeks, until study end 
including Extended EOT visit and Extended EOS visit 
ECG measurements should, if possible, always precede blood sampling to avoid impact of 
sampling on the ECG results.
Signed and dated printouts of either ECG tracings or electronic ECG reports will be kept in 
the subject’s/patient’s medical file.
5.2.5
Assessment of other safety parameters
Vital signs
Vital signs include blood pressure (BP), pulse rate (PR), respiratory rate (RR), and oral or 
tympanic body temperature.


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Systolic and diastolic BP as well as PR (by palpation, counted for 1 minute) will be measured 
after 5 minutes of rest in the supine position. (cf. Flow Chart for time points). 
Measurements of vital signs should, if possible, always precede blood sampling to avoid 
impact of sampling on the results of vital signs.
Medical examination
Complete physical examination will include vital sign assessment and general appearance as 
well as evaluation of all organ systems (eyes, ears, nose, mouth, and throat, neck, respiratory, 
cardiovascular, chest, gastrointestinal, lymphatic, musculoskeletal, skin, neurologic and 
psychiatric). Targeted physical examination will include vital sign assessment and evaluation 
of organ systems associated with AE(s) symptoms or laboratory abnormalities.
The medical examination carried out at the initial roll-over visit, will include documentation 
of patient information, informed consent, demographics including weight and waist 
circumference, smoking and alcohol history, relevant medical history and concomitant 
medication, review of inclusion/exclusion criteria, review of vital signs, 12-lead ECG and 
laboratory, and a complete physical examination.
Local tolerability
Local tolerability at the administration site of the subcutaneous injection will be assessed by 
the investigator according to “swelling”, “induration”, “heat”, “redness”, “pain”, or “other 
findings”.
5.3
OTHER
5.3.1
Other endpoint(s) 
Not applicable
5.3.2
Other assessment(s) 
Not applicable
5.3.3
Pharmacogenomic evaluation
No pharmacogenetic samples will be collected in this study, as those samples will be 
available from the preceding trial. 
5.4
APPROPRIATENESS OF MEASUREMENTS
The majority of measurements performed during this trial are standard measurements and 
will be performed in order to monitor safety aspects and to determine efficacy, PK and PD 
parameters in an appropriate way.
The scheduled measurements are appropriate to see drug induced changes in vital signs, 
standard laboratory values and ECG. These safety measurements standard and accepted for 


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evaluation of safety and tolerability of an s.c. drug, and they are widely used in this kind of 
study.
The PK parameters and measurements outlined in Section 5.5 are generally used as 
measurements to assess drug exposure.
The efficacy endpoints are standard for assessment of patients with moderate to severe 
psoriasis. In addition, a number of exploratory PD measures (biomarkers) are also 
incorporated in this CTP. As these biomarkers have not been validated as prognostic 
measures, they may be analysed selectively and may not be included in the clinical trial 
report.
5.5
DRUG CONCENTRATION MEASUREMENTS AND 
PHARMACOKINETICS
Time points for dosing, PK and ADA sampling are listed in Flow Chart. Date and exact clock 
time of administration as well as pharmacokinetic and ADA sampling time points will be 
recorded. They will be documented in the CRFs by the medical personnel.
5.5.1
Pharmacokinetic endpoint(s)
PK samples will serve to determine the following endpoints:
#
steady state trough concentrations of BI 655066.
Individual concentration-time data with descriptive statistics for trough concentrations will be 
presented in the CTR. If deemed necessary, further appropriate pharmacokinetic parameters 
might be calculated.
Pharmacokinetic data may additionally be analysed using population pharmacokinetic 
approach. For this purpose data may also be combined with data from other trials. Modelling 
activities will be planned and documented separately.
5.5.2
Methods of sample collection
5.5.2.1
Plasma sampling for pharmacokinetic analysis
For the quantification of analyte plasma concentrations, approximately 2.5 mL of blood will 
be taken from a forearm vein into a K3EDTA (ethylendiaminetetraacetic acid) anticoagulant 
blood-drawing tube at the time points listed in Flow Chart under PK sampling.
Mix the K3EDTA-anticoagulated blood samples gently and place on ice until centrifugation 
at approximately +4°C.  The blood should be centrifuged to produce plasma as soon as 
possible after collection, but not later than 30 minutes after withdrawal. Centrifugation will 
last for approximately 10 minutes (at 2000 x g to 4000 x g) at approximately +4°C. Two 
aliquots of EDTA plasma samples will be obtained in two polypropylene cryotubes. The two 
aliquots should contain approximately 0.5 mL of plasma each. Until shipment on dry ice to 
the analytical laboratory, the plasma samples will be stored at -20°C or below at the clinical 


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site and at the analytical laboratory until analysis.  Both aliquots will be shipped (in separate 
shipments) to the assay laboratory for the determination of BI 655066.  Both aliquots will be 
stored until the finalization of the clinical trial report and permission for sample disposal is 
provided. Samples will be shipped on dry ice sufficient for 3 days transit.
5.5.2.2
Plasma sampling for assessment of anti-drug antibody
For the assessment of anti-drug antibody, approximately 2.5 mL of blood will be taken from 
a forearm vein into a K3EDTA anticoagulant blood-drawing tube at the time points listed in 
the Flow Chart under ADA.
Mix the K3EDTA-anticoagulated blood samples gently and place on ice until centrifugation 
at approximately +4°C.  The blood should be centrifuged to produce plasma as soon as 
possible after collection, but not later than 30 minutes after withdrawal.  Centrifugation will 
last for approximately 10 minutes (at 2000 x g to 4000 x g) at approximately +4°C. Two 
aliquots of EDTA plasma samples will be obtained in two polypropylene cryotubes. Both 
aliquots should contain approximately 0.5 mL of plasma each.  Until shipment on dry ice to 
the analytical laboratory, the plasma samples will be stored at -20°C or below at the clinical 
site and at the analytical laboratory until analysis. Both aliquots will be shipped (in separate 
shipments) to the assay laboratory for the assessment of potential ADA to BI 655066. The 
ADA sample aliquots will be banked for possible/ additional ADA characterization in the 
future. Samples will be shipped on dry ice sufficient for 3 days transit. 
5.5.3
Analytical determinations
BI 655066 concentrations will be determined by a validated Enzyme Linked Immunosorbent 
Assay (ELISA).  
The presence of ADA to BI 655066 will be assessed via a tiered approach using a validated 
electrochemiluminescence assay (screening, confirmatory, and titration analysis as 
appropriate). Samples that are confirmed positive will then be characterized in a validated 
neutralizing antibody (NAb) assay. 
5.6
BIOMARKER(S)
Biomarkers associated with psoriatic disease and the IL-23 pathway will be assessed in 
plasma and serum from psoriasis patients, post treatment with BI 655066.
Blood samples (serum and plasma) will be collected at time points indicated in Flow Chart 
for the analysis of biomarkers. After completion of the study these samples may be used for 
not yet specified non-genetic biomarker analyses associated with autoimmune diseases as 
well as method development and evaluation. Samples will be stored for a maximum of 3 
years (under consideration of local legislation) upon signature of the final study report.


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5.6.1
Endpoints based on biomarker(s)
Serum and plasma will be collected to assess changes in protein levels of disease specific 
markers such as but not limited to ∃defensin 2, neutrophil gelatinase associated lipocalin 
(NGAL), and S-100 proteins (A7, A8, A12) post treatment with BI 655066. These 
biomarkers are considered exploratory biomarkers and respective assays will need to be 
qualified to meet the required performance criteria.
5.6.2
Methods of sample collection
For the assessment of soluble protein biomarkers in serum, approximately 8 ml of blood will 
be collected from a forearm vein in a serum separation tube at time points indicated in the 
Flow Chart. The blood will be thoroughly mixed with clotting activation agent by inverting 
the tube not less than five times and will be allowed to clot for 30 minutes with the tube 
standing upright. The tube is then centrifuged at 1500 to 2000 x g for 15 minutes until clot 
and serum are separated by a well formed barrier. The serum will then be aliquoted in at least 
6 aliquots (in polypropylene tubes) of at least 500 μl and should be frozen immediately at -
20°C or below until shipment on dry ice to the analytical laboratory.
For the assessment of soluble protein biomarkers in plasma, approximately 8 ml of blood will 
be collected from a forearm vein in a potassium -EDTA (ethylendiaminetetraacetic acid)-
anticoagulant blood drawing tube at the time points indicated in the Flow Chart. Tube content 
will be mixed immediately by gently inverting the tube at least 8 to 10 times and tube will 
then be transferred into an ice bath until centrifugation. The EDTA-anticoagulated blood 
sample will be centrifuged within 30 minutes after collection (intermittent storage in ice 
water or on ice). Centrifugation will last for about 10 minutes at 2000-4000 x g at 4-8°C until 
cells and plasma are well separated. After centrifugation, the EDTA plasma will be aliquoted 
in at least 6 aliquots (in polypropylene tubes) of at least 500 μl and will be frozen 
immediately at -20°C or below.
5.6.3
Analytical determinations
Characteristics of the analytical methods for the analysis of serum and plasma biomarkers 
will be given in detail in the clinical trial report or in an accompanying technical/biomarker 
report.
5.7
PHARMACODYNAMICS
Serum and plasma will be collected to assess changes in the levels of disease specific markers 
such as but not limited to ∃defensin 2, neutrophil gelatinase associated lipocalin (NGAL),  
and S-100 proteins (A7, A8, A12).
5.7.1
Pharmacodynamic endpoints
Cf. section 5.6.1.


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5.7.2 
Methods of sample collection
Cf. section 5.6.2.
5.8
PHARMACOKINETIC - PHARMACODYNAMIC RELATIONSHIP
No formal analysis of pharmacokinetic/pharmacodynamic relationships is planned.
If the data suggest a pharmacokinetic/pharmacodynamic relationship of special parameters, 
e.g. PASI, a detailed analysis may be performed.
Correlation between drug concentration and response may be made if adequate data are 
available. In addition, exploratory correlations may also be made between drug concentration 
and AEs.
Data may also be used to develop pharmacokinetic/pharmacodynamic models using nonlinear 
mixed effect modelling techniques, if feasible. For this purpose data may also be combined 
with data from other trials. Modelling activities will be planned and documented separately 
according to internal and external guidelines and SOP.


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6.
INVESTIGATIONAL PLAN
6.1
VISIT SCHEDULE
All subjects have to adhere to the visit schedule as specified in Flow Chart. Any missed 
appointments should be re-scheduled as soon as possible. If any visit has to be rescheduled, 
subsequent visits should follow the original visit date scheduled. The investigator/sponsor 
could decide to arrange an unscheduled visit if deemed necessary (e.g. for safety follow-up 
reasons).
For detailed description of the trial procedures, please refer to Flow Chart.
In general, if several measurements including venipuncture are scheduled for the same point 
of time, venipuncture should, if possible, be the last of the measurements due to its mild 
discomfort to the patient and possible influence on physiologic parameters. 
6.2
DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS
6.2.1
Screening and run-in period(s)
Patients in the 1311.2 trial that fulfil the criteria for roll over, either by response < PASI50
between week 24 and week 44, or completing the entire preceding trial reaching week 48
according to protocol, will be asked to participate in this open label extension trial. Upon 
their agreement, they will immediately enter the treatment phase. Therefore, no screening or 
run-in procedures are defined in this protocol. 
6.2.2
Treatment period(s)
6.2.2.1 Rollover visit - Extended visit 1
After the approval of this protocol amendment in each respective country, all patients will 
follow Flow Chart (Extended dosing period) and receive 90mg BI 655066 subcutaneously at 
their Extended visit 1 (EV1). From EV1 onwards, BI655066 will be administered 
subcutaneously every 12 weeks during the trial. At EV2, if there is inadequate response, 
defined as <PASI90, the dose should be increased to 180mg for the remainder of the trial.
For ongoing patients from under the previous amendment (Pre-Extended Dosing Period, see 
Figure 3.1.3), EV1 should be conducted at the following time points:
1. For ongoing patients with ≥12 weeks since the EOT visit: Conduct EV1 as soon as 
possible 
2. For ongoing patients still undergoing treatment or with <12 weeks since the EOT 
visit: Conduct EV1 at the time of the next scheduled treatment or follow up visit 
(note: EV1 should not be conducted at the time point of Visit 2 under the previous 
protocol, patients with Visit 2 as their next scheduled visit should have their EV1 
replacing their Visit 3 instead)


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Patients completing their EOS of 1311.2 and rolling over after approval of this protocol
amendment, is immediately entering the Extended dosing period at EV1 of this trial. Eligible 
patients from 1311.2 who sign the informed consent for trial 1311.13, should preferably have 
Extended visit 1 of trial 1311.13 performed on the same day as the last visit in 1311.2, or 
within an interim period of up to 6 weeks thereafter. 
Assessments performed at EOS in the previous trial do not have to be repeated at Extended 
visit 1 in this trial, if performed as combined visits. If EV1 is performed as a separate visit to 
1311.2 EOS, all EV1assessments should be performed, but specific assessments are only 
required at EV1 for patients that are having EV1 as their first 1311.13 visit, see Flow Chart 
for further instructions. 
Written informed consent in accordance with GCP and local legislation must be obtained 
prior to any study related procedure taking place. If not performed as combined visits, 
informed consent must therefore be signed before the roll-over visit due to lab sampling 
fasting at EV1 in trial 1311.13.
Review of the following inclusion/exclusion criteria will be based on the last available lab 
result from previous trial, at the time of roll-over, and needs to be re-assessed as soon as 
1311.2 EOS/1311.13 roll-over visit results are available:
#
Inclusion criteria 3 (Negative serum ß-Human Chorionic Gonadotropin (ß-HCG)) 
Exclusion criteria 8 (Any clinically significant laboratory abnormalities)
Check consistency in medical history with the data obtained at visit 1 of the previous trial. 
All changes in medical history must be documented as adverse events and will be followed 
up as such during this trial. 
Re-record ongoing adverse events/concomitant medications from the previous trial and 
record any adverse events/concomitant medications that may have started between the two 
trials, in the event that the 6 week time-window between trials was used. 
All patients will be administered 90 mg BI 655066 s.c. at Extended visit 1. 
6.2.2.2 Extended Dosing Period
After 12 weeks, if there is a lack of response, defined as response below PASI90 at Extended 
visit 2, the dose should be increased to 180 mg, and 180 mg dosing will occur every 12 weeks 
until Extended EOT.
Self-administered patient questionnaire (DLQI) should be completed by the patient before 
any other visit assessments or treatments. 
For detailed description of the trial procedures, please refer to Flow Chart. 


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6.2.3
End of trial and Extended follow-up period
Trial 1311.13 is an open label extension trial which was set up in order to assess the long 
term safety and efficacy of Risankizumab (BI 655066) in patients with plaques psoriasis who 
have completed the phase 2 trial 1311.2. Moreover, this trial was meant to offer patients 
continuous treatment with Risankizumab until the marketing approval and availability of 
Risankizumab in the respective participating countries.
In the course of the acquisition of Risankizumab by Abbvie and the transition of 
responsibilities from BI to Abbvie it is planned to transfer the patients who are treated in 
1311.13 into M15-997 which is sponsored and conducted by Abbvie. M15-997 is an open 
label extension trial in which patients who have completed one of the Risankizumab pivotal 
trials in the indication of plaques psoriasis receive 150 mg Risankizumab every 12 weeks.
For patients who discontinue study medication before Extended end of treatment (for any 
reason), or before approval of this amendment and start to rollover patients to the M15-997 
from 01-May-2018 an early Extended EOT visit should be scheduled. If the decision to 
discontinue study participation is taken at a regular study visit, the visit should be turned into 
an Extended EOT visit. If the decision to discontinue study participation is taken in between 
study visits, an Extended EOT visit is to be scheduled at the earliest convenience and by the 
latest at the next upcoming visit according to the Flow Chart. This early Extended EOT visit 
will include the same procedures as the normal EOT, and the patient will subsequently enter a 
follow up period of 12 weeks, until a final Extended EOS visit is performed. If the decision to 
discontinue is taken in the Extended follow up period, the Extended EOS visit is to be 
scheduled at the earliest convenience. The procedures described at Extended EOS will be 
performed and the information will be recorded in the CRFs.
The end of study procedures are listed in Flow Chart. 
6.2.3.1 Vital status
In case of early discontinuation, information should be collected to differentiate between 
patients lost to follow-up (investigator not able to contact the patient despite multiple 
attempts) versus patients the investigator was able to contact who elected to discontinue study 
participation for any reason. Patients will be asked to give consent to be contacted (or for 
their primary care physician to be contacted) by the study team to obtain vital status 
information preferably at the time of study entry. This consent must be documented in the 
patient notes. Patient’s vital status, including cause of death, will be collected every 12 
months from Extended EOS until the last patient completes the regular scheduled Extended 
EOS. Vital status data will be collected in the eCRFs.
All clinically significant abnormal values (including laboratory parameters) will be followed 
up using the appropriate tests until a return to a medically acceptable level is achieved. AEs 
persisting after trial completion must be followed up, until they have normalised or been 
sufficiently characterised.


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7.
STATISTICAL METHODS AND DETERMINATION OF
SAMPLE SIZE
7.1
STATISTICAL DESIGN - MODEL
This is a double arm extension trial of patients treated with BI 655066 after participation in a 
clinical trial of BI 655066.  Descriptive statistical models include a responder analysis (e.g., 
achieving PASI90, sPGA of clear or almost clear, etc.), time to loss of response (e.g., 
achieving PASI90, sPGA of clear or almost clear, etc.), time to AESI, and time to antibody 
development formation.  No statistical testing will be done.
7.2
NULL AND ALTERNATIVE HYPOTHESES
The primary hypothesis is that BI 655066 will sustain effectiveness without emergent safety 
issues during the extended visit period. This will be characterized descriptively. There is no 
formal statistical hypothesis testing in this study.
7.3
PLANNED ANALYSES
The descriptive analyses will be based on proportions of patients achieving a response (e.g., 
achieving PASI90, sPGA of clear or almost clear, etc.), Kaplan Meier empirical survival 
curves to describe patterns of event incidence, and cumulative event rates at critical time-
point.
The study is designed to gain as much exposure as possible with adequate documentation of 
safety, efficacy, and antibody emergence.  
For all analyses, baseline refers to the baseline value in the 1311.2 study.
7.3.1
Primary analyses
The achievement of PASI90 at week 48 in the Extended dosing period is the primary efficacy 
endpoint, which is a binary variable. 
For primary safety, the overall incidence rates of AEs, drug related AEs, and SAEs will be 
calculated.
7.3.2
Secondary analyses
The same methods as discussed for the primary analyses will be used to analyse all binary 
secondary and other endpoints, which include achievement of PASI50 / PASI75 / PASI90 / 
PASI100 at all Extended dosing period visits where PASI is collected and achievement of 
sPGA of clear or almost clear at all Extended dosing period visits where sPGA is collected.
Time to loss of PASI50 / PASI75 / PASI90 / PASI100, and time to loss of sPGA of clear or 
almost clear will be analysed using a Kaplan-Meier estimate. 


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Percent change from baseline in Pain-VAS for patients with non-zero baseline will be 
summarized descriptively at time points collected. 
DLQI will be summarized descriptively at time points collected.
Additional information on these analyses will be provided in the trial statistical analysis plan.
7.3.3
Safety analyses
All subjects who received one dose of study drug will be included in the safety evaluation.
Safety analyses will focus on adverse events related to early discontinuation, immune 
suppression and injection site effects. AEs will be coded using the Medical Dictionary for 
Drug Regulatory Affairs (MedDRA). All AEs occurring up to 12 weeks after the last trial 
medication administration will be assigned to the treatment period for evaluation. The 
evaluation of adverse events will comprise various frequency tabulations. The additional 
analyses of pre-defined AESI will consider the frequency, intensity, time to first onset of the 
AE, duration of the AE and clinical consequences (e.g. study discontinuation).
Analysis of laboratory measures will similarly focus on hematologic measures of immune 
suppression. Descriptive statistics of laboratory values over time and for the difference from 
baseline will be provided. Frequency tables of changes with respect to the reference range 
between baseline and last/worst value on treatment and patients with possible clinically 
significant abnormalities will also be presented.
Immunogenicity will be evaluated in terms of time to antibody emergence starting from the 
time of first exposure to BI 655066 in either 1311.2 or 1311.13. This will be analysed using a 
Kaplan-Meier estimate.
Safety will also be assessed by evaluation of vital signs (BP, PR, RR, oral or tympanic body 
temperature) and local tolerability.
7.3.4
Interim analyses
Results will be analysed periodically by the sponsor and DMC in order to review the
accumulating safety data of BI 655066 in psoriasis.
7.3.5
Pharmacokinetic analyses
Individual concentration-time data with descriptive statistics for trough concentrations will be 
presented in the clinical trial report.
Population pharmacokinetic/pharmacodynamic analysis, if performed, will be reported 
separately.


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7.3.6
Pharmacodynamic analyses
Serum/plasma biomarkers will be summarized over time and correlated with clinical 
endpoints (i.e. PASI, PGA).
7.3.7
Pharmacogenomic analyses
Not applicable. 
7.4
HANDLING OF MISSING DATA
Use of inappropriate concomitant medication to treat psoriasis will be considered as failure 
when deriving response variables, e.g. PASI90. 
Further details on the handling of missing data will be provided in the Trial Statistical 
Analysis Plan.
7.5
RANDOMISATION
There is no randomisation for this study.  All patients will be assigned to the same regimen 
and dose of BI 655066, regardless of the treatment and dose received in the 1311.2 study.
7.6
DETERMINATION OF SAMPLE SIZE
The sample size is determined by the completion of previous trial and the consenting for the 
extension. 


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8.
INFORMED CONSENT, DATA PROTECTION, TRIAL 
RECORDS
The trial will be carried out in compliance with the protocol, the principles laid down in the 
Declaration of Helsinki, in accordance with the International conference on harmonisation 
(ICH) Harmonised Tripartite Guideline for Good Clinical Practice (GCP) and relevant BI 
Standard Operating Procedures (SOPs). Standard medical care (prophylactic, diagnostic and 
therapeutic procedures) remains in the responsibility of the treating physician of the patient.
The investigator should inform the sponsor immediately of any urgent safety measures taken 
to protect the study subjects against any immediate hazard, and also of any serious breaches 
of the protocol/ICH GCP.
The rights of the investigator and of the sponsor with regard to publication of the results of 
this trial are described in the investigator contract. As a general rule, no trial results should be 
published prior to finalisation of the Clinical Trial Report.
Insurance Cover: The terms and conditions of the insurance cover are made available to the 
investigator and the patients via documentation in the ISF (Investigator Site File).
8.1
STUDY APPROVAL, PATIENT INFORMATION, AND INFORMED 
CONSENT
This trial will be initiated only after all required legal documentation has been reviewed and 
approved by the respective Institutional Review Board (IRB) / Independent Ethics Committee 
(IEC) and competent authority (CA) according to national and international regulations. The 
same applies for the implementation of changes introduced by amendments.
Prior to patient participation in the trial, written informed consent must be obtained from each 
patient (or the patient’s legally accepted representative) according to ICH GCP and to the 
regulatory and legal requirements of the participating country. Each signature must be 
personally dated by each signatory and the informed consent and any additional patient-
information form retained by the investigator as part of the trial records. A signed copy of the 
informed consent and any additional patient information must be given to each patient or the 
patient’s legally accepted representative.
The patient must be informed that his/her personal trial-related data will be used by 
Boehringer Ingelheim in accordance with the local data protection law. The level of 
disclosure must also be explained to the patient.
The patient must be informed that his / her medical records may be examined by authorised 
monitors (CML/CRA) or Clinical Quality Assurance auditors appointed by Boehringer 
Ingelheim, by appropriate IRB / IEC members, and by inspectors from regulatory authorities.
8.2
DATA QUALITY ASSURANCE
A quality assurance audit/inspection of this trial may be conducted by the sponsor or 
sponsor’s designees or by IRBs/IECs or by regulatory authorities. The quality assurance 


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auditor will have access to all medical records, the investigator’s trial-related files and 
correspondence, and the informed consent documentation of this clinical trial.
8.3
RECORDS
Case Report Forms (CRFs) for individual patients will be provided by the sponsor, either on 
paper or via remote data capture. For drug accountability, refer to Section 4.1.8.
8.3.1
Source documents
Source documents provide evidence for the existence of the patient and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site.
Data entered in the eCRFs that are transcribed from source documents must be consistent 
with the source documents or the discrepancies must be explained. The investigator may need 
to request previous medical records or transfer records, depending on the trial; also current 
medical records must be available.
For eCRFs all data must be derived from source documents.
8.3.2
Direct access to source data and documents
The investigator / institution will permit trial-related monitoring, audits, IRB / IEC review 
and regulatory inspection, providing direct access to all related source data / documents. 
CRFs/eCRFs and all source documents, including progress notes and copies of laboratory and 
medical test results must be available at all times for review by the sponsor’s clinical trial 
monitor, auditor and inspection by health authorities (e.g. Food and Drug Administration 
(FDA)). The Clinical Research Associate (CRA) / on site monitor and auditor may review all 
CRFs/eCRFs, and written informed consents. The accuracy of the data will be verified by 
reviewing the documents described in Section 8.3.1.
8.4
LISTEDNESS AND EXPEDITED REPORTING OF ADVERSE EVENTS
8.4.1
Listedness
To fulfil the regulatory requirements for expedited safety reporting, the sponsor evaluates 
whether a particular adverse event is "listed", i.e. is a known side effect of the drug or not.
Therefore a unique reference document for the evaluation of listedness needs to be provided. 
For the BI 655066 this is the current version of the Investigator’s Brochure (U12-3042). The 
current version of this reference document is to be provided in the ISF. No AEs are classified 
as listed for matching placebo, study design, or invasive procedures.
8.4.2
Expedited reporting to health authorities and IECs/IRBs
Expedited reporting of serious adverse events, e.g. suspected unexpected serious adverse 
reactions (SUSARs) to health authorities and IECs/IRBs, will be done according to local 
regulatory requirements. Further details regarding this reporting procedure are provided in the 
Investigator Site File.


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8.5
STATEMENT OF CONFIDENTIALITY
Individual patient medical information obtained as a result of this trial is considered 
confidential and disclosure to third parties is prohibited with the exceptions noted below. 
Patient confidentiality will be ensured by using patient identification code numbers.
Treatment data may be given to the patient’s personal physician or to other appropriate 
medical personnel responsible for the patient’s welfare. Data generated as a result of the trial 
need to be available for inspection on request by the participating physicians, the sponsor’s 
representatives, by the IRB / IEC and the regulatory authorities i.e. the CA.
8.6
COMPLETION OF TRIAL
The EC/competent authority in each participating EU member state needs to be notified about 
the end of the trial (last patient out, unless specified differently in Section 6.2.3 of the CTP) 
or early termination of the trial. 


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9.
REFERENCES
9.1
PUBLISHED REFERENCES
P06-11555
Filipe-Santos O, Bustamante J, Chapgier A, Vogt G, Beaucoudrey L de, 
Feinberg J, Jouanguy E, Boisson-Dupuis S, Fieschi C, Picard C, Casanova JL. 
Inborn errors of IL-12/23- and IFN-gamma-mediated immunity: molecular, 
cellular, and clinical features. Semin Immunol 2006. 18(6):347-361.  
R03-1207
A new scoring system to determine if clinically significant improvement has 
occurred in clinical trials that assess the effect of therapy on psoriasis (version 
6, Aug 22, 2001). Medical Advisory Board of the National Psoriasis 
Foundation 2001
R03-1208
NPF psoriasis score. Psoriasis Forum 2002. 8(2) 
R05-2548 
Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI) - a simple
practical measure for routine clinical use. Joint Ann Mtg of the British 
Association of Dermatologists and the Canadian Dermatology Association, 
Oxford, 6 - 10 Jul 1993 Clin Exp Dermatol 1994. 19:210-216.
R08-1089 
Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis. 
Nature 2007; 445(7130):866-873.
R11-1204
Ghilardi N, Kljavin N, Chen Q, Lucas S, Gurney AL, Sauvage FJ de. 
Compromised humoral and delayed-type hypersensitivity responses in IL-23-
deficient mice. J Immunol 2004. 172:2827-2833.
R11-1236
Meeran SM, Mantena SK, Meleth S, Elmets CA, Katiyar SK. Interleukin-12-
deficient mice are at greater risk of UV radiation-induced skin tumors and 
malignant transformation of papillomas to carcinomas. Mol Cancer Ther 2006. 
5(4):825-832.
R11-1257 
Nestle FO, Kaplan DH, Barker J. Mechanisms of disease: psoriasis. N Engl J 
Med 2009; 361(5):496-509.
R11-1259 
Menter A, Griffiths CEM. Psoriasis 2: current and future management of 
psoriasis. Lancet 2007; 370:272-284.
R11-1261 
Leon A, Nguyen A, Letsinger J, Koo J. An attempt to formulate an evidence-
based strategy in the management of moderate-to-severe psoriasis: a review of 
the efficacy and safety of biologics and prebiologic options. Expert Opin 
Pharmacother 2007; 8(5):617-632.
R11-1529 
Gordon KB, Langley RG, Gottlieb AB, Papp KA, Krueger GG, Strober BE, et 
al. A phase III, randomized, controlled trial of the fully human IL-12/23/mAb 
briakinumab in moderate-to-severe psoriasis. J Invest Dermatol e-pub ahead of 
print 20 October 2011.


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R11-4193 
Ryan C, Leonardi CL, Krueger JG, Kimball AB, Strober BE, Gordon KB, et 
al. Association between biologic therapies for chronic plaque psoriasis and 
cardiovascular events: a meta-analysis of randomized controlled trials. JAMA 
2011; 306(8):864-871.
R12-1008
Iwakura Y, Nakae A, Saijo S, Ishigame H. The roles of IL-17A in 
inflammatory immune responses and host defense against pathogens. Immunol 
Rev 2008. 226:57-79.
R12-1010
Reich K, Langley RG, Papp KA, Ortonne JP, Unnebrink K, Kaul M, Valdes 
JM. A 52-week trial comparing briakinumab with methotrexate in patients 
with psoriasis. N Engl J Med 2011. 365(17):1586-1596.
R12-1011
Chackerian AA, Chen SJ, Brodie SJ, Mattson JD, McClanahan TK, Kastelein 
RA, Bowman EP. Neutralization or absence of the interleukin-23 pathway 
does not compromise immunity to mycobacterial infection. Infect Immun 
2006. 74(11):6092-6099.
R13-3515 
Woodworth T et al.. Standardizing Assessment and Reporting of Adverse 
Effects in Rheumatology Clinical Trials II: the Rheumatology Common 
Toxicity Criteria v. 2.0. J Rheumatol 2007; 34:1401-14.
R13-3518 
Papp-KA, Griffiths-CEM, Gordon-K, Lebwohl-M, Szapary-PO, Wasfi-Y, 
Chan-D, Hsu-MC, Ho-V, Gishlain-PD, Strober-B, Reich-K. Long-term safety 
of ustekinumab in patients with moderate-to-severe psoriasis: final results 
from 5 years of follow-up. Br J Dermatol 2013; 168:844-854.
R96-3541 
Fredriksson T, Pettersson U. Severe psoriasis - oral therapy with a new 
retinoid. Dermatologica 1978; 157:238-244.
R13-3802
Husni ME, Meyer KH, Cohen DS, Mody E, Qureshi AA
The PASE questionnaire: pilot-testing a psoriatic arthritis screening and 
evaluation tool.J Am Acad Dermatol 57 (4), 581 - 587 (2007)
9.2
UNPUBLISHED REFERENCES
U12-3042
Investigator’s Brochure BI 655066, Psoriasis, Crohn’s Disease, Ankylosing 
Spondylitis, 1311.P1/1311.P2/1311.P3
M14-0004 
Manuscript: Anti-IL-23 monoclonal antibody BI 655066 in treatment of   
psoriasis: Safety, efficacy pharmacokinetics and biomarker results of a single 
rising dose, randomized, double-blind, placebo-controlled trial
Submitted for publication


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10.
APPENDICES
10.1
PASI SCORE DEFINITION AND INSTRUCTIONS
The PASI score is an established measure of clinical efficacy for psoriasis medications. (R96-
3541)
To calculate the PASI score, the four main body areas are assessed: head (h), trunk (t), 
upper extremities (u) and lower extremities (l). These correspond to 10, 30, 20 and 40% of 
the total body area respectively.
The area of psoriatic involvement of these four areas (Ah, At, Au, and Al) is given a 
numerical value: 0 = no involvement, 1 = <10%, 2 = 10 to <30%, 3 = 30 to <50%, 4 = 50 to 
<70%, 5 = 70 to <90%, and 6 = 90 to 100% involvement.
The signs of severity, erythema (E), infiltration (I) and desquamation (D) of lesions are 
assessed using a numeric scale 0-4 where 0 is a complete lack of cutaneous involvement and
4 is the severest possible involvement; scores are made independently for each of the areas, h, 
t, u and l and represents a composite score for each area. An illustration of judging erythema 
follows: 0 = no erythema, 1 = slight erythema, 2 = moderate erythema, 3 = striking erythema, 
and 4 = exceptionally striking erythema.
The PASI score is calculated according to the following formula:
PASI = 0.1(Eh+Ih+Dh)Ah + 0.3(Et+It+Dt)At + 0.2(Eu+Iu+Du)Au + 0.4(El+Il+Dl)Al


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10.2 
STATIC PHYSICIAN'S GLOBAL ASSESSMENT (SPGA) OF THE NPF 
PSORIASIS SCORE (NPFPS)
The NPF Psoriasis Score (NPFPS) was devised by the National Psoriasis Foundation Medical
Advisory Board to address deficiencies inherit in the PASI, and to provide a dynamic, 
reproducible, and easy 5-component method to measure clinically significant improvement in 
trials of new or existing psoriatic therapies (R03-1207, R03-1208). The static Physician 
Global Assessment (sPGA) is one of five components of the NPFPS, and may be used 
independently (R03-1207, R03-1208).
The primary sPGA variable to be analysed will be the proportion of patients that are "clear or 
almost clear". This has been shown to correlate well with PASI75 or higher score.
For patients to be considered “clear,” the average of the 3 components must be zero (with 
standard rounding rules, i.e., 0.333 rounds to 0) and the score for thickness must equal zero.
For patients to be considered “almost clear,” the average of the 3 components must be 1 (with 
standard rounding rules, i.e., 1.333 rounds to 1) and each of the individual components must 
be less than 3 (in other words, each of the 3 components must be equal 0, 1, or 2).
Additionally, patients with an average of the 2 components equal to zero but with a thickness 
score of 1 will be considered as “almost clear.”
Static Physician Global Assessment (averaged over all lesions)
0
clear
= cleared, except for residual discoloration
1
almost clear
= majority of lesions have individual scores for thickness (a), erythema 
(b) and scaling (c) that averages 1.
2
mild
= majority of lesions have individual scores for thickness (a), erythema 
(b) and scaling (c) that averages 2.
3
moderate
= majority of lesions have individual scores for thickness (a), erythema 
(b) and scaling (c) that averages 3.
4
marked
= majority of lesions have individual scores for thickness (a), erythema 
(b) and scaling (c) that averages 4.
5
severe
= majority of lesions have individual scores for thickness (a), erythema 
(b) and scaling (c) that averages 5.
(a) Thickness (averaged over all lesions)
0 = no evidence of plaque elevation
1 = minimal plaque elevation, ≈ 0.25 mm
2 = mild plaque elevation, ≈ 0.5 mm


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3 = moderate plaque elevation, ≈ 0.75 mm
4 = marked plaque elevation, ≈ 1 mm
5 = severe plaque elevation, ≈1.25 mm or more
Thickness in the sPGA may be graded with the aid of a reference card, which has embossed 
elevations ranging from 0 to 1.25 mm that increase linearly at 0.25 mm increments 
corresponding to varying levels of thickness (0-5) for each target lesion. The dermatologist 
should select 3 or more representative lesions (e.g., lesions not on the face, scalp, 
intertriginous areas or only on elbows or knees) at the time of the visit and measure their 
thickness. These can be averaged to derive the thickness score. The investigator should assess 
the average degree of thickness and then select the number that most represents this. For any 
assessments that fall half way between any two numbers on the scale, the investigator will be 
told to always round up to the higher number. This would result in then the following implied 
range: 0 = 0 to <0.125 mm, 1 = ≥0.125 to <0.375 mm, 2 = ≥0.375 to <0.625mm, 3 = ≥0.625 
to <0.875mm, 4 = ≥0.875 to <1.25mm and 5 = ≥1.25mm.
(b) Erythema (averaged over all lesions)
0 = no evidence of erythema, hypo- or hyper-pigmentation may be present
1 = faint erythema
2 = light red coloration
3 = moderate red coloration
4 = bright red coloration
5 = dusky to deep red coloration
(c) Scaling (averaged over all lesions)
0 = no evidence of scaling
1 = minimal; occasional fine scaling over less than 5% of the lesion
2 = mild; fine scaling predominates
3 = moderate; coarse scaling predominates
4 = marked; thick, non-tenacious scaling predominates
5 = severe; very thick tenacious scaling predominates
10.3
PAIN VISUAL ANALOG SCALE (VAS)
If a patient has psoriatic arthritis, the patient will assess their psoriatic arthritis at each 
protocol defined time point. A global estimate of pain caused by joint disease will be 
estimated by the patient’s response to the question: “The very left end of the scale is 
equivalent to “no pain” at all whereas the right end of the scale is equivalent to “worst 
possible pain”. How much pain have you had because of your illness in the past week?” 
Response is captured using a VAS (range 0 to 100, where 100 is highest severity) and results 
will be summarized.


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10.4
DERMATOLOGY LIFE QUALITY INDEX
DLQI is a subject-administered,10-question, validated, quality of life questionnaire that 
covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, 
personal relationships and treatment. Response categories include “not relevant” (score of 0), 
“not at all” (score of 0), “a little” (score of 1), “a lot” (score of 2) and “very much” (score of 
3). Question 7 is a “yes”/ “no” question where “yes” is scored as 3.
The DLQI will be analysed under six headings as follows (R05-2548): 
Domain
Question Number
Score                  
Symptoms and feelings
Questions 1 and 2
Score maximum 6
Daily activities
Questions 3 and 4
Score maximum 6
Leisure
Questions 5 and 6
Score maximum 6
Work and school
Question 7
Score maximum 3
Personal relationships
Questions 8 and 9
Score maximum 6
Treatment
Question 10
Score maximum 3
DLQI total score is calculated by summing the scores of each question resulting in a range of 
0 to 30 where 0-1 = no effect on subject’s life, 2-5 = small effect, 6-10 = moderate effect, 11-
20 = very large effect, and 21-30 = extremely large effect on subject’s life. The higher the 
score, the more the quality of life is impaired. If the answer to one question in a domain is 
missing, that domain is treated as missing. If 2 or more questions are left unanswered 
(missing), DLQI total score is treated as missing. A 5-point change from baseline is 
considered a clinically important difference.
10.5
PSORIATIC ARTHRITIS SCREENING AND EVALUATION TOOL
If a patient has psoriatic arthritis or if psoriatic arthritis is suspected at the roll-over visit , the 
psoriatic arthritis screening and evaluation (PASE) questionnaire should be performed. It will 
then be measured once per year until study end. The PASE questionnaire is a self-
administered tool that can be used to screen for psoriatic arthritis among patients with 
psoriasis. PASE can distinguish between symptoms of psoriatic arthritis and osteoarthritis 
(R13-3802).
Psoriatic Arthritis Screening and Evaluation (PASE) Questionnaire
Please circle or mark ONLY ONE of the five choices on the following 15 questions. The 
answers to these questions will help us better understand your symptoms. This should take 
about 5 to 6 minutes to complete. Thank you for your time.


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Symptoms subscale
Strongly 
disagree
Disagree
Neutral
Agree
Strongly 
agree
1. I feel tired for the most of the day
1
2
3
4
5
2. My joints hurt
1
2
3
4
5
3. My back hurts
1
2
3
4
5
4. My joints become swollen
1
2
3
4
5
5. My joints feel “hot”
1
2
3
4
5
6. Occasionally, an entire finger or toe 
becomes swollen, making it look like a 
“sausage”
1
2
3
4
5
7. I have noticed that the pain in my joints 
moves from one joint to another, e.g. my wrist 
will hurt for a few days then my knee will 
hurt and so on
1
2
3
4
5
Symptom Score (Max 35)
Add scores for questions 1-7 and write next to A
A.
Function subscale
Strongly 
disagree
Disagree
Neutral
Agree
Strongly 
agree
8. I feel that my joint problems have affected 
my ability to work
1
2
3
4
5
9. My joint problems have affected my ability 
to care for myself, e.g. getting dressed or 
brushing my teeth
1
2
3
4
5
10. I have had trouble wearing rings on my 
fingers or my watch 
1
2
3
4
5
11. I have had trouble getting into or out of a 
car
1
2
3
4
5
12. I am unable to be as active as I used to be
1
2
3
4
5
13. I feel stiff for more than two hours after 
waking up in the morning
1
2
3
4
5
14. The morning is the worst time of the day 
for me
1
2
3
4
5
15. It takes me a few minutes to get moving to 
the best of my ability, any time of the day
1
2
3
4
5
Function Score (Max 40)
Add scores for questions 8-15 and write next to B
B.
Total PASE Score (Max 75)
Add scores in boxes A and B and write next to C 
C.


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10.6
CLINICAL EVALUATION OF LIVER INJURY
10.6.1
Introduction
Alterations of liver laboratory parameters, as described in Section 5.2.2.1 (Adverse Events of 
Special Interest), are to be further evaluated using the following procedures: 
10.6.2
Procedures
Repeat the following laboratory tests: ALT, AST, and bilirubin (total and direct) - within 48 
to 72 hours and provide additional blood sample to the central laboratory for automatic reflex 
testing of the below listed laboratory parameters. Only in case whereby the central laboratory 
is not immediately available (e.g. if the logistics are such that the patient´s repeat specimen 
would not reach the central laboratory in a reasonable timeframe), ALT, AST, and bilirubin 
(total and direct) will be evaluated by local laboratory and results are made available to the 
investigator and to BI as soon as possible. If in such a case ALT and/or AST >3 fold ULN 
combined with an elevation of total bilirubin >2 fold ULN are confirmed, results of the 
laboratory parameters described below must be made available to the investigator and to BI 
as soon as possible.
In addition, 
o
obtain a detailed history of current symptoms and concurrent diagnoses and 
medical history according to the “DILI checklist” provided in the ISF 
o
obtain history of concomitant drug use (including non-prescription 
medications, herbal and dietary supplement preparations), alcohol use, 
recreational drug use, and special diets according to the “DILI checklist” 
provided in the ISF;
o
obtain a history of exposure to environmental chemical agents (consider home 
and work place exposure) according to the “DILI checklist” provided in the 
ISF;
and report these via the CRF.
Clinical chemistry
alkaline phosphatase, albumin, PT or INR, CK, CK-MB, ceruloplasmin, α-1 antitrypsin, 
transferrin, amylase, lipase, fasting glucose, cholesterol, triglycerides
Serology
Hepatitis A (Anti-IgM, Anti-IgG), Hepatitis B (HbsAg, Anti-HBs, DNA), Hepatitis C (Anti-
HCV, RNA if Anti-HCV positive), Hepatitis D (Anti-IgM, Anti-IgG), Hepatitis E (Anti-
HEV, Anti-HEV IgM, RNA if Anti-HEV IgM positive), Anti-Smooth Muscle antibody 
(titer), Anti-nuclear antibody (titer), Anti-LKM (liver-kidney microsomes) antibody, Anti-
mitochondrial antibody


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Hormones, tumormarker
TSH
Haematology
Thrombocytes, eosinophils
o
Provide abdominal ultrasound to rule out biliary tract, pancreatic or 
intrahepatic pathology, e.g. bile duct stones or neoplasm.
o
Initiate close observation of subjects by repeat testing of ALT, AST, and total 
bilirubin (with fractionation by total and direct) at least weekly until the 
laboratory ALT and / or AST abnormalities stabilize or return to normal, then 
according to the protocol. Depending on further laboratory changes, additional 
parameters identified e.g. by reflex testing will be followed up based on 
medical judgement and Good Clinical Practices (GCP).


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10.7  
SEVERITY OF AE AS DESCRIBED IN THE RHEUMATOLOGY COMMON TOXICITY CRITERIA V. 2.0
1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
Asymptomatic, or 
transient 
Short duration (< 1 
week)
No change in life style 
No medication or over 
the counter medication 
(OTC)
Symptomatic
Duration (1–2 weeks) 
Alter lifestyle 
occasionally 
Meds relieve. (may be 
prescription),
Study drug continued
Prolonged symptoms, 
reversible, major 
functional impairment 
Prescription meds/partial 
relief 
May be hospitalized < 
24h
Temporary study drug 
discontinuation, or/and 
dose reduced
At risk of death
Substantial disability, 
especially if permanent.
Multiple meds
Hospitalization > 24h
Study drug discontinued
A. ALLERGIC/IMMUNOLOGIC
A1. Allergic 
reaction/hyper-
sensitivity (including 
drug fever)
Transient rash; drug 
fever < 38°C: transient 
asymptomatic 
bronchospasm
Generalised urticaria 
responsive to meds; or 
drug fever > 38° C, or 
reversible bronchospasm
Symptomatic 
bronchospasm, requiring 
meds; symptomatic 
urticaria persisting with 
meds, allergy related 
oedema/angioedema
Anaphylaxis, laryngeal/ 
pharyngeal oedema, 
requiring resuscitation


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
A. ALLERGIC/IMMUNOLOGIC
A2. Autoimmune 
reaction
Serologic or other 
evidence of 
autoimmune reaction, 
but patient 
asymptomatic: all organ 
function normal and no 
treatment is required 
(e.g. vitiligo)
Evidence of autoimmune 
reaction involving a non-
essential organ or 
functions, requiring 
treatment other than 
immunosuppressive 
drugs (e.g. 
hypothyroidism)
Reversible autoimmune 
reaction involving 
function of a major organ 
or toxicity requiring short 
term immunosuppressive 
treatment (e.g. transient 
colitis or anaemia)
Causes major organ 
dysfunction,
or progressive, not 
reversible, or requires 
long term administration 
of high dose 
immunosuppressive 
therapy
A3. Rhinitis (includes 
sneezing, nasal 
stuffiness, post-nasal 
discharge)
Transient, non-
prescription meds 
relieve
Prescription med. 
required, 
slow 
Corticosteroids or other 
prescription med. with 
persistent disabling 
symptoms such as 
impaired exercise 
tolerance 
NA


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
ALLERGIC/IMMUNOLOGIC
A4. Serum sickness
Transient, non-
prescription meds 
relieve
Symptomatic, slow 
response to meds (e.g. 
oral corticosteroids)
Prolonged; symptoms 
only partially relieved by 
meds; parenteral 
corticosteroids required
Major organ dysfunction, 
requires long-term high-
dose immunosuppressive 
therapy
A5. Vasculitis
Localised, not requiring 
treatment; or rapid 
response to meds; 
cutaneous
Symptomatic, slow 
response to meds (e.g. 
oral corticosteroids)
Generalised, parenteral 
corticosteroids required 
or/and short duration 
hospitalisation 
Prolonged, 
hospitalisation, ischemic 
changes, amputation
B. CARDIAC
B1. Arrhythmia 
Transient, 
asymptomatic
Transient, but 
symptomatic or 
recurrent, responds to 
meds
Recurrent/persistent; 
maintenance prescription
Unstable, hospitalisation 
required; parenteral meds


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
B. CARDIAC
B2. Cardiac function 
decreased
Asymptomatic decline 
in resting ejection 
fraction by > 10%, but 
< 20% of baseline value
Asymptomatic decline of 
resting ejection fraction ≥
20% of baseline value
Congestive heart failure
(CHF) responsive to 
treatment
Severe or refractory CHF
B3. Edema 
Asymptomatic (e.g. 1+ 
feet/calves), self-
limited, no therapy 
required
Symptomatic (e.g. 2+ 
feet/calves), requires 
therapy
Symptoms limiting 
function (e.g. 3+ 
feet/calves, 2+ thighs), 
partial relief with 
treatment, prolonged
Anasarca; no response to 
treatment
B4. Hypertension 
(new onset or 
worsening)
Asymptomatic, 
transient increase by > 
20 mm Hg (diastolic), 
or to > 150/100 if 
previously normal, no 
therapy required
Recurrent or persistent 
increase > 150/100 or by 
> 10 mmHg (diastolic), 
requiring and responding 
readily to treatment 
Symptomatic increase > 
150/100 > 20 mm Hg, 
persistent, requiring 
multi-agent therapy, 
difficult to control
Hypertensive crisis


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
B. CARDIAC
B5. Hypotension 
(without underlying 
diagnosis)
Transient, intermittent, 
asymptomatic 
orthostatic decrease in 
blood pressure> 20 mm 
Hg
Symptomatic, without 
interference with 
function, recurrent or 
persistent > 20 mm Hg 
decrease, responds to 
treatment
Syncope or symptomatic, 
interferes with function, 
requiring therapy and 
sustained medical 
attention, dose 
adjustment or drug 
discontinuation
Shock
B6. Myocardial 
ischaemia 
Transient chest 
pain/ECG changes; 
rapid relief with nitro
Recurring chest pain, 
transient ECG ST-T 
changes; treatment 
relieves
Angina with infarction, 
no or minimal functional 
compromise, reduce dose
or discontinue study drug
Acute myocardial 
infarction, arrhythmia 
or/and CHF
B7. 
Pericarditis/pericardial 
effusion
Rub heard, 
asymptomatic
Detectable effusion by 
echocardiogram, 
symptomatic, NSAID 
required
Detectable on chest x-
ray, dyspnea; or 
pericardiocentesis; 
requires corticosteroids
Pulsus alternates with 
low cardiac output; 
requires surgery
B8. 
Phlebitis/thrombosis/ 
embolism (excludes 
injection sites)
Asymptomatic, 
superficial, transient, 
local, or no treatment 
required
Symptomatic, recurrent, 
deep vein thrombosis, no 
anticoagulant therapy 
required 
Deep vein thrombosis 
requiring anticoagulant 
therapy
Pulmonary embolism


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
C. GENERAL (constitutional)
C1. Fatigue/malaise 
(asthenia)
Increase over baseline; 
most usual daily 
functions maintained, 
short term
Limits daily function 
intermittently over time
Interferes with basic 
ADL, persistent 
Unable to care for self, 
bed or wheelchair bound 
> 50% of day 
debilitating, 
hospitalisation
C2. Fever (pyrexia) 
(note: fever due to 
drug allergy should be 
coded as allergy)
Transient, few 
symptoms 37.7–38.5°C
Symptomatic, recurrent, 
38.6-39.9°C. Relieved by 
meds. 
≥ 40°C; ≤ 24h, persistent 
symptoms; partial 
response to meds.
≥ 40°C, debilitating,
> 24h, hospitalisation; no 
relief with meds
C3. Headache
Transient or 
intermittent, no meds or 
relieved with OTC 
Persistent, recurring, 
non-narcotic analgesics 
relieve
Prolonged, with limited 
response to narcotic 
medicine
Intractable, debilitating, 
requires parenteral meds.


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
C. GENERAL
C4. Insomnia
Difficulty sleeping, 
short term, not 
interfering with 
function
Difficulty sleeping, 
interfering with function, 
use of prescription med.
Prolonged symptoms, 
with limited response to 
narcotic meds.
Debilitating, 
hospitalisation; no relief 
with meds
C5. Rigors, chills
Asymptomatic, 
transient, no meds, or 
non-narcotic meds 
relieve
Symptomatic, narcotic 
meds relieve.
Prolonged symptoms, 
with limited response to 
narcotic meds.
Debilitating, 
hospitalisation; no relief 
with meds
C6. Sweating 
(diaphoresis)
Episodic, transient 
Frequent, short term 
Frequent, drenching, 
disabling
Dehydration, requiring 
IV fluids/hospitalization 
> 24hr
C7. Weight gain 
5–9.9% 
10–19.9% 
20–30%
NA
C8. Weight loss 
5–9.9% 
10–19.9% 
20–30%
NA


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
D. DERMATOLOGIC
D1. Alopecia 
Subjective, transient 
Objective, fully 
reversible 
Patchy, wig used, partly 
reversible 
Complete or irreversible 
even if patchy
D2. Bullous eruption 
Localised, 
asymptomatic 
Localised, symptomatic, 
requiring treatment
Generalised, responsive 
to treatment; reversible
Prolonged, generalised, 
or requiring 
hospitalisation for 
treatment
D3. Dry skin 
Asymptomatic, 
controlled with 
emollients
Symptoms eventually (1-
2 wks) controlled with 
emollients
Generalised, interfering 
with ADL >2 wks, 
persistent pruritus, 
partially responsive to 
treatment
Disabling for extended 
period, unresponsive to 
ancillary therapy and 
requiring study drug 
discontinuation for relief
D4. Injection site 
reaction
Local erythema, pain 
pruritus, < few days
Erythema, pain, oedema, 
may include superficial 
phlebitis, 1-2 wks
Prolonged induration, 
superficial ulceration; 
includes thrombosis
Major ulceration necrosis 
requiring surgery
D5. Petechiae
(without vasculitis)
Few, transient 
asymptomatic
Dependent areas, 
persistent up to 2 wks
Generalised, responsive 
to treatment; reversible
Prolonged, irreversible, 
disabling


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
D. DERMATOLOGIC
D6. Photosensitivity 
Transient erythema 
Painful erythema and 
oedema requiring topical 
treatment
Blistering or 
desquamation, requires 
systemic corticosteroids
Generalised exfoliation
or hospitalisation
D7. Pruritus 
Localised, 
asymptomatic, 
transient, local 
treatment
Intense, or generalised, 
relieved by systematic 
medication
Intense or generalised; 
poorly controlled despite 
treatment
Disabling, irreversible
D8. Rash (not bullous) Erythema, scattered 
macular/papular 
eruption; pruritus 
transient, OTC or no 
meds
Diffuse macular/papular 
eruption or erythema 
with pruritus; dry 
desquamation; treatment 
required
Generalised, moist 
desquamation, requires 
systemic corticosteroids; 
responsive to treatment; 
reversible
Exfoliative or ulcerating; 
or requires 
hospitalisation; or 
parenteral corticosteroids
D9. 
Induration/fibrosis/
Thickening (not 
sclerodermal)
Localized, high density 
on palpation, reversible, 
no effect on ADL and 
no disfiguring
Local areas < 50% body 
surface, not disfiguring, 
transient interference 
with ADL, reversible
Generalised, disfiguring, 
interferes with ADL, 
reversible
Disabling, irreversible, 
systemic symptoms


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
E. EAR/NOSE/THROAT
E1. Hearing loss
Transient, intermittent, 
no interference with 
function
Symptomatic, treatment 
required, reversible
Interferes with function; 
incomplete response to 
treatment
Irreversible deafness
E2. Sense of smell 
Slightly altered
Markedly altered
Complete loss, reversible
Complete loss, without 
recovery
E3. Stomatitis
Asymptomatic
Painful, multiple, can eat
Interferes with nutrition, 
slowly reversible
Requires enteral support, 
residual dysfunction
E4. Taste disturbance 
(dysgeusia)
Transiently altered; 
metallic
Persistently altered; 
limited effect on eating
Disabling, effect on 
nutrition 
NA
E5. Tinnitus
Intermittent, transient, 
no interference with 
function
Requires treatment, 
reversible
Disabling, or associated 
with hearing loss
Irreversible deafness
E6. Voice changes 
(includes hoarseness, 
loss of voice, 
laryngitis)
Intermittent hoarseness, 
able to vocalise
Persistent hoarseness, 
able to vocalise
Whispered speech, slow 
return of ability to 
vocalise
Unable to vocalize for 
extended


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
E. EAR/NOSE/THROAT
E7. Xerostomia (dry 
mouth)
Transient dryness
Relief with meds
Interferes with nutrition, 
slowly reversible
Extended duration 
interference with 
nutrition, requires 
parenteral nutrition
F. EYE/OPHTHALMOLOGIC     
F1. Cataract
Asymptomatic, no 
change in vision, non-
progressive
Symptomatic, partial 
visual loss, progressive
Symptoms impairing 
function, vision loss 
requiring treatment, 
including surgery
NA
F2. Conjunctivitis 
Asymptomatic, 
transient, rapid 
response to treatment 
Symptomatic, responds 
to treatment, changes not 
interfering with function
Symptoms prolonged, 
partial response to 
treatment, interferes with 
function
NA
F3. Lacrimation 
increased (tearing, 
watery eyes)
Symptoms not requiring 
treatment, transient
Symptomatic, treatment 
required, reversible
Unresponsive to 
treatment with  major 
effect on function
NA


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
F. EYE/OPHTALMOLOGIC
F4. Retinopathy
Asymptomatic, non-
progressive, no 
treatment
Reversible change in 
vision; readily responsive 
to treatment
Disabling change in 
vision ophthalmological 
findings reversible, sight 
improves over time
Loss of sight
F5. Vision changes 
(e.g. blurred, 
photophobia, night 
blindness, vitreous 
floaters)
Asymptomatic, 
transient, no treatment 
required
Symptomatic, vision 
changes not interfering 
with function, reversible
Symptomatic, vision 
changes interfering with 
function
Loss of sight
F6. Xerophthalmia 
(dry eyes)
Mild scratchiness
Symptomatic without 
interfering with function, 
requires artificial tears
Interferes with 
vision/function, corneal 
ulceration
Loss of sight
G. GASTROINTESTINAL
G1. Anorexia 
Adequate food intake, 
minimal weight loss
Symptoms requiring oral 
nutritional 
supplementation
Prolonged, requiring iv 
support
Requires hospitalization 
for nutritional support


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
G. GASTROINTESTINAL
G2. Constipation
Asymptomatic, 
transient, responds to 
stool softener, OTC 
laxatives
Symptomatic, requiring 
prescription laxatives, 
reversible
Obstipation, requiring 
medical intervention
Bowel obstruction. 
Surgery required.
G3. Diarrhea 
Transient, increase of 
2–3 stools/day over pre-
treatment (no blood or 
mucus), OTC agents 
relieve
Symptomatic, increase 
4–6 stools/day, nocturnal 
stools, cramping, 
requires treatment with 
prescription meds.
Increase > 6 stools/day, 
associated with disabling 
symptoms, e.g. 
incontinence, severe 
cramping, partial 
response to treatment
Prolonged, dehydration, 
unresponsive to 
treatment, requires 
hospitalization.
G4. Dyspepsia 
(heartburn) 
Transient, intermittent, 
responds to OTC 
antacids, H-2 blockers
Prolonged, recurrent, 
requires prescription 
meds, relieved by meds
Persistent despite 
treatment, interferes with 
function, associated with 
GI bleeding
NA


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
G. GASTROINTESTINAL
G5. GI bleed 
(gastritis, gastric or 
duodenal ulcer 
diagnosed-define 
aetiology)
Asymptomatic, 
endoscopic finding, 
haemocult + stools, no 
transfusion, responds 
rapidly to treatment
Symptomatic, transfusion 
≤2 units needed; 
responds to treatment
Haematemesis, 
transfusion 3–4 units, 
prolonged interference 
with function
Recurrent, transfusion > 
4 units, perforation, 
requiring surgery, 
hospitalisation
G6. Haematochezia 
(rectal bleeding)
Haemorrhoidal, 
asymptomatic, no 
transfusion
Symptomatic, transfusion 
≤2 units, reversible
Recurrent, transfusion > 
3–4 units
> 4 units, hypotension, 
requiring hospitalization
G7. Hepatitis
Laboratory 
abnormalities, 
asymptomatic, 
reversible
Symptomatic laboratory 
abnormalities, not 
interfering with function, 
slowly reversible
Laboratory abnormalities 
persistent >2wks, 
symptoms interfere with 
function
Progressive, hepato-
renal, anasarca, pre-coma 
or coma
G8. Nausea, or 
nausea/vomiting (use 
diagnostic term)
Transient, intermittent, 
minimal interference 
with intake, rapid 
response to meds.
Persistent, recurrent, 
requires prescription 
meds, intake maintained
Prolonged, interferes 
with daily function and 
nutritional intake, 
periodic iv fluids
Hypotensive, 
hospitalization, 
parenteral nutrition, 
unresponsive to out-
patient management


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
G. GASTROINTESTINAL
G9. Pancreatitis
Amylase elevation, 
intermittent 
nausea/vomiting, 
transient, responds 
rapidly to treatment
Amylase elevation with 
abdominal pain, nausea, 
occasional vomiting, 
responsive to treatment
Severe, persistent 
abdominal pain with 
pancreatic enzyme 
elevation, incomplete or 
slow response to 
treatment
Complicated by shock, 
haemorrhage (acute 
circulatory failure)
G10. Proctitis 
Perianal pruritus, 
haemorrhoids (new 
onset), transient, or 
intermittent, relieved by 
OTC meds
Tenesmus or ulcerations, 
anal fissure, responsive 
to treatment, minimal 
interference with 
function
Unresponsive to 
treatment, marked 
interference with 
function
Mucosal necrosis with 
haemorrhage, infection, 
surgery required.
H. MUSCULOSKELETAL
H1. Avascular 
necrosis 
Asymptomatic
Magnetic resonance 
imaging (MRI)
changes, non-
progressive
MRI changes and 
symptoms responsive to 
rest and analgesia
MRI changes, symptoms 
requiring surgical 
intervention
Wheelchair bound; 
surgical repair not 
possible


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
H. MUSCULOSKELETAL
H2. Arthralgia
Intermittent transient 
symptoms, no meds or 
relieved by OTC meds
Persistent or recurrent 
symptoms, resolve with 
meds, little effect on 
function
Severe symptoms despite 
meds impairs function
Debilitating, 
hospitalisation required 
for treatment
H3. Leg cramps
Transient, intermittent, 
does not interfere with 
function
Recurrent symptoms, 
minimally interferes with 
function or sleep, 
respond to meds
Persistent, prolonged 
interference with 
function or sleep, partial 
or no response to meds
NA
H4. Myalgia
Occasional; does not 
interfere with function
Frequent, requires meds 
(non- narcotic); minor 
effect on function
Major change in 
function/lifestyle, 
narcotic pain meds
Debilitating, profound 
weakness, requires 
wheelchair, unresponsive 
to meds
I. NEUROPSYCHIATRIC
I-1. Anxiety or 
Depression (mood 
alteration)
Symptomatic, does not 
interfere with function; 
no meds
Frequent symptoms, 
responds to meds; 
interferes with ADL at 
times
Persistent, prolonged 
symptoms; partial or no 
response to meds, limits 
daily function
Suicidal ideation or 
danger to self


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
I. NEUROPSYCHIATRIC
I-2. Cerebrovascular 
ischaemia
NA
Single transient 
ischaemic event, 
responsive to treatment
Recurrent transient 
ischemic events
Cerebrovascular vascular 
accident with permanent 
disability
I-3. Cognitive 
disturbance
Subjective symptoms, 
transient, intermittent, 
not interfering with 
function
Objective symptoms, 
persisting, interferes with 
daily function 
occasionally
Persistent, or worsening 
objective symptoms; 
interferes with daily 
routine
Debilitating/disabling 
and permanent; toxic 
psychosis
I-4. Depressed 
consciousness 
(somnolence)
Observed, transient, 
intermittent, not 
interfering with 
function
Somnolence or sedation, 
interfering with function
Persistent, progressive, 
obtundation, stupor
Coma
I-5. Inability to 
concentrate
Subjective symptoms, 
does not interfere with 
function
Objective findings, 
interferes with function
Persistent, prolonged 
objective findings; or 
organic cause
NA


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
I. NEUROPSYCHIATRIC
I-6. Insomnia (in 
absence of pain)
Occasional difficulty 
sleeping, transient 
intermittent, not 
interfering with 
function
Recurrent difficulty 
sleeping; requires meds 
for relief; occasional 
interference with 
function
Persistent or worsening 
difficulty sleeping; 
severely interferes with 
routine daily function
NA
I-7. Libido decreased
Decrease in interest
Loss of interest; 
influences relationship
Persistent, prolonged, 
interfering with 
relationship
NA
I-8. Peripheral motor 
neuropathy
Subjective or transient 
loss of deep tendon 
reflexes; function 
maintained
Objective weakness, 
persistent, no significant 
impairment of daily 
function
Objective weakness with 
substantial impairment of 
function
Paralysis
I-9. Peripheral sensory 
neuropathy (sensory 
disturbance)
Subjective symptoms 
without objective 
findings, transient, not 
interfering with 
function
Objective sensory loss, 
persistent, not interfering 
with function
Prolonged sensory loss or 
paraesthesias interfering 
with function
NA


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
I. NEUROPSYCHIATRIC
I-10. Seizure
NA
Recurrence of old 
seizures, controlled with 
adjustment of medication
Recurrence/exacerbation 
with partial response to 
medication
Recurrence not 
controlled, requiring 
hospitalization; new 
seizures
I-11. Vertigo 
(dizziness)
Subjective symptoms, 
transient, intermittent, 
no treatment
Objective findings, 
recurrent, meds relieve, 
occasionally interfering 
with function
Persistent, prolonged, 
interfering with daily 
function; partial response 
to medication
Debilitating without 
response to medication, 
hospitalization
J. PULMONARY
J1. Asthma 
Occasional wheeze, no 
interference with 
activities
Wheezing, requires oral 
meds, occasional 
interference with 
function
Debilitating, requires 
nasal O2
Requires ventilator 
assistance
J2. Cough 
Transient, intermittent, 
occasional OTC meds 
relieve
Persistent, requires 
narcotic or other 
prescription meds for 
relief
Recurrent, persistent 
coughing spasms without 
consistent relief by meds, 
interferes with function
Interferes with 
oxygenation; debilitating


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
J. PULMONARY
J3. Dyspnea
Subjective, transient, no 
interference with 
function
Symptomatic, 
intermittent or recurring, 
interferes with exertional 
activities
Symptomatic during 
daily routine activities, 
interferes with function, 
treatment with 
intermittent nasal O2
relieves
Symptomatic at rest, 
debilitating, requires 
constant nasal O2
J4. Pleuritic pain
(pleurisy)
Transient, intermittent 
symptoms, no treatment 
or OTC meds relieve
Persistent symptoms, 
requires prescription 
meds for relief
Prolonged symptoms, 
interferes with function, 
requires frequent narcotic 
pain relief
Debilitating, requiring 
hospitalisation
J5. Pneumonitis 
(pulmonary infiltrates)
Asymptomatic 
radiographic changes, 
transient, no treatment 
required
Symptomatic, persistent, 
requiring corticosteroids
Symptomatic, requiring 
treatment including O2
Debilitating, not 
reversible; or requiring 
assisted ventilation


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
J. PULMONARY
J6. Pulmonary 
function decreased 
(Forced vital capacity
(FVC) or carbon 
monoxide diffusion 
capacity— DLCO)
76–90% of pre-
treatment value
51–75% of pre-treatment 
value
26–50% of pre-treatment 
value
≤25% of pre-treatment 
value
LABORATORY DATA
K. HAEMATOLOGY
K1. Hgb (g/dl) 
decrease from pre-
treatment
1.0–1.4
1.5–2.0
2.1–2.9; or Hgb < 8.0, > 
7.0
≥3.0; or Hgb < 7.0
K2. Leukopenia (total 
WBC) x 1000
3.0–3.9
2.0–2.9
1.0–1.9
< 1.0
K3. Neutropenia (x 
1000) 
1.5–1.9 
1.0–1.4 
0.5–0.9 
< 0.5


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
LABORATORY DATA
K. HAEMATOLOGY
K4. Lymphopenia (x 
1000)
1.5–1.9
1.0–1.4
0.5–0.9
< 0.5
K5. Platelets (x 1000)
75– Lower limit of 
normal (LLN)
50–74.9
20–49.9; platelet 
transfusion required
< 20; recurrent platelet 
transfusions
LABORATORY DATA
L. CHEMISTRY
L1. Hypercalcaemia 
(mg/dl) 
1.1 x ULN–11.5 
11.6–12.5 
12.6–13.5; or symptoms 
present 
> 13.5; or associated 
coma
L2. Hyperglycaemia 
(mg/dl)
Fasting
140–160 
161–250 
251–500 
>500, or associated with 
fasting ketoacidosis


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
LABORATORY DATA
L. CHEMISTRY
L3. Hyperkalaemia 
(mg/dl)
5.5–5.9
6.0–6.4
6.5–7.0 or any ECG 
change
> 7.0 or any arrhythmia
L5. Hypocalcaemia 
(mg/dl)
0.9 x LLN–7.8
7.7–7.0
6.9–6.5; or associated 
with symptoms
< 6.5, or occurrence of 
tetany
L6. Hypoglycemia 
(mg/dl) 
55–64 (no symptoms) 
40–54 (or symptoms 
present) 
30–39 (symptoms impair 
function)
< 30, or coma
L7. Hyponatraemia 
(mg/dl) 
NA
125–129
120–124
< 120
L8. Hypokalaemia 
(mg/dl) 
NA
3.0–3.4
2.5–2.9
< 2.5
L9. CPK (also if 
polymyositis- disease)
1.2–1.9 x ULN 
2.0–4.0 x ULN 
> 4.0 x ULN with 
weakness but without 
life-threatening signs or 
symptoms 
> 4.0 x ULN with signs 
or symptoms of 
rhabdomyolysis or life-
threatening


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
LABORATORY DATA
L. CHEMISTRY
L10.Serum uric acid 
1.2–1.6 x ULN 
1.7–2.9 x ULN 
3.0–5.0 x ULN or gout 
NA
L11. Creatinine 
(mg/dl) 
1.1–1.3 x ULN 
1.3–1.8 x ULN 
1.9–3.0 x ULN 
> 3.0 x ULN
L12. SGOT (AST) 
1.2–1.5 x ULN 
1.6–3.0 x ULN 
3.1–8.0 x ULN 
> 8.0 x ULN
L13. SGPT (ALT) 
1.2–1.5 x ULN 
1.6–3.0 x ULN 
3.0–8.0 x ULN 
> 8.0 x ULN
L14. Alkaline 
phosphatase 
1.1–2.0 x ULN 
1.6–3.0 x ULN 
3.0–5.0 x ULN 
> 5.0 x ULN
L15. T. bilirubin 
1.1–1.4 x ULN 
1.5–1.9 x ULN 
2.0–3.0 x ULN 
> 3.0 x ULN
L16. LDH 
1.3–2.4 x ULN 
2.5–5.0 x ULN 
5.1–10 x ULN 
> 10 x ULN


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
LABORATORY DATA
M. URINALYSIS
M1. Haematuria 
Micro only 
Gross, no clots 
Clots, transfusion < 2 
units 
Transfusions required
M2. Proteinuria (per 
24 h) 
300–500 mg (tr/1+) 
501–1999 mg (2+) 
2–5.0 mg (3+) nephrotic 
syndrome 
> 5.0 g (4+) anasarca
M3. WBC in urine 
NA
NA
Indicating acute 
interstitial nephritis 
Associated with 
acuterenal failure
M4. Uric acid crystals 
Present without 
symptoms 
NA
With stones or symptoms 
of stones (e.g. renal 
colic) 
Causing renal outflow 
obstruction and 
hospitalization


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11.
DESCRIPTION OF GLOBAL AMENDMENT(S)
Number of global amendment
1
Date of CTP revision
26 September 2014
EudraCT number
2014-001687-36
BI Trial number
1311.13
BI Investigational Product(s)
BI 655066
Title of protocol
An open label extension trial assessing the safety 
and efficacy of BI 655066 administered 
subcutaneously in patients with moderate to 
severe chronic plaque psoriasis.
To be implemented only after 
approval of the 
IRB/IEC/Competent 
Authorities
To be implemented 
immediately in order to 
eliminate hazard –
IRB / IEC / Competent 
Authority to be notified of 
change with request for 
approval
Can be implemented without 
IRB/IEC/ Competent 
Authority approval as changes 
involve logistical or 
administrative aspects only
Section to be changed
CLINICAL TRIAL PROTOCOL SYNOPSIS,
Trial site(s)
Description of change
Change wording to ‘Multicenter, multi national’ 
Rationale for change
Number of sites and countries will change during 
the trial conduct. 
Section to be changed
CLINICAL TRIAL PROTOCOL SYNOPSIS,
Objective(s)
Description of change
Change from ‘Long term’ to ‘Additional’ safety 
and efficacy data.
Rationale for change
Modification of Objective to correlate with FDA 
requirement of maximum duration of 
administration of BI655066 of one year.


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Section to be changed
CLINICAL TRIAL PROTOCOL SYNOPSIS,
Duration of treatment
Description of change
Change from ‘Approximately 4 years’ to 
‘Maximum duration of administration to patient is 
one calendar year after receiving first dose of BI 
655066’
Rationale for change
Modification to correlate with FDA requirement
Section to be changed
CLINICAL TRIAL PROTOCOL SYNOPSIS,
Criteria for efficacy
Description of change
Modification of endpoint due to reduction in 
study duration and maximum administration of 
study medication of one year.
Rationale for change
Modification to correlate with FDA requirement
Section to be changed
FLOW CHART 1
Description of change
Change of duration of treatment period and 
Follow up period, as well as correct footnotes and 
numbering. Additional text is added to footnote 1 
to better explain roll-over from trial 1311.2, 
footnote 4 covering visits beyond visit 18 is 
deleted and wording for footnote 5 describing 
variable timing of EOT is modified to adapt the 
maximum duration of administration of one year. 
Corrective words have been added to footnote 9 
and 12, Vital signs has been added to all 
scheduled visits, and footnote 19 has been added 
to better describe drug administration.
Rationale for change
These are administrative changes to correct 
duration of treatment period and follow up period, 
numbering of footnotes and to correct wordings in 
the footnotes to correlate with FDA requirement 
of maximum duration of administration of 
BI655066 of one year.
Section to be changed
2.1 RATIONALE FOR PERFORMING THE 
TRIAL
Description of change
Change of wording from ‘Long term’ to 
‘Additional’ safety and efficacy data, and add 
wording for 48 week follow up.
Rationale for change
Modification due to reduction in study duration 
and maximum administration of study medication 
of one year.


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Section to be changed
2.2 TRIAL OBJECTIVES
Description of change
Change of wording from ‘Long term’ to 
‘Additional’ safety and efficacy data.
Rationale for change
Modification due to reduction in study duration to 
one year administration of study medication.
Section to be changed
2.3 BENEFIT – RISK ASSESSMENT
Description of change
Further description of signs of hypersensitive 
reactions is added.
Rationale for change
Include further, adequate details concerning the 
performance of monitoring after IMPs injections,
for all treated patients.
Section to be changed
3.1 OVERALL TRIAL DESIGN AND PLAN
Description of change
Change of wording from ‘Long term’ to 
‘Additional’ safety and efficacy data.
Rationale for change
Modification due to reduction in study duration to 
one year administration of study medication.
Section to be changed
3.1 OVERALL TRIAL DESIGN AND PLAN
Description of change
Description of how to proceed if a subject is 
eligible for 1311.13 and the protocol is not yet 
approved.
Rationale for change
To be able to re-evaluate subjects eligible for 
1311.13 while protocol not yet approved. This 
situation is applicable for possible roll-overs from 
1311.2 during the period the study initiation has 
been on hold. Procedures for re-evaluation is 
specified.
Section to be changed
3.1 OVERALL TRIAL DESIGN AND PLAN
Description of change
Figure 3.1:2 ‘Drug Administration in trial 
1311.13’ is added
Rationale for change
Table is added to explain drug administration at 
different visit throughout the trail. 
Section to be changed
3.1 OVERALL TRIAL DESIGN AND PLAN
Description of change
Delete text describing adjustment of dosing to 
180 mg and text describing possible reduction of 
dosing after study data from 1311.2 is revealed.
Rationale for change
Due to FDA regulation, maximum dosage is 90 
mg per 12 week, 180 mg dose is no longer 
applicable in this trial.


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Section to be changed
3.1 OVERALL TRIAL DESIGN AND PLAN
Description of change
PASI75 is added as standard clinical endpoint and 
to be assessed at each visit.
Rationale for change
The plaque psoriasis will be evaluated by PASI 
score at each visit. The standard clinical endpoints 
of PASI50, PASI75 and PASI90 will be assessed at 
each visit.
Section to be changed
FIG 3.1:2 Guideline for assessment dose 
adjustment
Description of change
Figure is deleted.
Rationale for change
Figure describes possible dose adjustment 
between 90 mg and 180 mg dose. Due to FDA 
regulation, maximum dosage is 90 mg per 12 
week, 180 mg dose is no longer applicable in this 
trial.
Section to be changed
3.1.1 ADMINISTRATIVE STRUCTURE OF 
THE TRIAL
Description of change
Change of number of participating sites and 
countries.
Rationale for change
Number of participating sites and countries has 
been modified, to reflect the current status for 
this.
Section to be changed
3.2 DISCUSSION OF TRIAL DESIGN
Description of change
Delete text describing adjustment of dosing to 
180 mg.
Rationale for change
Due to FDA regulation, maximum dosage is 90 
mg per 12 week, 180 mg dose is no longer 
applicable in this trial.
Section to be changed
3.2 DISCUSSION OF TRIAL DESIGN
Description of change
Change of wording from ‘Long term’ to 
‘Additional’ safety and efficacy data, and adding 
‘following one year drug administration’.
Rationale for change
Modification due to reduction in study duration 
and administration of study medication.
Section to be changed
3.3.4.1 REMOVAL OF INDIVIDUAL 
PATIENTS 
Description of change
Corrections to reflect new study duration of 48 
week follow up instead of 15 days.
Rationale for change
Study duration changed to 48w follow up after 
one year maximum study drug administration.


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Section to be changed
4.1.2 METHOD OF ASSIGNING PATIENTS 
TO TREATMENT GROUPS
Description of change
Delete text describing adjustment of dosing to 
180 mg.
Rationale for change
Due to FDA regulation, maximum dosage is 90 
mg per 12 week, 180 mg dose is no longer 
applicable in this trial.
Section to be changed
4.1.3 SELECTION OF DOSES IN THE TRIAL
Description of change
Delete text describing adjustment of dosing to 
180 mg and possible adjustment of dosing once 
the 1311.2 study results are available.
Rationale for change
Due to FDA regulation, maximum dosage is 90 
mg per 12 week, 180 mg dose is no longer 
applicable in this trial.dose applicable for this 
study. 
Section to be changed
TABLE 4.1.4.1. Dose regimens
Description of change
Table is deleted.
Rationale for change
Table describes dose regimens for 90 mg and 180 
mg dose. Dose of 90 mg is the only dose 
applicable for this study.
Section to be changed
4.1.4 DOSE ASSIGNMENT AND 
ADMINISTRATION OF DOSES
Description of change
Further description of signs of hypersensitive 
reactions is added.
Rationale for change
Include further, adequate details concerning the 
performance of monitoring after IMPs injections,
for all treated patients. Requirement from French 
HA.
Section to be changed
5.1.1 ENDPOINTS OF EFFICACY
Description of change
Time of evaluation of primary and secondary 
endpoints has been changed from 12 week to 48 
week.
Rationale for change
Change of timing of evaluation for endpoints 
necessary to reflect maximum study drug 
administration of one calendar year.


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Section to be changed
TABLE 5.2.3:2 SAFETY LABORATORY 
TESTS
Description of change
Test for ESR (erythrocyte sedimentation rate after 
1 hour) is deleted.
Rationale for change
ESR test is not to be performed, due to 
evaluations from 1311.2. The test had to be 
performed at local lab, and the interpretation of 
the test results is not validated to give reliable 
values.
Section to be changed
6.2.2 TREATMENT PERIOD(S)
Description of change
Description of how to proceed if a subject is 
eligible for 1311.13 and the amended protocol is 
not yet approved. Also added in section 3.1.
Rationale for change
To be able to re-evaluate subjects eligible for 
1311.13 while protocol not yet approved. This 
situation is applicable for possible roll-overs from 
trial 1311.2 during the period the study 1311.13 
has not yet been initiated due to review of 
protocol amendment. Procedures for re-evaluation 
are specified.
Section to be changed
6.2.2 TREATMENT PERIOD(S)
Description of change
Text describing adjustment of dosing to 180 mg is 
deleted.
Rationale for change
Dose of 90 mg is the only dose applicable for this 
study. 
Section to be changed
6.2.3 END OF TRIAL AND FOLLOW_UP 
PERIOD
Description of change
Specification of end of trial is changed, adding 
description of 48 week follow up period.
Rationale for change
Specification of end of trial is changed due to 
reduction in study duration and administration of 
study medication of maximum one year.
Section to be changed
7.2 NULL AND ALTERNATIVE HYPETHESIS
Description of change
Change of wording regarding duration of study 
drug administration.
Rationale for change
Modification due to reduction in study duration 
and maximum administration of study medication 
of one year.


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Section to be changed
7.3 PLANNED ANALYSIS
Description of change
Deleting text describing critical time-points 
beyond 1 year.
Rationale for change
Modification due to reduction in study duration 
and maximum administration of study medication 
of one year.
Section to be changed
7.3.1 PRIMARY ANALYSIS
Description of change
Modification of endpoint due to reduction in 
study duration and maximum administration of 
study medication of one year.
Rationale for change
Modification to correlate with FDA requirement


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Number of global amendment
2
Date of CTP revision
15 October 2014
EudraCT number
2014-001687-36
BI Trial number
1311.13
BI Investigational Product(s)
BI 655066
Title of protocol
An open label extension trial assessing the safety 
and efficacy of BI 655066 administered 
subcutaneously in patients with moderate to 
severe chronic plaque psoriasis.
To be implemented only after 
approval of the 
IRB/IEC/Competent
Authorities
To be implemented 
immediately in order to 
eliminate hazard –
IRB / IEC / Competent 
Authority to be notified of 
change with request for 
approval
Can be implemented without 
IRB/IEC/ Competent 
Authority approval as changes 
involve logistical or 
administrative aspects only
Section to be changed
FLOW CHART 1
Description of change
Change of wording for day and week to relate to 
EOT instead of absolute numbers. Change of text 
in footnote 4 to better explain drug 
administrations. Addition of footnote 20 and 21 to 
better explain procedures for prematurely 
discontinuation and collection of vital signs and 
vital status follow up. Assessment for Tolerability 
(safety and efficacy) has been deleted, as this was 
primarily for evaluation of dose adjustments 
which are no longer applicable, so has local 
tolerability test for follow up period after FU2.  
Rationale for change
These are administrative changes to clarify timing 
of visit, and study procedures for drug 
administrations, withdrawals and collection of 
vital signs and vital status follow up. 


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Section to be changed
3.1 OVERALL TRIAL DESIGN AND PLAN
Description of change
Study number 1311.13 added in text to clarify 
drug administration for patients that did not 
receive BI655066 in trial 1311.2 
Rationale for change
Text added to clarify.
Section to be changed
3.1 OVERALL TRIAL DESIGN AND PLAN
Description of change
Figure 3.1:2 deleted and replaced by Flow Chart 2 
to better explain drug administration 
Rationale for change
Figure revised to clarify drug administration.
Section to be changed
3.3.4 REMOVAL OF PATIENTS
Description of change
Text added to clarify procedures for withdrawal 
in follow up period 
Rationale for change
Text added to clarify.
Section to be changed
5.2.5 ASSESSMENT OF OTHER SAFETY 
PARAMETER
Description of change
Text explaining ‘Tolerability (safety and 
efficacy)’ has been deleted, as this was primarily 
for evaluation of dose adjustments which are no 
longer applicable.
Rationale for change
Assessment no longer applicable, as only one 
dose applicable in this trial.
Section to be changed
6.2.2.TREATMENT PERIOD
Description of change
‘EOT’ removed from text to avoid mix with EOS. 
Added text regarding study window removed, 
misleading.  
Rationale for change
Text removed to clarify.
Section to be changed
6.2.2.TREATMENT PERIOD
Description of change
Text added to clarify drug administration for 
patients that did not receive BI655066 in trial 
1311.2. Also ref to Flow Chart 2 added to clarify.
Rationale for change
Text and reference to Flow Chart 2 added to 
clarify.
Section to be changed
6.2.3 END OF TRIAL AND FOLLOW-UP 
PERIOD
Description of change
Text added to clarify procedures for withdrawal 
in follow up period 
Rationale for change
Text added to clarify.
Section to be changed
6.2.3 END OF TRIAL AND FOLLOW-UP 
PERIOD
Description of change
Text added to describe collection of consent for 


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vital status follow up.   
Rationale for change
Text added to clarify.
Number of global amendment
3
Date of CTP revision
10 June 2015
EudraCT number
2014-001687-36
BI Trial number
1311.13
BI Investigational Product(s)
BI 655066
Title of protocol
An open label extension trial assessing the safety 
and efficacy of BI 655066 administered 
subcutaneously in patients with moderate to 
severe chronic plaque psoriasis.
To be implemented only after 
approval of the 
IRB/IEC/Competent 
Authorities
To be implemented 
immediately in order to 
eliminate hazard –
IRB / IEC / Competent 
Authority to be notified of 
change with request for 
approval
Can be implemented without 
IRB/IEC/ Competent 
Authority approval as changes 
involve logistical or 
administrative aspects only
Section to be changed
CLINICAL TRIAL PROTOCOL SYNOPSIS,
Objective(s)
Description of change
Change from ‘Additional’ to ‘Long term’ safety 
and efficacy data.
Rationale for change
Return to original CTP wording with approx 4
years duration of treatment. New toxicity data 
cancel FDA requirement of maximum duration of 
administration of BI655066 of one year.
Section to be changed
CLINICAL TRIAL PROTOCOL SYNOPSIS,
No. patients each treatment 
Description of change
Text including possible increase to 180 mg dosing 
every 12 week is added. 
Rationale for change
Possibility to increase to 180 mg dosing 
depending on efficacy at 12 week added. Patients 


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should all reach >PASI90.
Section to be changed
CLINICAL TRIAL PROTOCOL SYNOPSIS,
Test product (s) 
Description of change
‘180 mg dosing every 12 week’ added 
Rationale for change
Possible increase to 180 mg dosing depending on 
efficacy at 12 week. 
Section to be changed
CLINICAL TRIAL PROTOCOL SYNOPSIS,
Duration of treatment
Description of change
Change from ‘Maximum duration of one calendar 
year’ to ‘Approximately four years of 
administration’. ’48 week follow up period’ 
deleted.
Rationale for change
Return to original CTP wording with approx 4 
years duration of treatment. New toxicity data 
cancel FDA requirement of maximum duration of 
administration of BI655066 of one year. Follow 
up period will now be REP i.e. 12 weeks.
Section to be changed
CLINICAL TRIAL PROTOCOL SYNOPSIS,
Criteria for efficacy
Description of change
Added ‘in the Extended dosing period’ 
Rationale for change
To clarify that point of achievement will be at 48 
week in the extended dosing period only.
Section to be changed
FLOW CHART 
Description of change
Previous Flow Chart 1 deleted and replaced by a 
new. Visit scheduling of previous Flow Chart 1 is 
now added as Figure 3.1.3. New Flow Chart is 
called ‘Extended dosing period’. Change of 
wording for visit to relate to Extended period. 
Footnotes added or modified to explain new study 
procedures related to the extension of the trial and 
possible re-start of treatment. 
Rationale for change
Flow Chart has been modified to reflect 
procedures and timing related to the extension of 
the trial and possible re-start of treatment for the 
patients with low response (<PASI90) at week 12. 
Section to be changed
FLOW CHART 2
Description of change
Flow Chart 2 is deleted. (Replaced by Fig 3.1.3)
Rationale for change
Flow Chart 2 is no longer applicable, due to no 
limitation of maximum one year dosing per 


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patient. Headings kept as reference in Fig 3.1.3
Section to be changed
ABBREVIATIONS
Description of change
Abbreviations added for PASE, EV, OPU, ISF, 
Th and IgG.
Rationale for change
Missed or added since previous amendment.
Section to be changed
2.1 RATIONALE FOR PERFORMING THE 
TRIAL
Description of change
Change from ‘one’ to ‘approximately four years’ 
treatment, ‘48 weeks follow up’ deleted.
Rationale for change
Return to original CTP wording with approx 4 
years duration of treatment. New toxicity data 
cancel FDA requirement of maximum duration of 
administration of BI655066 of one year.
Section to be changed
2.2 TRIAL OBJECTIVES
Description of change
Change from ‘one’ to ‘approximately four years’ 
treatment, change from ‘up to one year’ and 
‘additional’ to ‘long term’.
Rationale for change
Return to original CTP wording with approx 4 
years duration of treatment. New toxicity data 
cancel FDA requirement of maximum duration of 
administration of BI655066 of one year.
Section to be changed
2.3 BENEFIT – RISK ASSESSMENT
Description of change
‘Visit 1’ replaced by ‘rollover visit’ . ‘Extended’ 
added.
Rationale for change
TB testing only to be performed at the initial roll-
over visit. Extended EOT replacing previous 
EOT.
Section to be changed
3.1 OVERALL TRIAL DESIGN AND PLAN
Description of change
Change from ‘total of one’ to ‘approximately four 
years’ treatment. Description of study end added.
Rationale for change
Return to original CTP wording with approx 4 
years duration of treatment. The study is planned 
to continue until marketing approval of BI655066 
in each country.
Section to be changed
3.1 OVERALL TRIAL DESIGN AND PLAN
Description of change
Procedure for roll-over to ‘Extended visit 1’ 
described in the text and Figure 3.2.3.added to 
refer to previous visit schedule. 
Rationale for change
New visit schedule for ‘Extended dosing period’ 
is implemented, procedures for how to roll-over 
new and existing patients into this are added.


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Section to be changed
3.1 OVERALL TRIAL DESIGN AND PLAN
Description of change
Figure 3.1.2.added 
Rationale for change
Figure added to give guideline for assessment of 
dose adjustment.
Section to be changed
3.1 OVERALL TRIAL DESIGN AND PLAN
Description of change
Figure 3.1.3.added 
Rationale for change
Headings from previous Flow Chart kept as 
reference to visit schedule naming. 
Section to be changed
3.1 OVERALL TRIAL DESIGN AND PLAN
Description of change
‘PASI100’ and ‘Extended’ added.
Rationale for change
To be in accordance with section 5.1.1.1.2 and 
7.3.2.
Section to be changed
3.1 OVERALL TRIAL DESIGN AND PLAN
Description of change
Number of sites and countries corrected.
Rationale for change
Since last AM, number of participating sites and 
countries has been modified.
Section to be changed
3.2 DISUSION OF TRIAL DESIGN…
Description of change
‘…option of moving to a higher dose (180 mg) if 
loss of clinically activity is noted’ is added.
Rationale for change
Possible increase to 180 mg dosing depending on 
efficacy at 12 week. Patients should all reach 
>PASI90.
Section to be changed
3.3 SELECTION OF TRIAL POPULATION
Description of change
‘Visit 1’ changed to ‘roll-over visit’ in inclusion 
and exclusion criteria. REP changed from 15 to 
12 weeks.
Rationale for change
To adapt wording to new visit schedule naming 
and design. REP changed according to new IB ver 
5 for BI 6550066.
Section to be changed
3.3.4 REMOVAL OF PATIENTS FROM 
THERAPY
Description of change
Sentence regarding FU visit is deleted. 
‘Extended’ added to all visits mentioned in the 
text. Follow up period changed from 48 to 12 
weeks. ‘Visit 1’ replaced by ‘roll-over visit’.
Rationale for change
FU visits no longer in the revised Flow Chart. 
‘Extended’ added to reflect visit schedule naming 
in new flow Chart.
Section to be changed
4.1 TREATMENT TO BE ADMINISTERED


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Description of change
Text added to describe possible increase in dosing 
to 180 mg if lack of response. Text to explain 
selection of dose has been modified. Instruction 
for injection of 180 mg added. 
Rationale for change
Possible increase to 180 mg dosing depending on 
efficacy at 12 week. Text to explain selection of 
dose has been modified to reflect new findings 
from the interim analysis of 1311.2. 
Section to be changed
4.2.2 RESTRICTIONS
Description of change
‘Extended’ added  and Visit 1’ changed to ‘roll-
over visit’ in Table 4.2.2.1 
Rationale for change
‘Extended’ added to reflect visit schedule naming 
in new flow Chart.
Section to be changed
5.1 EFFICACY -PHARMACODYNAMICS
Description of change
‘in Extended dosing period’ added in text. 
Rationale for change
Added to clarify that prim endpoint will be 
achieved at 48 w in Extended dosing period only. 
Section to be changed
5.2.2. ASSESSMENT OF ADVERSE EVENTS
Description of change
Time window for EV1 changed to 6 weeks. REP 
changed from 15 to 12 weeks.
Rationale for change
Time window for entering EV1 from EOS of 
1311.2 changed from 7 days to 6 weeks, to be 
able to include patients that had to wait for the 
approval of this amendment for their roll-over. 
REP changed to 12 weeks/ 84 days according to 
IB ver 6 for IB655066.
Section to be changed
5.2.3 ASSESSMENT OF SAFETY 
LABORATORY PARAMETERS  
Description of change
‘Visit 1’ changed to ‘roll-over visit’ in table 
5.2.3:2. ‘Extended’ added.
Rationale for change
Changed to clarify and reflect visit schedule 
naming in new flow Chart.
Section to be changed
5.2.4 ELECTROCARDIOGRAM  
Description of change
Specification of visits were ECG will be obtained 
is deleted.
Rationale for change
ECG will be obtained every 24 weeks according 
to new Flow Chart.
Section to be changed
5.2.5 ASSESSMENT OF OTHER SAFETY 
PARAMETERS  
Description of change
‘Visit 1’ changed to ‘roll-over visit’ 
Rationale for change
Changed to clarify procedure according to new 
visit schedule.


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Section to be changed
6.2.2 TREATMENT PERIOD  
Description of change
Text modified and added to reflect procedures 
and assessments according to current Flow Chart.
Rationale for change
Flow Chart with footnotes covering Extended 
Dosing Period will replace former visit schedule 
and procedures.
Section to be changed
6.2.3. END OF TRIAL AND FOLLOW UP 
PERIOD  
Description of change
Text modified and added to reflect procedures 
and assessments according to current Flow Chart. 
Text regarding collection of vital status changed 
to open for collection of consent also at EV1.
Rationale for change
Flow Chart with footnotes covering Extended 
Dosing Period will replace former visit schedule 
and procedures.
Section to be changed
7.1 STATISTICAL DESIGN  
Description of change
Text ‘single’ arm replaced by ‘double’ arm.
Rationale for change
Double arm design due to introduction of possible 
180 mg dose at EV2.
Section to be changed
7.2 NULL AND ALTERNATIVE HYPETHESIS 
Description of change
‘one year’ replaced by ‘extended visit period’.
Rationale for change
Text changed to reflect current visit schedule.
Section to be changed
7.3 PLANNED ANALYSIS 
Description of change
‘in Extended dosing period’ added. REP changed 
to 12 weeks from 15 weeks.
Rationale for change
Added to specify time of efficacy endpoint. REP 
changed according to current IB ver 6.
Section to be changed
10.5 PASE  
Description of change
‘Visit 1’ replaced by ‘roll-over visit’ to reflect 
current flow chart and procedures
Rationale for change
To reflect current flow chart and procedures for 
EV1.


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Number of global amendment
4
Date of CTP revision
12 October 2016
EudraCT number
2014-001687-36
BI Trial number
1311.13
BI Investigational Product(s)
BI 655066
Title of protocol
An open label extension trial assessing the safety 
and efficacy of BI 655066/ ABBV-066/ 
(risankizumab) administered subcutaneously in 
patients with moderate to severe chronic plaque 
psoriasis.
To be implemented only after 
approval of the 
IRB/IEC/Competent 
Authorities
To be implemented 
immediately in order to 
eliminate hazard –
IRB / IEC / Competent 
Authority to be notified of 
change with request for 
approval
Can be implemented without 
IRB/IEC/ Competent 
Authority approval as changes 
involve logistical or 
administrative aspects only
Section to be changed
Title page, Synopsis
Description of change
Changed BI drug or BI investigational product or 
BI 655066 to refer to either names for this 
compound:   BI 655066/ ABBV-
066/risankizumab.
Rationale for change
In February 2016, AbbVie entered into a license 
agreement with BI related to risankizumab, and in 
October 2016, the US IND for risankizumab 
transitioned from BI to AbbVie.   This protocol 
change reflects that AbbVie will now be the 
Sponsor of this study in the US, as well as the 
modifications to certain study conduct 
responsibilities as a result of that license 
agreement are listed as separate changes below.
Section to be changed
3.1.1 ADMINISTRATIVE STRUCTURE OF 
THE TRIAL


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Description of change
1. Changed sponsor from Boehringer Ingelheim 
(BI) to AbbVie in the US and BI for all other 
participating countries.
2. Changed text to specify Statistical Evaluation 
will be done by AbbVie according to their SOPs.
Rationale for change
Refer to rational for first change listed
Section to be changed
3.3.4.2 DISCONTINUATION OF THE TRIAL 
BY THE SPONSOR
Description of change
Updated text to “AbbVie/Boehringer Ingelheim 
reserves the right to discontinue the trial overall 
or at a particular trial site at any time for the 
following reasons”.
Rationale for change
Refer to rational for first change listed


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Number of global amendment
5
Date of CTP revision
30 January 2018
EudraCT number
2014-001687-36
BI Trial number
1311.13
BI Investigational Product(s)
BI 655066
Title of protocol
An open label extension trial assessing the safety 
and efficacy of BI 655066/ ABBV-066/ 
(risankizumab) administered subcutaneously in 
patients with moderate to severe chronic plaque 
psoriasis.
To be implemented only after 
approval of the 
IRB/IEC/Competent 
Authorities
To be implemented 
immediately in order to 
eliminate hazard –
IRB / IEC / Competent 
Authority to be notified of 
change with request for 
approval
Can be implemented without 
IRB/IEC/ Competent 
Authority approval as changes 
involve logistical or 
administrative aspects only
Section to be changed
FLOW CHART-extended dosing period
Description of change
Added at the EOS visit:
After the approval of this protocol amendment in 
each respective country patients who have 
completed the study without early treatment 
discontinuation will be offered to roll over to 
M15-997 open label extension (OLE) trial if they 
fulfil the in- and exclusion criteria for the M15-
997 trial. Refer to section 6.2.3.
Next visit and also the last visit after 1st May and 
approval of this amendment will be the extended 
EOS visit .Termination of trial medication page 
should be completed in the eCRF and treatment 
completed registered in IRT.
Rationale for change
Transition of patients from 1311.13 to M15-997 
study


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Section to be changed
FLOW CHART-extended dosing period
Description of change
Serum pregnancy testing and TB screening added 
to the EOS visit.
Rationale for change
Added to the EOS visit because this will be the 
last visit in the study instead for EOT visit for 
patients not prematurely discontinued.
Section to be changed
FLOW CHART-extended dosing period
Description of change
Consent for vital status follow up deleted from 
EOS visit.
Rationale for change
No longer applicable as the patients will be 
transferred to the M15-997 and this study will 
end.
Section to be changed
FLOW CHART-extended dosing period
Description of change
•Footnote 4: Variable depending on marketing 
approval of BI 655066 deleted
•Footnote 5: If study is ongoing beyond Extended 
visit 18, forthcoming visits should be repeated in 
cycles as described in Extended visit 6 -18 until 
the patient withdraws, or the end of study is 
declared. Visits will be numbered consecutively 
(Extended visit 19, Extended visit 20, …) deleted
Rationale for change
No longer applicable as it is decided when the 
study will end.
Section to be changed
3.1OVERALL TRIAL DESIGN AND PLAN
Description of change
Text deleted: The study is planned to continue in 
each country in which it is conducted, until BI 
655066 is approved and available on the market 
in that country.
Text added: After 01-May-2018 and approval of 
this protocol amendment in each respective 
country, the next study visit will be the Extended 
EOS visit and therewith the last visit in this study. 
Patients who have completed the study without 
early treatment discontinuation will be offered to 
roll over to M15-997 open label extension (OLE) 
trial if they fulfil the in- and exclusion criteria for 
the M15-997 trial. Refer to section 6.2.3.
Rationale for change
Transition of patients from 1311.13 to M-15-997
Section to be changed
6.3 End of trial and Extended follow-up period
Description of change
Update why and how the 1311.13 study should 
end
Rationale for change
Study drug is not marketed yet and the patient 


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will be offered to roll over to M15-997 open label 
extension study and have the opportunity to 
continue with Risankizumab (BI 655066).


 
 
 
APPROVAL / SIGNATURE PAGE 
Document Number: 
 
Technical Version Number:
Document Name: 
                                                                                                                 
 
Title: 
                                                                                                                   
Signatures (obtained electronically) 
Meaning of Signature  
Signed by 
Date Signed 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Boehringer Ingelheim 
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Document Number: 
 Technical Version Number:
 
 
 
(Continued) Signatures (obtained electronically) 
 
Meaning of Signature  
Signed by 
Date Signed 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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

SAP_001.pdf: 
Risankizumab
M16-009 – Statistical Analysis Plan
Version 1.0 – 19 Sep 2018
1
1.0
Title Page
Statistical Analysis Plan
Study M16-009 (1311.13)
An open label extension trial assessing the safety 
and Efficacy of Risankizumab administered 
subcutaneously in patients with moderate to severe 
chronic plaque psoriasis.
Date:  19 Sep 2018
Version 1.0
NCT02203851


Risankizumab
M16-009 – Statistical Analysis Plan
Version 1.0 – 19 Sep 2018
2
2.0
Table of Contents
1.0
Title Page ...............................................................................1
2.0
Table of Contents ..................................................................2
3.0
Introduction...........................................................................4
4.0
Study Objectives, Design and Procedures............................4
4.1
Primary Study Objective......................................................................... 4
4.2
Design Diagram ..................................................................................... 4
4.3
Sample Size............................................................................................ 7
4.4
Interim Analysis ..................................................................................... 7
5.0
Analysis Populations .............................................................8
5.1
Definition for Analysis Populations ........................................................ 8
5.2
Variables Used for Stratification of Randomization ................................ 8
6.0
Analysis Conventions ............................................................8
7.0
Demographics, Baseline Characteristics, Medical 
History, and Previous/Concomitant Medications..............11
7.1
Demographic and Baseline Characteristics ........................................... 11
7.2
Medical History.................................................................................... 13
7.3
Previous Treatment and Concomitant Medications ............................... 13
7.4
Protocol Deviation................................................................................ 14
8.0
Patient Disposition...............................................................14
9.0
Study Drug Exposure and Compliance..............................15
10.0
Efficacy Analysis .................................................................15
10.1
General Considerations......................................................................... 15
10.2
Key Efficacy Variables......................................................................... 16
10.3
Additional Efficacy Analyses ............................................................... 16
11.0
Safety Analysis.....................................................................17
11.1
General Considerations......................................................................... 17
11.2
Analysis of Adverse Events.................................................................. 17
11.2.1
Treatment Emergent Adverse Events.................................................... 17
11.2.2
SAEs (Including Deaths) and Adverse Events Leading to Study 
Drug Discontinuation ........................................................................... 24
11.3
Analysis of Laboratory Data................................................................. 25


Risankizumab
M16-009 – Statistical Analysis Plan
Version 1.0 – 19 Sep 2018
3
11.3.1
Variables and Criteria Defining Abnormality........................................ 25
11.3.2
Statistical Methods ............................................................................... 27
11.4
Analysis of Vital Signs and Weight ...................................................... 30
11.4.1
Variables and Criteria Defining Abnormality........................................ 30
11.4.2
Statistical Methods ............................................................................... 31
11.5
Local Tolerability................................................................................. 31
12.0
Pharmacokinetic Analysis...................................................31
13.0
Biomarkers Analysis ...........................................................31
14.0
Summary of Changes ..........................................................31
15.0
Appendix..............................................................................31
16.0
References............................................................................32
List of Tables
Table 1.
Visit Windows for Analysis of PASI, sPGA, Pain Vas, DLQI, 
Study Drug Injections, Local Tolerability Assessment, Clinical 
Laboratory Tests, and Vital Signs......................................................... 10
Table 2.
Areas of Safety Interest ........................................................................ 21
Table 3.
Clinical Laboratory Tests ..................................................................... 26
Table 4.
Criteria for Potentially Clinically Important Chemistry Values ............. 29
Table 5.
Criteria for Potentially Clinically Important Hematology Values .......... 29
Table 6.
Criteria for Potentially Clinically Significant Vital Sign Findings ......... 30
List of Figures
Figure 1.
Guideline for roll over of patients from Study 1311.2 to this study ......... 5
Figure 2.
Guideline for assessment of dose adjustment .......................................... 6
Figure 3.
Visit schedule Pre-Extended Dosing Period............................................ 7


Risankizumab
M16-009 – Statistical Analysis Plan
Version 1.0 – 19 Sep 2018
4
3.0
Introduction
This statistical analysis plan (SAP) describes the statistical analysis to be completed by 
the AbbVie Clinical Statistics Department for study Protocol M16-009 Amendment 6
dated 30 January 2018. 
This SAP will provide details to further elaborate statistical methods as outlined in the 
Protocol M16-009 and will describe analysis conventions to guide the statistical 
programming work. The SAP will be signed off before the study database is locked. 
Analyses will be performed using SAS® version 9.4 (SAS Institute, Inc., Cary, NC 
27513) or higher using the UNIX operating system.
4.0
Study Objectives, Design and Procedures
4.1
Primary Study Objective
The primary objective of this study is to investigate long-term safety and efficacy of 
risankizumab during open-label treatment in patients with moderate to severe chronic 
plaque psoriasis.
4.2
Design Diagram
This open label extension trial (OLE), investigates the additional safety and efficacy of 
the 90 mg dose of risankizumab. Approximately 100 patients who meet the entry criteria 
are planned for inclusion in this trial, rolling over from the preceding Study 1311.2 trial. 
The treatment will be open label.
The treatment period will be approximately four years of administration starting with 
first administration of risankizumab in either Trial 1311.2 or this study, followed by a 
12 week follow up period. After 01-May-2018 and approval of the protocol 
Amendment 6 in each respective country, the next study visit will be the Extended EOS 
visit and therewith the last visit in this study. Patients who have completed the study 
without early treatment discontinuation will be offered to roll over to Study M15-997


Risankizumab
M16-009 – Statistical Analysis Plan
Version 1.0 – 19 Sep 2018
5
open label extension (OLE) trial if they fulfill the inclusion and exclusion criteria for the 
Study M15-997 trial.
Patients rolling over from the preceding Trial 1311.2 will have to complete the treatment 
period in that trial, or complete the entire trial including the follow up period, reaching 
end of study. If, during the follow up period of the preceding trial (at any visit from 
Week 24 and onwards in Trial 1311.2) loss of response is detected, the patient can roll 
over in this extension trial. For this, loss of response is defined as < PASI 50.
Extended Visit 1of this trial should preferably be performed as a combined visit the same 
day as End of Study visit of Study 1311.2, or within an interim period of maximum 
6 weeks thereafter.
Figure 1.
Guideline for roll over of patients from Study 1311.2 to this study
After the approval of protocol Amendment 6 in each respective country, all patients will 
follow Flow Chart (Extended Dosing Period) in the protocol and receive 90 mg 
risankizumab subcutaneously at their Extended Visit 1 (EV1). From EV1 onwards, 
risankizumab will be administered subcutaneously every 12 weeks during the trial. At 
EV2, if there is a lack of response, defined as < PASI 90, the dose should be increased to 
180 mg for the remainder of the trial (see Figure 2).


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For ongoing patients under the previous protocol amendment (Pre-Extended Dosing 
Period, see Figure 3), EV1 should be conducted at the following time points:
1.
For ongoing patients with ≥12 weeks since the EOT visit: Conduct EV1 as soon 
as Possible.
2.
For ongoing patients still undergoing treatment or with < 12 weeks since the EOT 
visit: Conduct EV1 at the time of the next scheduled treatment or follow up visit 
(note: EV1 should not be conducted at the time point of Visit 2 under the previous 
protocol, patients with Visit 2 as their next scheduled visit should have their EV1 
replacing their Visit 3 instead)
Figure 2.
Guideline for assessment of dose adjustment


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Figure 3.
Visit schedule Pre-Extended Dosing Period
If there are any tolerability issues, as assessed by the investigator, the patient will be 
discontinued.
The plaque psoriasis will be evaluated by PASI score at each visit. The standard clinical 
endpoints of PASI 50, PASI 75, PASI 90 and PASI 100 will be assessed at each visit 
based on the baseline PASI from Study 1311.2.
The end of study is defined as the date the last subject completes the Extended End-of-
study visit.
4.3
Sample Size
The sample size is determined by the completion of Study 1311.2 and the consenting for 
the extension.
Eligible subjects from Study 1311.2 will be offered participation in this OLE study at 
their respective or referring sites. The check for subject eligibility will be based upon a 
successful completion of the Study 1311.2, signing the informed consent for this study, 
and the other inclusion and exclusion criteria.
4.4
Interim Analysis 
Data will be reviewed periodically during the study by an independent Data Monitoring 
Committee (DMC). 


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5.0
Analysis Populations
5.1
Definition for Analysis Populations
Intent to Treat (ITT) Populations:  
The ITT Population is defined as all subjects who receive at least one dose of study drug 
in the study. 
Safety Population:
Safety Population is the same as ITT Population for this study. This population will be 
used to provide a comprehensive summary of safety. 
5.2
Variables Used for Stratification of Randomization
For this open-label study, no randomization of subjects into different treatment groups or 
stratification of randomization is required.
6.0
Analysis Conventions
Since this is a single arm open-label continuation study, no statistical test will be 
conducted. Summary statistics will be provided. 
Definition of Baseline
1.
Baseline is defined as the last non-missing value on or before the date of the 
first dose of study drug in Study 1311.2. The efficacy analyses will use these 
baseline values. These baseline values will be referred to as "BL" in this 
document.
2.
RZB baseline is defined as the last non-missing value on or before the date of the 
first dose of risankizumab either in Study 1311.2 or this study. For vital sign 
assessments, only assessments prior to first dose time will be considered, since 
vital signs are to be assessed both pre- and post-dose in some visits.  These values 


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will be referred to as BL_RZB in this document. BL_RZB will be used for safety 
analyses.  
Definition of Final Observation (Applicable to Safety Analyses)
Final observation in the entire study is defined as the last non-missing observation 
collected within 105 days after the last dose of risakizumab.
Definition of Rx Days (Days Relative to the Date of First Dose of Study Drug)
Rx days are calculated for each time point relative to the date of first dose of risakizumab
in this study. They are defined as the number of days between the day of the first dose of 
risakizumab and the specific time point. Rx days are negative values when the time point 
of interest is prior to the first risakizumab dose day. Rx days are positive values when the 
time point of interest is on or after the first risakizumab dose day. The day of the 
first dose of risakizumab is defined as Rx Day 1, while the day prior to the 
first risakizumab dose is defined as Rx Day –1 (there is no Rx Day 0). 
Definition of Analysis Windows 
All time points and corresponding time windows are defined based on Rx Days.
For efficacy analyses, local tolerability, laboratory parameters, study drug injections, and 
vital sign variables, analysis windows are constructed using the following algorithm:  
●
Determine the nominal Rx day for each visit (e.g., Week 4 [4 weeks after 
Baseline visit] equals Rx Day 29).
●
In order to include all post baseline data, the first post-baseline interval starts 
on the first day after the first dose of risakizumab (Rx Day 2).
●
Determine the window around a specific nominal Rx day by adding or 
subtracting half of the interval between adjacent visits (e.g., days between 
Week 2 and Week 4 is 14). The threshold between adjacent visits is 
determined by splitting the interval evenly between the visits. If the resulting 


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split is between Rx days, then the threshold is determined as the midpoint 
between the adjacent visits. If the resulting split is on an Rx day, then the 
threshold is determined as being between that Rx day and the Rx day prior to it 
(e.g., the split between Week 2 and Week 4 would be between Rx Days 22 and 
23).
●
If more than one assessment is included in a time window the assessment 
closest to the nominal day will be used. If there are two observations 
equidistant to the nominal day, the one after the nominal day will be used in 
analyses. If more than one post baseline assessment is included on the same 
day, then the worst assessment on that day will be used in analyses, except 
those specified in Section 11.0.
The protocol specified visits and corresponding time windows used in the efficacy 
analyses, study drug injections, local tolerability, clinical laboratory tests, and vital sign 
variables, are presented in the following Table 1. 
Table 1.
Visit Windows for Analysis of PASI, sPGA, Pain Vas, DLQI, Study 
Drug Injections, Local Tolerability Assessment, Clinical 
Laboratory Tests, and Vital Signs
Window label
Target day
Interval
Entry of this studya
1
≤1b
Week 12
85
[2, 127]
Week 24
169
[128, 211]
Week 36
253
[212, 295]
…
…
…
Week K
K × 7 + 1
[K × 7 – 40, K × 7 + 43]
a.
There is no local tolerability measurements at entry of this study (Extended Visit 1).
b.
If time is collected in vital signs, restrict to records prior to the first dose of RZB.
Note:
Rx Day calculated relative to first dose date of risakizumab in this study.


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Definition of Missing Data Imputation
No global imputation is taking place at the database level.  Efficacy related imputations 
are outlined in Section 10.0.  There is no imputation for missing values in the safety 
analyses.
Rounding of Numeric Results
Rounding will be performed for presentation of results. No rounding will be performed 
before or during analyses. The ROUND function of SAS will be used to round results. 
When dichotomizing continuous variables, associated continuous variables will be 
rounded to 9 decimal points before applying the cutoff point to determine the response 
status (for example, percent change from baseline in PASI score will be rounded to 
9 decimal places before comparing to 90%).
The mean and median will be rounded for presentation to 1 decimal more than the data 
entered into the database. The standard deviation will be rounded to 2 decimal places 
more than the data entered into the database. The minimum and maximum values will be 
presented as entered into the database.
Probabilities will be rounded to 3 decimal places before assignment of statistical 
significance and will be presented in rounded format. Probabilities that round to zero or 
are reported by SAS as zero will be presented as "< 0.001." Probabilities that round to 1 
or are reported by SAS as 1 will be presented as "> 0.999."
7.0
Demographics, Baseline Characteristics, Medical 
History, and Previous/Concomitant Medications
7.1
Demographic and Baseline Characteristics
Demographics and Baseline characteristics will be summarized for ITT population. 
Continuous variables will be summarized with the number of non-missing observations 
by mean, standard deviation, median, minimum and maximum values. Categorical data 


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will be summarized using frequencies and percentages. No Statistical tests will be 
performed for this study. 
The following demographic and baseline parameters will be summarized.
Subject Demographics
●
Sex (male, female)
●
Age (years), defined as the number of years from date of birth to date of 
first drug
●
Age categories (< 40 years, ≥ 40 – < 65 years, ≥ 65 years.)
●
Race (American Indian or Alaska Native, Asian, Black or African American, 
Native Hawaiian or Other Pacific Islander, White, Multiple)
●
Ethnicity (Hispanic or Latino, Not Hispanic or Latino)
●
Body weight (kg)
●
Body weight category (≤ 100 kg, > 100 kg)
●
Height (cm)
●
BMI (kg/m2)
●
BMI category (< 25, ≥ 25 – < 30, ≥ 30)
●
Prior exposure to TNF antagonists (0 versus ≥ 1)
General Baseline Characteristics
●
PASI (Psoriasis Area and Severity Index)
●
BSA (Body Surface Area)
●
sPGA (Static Physician Global Assessment)
●
NAPSI (Nail Psoriasis Severity Index)
●
PSSI (Psoriasis Scalp Severity Index)
●
PPASI (Palmoplantar Psoriasis Area Severity Index)
●
Dermatology Life Quality Index (DLQI)


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Psoriasis and Cardiovascular History
●
Psoriatic arthritis (diagnosed, suspected, no)
●
Cardiovascular Diseases (angina pectoris, atherosclerosis, cerebrovascular 
accident, congestive heart failure, coronary artery disease, myocardial 
infarction, peripheral arterial disease, stroke, transient ischemic attack)
●
Cardiovascular Risk Factors (hypertension, hyperlipidemia, diabetes mellitus 
(includes both type 1 and type 2))
General Use 
●
Smoking status (Never-smoked, Ex-smoker, Currently smokes)
●
Alcohol status (Non-drinker, drinks – no interference, drinks – possible 
interference)
Also, Physical Exam and Pregnancy Test will be presented in listing format.
7.2
Medical History
Medical history (at the time of enrollment in the Study 1311.2) will be summarized using 
body systems and condition/diagnosis as captured on the eCRF. The body systems will 
be presented in alphabetical order and the conditions/diagnoses will be presented in 
alphabetical order within each body system. The number and percentage of subjects with 
a particular condition/diagnosis will be summarized for each treatment arm. Subjects 
reporting more than one condition/diagnosis within a body system will be counted only 
once for that body system.
7.3
Previous Treatment and Concomitant Medications
Number of prior and concomitant medications per subject, and by generic name will be 
summarized.
A prior medication is defined as any medication taken at the time of entry into 
Study 1311.2 and prior to the first dose of risankizumab. A concomitant medication is 


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defined as any medication that started prior to the first dose of risankizumab in 
Study 1311.2 or Study 1311.13 and continued to be taken after the first dose of 
risankizumab or any medication that started after the first dose of risankizumab, but not 
after the last dose of risankizumab + 21 days. The number and percentage of subjects 
who had taken medications will be summarized by generic drug name assigned by the 
World Health Organization (WHO) for both prior and concomitant medications.
7.4
Protocol Deviation
Number and percentage of subjects who reported at least one of the following protocol 
deviation categories will be provided.
●
Subject entered into the study even though she/he did not satisfy entry criteria
●
Subject who developed withdrawal criteria during the study and was not 
withdrawn
●
Subject who received wrong treatment or incorrect dose
●
Subject who received excluded or prohibited concomitant 
8.0
Patient Disposition 
The number and percentage of subjects for each of the following categories will be 
summarized by investigator: 
●
Number of subjects treated
●
Subjects completed
●
Subjects who discontinued study drug (by reason)
●
Subjects who discontinued study (by reason)


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9.0
Study Drug Exposure and Compliance
Study drug exposure (days) will be summarized using the sample size, mean, standard 
deviation, minimum, median and maximum. Study drug exposure will be summarized as 
follows:  
Risankizumab Exposure (in Days):
The Risankizumab Exposure (total duration during Study 1311.2 and this study) will be 
defined as follows:  
The Risankizumab Exposure = Last risankizumab dose date – First risankizumab dose 
date (either in this study or Study 1311.2) + 84.
Compliance
There will be a summary of the number of subjects receiving study drug and dose at each 
study drug administration visit. This will be repeated on the cumulative number of doses.
When computing compliance at each study drug administration visit, the denominator will 
include all subjects who have not prematurely discontinued the study drug prior to the 
scheduled study drug injection. Subjects who have prematurely discontinued the study 
drug but have not prematurely discontinued the study are not used in the denominator.
10.0
Efficacy Analysis
10.1
General Considerations
The efficacy analysis will be performed for ITT population. The efficacy analysis will 
use the data from this study with baseline from Study 1311.2 and will be summarized by 
treatment groups in Study 1311.2. 
Continuous variables will be summarized by the number of observations, mean, standard 
deviation, median, minimum, maximum, as well as the 95% confidence intervals (CIs) of 
the mean values. Categorical variables will be summarized by counts and percentages, as 


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well as the 95% CIs of the percentages. No statistical tests will be performed in this 
study.
No missing data imputation will be applied.  All efficacy analyses will be based on 
Observed Cases (OC) analysis, and thus a subject who does not have an evaluation at the 
analysis time point will not be included.
All endpoints will be analyzed up to the last visit at least one subject has observed 
measurements of that variable.
10.2
Key Efficacy Variables
The following key efficacy variables will be summarized at Week 48:  
●
Proportion of subjects achieving ≥ 90% reduction in Psoriasis Area and 
Severity Index (PASI) score (PASI 90)
●
Proportion of subjects achieving the Static Physician Global Assessment 
(sPGA) score of clear or almost clear
●
Proportion of subjects achieving ≥ 50% reduction in PASI score (PASI 50)
●
Proportion of subjects achieving ≥ 75% reduction in PASI score (PASI 75)
●
Proportion of subjects achieving 100% reduction in PASI score (PASI 100)
●
Proportion of subjects achieving the sPGA score of clear 
10.3
Additional Efficacy Analyses
The following additional efficacy variables will be summarized at all Extended dosing 
period visits:  
●
Proportion of subjects achieving PASI 50/75/90/100
●
Proportion of subjects achieving the sPGA score of clear or almost clear
●
Change from baseline in Pain-VAS (in subgroup of patients with diagnosed 
and suspected psoriatic arthritis)
●
Change from baseline in DLQI.


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●
Proportion of subjects achieving DLQI score of 0 and 0/1;
11.0
Safety Analysis
11.1
General Considerations
Safety analyses will include adverse events, clinical laboratory, local tolerability, and vital 
sign measurements.
11.2
Analysis of Adverse Events
11.2.1
Treatment Emergent Adverse Events
Treatment emergent adverse events (TEAEs) are defined as any event with an onset that is 
after the first dose of risankizumab in this study and with an onset date within 105 days 
after the last dose of study drug in the analysis period.
Events where the onset date is the same as the study drug start date are assumed to be 
treatment emergent, unless the adverse event start time is prior to the study drug start 
time. If an incomplete onset date is collected for an adverse event, the event will be 
assumed to be treatment-emergent unless there is other evidence that confirms that the 
event is not treatment-emergent (e.g., the event end date is prior to the study drug start 
date).
The number and percentage of subjects experiencing treatment-emergent TEAEs will be 
tabulated using the Medical Dictionary for Drug Regulatory Activities (MedDRA®) 
system organ class and preferred term.
Considering the fact that some subjects had dose escalation due to lack of efficacy at EV2, 
selected safety tables will be generated breaking down by the group of subjects who 
remained at 90 mg throughout the study, the group of subjects who received 180 mg at 
EV2, and total.


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Summary tables will be presented as follows:
1.
Adverse Event Overview
The number and percentage of subjects experiencing treatment-emergent adverse 
events will be summarized for the following adverse event categories:  
○
Any TEAE
○
Any TEAE with reasonable possibility of being related to study drug
○
Any treatment emergent severe adverse event
○
Any treatment emergent serious adverse event (SAE)
○
Any SAE with reasonable possibility of being related to study drug
○
Any TEAE leading to discontinuation of study drug.
○
Any TEAE results in death.
○
All death
2.
Adverse Events by System Organ Class and Preferred Term
TEAEs will also be summarized and presented using primary Medical Dictionary 
for Regulatory Activities (MedDRA) system organ classes (SOCs) and preferred 
terms (PTs).  The SOCs will be presented in alphabetical order, and the PTs will be 
presented in alphabetical order within each SOC.
Subjects reporting more than one adverse event for a given MedDRA preferred 
term will be counted only once for that term (most severe incident for the severity 
tables and most related incident for the relationship tables). Subjects reporting 
more than one type of adverse event within a SOC will be counted only once for 
that SOC. Subjects reporting more than one type of adverse event will be counted 
only once in the overall total.
In addition, the number and percentage of adverse events events with causal 
relationship between the events and the study drug will be summarized using the 
same conventions described above.


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Adverse Events by Maximum Severity
The severity grading of AEs follows Rheumatology Common Toxicity Criteria 
(RCTC).
○
Grade 1 – mild
○
Grade 2 – moderate
○
Grade 3 – severe
○
Grade 4 – life threatening
Adverse events will also be summarized by maximum severity. If a subject has an 
adverse event with unknown severity, then the subject will be counted in the 
severity category of "unknown," even if the subject has another occurrence of the 
same event with a severity present. The only exception is if the subject has another 
occurrence of the same adverse event with the most extreme severity – ("Life-
threatening"). In this case, the subject will be counted under the "Life-threatening" 
category.
The following summaries of TEAEs by SOC and PT will be generated:
○
Any TEAE
○
Any TEAE with causal relationship to study drug
○
TEAE by maximum severity
In addition, summary of AEs by PT and by decreasing frequency of risankizumab 
total will be generated.
3.
Areas of Safety Interest (ASI):
ASIs will be summarized and presented using ASI Grouping and PT. ASI 
groupings are listed in Table 2. These events are of interest due to a higer rate in 
the moderate to severe Ps population, or of interest for all Ig products or products in 
general (DILI).


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The final list will be based on the most updated final version of risankizumab 
Product Safety Statistical Analysis Plan, which is consistent to the most updated 
risankizumab Risk Management Plan.


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Table 2.
Areas of Safety Interest
ASI Grouping
Categories 
(ASI)
Search Criteria
Terms to Display
Include 
in AE 
Overview 
(Y/N)
Adjudicated 
CV Events
Major adverse 
cardiovascular 
events (MACE)
Adjudicated events
Display underlined terms defined by 
the following adjudicated terms:  
!
CV Death which includes 
CETERM values:  Fatal 
CV, Fatal PE, Fatal Non-
Cardiac/Non-Neuro Arterial 
Thrombosis/Thromboembol
ism, Undetermined Death, 
Not assessable death 
(cardiac/neuro/thrombotic), 
Fatal Stroke
!
Myocardial infarction
!
Stroke
Y
Extended 
MACE
Adjudicated events
Display underlined terms from 
MACE and underlined terms below:  
!
Hospitalization for Unstable 
Angina
!
Coronary Revascularization 
Procedures
N
Other CV 
events
Adjudicated events
Display underlined terms defined by 
the following adjudicated terms:  
!
Thrombotic events which 
includes CETERM values: 
Deep Vein Thrombosis, 
TIA, Pulmonary Embolism, 
Non-fatal Non-
Cardiac/Non-Neurological 
Arterial 
Thrombosis/Thromboembol
ism, Other Venous 
Thrombosis, specified (non-
fatal)
!
Cardiac arrhythmia which 
includes CETERM of:  
Clinically Significant 
Arrhythmia
!
Congestive heart failure
which includes CETERM 
of Heart Failure
!
Hypertensive emergency
N


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Table 2.
Areas of Safety Interest (Continued)
ASI Grouping
Categories 
(ASI)
Search Criteria
Terms to Display
Include 
in AE 
Overview 
(Y/N)
Serious 
infections, TB, 
fungal and 
opportunistic 
infections 
(including 
herpes zoster)
Serious 
infections
Serious PTs of the 
CMQ (company 
MedDRA query)
Infections 
(CMQ 80000018)
PTs
Y
TB
Tuberculosis (including 
Investigations) CMQ 
(code 80000033)
PTs
Y
Opportunistic 
infections
Opportunistic infections 
CMQ (code 80000073)
PTs
N
Fungal 
infections
Fungal infections CMQ 
(code 80000063)
PTs
N
Herpes Zoster
Herpes zoster CMQ 
(code 80000175)
PTs
N
Malignancies
All possible 
malignancies
Narrow - Malignancies 
(SMQ 20000090) 
PTs
N
Malignant 
Tumours
Narrow - Malignant 
tumours 
(SMQ 20000194)
PTs
Y
Non-melanoma 
skin cancer 
(NMSC)
Broad - Skin malignant 
tumours 
(SMQ 20000204) 
excluding terms 
identified by the 
Melanoma CMQ 
(code 80000119)
PTs
N
Malignant 
Tumours 
excluding 
NMSC
'Malignant Tumours 
excluding NMSC' is 
identified by the 
'Malignant Tumours'
search excluding terms 
identified by the 'Non-
melanoma skin cancer 
(NMSC) search.
PTs
Y


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Table 2.
Areas of Safety Interest (Continued)
ASI Grouping
Categories 
(ASI)
Search Criteria
Terms to Display
Include 
in AE 
Overview 
(Y/N)
Hypersensitivity 
Reaction
Hypersensitivity
Narrow -
Hypersensitivity 
(SMQ 20000214)
PTs
Y –
serious 
events 
only
Anaphylactic 
Reaction
Narrow - Anaphylactic 
reaction 
(SMQ 20000021)
PTs
N
Hepatic Events
Hepatic Events
Broad - Hepatic failure, 
fibrosis and cirrhosis 
and other liver damage-
related conditions 
(SMQ 20000013) 
Broad - Hepatitis, non-
infectious 
(SMQ 20000010) 
Broad - Cholestasis and 
jaundice of hepatic 
origin (SMQ 20000009) 
Broad - Liver related 
investigations, signs
and symptoms 
(SMQ 20000008) 
Narrow - Liver-related 
coagulation and 
bleeding disturbances 
(SMQ 20000015)
PTs
N
4.
Adverse Event per 100 Patient-years of Exposure
Adverse events occurring during the entire study will be presented by event rate per 
100 patient-year. 
AEs per 100 patient-years of exposure is defined as the number of AEs divided by the 
total exposure in 100 patient-years.  Note that one event per preferred term per day per 
subject will be counted in the calculation of the number of AEs (i.e., a preferred term will 
not be counted twice on the same day for the same subject).  See the calculation method 
below.


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where total patient years is defined as the sum of the study drug exposure (defined as date 
of last dose – date of first dose + 105 days (5 half-lives)) of all subjects normalized by 
365.25, and rounded to one decimal place.
The following summaries of AEs per 100 patient-years of exposure will be generated:
●
Adverse event overview
●
TEAE by SOC and PT
●
SAE
●
Treatment emergent adjudicated CV events
●
Treatment emergent malignancies
●
Serious treatment emergent malignancies
11.2.2
SAEs (Including Deaths) and Adverse Events Leading to 
Study Drug Discontinuation
Deaths, AE leading to study drug discontinuation, and all SAEs will be presented in 
listing format. A listing of all pretreatment (i.e., events start prior to the first study drug 
injection) serious adverse events will be provided. 
The following summaries of AEs by SOC and PT will be generated:
●
Any SAE
●
Any SAE with causal relationship to study drug
●
Any TEAE leading to discontinuation of study drug
●
Any TEAE leading to discontinuation of study drug with causal relationship to 
study drug
Years
Patient 
Total
TEAEs
of
Number 
100 ∀


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11.3
Analysis of Laboratory Data
Listing and descriptive statistics of laboratory values over time and extreme abnormal 
value on treatment will be provided. Baseline is the last non-missing values on or before 
the date of the first dose of risankizumab either in Study 1311.2 or this study. Extreme 
abnormal value on treatment is the on treatment laboratory value which is most 
significantly away from the reference range. Frequency of subjects with transitions 
relative to reference range and listing of subjects with significant abnormal laboratory 
values will be presented as well.
11.3.1
Variables and Criteria Defining Abnormality
Clinical laboratory tests performed are listed in Table 3.


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Table 3.
Clinical Laboratory Tests
Category
Test name
Haematology
Hematocrit (Hct)
Hemoglobin (Hb)
Red Blood Cell Count/Erythrocytes
Reticulocyte Count
Glycosylated Hbc (HbA1c)
White Blood Cells/Leukocytes
Platelet Count/Thrombocytes
Diff. Automatic
Neutrophils (relative and absolute count)
Eosinophils (relative and absolute count)
Lymphocytes (relative and absolute count)
Basophils (relative and absolute count)
Monocytes (relative and absolute count)
Diff Manual
(if Diff Automatic is 
abnormal)
Neutrophils, Bands (Stabs)
Neutrophils, Polymorphonuclear (PMN)
Eosinophils
Basophils
Monocytes
Lymphocytes
Enzymes
Aspartate Aminotransferase/Glutamate-Oxaloacetate Transaminase
(AST/GOT)
Alanine transaminase (Glutamic Pyruvate Transaminase (ALT/GPT)
Alkaline Phosphatase (AP/ALP)
Creatine Kinase (CK)
CK-MB if CK is elevated
Lactic Dehydrogenase (LDH)
Coagulation
Partial Thromboplastin Time (= aPTT)
Prothrombin Time (Quick and International normalised ratio (INR))
Electrolytes
Calcium
Sodium
Potassium


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Table 3.
Clinical Laboratory Tests (Continued)
Category
Test name
Substrates
Glucose
Creatinine
Blood urea nitrogen
Bilirubin Total
Bilirubin Direct
Protein, Total
C-Reactive Protein (CRP)
Uric Acid
Cholesterol, total
High density lipoprotein (HDL) Cholesterol
Calculated low density lipoprotein (LDL) Cholesterol
Triglycerides
Urinalysis (Stix)
Urine Nitrite
Urine Protein
Urine Glucose
Urine Ketone
Urobilinogen
Urine Bilirubin
Urine RBC/Erythrocyte
Urine WBC/Leukocytes
Urine pH
Urine albumin (microalbumin urine test) (roll-over visit only)
Urine-Sediment
(microscopic examination)
(if urine analysis abnormal)
Urine Sediment Bacteria
Urine Cast in Sediment
Urine Squamous Epith Cells
Urine Sediment Crystals, Unspecified
Urine Sediment red blood cell count (RBC)/Erythrocytes
Urine Sediment white blood cell count (WBC)/Leucocytes
11.3.2
Statistical Methods
Analysis of Quantitative Laboratory Parameters
Though the protocol indicates utilizing the Rheumatology Common Toxicity Criteria 
(RCTC) scale for grading laboratory values, given that the National Cancer Institute 
Common Toxicity Criteria for Adverse Events (NCI CTCAE) scale includes a more
comprehensive list of laboratory values, the sponsor will present the lab analyses based on 
the NCI CTCAE scale. Observed values at each scheduled visit in continuous laboratory 


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parameters will be summarized with the mean, standard deviation, median, minimum and 
maximum. If there are multiple post-baseline measurements on the same day, average 
value will be used.
Shift Tables
Shift tables will be provided for each hematology, clinical chemistry parameter. Shifts 
from Baseline to the following endpoints will be considered: post-Baseline value and 
final value. This analysis will be performed only for category of "low or normal" at 
Baseline which shift to 'high' and category of "high or normal" at Baseline which shift to 
category of 'low.' If there are multiple post-baseline measurements on the same day, 
last value will be used.
Potentially Clinically Significant Laboratory Values
Frequencies and percentages of subjects with post Baseline lab values met the following 
criteria in Table 4 and Table 5 will be summarized.  Of note, a post baseline value must be 
more extreme than the baseline value to be considered a potentially clinically important 
finding.


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Table 4.
Criteria for Potentially Clinically Important Chemistry Values
Chemistry Variables
Units
Definition of Potentially Clinically Important
Current (Version 4) NCI CTCAE Grade 3 or 
greater
Very Low
Very High
Bilirubin Total
mcmol/L
> 3.0 × ULN
AST (GOT)
U/L
> 5.0 × ULN
ALT (GPT)
U/L
> 5.0 × ULN
Glucose
mmol/L
< 2.2
> 13.9
Triglycerides
mmol/L
> 5.7
Creatinine
mcmol/L
> 3.0 × ULN
Sodium
mmol/L
< 130
> 155
Potassium
mmol/L
< 3.0
> 6.0
Calcium
mmol/L
< 1.75
> 3.1
CK
U/L
> 5.0 × ULN
Cholesterol, total
mmol/L
> 10.34
ALP
> 5.0 × ULN
Table 5.
Criteria for Potentially Clinically Important Hematology Values
Hematology Variables
Units
Definition of Potentially Clinically Important
Current (Version 4) Grade 3 or greater
Very Low
Hemoglobin
g/dL
< 8.0
Platelets count
109/L
< 50.0
White Blood Cells
109/L
< 2.0
Neutrophils
109/L
< 1.0
Lymphocytes
109/L
< 0.5
A separate listing will be provided that presents all of the subjects and values that are NCI 
CTCAE toxicity grade 3 or above. For each of these subjects, the whole course of the 
respective parameter will be listed.
If there are multiple measurements on the same day, the worst value will be used.


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Liver Function Tests
A listing of possible Hy's Law cases, defined as those who meet all of the following 
conditions will be provided:
●
ALT > 3 × ULN or AST > 3 × ULN
●
Associated with an increase in bilirubin ≥ 2 × ULN
●
Alkaline phosphatase < 2 × ULN
11.4
Analysis of Vital Signs and Weight
11.4.1
Variables and Criteria Defining Abnormality
The following vital sign parameters will be assessed: Systolic blood pressure [mmHg], 
Diastolic blood pressure [mmHg], Pulse [beats per minute], Respiratory rate [breaths per 
minute], Temperature [°C], Weight [kg]. The following Table 6 presents the Criteria for 
Potentially Clinically Significant Vital Sign Findings.  Of note, a post baseline value must 
be more extreme than the baseline value to be considered a potentially clinically important 
finding.
Table 6.
Criteria for Potentially Clinically Significant Vital Sign Findings
Vital Sign
Category
Criteria for Potential Clinically Significant Vital Signs
Systolic Blood Pressure
Low Value
≤ 90 mmHg and decrease ≥ 20 mmHg from Baseline
High Value
≥ 160 mmHg and increase ≥ 20 mmHg from Baseline
Diastolic Blood Pressure
Low Value
≤ 50 mmHg and decrease ≥ 15 mmHg from Baseline
High Value
≥ 105 mmHg and increase ≥ 15 mmHg from Baseline
Pulse
Low Value
≤ 50 bpm and decrease ≥ 15 bpm from Baseline
High Value
≥ 120 bpm and increase ≥ 15 bpm from Baseline


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11.4.2
Statistical Methods
Observed values at each scheduled visit in vital sign parameters will be summarized with 
the mean, standard deviation, median, minimum and maximum. If there are multiple 
post-baseline measurements on the same day, average value will be used.
For systolic blood pressure, diastolic blood pressure and pulse, a listing of all subjects 
with any vital sign value meeting criteria for potentially clinically important values will be 
provided.  For each of these subjects, the whole course of the respective parameter will be 
listed.  The number and percentage of subjects who have at least one value meeting 
criteria for potentially clinically important values will be provided for each vital sign 
parameter.
11.5
Local Tolerability
Local tolerability of the subcutaneous injection will be assessed by the investigator 
according to 6 items: swelling, induration, heat, redness, pain, and other findings.  
Number and proportion of subjects reporting each condition will be summarized.
12.0
Pharmacokinetic Analysis
Pharmacokinetic analysis will not be covered in this SAP.
13.0
Biomarkers Analysis
Biomarker Analysis is not covered in this SAP.
14.0
Summary of Changes
Not applicable. This is the first version of the SAP.
15.0
Appendix
None.


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16.0
References
Not applicable.