Conditions: Psoriasis
Keywords: ABBV-066 BI 655066 risankizumab
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 507
Healthy volunteers: no

Brief summary:
This was a multinational, multicenter, randomized, double-blind, placebo controlled study with randomized withdrawal and retreatment, evaluating the safety and efficacy of risankizumab 150 mg subcutaneous (SC) in participants with moderate to severe chronic plaque psoriasis.

Detailed description:
In Part A1, eligible participants were randomized at Baseline at a ratio of 4:1, stratified by weight and prior exposure to tumor necrosis factor antagonists to receive double-blind (DB) risankizumab 150 mg or placebo at Weeks 0 and 4. In Part A2, participants randomized at Baseline to receive DB placebo then received risankizumab 150 mg at Weeks 16 (Part A2) and at Week 28 and every 12 weeks up to 88 weeks (Part B); participants randomized to risankizumab 150 mg continued to receive risankizumab 150 mg at Week 16. Participants who received risankizumab in Part A and were nonresponders (sPGA \>2) at Week 28 received risankizumab 150 mg at Week 28 and every 12 weeks up to 88 weeks (Part B). In Part B, participants who received risankizumab in Part A and were responders (sPGA ≤2) at Week 28, were rerandomized at a ratio of 1:2 to receive DB risankizumab 150 mg or placebo at Week 28 and every 12 weeks up to 88 weeks (Part B). Starting at Week 32, rerandomized participants who reached relapse (defined as sPGA ≥3) were switched to risankizumab 150 mg every 12 weeks.

Arms:
arm 1: Participants randomized at Baseline to receive double-blind (DB) risankizumab 150 mg by subcutaneous injection at Weeks 0 and 4 (Part A1). arm 2: Participants randomized at Baseline to receive double-blind (DB) placebo by subcutaneous injection at Weeks 0 and 4 (Part A1).

Interventions: intervention 1: Risankizumab intervention 2: Placebo
Intervention descriptions: intervention 1: Risankizumab administered by subcutaneous injection intervention 2: Placebo for risankizumab administered by subcutaneous injection

Protocol document:
Prot_000.pdf: 
Clinical Trial Protocol
 P
Document Number:
c03357704-04
EudraCT No.:
2014-005102-38
BI Trial No.:
1311.4
BI Investigational 
Product:
BI 655066/ ABBV-066 (risankizumab)
Title:
BI 655066 / ABBV-066 (risankizumab) versus placebo In a 
Multicenter randomized double-blind study in patients with 
Moderate to severe chronic plaque psoriasis evaluating the 
efficacy and safety with randomized withdrawal and re-treatment 
(IMMhance)
Brief Title:
BI 655066 / ABBV-066 (risankizumab) in moderate to severe
chronic plaque psoriasis with randomized withdrawal and re-
treatment.
Clinical Phase:
III
Trial Clinical 
Monitor:
Boehringer Ingelheim Pharmaceuticals
900 Ridgebury Road
Ridgefield CT  USA 06877
Coordinating 
Investigator:
Status:
Revised Protocol (based on Global Amendment #3)
Version and Date:
4.0
Date: 11-Oct-2016
Page 1 of 101
Proprietary confidential information.
! 2016 Boehringer Ingelheim International GmbH or one or more of its affiliated companies. All rights reserved.
This document may not - in full or in part - be passed on, reproduced, published or otherwise used without prior written permission.
NCT02672852


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CLINICAL TRIAL PROTOCOL SYNOPSIS
Name of company:
Boehringer Ingelheim
Name of finished product:
Not Applicable
Name of active ingredient:
BI 655066/ ABBV-066 (risankizumab)
Protocol date:
22-Oct-2015
Trial number:
1311.4
Revision date:
11-Oct-2016
Title of trial:
BI 655066 / ABBV-066 (risankizumab) versus placebo In a 
Multicenter randomized double-blind study in patients with 
Moderate to severe cHronic plAque psoriasis evaluatiNg the 
effiCacy and safety with randomized withdrawal and rE-treatment 
(IMMhance)
Coordinating
Investigator:
Trial site(s):
Multicentre Trial conducted in approximately 10 countries
Clinical phase:
III
Objective(s):
The primary objectives of this trial are to assess the safety and 
efficacy of BI 655066 150 mg in comparison to placebo in patients 
with moderate to severe chronic plaque psoriasis with the primary 
efficacy evaluation at 16 weeks.  Following drug withdrawal, the 
maintenance of response as well as the response to retreatment after 
relapse will be evaluated.
In a subset of psoriasis patients with concomitant psoriatic arthritis, 
the signs and symptoms of psoriatic arthritis will be evaluated to 
assess improvement during the trial. 
Methodology:
This is a confirmatory, multinational, multicenter, randomized, 
double-blind, placebo controlled study. Patients will be randomized 
at a ratio of 4:1 to either BI 655066 150 mg or to placebo.
Randomisation will be stratified with to respect weight (C 100 kg vs. 
>100 kg) and prior exposure to TNF antagonists (0 vs. F1)


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Trial Protocol
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Proprietary confidential information © 2016 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Name of company:
Boehringer Ingelheim
Name of finished product:
Not Applicable
Name of active ingredient:
BI 655066/ ABBV-066 (risankizumab)
Protocol date:
22-Oct-2015
Trial number:
1311.4
Revision date:
11-Oct-2016
All patients will receive the first dose of study medication on day 1 
(Randomisation), the second dose at Week 4, and then every 12 
weeks thereafter with the last dose at Week 88.  After the end of 
treatment, patients will continue in the 16 week follow up period.
Patients will be offered to roll over into an open label extension 
(OLE) trial, if they have completed the study and meet the inclusion 
criteria for the OLE trial at the End of Observation (EOO) visit.
No. of patients: 
total entered:
Approximately 500 patients
each treatment:
400 BI 655066, 100 placebo
Diagnosis :
Moderate to severe chronic plaque psoriasis
Main criteria
for inclusion:
-
Male or female patients with age F 18 years at screening
-
Have a diagnosis of chronic plaque psoriasis (with or without 
psoriatic arthritis) for at least 6 months before the first 
administration of study drug.
-
Have stable moderate to severe chronic plaque psoriasis with or 
without psoriatic arthritis at both Screening and Baseline 
(Randomisation):
∀
Have an involved body surface area (BSA) F 10% and
∀
Have a Psoriasis Area and Severity Index (PASI) score F 
12 and
∀
Have a static Physician Global Assessment (sPGA) score 
of F 3.
-
Must be candidates for systemic therapy or phototherapy for 
psoriasis treatment, as assessed by the investigator 


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Name of company:
Boehringer Ingelheim
Name of finished product:
Not Applicable
Name of active ingredient:
BI 655066/ ABBV-066 (risankizumab)
Protocol date:
22-Oct-2015
Trial number:
1311.4
Revision date:
11-Oct-2016
Test product(s):
BI 655066
dose:
150 mg (2 syringes, 75mg each) at week 0, 4 and every 12 weeks
mode of 
administration:
s.c.
Comparator products:
Placebo
dose:
Not applicable
mode of 
administration:
s.c.
Duration of treatment:
88 weeks
Endpoints
Primary Endpoints:
∀
Achievement of F 90% reduction from baseline PASI score 
(PASI 90) at Week 16
∀
Achievement of an sPGA score of clear or almost clear (0 or 
1) at Week 16
Key Secondary Endpoints:
∀
Achievement of 75% reduction from baseline PASI score 
(PASI75) at Week 16
∀
Achievement of 100% reduction from baseline PASI score 
(PASI100) at Week 16
∀
Achievement of an sPGA score of clear (0) at Week 16
∀
Achievement of a Dermatology Life Quality Index (DLQI)
score of 0 or 1 at Week 16
∀
Achievement of an sPGA score of clear or almost clear (0 or 
1) at Week 52 
Other Secondary Endpoints:
∀
Achievement of PASI 75 at Week 52  
∀
Achievement of PASI 90 at Week 52


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Name of company:
Boehringer Ingelheim
Name of finished product:
Not Applicable
Name of active ingredient:
BI 655066/ ABBV-066 (risankizumab)
Protocol date:
22-Oct-2015
Trial number:
1311.4
Revision date:
11-Oct-2016
∀
Achievement of PASI 100 at Week 52
Note that all key and other secondary endpoints at Week 52 will only 
be assessed for patients re-randomised at Week 28.
Safety criteria:
Physical examinations, vital signs, 12 lead electrocardiogram (ECG), 
laboratory testing, adverse events, local tolerability
Statistical methods:
Co-primary analysis: The achievement of PASI 90 and sPGA of 
clear or almost clear at Week 16 are the co-primary endpoints and 
are binary variables with values of 0 or 1. The difference in 
proportion responding between the BI 655066 arm and placebo arm 
will be estimated and tested using the Cochran-Mantel-Haenszel risk 
difference estimate stratified by the randomisation factors of weight 
(C 100 kg versus >100 kg) and prior exposure to TNF antagonists (0 
versus F1) with weights proposed by Greenland & Robins.
Secondary analysis: The same methods for the primary analyses will 
be used to analyse all secondary endpoints since they are all binary 
endpoints. 
All hypotheses will be tested in a hierarchical order using two-sided 
tests with a type I error of 0.05.


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FLOW CHART 1
Trial Period
Screening
Treatment
Follow-up
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
EOT
Follow-up 
#112
Follow-up #2
(EOO)
Week
4
8
12
16
20
24
28
32
36
40
44
48
52
58
64
70
76
82
88
94 
EOT+
6wks
104
EOT+
16wks
Day 
-42 to -7
1
28
56
84
112
140
168
196
224
252
280
308
336
364
406
448
490
532
574
616
658
728
Visit window (days)
N/A
±3
±7
±7
±3
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
Informed consent
X
Demographics
X
Medical history
X
Smoking , alcohol history
X
Psoriatic arthritis Medical 
History19
X
Inclusion-/exclusion 
criteria
X
X
% BSA involvement
X
X
Psoriasis therapy history
X
Height
X
Weight, waist 
circumference9
X
X
X
X
X
CASPAR for PsA8
X
Vitals
X
X13
X13
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical examination4
Xc
Xt
Xt
Xt
Xt
Xt
Xt
Xc
Xt
Xt
Xt
Xt
Xt
Xt
Xc
Xt
Xt
Xt
Xc
Xt
Xc
Xt
Xc
12 lead-ECG
X
X
X
X
X
X
X
X
X
X
X
Safety laboratory testing14
X
X
X
X
X
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant therapy
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Infection Testing 23
X
X
X
Pregnancy testing1
Xs
Xu
Xu
Xu
Xu
Xu
Xu
Xu
Xu
Xu
Xu
Optional DNA Banking2,
X
Randomisation via IRT5
X
X
Contact IRT 
X
X
X
X
X
X11
X11
X
X11
X11
X
X11
X
X11
X
X11
X
X
Administer trial drug24
X
X
X
X
X
X
X
X
X
Local tolerability 
assessment
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood sampling for PK
X7
X7
X
X7
X7
X
X7
X7
X
X7
X
X7
X7
X
ADA assessment sampling 
X7
X7
X7
X7
X7
X7
X7
X7
X7
X
Biomarker sampling10,
X
X
X
X
X
X
X
X
X
X
PASI,  sPGA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
NAPSI, PSSI, PPASI
X
X
X
DLQI 3
X
X
X
HAQ-DI, Pain VAS/ PtGA 
VAS3
X
X
X
X
X
X




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10.
Biomarker sampling should be done prior to administration of study drug at dosing visits. See Section 5.5 and lab manual for procedure
11.
For those patients continuing in the double-blind portion of the trial an additional IRT call will be needed when patients in the randomized 
withdrawal part of trial reach sPGAF3 at a non-dosing visit starting at Week 32. See also footnote # 17 and #18.
12.
Follow-up Visit #1 is not required for patients discontinuing treatment early.  After completing the EOT visit, these patients go right to EOO visit 
(end of treatment + 16 weeks). See Section 6
13.
Vital signs will be assessed prior to treatment as well as approximately 5 and 60 minutes post dose (after last injection) at the first 2 dosing visits 
(V2, V3). 
14.
Blood samples should be taken after patient has fasted for at least 8 hours prior (except screening visit).  If not fasted mark on laboratory 
requisition.
15.
Patients that terminate trial medication early should remain in the trial and complete all remaining Treatment Period visits and, FU1 and FU2 
Visits.   Termination of trial medication eCRF should be completed and end of study registered as a non-completer in IRT. Refer to Section 6.2.3
for details and further instruction if patient cannot or will not continue in the trial. 
16.
Tender and swollen joint counts (TJC/SJC) and Disease Activity Score (DAS28) will be done at selected sites for confirmed psoriatic arthritis 
patients (See Appendix 10.6)
17.
The patient will be switched to Flow Chart 2 if relapse occurs between Week 32 through Week 70 (inclusive). The R1 visit from the Flowchart 2 
must be conducted instead of the current scheduled or unscheduled visit. See also Flow Chart 2 and Sections 3.1 and 6.2.2.
18.
The patient will be switched to Flow Chart 3 if they relapse after week 70 through to week 82 (inclusive). The R1 visit from Flowchart 3 must be 
conducted instead of the current scheduled or unscheduled visit. See also Flow Chart 3 and Sections 3.1 and 6.2.2.
19.
History for psoriatic arthritis is done on all patients at all sites
20.
For patients who discontinue early, vital status should be collected every 12 months after discontinuation up to the original planned EOO.
21.
Patients relapsing after Week 82 through Week 88 will immediately follow EOT procedures per Flow Chart 1 (see also Section 3.1 and 6.2.2).
22.
For patients re-randomized at Week 28 continuing in the double blind treatment portion of the study, assessment of relapse is defined as having an
sPGA F 3. If the sPGA is F 3, the result is entered into IRT and IRT will immediately dispense open label BI 655066.
23.
Infection Testing: Note that at the Screening Visit (or prior to randomization) only TB testing is required. See Section 5.3.3:1 for a complete list of 
testing required.
24.
Patients should be closely monitored for signs and symptoms of hypersensitivity reactions for approximately 2 hours after the last injection at Visit 
2 and for approximately one hour after the last injection at all other visits where drug is administered. Hypersensitivity reactions should be treated 
according to medical standards.


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FLOW CHART 2     FOR RELAPSED AND RE-TREATED PATIENTS FROM WEEK 32 THROUGH WEEK 70                        
Re-Treatment
Follow-up
Relapse Visit
R1
R2
R3
R4
R5
(EOT)
Follow-up #1
Follow-up #2
EOO
Weeks of Re-Treatment
4
8
12
16
EOT+
6wks
EOT+
16wks
Day of Re-Treatment
1
28
56
84
112
154
224
Visit window (days)
±3
±7
±7
±7
±7
±7
Weight, waist 
circumference4
X
X
Vitals
X
X
X
X
X
X
X
Physical examination2
Xc
Xt
Xt
Xt
Xc
Xt
Xc
12 lead-ECG
X
X
X
X
Safety laboratory testing5
X
X
X
X
Adverse events
X
X
X
X
X
X
X
Concomitant therapy
X
X
X
X
X
X
X
Infection Testing
X11
X
Pregnancy testing1
Xu
Xu
Xu
Xu
Contact IRT 
X
X
X
X
Local tolerability 
assessment
X
X
X
X
X
Blood sampling for PK
X7
X7
X7
X
ADA assessment sampling 
X7
X7
X7
X
Biomarker sampling8
X
X
X
X
PASI, sPGA
X
X
X
X
X
X
X
HAQ-DI, Pain VAS/PtGA 
VAS3
X
X
X
TJC/SJC, DAS289
X
X
X
Administer trial drug12
X
X(load)
X
Termination of trial drug
X
Trial completion
X
Open label extension6
X
Vital status10
X


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Flow Chart 2 Footnotes
1.
Pregnancy Testing:  Xu= onsite urine testing. Serum pregnancy done as a reflex if urine test is positive.
2.
Physical exams:  T = targeted, C = complete. Refer to Section 5.3.1 for details
3.
PRO= Patient Reported Outcomes are performed electronically at clinic visits and completed by patients in a quiet place prior to any other visit 
procedure. The order will be as follows ( see also Appendix 10.6 and Appendix 10.7):
a)
HAQ-DI [for psoriatic arthritis patients at selected sites]
b) Pain VAS [for psoriatic arthritis patients at selected sites]
c)
Patient Global Assessment (PtGA) VAS [for psoriatic arthritis patients at selected sites]
4.
For detailed instruction how to measure waist circumference see Section 5.3.1.1 of the protocol
5.
Blood samples should be taken after patient has fasted for at least 8 hours prior (except screening visit).  If not fasted mark on laboratory requisition.
6.
Patients who have completed the study (which is defined as patients completing the EOO visit within the specified window per the flow charts, who 
have not discontinued drug prematurely and who also meet the eligibility criteria) will be offered to roll over into an open label extension (OLE) 
trial. Refer to CTP Section 6.2.3 for additional information on the OLE trial.
7.
Blood samples for PK  and Anti-drug antibodies (ADA) should be taken within 60 minutes before the subcutaneous injection (pre-dose)  
8.
Biomarker sampling should be done prior to administration of study drug at dosing visits. See Section 5.5 and lab manual for procedure
9.
Tender and swollen joint counts (TJC/SJC) and Disease Activity Score (DAS28) will be done at selected sites for confirmed psoriatic arthritis 
patients (See Appendix 10.6)
10. For relapsed and retreated patients following Flow Chart #2 and who discontinue early, Vital Status should be collected after discontinuation up to the 
new planned EOO per Flow Chart #2.
11. Infection Testing at R1 visit only for patients relapsing on or before Visit 15 (Week 52)
12. Patients should be closely monitored for signs and symptoms of hypersensitivity reactions for approximately 2 hours after the last injection at Visit 2 
and for approximately 1 hour after the last injection at all other visits where drug is administered. Hypersensitivity reactions should be treated 
according to medical standards.


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FLOW CHART 3   FOR RELAPSE AND RE-TREATED PATIENTS AFTER WEEK 70 THROUGH WEEK 82                            
Re-treatment
Follow-up
Relapse Visit
R1
R2
(EOT)
Follow-up #1
Follow-up #2
EOO
Weeks of Re-Treatment
4
EOT+
6wks
EOT+
16wks
Day of Re-Treatment
1
28
Visit window (days)
±3
±7
±7
Weight, waist 
circumference4
X
X
Vitals
X
X
X
X
Physical examination2
Xc
Xc
Xt
Xc
12 lead-ECG
X
X
X
Safety laboratory testing5
X
X
X
Adverse events
X
X
X
X
Concomitant therapy
X
X
X
X
Infection Testing
X
Pregnancy testing1
Xu
Xu
Xu
Contact IRT 
X
X
X
Local tolerability 
assessment
X
X
Blood sampling for PK
X7
X7
X
ADA  assessment sampling 
X7
X7
X
Biomarker sampling8
X
X
X
PASI, sPGA
X
X
X
X
HAQ-DI, Pain VAS/ PtGA 
VAS3
X
X
X
TJC/SJC, DAS289
X
X
X
Administer trial drug11
X
X(load)
Termination of trial drug
X
Trial completion
X
Open label extension6
X
Vital status10
X
Note:  Patients relapsing after Week 82 will immediately follow EOT procedures, and then return for Follow-up #1 and Follow-up #2.
A loading dose will not be administered. 


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Flow Chart 3 Footnotes
1.
Pregnancy Testing:  Xu= onsite urine testing. Serum pregnancy done as a reflex if urine test is positive.
2.
Physical exams:  T = targeted, C = complete. Refer to Section 5.3.1 for details
3.
PRO= Patient Reported Outcomes are performed electronically at clinic visits and completed by patients in a quiet place prior to any other visit 
procedure. The order will be as follows (see also Appendix 10.6 and Appendix 10.7):
a)
HAQ-DI [for psoriatic arthritis patients at selected sites]
b) Pain VAS [for psoriatic arthritis patients at selected sites]
c)
Patient Global Assessment (PtGA) VAS [for psoriatic arthritis patients at selected sites]
4.
For detailed instruction how to measure waist circumference see Section 5.3.1.1 of the protocol
5.
Blood samples should be taken after patient has fasted for at least 8 hours prior (except screening visit).  If not fasted mark on laboratory requisition.
6.
Patients who have completed the study (which is defined as patients completing the EOO visit within the specified window per the flow charts) who 
have not discontinued drug prematurely and who also meet the eligibility criteria will be offered to roll over into an open label extension (OLE) 
trial. Refer to CTP Section 6.2.3 for additional information on the OLE trial.
7.
Blood samples for PK  and Anti-drug antibodies (ADA) should be taken within 60 minutes before the subcutaneous injection (pre-dose)  
8.
Biomarker sampling should be done prior to administration of study drug at dosing visits. See Section 5.5 and lab manual for procedure
9.
Tender and swollen joint counts (TJC/SJC) and Disease Activity Score (DAS28) will be done at selected sites for confirmed psoriatic arthritis 
patients (See Appendix 10.6)
10. For relapsed and re-treated patients following Flow Chart #3 who discontinue early, Vital Status should be collected after discontinuation up to the 
new planned EOO per Flow Chart #3.
11. Patients should be closely monitored for signs and symptoms of hypersensitivity reactions for approximately 2 hours after the last injection at Visit 2 
and for approximately 1 hour after the last injection at all other visits where drug is administered. Hypersensitivity reactions should be treated 
according to medical standards.


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TABLE OF CONTENTS
TITLE PAGE...........................................................................................................................1
CLINICAL TRIAL PROTOCOL SYNOPSIS .....................................................................2
FLOW CHART 1.....................................................................................................................6
FLOW CHART 2     FOR RELAPSED AND RE-TREATED PATIENTS FROM WEEK 
32 THROUGH WEEK 70 ....................................................................................9
FLOW CHART 3   FOR RELAPSE AND RE-TREATED PATIENTS AFTER WEEK 70 
THROUGH WEEK 82 .......................................................................................11
TABLE OF CONTENTS ......................................................................................................13
ABBREVIATIONS................................................................................................................17
1.
INTRODUCTION...............................................................................................20
MEDICAL BACKGROUND.............................................................................20
1.1
1.2
DRUG PROFILE................................................................................................20
2.
RATIONALE, OBJECTIVES, AND BENEFIT - RISK ASSESSMENT .....22
RATIONALE FOR PERFORMING THE TRIAL.........................................22
2.1
TRIAL OBJECTIVES........................................................................................22
2.2
2.3
BENEFIT - RISK ASSESSMENT ....................................................................22
3.
DESCRIPTION OF DESIGN AND TRIAL POPULATION.........................24
OVERALL TRIAL DESIGN AND PLAN .......................................................24
3.1
3.1.1
Administrative structure of the trial.................................................................25
3.1.2
Data Monitoring Committee (DMC).................................................................26
3.1.3
MACE Adjudication Committee.......................................................................27
DISCUSSION OF TRIAL DESIGN, INCLUDING THE CHOICE OF 
3.2
CONTROL GROUP(S)......................................................................................27
SELECTION OF TRIAL POPULATION .......................................................27
3.3
3.3.1
Main diagnosis for trial entry............................................................................27
3.3.2
Inclusion criteria.................................................................................................28
3.3.3.
Exclusion criteria ................................................................................................28
3.3.4
Removal of patients from therapy or assessments...........................................29
3.3.4.1
Removal of individual patients.............................................................................29
3.3.4.2 
Discontinuation of the trial by the sponsor...........................................................30
4.
TREATMENTS...................................................................................................32
TREATMENTS TO BE ADMINISTERED.....................................................32
4.1
4.1.1
Identity of BI investigational product and reference product........................32
4.1.2
Method of assigning patients to treatment groups ..........................................33
4.1.3
Selection of doses in the trial..............................................................................33
4.1.4
Drug assignment and administration of doses for each patient .....................34
4.1.5
Blinding and procedures for unblinding ..........................................................36
4.1.5.1
Blinding.................................................................................................................36
4.1.5.2
Unblinding and breaking the code........................................................................36
4.1.6
Packaging, labelling, and re-supply ..................................................................37
4.1.7
Storage conditions...............................................................................................37


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4.1.8
Drug accountability ............................................................................................37
CONCOMITANT THERAPY, RESTRICTIONS, AND RESCUE   
4.2
TREATMENT.....................................................................................................38
4.2.1
Rescue medication, emergency procedures, and additional treatment(s) .....38
4.2.2
Restrictions..........................................................................................................38
4.2.2.1 
Restrictions regarding concomitant treatment ......................................................38
4.2.2.2
Restrictions on diet and life style..........................................................................39
4.2.2.3
Restrictions regarding women of childbearing potential......................................40
TREATMENT COMPLIANCE........................................................................40
4.3
5.
VARIABLES AND THEIR ASSESSMENT ....................................................41
5.1
TRIAL ENDPOINTS..........................................................................................41
5.1.1
Primary Endpoint(s)...........................................................................................41
5.1.2
Secondary Endpoints..........................................................................................41
5.1.3.
Further Endpoints ..............................................................................................41
5.2
ASSESSMENT OF EFFICACY........................................................................42
5.3
ASSESSMENT OF SAFETY.............................................................................42
5.3.1
Physical examination ..........................................................................................43
5.3.2
Vital Signs............................................................................................................43
5.3.3
Safety laboratory parameters............................................................................44
5.3.4
Electrocardiogram..............................................................................................46
5.3.5
Other safety parameters.....................................................................................47
5.3.5.1         Local Tolerability ................................................................................................47
5.3.6
Assessment of adverse events.............................................................................47
5.3.6.1        Definitions of AEs ................................................................................................47
5.3.7
Adverse event collection and reporting.............................................................49
5.4
DRUG CONCENTRATION MEASUREMENTS AND 
PHARMACOKINETICS...................................................................................51
5.4.1
Assessment of Pharmacokinetics.......................................................................51
5.4.2
Methods of sample collection.............................................................................51
5.4.2.1       Plasma sampling for pharmacokinetic analysis.....................................................51
5.4.2.2       Plasma sampling for ADA.....................................................................................51
5.4.3
Analytical determinations ..................................................................................51
5.4.4
Pharmacokinetic-Pharmacodynamic Relationship .........................................52
5.5
ASSESSMENT OF EXPLORATORY BIOMARKERS.................................52
5.5.1
Assessment of soluble protein biomarkers in blood ........................................52
5.5.1.1
Methods of sample collection...............................................................................52
5.5.1.2
Analytical determinations.....................................................................................52
5.5.2
DNA Banking ......................................................................................................52
5.5.2.1.
Methods of sample collection...............................................................................52
5.5.2.2.
Analytical determinations.....................................................................................53
5.5.3
Biomarker sample banking................................................................................53
5.6
OTHER ASSESSMENTS ..................................................................................53
5.7
APPROPRIATENESS OF MEASUREMENTS..............................................53
6.0
INVESTIGATIONAL PLAN ............................................................................54
6.1
VISIT SCHEDULE.............................................................................................54
6.2
DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS .................54
6.2.1
Screening period..................................................................................................54
6.2.2
Treatment period ................................................................................................55


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6.2.3
Follow up Period and Trial Completion...........................................................57
7.0
STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE58
7.1
STATISTICAL DESIGN - MODEL.................................................................58
7.2
NULL AND ALTERNATIVE HYPOTHESES ...............................................58
7.3
PLANNED ANALYSES.....................................................................................59
7.3.1
Primary endpoint analyses.................................................................................59
7.3.2
Secondary endpoint analyses .............................................................................60
7.3.3
Further endpoint analyses..................................................................................61
7.3.4
Safety analyses.....................................................................................................62
7.3.5
Pharmacokinetic analyses ..................................................................................62
7.3.6
Pharmacodynamic analysis................................................................................62
7.3.7
Biomarker analyses.............................................................................................63
7.4
INTERIM ANALYSES .....................................................................................63
7.5
HANDLING OF MISSING DATA ..................................................................63
7.6
RANDOMISATION ..........................................................................................64
7.7
DETERMINATION OF SAMPLE SIZE........................................................64
8.0
INFORMED CONSENT, DATA PROTECTION, TRIAL RECORDS........66
8.1
TRIAL APPROVAL, PATIENT INFORMATION, AND INFORMED 
CONSENT ...........................................................................................................66
8.2
DATA QUALITY ASSURANCE.....................................................................67
8.3
RECORDS...........................................................................................................67
8.3.1
Source documents ...............................................................................................67
8.3.2
Direct access to source data and documents.....................................................67
8.3.3
Storage period of records (Applicable to Japan only).....................................67
8.4
LISTEDNESS AND EXPEDITED REPORTING OF ADVERSE EVENTS68
8.4.1
Listedness.............................................................................................................68
8.4.2
Expedited reporting to health authorities and IEC / IRB...............................68
8.5 
STATEMENT OF CONFIDENTIALITY........................................................68
8.6 
END OF TRIAL..................................................................................................68
8.7
PROTOCOL VIOLATIONS............................................................................68
8.8
COMPENSATION AVAILABLE TO THE PATIENT IN THE EVENT OF 
TRIAL RELATED INJURY .............................................................................69
9.0
REFERENCES....................................................................................................70
9.1 
PUBLISHED REFERENCES ...........................................................................70
9.2
UNPUBLISHED REFERENCES.....................................................................71
10
APPENDICES....................................................................................................73
10.1
PASI  DEFINITIONS AND USE......................................................................73
10.2 
STATIC PHYSICIAN GLOBAL ASSESSMENT (SPGA) ............................74
10.3
NAPSI – NAIL PSORIASIS SEVERITY INDEX..........................................76
10.4 
PPASI – PALMOPLANTAR PSORIASIS SEVERITY INDEX ................... 77
10.5
PSORIASIS SCALP SEVERITY INDEX (PSSI)............................................ 78
10.6
DIAGNOSIS AND ASSESSMENTS FOR PATIENTS WITH PSORIATIC 
ARTHRITIS (AT SELECTED SITES ONLY)................................................79
10.6.1
Disease Activity Score in 28 Joints (DAS 28)...................................................80
10.7
HEALTH OUTCOMES/QUALITY OF LIFE ................................................81
10.7.1
Dermatology Life Quality Index........................................................................81
10.7.2
Health Assessment Questionnaire Disability Index (HAQ-DI) ......................83


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10.7.3
Pain VAS..............................................................................................................86
10.7.4
Patient global assessment VAS ..........................................................................86
11.
DESCRIPTION OF GLOBAL AMENDMENTS............................................87


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ABBREVIATIONS
ADA
AE
Anti-drug antibodies
Adverse Event
AESI
ALT
AP
aPTT
AST
Adverse events of special interest
Alanine transferase
Alkaline Phosphatase
Activated Partial Thromboplastin Time
Aspartate transferase
AUC
BI
Area under the Curve
Boehringer Ingelheim
BSA 
BUN                 
CA
CASPAR
CK
CK-MB
Body Surface Area
Blood Urea Nitrogen
Competent Authority
ClASsification criteria for Psoriatic Arthritis
Creatine Kinase
Creatine Kinase Muscle Brain
Cmax
maximal Concentration
CML
Local Clinical Monitor 
CRA
Clinical Research Associate
CRF
CRO
CRP
Case Report Form
Contract Research Organization
C-Reactive Protein
CTP
Clinical Trial Protocol
CTR
DAS
DEDP
DILI
DLQI
Clinical Trial Report
Disease Activity Score
Drug Exposure During Pregnancy
Drug induced liver injury
Dermatology Life Quality Index
DMC
DNA
ECG
eCOA
Data Monitoring Committee
Deoxyribonucleic acid
Electrocardiogram
Electronic Clinical Outcomes Assesssment
eCRF
eGFR
Electronic Case Report Form
Estimated glomerular filtration rate
ELISA
EOO
EOT
Enzyme Linked Immunosorbent Assay
End of Observation
End of Treatment
EudraCT
European Clinical Trials Database
FAS
Full Analysis Set
FC
Flow Chart
GCP
GGT
GRAPPA
HAQ-DI
Hb
Hct
HDL
Good Clinical Practice
Gamma-Glutamyl Transferase
The Group for Research and Assessment of Psoriasis and Psoriatic 
Arthritis
Health Assessment Questionnaire Disability Index
Hemoglobin
Hematocrit
High density lipoprotein
HIV
Human immunodeficiency virus


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HIPAA
HOMA-IR
Health insurance portability and accountability act
Homeostatis model assessment of insulin resistance
IB
IC
ICH
Investigator’s Brochure
Inhibitory Concentration
International conference on harmonisation
IEC
IgG
INR
IL
Independent Ethics Committee
Immunoglobulin G
International normalized ratio
Interleukin
IQR
IRB
Interquartile Range 
Institutional Review Board
IRT
Interactive Response Technology
ISF
Investigator Site File
i.v.
LDL
Intravenous
Low density lipoprotein
LOCF
mAb
MACE
Last observation carried forward
Monoclonal Antibody
Major adverse cardiovascular events
MedDRA
MMRM
Nab
NAPSI
NGAL
NOAEL
NRI
OLE
OPU
PASI
Medical Dictionary for Drug Regulatory Activities
Mixed effect Model Repeat Measurement
Neutralizing Antibody
Nail Psoriasis Severity Index
Neutrophil gelatinase associated lipocalin-2
No Observed Adverse Effect Level
No Response Imputation
Open label extension
Operative unit
Psoriasis Area and Severity Index
PD
Pharmacodynamics
PK
PoCC
PPASI
PPD
PPS
Pharmacokinetics
Proof of Clinical Concept
Palmoplantar Psoriasis Severity Index
Purified Protein Derivative
Per Protocol Set
PRO
Patient Reported Outcomes
PsA
PSI
PSSI
PtGA
RBC
RCTC
RDC
Psoriatic Arthritis
Psoriasis Symptom Inventory
Psoriasis Scalp Severity Index
Patient Global Assessment 
Red Blood Cells
Rheumatology Common Toxicity Criteria
Remote Data Capture
REP
RRS-PPS
Residual effect period, after the last dose of medication with measureable 
drug levels or pharmacodynamic effects still likely to be present
Re-Randomized Per Protocol Set
SAE
Serious Adverse Event
SAF
Safety Set
SD
SOP
s.c.
Standard deviation
Standard Operating Procedures
subcutaneous


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sPGA
SUSAR
TB
TJC/SJC
TMF
Static Physician Global Assessment
Suspected Unexpected Serious Adverse Reaction
Tuberculosis
Tender or swollen joint count
Trial Master File
TNF
Tumor Necrosis Factor
TSAP
TSH
ULN
Trial Statistical Analysis Plan
Thyroid Stimulating Hormone
Upper limit of normal
VAS
VEGF
WBC
Visual Analog Scale
Vascular endothelial growth factor
White Blood cells


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1.
INTRODUCTION
MEDICAL BACKGROUND
1.1
Psoriasis is a chronic inflammatory disease with well-demarcated erythematous plaques with 
adherent silvery scales (R11-1257). It is the most prevalent immune-mediated skin disease, 
affecting 2% of the world population (R08-1089). Twenty-five percent of patients have 
moderate to severe disease with considerable negative impact on psychosocial and economic 
status (R11-1259).  It is increasingly recognized that psoriasis is more than a superficial 
disease, with 30% of patients having joint involvement and a high correlation between psoriasis 
and obesity, diabetes, depression, metabolic syndrome, and cardiovascular risk (R15-1393).
While many psoriasis patients with mild disease are managed with topical therapies, those with 
severe and/or refractory disease may require phototherapy and/or systemic therapy. Oral 
systemic agents provide modest efficacy, but increasingly patients are treated with more 
effective biologic agents, such as TNF-alpha inhibitors (etanercept, adalimumab) and the p40 
IL-12/23 inhibitor (ustekinumab) (R14-5159). While the clinical efficacy of ustekinumab 
indicates a role for both IL-12 and IL-23 in the pathogenesis of psoriasis (R11-1547), more 
recent data suggest that IL-23 is disproportionately involved in the maintenance of chronic 
psoriasis (R11-1547). IL-23 is thought to act in the pathophysiology of psoriasis via induction 
and maintenance of Th17 cells as well as other IL-23 responsive cells. This is supported by 
recent clinical data indicating that monoclonal antibodies that block IL-17A, the cytokine 
produced by the Th17 cells, have high efficacy in psoriasis. 
There is still clinical need for increased efficacy as the most effective anti-TNF and IL12/23 
agents provide only 75% improvement in psoriasis in about 60-70% of patients, and these 
responses tend to be lost over time. While the anti-IL-17A agents provide better efficacy, they 
require monthly injections; thus, their long-term utility is still undetermined. BI 655066 is a 
humanized monoclonal antibody with high affinity for the p19 component of human IL-23 that 
specifically neutralizes IL-23. Proof of clinical concept (PoCC) for BI 655066 was 
demonstrated in a single dose phase I trial in 39 patients with moderate to severe plaque 
psoriasis, where 87% of patients achieved at least 75% reduction in Psoriasis Area and Severity 
Index (PASI 75) with no safety concerns (c02434648-01).
A 48-week Phase II dose ranging trial of BI 655066 vs. ustekinumab indicates a 37% greater 
improvement for BI 655066 (90 mg and 180 mg, pooled data) when compared to ustekinumab 
in the proportion of patients achieving 90% reduction in PASI (PASI 90) at Week 12. We 
propose the current trial to establish the safety and efficacy of BI 655066 in larger numbers of 
patients over a longer duration of treatment.
1.2
DRUG PROFILE  
BI 655066 is a fully humanized monoclonal antibody (mAb) of the IgG1 subclass directed 
towards IL-23p19. The antibody has been engineered to reduce FcT receptor and complement 
binding and potential charge heterogeneity. BI 655066 binds with high affinity to human IL-23
and inhibits IL-23 stimulated IL-17 production at IC 50 concentrations below 10 pM, as 
compared with 167 pM for ustekinumab in the same system. BI 655066 does not affect IL-12 at 
a maximum tested concentration (33 nM) and it does not inhibit IL-12 stimulated IFN-T 
production.


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The toxicology data suggest BI 655066 can be safely administered to humans, as supported by 
chronic administration to monkeys for up to 26 weeks. The monkey was identified as the most 
relevant toxicology species with a NOAEL of 50 mg/kg/dose, corresponding to an exposure 
(combined sex) of 677 Ug/mL for the Cmax and 86,250 Ug*h/mL for AUC0-168, respectively.
BI 655066 has been studied in approximately 200 patients with psoriasis without any 
unexpected adverse events or safety issue. Based on the efficacy and safety findings in the 
completed and ongoing studies, the risk benefit profile of BI 655066 is appropriate for initiation 
of Phase III studies. In Study 1311.1 (c02434648-01), a Phase I single rising dose trial in 39 
patients with chronic plaque psoriasis, administration of BI 655066 either intravenously (i.v.) or 
subcutaneously (s.c.) was well tolerated. Over the 24 weeks following a single i.v. or s.c. 
administration of BI 655066, 65% (20/31) of patients experienced an AE compared with 88% 
(7/8) of patients receiving placebo. The most frequently reported AEs were mild to moderate 
upper respiratory tract infections, mild nasopharyngitis and mild to moderate headache. The 
severity of AEs did not appear related to the dose of BI 655066. Injection site reactions were 
reported in 2/18) patients receiving BI 655066 i.v., in 1/6 patients receiving placebo i.v. and in 
none of the patients receiving BI 655066 or placebo s.c.
In patients receiving BI 655066 either i.v. (n=18) or s.c. (n=13), 87% achieved at least 75% 
reduction in Psoriasis Severity and Area Index (PASI 75) by Week 12, compared to none in the 
placebo group. Twenty four weeks after a single administration of BI 655066, 71% of patients 
maintained at least a PASI 75; nearly half (48%) had 90% reduction in PASI (PASI 90) and 29% 
had complete resolution of lesions (PASI 100). A protocol amendment allowed an optional 
extension of follow-up beyond Week 24 for patients in the s.c. dose cohort; six of thirteen 
originally enrolled patients maintained a PASI 100 improvement for 41–66 weeks after 
treatment.
After a single i.v. administration, BI 655066 geometric mean AUC0–inf ranged from 2.93–
1650 day*Ug/mL and Cmax from 0.311–110 Ug/mL, with exposure increasing in a dose-
proportional manner. Group mean clearance and terminal phase volume of distribution were 
0.33 L/day and 10.8 L, respectively PK parameter variability, expressed as gCV (%) was <50%. 
After a single s.c. administration of BI 655066, maximal exposures were reached between 5-13
days and subcutaneous bioavailability was 73% (expressed as the ratio of geometric mean dose 
normalised AUC0–inf after s.c. and i.v. administration).
For a more detailed description of the drug profile refer to the current Investigator’s Brochure 
(IB) (c01569420-06) which is included in the Investigator Site File (ISF).


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2.
RATIONALE, OBJECTIVES, AND BENEFIT - RISK 
ASSESSMENT
RATIONALE FOR PERFORMING THE TRIAL
2.1
Psoriasis is a chronic inflammatory disease affecting 2% of the world population with 
significant impact on patient quality of life with significant systemic disease (R08-1089).
IL-23 plays a key role in the pathophysiology of psoriasis through induction and maintenance 
of Th17 type cells that secrete inflammatory cytokines.  BI 655066 is a humanized monoclonal 
antibody that specifically neutralizes the IL-23 axis. Proof of clinical concept (PoCC) for BI 
655066 was demonstrated in a single dose phase I trial in 39 patients with moderate to severe 
plaque psoriasis where 87% of patients achieved at least 75% reduction in Psoriasis Area and 
Severity Index (PASI 75) with no safety concerns (c02434648-01).
This trial is being performed to assess the safety and efficacy of BI 655066 to support a 
registration for the treatment of moderate to severe plaque psoriasis in adult patients. 
TRIAL OBJECTIVES
2.2
The primary objectives of this trial are to assess the safety and efficacy of BI 655066 150 mg in 
comparison to placebo in patients with moderate to severe chronic plaque psoriasis. The 
primary efficacy evaluation will be performed at 16 weeks.  In addition, the maintenance of 
response following drug withdrawal will be assessed after Week 28 through Week 104.  
Subsequent to drug withdrawal, patients who experience relapse will be retreated with BI 
655066 to assess response after retreatment.
In addition, this trial will assess PK and the emergence of anti-drug antibodies (ADA) and their 
effect on efficacy and safety. Moreover, it will be explored how the use of BI 655066 may 
influence gene and protein expression levels and disease specific protein markers.
In a subset of psoriasis patients with concomitant psoriatic arthritis, the signs and symptoms of 
psoriatic arthritis will be evaluated to assess improvement during the trial.
Lastly, the influence of study treatment on some metabolic risk factors will be evaluated.
2.3
BENEFIT - RISK ASSESSMENT
Participation in this study may help to generate future benefit for larger groups of patients with 
psoriasis if BI 655066 proves to be successful in treating this disease. BI 655066 has been 
studied in approximately 200 patients with moderate to severe plaque psoriasis. In these 
studies, the majority of patients receiving BI 655066 achieved 90% improvement of their 
disease. The most common adverse events reported in these trials were mild symptoms of the 
upper respiratory tract, including nasal stuffiness, sore throat, influenza, and headache. These 
events were not considered to be related to drug treatment. Local reactions following 
subcutaneous administration of BI 655066 were uncommon, and limited to mild redness, 
swelling or induration at the injection site. No serious drug related adverse events were 
reported. 
As with many immune modulating agents, BI 655066 may impair immune function resulting in 
a risk of infection. This will be monitored by collection of all AEs during the treatment and 


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observation periods. Patients with clinically important active infection will not be included in 
the study.
IL-23 inhibition is not known to increase the risk of TB infection or impair the response to TB 
infection in animal models (R15-5488; R15-5495). Thus, low risk patients with positive 
Quantiferon testing do not need to be treated with anti-tuberculosis therapy prior to receiving 
BI-655066, but should be carefully monitored for any sign of TB reactivation. Absence of TB 
reactivation, despite not receiving anti-tuberculosis prophylaxis will provide important 
information in humans as to whether TB testing is required prior to treatment with BI 655066 
(R15-5497).
There is not enough information at this time to rule out a risk of cancer with BI 655066, but this 
risk is considered small with this type of compound because long-term experience with the anti-
IL-12/23 mAb ustekinumab has not been associated with significant cancer risk. Patients will be 
monitored for signs and symptoms of malignancy at each visit.
Increases in major adverse cardiovascular events (MACE) including myocardial infarction, 
cerebrovascular accident, and cardiovascular death, reported initially with anti-IL-12/23 agents, 
such as ustekinumab, have not been observed in longer term studies. While the likelihood of 
increased MACE is small, all cardiovascular events (serious or non-serious) observed in this 
study will be adjudicated by an independent MACE Adjudication Committee.
A patient will have a 20% (1 in 5) chance in being randomized to the placebo arm.  Patients 
assigned to placebo will have a low rate of response.  These patients will be crossed over to 
active BI 655066 treatment at Week 16 of study participation.  The knowledge gained from the 
placebo treatment group in a relatively short period of time can be used to control for bias and 
effect size. The delay in starting treatment does not diminish the potential benefit of treatment 
or introduce any risk. Patients will be monitored with study visits every 4 weeks through the 
end of the placebo period at Week 16. 
Although rare, a potential for drug-induced liver injury is under constant surveillance by 
sponsors and regulators. Therefore, this trial requires timely detection, evaluation, and follow-
up of laboratory alterations in selected liver laboratory parameters to ensure patients´ safety, see 
Section 5.3.6.1.
In conclusion, the benefit-risk profile is considered appropriate for this stage of clinical 
development.  In order to recognize any safety signals as early as possible, an independent 
DMC will monitor all studies where patients are receiving BI 655066. 


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3.
DESCRIPTION OF DESIGN AND TRIAL POPULATION
OVERALL TRIAL DESIGN AND PLAN
3.1
This is a confirmatory, multinational, multicenter, randomized, double-blind, placebo 
controlled, study that includes up to a 42 day screening period, an 88 week treatment period and 
a 16- week follow-up period. The primary objectives of this trial are to assess the safety and 
efficacy of BI 655066 in comparison to placebo in patients with moderate to severe chronic 
plaque psoriasis. The primary efficacy will be evaluated at 16 weeks.  In addition, the 
maintenance of response following drug withdrawal in patients who respond to treatment prior 
to Week 28 will be assessed after Week 28 through Week 104.  Subsequent to drug withdrawal, 
patients who experience relapse will be retreated with BI 655066 to assess response after 
retreatment.
In total, approximately 500 patients with moderate to severe chronic plaque psoriasis will be 
randomised and receive study treatment in this trial. A sufficient number of patients will be 
screened to meet this randomized goal. Patients are considered enrolled in the study once they 
have signed the informed consent. 
Patients suitable after screening will be eligible to participate in this study and will be 
randomized at a ratio of 4:1 to one of two treatment arms as shown in Figure 3.1:1. Arm 1 
refers to those patients originally randomized to BI 655066 and Arm 2 refers to those patients 
originally randomized to placebo. Randomisation will be stratified as listed in Section 7.6.
All patients will receive the first dose of study medication on day 1 (Randomisation), the 
second dose at Week 4, and then every 12 weeks thereafter with the last dose at Week 88.
After the end of treatment, patients will continue in the 16- week follow- up period.
At the Week 16 visit (primary endpoint), all patients randomized to Arm 2 (placebo) will start 
receiving 150 mg BI 655066 active treatment every 12 weeks and continue until the end of the 
treatment period. In order to maintain the blind, this will be performed in a blinded fashion at 
Week 16. 
At the Week 28 visit, all patients will be assessed for responsiveness. Patients not meeting the 
protocol defined response criteria (sPGA is F 2) (Week 28 non-responders), will receive open 
label BI 655066 150 mg from Week 28 until the end of the treatment period (Week 88), 
regardless of originally randomized treatment arm. Patients who meet the protocol defined 
responder criteria (sPGA of 0 or 1) (Week 28 responders), will continue to receive blinded drug. 
In Arm 1, patients will be re-randomized; in Arm 2, they will continue to receive blinded 
BI655066 treatment as described in Section 7.6.
Starting with Week 32, Week 28 responders will have their sPGA assessed for protocol defined 
relapse (sPGA of F 3). Once a patient reaches a sPGA of F 3, they will be switched to open 
label BI 655066. If this relapse occurs anytime between Week 32 through Week 70, the patients 
will follow Flow Chart #2 and be re-treated for 16 weeks. If this relapse occurs after Week 70 
through Week 82, the patient will follow Flow Chart #3 and be re-treated for 28 days. If the 
relapse occurs after Week 82 through Week 88 the patient will immediately have the EOT 
procedures performed, including the final dose of study medication and continue into the 16-
week Follow-Up Period. This process will be managed by IRT.


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Patients will be offered to roll over into an open label extension (OLE) trial, if they have 
completed the study and meet the inclusion criteria for the OLE trial at the End of Observation 
(EOO) visit. See Section 6.2.2 and Section 6.2.3.
Patients who discontinue from the trial will not have the possibility to participate in the OLE 
study.                                                                                                               
There will not be an interim analysis from a statistical standpoint however a primary endpoint 
analysis will be conducted after the last patient has been in the study for 52 weeks (or 
discontinued). See Section 7.4.
Individual patient participation is concluded when the patient has completed the last planned 
visit.  The “last-patient-last-visit-primary-endpoint” is the last scheduled primary endpoint visit 
(Week 16) completed by the last patient.  The end of the trial is defined as “last patient out”, i.e. 
last scheduled visit completed by last patient.  
Part A is defined as the induction and response period from initial randomisation through Week 
28. Part B is defined as the withdrawal and re-treatment period from Week 28 through Week 
88. 
Figure 3.1:1
Trial Design
3.1.1
Administrative structure of the trial
The trial is sponsored by AbbVie in the USA and Boehringer Ingelheim (BI) for all other non-
USA participating countries.


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Boehringer Ingelheim has appointed a Trial Clinical Monitor, responsible for coordinating all 
required activities, in order to 
-
manage the trial in accordance with applicable regulations and internal SOPs;
-
direct the clinical trial team in the preparation, conduct, and reporting of the trial;
-
order the materials as needed for the trial; and
-
ensure appropriate training and information of 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.
Tasks and functions assigned in order to organise, manage, and evaluate the trial will be 
defined according to BI SOPs. A list of responsible persons and relevant local information can 
be found in the ISF.
The organisation of the trial in the participating countries will be performed by the respective 
local BI-organisation (Operative Unit (OPU) or by a Contract Research Organisation (CRO) 
which the responsibilities and tasks will 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.
A Coordinating Investigator will be responsible to coordinate investigators at different centres 
participating in this multicentre trial. Tasks and responsibilities will be defined in a contract. 
Relevant documentation on the participating (Principal) Investigators and other important 
participants, including their curricula vitae, will be filed in ISF.
Details of the trial supplies including responsible institutions are given in Section 4 of this 
protocol. 
The 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 vendors for ECG, eCOA and an IRT (Interactive Response 
Technology) will be used in this trial. Details will be provided in the applicable manuals
available in the ISF.
3.1.2
Data Monitoring Committee (DMC)
A data monitoring committee (DMC), independent of the Sponsor will be established to assess 
the progress of the clinical trial, including unblinded safety assessments at specified intervals, 
and to recommend to the Sponsor whether to continue, modify, or stop the trial. 
Any efficacy data provided to the DMC will only be used for DMC's obligation to assess the 
full benefit-to-risk of the treatments. Thus, no statistical penalty will be imposed since efficacy 
analyses will not be the basis for any potential early trial termination.
Measures are in place to ensure blinding of the Sponsor and all other trial participants. The 
Sponsor will remain blinded until after the last patient completes the Week 52 visit. See Section 
7.4 for more information. The tasks and responsibilities of the DMC will be specified in a 
charter. The DMC will maintain written records of all its meetings.


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3.1.3
MACE Adjudication Committee 
An independent adjudication committee will be used to adjudicate all observed cardio- and 
cerebro-vascular and thrombotic events reported during the conduct of the study to assure 
consistent assessment of major adverse cardiovascular events (MACE).This review will be 
blinded to treatment allocation; the events that are to be adjudicated and the adjudication 
process will be detailed in the MACE Adjudication Committee Charter.
DISCUSSION OF TRIAL DESIGN, INCLUDING THE CHOICE OF 
3.2
CONTROL GROUP(S)
This is a randomized double blind, placebo controlled, parallel design study. This design is 
appropriate for assessing the safety and efficacy of BI 655066 compared to placebo in patients 
with moderate to severe chronic plaque psoriasis. While there is a low rate of response with 
placebo treatment, it is important to have a placebo control early in the study to control for 
confounding factors, such as potential investigator bias or regression to the mean in PASI 
scoring. 
In order to enroll patient participants, it is necessary to allow patients initially assigned to 
placebo to receive active treatment. Thus, only adverse events reported during the first 16 
weeks of the trial can be directly compared to placebo. In this trial, patients originally 
randomized to BI 655066 who are considered to be BI 655066 responders will be re-
randomized to receive either placebo or continued BI 655066 starting at Week 28. Patients in 
this phase of the study will be assessed for an additional 76 weeks for a total of 104 weeks. This 
is necessary to adequately capture the loss of response for patients taking BI 655066.  
Furthermore, patients losing response will be retreated with BI 655066 and response after 
retreatment will be assessed.
SELECTION OF TRIAL POPULATION
3.3
A total of approximately 500 patients is planned to be randomized in this trial. A sufficient 
number of patients will be screened to meet this randomized goal.  Patients will be recruited at 
multiple investigative sites in multiple countries. Approximately 85 sites are planned with 
approximately 5-10 patients to be randomized per site. Recruitment will be competitive. 
A log of all patients enrolled into the trial (i.e. signed informed consent) will be maintained in 
the ISF at the investigational sites, whether these patients have been treated with investigational 
drug or not.
3.3.1
Main diagnosis for trial entry
Patients must have moderate to severe chronic plaque psoriasis, defined as F 10% body surface 
area involvement, a Psoriasis Area and Severity Index F 12 and static Physician Global 
Assessment score  3.
Please refer to Section 8.3.1 (Source Documents) for the documentation requirements 
pertaining to the inclusion and exclusion criteria.


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3.3.2
Inclusion criteria   
1. Male or female patients. Women of childbearing potential* must be ready and able to 
use highly effective methods of birth control per ICH M3(R2) that result in a low 
failure rate of less than 1% per year when used consistently and correctly. A list of 
contraception methods meeting these criteria is provided in the patient information.
*Women of childbearing potential are defined as:
∀
Having experienced menarche and are
∀
Not postmenopausal (12 months with no menses without an alternative 
medical cause) and are
∀
Not permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral 
oophorectomy or bilateral salpingectomy).
2. Age F 18 years at screening
3. Have a diagnosis of chronic plaque psoriasis (with or without psoriatic arthritis) at least 
6 months before the first administration of study drug. Duration of diagnosis may be 
reported by the patient.
4. Have stable moderate to severe chronic plaque psoriasis with or without   psoriatic 
arthritis at both Screening and Baseline (Randomisation);
∀
Have an involved body surface area (BSA) F 10%  and
∀
Have a Psoriasis Area and Severity Index (PASI) F 12 and
∀
Have a static Physician Global Assessment (sPGA) score of  3.
5. Must be a candidate for systemic therapy or phototherapy for psoriasis treatment, as 
assessed by the investigator 
6. Signed and dated written informed consent prior to admission to the study and 
performance of any study procedures in accordance with GCP and local legislation
3.3.3. Exclusion criteria
1. Patients with 
∀
nonplaque forms of psoriasis (including guttate, erythrodermic, or 
pustular) 
∀
current drug-induced psoriasis (including a new onset of psoriasis or an 
exacerbation of psoriasis from beta blockers, calcium channel blockers,
or lithium) 
∀
active ongoing inflammatory diseases other than psoriasis and psoriatic 
arthritis that might confound trial evaluations according to the 
investigator’s judgment


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2. Previous exposure to  BI 655066 
3. Currently enrolled in another investigational study or less than 30 days (from screening) 
since completing another investigational study (participation in observational studies is 
permitted).
4. Use of any restricted medication as noted in Table 4.2.2.1:1 or any drug considered 
likely to interfere with the safe conduct of the study.
5. Major surgery performed within 12 weeks prior to randomisation or planned within 12 
months after screening (e.g. hip replacement, removal aneurysm, stomach ligation,).  
6. Known chronic or relevant acute infections, such as HIV (Human Immunodeficiency 
Virus), \viral hepatitis, or tuberculosis. QuantiFERON® TB test or Purified Protein 
Derivative (PPD) skin test will be performed during screening. Patients with a positive
test result may participate in the study if further work up (according to local 
practice/guidelines) establishes conclusively that the patient has no evidence of active 
tuberculosis. If presence of latent tuberculosis is established, patients who are at low risk 
of reactivation, defined by local guidelines and investigator judgment, do not need to be 
treated with prophylactic anti-tuberculosis prior to or during the trial.
7. Any documented active or suspected malignancy or history of malignancy within 5 
years prior to screening, except appropriately treated basal cell carcinoma or squamous 
cell carcinoma of the skin or in situ carcinoma of uterine cervix.
8.
Evidence of a current or previous disease (including chronic alcohol or drug abuse), 
medical condition other than psoriasis, surgical procedure (i.e., organ transplant), 
medical examination finding (including vital signs and ECG), or laboratory value at the 
screening visit outside the reference range  that in the opinion of the Investigator, is 
clinically significant and would make the study participant unable to adhere to the 
protocol or to complete the trial, compromise the safety of the patient, or compromise 
the quality of the data.                               
9. History of allergy/hypersensitivity to a systemically administered biologic agent or its 
excipients.
10. Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
11. Previous enrolment in this trial.
3.3.4
Removal of patients from therapy or assessments
3.3.4.1
Removal of individual patients
All patients have the right to withdraw from the study at any time without the need to justify 
their decision. The investigator has the right to remove patients from the study for non-


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compliance, administrative or other reasons. It should be clearly understood that an excessive 
rate of withdrawals can render the study results uninterpretable. The sponsor reserves the right 
to remove any study patient from the trial for non-compliance.
Given the patient’s agreement, the patient will undergo the procedures for early treatment 
discontinuation and follow up as outlined in the Flow Charts and Section 6.2.3.
An individual patient is to be withdrawn from study medication if:
∀
The patient withdraws consent for study treatment or study participation, without the 
need to justify the decision.
∀
The patient can no longer be treated with study medication for other medical reasons 
(such as surgery, adverse events, other diseases, or pregnancy). 
∀
Development of a toxicity or adverse event that warrants BI 655066 discontinuation 
including but not limited to SAEs or SUSARs
∀
If prohibited medication is used during the study for any indication, the patient must 
discontinue use of the prohibited medication if he/she wants to continue in this study. In 
case of undue safety risk for the subject, the subject should discontinue study treatment 
at the discretion of the investigator. If the subject received a live virus vaccination 
during the study, the subject must discontinue study treatment.
∀
If the patient experiences an intolerable increase of psoriasis during the course of the 
trial the patient will be discontinued from the trial to receive rescue treatment as deemed 
appropriate by the investigator.
Of note: Discontinuation of study medication should not necessarily lead to withdrawal from 
the study. If possible the patient should complete all study visits and procedures as initially 
planned.
If a patient becomes pregnant during a trial, the study medication needs to be discontinued, and 
the patient will complete EOT Visit procedures, and Follow-up 2 (EOO) Visit procedures. The 
patient will be followed up until birth or otherwise termination of the pregnancy.
Patients who discontinue the trial after receiving the first dose of study medication at visit 2 
will not be replaced.
For all patients the reason for withdrawal (e.g. adverse events) must be recorded in the eCRF. 
These data will be included in the trial database and reported.
Vital Status   
For randomized patients leaving the study early (before the planned EOO in their current 
applicable flow chart), vital status should be collected every 12 months after discontinuation up 
to the planned EOO. 
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:
1. Failure to meet expected enrolment goals overall or at a particular trial site,


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2. Emergence of any efficacy/safety information that could significantly affect 
continuation of the trial, or any other administrative reasons, i.e. problems with 
availability of the study medication, discontinuation of development of BI 655066
3. Violation of GCP, the CTP, or a Contract disturbing the appropriate conduct of the trial.
The investigator / trial site will be reimbursed for reasonable expenses incurred in case of trial 
termination (except in case of the third reason).


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4.
TREATMENTS
TREATMENTS TO BE ADMINISTERED
4.1
Multiple doses of BI 655066 and/or Placebo to match BI 655066 will be administered 
subcutaneously. All products will be supplied by Boehringer Ingelheim. 
4.1.1
Identity of BI investigational product and reference product
Table 4.1.1:1
BI 655066
Substance
BI 655066: Anti-human IL-23p19 mAb
Pharmaceutical formulation:
Source:
Boehringer Ingelheim Pharma GmbH & Co. KG
Chemical form
Anti-human IL-23p19 mAb
Molecular weight
Approximately 148 kDa
Unit strength:
75 mg BI 655066 in a pre-filled syringe 
(concentration 90 mg/mL)
Posology
Week 0, Week 4, then every 12 weeks with last 
injection at Week 88
Route of administration:
Subcutaneous injection
Table 4.1.1:2
Placebo to BI 655066
Substance:
Placebo to match BI 655066
Pharmaceutical formulation:
Source:
Boehringer Ingelheim Pharma GmbH & Co. KG
Chemical form
N.A
Molecular weight
N.A
Unit strength:
Sodium chloride solution in a pre-filled syringe
Posology
Week 0, Week 4, then every 12 weeks with last 
injection at Week 88
Route of administration:
Subcutaneous injection


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4.1.2
Method of assigning patients to treatment groups
During Visit 2 and after the patient’s eligibility has been confirmed, the treatment will be 
assigned via Interactive Response Technology (IRT). To facilitate the use of the IRT, the 
Investigator will receive all necessary instructions.
Patients will be randomised to receive BI 655066 150 mg or matching placebo in a ratio of 4:1.
Randomisation will be stratified by weight (C 100 kg vs. >100 kg) and prior exposure to TNF 
antagonists (0 vs. F1).
At each subsequent visit where study medication is to be administered the site is required to
complete the medication resupply module in the IRT. At randomisation as well as subsequent 
medication administration visits, IRT will assign medication numbers. Site personnel will enter 
the medication numbers in the eCRF.
Re-randomisation will occur at Week 28 for those patients who have met the responder criteria 
in Arm 1 (c.f. Section 7.6).   Re-randomisation will be stratified by weight (C 100 kg vs. >100 
kg) and prior exposure to TNF antagonists (0 vs. F1).  For Week 28 responders in Arm 2, 
blinded BI 655066 treatment will be assigned from IRT to maintain blinding. 
Details regarding the use of the IRT are described in the site-user manual available in the ISF.
4.1.3
Selection of doses in the trial
The dose selection strategy for phase III involved analyses of data from the completed phase I 
study (Trial 1311.1), (c02434648-01) the ongoing phase II study (Trial 1311.2), (c03272682-
01) and PK-PD modelling of all available data from phase I and II.
The phase I and phase II data demonstrated an exposure-response relationship for BI 655066 
where doses less than 0.25 mg/kg (intravenously or subcutaneously) were associated with lower 
clinical efficacy (assessed as decrease from baseline in the PASI score) while doses greater than 
1.0 mg/kg achieved near maximal efficacy.
This exposure-response relationship was confirmed in the Phase II study where the 18 mg 
single injection of BI 655066 (approximately equivalent to 0.25 mg/kg in a 90 kg patient) had 
the lowest efficacy, while the 90 mg dose (approximately equivalent to 1 mg/kg) given at 0, 4 
and 16 weeks had considerably higher efficacy (90% reduction in PASI achieved in 73.2% vs.
32.6%, p < 0.01). Thus the dose-response (range) from 0.25 to 1.0 mg/kg identified in the phase 
I trial was roughly replicated in the phase II trial. 
Furthermore, the 180 mg dose of BI 655066 was associated with a numerically higher 
proportion of patients achieving PASI 90, compared to the 90 mg dose (81.0% vs. 73.2%). 
Although not statistically significant, this improved efficacy was noted in every endpoint (PASI 
90, PASI 100 and sPGA) at each time point and was not associated with a safety issue.
PK-PD Modelling to Support Dose Selection
A semi-mechanistic, indirect response PK-PD model was developed using available PK and 
PASI data across all currently available 1311.1 and 1311.2 PASI time course data. Similar PK-
PD models for efficacy have been utilized across many development programs in psoriasis.


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A model-based assessment of exposure vs. safety response was not currently feasible, as no 
dose-dependent AEs have been observed currently.
The current PK-PD modelling results indicate BI 655066 pharmacokinetics are linear with 
respect to time and dose, and are comparable to other IgG monoclonal antibodies binding 
soluble targets. PASI pharmacodynamics reflect endogenous psoriatic plaque formation rate 
similar to the reported literature values. The half-maximal inhibition (IC50) concentration in the 
range of 1 ng/mL confirms the high (in vivo) potency of BI 655066.
The PK-PD modelling confirmed the conclusions of the clinical data that 180 mg provided 
optimal efficacy, defined at least 70% of patients achieving PASI 90. Doses above 180 mg were 
also modelled and these results indicated minimal improvements (<5%) in the proportion of 
patients achieving PASI 90. For example a dose of 300 mg was predicted to yield a PASI 90 
at Week 12 of 71% (63 – 78%) compared to 68% (61 -76%) for 180 mg. The modelling also 
predicted that inclusion of the additional dose at Week 4 (“loading dose”) would provide higher 
PASI 90 response rates at earlier time points e.g. Week 12 and Week 16 compared to regimens 
without this additional dose. 
The model was also used to examine alternative dosing regimens, both longer (i.e. every 16 
weeks) or shorter (i.e. every 8-week) dosing intervals. Compared to every 12 weeks dosing, 
decreases in efficacy were predicted when the 16 week dosing interval was examined, while 
increasing the dosing frequency to every 8 weeks provided only minor improvement in 
efficacy, i.e. 3-5% increase in the proportion of patients achieving PASI 90. Finally, the 
modelling predicts that at a dose of 180 mg administered at Weeks 0, 4 and 16 the effect of 
body weight on PASI response rates was minimal, when this covariate was included as part of 
the PK model.
In addition to the observed clinical data (safety and efficacy) and PK-PD modelling, the final 
dose selection for Phase III was influenced by formulation and patient acceptability factors. The 
highest concentration of BI 655066 that can be formulated in 1 mL (and thus administered with 
a single injection) is 150 mg. Given that administration involving more than one injection on an 
ongoing basis could limit patient acceptability, modelling was used to predict PASI responses 
for a 150 mg dose administered at Weeks 0, 4 and every 12 weeks thereafter.
PK-PD analyses indicated no relevant reduction in efficacy when the dose was changed from 
180 mg to 150 mg (based on interpolation). In summary, taking into consideration expert 
advisor recommendation and prescriber preferences, the proposed dosing for BI 655066 in the 
upcoming phase 3 trials is 150 mg at Weeks 0 and 4, followed by every 12 weeks. This regimen 
is anticipated to provide a favourable risk-benefit profile with a dosing schedule that is 
consistent with standard clinical practice. 
In this trial the 150 mg dose will be administered as two prefilled syringes of 75 mg active drug 
each, as the 150 mg/mL formulation of BI 655066 is still being developed.
4.1.4
Drug assignment and administration of doses for each patient
IRT will be used to allocate medication to patients. At randomisation as well as subsequent 
medication administration visits, IRT will assign medication numbers. At visits where study 
medication is to be administered (Refer to Flow Chart) study sites will be required to complete 
the appropriate module in the IRT system. 


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Study medication will be administered exclusively at the study site, by the investigator or 
authorized study personnel (e.g. study nurse). 
BI 655066 and/or matching placebo will be administered as a subcutaneous injection in the 
abdomen, thighs, gluteal regions, or upper arms.
Injections should be at least 2 cm. apart and should not be close to a vein. The injection sites 
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.
Injections will be given in a double blind fashion with each patient receiving 2 injections of BI 
655066 or matching placebo administered within approximately 5 minutes at each dosing visit 
as indicated in the Flow Charts. 
In the eCRF, the study drug administration time is always the time of the first injection.
Further information regarding the technique of injection and injection materials (syringes, 
needles) will be provided in the ISF.
Patients should be closely monitored for signs and symptoms of hypersensitivity reactions for 
approximately 2 hours after the last injection at Visit 2 and for approximately 1 hour after the 
last injection at all other visits where drug is administered. 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.
The injections at each dosing visit are presented in Table 4.1.4: 1.  
Table 4.1.4:1
Dosing schedule 
Day 1 +
Week 4
Week 16
Week 28, 40, 52, 64, 76, 88
Arm 1
BI 
655066 
150 mg
(2)  
 ml (75 mg) 
BI 655066 
(blinded)
(2)  
 ml (75 mg)
BI 655066 
(blinded)
(2) 
ml (75 mg)
blinded or open label BI 655066
Or 
(2) PTM 
 ml (75 mg)
BI 655066 (blinded)
Arm 2
Placebo 
to 
BI 
655066 
150 mg
(2) PTM 
 ml (75 mg)
BI 655066 
(blinded)
(2) 
 ml (75 mg)
BI 655066 
(blinded)
(2) 
ml (75 mg) 
blinded or open label BI 655066
PTM= Placebo to match


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4.1.5
Blinding and procedures for unblinding
4.1.5.1
Blinding
During “Part A” of this trial all patients receive double-blind treatment. Patients, investigators 
and everyone involved in trial conduct or analyses of this double-blind study will remain 
blinded with regard to the randomized treatment assignments.
Arm 1 refers to patients originally randomized to BI 655066, and Arm 2 refers to patients 
originally randomized to placebo at Visit 2.
At Week 28, the start of “Part B”, non-responders (sPGAF 2) from Arm 1 and 2 will receive 
open label drug and will know future treatments are BI 655066.
At Week 28, responders (sPGA of 0 or 1) from Arm 1 in “Part A” will be re-randomized to 
either maintain treatment of BI 655066 or to receive placebo; these treatments will also be 
double-blinded to ensure that patients and investigators remain blinded to re-randomized 
treatment during “Part B.”   To maintain blinding, if a patient in Arm 2 reaches a sPGA of 0 or 
1 at Week 28, she/he will continue to receive blinded BI 655066 treatment assigned from IRT.
After the last patient has been in the study for 52 weeks (or has discontinued), the Sponsor will 
be unblinded in order to summarize the trial. Blinded treatment assignments will not be 
disseminated to the sites, investigators, and patients until the end of study database lock.
The randomisation code will be kept secret by Clinical Trial Support up to database lock. Refer 
to Section 4.1.5.2 for rules of breaking the blinding code for an individual or for all patients in 
emergency situations.
The randomisation codes will be provided to bioanalytics prior to last patient out to allow them 
to exclude PK samples taken from placebo patients from the bioanalytical analyses. 
Bioanalytics will not disclose the randomisation code or the results of their measurements until 
the study is officially unblinded.
Serum drug levels and demographic data together with treatment assignments and dosing 
information may be made available to individuals outside of the trial team for the purpose of 
PK dataset generation and analysis in accordance with sponsor’s standard procedures.
4.1.5.2
Unblinding and breaking the code
Emergency unblinding will be available to the Investigator / Pharmacist / investigational drug 
storage manager via IRT. It must only be used in an emergency situation when the identity of 
the trial drug must be known to the Investigator in order to provide appropriate medical 
treatment or otherwise assure safety of trial participants. The reason for unblinding must be 
documented in the source documents and/or appropriate CRF page along with the date and the 
initials of the person who broke the code.
If the treatment code for a patient is broken, the sponsor must be informed immediately. 
Due to the requirements to report Suspected Unexpected Serious Adverse Reactions (SUSARs), 
it may be necessary for a representative from BI’s drug safety group to access the 
randomisation code for individual patients during study conduct via the IRT system. In such 
cases, access to the code will only be permitted by authorised drug safety representatives.


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For Japan only: 
In this blinded trial, an emergency code break will be available to the Investigator via the IRT 
system. This code break may only be accessed in emergency situations when the identity of the 
trial drug must be known to the Investigator in order to provide appropriate medical treatment 
or if required to assure the safety of trial participants. Each site receives a manual from the IRT 
provider that contains instructions on how to
unblind the treatment of a patient via the IRT (via 24-hour Emergency helpline). If the code 
break for a patient is accessed, the sponsor must be informed immediately. The reason for 
accessing the code break, together with the date, must be documented on the appropriate eCRF 
page. In case a third party needs to break the code when the Investigator cannot be reached, the 
code can be opened by calling emergency code manager.
4.1.6
Packaging, labelling, and re-supply
BI 655066 and placebo supplies will be provided by Boehringer Ingelheim Pharma GmbH & 
Co KG, Biberach, Germany (see Section 4.1.1 for more details). 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.
There are approximately four re-supply campaigns planned. IRT will manage the inventory and 
re-supply of study medication.  
4.1.7
Storage conditions
Drug supplies will be kept in their original packaging and in a secure limited access storage 
area according to the recommended storage conditions on the medication label. A temperature 
log must be maintained for documentation.
If the storage conditions are found to be outside the specified range, the local clinical monitor 
(as provided in the list of contacts) must be contacted immediately.
Trial medication must be securely stored, e.g. in a locked refrigerator or at a pharmacy. The 
medication may only be dispensed to trial patients according to the CTP by authorized 
personnel as documented in the trial staff list.
4.1.8
Drug accountability
Drug supplies will be provided by the sponsor.
The Investigator < and/or > pharmacist < and/or > investigational drug storage manager will 
receive the investigational drugs delivered by the Sponsor when the following requirements are 
fulfilled:
∀
Approval of the trial protocol by the IRB / ethics committee, 
∀
Availability of a signed and dated clinical trial contract between the Sponsor and the head 
of the investigational site,
∀
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
∀
Availability of the proof of a medical license for the principal Investigator 
∀
Availability of Form 1572 (only for US sites)


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All unused medication must be returned to the sponsor. Used medication will be destroyed per 
local guidelines. Account must be given for any discrepancies.
Receipt, usage, and return must be documented. Account must be given for any discrepancy.
These records will include dates, quantities, batch / serial numbers, expiry (‘use- by’) dates, and 
the unique code numbers assigned to the investigational product and trial patients. The 
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 products received from the Sponsor. At the time of return to the 
Sponsor < and/or > appointed CRO, the Investigator / pharmacist / investigational drug storage 
manager must verify that all unused or partially used drug supplies are not remaining in the 
Investigator’s possession.
CONCOMITANT THERAPY, RESTRICTIONS, AND RESCUE 
4.2
TREATMENT
4.2.1
Rescue medication, emergency procedures, and additional 
treatment(s)
There are no special emergency procedures to be followed.
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), are 
permissible. All concomitant medications should be carefully evaluated by the investigator, and 
the CML should be contacted when there are questions regarding concomitant medications.   
If the patient experiences an intolerable increase of psoriasis during the course of the trial as 
deemed by the investigator, the patient will be discontinued from the trial to receive rescue 
treatment.
In case of adverse events in need of treatment symptomatic therapy according to investigator 
judgment will be permitted. All concomitant and/or rescue therapies will be recorded on the 
appropriate pages of the eCRF. 
4.2.2
Restrictions
4.2.2.1 
Restrictions regarding concomitant treatment
The medications (or classes of medications) listed in Table 4.2.2.1:1 must not be taken for the 
specified times prior to randomisation and for the whole duration of the study.
If prohibited medication is used during the study for any indication, the patient must 
discontinue use of the prohibited medication if he/she wants to continue in this study. If a 
patient receives a live virus during the study, they must be discontinued.


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Table 4.2.2.1:1
Restricted medications 
Medication or class of medications
Restriction duration
(through EOO Visit)
guselkumab, tildrakizumab
not allowed prior or during trial 
participation
briakinumab, secukinumab (Cosentyx®), ustekinumab 
(Stelara®)
6 months prior to 
randomisation
brodalumab, ixekizumab 
4 months prior to 
randomisation
adalimumab (Humira®) , infliximab (Remicade®)
12 weeks prior to 
randomisation
investigational products for psoriasis (non biologics)
etanercept (Enbrel®) 
6 weeks prior to randomisation
live virus vaccinations
6 weeks prior to randomisation
  investigational device or product (excludes psoriasis products)
30 days prior to randomisation
other systemic immunomodulating treatments (e.g. 
methotrexate, cyclosporine A, 
corticosteroids1,cyclophosphamide, tofacitinib (Xeljanz®),
apremilast (Otezla®)
other systemic psoriasis treatments (e.g. retinoids, fumarates, 
any other drug known to possibly benefit psoriasis)
photochemotherapy (e.g., PUVA)
phototherapy (e.g., UVA, UVB)
14 days prior to randomisation
topical treatment for psoriasis or any other skin condition (e.g. 
corticosteroids2, vitamin D analogues, vitamin A analogues, 
pimecrolimus, retinoids, salicylvaseline, salicylic acid, lactic 
acid, tacrolimus, tar, urea, andanthralin, `-hydroxy, fruit acids)
1 No restriction on corticosteroids with only a topical effect (e.g. inhalant corticosteroids to treat asthma 
or corticosteroid drops used in the eye or ear).
2 Exception: 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 with a restriction of 
use within 24 hours prior to clinic visits  when PASI is assessed.
4.2.2.2
Restrictions on diet and life style
Patients should be fasted for at least 8 hours prior to the collection of all safety laboratory 
samples starting with Visit 2.


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Moisturizers/emollients containing retinoids and the use of tanning beds are not allowed during 
the study.
4.2.2.3 Restrictions regarding women of childbearing potential
Female patients of childbearing potential need to follow inclusion criterion 1 in Section 3.3.2 of 
this CTP and the informed consent form with regard to acceptable contraception.
TREATMENT COMPLIANCE
4.3
Study medication will be administered in accordance with the protocol by authorized study 
personnel (e.g. study nurse). The measured plasma concentrations will provide additional 
information about compliance.
Any missed dose has to be documented and reported to the CML. 


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5.
VARIABLES AND THEIR ASSESSMENT 
5.1
TRIAL ENDPOINTS
5.1.1
Primary Endpoint(s)
There are co-primary endpoints to assess the efficacy of BI 655066 for the treatment of 
moderate to severe plaque psoriasis. These are as follows:
∀
Achievement of F 90% reduction from baseline PASI score (PASI 90) at Week 16
∀
Achievement of an sPGA score of clear or almost clear (0 or 1) at Week 16
At the trial level, the co-primary endpoints will be the proportion of patients achieving PASI 90 
and an sPGA score of clear or almost clear at Week 16 in each of the treatment groups. 
None of the primary endpoints are safety issues.
5.1.2
Secondary Endpoints
None of the Secondary endpoints are safety issues.
Key Secondary Endpoints:
The key secondary endpoints are as follows:
∀
Achievement of 75% reduction from baseline PASI score (PASI 75) at Week 16
∀
Achievement of 100% reduction from baseline PASI score (PASI 100) at Week 16
∀
Achievement of an sPGA score of clear (0) at Week 16
∀
Achievement of a Dermatology Life Quality Index (DLQI) score of 0 or 1 at Week 16
∀
Achievement of an sPGA score of clear or almost clear (0 or 1) at Week 52 
Other Secondary Endpoints:
The secondary endpoints are as follows:
∀
Achievement of PASI 75 at Week 52  
∀
Achievement of PASI 90 at Week 52
∀
Achievement of PASI 100 at Week 52
Note that all key and other secondary endpoints at Week 52 will only be assessed for patients 
re-randomised at Week 28.
5.1.3.
Further Endpoints
The further endpoints are as follows:
∀
Achievement of PASI 50 at all visits collected
∀
Achievement of PASI 75 at all visits collected
∀
Achievement of PASI 90 at all visits collected
∀
Achievement of PASI 100 at all visits collected
∀
Time until the first achievement of PASI 50, PASI 75, PASI 90,and PASI 100


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∀
Time until loss of PASI 50, PASI 75, PASI 90, and PASI 100 response for patients re-
randomised at Week 28
∀
Change and percent change from baseline in PASI at all visits collected
∀
Absolute PASI of < 3 at all visits collected
∀
Achievement of an sPGA score of clear or almost clear at all visits collected
∀
Achievement of an sPGA score of clear at all visits collected
∀
Time until the first achievement of sPGA of 0 or 1
∀
Time until loss of sPGA of 0 or 1 response for patients re-randomised at Week 28
∀
Time until sPGA score of F 3 (relapse) for patients re-randomised at Week 28
∀
Change from baseline in DLQI at all visits collected
∀
Achievement of a DLQI score of 0 or 1 at all visits collected
∀
Achievement of a reduction of 5 or more points from baseline in DLQI score at all visits 
collected
∀
Change from baseline in HAQ-DI at all visits collected, in patients selected for PsA 
assessment.
∀
Change and percent change from baseline on patient Pain VAS
∀
Change and percent change from baseline on patient Global Assessment VAS
∀
Change from baseline in Swollen or Tender Joint Count (28 joints) at all visits collected 
in patients selected for PsA assessment.
∀
Change from baseline in DAS28 at all visits collected in patients selected for PsA 
assessment. 
∀
Change and percent change from baseline in Nail Psoriasis Severity Index (NAPSI) at 
all visits collected
∀
Change and percent change from baseline in Palmoplantar Psoriasis Severity Index 
(PPASI) at all visits collected
∀
Change and percent change from baseline in Psoriasis Scalp Severity Index (PSSI) at all 
visits collected
∀
Change of metabolic risk factors from baseline (waist circumference, body weight, 
HOMA-index)
See the Flow Chart for when the above measures are collected.  The above endpoints will 
be analyzed, where appropriate, for re-randomized subjects after receiving open-label study 
drug for retreatment (Flow Chart 2 and 3). 
5.2
ASSESSMENT OF EFFICACY
∀
The skin condition will be assessed by using the PASI, sPGA, and other relevant scores 
as described in CTP Section 5.1, Appendix 10, and the ISF.
∀
Symptoms, quality of life, and physical function will be assessed by DLQI and HAQ-
DI.
Details of the efficacy assessments are listed in the Appendix (Section 10).
5.3
ASSESSMENT OF SAFETY
Safety will be assessed descriptively based on: 


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∀
Adverse events
∀
Serious adverse events
∀
Clinical laboratory values (haematology, clinical chemistry and urinalysis) 
∀
Intensity of adverse events will be assessed by Rheumatology Common Toxicity 
Criteria (RCTC) version 2.0 (refer to ISF for details)
5.3.1
Physical examination
Complete physical examinations will be performed at visits noted in the Flow Charts.
A complete physical examination will include vital sign assessment, and general appearance as 
well as evaluation of all relevant organ systems.
A targeted physical examination will be performed at visits noted in the Flow Charts. This
includes vital sign assessment as well as an evaluation of the organ systems associated with 
AE(s) symptoms or laboratory abnormalities.
Clinically relevant abnormal findings will be reported as baseline conditions or AE’s.
5.3.1.1
Waist circumference
Waist circumference measurements should be made around a patient’s bare midriff, after the 
patient exhales while standing without shoes and with both feet touching and arms hanging 
freely. The tape should be placed perpendicular to the long axis of the body and horizontal to 
the floor and applied with sufficient tension to conform to the measurement surface. Waist 
circumference should be determined by measuring the midpoint between the lowest rib and the 
iliac crest.
5.3.1.2. Body weight
The scale used to capture body weight for each patient should remain consistent during the trial.
In order to get comparable body weight values, it should be performed in the following way:
∀
Fasting (except for the screening visit);
∀
After the urine sampling (body weight after bladder voiding); 
∀
Shoes and coat/jackets should be taken off; and
∀
Pockets should be emptied of heavy objects (i.e. keys, coins etc.)
5.3.2
Vital Signs
Vital sign evaluations will be performed at every visit as shown in the Flow Charts and includes 
temperature, pulse rate, systolic/diastolic blood pressure and respiratory rate. Respiratory rate, 
pulse rate, and blood pressure will be measured after patients have been sitting comfortably for 
at least five minutes. Measurement of vital signs should precede blood sampling to avoid the 
impact of blood sampling on the vital measurements.  At dosing visits vital sign evaluations will 
be performed pre-dose. In addition at Visit 2 and Visit 3 vital sign evaluations will be taken at 
approximately 5 minutes post-dose (5 minutes after last injection) and approximately 60 
minutes post-dose (60 minutes after last injection). 
Patients should be closely monitored for signs and symptoms of hypersensitivity reactions for 
approximately 2 hours after the last injection at Visit 2 and for approximately 1 hour after the 


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last injection at all other visits where drug is administered. 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.
5.3.3
Safety laboratory parameters
For the visit schedule requiring safety laboratory sampling, see the Flow Charts.
The laboratory tests listed in Table 5.3.3: 1 will be performed at the central laboratory service 
provider. A local laboratory may be used for selected tests in exceptional cases. Patients should 
be fasting for at least 8 hours prior to the blood sample being taken (except screening visit).
Instructions regarding sample collection, sample handling/ processing and sample shipping are 
provided in the Laboratory Manual in the ISF. 
Laboratory results (i.e. all safety laboratory and clinical laboratory data relevant for current 
clinical practice of psoriasis patients) of the patients will be available in real time to the 
respective investigator (via laboratory reports) and to the sponsor (via the central laboratory 
website) and selected abnormal laboratory alerts will be flagged to the site and sent to sponsor 
in real time. 
Clinically relevant abnormal findings will be reported as baseline conditions or AE’s.
A clinically relevant value may be either inside or outside the reference range. Clinically 
relevant abnormal laboratory test results must be confirmed using an unscheduled visit 
laboratory kit and should be repeated until normalisation or stabilisation or until an alternative 
explanation has been found. Abnormal laboratory values will be also graded for intensity by 
using RCTC Version 2.0 criteria (R13-3515).


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Table 5.3.3:1 Laboratory tests  
Category
Test name
Haematology
Hematocrit (Hct)
Hemoglobin (Hb)
Glycosylated Hb (HbA1c)
Red Blood Cell Count/ Erythrocytes
Reticulocyte Count
White Blood Cells / Leukocytes
Platelet Count/ Thrombocytes
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
Activated Partial Thromboplastin Time (aPTT)
Prothrombin time (INR)
Fibrinogen
Enzymes
AST(GOT)
ALT(GPT)
Alkaline Phosphatase (AP)
Creatine Kinase (CK)
CK-MB, (Only if CK is elevated)
Gamma-Glutamyl Transferase (GGT/T-GT)
Lactic Dehydrogenase (LDH)
Amylase
Lipase
Electrolytes
Calcium
Sodium
Potassium
Chloride
Bicarbonate
Substrates
Glucose
BUN
Uric acid
Creatinine
eGFR (estimated by CKD-EPI formula)
Bilirubin Total
Bilirubin Direct (if total is elevated)
Bilirubin Indirect (if total is elevated)
Troponin (Reflex when CK is elevated)
Albumin
C-Reactive Protein (high sensitivity)
Cholesterol, total
Triglycerides
LDL-Cholesterol (calculated)
HDL-Cholesterol
HOMA-IR (V2, V9, V15, V19, EOO)
Urine Pregnancy test1
Human Chorionic Gonadotropin in the urine
Serum Pregnancy test2
Human Serum Chorionic Gonadotropin 


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Table 5.3.3:1 Laboratory tests
Category
Test name
Hormones (screening)
TSH, 
(free T3 and free T4 in case of abnormal TSH 
results) 
Autoantibodies (screening)
Rheumatoid Factor 
Urinalysis (Stix)
Urine Nitrite
Urine Protein
Urine Glucose
Urine Ketone
Urobilinogen
Urine Bilirubin
Urine RBC/ Erythrocytes
Urine WBC/ Leukocytes
Urine pH
Urine-Sediment (microscopic examination, only if 
urine analysis abnormal)
Urine Sediment Bacteria
Urine Cast in Sediment
Urine Squamous Epithelial Cells
Urine Sed. Crystals., Unspecified
Urine Sediment RBC/ Erythrocytes
Urine Sediment WBC/ Leucocytes
Urinalysis 
Albumin (quantitative)
Creatinine
Albumin/Creatinine ratio
Infection Testing ( Screening 3 V15, EOO)
Hepatitis B Surface Antigen (qualitative)
Hepatitis C Antibodies (qualitative)
HIV-1, and HIV-2 Antibody (qualitative)
QuantiFERON®-TB3
1. Urine pregnancy test performed on-site at all dosing visits (pre-dose) as well as EOT and EOO. (only for 
female patients of childbearing potential)
2. Serum pregnancy test at screening as well as confirmation of positive urine pregnancy test. (only for female 
patients of child bearing potential at screening as well as reflex for positive urine pregnancy test)    
3. At Screening only TB testing is required. There is the site option to perform a PPD skin test, although this
will not be provided or performed at Central Lab                                 
5.3.4
Electrocardiogram
The 12-lead ECGs will be performed as scheduled in the Flow Chart(s).
ECGs will be recorded after the patients have rested for at least 5 minutes in a supine position 
and will always precede blood sampling. Six limb leads, as specified by Einthoven (I, II and III) 
and Goldberger (aVR, aVL, aVF), and six pre-cordial leads (V1–V6), according to Wilson, will 
be used. 
ECGs will be read and evaluated by a central vendor. The study site will be informed about the 
results of the assessment of the ECG obtained at screening and if there are findings that would 
exclude the patient from study participation according to Exclusion Criterion #8.
The electronic version of the ECG is regarded as source data. 


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ECGs may be repeated for quality reasons and the repeat used for analysis. Additional ECGs 
may be collected for safety reasons. Clinically significant abnormal findings will be reported as 
AE’s. 
Information about the details of ECG collection and the parameters assessed will be provided in 
the ISF.
5.3.5
Other safety parameters
5.3.5.1         Local Tolerability
Local tolerability at the administration sites of the subcutaneous injections will be assessed 
according to “swelling”, “induration”, “heat”, “redness”, “pain”, or “other findings” at the 
specified visits during the treatment period according to the flow chart. On visits where drug is 
administered this assessment should be done pre-dose.
Clinically relevant findings will be reported as AE’s. 
5.3.6
Assessment of adverse events
5.3.6.1        Definitions of AEs
Adverse event
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical 
investigation patient administered a medicinal product and which does not necessarily have to 
have a causal relationship with this treatment.
An AE can therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
product, whether or not considered related to the medicinal product.
Serious adverse event
A serious adverse event (SAE) is defined as any AE which:
∀
results in death,
∀
is life-threatening,
∀
requires inpatient hospitalisation or prolongation of existing hospitalisation,
∀
results in persistent or significant disability or incapacity,
∀
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 judgment which may jeopardize the patient and may 
require medical or surgical intervention to prevent one of the other outcomes listed in 
the above definitions.


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Life-threatening in this context refers to an event in which the patient was at risk of death at the 
time of the event; it does not refer to an event that hypothetically might have caused death if 
more severe.
For Japan only, the following events will be handled as “deemed serious for any other reason”. 
An AE which possibly leads to disability will be reported as an SAE.
AEs considered “Always Serious”
In accordance with the European Medicines Agency initiative on Important Medical Events, 
Boehringer Ingelheim has set up a list of AEs, which by their nature, can always be considered 
to be “serious” even though they may not have met the criteria of an SAE as given above.
The latest list of “Always Serious AEs” can be found in the Remote Data Capture (RDC)
system. These events should always be reported as SAEs.
Adverse events of special interest (AESIs)
The term AESI relates to any specific AE that has been identified at the project level as being 
of particular concern for prospective safety monitoring and safety assessment within this trial, 
e.g. the potential for AEs based on knowledge from other compounds in the same class. AESI 
need to be reported to the Sponsor’s Pharmacovigilance Department within the same timeframe 
that applies to SAE, see Section 5.3.7.
The following are considered as AESIs:
Hepatic injury
A hepatic injury is defined by the following alterations of hepatic laboratory parameters: 
∀
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 same blood draw sample, and/or
∀
marked peak aminotransferase (ALT, and/or AST) elevations F10 fold ULN
These lab findings constitute a hepatic injury alert and the patients showing these lab 
abnormalities need to be followed up according to the “DILI checklist” provided in the ISF and 
the RDC-system.
In case of clinical symptoms of hepatic injury (icterus, unexplained encephalopathy, 
unexplained coagulopathy, right upper quadrant abdominal pain, etc.) without lab results (ALT, 
AST, total bilirubin) available, the investigator should make sure these parameters are analysed, 
if necessary in an unscheduled blood test. Should the results meet the criteria of hepatic injury 
alert, the procedures described in the DILI checklist should be followed.
Intensity of AEs
The intensity grading of AEs will be performed according to Rheumatology Common Toxicity 
Criteria (RCTC) Version 2.0 developed by OMERACT (R13-3515). Refer to the ISF for
intensity/severity classification.
Intensity options are:
Grade 1: MILD
Grade 2: MODERATE
Grade 3: SEVERE
Grade 4: LIFE-THREATENING


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Causal relationship of AEs
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. 
The causal relationship must be provided by the Investigator for all potential trial drugs, i.e. the 
BI trial drug and for all other trial drugs (such as any active comparator or placebo and for trial 
procedure).
For Japan, the reason for the decision on causal relationship for unlisted AEs needs to be 
provided in the eCRF
5.3.7
Adverse event collection and reporting
AE Collection
The following must be collected and documented in the eCRF by the Investigator:
•
From signing the informed consent onwards through the Residual Effect Period until a
patient’s end of trial participation, all AEs (serious and non-serious), and AESIs must be 
collected.
•
After the individual patient’s completion of trial: 
The investigator does not need to actively monitor the patient for AEs, but should only 
report relevant SAEs and relevant AESIs of which the investigator may become aware 
of.
The REP is defined as 15 weeks after the last trial medication administration. All AEs that 
occur during the treatment phase and throughout the REP will be considered as on treatment
(see Section 7.3.4). Events that occur after the REP will be considered as post treatment events.
AE reporting to sponsor and timelines


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The Investigator must report SAEs, AESIs, and non-serious AEs which are relevant for the 
reported SAE or AESI, on the BI SAE form via fax immediately (within 24 hours ) to the 
Sponsor’s unique entry point (country specific contact details will be provided in the ISF). The 
same timeline applies if follow-up information becomes available. In specific occasions the 
Investigator could inform the Sponsor upfront via telephone. This does not replace the 
requirement to complete and fax the BI SAE form.
In Japan, all SAEs and AESIs must be reported immediately to the head of the trial site.
With receipt of any further information to these events, a follow-up SAE form has to be 
provided. For follow-up information the same rules and timeline apply as for initial information.
Information required
For each AE, the Investigator should provide the information requested on the appropriate 
eCRF pages and the BI SAE form, e.g. onset, end date, intensity, treatment required, outcome, 
seriousness, and action taken with the investigational drug(s). The Investigator should 
determine the causal relationship to the trial medication, and the trial procedures outlined under 
Section 6.2.
The following should also be recorded as an (S)AE in the eCRF and SAE form (if applicable):
∀Worsening of the underlying disease or of other pre-existing conditions
∀Changes in vital signs, ECG, physical examination and laboratory test results, if they are 
judged clinically relevant by the Investigator.
If such abnormalities already pre-exist prior trial inclusion they will be considered as 
baseline conditions.
All (S)AEs, including those persisting after individual patient’s end of trial must be followed up 
until they have resolved, have been sufficiently characterized, or no further information can be 
obtained.
Screening failures:
SAEs which occurred during the screening period are to be reported according to standard 
procedures.
Pregnancy
In the rare case that a female patient participating in this clinical trial becomes pregnant after 
having taken trial medication, the Investigator must report immediately (within 24 hours) the 
drug exposure during pregnancy (DEDP) to the Sponsor’s unique entry point (country-specific 
contact details will be provided in the ISF). The Pregnancy Monitoring Form for Clinical Trials 
(Part A) should be used. 
If a patient becomes pregnant during a trial, the study medication needs to be discontinued, and 
the patient will complete the EOT Visit procedures and Follow-up 1 and Follow-up 2 (EOO) 
Visit procedures.  The patient will be followed up until birth or otherwise termination of the 
pregnancy.
The outcome of the pregnancy associated with the drug exposure during pregnancy must be 
followed up and reported to the Sponsor’s unique entry point on the Pregnancy Monitoring 
Form for Clinical Trials (Part B). 


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As pregnancy itself is not to be reported as an AE, in the absence of an accompanying SAE, 
only the Pregnancy Monitoring Form for Clinical Trials and not the SAE form is to be 
completed. If there is an SAE associated with the pregnancy then the SAE has to be reported on 
the SAE form in addition. 
The ISF will contain the Pregnancy Monitoring Form for Clinical Trials (Part A and B).
5.4
DRUG CONCENTRATION MEASUREMENTS AND 
PHARMACOKINETICS
5.4.1
Assessment of Pharmacokinetics
BI 655066 concentrations will be reported descriptively.  No PK parameters will be calculated. 
PK data will be incorporated into a larger pharmacometric analysis with other trials of BI 
655066 project.  The relationship between PK and selected efficacy endpoints, biomarkers and 
AEs may be assessed. 
PK and demographic data together with treatment assignments and dosing information may be 
made available to individuals outside of the trial team for the purpose of PK dataset generation 
in accordance with sponsor’s standard procedures.
Refer to the Flow Charts for the visits requiring PK and ADA sampling. The date and exact 
clock time of drug administration and PK and ADA sampling will be recorded on the eCRF. 
These actual administration and sampling times will be used for determination of PK 
parameters. On visits with study medication dosing, PK and ADA sampling should be collected 
prior to administration of study drug.
After completion of the study, PK and ADA plasma samples may be used for further 
methodological investigations, e.g., stability testing.  However, only data related to the analyte 
will be generated by these additional investigations.  
5.4.2
Methods of sample collection
5.4.2.1      Plasma sampling for pharmacokinetic analysis
For quantification of analytic plasma concentrations, approximately 2.5 mL of blood will be 
taken at the time points listed in the Flow Chart under PK sampling.
Detailed instructions for pharmacokinetic sampling, handling, and shipment of plasma samples 
are provided in the laboratory manual.
5.4.2.2       Plasma sampling for ADA
For ADA assessment, approximately 2.5 mL of blood will be taken at the time points listed in 
the Flow Chart under ADA sampling. Detailed instructions for ADA sampling, handling, and 
shipment of plasma samples are provided in the laboratory manual.
5.4.3
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). 


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Samples that are confirmed positive may be further characterized in a validated neutralizing 
antibody (NAb) assay.
5.4.4
Pharmacokinetic-Pharmacodynamic Relationship
Refer to Section 7.3.6.
5.5
ASSESSMENT OF EXPLORATORY BIOMARKERS
5.5.1
Assessment of soluble protein biomarkers in blood
Serum will be collected pre and post treatment with BI 655066 to assess changes in protein 
levels of disease specific markers such as but not limited to #-defensin 2, neutrophil gelatinase 
associated lipocalin-2 (NGAL) and S-100 A8 protein.
In addition changes in levels of biomarkers related to metabolic syndrome, such as leptin, 
resistin, TNFa, IL-6 and vascular endothelial growth factor (VEGF) will be explored.   
Blood samples will be stored for a maximum of 3 years (under consideration of local 
legislation) upon signature of the final study report unless the patient agrees to long-term 
storage (15 years) of the biomarker samples for biomarker sample banking (Section 5.5.3).  
5.5.1.1 Methods of sample collection
For the assessment of soluble protein biomarkers in serum, approximately 12.5 ml of blood will
be collected at the time points indicated in the flow charts. Samples should be collected prior to 
the administration of study drug at dosing visits. For details on sample collection, processing
and logistics refer to the ISF (Laboratory Manual).  
5.5.1.2 Analytical determinations
These biomarkers are considered exploratory and respective assays will need to be qualified to 
meet the required performance criteria. 
5.5.2
DNA Banking
Participation in the DNA Banking sampling is voluntary and not a prerequisite for participation 
in the trial. The patient must provide informed consent for participation in this optional testing 
prior to any blood sampling used for DNA Banking. 
The DNA Banking sample will be stored in accordance with local ethical and regulatory 
requirements.
5.5.2.1.
Methods of sample collection 
One blood sample for DNA banking will be taken at Visit 2. A maximum of 8.5 mL blood will 
be collected per PaxGene DNA blood sampling tube. For details on sample handling and 
logistics refer to the ISF (Laboratory Manual).


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5.5.2.2.
Analytical determinations
The DNA Banking sample, derived from the original blood sample, will be stored at AbbVie or 
a third party delegate (e.g. Boehringer Ingelheim Pharma GmbH & Co. KG; Birkendorfer Str. 
65, 88397 Biberach, Germany). The stored DNA may be retrospectively analysed, e.g. to
identify whether there are other genetic factors that could contribute to a better therapeutic 
outcome or a higher risk of developing treatment-related adverse drug reactions.
5.5.3
Biomarker sample banking
After completion of the study any unused serum, collected for biomarker sampling as listed in 
Section 5.5.1. may be used for further investigations, (e.g., additional biomarkers for 
immunological & inflammatory diseases) if informed consent for biomarker sample banking is 
agreed upon by the patient.  
Declination to allow storage and use of these unused samples will not preclude participation in 
this study. The study samples will be stored for a maximum period of 15 years (under 
consideration of local legislation and if consented by the patient) upon archiving of the final 
study report after study termination.
5.6
OTHER ASSESSMENTS  
Not applicable
5.7
APPROPRIATENESS OF MEASUREMENTS
All measurements performed during this trial are standard measurements in psoriasis treatment 
trials and will be performed in order to monitor safety aspects or assess treatment response in 
an appropriate way.
Information about race should be obtained from all study participants as allowed by local 
regulations. This is because the prevalence and characteristics of psoriasis differ widely 
between patients of different racial origin. It will thus be worthwhile to assess if patients of 
different race will respond differently to the study treatment.


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6.0
INVESTIGATIONAL PLAN
6.1
VISIT SCHEDULE
All patients have to adhere to the visit schedule as specified in the Flow Charts. Each visit date 
(with its window) is to be counted from Day 1.
If any visit has to be rescheduled, subsequent visits should follow the original visit date 
scheduled. Additional visits for the purpose of re-testing of laboratory parameters or AE 
monitoring may be included as deemed necessary by the investigator.
For detailed description of the trial procedures, please refer to the Flow Charts.
6.2
DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS
Study procedures to be performed at each visit are listed in the Flow Charts and the respective 
protocol sections.  Refer to Section 5.3 and the Appendix Section 10 for explanations of the 
procedures.  Additional details on select procedures are provided below.
Patients should be seen for all visits on the designated day within the allowed “visit window” as
specified in the Flow Charts. Measurement of vital signs should precede blood sampling and be 
assessed pre-dose at all dosing visits. Patient reported outcomes (PROs) should be completed 
electronically during clinic visits by the patient on his/her own in the following order, as 
programmed in the electronic device:
(1) DLQI
(2) HAQ-DI [for psoriatic arthritis patients at selected sites]
(3) Pain VAS [for psoriatic arthritis patients at selected sites]
(4) Patient Global Assessment (PtGA) VAS [for psoriatic arthritis patients at selected 
sites]
PROs should be completed by the patient in a quiet area/room before any other visit 
assessments or treatments, and, when possible, before any interaction with the investigator or 
other members of the study team.  Timing for downloading the data of PROs will be available 
in the ISF.
The following psoriasis efficacy assessments (PASI, sPGA, NAPSI, PPASI and PSSI) and 
psoriatic arthritis assessments (CASPAR and Tender or Swollen joint counts (TJC/SJC)) will 
be performed by a qualified efficacy assessor at the site by direct capture using an electronic 
device. Efficacy assessor qualifications and The Group for Research and Assessment of 
Psoriasis and Psoriatic Arthritis (GRAPPA) training requirements will be available in the ISF.
Tuberculosis (TB) Testing
Patients will be tested for TB (Quantiferon or PPD) at Screening, Week 52 and EOO. Patients 
who test positive and are at low risk of TB reactivation, per local guidelines and investigator 
judgment, do not need to be treated with prophylactic anti-tuberculosis medication and can be 
entered or continue in the trial.
6.2.1
Screening period
After patients have been informed about the trial, written informed consent in accordance with 
GCP and the local legislation must be obtained prior to performing any study related 
procedures. Once they have consented, the patient is considered to be enrolled in the trial and 
have started screening.  The patient should be recorded on the enrolment log and be registered 


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in IRT as a screened patient. Patients will be assigned a patient number and enrolment must be 
recorded in eCRF pages.
The Screening period is defined as the period from the Screening visit to Randomisation (first 
study drug administration). The screening period should be no longer than 42 days and no less 
than 7 days and will be used to assess eligibility of the patients and to taper the patients off
disallowed medications. Thus patients will not be randomized until all screening procedures are 
completed and results are reviewed to verify study eligibility. Screening procedures may be 
extended to more than 1 physical visit if needed. 
Re-Screening
Re-screening will not be permitted.  Patients who fail screening following Visit 1 assessments 
should be registered as a screen failure in IRT within the protocol defined screening period.
For the comprehensive list of the trial procedures required at the Screening Visit (Visit 1) 
please refer to Flow Chart #1.
Demographics
Informed consent date, HIPAA status (US patients only), sex, ethnicity and race (if allowed by 
local law) will be collected and reported in the eCRF.
Baseline Conditions
Chronic diseases, current observable conditions, any new clinically relevant findings 
discovered from the Physical Exam, ECG, safety labs, and any condition requiring therapy 
(excluding psoriasis) will be reported on the Baseline Condition eCRF page.
History for Psoriatic Arthritis 
At Visit 1, all patients at all sites will be evaluated for history of psoriatic arthritis.
Psoriatic Arthritis Diagnosis Assessment
At Visit 1 at pre-selected study sites, all patients with a positive medical history of psoriatic 
arthritis will be further evaluated for psoriatic arthritis (PsA) diagnosis based on CASPAR 
(ClASsification of Psoriatic Arthritis) criteria. See Appendix 10.6 for further details
IRT
All patients that are screened must be registered with IRT.  If the patient results in a screen 
failure, IRT should be notified as soon as possible and within the 42- day screening period. 
Details of IRT procedures can be found in the IRT manual located in the ISF
6.2.2
Treatment period
The Treatment period consists of a maximum of 20 visits (Visits 2-21). Visit 2 is the 
Randomisation Visit and Visit 21 is end of treatment (EOT) visit, where the last dose of 
medication will be administered.
Unscheduled Visits
During the treatment period patients may be seen at an unscheduled visit if they experience 
deterioration of psoriasis (i.e. between Weeks 32 and 88 for patients in the double blind portion 
of the study to assess relapse), or have AEs that in the opinion of the investigator need 
intervention or repeated laboratory testing.


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Safety laboratory testing
All visits after screening requiring safety laboratory sampling will be performed in a fasted 
state (8 hours no food and only water).  If a patient comes in non-fasted where a fasting 
condition is required, the visit should be performed, the non-fasted condition documented on 
the laboratory requisition, and the patient reminded about the expected conditions.  
Pregnancy testing
Urine pregnancy testing for all woman of childbearing potential will be conducted on-site prior 
to every dosing and must be negative to further treat the patient.  A positive urine test must be 
confirmed with a serum pregnancy test.
Psoriatic arthritis assessments (at selected study sites)
Refer to the Flow charts as well as Appendix 10.6 for timing and assessments.
C-Reactive protein (CRP)
Safety laboratory assessments include CRP testing.  The result of the CRP will be used to 
calculate the DAS28 at the associated visit. See also Appendix 10.6.1.
At treatment period visits all the study procedures described in the Flow-Charts will be 
performed before the administration of the study medication.
Randomisation (Visit 2)
Randomisation via IRT and administration of the first dose of study medication should be the 
last activity at Visit 2. 
Week 28 Visit
At Week 28, each patient’s sPGA score will be entered into IRT. Refer to the ISF for details 
pertaining to IRT procedures and requirements. 
All patients that are responding to treatment (sPGA of 0 or 1) at Week 28 will be dispensed 
blinded medication kits; see (Section 7.6.).
All patients who are non-responders (sPGA F 2 ) at week 28, regardless of initial treatment arm,
should continue in this trial and will be dispensed open label BI 655066 medication kits until 
the end of the treatment period (Week 88).
Randomized withdrawal period (Re-randomized patients)
Between Week 32 and Week 82, at scheduled or unscheduled visits, once any Week 28 
responder’s sPGA increases to F 3 (relapse) the site will enter this result into IRT, and IRT will 
immediately dispense open label BI 655066 medication. The patient will immediately follow 
Flowchart #2 or Flowchart #3 depending on the time of relapse.  The patient will be re-treated 
for a maximum of 16 weeks and then have the opportunity to roll-over to the OLE study for 
further treatment. (See Section 6.2.3). All patients following Flow Chart 2 or Flow Chart 3 will 
receive a loading dose 4 weeks after the first re-treatment.   
Patients relapsing at either an unscheduled visit between Week 82 and Week 88 or at the 
scheduled Week 88 visit will have the EOT visit procedures performed and return for Follow-
up 1 and Follow-up #2 visits as scheduled. A loading dose will not be administered. These 
patients will also have the opportunity to rollover to the OLE study (See Section 6.2.3)


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6.2.3
Follow up Period and Trial Completion
For all randomized patients termination of trial medication and trial completion must be 
recorded on the corresponding eCRF.  
The follow-up period within this trial is 16 weeks after receiving the last dose of study 
medication.   Refer to the flow charts for the list of procedures required.
Early treatment and trial termination 
If study medication is discontinued prior to the planned Flow Chart EOT visit, every effort 
should be made to have the patient continue in the trial and complete all of the remaining 
Treatment Period Visits, as well as Follow-Up 1 and Follow-Up 2 Visits.  Trial termination 
should be completed at Follow-Up 2 Visit. 
If a patient cannot or will not continue in the trial, the patient should complete EOT visit 
procedures instead of the planned treatment period visit and return to the clinic for Follow-Up 
2/End of Observation (FU2/EOO) Visit 16 weeks after last dose of study medication.
Patients who discontinue treatment early should be registered as withdrawn/discontinued in 
IRT and will not have the option to participate in the OLE trial.        
Successful trial completion
Patients who complete treatment according to the applicable planned Flow Chart visit schedule
will return to the clinic for Follow-up Visit 1, (6 weeks after last dose of study medication) and 
for the EOO visit (16 weeks after last dose of study medication). Trial completion is defined as 
patients completing the EOO visit within the specified window per the flow charts, and who 
have not discontinued drug prematurely. These patients should be registered as completed in 
IRT at the EOO visit. These patients will have the option to participate in the open label 
extension (OLE) trial once EOO procedures are completed. 
Refer to ISF for OLE trial entry details.
Vital Status
For randomized patients leaving the study early (before the planned EOO in their current 
applicable flow chart), vital status should be collected every 12 months after discontinuation up 
to the planned EOO. 


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7.0
STATISTICAL METHODS AND DETERMINATION OF
SAMPLE SIZE
7.1
STATISTICAL DESIGN - MODEL
This is a confirmatory, multicenter, randomized, double-blind, placebo controlled study with
randomized withdrawal and re-treatment, evaluating the efficacy and safety of BI 655066 in
patients with moderate to severe chronic plaque psoriasis. The primary objectives of this trial 
are to assess the safety and efficacy of BI 655066 in comparison to placebo in patients with 
moderate to severe chronic plaque psoriasis. The primary efficacy will be evaluated at 16 
weeks.  In addition, the maintenance of response following drug withdrawal will be assessed 
after Week 28 through Week 104.  Subsequent to drug withdrawal, patients who experience 
relapse (sPGA F3) will be retreated with BI 655066 to assess response after retreatment.
Randomisation will be stratified by weight (C 100 kg vs. >100 kg) and prior exposure to TNF 
antagonists (0 vs. F1). Based upon these design considerations and the binary nature of the co-
primary endpoints of PASI 90 and sPGA 0 or 1, the trial will be analysed using the Cochran-
Mantel-Haenszel risk difference estimate stratified by the randomisation factors mentioned 
previously.  Baseline refers to the measurement recorded at randomisation (Visit 2); if data at 
Visit 2 is missing or not collected per protocol, then data from Visit 1 will be considered 
baseline.
In addition, this trial will assess PK and the emergence of anti-drug antibodies (ADA) and their 
effect on efficacy and safety. Moreover, it will be explored how the use of BI 655066 may 
influence gene and protein expression levels and disease specific protein markers. More details 
on these analyses will be provided in the Trial Statistical Analysis Plan (TSAP).
The percent reduction from baseline is calculated by % PASI reduction from baseline = ((PASI 
at baseline - PASI at Visit Y) / PASI at baseline) * 100, at all follow up visits.  Achieving an 
X% or larger reduction from baseline PASI score is denoted as PASI X.  
Re-randomisation at Week 28 will also be stratified by weight (C 100 kg vs. >100 kg) and prior 
exposure to TNF antagonists (0 vs. F1).
7.2
NULL AND ALTERNATIVE HYPOTHESES  
The primary hypotheses are that BI 655066 is different than placebo in achieving F 90% 
reduction from baseline in the Psoriasis Area and Severity Index score (PASI 90) and sPGA of 
0 or 1 at Week 16 in participants with moderate to severe chronic plaque psoriasis. For the 
primary analyses, this study has 2 treatment arms:
Arm 1 – Patients randomised at visit 2 to receive 150 mg of BI 655066  
Arm 2 – Patients randomised at visit 2 to receive placebo  
For Part B of the trial, patients randomised to receive BI 655066 at visit 2 and have an sPGA 
response of 0 or 1 at Week 28 will be re-randomised to one of the following treatment arms:
Arm A – Patients re-randomised to continue to receive BI 655066 during Part B
Arm B – Patients re-randomised to receive placebo during Part B


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The following null hypotheses will be tested in a hierarchical order using two-sided tests with a 
type I error of 0.05. The two co-primary endpoints need to be significant simultaneously, 
therefore no alpha adjustment is necessary.
1. BI 150 mg (Arm 1) is not different from placebo (Arm 2) with respect to PASI 90 or 
sPGA 0 or 1 response at Week 16
2. BI 150 mg (Arm 1) is not different from placebo (Arm 2) with respect to PASI 75 
response at Week 16
3. BI 150 mg (Arm 1) is not different from placebo (Arm 2) with respect to PASI 100 
response at Week 16
4. BI 150 mg (Arm 1) is not different from placebo (Arm 2) with respect to achieving 
an sPGA score of clear (0) at Week 16
5. BI 150 mg (Arm 1) is not different from placebo (Arm 2) with respect to achieving a 
DLQI score of 0 or 1 at Week 16.
For the re-randomized patients, the following null hypothesis will be performed with a type I 
error of 0.05.
∀
Arm A (patients re-randomised to BI 655066) is not different from Arm B (patients 
re-randomised to placebo) with respect to sPGA 0 or 1 response at Week 52.
7.3
PLANNED ANALYSES
The efficacy analyses will be based on the intent-to-treat principle, comprising all participants
who were randomized and received at least one dose during the trial. Misrandomized patients 
are by definition screening failures and therefore are not included in the intended to treat 
population. Efficacy analyses will be based on the planned treatment (i.e., the treatment 
assigned at randomisation); this set of patients is called the Full Analysis Set (FAS). Safety 
analyses will be based on the actual treatment received at the randomisation visit; this set of 
patients is called the Safety Set (SAF).
All efficacy analyses will be conducted on the FAS.  All safety analyses will be conducted on 
the SAF. 
Important violations of the protocol will include key inclusion and exclusion violations, 
incorrect medications taken, compliance with study medication, incorrectly re-randomized or 
not re-randomized, concomitant use of restricted medications, and any other violations of the 
protocol deemed important by the study team. All decisions concerning important protocol 
violations will be made prior to unblinding of the database. A per-protocol set (PPS) will be 
defined excluding patients with violations that affect Week 16 efficacy. A secondary re-
randomized per-protocol set (RRS-PPS) will be defined excluding those patients with 
violations affecting Week 52 efficacy of randomized withdrawal.  The hypothesis tests as 
described in Section 7.2 will be repeated on the PPS or RRS-PPS populations, as appropriate.
7.3.1
Primary endpoint analyses
The achievement of PASI90 at Week 16 is the first co-primary endpoint and is a binary variable 
with values of 0 or 1. The difference in proportion responding between the BI 150 mg arm and 
placebo arm will be estimated and tested using the Cochran-Mantel-Haenszel risk difference 


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estimate stratified by the randomisation factors of weight (C 100 kg vs. >100 kg) and prior 
exposure to TNF antagonists (0 vs. F1) with weights proposed by Greenland & Robins, which 
is calculated as follows:
 =
	

  


	




, where
 = 

 

denotes the risk difference in stratum &, & = 1, ( , )

 =   
 + 
denotes the weight of stratum &, & = 1, ( , )
 denotes the number of patients with event in treatmentin stratum i, & = 1, ( , )
 denotes the number of patients with event in treatment/in stratum i, & = 1, ( , )
 denotes the number of patients on treatmentin stratum i, & = 1, ( , )
 denotes the number of patients on treatment/in stratum i, & = 1, ( , )
The estimated variance of  is calculated as:
012
3 45 =
	
6


(	




)/
where 6 = (  ) 
9 + (  ) 
9
    ( + )/
, & = 1, ( , )
Assuming a normal distribution of  , an approximate 95% CI is given as follows, where 
:;.=>? is the 97.5% quantile of the standard normal distribution:
@A = B ± :;.=>?  D012
3 45E
Also, the approximate p-value can be calculated using the following:
pvalue = 2  Pr
I
J
J
K
L > NN

D012
3 45
NN
O
P
P
Q
, where L ~ S(0, 1)
If there is a stratum for a treatment group that has 0 patients in it, the 0 count will be replaced 
by 0.1 in order to prevent dividing by 0 in the above equations, as suggested in Greenland & 
Robins (R09-1299).  Pairwise comparisons of the BI 150 mg arm and placebo arm will include 
both a p-value and 95% confidence interval. 
The achievement of an sPGA score of clear or almost clear at Week 16 is the second co-
primary endpoint and is a binary variable with values of 0 or 1. The analysis of the sPGA co-
primary endpoint will be identical to that of the PASI90 co-primary endpoint detailed above.
7.3.2
Secondary endpoint analyses
Key Secondary Endpoints:
The achievement of PASI75 at Week 16 is a binary variable with values of 0 or 1. The analysis 
of this endpoint will be identical to that of the PASI90 co-primary endpoint detailed in Section 
7.3.1.
The achievement of PASI100 at Week 16 is a binary variable with values of 0 or 1. The 
analysis of this endpoint will be identical to that of the PASI90 co-primary endpoint detailed in 
Section 7.3.1.


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The achievement of an sPGA score of clear at Week 16 is a binary variable with values of 0 or 
1. The analysis of this endpoint will be identical to that of the PASI90 co-primary endpoint 
detailed in Section 7.3.1.
The achievement of a DLQI score of 0 or 1 at Week 16 is a binary variable with values of 0 or 
1. The analysis of this endpoint will be identical to that of the PASI90 co-primary endpoint 
detailed in Section 7.3.1.
The achievement of an sPGA score of clear or almost clear at Week 52 is a binary variable with 
values of 0 or 1. The analysis of this endpoint will be identical to that of the PASI90 co-primary 
endpoint detailed in Section 7.3.1. Note that this endpoint will only be analysed for patients re-
randomised at Week 28 (i.e., only for Arm A and Arm B defined in Section 7.2).
Other Secondary Endpoints:
All of the other secondary endpoints are binary variables with values of 0 or 1. The analysis of 
these endpoints will be identical to that detailed in Section 7.3.1.
Note that all other secondary endpoints will only be analysed for patients re-randomised at 
Week 28 (i.e., only for Arm A and Arm B defined in Section 7.2).
7.3.3
Further endpoint analyses
Further endpoints will be summarized, with number and proportion of responders for 
dichotomous endpoints and mean, median, SD and IQR presented for continuous variables.
Time to onset of Endpoint, the time to event will be calculated as: 
∀
Time to first onset (with observed event) = [date of first onset] – [date of first active 
treatment] + 1
∀
If a patient never attains Endpoint (e.g., PASI75 or PASI90), then that patient’s time to 
first onset will be censored at the last visit where the Endpoint was measured (e.g., 
PASI).
Time to Loss of Endpoint will only be performed for patients that are re-randomised at Week 
28 (i.e., Arms A and B defined in Section 7.2), where day 0 is defined as the date of the Week 
16 visit.  Time to loss is defined using the following algorithm:
a) Never attains Endpoint (Failure at day 0)
b) After achieving Endpoint, patient will be a failure if they subsequently do not 
achieve Endpoint and either discontinue from the study or switch therapy while 
still not achieving Endpoint. Time to failure will be calculated using date of first 
failure to achieve Endpoint.
c) Patients that take prohibited meds to treat Psoriasis will be counted as failures at 
the time when they first take the prohibited med.
d) Patients that switch therapy while maintaining response will be censored at their 
last measurement prior to switching treatment. A switch from active medication 
to Placebo does not consititute a change in treatment.
e) Patients who maintain Endpoint throughout the study will be censored at their 
last measurement.
Time to Loss of Endpoint (from time of achieving Endpoint or from specific point in time) will 
be defined as above but only for those patients that have achieved Endpoint. 


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All Time to Event endpoints will be presented using Kaplan-Meier curves with comparisons 
made between treatment groups using stratified Log-Rank test. Further information will be 
provided in the TSAP.
7.3.4
Safety analyses  
Adverse events will be coded using the Medical Dictionary for Drug Regulatory Activities 
(MedDRA) coding dictionary. Standard AbbVie summary tables and listings will be produced. 
All adverse events with an onset between start of treatment and end of the residual effect period 
(REP), a period of 15 weeks days after the last dose of trial medication, will be assigned to the 
treatment period for evaluation.
All treated patients will be included in the safety analysis. In general, safety analyses will be 
descriptive in nature and will be based on AbbVie standards. No hypothesis testing is planned.
Statistical analysis and reporting of adverse events will concentrate on treatment-emergent 
adverse events. To this end, all adverse events occurring between start of treatment and end of 
the residual effect period will be considered ‘treatment-emergent’.   Adverse events that start 
before first drug intake and deteriorate under treatment will also be considered as ‘treatment-
emergent’.
Frequency, severity, and causal relationship of adverse events will be tabulated by system organ 
class and preferred term after coding according to the current version of the Medical Dictionary 
for Drug Regulatory Activities (MedDRA).
Laboratory data will be analysed both quantitatively as well as qualitatively. The latter will be 
done via comparison of laboratory data to their reference ranges. Values outside the reference 
range as well as values defined as clinically relevant will be highlighted in the listings. 
Treatment groups will be compared descriptively with regard to distribution parameters as well 
as with regard to frequency and percentage of patients with abnormal values or clinically 
relevant abnormal values.
Vital signs, physical examinations, or other safety-relevant data observed at screening, baseline, 
during the course of the trial and at the end-of-trial evaluation will be assessed with regard to 
possible changes compared to findings before start of treatment.
More information on the analysis of safety will be given in the TSAP.
7.3.5
Pharmacokinetic analyses
Descriptive statistics of BI 655066 concentration measurements by treatment group and visit
will be provided.  
Pharmacokinetic data will be analyzed using population pharmacokinetic approaches. For this 
purpose, data may also be combined with data from other trials.
7.3.6
Pharmacodynamic analysis
No formal analysis of pharmacokinetic-pharmacodynamic relationships is planned. As the data 
from previous trials with BI 655066 suggest a pharmacokinetic (PK)-pharmacodynamic (PD) 


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relationship for efficacy endpoints such as PASI, population PK-PD analyses will be performed. 
For this purpose, data may also be combined with data from other trials. Model-based analyses 
will be planned and documented separately according to internal and external guidelines and 
SOPs. Other exploratory analyses of drug concentration, biomarker or safety data may be 
performed using data obtained as part of this trial. 
All modeling activities will be planned and documented separately according to internal and 
external guidelines and SOP.
7.3.7
Biomarker analyses
Changes in serum protein biomarker levels over time will be described by treatment group. The 
details of these analyses will be included in the TSAP.
7.4
INTERIM ANALYSES
There will not be an interim analysis from a statistical standpoint. An analysis will be 
conducted after the last patient either has been in the study for 52 weeks or discontinues from 
the study. All primary and key secondary endpoints are collected by Week 52; hence no alpha
adjustment is required at this analysis. For this analysis all efficacy endpoints and safety will be 
analysed. The Sponsor will be unblinded to perform this analysis. Blinded treatment 
assignments will not be disseminated to the sites, investigators, and patients until the end of 
study database lock. If needed, more details about this analysis will be specified in the TSAP. 
7.5
HANDLING OF MISSING DATA
Every effort should be made to collect complete data at all visits.
The following rules will be used to impute for missing data:
- For all non-binary endpoints, last observation carried forward (LOCF) will be used to impute 
missing values
- For all binary endpoints (i.e. endpoints that are either 1 (patient responded) or 0 (patient did 
not respond)):
- If no data after that visit*, then impute as failure (NRI [No Response Imputation])
- If data at visits* before and after, only impute as success if both visits are successes; 
else impute as failure
* Patients that take prohibited medications to treat Psoriasis will be treated the same as those 
that discontinued from the trial – i.e. subsequent visits following start of prohibited medication 
will be considered as failure for binary endpoints.
Missing items from the PRO questionnaires will be handled according to the measure 
instructions (Section 10.7). If there is no data for a particular visit, then it will be imputed 
following the same rules as described above.
Sensitivity analyses to assess the robustness of the hypothesis testing results will include the 
following methods where applicable:
∀
LOCF (for binary endpoints)
∀
Logistic regression


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∀
Mixed effect Model Repeat Measurement (MMRM) (for continuous endpoints)
∀
Multiple imputation (for binary endpoints)
Of note, for randomized withdrawal analyses, subjects who received retreatment will be 
counted as non-responders in all visits after the date of retreatment.
7.6
RANDOMISATION
At Visit 2, patients will be randomized in blocks to double-blind treatment to either BI 655066 
150 mg or placebo in a 4:1 ratio. Randomisation will be stratified with respect to weight (C 100 
kg vs. >100 kg) and prior exposure to TNF antagonists (0 vs. F1).
At week 28, patients will be separated into “responder” and “non-responder” groups. A patient 
will be considered as a “responder” if the week 28 sPGA is clear or almost clear (0 or 1); 
otherwise the patient will be considered a “non-responder”. 
Among responders, patients originally randomized to BI 655066 150 mg (Arm 1) will be re-
randomized in a 1:2 ratio to either 150 mg of BI 655066 or placebo in a second double-blinded 
portion (Part B) of the trial. Re-randomisation will be stratified by weight (C 100 kg vs. >100 
kg) and prior exposure to TNF antagonists (0 vs. F1). Patients originally randomized to 
placebo (Arm 2) will continue to receive blinded study drug every 12 weeks in Part B of the 
trial, to maintain the blind to the original randomized treatment arm. 
Regardless of originally randomized treatment group, non-responders will receive open label BI 
655066 every 12 weeks, starting at Week 28, for the remainder of the trial. BI will arrange for 
the randomisation and the packaging and labelling of trial medication. The randomisation lists
will be generated using a validated system, which involves a pseudo-random number generator 
so that the resulting treatment will be both reproducible and non-predictable. The block sizes
will be documented in the Clinical Trial Report (CTR). Access to the codes will be controlled 
and documented.
7.7
DETERMINATION OF SAMPLE SIZE
This study is designed to show a difference between BI 655066 and placebo in terms of PASI90
response and sPGA scores of clear or almost clear at Week 16. However, this study was also 
powered to show a difference in sPGA response at Week 52 between the patients randomized to 
continue on BI 655066 vs. patients randomized to placebo at Week 28.
Based on the interim results from 1311.2 (c03272682-01), it is assumed at most 10% of the 
patients in the re-randomized BI 655066 arm will lose sPGA response of clear or almost clear 
(0 or 1) at Week 52 whereas approximately 25% of patients in the re-randomized placebo arm 
will lose response. Using a 1:2 re-randomisation scheme (BI 655066:placebo), 102 patients in 
the BI 655066 arm and 204 patients in the placebo arm will provide at least 90% power to 
detect the difference in sPGA response rate at Week 52. Assuming that 80% of patients on BI 
655066 at baseline will achieve sPGA of clear or almost clear at Week 28, the total sample size 
required for the initial BI 655066 arm at Visit 2 is (102)(3)÷0.8=383. See Table 7.7:1 for more
sample size calculations to have at least 90% power.  


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Table 7.7:1 Sample sizes for randomized withdrawal comparison 
Response Rate at Week 52 
Randomisation ratio at 
Week 28  
active:placebo = Total N 
Total N at 
randomisation
Active
Placebo
Delta
1:2
90%
72.5%
17.5%
79:158 = 237
297
90%
75%
15%
102:204 = 306
383
90%
77.5%
12.5%
138:276 = 414
518
               Calculated using ADDPLAN Version 6.0.4.
Thus 400 patients in the original BI 655066 arm, provide at least 90% power for the 
randomized withdrawal comparison. Using a 4:1 randomisation will yield a total sample size of 
500 = 400:100 for BI 655066: placebo.
Based on the outcome from trials 1311.1 and 1311.2, the PASI90 response rate at Week 16 is 
assumed to be at least 65% in the BI 655066 arm and approximately 5% for placebo. For sPGA 
clear or almost clear at Week 16, the response rate for the BI 655066 arm is assumed to be at 
least 80% and approximately 5% for placebo. This trial will have >99% power for comparing 
each BI 655066 arm to placebo on both of these endpoints.
All calculations were performed using ADDPLAN Version 6.0.4, an Aptiv Solutions Company.


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8.0
INFORMED CONSENT, DATA PROTECTION, TRIAL
RECORDS
The trial will be carried out in compliance with the protocol, the ethical principles laid down in 
the Declaration of Helsinki, in accordance with the ICH Harmonized Tripartite Guideline for 
Good Clinical Practice (GCP), relevant BI Standard Operating Procedures (SOPs), the EU 
regulation 536/2014, the Japanese GCP regulations (Ministry of Health and Welfare Ordinance 
No. 28, March 27, 1997) and other relevant regulations.
The Investigator will inform the Sponsor immediately of any urgent safety measures taken to 
protect the trial patients against any immediate hazard, and also of any serious breaches of the 
protocol or of 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 finalization 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.
Standard medical care (prophylactic, diagnostic and therapeutic procedures) remains in the 
responsibility of the treating physician of the patient.
8.1
TRIAL 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 following paragraph pertains to Japan only:
The Investigator must give a full explanation to trial patients including the items listed below in 
association with the use of the patient information form, which is prepared avoiding the use of 
technical terms and expressions. The patient is given sufficient time to consider participation in 
the trial. The Investigator obtains written consent of the patient’s own free will with the 
informed consent form after confirming that the patient understands the contents. The 
Investigator must sign (or place a seal on) and date the informed consent form. If a trial 
collaborator has given a supplementary explanation, the trial collaborator also signs (or places a 
seal on) and dates the informed consent.
Re-consenting may become necessary when new relevant information becomes available and 
should be conducted according to the sponsor’s instructions.


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8.2
DATA QUALITY ASSURANCE
A quality assurance audit/inspection of this trial may be conducted by the Sponsor, Sponsor’s 
designees, or by IRB / IEC or by regulatory authorities. The quality assurance 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 via remote 
data capture. See Section 4.1.5.2 for rules about emergency code breaks. 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 reported on the CRF must be consistent with the source data or the discrepancies must be 
explained. The Investigator may need to request previous medical records or transfer records, 
depending on the trial; current medical records must also be available. For eCRFs all data must 
be derived from source documents.
8.3.2
Direct access to source data and documents
An adaptive approach to clinical trial monitoring will be utilised. This is initiated by an 
assessment of the risk associated with the trial combined with identification of critical data and 
processes. An Integrated Quality and Risk Management Plan documents the strategies involved 
with the implementation of onsite, offsite and central monitoring activities in order to direct 
focus to the areas of greatest risk which have the most potential impact to patient safety and 
data quality. Trial oversight is achieved by regular review of a report of risk, which then 
influences any monitoring adaptations.
The Investigator / institution will permit trial-related monitoring, audits, IRB / IEC review and 
regulatory inspection, providing direct access to all related source data / documents. eCRF 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. FDA). The Clinical Research Associate (CRA) / on site 
monitor and auditor may review all eCRF, and written informed consents. 
8.3.3
Storage period of records (Applicable to Japan only)
Trial site(s):
The trial site(s) must retain the source documents and essential documents for a period defined 
by the Japanese GCP regulation and trial site’s contract with the sponsor.
Sponsor:
The Sponsor must retain the essential documents according to the Sponsor’s SOPs.
When it is no longer necessary for the trial site to retain the source documents and essential 
documents, the Sponsor must notify the head of trial site.


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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 study drug BI 655066, this is the current version of the Investigator’s Brochure 
(c01569420-06), which is provided in the ISF.
No AEs are classified as listed for matching placebo, trial design, or invasive procedures 
8.4.2
Expedited reporting to health authorities and IEC / IRB
Expedited reporting of serious adverse events, e.g. suspected unexpected serious adverse 
reactions (SUSAR) to health authorities and IEC / IRB, will be done according to local 
regulatory requirements.
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.
8.6 
END OF TRIAL
The end of the trial is defined as written in Section 6.2.3.
The IEC / competent authority in each participating EU member state will be notified about the 
end or early termination of the trial.
For Japan: When the trial is completed, the Investigator should inform the head of the trial site 
of the completion in writing, and the head of the trial site should promptly inform the IRB and 
Sponsor of the completion in writing.
8.7
PROTOCOL VIOLATIONS 
This Section is applicable to Japan only
The investigator should document any deviation from the protocol regardless of their reasons. 
Only when the protocol was not followed in order to avoid an immediate hazard to trial patients 
or for other medically compelling reason, the principal investigator should prepare and submit 
the records explaining the reasons thereof to the sponsor, and retain a copy of the records.


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8.8
COMPENSATION AVAILABLE TO THE PATIENT IN THE EVENT OF 
TRIAL RELATED INJURY
This Section is applicable to Japan only
In the event of health injury associated with this trial, the Sponsor is responsible for 
compensation based on the contract signed by the trial site.


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9.0
REFERENCES
9.1 
PUBLISHED REFERENCES
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.
R09-1299 
Greenland S, Robins M. Estimation of a common effect parameter from
sparse follow-up data, Biometrics 41, 55-68, 1985
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.
R11-1547
Smith RLI, Warren RB, Eyre S, Ho P, Ke X, Young HS, Griffiths CEM,  
Worthington J. Polymorphisms in the IL-12beta and IL-23R genes are 
associated with psoriasis of early onset in a UK cohort. J Invest Dermatol 2008. 
128:1325-1327.
R13-3515
Woodworth T, Furst DE, Alten R, Bingham C, Yocum D, Sloan V, Tsuji W, 
Stevens R, Fries J, Witter J, Johnson K, Lassere M, Brooks P. Standardizing 
assessment and reporting of adverse effects in rheumatology clinical trials II: the 
Rheumatology Common Toxicity Criteria v.2.0. J Rheumatol 2007. 34(6):1401-
1414.
R14-5159
Reich K, Puig L, Paul C, Kragballe K, Luger T, Lambert J, Chimenti S, 
Girolomoni G, Nicolas JF, Rizova E, Brunori M, Mistry S, Bergmans P, Barker 
J, TRANSIT Investigators. One-year safety and efficacy of ustekinumab and 
results of dose adjustment after switching from inadequate methotrexate 
treatment: the TRANSIT randomized trial in moderate-to-severe plaque 
psoriasis. Br J Dermatol 2014. 170(2):435-444.
R15-1001 
Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H; 
CASPAR Study Group. Classification criteria for psoriatic arthritis: 
development of new criteria from a large international study. Arthritis Rheum 
2006;54:2665-73.
R15-1393
Davidovici BB, Sattar N, Joerg PC, Puig L, Emery P, Barker JN, Kerkhof P van 
de, Stahle M, Nestle FO, Girolomoni G, Krueger JG, Psoriasis Education and 
Learning Syllabus (PEARLS). Psoriasis and systemic inflammatory diseases: 
potential mechanistic links between skin disease and co-morbid conditions. J 
Invest Dermatol 2010. 130(7):1785-1796.


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R15-3846
Bruce B, Fries JF. The Stanford Health Assessment Questionnaire: a review of 
its history, issues, progress, and documentation. J Rheumatol 2003. 30(1):167-
178.
R15-3849
The Health Assessment Questionnaire (HAQ) and the improved HAQ (formerly 
called the PROMIS HAQ) (revised June 2009). 
http://aramis.stanford.edu/downloads/HAQ%20Instructions%20(ARAMIS)%20
6-30-09.pdf (access date: 15 July 2015) ; Stanford: Stanford University School 
of Medicine, Division of Immunology & Rheumatology 2009
R15-5200
Langley RGB, Feldman SR, Nyirady J, Kerkhof P van de, Papavassilis C. The 5-
point Investigator's Global Assessment (IGA) scale: a modified tool for 
evaluating plaque psoriasis severity in clinical trials. J Dermatol Treat 2015. 
26(1):23-31.
R15-5488 
Khader SA, Pearl JE, Sakamoto K, Gilmartin L, Bell GK, Jelley-Gibbs DM, et 
al. IL-23 compensates for the absence of IL-12p70 and is essential for the IL-17 
response during tuberculosis but is dispensable for protection and antigen-
specific IFN-y responses if IL-12p70 is available.  J of Immunol 2005; 175:788-
795.
R15-5495 
O’Garra A, Redford PS, McNab FW, Bloom CI, Wilkinson RJ, Berry MPR. The 
immune response in tuberculosis. Annu Rev Immunol 2013; 31:475-527.
R15-5497 
Tsai TF, Blauvelt A, Gong Y, Huang J, Fox T. Secukinumab treatment shows no 
evidence for reactivation of previous or latent TB infection in subjects with 
psoriasis: A pooled phase 3 safety analysis. J Am Acad Dermatol 2015; 607.
R16-2653 
Tuong W, Armstrong AW. Scalp Psoriasis: Clinical Features and Assessment, 
In: Adebajo A, Boehncke WH, Gladman DD, Mease PJ, editors. Psoriatic 
Arthritis and Psoriasis: Pathology and Clinical Aspects. Cham: Springer, 139 –
141 (2016)
R16-2654
Rich P, Scher RK. Nail Psoriasis Severity Index: A useful tool evaluation of nail 
psoriasis. J AM Acad Dermatol 49 (2), 206 – 212 (2003)
R96-3541 
Fredriksson T, Pettersson U. Severe psoriasis - oral therapy with a new retinoid. 
Dermatologica 1978; 157:238-244.
9.2
UNPUBLISHED REFERENCES
c01569420-06 Investigator’s Brochure BI 655066, Psoriasis, Crohn’s Disease, Ankylosing 
Spondylitis,   Asthma, Psoriatic Arthritis
1311.P1/1311.P2/1311.P3/1311.P4/1311.P5
c03272682-01 Summary report of interim analysis at Week 48, Trial 1311.2. 05 May 2015


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c02434648-01 Dorleacq, N., Steimle-Goerttler, C., Bai, X., Joseph, D. Safety, tolerability,
efficacy, pharmacokinetics, and pharmacodynamics of single rising i.v.
(Stage 1) and s.c. (Stage 2) doses of BI 655066 in male and female patients
with moderate to severe psoriasis (randomised, double-blind, placebo controlled
within dose groups). Clinical Trial Report.


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10
APPENDICES
10.1
PASI DEFINITIONS AND USE 
The PASI is an established measure of clinical efficacy for psoriasis medications. (R96-3541)
The PASI is a tool that provides a numeric scoring for patients overall psoriasis disease state, 
ranging from 0 to 72. It is a linear combination of percent of surface area of skin that is affected 
and the severity of erythema, infiltration, and desquamation over four body regions. 
The endpoints used are based on the percent reduction from baseline, generally summarized as 
a dichotomous outcome based on achieving over an X% reduction (or PASIX), where X is 50, 
75, 90 and 100.
To calculate the PASI, 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 GLOBAL ASSESSMENT (SPGA)
The sPGA is a 5 point score ranging from 0 to 4, based on the physician’s assessment of the 
average thickness, erythema, and scaling of all psoriatic lesions (R15-5200).
The assessment is considered “static”, which refers to the patients disease state at the time of 
the assessments, without comparison to any of the patient’s previous disease states, whether at 
Baseline or at a previous visit.
A lower score indicates less body coverage, with 0 being clear and 1 being almost clear. 
Erythema
0
Normal (post-inflammatory hyper/hypopigmentation may be present)
1
Faint, diffuse pink or slight red coloration 
2
Mild (light red coloration)
3
Definite red coloration (Dull to bright red)
4
Bright to Deep red coloration of lesions
Induration (plaque elevation)
0
None
1
Just detectable (slight elevation above normal skin) 
2
Mild thickening (slight but definite elevation, typically edges are indistinct or 
sloped)
3
Clearly distinguishable to moderate thickening (marked definite elevation with 
rough or sloped edges)
4
Severe thickening with hard edges (marked elevation typically with hard or sharp 
edges)
Scaling
0
No scaling
1
Minimal focal scaling (surface dryness with some desquamation)
2
Predominately fine scaling (fine scale partially or mostly covering lesions)
3
Moderate scaling (coarser scale covering most or all of the lesions)
4
Severe /coarse scaling covering almost all or all lesions (coarse, non-tenacious scale 
predominates)
Scoring:
Clear 
0 = 0 for all three 
Almost clear 1 = mean >0, <1.5
Mild
2 = mean >= 1.5, <2.5
Moderate 
3 = mean >= 2.5, <3.5
Severe
4 = mean >= 3.5


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sPGA Rating Scale for Overall Psoriatic Disease
Score
Short description
Detailed description
0
clear
No signs of psoriasis.  Post-inflammatory 
hyper/hypopigmentation may be present
1
Almost clear
Normal to pink coloration;
Just detectable (possible slight elevation above normal 
skin)
No to minimal focal scaling
2
mild
  Pink to light red coloration
  Mild thickening (slight but definite elevation, typically 
edges  are indistinct or sloped)
Predominantly fine scaling
3
moderate
Dull to bright red coloration
Clearly distinguishable to moderate thickening
Moderate scaling
4
severe
Bright to deep dark red coloration;
Severe thickening with hard edges
Severe coarse scaling covering almost all or all lesions
The scale used was static, i.e., it referred exclusively to the patient’s disease
state at the time of the assessments, without comparison to any of the patient’s previous
disease states, whether at Baseline or at a previous visit.


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10.3
NAPSI – NAIL PSORIASIS SEVERITY INDEX
The NAPSI assesses how much of the fingernail is affected with psoriasis with scores ranging 
from 0 to 80. (R16-2654)
If a patient has nail psoriasis, the physician will assess the nail psoriasis at each protocol 
defined time point. Fingers (5) on each hand will be individually examined for two distinct 
assessments and are graded as follows:
Nail Matrix Assessment:
0 = None
1 = present in 1 quadrant of nail
2 = present in 2 quadrants of nail
3 = present in 3 quadrants of nail
4 = present in 4 quadrants of nail
Nail Bed Assessment:
0 = None
1 = present in 1 quadrant of nail
2 = present in 2 quadrants of nail
3 = present in 3 quadrants of nail
4 = present in 4 quadrants of nail
The sum of the scores will be added resulting a range of 0 to 80. If an individual finger 
assessment is missing (not done), the average of the remaining measured digits will be imputed 
and added to the sum. If < 50% of the finger assessments are missing the imputation will be 
performed. If more than 50% of the assessments are missing then the sum of the scores will be 
left as missing.


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10.4 
PPASI – PALMOPLANTAR PSORIASIS SEVERITY INDEX
The PPASI provides a numeric scoring for psoriasis affecting the hands and feet with scores 
ranging from 0 to 72. It is a linear combination of percent of surface area of hands and feet that 
are affected and the severity of erythema, induration, and desquamation. 
If a patient has palmoplantar psoriasis, the physician will assess the psoriasis at each protocol 
defined time point. Both palms and soles on each hand and foot will be individually assessed 
for erythema, induration, desquamation and percentage of area affected as follows:
Erythema, Induration and Desquamation:
0 = None
1 = Slight
2 = Moderate
3 = Severe
4 = Very Severe
Percent of Palm and Sole Area Covered:
0 = Clear
1 = <10%
2 = 10-29%
3 = 30-49%
4 = 50-69%
5= 70-89%
6= 90-100%
The PPASI is a composite score and will be computed for each palm and sole, left and right and 
is derived from the sum of the scores for erythema (E), induration (I) and desquamation (D) 
multiplied by the score recorded for the extent of palm and sole area involved. PPASI is 
calculated as follows: (sum of scores for E+I+D)*Area *0.2(location: right palm) + (sum of 
scores for E+I+D)*Area *0.2(location: left palm) + (sum of scores for E+I+D)*Area 
*0.3(location: right sole) + (sum of scores for E+I+D)*Area *0.3(location: left sole). The range 
is 0 to 72.


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10.5
PSORIASIS SCALP SEVERITY INDEX (PSSI)
If a patient has scalp psoriasis, the physician will assess the erythema (redness), induration 
(hardness), desquamation (shedding of skin) and percent of scalp covered at each protocol 
defined time point. (R16-2653).
Erythema, Induration and Desquamation:
0 = None
1 = Slight
2 = Moderate
3 = Severe
4 = Very Severe
Percent of Scalp Covered:
1 = <10%
2 = 10-29%
3 = 30-49%
4 = 50-69%
5 = 70-89%
6 = 90-100%
The PSSI is a composite score derived from the sum of the scores for erythema, induration and 
desquamation multiplied by the score recorded for the extent of scalp area involved. The range 
is 0 to 72.


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10.6
DIAGNOSIS AND ASSESSMENTS FOR PATIENTS WITH PSORIATIC 
ARTHRITIS (AT SELECTED SITES ONLY)
At Visit 1 at selected study sites, patients with a positive history of PsA or suspected to have 
PsA will be further evaluated for PsA diagnosis based on CASPAR (ClASsification of Psoriatic 
Arthritis) criteria (R15-1001).
To be classified has having PsA, a patient must have inflammatory articular disease (joint, 
spine, or entheseal) with at least 3 points total from the 5 categories in Table 10.6: 1, All trial 
participants will have 2 points assigned due to evidence of current psoriasis per trial entry 
criteria and will require at least one additional point for diagnosis of PsA.
Table 10.6:1
CASPAR criteria
Category
Point assignment
Evidence of current psoriasis, a personal history of psoriasis, or a 
family history of psoriasis
2 points
Typical psoriatic nail dystrophy, including onycholysis, pitting, or 
hyperkeratosis observed on current physical examination
1 point
A negative test result for rheumatoid factor by any method except
latex
1 point
Either current dactylitis, defined as swelling of an entire digit, or a 
history of dactylitis recorded by a rheumatologist
1 point
Radiographic evidence of juxta-articular new bone formation 
appearing as ill-defined ossification near joint margins (but excluding 
osteophyte formation) on plain radiographs of the hand or foot
1 point
If a diagnosis of PsA is confirmed by CASPAR and the patient meets all study entry criteria 
for participation, the following will be performed at Visit 2.
∀
HAQ-DI (see Appendix 10.7.2)
∀
Pain VAS (see Appendix 10.7.3)
∀
Patient global assessment VAS (see Appendix 10.7.4)
∀
Tender or Swollen joint counts (TJC/SJC) on 28 joints (refer to Table 10.6: 2)
∀
Entry of data for calculation of DAS28 on electronic device (Refer to Appendix 10.6.1)
During the treatment period and EOO the following will continue to be performed at the visits 
noted in the Flow Charts if the TJC/SJC is ≥3 at Visit 2.
∀
HAQ-DI (see Appendix 10.7.2)
∀
Pain VAS (see Appendix 10.7.3)
∀
Patient global assessment VAS (see Appendix 10.7.4)
∀
Tender or Swollen joint counts (TJC/SJC) on 28 joints (refer to Table 10.6: 2)
∀
Entry of data for calculation of DAS28 on electronic device (Refer to Appendix 10.6.1)


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Table 10.6:2 Tender or Swollen Joint Count (28)
Joint
Right
Left
Tender
Swollen
Tender
Swollen
Shoulder
Elbow
Wrist
MCP1
MCP2
MCP3
MCP4
MCP5
IP of the thumb
PIP of fingers 2
PIP of fingers 3
PIP of fingers 4
PIP of fingers 5
Knee
Metacarpal-phalangeal joints (MCP); Interphalangeal joints (IP); Proximal interphalangeal 
joints (PIP)
Tenderness and swelling will be evaluated as “0” absent or “1” present.  
10.6.1
Disease Activity Score in 28 Joints (DAS 28)
DAS28, which stands for "disease activity score," is a modified version of the original DAS. 
DAS28 will be calculated using a formula that includes the number of tender joints and swollen 
joints (28 joints), CRP (C-reactive protein) and a patient self-assessment (patient global health-
VAS).
DAS 28 will be calculated using the following formula from the electronic device where the 
VAS pertains to the patient’s global assessment of disease VAS:
∀
DAS28=0.56*√(tender joint count) + 0.28*√(swollen joint count) + 
0.36*Ln(CRP+1) + 0.014* (patient global assessment VAS) + 0.96
For the DAS 28 calculation, the CRP value from laboratory report of current visit will be 
entered on the electronic device.  Data from swollen and tender joint count (28 joints) and the 
patient global assessment VAS will have already been recorded on the electronic device.


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10.7
HEALTH OUTCOMES/QUALITY OF LIFE
10.7.1
Dermatology Life Quality Index
The DLQI is a patient-administered, ten-question, quality of life questionnaire that covers six
domains including symptoms and feelings, daily activities, leisure, work and school, personal 
relationships and treatment (R05-2548). The DLQI has a one-week recall period. 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 self-administered by the patient at visits indicated in the flowchart. 
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 patient’s life, 2-5 = small effect, 6-10 = moderate effect, 11-20 = 
very large effect, and 21-30 = extremely large effect on patient’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.


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10.7.2
Health Assessment Questionnaire Disability Index (HAQ-DI)
The HAQ-DI will be self-administered by the patient [for psoriatic arthritis patients at selected 
sites] at visits indicated in the flowchart.
The HAQ-DI is a twenty-item patient reported outcome instrument that assesses current 
physical function/ disability. The HAQ-DI covers eight categories (dressing and grooming, 
hygiene, arising, reach, eating, grip, walking and common daily activities). There are four 
response options, ranging from 0 (no difficulty) to 3 (unable to do). HAQ-DI score is reported 
as a mean score between 0 and 3 by dividing the total score by the number of items answered 
(R15-3849).
The HAQ-DI has been the most-widely used instrument to assess physical function clinical 
trials of treatments for rheumatoid and psoriatic arthritis and has extensive evidence of its 
validity and other psychometric properties in this context (R15-3846).


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10.7.3
Pain VAS
The Pain VAS will be self-administered by the patient [for psoriatic arthritis patients at 
selected sites] at visits indicated in the flowchart.
The patient’s assessment of pain will be performed using a horizontal 15cm visual analog 
scale (VAS), ranging from 0 (no pain) to 100 (severe pain) after the question:
“How much pain have you had because of your psoriatic arthritis in the past week? Place a 
vertical (│) mark on the line to indicate the severity of the pain.” 
10.7.4
Patient global assessment VAS
The patient global assessment VAS will be self-administered by the patient [for psoriatic 
arthritis patients at selected sites] at visits indicated in the flowchart.
The patient’s global assessment of disease activity will be performed using a horizontal 15cm 
VAS, ranging from 0 (very well) to 100 (very poor) after the question:
“Considering all the ways your psoriatic arthritis affects you, how would you rate the way 
you felt over the past week? Place a vertical (│) mark on the line to indicate how you felt.”


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11.
DESCRIPTION OF GLOBAL AMENDMENTS
Number of global amendment
1.0
Date of CTP revision
11-Mar-2016
EudraCT number
2014-005102-38
BI Trial number
1311.4
BI Investigational Product(s)
BI 655066
Title of protocol
BI 655066 (risankizumab) versus placebo In a 
Multicenter randomized double-blind study in 
patients with Moderate to severe chronic plaque 
psoriasis evaluating the efficacy and safety with 
randomized withdrawal and re-treatment 
(IMMhance)
To be implemented only after 
approval of the IRB / IEC /
Competent Authorities
X
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 
1. Added Infection Testing (TB) to Screening. 
2. Footnote #23 added for clarification to TB. 
3.ADA sampling added to Week 4
4. Footnote #5, Visit 28 corrected to Week 28
5. Footnote #17, Visit 32 and Visit 70 corrected to 
    Week 32 and Week 70
6.Text regarding hypersensitivity 
removed
      from Footnote #13 and placed accordingly in a
    new footnote #24 
7. Line item “biologic therapy history” 
changed to “psoriasis therapy history
8. Footnote #22 was re-worded


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9. % BSA involvement added as a line 
item 
Rationale for change
1.Request from Health Authorities
2. Request from Health Authorities
3. Request from Health Authorities
4. Error in original CTP
5. Error in original CTP
6. Clarification
7. Clarification
8. Clarification
9. % BSA is collected on the electronic device at 
screening and prior to randomization as an 
inclusion criteria
Section To be changed
All Flow Charts
Description of change
1. Footnote #6
The criterion for missing more than 1 study 
treatment was removed from the completer 
definition for entry into the OLE study.
“Patients who have completed the study (which is 
defined as patients completing the EOO visit 
within the specified window per the flow charts.)  
and who also meet the eligibility criteria will be 
offered to roll over into an open label extension 
(OLE) trial.
2. Footnote #7-
PK and ADA samples are to be taken within 60 
minutes before the subcutaneous injection
3. Footnote #3
Re-written as well as DLQI removed from flow 
chart 2 and 3 footnote 3
Rationale for change
1. Clarification
2. Clarification
3. DLQI not needed for flow Chart #2 and Flow 
Chart #3. Also footnote as originally written was 
redundant
Section to be changed
Flow Charts 2 and 3 ( Footnote #10) 
Description of change
Vital Status information:  patients must follow 
their current flow chart for ‘planned EOO”)
Rational for change
Clarification for relapsed and re-treated patients 
with respect to Vital Status as they follow Flow 


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Charts 2 and 3 which do not have an EOO at 104 
weeks.
Section to be changed
Flow Chart #2 and Flow Chart #3
Description of change
Removed DLQI from Footnote #3
Rationale for change
Error in original CTP footnote
Section to be changed
Section 2.3-Benefit Risk Assessment
Description of change
Provided justification for not treating latent TB
Rationale for change
Due to update of Exclusion #6 for TB
Section to be changed
Section 3.1.2-Data Monitoring
Description of change
Clarification on how efficacy data will be used 
upon submission to the DMC as well as additional 
information on unblinding
Rationale for change
Clarification
Section to be changed
Section 3.1.3, MACE Adjudication Committee
Description of change
Added “thrombotic events” 
Rationale for change
Clarification
Section to be changed
Section 3.3.3- Exclusion Criteria #6
Description of change
Updated exclusion criteria to clarify latent TB and 
treatment for TB. ”Patients with a positive test 
result may participate in the study if further work 
up (according to local practice/guidelines) 
establishes conclusively that the patient has no 
evidence of active tuberculosis. If presence of
latent tuberculosis is established, patients who are 
at low risk of reactivation, defined by local 
guidelines and investigator judgment, do not need 
to be treated with prophylactic anti-tuberculosis 
prior to or during the trial”.
Rationale for change
Due to inclusion of TB testing at Screening
Section to be changed
Section 3.3.4.1, Removal of Individual Patients
Description of change
1.Patients discontinuing treatment early should 
remain in the study


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2. Updated Vital Status to clarify that EOO is the 
current applicable flow chart
Rationale for change
1. When possible patients should continue with 
remaining visits
2. To clarify and distinguish relapse and re-treated 
patients following flow charts #2 and #3
Section to be changed
Section 4.1.4, Drug assignment and administration
Description of change
Added additional areas and wording for 
subcutaneous injection “(gluteal and upper arms) 
as well as contralateral to PK/ADA sampling”
Rationale for change
Omitted from original CTP
Section to be changed
Table 4.2.2.1:1, restricted medications
Description of change
1.Added the following medications tofacitinib 
(Xeljanz®), apremilast (Otezla®)
2. Removed efalizumab (Raptiva®)  
Rational for Change
1.Additional medications requiring washout
2. Medication not available
Section to be changed
Section 5.1.3-Further Endpoints
Description of change
Added “absolute PASI of <3 at all visits collected
Rationale for change
Change to CTP
Section to be changed
Laboratory Table 5.3.3:1
Description of Change 
The requirement for TB at screening was added to 
the Infection Testing category and footnote #3
Rationale for change
Request from Health Authorities
Section to be changed
Section 6.2, Details of Trial Procedures
Description of change
  Added a paragraph for TB testing: “Patients will 
be tested for TB (Quantiferon or PPD) at 
Screening, Week 52 and EOO. Patients who test 
positive and are at low risk of TB reactivation, per 
local guidelines and investigator judgment, do not 
need to be treated with prophylactic anti-
tuberculosis medication and can be entered or 
continue in the trial”. 
Rational for change
New screening procedure and information on 


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treatment upon testing positive.
Section to be changed
Section 6.2.1, Screening period
Description of change
The maximum of 2 visits that a patient may need 
for screening was deleted
Rationale for change
Patients may require more than 2 visits to the clinic 
during screening
Section to be changed
Section 6.2.3, Follow-up Period and Trial 
Completion
Description of change
1.Vital status- patients must follow their current 
flow chart for EOO
2. Removed criteria for missing one dose for 
eligibility for OLE study
3.Patients discontinuing treatment early should 
continue in the study
Rationale for change
1.Clarification for relapse and re-treated patients 
following FC#2 and FC#3
2. Clarification
3. Added for Clarification
Section for change
Section 7.2 Null and Alternative Hypothesis
Description of change
Separated out re-randomized hypothesis from 
hypotheses tested on all randomized patients
Rationale for change
The re-randomized portion of the trial can be 
treated as a separate study and thus tested with its 
own alpha = 0.05.
Section for change
Section 7.3-  Planned Analysis
Description of change
1.Clarifying the definition of analysis sets
2. deleted wording that IPV’s would be provided in 
TSAP and added verbiage about IPVs and PPS 
sensitivity analyses
3. Added “The hypothesis tests as described in 
Section 7.2 will be repeated on the PPS or RRS-
PPS populations, as appropriate".  
Rationale for change
In response to questions from Health Authorities. 
Section for change
Section 7.4-Interim analysis
Description of change
Removal of DMC information


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Rationale for change
Redundant as included in DMC section
Section for change
Section 7.5 Handling of Missing data
Description of change
Removed sentence that additional information may 
be included in TSAP and added information 
pertaining to the sensitivities analyses that will be 
done
Rationale for change
Provide as much information concerning primary 
and secondary endpoints to be pre-defined in the 
protocol.
Section to be changed
Appendix 10.6
Description of change
Order of PsA assessments changed at Visit 2
Rationale for change
To match order of assessments on the electronic 
device and due to requirement to perform joint 
counts last
Section for change
Section 1.2, Drug Profile, Listedness Section 8.4.1, 
and Unpublished Reference Section 9.2
Description of change
Document ID for the new version of the 
Investigator Brochure has changed to “c01569420-
06”
Rationale for change
Updated Document ID
Section for change
Published Reference Section 9.1
Description of change
Three references added,R15-5488, R15-5495, R15-
5497
Rationale for change
Due to addition information added to Section 2.3
Section for change
Pages 1,2 Title pages 
Description of change
Added risankizumab after BI 655066
Rationale for change
New name added for completeness


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Number of global amendment
2.0
Date of CTP revision
28-Jul-2016
EudraCT number
2014-005102-38
BI Trial number
1311.4
BI Investigational Product(s)
BI 655066 (risankizumab)
Title of protocol
BI 655066 (risankizumab) versus placebo In a 
Multicenter randomized double-blind study in 
patients with Moderate to severe chronic plaque 
psoriasis evaluating the efficacy and safety with 
randomized withdrawal and re-treatment 
(IMMhance)
To be implemented only after 
approval of the IRB / IEC / 
Competent Authorities
X
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 and Synopsis
Description of change
Added (risankizumab) to BI investigational product 
on title page and to active ingredient section in 
Synopsis
Rationale for change
New name added for completeness
Section To be changed
Throughout document
Description of change
The following abbreviations are now spelled out due 
to first use in the text: ECG (synopsis); RDC 
(5.3.6.1); PPD (3.3.3); VEGF (5.5.1);ULN (5.3.6.1); 
GRAPPA (6.2); NRI, LOCF, MMRM (7.5); CTR 
(7.6); CTP (flowchart #1 footnote 6)
Rationale for change
Omitted from original CTP
Section to be changed
All Flow Charts
Description of Change 
a. Added to footnote #6  “ who have not discontinued 
drug prematurely” 
b. Revision to footnote #24 on FC #1, footnote #12 
on FC #2 and footnote #11 on FC #3,   “Patients 


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should be closely monitored for signs and symptoms 
of hypersensitivity reactions for approximately 2 
hours after the last injection at Visit 2 and for 
approximately one hour after the last injection at all 
other visits where drug is administered
Rationale for change
a. Additional criteria for a study completer  and entry 
into OLE study
b. Provide additional details of monitoring 
hypersensitivity with respect to injection times
Section To be changed
Flow Chart 1
Description of change
Added to Footnote #15
“Patients that terminate trial medication early should 
remain in the trial and complete all remaining 
Treatment Period visits and, FU1 and FU2 Visits.   
Termination of trial medication eCRF should be 
completed and end of study registered as a non-
completer in IRT. Refer to Section 6.2.3 for details 
and further instruction if patient cannot or will not 
continue in the trial. 
Rationale for change
Additional clarification needed for proper procedure 
when a patient discontinues treatment but remains in 
the study
Section to be changed
Flow Chart #1
Description of change
Added the following to Footnote #13 “(after last 
injection)”
Rationale for change
To clarify when vitals post dose are expected at 
Visits 2 and 3
Section to be changed
Abbreviations
Description of change
Added the following abbreviations: aPTT, CRO, 
PPD, RCTC, Nab, NGAL, VEGF, TJC/SJC, 
GRAPPA, CRP, PPS, RBC, RRS-PPS, NRI, 
MMRM, AP, BUN, CK, CK-MB, eGFR, GGT, Hb, 
Hct, HDL, LDL, TSH, INR, RDC
Abbreviation PoC corrected to PoCC
Abbreviation OPU corrected to “Operative”
Rationale for change
Omitted from original or CTP V 2.0
Section to be changed
Table of Contents
Description of change
Formatting update to title of sections  5.3.5.1, 5.4.2.1, 
5.4.2.2, 5.5.1.2 and 7.3.7 in order to show in the table 
of contents
Rationale for change
Formatting error in original CTP
Section to be changed
Section 3.1- Overall Trial Design and Plan
Description of change
Section re-written and Figure 3.1:1 was replaced with 
new trial design.  In summary:    At the Week 28 
visit, all patients will be assessed for responsiveness. 
Patients not meeting the protocol defined response 
criteria (sPGA is ≥ 2) (Week 28 non-responders), 
will receive open label BI 655066 150 mg from 


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Week 28 until the end of the treatment period (Week 
88), regardless of originally randomized treatment 
arm.  Patients who meet the protocol defined 
responder criteria (sPGA of 0 or 1) (Week 28 
responders), will continue to receive blinded drug.  In 
Arm 1, patients will be re-randomized; in Arm 2, 
they will continue to receive   blinded BI655066 
treatment as described in Section 7.6.
Starting with Week 32, Week 28 responders will 
have their sPGA assessed for protocol defined 
relapse (sPGA of ≥ 3).
Rationale for change
This change is to be  implemented  to ensure that no 
bias is introduced by knowing patients’ original 
treatment assignment after the Week 28 visit
Section to be changed
3.1 Overall Trial Design and Plan
Description of change
“a primary endpoint analysis will be conducted after 
the last patient has been in the study for 52 weeks (or 
discontinued)”.  The previous wording was “when 
the last patient completes the Week 52 visit.
Rationale for change
To incorporate the possibility that patients may 
discontinue from the study prior to Week 52.
Section to be changed
Section 3.1.1 Administrative structure of the trial
Description of change
Operating unit changed to Operative Unit
Rationale for change
Protocol template error
Section to be changed
3.3.4.1  Removal of individual patients
Description of change
The word “necessarily” was added to: 
“Discontinuation of study medication should not 
necessarily lead to withdrawal from the study”.
Rationale for change
Clarification as  patients that discontinue study 
medication should complete all study visits and 
procedures as initially planned, if possible
Section to be changed
3.3.4.2
Description of change
Bullet #2 re-written to “Emergence of any 
efficacy/safety information that could significantly 
affect continuation of the trial, or any other 
administrative reasons, i.e. problems with availability 
of the study medication, discontinuation of 
development of BI 655066
Original Bullet #3 removed “Emergence of any 
efficacy/safety information invalidating the earlier 
positive benefit-risk-assessment that could 
significantly affect the continuation of the trial 
(including those based on DMC recommendation)
Rationale for change
Error in original CTP
Section to be changed
Section 4.1.2 Methods of assigning patients to 
treatment groups
Description of change
Section re-written according to new study design to 


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be consistent with section 3.1
Rationale for change
Design change
Section to be changed
Section 4.1.3 Selection of doses in the trial
Description of change
650666 changed to 655066
Rationale for change
Error in original CTP
Section to be changed
4.1.4 Drug assignment and administration of doses 
for each patient
Description of change
a. Added that the 2 injections need to be administered 
within approximately 5 minutes.
b. Added that the IMP time in the eCRF is the time 
of injection # 1.
c. Added the underlined words to the sentence; 
“Patients should be closely monitored for signs and 
symptoms of hypersensitivity reactions for 
approximately 2 hours after the last injection at Visit 
2 and for approximately one hour after the last 
injection at all other visits where drug is 
administered.
d. Deleted: (contra-lateral to that used for PK/PD 
samples) from sentence “BI 655066 and/or matching 
placebo will be administered as a subcutaneous 
injection in the abdomen, thighs, gluteal regions, or 
upper arms”.
Rationale for change
a,b. Provide clarity and further details on timing of 
injections and eCRF completion
c.To specify timing of monitoring hypersensitivity 
with respect to injection times.
d. not required as PK samples are only taken pre-
dose (trough)
Section to be changed
4.1.5.1 Blinding
Description of change
Section re-written according to new study design to 
be consistent with section 3.1, clarifying the criteria 
for receiving open label drug and knowing future 
treatments are BI 655066. 
Rationale for change
New study design as noted in section 3.1
Section to be changed
4.2.2.3 Restrictions regarding women of childbearing 
potential
Description of change
Deleted reference to Section 3.3.3, and corrected to 
3.3.2
Rationale for change
Error in original protocol
Section to be changed
5.1.3 Further endpoints
Description of change
Text added “The above endpoints will be analyzed, 


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where appropriate, for re-randomized subjects after 
receiving open-label study drug for retreatment (Flow 
Chart 2 and 3)”.
Rationale for change
To clarify that these endpoints will also be analyzed 
among retreatment patients at visits collected.
Section to be changed
5.3.2 Vital Signs
Description of change
The underlined wording was added to the following 
sentences.  “In addition at Visit 2 and Visit 3 vital 
sign evaluations will be taken at approximately 5 
minutes post-dose (5 minutes after last injection) and 
approximately 60 minutes post-dose (60 minutes after 
last injection). “Patients should be closely monitored 
for signs and symptoms of hypersensitivity reactions 
for approximately 2 hours after the last injection at 
Visit 2 and for approximately one hour after the last 
injection at all other visits where drug is administered
Rationale for change
To specify timing of vitals relative to injection times 
and also timing of  monitoring hypersensitivity with 
respect to injection times.
Section to be changed
Table 5.3.3:1 laboratory tests
Description of change
Added absolute count to differential
Added “activated to aPTT
Deleted “MB” from Troponin reflex
Added “calculated” to LDL
Deleted “creatinine” from urinalysis stix
Added “creatinine” to urinalysis
Added Albumin/creatinine ratio to Urinalysis
Rationale for change
Was omitted from original CTP or needed further 
clarification
Section to be changed
6.2 Details of Trial Procedures At Selected Visits
Description of change
Added paragraph to note that efficacy questionnaires 
are direct data capture on an electronic device
Rationale for change
Omitted from original CTP
Section to be changed
Section 6.2.2, Week 28 Visit and Randomized 
withdrawal period (Re-randomized patients)
Description of change
Wording revised due to implementation of continuing 
blinded treatment
Rationale for change
Design change for Week 28
Section to be changed
Section 6.2.2 Treatment period
Description of change
Added “a maximum of”  20 visits
Rationale for change
Clarification as patients who relapse and get retreated 
may have less visits during treatment depending on 
time of relapse
Section to be changed
Section 6.2.3 Early Treatment and trial termination
Description of change
Further instructions given for staying in the trial or 
terminating from the trial when a patient ends 
treatment early


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Rationale for change
Update to original CTP
Section to be changed
Section 6.2.3 Successful Trial Completion
Description of change
Added “and who have not discontinued drug 
prematurely” to definition of trial completion
Rationale for change
Clarifying definition of trial completion
Section to be changed
Section 7.1
Description of change
“or not collected per protocol” was added to the last 
sentence in first paragraph
Rationale for change
clarification
Section to be changed
Section 7.3 Planned Analyses
Description of change
Second to last sentence of last paragraph wording 
“the patients included in the Week 52 assessment of
randomized withdrawal “ Replaced with “affecting 
Week 52 efficacy of randomized withdrawal.
Rationale for change
To clarify that this per-protocol set will exclude 
patients with violations affecting their efficacy 
evaluation, not affecting patients in general.
Section to be changed
7.3.3 Further endpoint analyses
Description of change
“descriptively” removed from “Further endpoints 
will be summarized descriptively
Rationale for change
“summarized” already means that 
descriptive/summary statistics will be provided, the 
word “descriptively” seems duplicated here and is 
removed.
Section to be changed
7.4 Interim Analyses
Description of change
a. Updated to “An analysis will be conducted after 
the last patient either has been in the study for 52 
weeks or discontinues from study”.
b. Updated to: 
“hence no alpha adjustment is required at this 
analysis”.
Rationale for change
a. To incorporate the possibility that patients 
may discontinue from the study prior to Week 
52.
b. To clarify that this analysis will not require 
type-I error rate adjustment.
Section to be changed
7.5 Handling of Missing Data
Description of change
a. Added “Of note, for randomized withdrawal 
analyses, subjects who received retreatment will be 
counted as non-responders in all visits after the date 
of retreatment.”
b. Added “the following methods where applicable” 
to the end of this sentence, “Sensitivity analyses to 
assess the robustness of the hypothesis testing results 
will include”:
Rationale for change
a. To clarify that patients who received retreatment 
will be counted as non-responders, since the decision 


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of retreatment is due to lack of efficacy.
b. To clarify that the listed methods for sensitivity 
analyses will be conducted based on data availability 
and method validity, because not all methods are 
applicable at all cases.  
Section to be changed
7.6 Randomisation
Description of change
Section re-written according to new study design to 
be consistent with section 3.1
Rationale for change
CTP update
Section to be changed
Table 7.7.1
Description of change
Changed PBO to “placebo”
Rationale for change
“placebo” used throughout CTP
Section to be changed
Section 9.1 Published References
Description of change
Added R16-2653 and R16-2654
Rationale for change
Omitted from original CTP
Section to be changed
10.3 NAPSI-Nail Psoriasis Severity Index 
Description of change
Addition of Reference number R16-2654
Rationale for change
Update to CTP
Section to be changed
10.4 PPASI-Palmoplantar psoriasis severity index 
Description of change
Correction of wording from “scored” to “scores”
Rationale for change
Correction
Section to be changed
10.5 Psoriasis scalp severity index (PSSI) 
Description of change
Addition of Reference number R16-2653
Rationale for change
Omitted from original CTP
Section to be changed
10.7.1 Dermatology life quality index (DLQI)
Description of change
Correction of response categories
Rationale for change
Update from original CTP
Section to be changed
3.1 Overall Trial Design and Plan  and 4.1.5.1 
Blinding
Description of change
Removed wording noting that data for all patients 
through week 16 must be entered into the eCRF prior 
to the patients receiving treatment at the week 28 
visit."
Rationale for change
As this amendment removes the blind break for week 
28 responders, this is no longer a requirement and is 
accordingly removed from the protocol.


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Number of global amendment
3.0
Date of CTP revision
11-Oct-2016
EudraCT number
2014-005102-38
BI Trial number
1311.4
BI Investigational Product(s)
BI 655066/ABBV-066 (risankizumab)
Title of protocol
BI 655066 (risankizumab) versus placebo In a 
Multicenter randomized double-blind study in 
patients with Moderate to severe chronic plaque 
psoriasis evaluating the efficacy and safety with 
randomized withdrawal and re-treatment 
(IMMhance)
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
X
Section To be changed
Title page and synopsis
Description of change
The compound name was revised to add “ABBV-
066” to BI 655066 (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
Section 3.1.1
Description of change
1. Changed sponsor from Boehringer Ingelheim (BI) 
to AbbVie in the USA and BI for non-USA
participating countries.
Rationale for change
2. Changed text to specify Statistical Evaluation will 
be done by AbbVie according to their SOPs.
Section To be changed
Section 3.3.4.2


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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
Section To be changed
Section 5.5.2.2
Description of change
Changed DNA banking sample storage from 
Boehringer Ingelheim to “AbbVie or a third party 
delegate (e.g. Boehringer Ingelheim Pharma GmbH 
& Co. KG; Birkendorfer Str. 65, 88397 Biberach, 
Germany)”.
Rationale for change
Refer to rational for first change listed
Section To be changed
Section 7.3.4
Description of change
Changed text to specify that AbbVie summary tables 
and listings will be produced and analyses based on 
AbbVie standards.
Rationale for change
Refer to rational for first change listed

SAP_001.pdf: 
Risankizumab
1311.4 – Statistical Analysis Plan
Version 2.0 – 12 Sep 2017
1
1.0
Title Page
Statistical Analysis Plan
Study 1311.4
Risankizumab Versus Placebo in a Multicenter 
Randomized Double-Blind Study in Patients with 
Moderate to Severe Chronic Plaque Psoriasis 
Evaluating the Efficacy and Safety with Randomized 
Withdrawal and Re-Treatment (IMMhance)
Date:  12 Sep 2017
Version 2.0
NCT02672852


Risankizumab
1311.4 – Statistical Analysis Plan
Version 2.0 – 12 Sep 2017
2
2.0
Table of Contents
1.0
Title Page ...............................................................................1
2.0
Table of Contents ..................................................................2
3.0
Introduction...........................................................................6
4.0
Study Objectives, Design and Procedures............................6
4.1
Primary Study Objective......................................................................... 6
4.2
Design Diagram ..................................................................................... 7
4.3
Sample Size............................................................................................ 9
4.4
Interim Analysis ................................................................................... 10
5.0
Analysis Populations ........................................................... 11
5.1
Definition for Analysis Populations ...................................................... 11
5.2
Variables Used for Stratification of Randomization .............................. 14
6.0
Analysis Conventions .......................................................... 15
7.0
Demographics, Baseline Characteristics, Medical 
History, and Previous/Concomitant Medications..............27
7.1
Demographic and Baseline Characteristics ........................................... 27
7.2
Medical History.................................................................................... 30
7.3
Previous Treatment and Concomitant Medications ............................... 30
7.4
Protocol Deviations .............................................................................. 30
8.0
Patient Disposition............................................................... 31
9.0
Study Drug Exposure and Compliance..............................32
10.0
Efficacy Analysis ................................................................. 34
10.1
General Considerations......................................................................... 34
10.1.1
Analyses of Categorical Variables ........................................................ 35
10.1.2
Analyses of Continuous Variables ........................................................ 36
10.1.3
Analyses of Time-to-Event Variables ................................................... 36
10.1.4
Missing Data Imputations..................................................................... 37
10.2
Primary Efficacy Analysis.................................................................... 39
10.2.1
Primary Efficacy Analysis in Part A..................................................... 39
10.2.2
Primary Efficacy Analysis in Part B ..................................................... 40
10.3
Secondary Efficacy Analyses ............................................................... 40
10.3.1
Ranked Secondary Efficacy Analysis ................................................... 40


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10.3.1.1
Ranked Secondary Efficacy Analysis in Part A..................................... 40
10.3.1.2
Ranked Secondary Efficacy Analysis in Part B..................................... 41
10.3.2
Other Secondary Efficacy Analysis ...................................................... 42
10.3.3
Further Efficacy Endpoints................................................................... 42
10.4
Handling of Multiplicity....................................................................... 43
10.5
Efficacy Subgroup Analysis ................................................................. 44
11.0
Safety Analysis.....................................................................44
11.1
General Considerations......................................................................... 44
11.2
Analysis of Adverse Events.................................................................. 45
11.2.1
Treatment-Emergent Adverse Events.................................................... 45
11.2.2
SAEs (Including Deaths) and Adverse Events Leading to Study 
Drug Discontinuation ........................................................................... 54
11.2.3
Safety Subgroup Analysis..................................................................... 54
11.3
Analysis of Laboratory Data................................................................. 55
11.3.1
Variables and Criteria Defining Abnormality........................................ 55
11.3.2
Statistical Methods ............................................................................... 57
11.4
Analysis of Vital Signs and Weight ...................................................... 60
11.4.1
Variables and Criteria Defining Abnormality........................................ 61
11.4.2
Statistical Methods ............................................................................... 61
11.5
Analysis of ECG Parameters ................................................................ 62
11.6
Local Tolerability................................................................................. 63
12.0
Pharmacokinetic Analysis................................................... 63
13.0
Biomarkers Analysis ........................................................... 63
14.0
Summary of Changes .......................................................... 63
14.1
Summary of Changes Between the Latest Version of Protocol and 
the Current SAP ................................................................................... 63
14.2
Summary of Changes Between the Previous Version and the 
Current Version of the SAP .................................................................. 64
15.0
Appendix.............................................................................. 64
16.0
References............................................................................64
17.0
List of Tables, Figures and Data Listings That are to 
Be Programmed................................................................... 64


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List of Tables
Table 1.
Notations for Treatment Groups ........................................................... 14
Table 2.
Visit Windows for Analysis of PASI, sPGA, Local Tolerability, 
and Vital Signs in Part A1 (ITT_A1/PP_A1/Safety_A1 
Populations) ......................................................................................... 18
Table 3.
Visit Windows for Analysis of DLQI in Part A1 (ITT_A1/PP_A1 
Populations) ......................................................................................... 18
Table 4.
Visit Windows for Analysis of Safety Laboratory Tests and ECG 
in Part A1 (Safety_A1 Population) ....................................................... 19
Table 5.
Windows for Analysis of Efficacy Variables Collected Only at 
Week 16 After Baseline in Part A1 (ITT_A1 Population) ..................... 19
Table 6.
Visit Windows for Analysis of PASI and sPGA in Part A2 
(ITT_A2 Population)............................................................................ 19
Table 7.
Visit Windows for Analysis of Efficacy Variables Only Collected 
at Week 28 in Part A2 (ITT_A2 Population)......................................... 20
Table 8.
Visit Windows for Analysis of PASI and sPGA, Local 
Tolerability, and Vital Signs in Part B 
(ITT_B_R/ITT_B_NR/PP_B_R/Safety_B_R/Safety_B_NR 
Populations) ......................................................................................... 20
Table 9.
Visit Windows for Analysis of Safety Laboratory Tests and ECG 
in Part B (Safety_B_R/Safety_B_NR Populations) ............................... 21
Table 10.
Visit Windows for Analysis of Other Efficacy Endpoints Only 
Collected at Week 52, 76, and 104 in Part B 
(ITT_B_R/ITT_B_NR/PP_B_R Populations) ....................................... 22
Table 11.
Visit Windows for Analysis of PASI and sPGA Across Part A2 
and B (ITT_ARM2 Population) ............................................................ 22
Table 12.
Visit Windows for Analysis of Other Efficacy Endpoints 
Collected at Week 28, 52, 76, and 104 in Part A2 and B 
(ITT_ARM2 Population)...................................................................... 23
Table 13.
Visit Windows for Analysis of PASI and sPGA During 
Retreatment with Risankizumab 
(ITT_B_PBO_RT/ITT_B_RZB_RT Populations)................................. 23
Table 14.
Visit Windows for Analysis of Other Efficacy Variables Only 
Collected at EOT and EOO Visits During Retreatment with 
Risankizumab (ITT__B_PBO_RT/ITT_B_RZB_RT Populations)........ 23


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Table 15.
Visit Windows for Analysis of Vital Signs and Local Tolerability 
in the ALL_RZB Population................................................................. 24
Table 16.
Visit Windows for Analysis of Safety Laboratory Tests and ECG 
in the ALL_RZB Population................................................................. 25
Table 17.
Visit Windows for Summary of Study Drug Injections for Part A1....... 25
Table 18.
Visit Windows for Summary of Study Drug Injections for Part A2....... 25
Table 19.
Visit Windows for Summary of Study Drug Injections for Part B......... 26
Table 20.
Visit Windows for Summary of Study Drug Injections for 
Subjects Retreated with Risankizumab for Relapse from Week 32 
Through Week 70 (Inclusive) ............................................................... 26
Table 21.
Visit Windows for Summary of Study Drug Injections for 
Subjects Retreated with Risankizumab for Relapse from Week 70 
Through Week 82 (Inclusive) ............................................................... 26
Table 22.
Visit Windows for Summary of Study Drug Injections for 
Subjects Retreated with Risankizumab for Relapse After Week 82....... 26
Table 23.
Areas of Safety Interest ........................................................................ 50
Table 24.
Clinical Laboratory Tests ..................................................................... 56
Table 25.
Criteria for Potentially Clinically Important Chemistry Values ............. 58
Table 26.
Criteria for Potentially Clinically Important Hematology Values .......... 58
Table 27.
NCI CTCAE Grading........................................................................... 59
Table 28.
Criteria for Potentially Clinically Important Vital Sign Findings........... 61
List of Figures
Figure 1.
Trial Design ........................................................................................... 9


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3.0
Introduction
This statistical analysis plan (SAP) describes the statistical analysis to be completed by 
the AbbVie Clinical Statistics Department for study Protocol 1311.4 dated 28 July 2016. 
This SAP will provide details to further elaborate statistical methods as outlined in the 
Protocol 1311.4 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 the initial randomized phase of the study (Part A1; see 
Section 4.2) is to assess the  efficacy of risankizumab 150 mg in comparison to placebo in 
subjects with moderate to severe chronic plaque psoriasis.  The primary objective of the 
second randomized phase of the study (Part B; see Section 4.2) is to evaluate the 
maintenance of response with continuous risankizumab treatment compared with 
withdrawal of treatment.
The primary efficacy evaluation will be performed at 16 weeks.  The maintenance of 
response following drug withdrawal will be assessed after Week 28 through the end of the 
study (primary evaluation at Week 52).  Subsequent to drug withdrawal, subjects who 
experience relapse will be retreated with risankizumab to assess response after 
retreatment.
Evaluations of risankizumab efficacy and safety in various populations will be performed 
in the study to provide a full picture of risankizumab benefits and risks.  These 
populations and the intent of the related analyses is specific in Section 5.2.


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In addition, this trial will assess pharmacokinetics (PK) and the emergence of anti-drug 
antibodies (ADA) and their effect on efficacy and safety.  Moreover, it will be explored 
how the use of risankizumab may influence gene and protein expression levels and 
disease specific protein markers.  PK and ADA analyses, as well as DNA banking, 
exploratory biomarker, and metabolic risk factor analyses, will not be included in this 
SAP.
4.2
Design Diagram
This is a confirmatory, multinational, multicenter, randomized, double-blind, placebo 
controlled study with randomized withdrawal and retreatment, evaluating the safety and 
efficacy of risankizumab 150 mg subcutaneous (SC) in patients with moderate to severe 
chronic plaque psoriasis.
The study consists of an up to 42 day screening period, a 16-week double-blind, placebo-
controlled initial treatment period (Part A1), a 12-week treatment period (Part A2), an up 
to 60-week continuous treatment and treatment withdrawal period (Part B) with possible 
retreatment with risankizumab for up to 16 weeks, and a 16 week follow-up period.
Part A1:  A 16-week double-blinded, placebo-controlled treatment period during which 
subjects will be randomized at a ratio of 4:1 to one of two treatment arms as shown in 
Figure 1.  Arm 1 refers to those subjects originally randomized to risankizumab and 
Arm 2 refers to those subjects originally randomized to placebo.  The first dose of study 
drug will be administered on Day 1 (Visit 2; Baseline) and the second dose will be 
administered at Week 4.  The randomization will be stratified with respect to weight 
(≤100 kg vs. > 100 kg) and prior exposure to TNF antagonists (0 vs. ≥ 1).
Part A2:  A 12-week treatment period.  At Week 16, all subjects will receive one dose of 
risankizumab 150 mg.
Part B:  At Week 28, non-responders (static Physician Global Assessment [sPGA] ≥ 2) 
will receive open label risankizumab 150 mg every 12 weeks with a last dose at Week 88 
(end-of-treatment, EOT), while responders (sPGA of 0 or 1) from Arm 1 will be 


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re-randomized in a 1:2 ratio to either maintain risankizumab 150 mg or matching placebo 
every 12 weeks with a last dose at Week 88 (EOT).  The re-randomization will be 
stratified with respect to weight (≤ 100 kg vs. > 100 kg) and prior exposure to TNF 
antagonists (0 vs. ≥ 1).  Responders from Arm 2 will continue to receive blinded 
risankizumab 150 mg every 12 weeks with a last dose at Week 88 (EOT) to maintain the 
blind.  Throughout the SAP, "re-randomized" or "re-randomization" refers to the 
randomization at Week 28 among subjects from Arm 1 of Part A.
Retreatment:  Starting from Week 32, subjects experiencing relapse (defined as an sPGA 
of ≥ 3), will receive open label risankizumab 150 mg.  If this relapse occurs anytime 
between Week 32 through Week 70, open label risankizumab 150 mg will be 
administered at 0, 4, and 16 weeks (EOT) after relapse.  If this relapse occurs after 
Week 70 through Week 82, open label risankizumab 150 mg will be administered 0 and 
4 weeks (EOT) after relapse.  If the relapse occurs after Week 82 through Week 88 the 
subject will immediately have the EOT procedures performed, including the final dose of 
study drug. 
Follow-Up Period:  Subjects who have completed their EOT visit will be followed up for 
16 weeks.  Follow-up Visit 1 is scheduled at 6 weeks after EOT.  And Follow-up Visit 2 
is scheduled at 16 weeks after EOT, which is the end of observation (EOO) visit.  
Subjects who have completed the EOO visit within the specified window, who have not 
discontinued drug prematurely, and who also meet the eligibility criteria will be offered to 
roll over into an open label extension study.


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Figure 1.
Trial Design
BI 655066 is risankizumab.
4.3
Sample Size
This study is designed to show a difference between risankizumab and placebo in terms of 
achieving 90% reduction in Psoriasis Area and Severity Index (PASI 90) response and 
sPGA of clear or almost clear (sPGA of 0 or 1) at Week 16.  This study was also powered 
to show a difference in sPGA response at Week 52 between the subjects re-randomized to 
continue on risankizumab vs. subjects randomized to placebo at Week 28.
Based on the interim results from Study 1311.2, it is assumed at most 10% of the subjects 
in the re-randomized risankizumab arm and approximately 25% of subjects in the 
re-randomized placebo arm will lose response.  Using a 1:2 re-randomization scheme 
(risankizumab:placebo), 102 subjects in the risankizumab arm and 204 subjects in the 


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placebo arm will provide at least 90% power to detect the difference in sPGA response 
rate at Week 52.  Assuming that 80% of subjects initially randomized to risankizumab at 
baseline will achieve sPGA of 0 or 1 at Week 28, the total sample size required for the 
initial risankizumab arm at Visit 2 is (102)(3) ÷ 0.8 = 383. 
A total sample size of 500 = 400:100 for risankizumab:  placebo was planned at Visit 2.
Based on the outcome from Trials 1311.1 and 1311.2, the PASI 90 response rate at 
Week 16 is assumed to be at least 65% in the risankizumab arm and approximately 5% for 
placebo.  For sPGA clear or almost clear at Week 16, the response rate is assumed to be at 
least 80% for the risankizumab arm and approximately 5% for placebo.  This trial will 
have > 99% power for comparing risankizumab arm to placebo on both of these 
endpoints.
All calculations were performed using ADDPLAN Version 6.0.4, an Aptiv Solutions 
Company.
4.4
Interim Analysis
Unblinded data will be reviewed during the study by an independent data monitoring 
committee (DMC).  The membership, roles and responsibilities and activities of the DMC 
will be defined in a written charter.  The DMC will include representatives from external 
safety experts who do not directly involve in the study.  Clinical site personnel and the 
study team will remain blinded to the randomized treatment assignments during the 
course of the study.  Communications from the DMC to the study team will not contain 
information that could potentially unblind the study personnel.  Since there is no efficacy 
analyses for early stopping, no alpha adjustment is needed.


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5.0
Analysis Populations
5.1
Definition for Analysis Populations
Efficacy Population:
Intent-to-Treat (ITT) Population:  The ITT Populations will be used for the efficacy 
analyses in different parts.
●
The ITT Population in Part A1 (ITT_A1) is defined as all subjects who are 
randomized at Baseline.  This Population will be analyzed for the efficacy of 
initial treatment.
●
The ITT Population in Part A2 from Arm 1 (ITT_A2) is defined as all subjects 
who were randomized to Arm 1 at Baseline.  Data from Part A2 will be used to 
evaluate the mid-term efficacy.
●
The ITT Population across Part A2 and B from Arm 2 (ITT_ARM2) is defined 
as all subjects who were randomized to Arm 2 at Baseline and received at least 
one dose of study drug on or after Week 16.  This Population will be analyzed 
for short and long term efficacy without initial loading dose.
●
The ITT Population in Part B for re-randomized subjects (ITT_B_R) is defined 
as all subjects who were randomized to Arm 1 and re-randomized at Week 28.  
The ITT_B_R Population will mainly be used to compare efficacy of 
continued treatment with risankizumab vs withdrawal from the treatment.  The 
risankizumab arm will also be summarized (including data after retreatment) 
for long-term efficacy with the option of re-load.
●
The ITT Population in Part B for Arm 1 non-responders at Week 28 
(ITT_B_NR) is defined as all subjects who were randomized to Arm 1 at 
Baseline, were non-responders (sPGA ≥ 2) at Week 28, and receive at least 
one dose of risankizumab on or after Week 28.  This population will be 
summarized for potential delayed response.
●
The ITT Population for Part B placebo patients who received retreatment 
(ITT_B_PBO_RT) is defined as all subjects who were re-randomized to 
placebo and received at least one dose of retreatment with open label 
risankizumab after relapse, and have the opportunity to have retreatment 
Week 16 assessments.


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●
The ITT Population for Part B risankizumab patients who receive retreatment 
(ITT_B_RZB_RT) is defined as all subjects who were re-randomized to 
risankizumab and received at least one dose of retreatment with open label 
risankizumab after relapse, and have the opportunity to have retreatment 
Week 16 assessment.  The population will be summarized to examine the 
efficacy of re-treatment with loading dose upon relapse on risankizumab.
ITT Populations will be analyzed by the treatment group as randomized.  
In addition, additional analysis will be performed on ITT_B_R subjects who are 
re-randomized to risankizumab 150 mg, in which all evaluations after re-randomization 
(including evaluations after retreatment with open label risankizumab after relapse) will 
be included along with the blinded assessments to evaluate the efficacy of continuous 
treatment. 
Per-Protocol (PP) Population:  To evaluate the impact of protocol deviations on the 
primary and ranked secondary endpoints, additional analyses will be performed on the 
Per-protocol Populations.  The Per-protocol Population will include those who were most 
compliant with the protocol in ways that could impact the primary and ranked secondary 
endpoints.  Final results and the criteria for exclusion of subjects will be finalized prior to 
database lock for data pertaining to the DB period. 
The PP Population at Part A1 (PP_A1; a.k.a. the PPS in study Protocol 1311.4) is defined 
as all subjects from the ITT_A1 Population who meet all the following criteria:
●
Subjects must receive at least 75% of planned study drug injections, per 
randomization, in Part A1.
●
Subjects must have either a PASI or sPGA assessment post-baseline in 
Part A1.
●
Inclusion Criterion 4:  Subjects must have stable moderate to severe chronic 
plaque psoriasis at baseline:
○
Have an BSA ≥ 10% and
○
Have a PASI ≥ 12 and


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○
Have an sPGA ≥ 3.
Primary and ranked secondary efficacy endpoints at Part A1 at Week 16 will be analyzed 
on the PP_A1 Population.
The PP Population at Part B for re-randomized subjects (PP_B_R; a.k.a. RRS-PPS in 
study Protocol 1311.4) is defined as all subjects from the ITT_B_R Population who meet 
all the following criteria:
●
Subjects must receive at least 75% of planned study drug injections, per 
re-randomization, in Part B.
●
Subjects must have at least one sPGA assessment post re-randomization in 
Part B.
●
Subjects must have sPGA < 2 at re-randomization.
The primary efficacy endpoint for Part B at Week 52 and ranked secondary endpoint for 
Part B at Week 104 will be analyzed on the PP_B_R Population.
PP Populations will be analyzed by the treatment group as randomized (or 
re-randomized).
Safety Population:
The Safety Populations will be used for safety analyses in different study parts.
Each ITT population will have a corresponding safety population (Safety) of the same 
study part, which includes all subjects who receive at least one dose of study drug during 
the analysis period. 
Complete safety tables will be provided for the Safety_A1 Population and the Safety_B_R 
population.  Only AE overview tables will be provided for other safety populations.
The Safety Population will be analyzed based on the actual treatment received at the 
randomization visit (Part A) and at the re-randomization visit (Part B).


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In addition, an All Risankizumab Treated Population (ALL_RZB) is defined as all 
subjects who receive at least one dose of risankizumab in the study.  The ALL_RZB 
Population will be used for safety analyses.  Complete safety tables will be provided in 
the ALL_RZB Population.
Table 1.
Notations for Treatment Groups
Population
Treatment Code
Definition
ITT_A1/PP_A1/
Safety_A1
RZB
Subjects who randomized to risankizumab 150 mg.
PBO
Subjects who randomized to placebo.
ITT_A2/Safety_A2
RZB/RZB
Subjects who randomized to risankizumab 150 mg.
ITT_ARM2/
Safety_ARM2
PBO/RZB
Subjects who randomized to placebo and received 
at least one dose of study drug on or after Week 16.
ITT_B_R/PP_B_R/
Safety_B_R
RZB/RZB/RZB
Subjects who re-randomized to risankizumab 
150 mg at Week 28.
RZB/RZB/PBO
Subjects who re-randomized to placebo at 
Week 28.
ITT_B_NR/Safety_B_NR
RZB/RZB/RZB
Subjects who randomized to risankizumab and are 
non-responders at Week 28.
ITT_B_PBO_RT/
Safety_B_PBO_RT
RZB/RZB/PBO/RZB
Subjects who received open-label risankizumab 
150 mg as retreatment, after re-randomized to 
placebo in Part B.
ITT_B_RZB_RT/
Safety_B_RZB_RT
RZB/RZB/RZB/RZB
Subjects who received open-label risankizumab 
150 mg as retreatment, after re-randomized to 
risankizumab in Part B.
ALL_RZB
RZB
Subjects who received at least one dose of 
risankizumab 150 mg.
5.2
Variables Used for Stratification of Randomization
At Visit 2, subjects will be randomized in blocks to double-blind treatment to either 
risankizumab 150 mg or placebo in a 4:1 ratio.  Randomization will be stratified with 
respect to weight (≤ 100 kg vs. > 100 kg) and prior exposure to TNF antagonists (0 vs. 
≥1).


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Subjects originally randomized to risankizumab 150 mg (Arm 1) who are responders at 
Week 16 will be re-randomized at Week 28 in a 1:2 ratio to either risankizumab 150 mg 
or placebo.  Re-randomization will also be stratified with respect to weight (≤ 100 kg vs. 
> 100 kg) and prior exposure to TNF antagonists (0 vs. ≥ 1).
6.0
Analysis Conventions
Definition of Baseline
The last non-missing measure collected on or before the date of the first dose of study 
drug injection will be used as Baseline for summary of demographics and disease 
characteristics, efficacy analyses, and safety analyses in each period, with the exception 
that:
●
The last evaluation on or prior to the first dose date of risankizumab will be 
used for the safety analyses for Safety_ARM2 and ALL_RZB populations.
●
For all 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.
For subjects who are randomized but do not take any study drug during the study, the last 
non-missing measurement collected on or before the date of randomization will be used as 
Baseline.
Definition of Final Observation (Applicable to Safety Analyses)
Final observation for the Part A1 is defined as:
●
The last non-missing observation collected within 105 days following the last 
dose of study drug in Part A1, for subjects who were not dosed in Part A2. 
●
The last non-missing observation collected on or before the first dose date of 
study drug on or after Week 16 and within 105 days following the last dose of 
study drug in Part A1, for subjects who were dosed in Part A2.  For vital sign 
assessments, only assessments prior to the first dose of study drug injection in 
Part A2 will be included in the analysis for Part A1.


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Final observation for the Part A2 is defined as:
●
The last non-missing observation collected within 105 days following the 
Week 16 dose of study drug in Part A2, for subjects who were not dosed in 
Part B. 
●
The last non-missing observation collected on or before the first dose date of 
Part B, or within 105 days following the last dose of study drug in Part A2, 
whichever comes first, for subjects who were dosed in Part B.  For vital sign 
assessments, only assessments prior to the first dose of study drug injection in 
Part B will be included in the analysis for Part A2.
Final observation in Part B is defined as the last non-missing observation collected within 
105 days following the last dose of study drug, and on or prior to the date first dose of 
retreatment with risankizumab for relapsed subjects, with the following exception:
For vital sign assessments, only assessments prior to the first dose of retreatment will be 
included in the analysis for Part B.
Final observation in the retreatment period is defined as the last non-missing observation 
collected within 105 days after the last dose of retreatment with risankizumab.
Final observation in the entire study is defined as the last non-missing observation 
collected within 105 days after the last dose of study drug.
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 study drug.  
They are defined as the number of days between the day of the first dose of study drug 
and the specific time point.  Rx days are negative values when the time point of interest is 
prior to the first study drug dose day.  Rx days are positive values when the time point of 
interest is on or after the first study drug dose day.  The day of the first dose of study drug 
is defined as Rx Day 1, while the day prior to the first study drug dose is defined as Rx 
Day –1 (there is no Rx Day 0).


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For analysis in each Part (A1, A2, or B), the Rx Day is calculated relative to the first dose 
of study drug in the specific study Part.  For analysis across Part A2 and Part B, the Rx 
days are calculated relative to the date of first dose of risankizumab injection in Part A2.
Definition of Analysis Windows 
All time points and corresponding time windows are defined based on Rx Days.
For efficacy analyses, local tolerability, ECG, laboratory parameters, 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 study drug (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 
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 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, local tolerability, ECG, laboratory parameters, and vital sign variables, are 


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presented in the following Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, 
Table 9, Table 10, Table 11, Table 12, Table 13, Table 14, Table 15 and Table 16.
Table 2.
Visit Windows for Analysis of PASI, sPGA, Local Tolerability, and 
Vital Signs in Part A1 (ITT_A1/PP_A1/Safety_A1 Populations)
Window Label
Target Day
Interval
Baseline
1
≤ 1a
Week 4
29
[2, 43]
Week 8
57
[44, 71]
Week 12
85
[72, 99]
Week 16
113
[100, 127b]
Rx Day calculated relative to first dose date of study drug. For subjects randomized but not dosed, Rx Day calculated 
relative to Randomization.
a.
There is no baseline for local tolerability measurements.  If time is collected in vital signs, restrict to records prior 
to the first dose of study drug.
b.
The minimum of upper bound and first dose date of study drug on or after Week 16 (and within 105 days of last 
dose for safety analyses).  If time is collected in vital signs, restrict to records prior to the first dose of study drug 
on or after Week 16.
Table 3.
Visit Windows for Analysis of DLQI in Part A1 (ITT_A1/PP_A1 
Populations)
Window Label
Target Day
Interval
Baseline
1
≤ 1
Week 12
85
[2, 99]
Week 16
113
[100, 127a]
Rx Day calculated relative to first dose date of study drug.  For subjects randomized but not dosed, Rx Day calculated 
relative to Randomization.
a.
The minimum of upper bound and first dose date of study drug on or after Week 16.


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Table 4.
Visit Windows for Analysis of Safety Laboratory Tests and ECG in 
Part A1 (Safety_A1 Population)
Window Label
Target Day
Interval
Baseline
1
≤ 1
Week 4
29
[2, 71]
Week 16
113
[72, 155a]
Rx Day calculated relative to first dose date of study drug.  For subjects randomized but not dosed, Rx Day calculated
relative to Randomization.
a.
The minimum of upper bound and first dose date of study drug on or after Week 16 (and within 105 days of last 
dose for safety analyses).
Table 5.
Windows for Analysis of Efficacy Variables Collected Only at 
Week 16 After Baseline in Part A1 (ITT_A1 Population)
Window Label
Target Day
Interval
Baseline
1
≤ 1
Week 16
113
[2, 225a]
Rx Day calculated relative to first dose date of study drug.  For subjects randomized but not dosed, Rx Day calculated 
relative to Randomization.
a.
The minimum of upper bound and first dose date/time on or after Week 16 study drug.
Table 6.
Visit Windows for Analysis of PASI and sPGA in Part A2 (ITT_A2 
Population)
Window Label
Target Day
Interval
Entry of A2
1
≤ 1
Week 20
29
[2, 43]
Week 24
57
[44, 71]
Week 28
85
[72, 99a]
Rx Day calculated relative to the date of Week 16 visit.
a.
The minimum of upper bound and first dose date on or after the first re-randomized dose for subjects with 
re-randomization or the first open label risankizumab dose for those who were not re-randomized.


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Table 7.
Visit Windows for Analysis of Efficacy Variables Only Collected at 
Week 28 in Part A2 (ITT_A2 Population)
Window Label
Target Day
Interval
Baseline
1
≤ 1
Week 28
85
[2, 169a]
Rx Day calculated relative to the date of Week 16 visit.
a.
The minimum of upper bound and first dose date on or after the first re-randomized dose for subjects with 
re-randomization or the first open label risankizumab dose for those who were not re-randomized.
Table 8.
Visit Windows for Analysis of PASI and sPGA, Local Tolerability, 
and Vital Signs in Part B 
(ITT_B_R/ITT_B_NR/PP_B_R/Safety_B_R/Safety_B_NR 
Populations)
Window Label
Target Day
Interval
Entry of B
1
≤ 1a
Week 32
29
[2, 43]
Week 36
57
[44, 71]
Week 40
85
[72, 99]
Week 44
113
[100, 127]
Week 48
141
[128, 155]
Week 52
169
[156, 190]
Week 58
211
[191, 232]
Week 64
253
[233, 274]
Week 70
295
[275, 316]
Week 76
337
[317, 358]
Week 82
379
[359, 400]
Week 88
421
[401, 442]
Week 94
463
[443, 498]
Week 104
533
[499, 568b]
Rx Day calculated relative to the first dose date of study drug in Part B.  For subjects re-randomized but not dosed in 
Part B, Rx Day calculated relative to the IRT date of Re-randomization evaluation.
a.
There is no local tolerability at re-randomization and after EOT.  If time is collected in vital signs, restrict to 
records prior to the first dose of study drug in Part B.


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Table 8.
Visit Windows for Analysis of PASI and sPGA, Local Tolerability, 
and Vital Signs in Part B 
(ITT_B_R/ITT_B_NR/PP_B_R/Safety_B_R/Safety_B_NR 
Populations) (Continued)
b.
The minimum of upper bound, the first dose date of retreatment with risankizumab for relapsed subjects (except the 
additional analysis as in footnote a), and within 105 days of last dose of study drug for safety analyses.  If time is 
collected in vital signs, restrict to records prior to the first dose of retreatment.
Note:
For additional PASI and sPGA analysis on ITT_B_R subjects re-randomized to risankizumab to evaluate 
continuous treatment, evaluations after retreatment with open label risankizumab will also be included along 
with blinded assessments.
Table 9.
Visit Windows for Analysis of Safety Laboratory Tests and ECG in 
Part B (Safety_B_R/Safety_B_NR Populations)
Window Label
Target Day
Interval
Entry of B
1
≤ 1
Week 40
85
[2, 127]
Week 52
169
[128, 211]
Week 64
253
[212, 295]
Week 76
337
[296, 379]
Week 88
421
[380, 477]
Week 104
533
[478, 589a]
Rx Day calculated relative to the first dose date of study drug in Part B.  For re-randomized subjects not dosed in Part B, 
Rx Day calculated relative to the IRT date of Re-randomization evaluation.
a.
The minimum of upper bound and first dose date of retreatment with risankizumab for relapsed subjects (and 
within 105 days of last dose of study drug for safety analyses).


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Table 10.
Visit Windows for Analysis of Other Efficacy Endpoints Only 
Collected at Week 52, 76, and 104 in Part B 
(ITT_B_R/ITT_B_NR/PP_B_R Populations)
Window Label
Target Day
Interval
Entry of B
1
≤ 1
Week 52
169
[2, 253]
Week 76
337
[254, 435]
Week 104
533
[436, 631a]
Rx Day calculated relative to  the first dose date of study drug in Part B.  For re-randomized subjects not dosed in 
Part B, Rx Day calculated relative to the IRT date of Re-randomization evaluation.
a.
The minimum of upper bound and first dose date of retreatment with risankizumab for relapsed subjects.
Table 11.
Visit Windows for Analysis of PASI and sPGA Across Part A2 and 
B (ITT_ARM2 Population)
Window Label
Target Day
Interval
Entry of A2
1
≤ 1
Week 20
29
[2, 43]
Week 24
57
[44, 71]
Week 28
85
[72, 99]
Week 32
113
[100, 127]
Week 36
141
[128, 155]
Week 40
169
[156, 183]
Week 44
197
[184, 211]
Week 48
225
[212, 239]
Week 52
253
[240, 274]
Week 58
295
[275, 316]
Week 64
337
[317, 358]
Week 70
379
[359, 400]
Week 76
421
[401, 442]
Week 82
463
[443, 484]
Week 88
505
[485, 526]
Week 94
547
[527, 582]
Week 104
617
[583, 652]
Rx Day calculated relative to first dose date of risankizumab.


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Table 12.
Visit Windows for Analysis of Other Efficacy Endpoints Collected 
at Week 28, 52, 76, and 104 in Part A2 and B (ITT_ARM2 
Population)
Window Label
Target Day
Interval
Entry of A2
1
≤ 1
Week 28
85
[2, 169]
Week 52
253
[170, 337]
Week 76
421
[338, 519]
Week 104
617
[520, 715]
Rx Day calculated relative to first dose date of risankizumab.
Table 13.
Visit Windows for Analysis of PASI and sPGA During Retreatment 
with Risankizumab (ITT_B_PBO_RT/ITT_B_RZB_RT 
Populations)
Window Label
Target Day
Interval
Entry of RTS
1
≤ 1
Week 8R
57
[2, 85]
Week 16R
113
≥ 86
Rx Day calculated relative to first dose date of retreatment with risankizumab.
Table 14.
Visit Windows for Analysis of Other Efficacy Variables Only 
Collected at EOT and EOO Visits During Retreatment with 
Risankizumab (ITT__B_PBO_RT/ITT_B_RZB_RT Populations)
Window Label
Target Day
Interval
Entry of RTS
1
≤ 1
Week 16R
113
≥ 2
Rx Day calculated relative to first dose date of retreatment with risankizumab.


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Table 15.
Visit Windows for Analysis of Vital Signs and Local Tolerability in 
the ALL_RZB Population
Window Label
Target Day
Interval
Baseline
1
≤ 1a
Week 4
29
[2, 43]
Week 8
57
[44, 71]
Week 12
85
[72, 99]
Week 16
113
[100, 155]
Week 28
197
[156, 239]
Week 40
281
[240, 323]
Week 52
365
[324, 407]
Week 64
449
[408, 491]
Week 76
533
[492, 575]
Week 88
617
[576, 673]
Week 104
729
[674, 785b]
Rx Day calculated relative to first dose date of risankizumab.
a.
Local tolerability not measured at Baseline and at Week 104.  If time is collected in vital signs, restrict to records 
prior to the first dose of risankizumab.
b.
The minimum of upper bound and within 105 days of last dose of risankizumab.


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Table 16.
Visit Windows for Analysis of Safety Laboratory Tests and ECG in 
the ALL_RZB Population
Window Label
Target Day
Interval
Baseline
1
≤ 1
Week 4
29
[2, 71]
Week 16
113
[72, 155]
Week 28
197
[156, 239]
Week 40
281
[240, 323]
Week 52
365
[324, 407]
Week 64
449
[408, 491]
Week 76
533
[492, 575]
Week 88
617
[576, 673]
Week 104
729
[674, 785a]
Rx Day calculated relative to first dose date of risankizumab.
a.
The minimum of upper bound and within 105 days of last dose of risankizumab.
The time windows specified in Table 17, Table 18, Table 19, Table 20, Table 21 and 
Table 22 will be used for the summary of study drug injections of each period.
Table 17.
Visit Windows for Summary of Study Drug Injections for Part A1
Window Label
Target Day
Interval
Week 0
1
≤ 1
Week 4
29
[2, 57a]
Rx Day calculated relative to the first dose date of study drug.
a.
Before the first dose date of study drug on or after Week 16.
Table 18.
Visit Windows for Summary of Study Drug Injections for Part A2
Window Label
Target Day
Interval
Week 16
1
≤ 1
Rx Day calculated relative to the Week 16 dose date.


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Table 19.
Visit Windows for Summary of Study Drug Injections for Part B
Window Label
Target Day
Interval
Week 28
1
≤ 1
Week 40
85
[2, 127]
Week 52
169
[128, 211]
Week 64
253
[212, 295]
Week 76
337
[296, 379]
Week 88
421
[380, 463a]
Rx Day calculated relative to the first dose date of study drug in Part B.
a.
Before retreatment.
Table 20.
Visit Windows for Summary of Study Drug Injections for Subjects 
Retreated with Risankizumab for Relapse from Week 32 Through 
Week 70 (Inclusive)
Window Label
Target Day
Interval
Week 0
1
≤ 1
Week 4R
29
[2, 71]
Week 16R
113
[72, 155]
Rx Day calculated relative to the first dose date of retreatment.
Table 21.
Visit Windows for Summary of Study Drug Injections for Subjects 
Retreated with Risankizumab for Relapse from Week 70 Through 
Week 82 (Inclusive)
Window Label
Target Day
Interval
Week 0
1
≤ 1
Week 4R
29
[2, 57]
Rx Day calculated relative to the first dose date of retreatment.
Table 22.
Visit Windows for Summary of Study Drug Injections for Subjects 
Retreated with Risankizumab for Relapse After Week 82
Window Label
Target Day
Interval
Entry of retreatment
1
≤ 1
Rx Day calculated relative to the first dose date of retreatment.


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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 each arm and for 
overall of the ITT populations.  Continuous variables will be summarized with the number 
of non-missing observations by mean, standard deviation, first quartile, median, 


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third quartile, minimum and maximum values.  Categorical data will be summarized using 
frequencies and percentages.  Statistical tests will be performed to assess the 
comparability of the two arms at Randomization on ITT_A1 and at Re-Randomization on 
ITT_B_R.  Per Protocol Populations will only be summarized in the accountability table.  
Treatment comparison will be made based on non-missing information.  Continuous 
variables will be analyzed using one-way analysis of variance (ANOVA).  Categorical 
variables will be analyzed using a two-sided Pearson's Chi-Square test (or an appropriate 
exact test if expected cell count < 5).
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, Multi Race)
●
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 categories


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●
NAPSI (Nail Psoriasis Severity Index)
●
PSSI (Psoriasis Scalp Severity Index)
●
PPASI (Palmoplantar Psoriasis Area Severity Index)
●
Dermatology Life Quality Index (DLQI)
●
HAQ-DI (HAQ Disability Index)
●
Pain VAS (Visual Analog Scale)/Patient Global Assessment (PtGA) VAS 
(Visual Analog Scale)
●
TJC/SJC (Tender/Swollen Joints)
●
DAS28 (Disease Activity)
Psoriasis and Cardiovascular History
●
Psoriatic arthritis (diagnosed, suspected, no)
●
Cardiovascular Diseases (myocardial infarction, angina pectoris, transient 
ischemic attack, stroke, deep vein thrombosis)
●
Cardiovascular Risk Factors (hypertension, hyperlipidemia, diabetes mellitus, 
obesity)
General Use 
●
Smoking status (Never-smoked, Ex-smoker, Currently smokes)
●
Alcohol status (Non-drinker, drinks – no interference with participation in 
trial, drinks – possible interference with participation in clinical trial)
Prior Treatment
●
Psoriasis Biologic Treatment History – by Response to Prior Treatment
●
Psoriasis Treatment – by Therapy Type (topical therapy, phototherapy, 
photochemotherapy, non-biologic systemic therapy, TNF antagonist, other 
biologic)
Also, Physical Exam and Pregnancy Test will be presented in listing format.


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7.2
Medical History
Medical history 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
Prior and concomitant medications will be summarized by generic name.  A prior 
medication is defined as any medication taken prior to the first dose of study drug.  A 
concomitant medication is defined as any medication that started prior to the first dose of 
study drug and continued to be taken after the first dose of study drug or any medication 
that started after the first dose of study drug, but not after the last dose of study drug plus 
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 Deviations
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 treatment


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8.0
Patient Disposition
The number of subjects for each of the following categories will be summarized, for 
overall and for each treatment group in the ITT_A1 Population:
●
Number of subjects randomized
●
Number of subjects treated during Part A1
●
Number of subjects who completed Part A1
●
Number of subjects who discontinued study drug during Part A1
●
Number of subjects who prematurely discontinued from Part A1
The number of subjects for each of the following categories will be summarized, for 
overall and for each treatment group in the ITT_B_R population:
●
Number of subjects re-randomized
●
Number of subjects treated at Part B
●
Number of subjects who completed the Part B
●
Number of subjects who received retreatment with risankizumab during Part B 
at different time points
●
Number of subjects who discontinued study drug during Part B
●
Number of subjects who prematurely discontinued from the Part B
In addition, the reasons for premature discontinuation will be summarized with 
frequencies and percentages. 
Disposition tables will also be summarized in the ITT_A2, ITT_ARM2, and ITT_B_NR 
Populations.
In addition to patient disposition, number of screening failures and reasons for screening 
failure will also be summarized among all screened subjects in a subject screening status 
table.


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9.0
Study Drug Exposure and Compliance
Summary of study drug exposure will be provided for each treatment arm for all ITT_A1, 
ITT_A2, ITT_ARM2, ITT_B_R, and ITT_B_NR populations, and the ALL_RZB 
population.  Study drug compliance will be summarized in ITT_A1, ITT_A2, and 
ITT_B_R populations.
Study drug exposure (days) will be summarized using the sample size, mean, standard 
deviation, minimum, median and maximum for each treatment part.  In addition 
cumulative exposure of RZB will be also summarized in the ALL_RZB Population.  
Study drug exposure will be summarized as follows:
Study Drug Exposure (in Days) in Each Period:
Part A1:
For subjects who did not continue into Part A2:
●
Date of last injection in Part A1 – Date of first injection in Part A1 + 84.
For subjects who continued into Part A2:  the minimum of
●
Date of first injection in Part A2 – Date of first injection in Part A1.
●
Date of last injection in Part A1 – Date of first injection in Part A1 + 84 days.
Part A2:
For subjects who did not continue into Part B:
●
Date of last injection in Part A2 – Date of first injection in Part A2 + 84 days.
For subjects who continued into Part B:  the minimum of
●
Date of first injection in Part B – Date of first injection in Part A2.
●
Date of last injection in Part A2 – Date of first injection in Part A2 + 84 days.


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Part B:
For subjects who did not receive retreatment with risankizumab:  the minimum of
●
Date of last injection in Part B – Date of first injection in Part B + 84 days.
●
Cutoff date of 01 September 2017 – Date of first injection in Part B (only for 
the primary analysis after the last patient either has completed Week 52 visit or 
discontinues from the study)
For subjects who received retreatment with risankizumab:  the minimum of
●
Date of first injection of retreatment – Date of first injection in Part B.
●
Date of last injection in Part B – Date of first injection in Part B + 84 days.
●
Cutoff date (01 September 2017) – Date of first injection in Part B (only for 
the primary analysis after the last patient either has completed Week 52 visit or 
discontinues from the study)
ALL_RZB:
For subjects who were re-randomized to placebo in Part B and received retreatment with 
risankizumab:  the minimum of
●
Date of last injection of risankizumab in Part A – Date of first injection of 
risankizumab + 84 days + Date of last retreatment of risankizumab – Date of 
first retreatment of risankizumab + 84 days.
●
Date of last injection of risankizumab in Part A – Date of first injection of 
risankizumab + 84 days + Cutoff date for retreatment (22 September 2017) –
Date of first retreatment of risankizumab (only for the primary analysis after 
the last patient either has completed Week 52 visit or discontinues from the 
study).
For all other subjects:  the minimum of
●
Date of last injection of risankizumab – Date of first injection of risankizumab 
+ 84 days.


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●
Cutoff date (01 September 2017) – Date of first injection of risankizumab 
(only for the primary analysis after the last patient either has completed 
Week 52 visit or discontinues from the study)
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 scheduled time point, the denominator for each 
week will include all subjects in each analysis population who have not prematurely 
discontinued 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 treatment effect will be evaluated based on a two-sided significance level of 0.05 
(when rounded to three decimal places).
The Primary Analysis for Period B re-randomized subjects will be conducted after the last 
patient either has completed Week 52 visit or discontinues from the study, and at the time 
approximate to the database lock of all other global pivotal Phase 3 psoriasis studies, 
whichever occurs later.  All endpoints will be analyzed up to Week 52, with the following 
exception:
●
Categorical endpoints related to PASI and sPGA, using the LOCF method 
(defined in Section 10.1.4), will be analyzed up to the last visit that at least 
one subject has observed PASI and sPGA measurements, respectively.


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To best maintain the study integrity for data beyond Week 52, blinded treatment 
assignments will not be disseminated to the sites, investigators, and patients until the end 
of study database lock.
Efficacy variables will be summarized in all efficacy populations.  The efficacy analysis 
will be conducted in the ITT_A1 and the ITT_B_R populations.  Only the primary and 
ranked secondary variables will be analyzed for the per-protocol populations using 
primary approach to handle missing data as described below.  
Subjects' actual weight category and prior TNF antagonist exposure will be used as the 
strata in the stratified analyses.
10.1.1
Analyses of Categorical Variables
For categorical variables, frequencies and percentages will be summarized.  Treatment 
comparison will be conducted using a Cochran-Mantel-Haenszel (CMH) test with 
stratification factors as strata for the analysis.  The CMH test will use weights proposed 
by Greenland & Robins, which is calculated as follows:
 =
∑

 ∙


∑




 , where
 = 

 − 

  denotes the risk difference in stratum &, & = 1, ⋯, )

 =  ∙
 + 
  denotes the weight of stratum &, & = 1, ⋯, )
 denotes the number of patients with event in treatmentin stratum i, & = 1, ⋯, )
 denotes the number of patients with event in treatment/in stratum i, & = 1, ⋯, )
 denotes the number of patients on treatmentin stratum i, & = 1, ⋯, )
 denotes the number of patients on  treatment/in stratum i, & = 1, ⋯, )
The estimated variance of  is calculated as:


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012
3 45 =
∑
6


(∑




)/
where 6 = ( −) 
9 + ( −) 
9
 ∙ ∙( + )/
 , & = 1, ⋯, )
Assuming a normal distribution of  , an approximate 95% CI is given as follows,
where :;.=>? is the 97.5% quantile of the standard normal distribution:
@A =  B  ± :;.=>? ∙D012
3 45E
Also, the approximate p-value can be calculated using the following:
pvalue =  2 ∙Pr
⎣
⎢
⎢
⎡
L > NN

D012
3 45
NN 
⎦
⎥
⎥
⎤
 , where L ~ S(0, 1)
If there is a stratum for a treatment group that has 0 subjects in any cell in the contingency 
table, all cells from the stratum will be added by 0.1 in order to prevent dividing by 0 in 
the above equations, as suggested in Greenland & Robins.
10.1.2
Analyses of Continuous Variables
For continuous variables, the model based mean and standard error will be presented.  The 
Baseline and visit means will also be presented for each treatment group for subjects who 
have both Baseline and post Baseline visit values.  The treatment groups will be compared 
using ANCOVA with treatment group, Baseline value, and stratification factors in the 
model.
10.1.3
Analyses of Time-to-Event Variables
Time to first achievement of endpoints will only be performed in ITT_A1 up to Week 16.  
The time to event will be calculated as:


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●
Time to first achievement (with observed event) = [date of first achievement] –
[date of first dose] + 1
●
If a subject never attains Endpoint at the end of evaluation period, that 
subject's time to first achievement will be censored at the last visit where the 
variable was measured
Time to loss-of-response (and time to relapse) endpoints will only be performed in 
ITT_B_R Population among those who achieved response at Re-Randomization.  The 
time to failure events will be calculated as:
●
Subjects will be a considered as failures if they subsequently lost the response, 
or discontinue from the study due to AE of "Worsening of disease under 
study," or receive retreatment with risankizumab.
●
Time to failure events = [date of failure] – [date of first dose in Part B] + 1
●
Subjects who maintain Endpoint throughout the study, or discontinued from 
the study due to reasons other than above, will be censored at their last 
measurement.
Both time to first achieving endpoints and time to loss-of-response endpoints will be 
analyzed using Kaplan-Meier estimates for each treatment group.  In the ITT_A1 and 
ITT_B_R populations, treatments will be compared using stratified Log-rank test.
10.1.4
Missing Data Imputations
Missing data will be imputed using the following methods for the efficacy analyses:
●
Non-Responder Imputation (NRI):  the NRI analysis will categorize any 
subject who does not have evaluation during a specific visit window as a non-
responder for that visit.  The only exception is when the subject is a responder 
both before and after a specific visit window, then the subject will be 
categorized as a responder for the visit.  Only observations within the same 
analysis period will be used except for summary of ITT_A2 from ARM 1, 
where subjects' observation from Part A1 can be used since the treatment is the 


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same.  The NRI will be the primary approach in the analyses of categorical 
variables.
●
Last Observation Carried Forward (LOCF):  The LOCF analyses will use the 
last observed non-missing evaluation (last completed non-missing evaluation, 
from composite endpoint) from the previous visit within the particular period 
for efficacy measures assessed to impute missing data at later visits in the same 
period.  Baseline efficacy evaluations will not be carried forward.  Of note, 
post-baseline observations from Part A1 can be carried forward to ITT_A2 
subjects from ARM 1 since treatment is the same.  LOCF will be the primary 
approach in the analyses of continuous variables, and the secondary approach 
in the analysis of categorical variables.
●
As-Observed Cases (OC):  The as-observed analysis will not impute values for 
missing evaluations, and thus a subject who does not have an evaluation on a 
scheduled visit will be excluded from the as-observed analysis for that visit.  
As-observed analysis will be the secondary approach in the analysis of 
continuous variables.
●
Multiple Imputation (MI):  The MI will be used as sensitivity approach to 
impute missing data in primary and ranked secondary endpoints.  The 
variables to be included in the imputation model are listed below.  If MI is not 
applicable due to the nature of our data (e.g., MCMC algorithm does not 
converge), logistic regression or mixed effect model repeat measurement 
(MMRM) methods will be applied as sensitivity approach, whichever 
applicable.
The Multiple Imputation analysis will be carried out in three steps.
●
Imputation of missing data.  The imputation will be generated for each efficacy 
endpoint measurement.  The variables to be included in the imputation model 
are:  Baseline disease severity (PASI and sPGA), Baseline weight (continuous 
variable), treatment group, actual prior TNF antagonist exposure, and 
measurements at each visit from randomization (or re-randomization) up to the 
end of the analysis period.  For each endpoint, 20 'complete' datasets will be 
generated using SAS PROC MI.  The imputed post-baseline measurements 


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will be rounded to the same precision as the observed data before the 
determination of responder status (e.g., PASI 90).
●
Analysis of imputed data sets.  A CMH test, stratified by stratification factors, 
will be used to analyze categorical endpoints in each imputed dataset.
●
Synthesis of imputation and analysis results.  SAS PROC MIANALYZE will 
be used to generate the final inferences of the risk difference between 
treatment groups.
Of note, subjects who discontinued due to AE of "Worsening of disease under study," or 
received retreatment with risankizumab for relapse during Part B, will be counted as non-
responders in all visits thereafter in the NRI and MI analyses, and will have their last 
observation prior to discontinuation or retreatment with risankizumab carried forward in 
the LOCF analyses.  
10.2
Primary Efficacy Analysis
10.2.1
Primary Efficacy Analysis in Part A
There are two co-primary endpoints to assess the efficacy of risankizumab 150 mg for the 
treatment of moderate to severe plaque psoriasis in Part A.  These are as follows:
●
Achievement of ≥ 90% reduction from baseline PASI score (PASI 90) at 
Week 16
●
Achievement of an sPGA of clear or almost clear (0 or 1) at Week 16
The primary null hypotheses are that risankizumab 150 mg is not different from placebo 
in achieving PASI 90 and in achieving sPGA of clear or almost clear at Week 16. 
The achievement of PASI 90 at Week 16 is the first co-primary endpoint.  The difference 
in proportion of subjects achieving PASI 90 between treatment arms will be estimated and 
tested using the Cochran-Mantel-Haenszel risk difference estimate stratified by the 
stratification factors of baseline weight (≤ 100 kg vs. > 100 kg) and prior exposure to TNF 
antagonists (0 vs. ≥ 1).


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The achievement of a sPGA of clear or almost clear at Week 16 is the second co-primary 
endpoint.  The analysis method for the sPGA co-primary endpoint will be identical to that 
of the PASI 90 co-primary endpoint detailed above.
The co-primary endpoints of PASI 90 and sPGA clear or almost clear need to be 
significant simultaneously.  Both endpoints will be tested using a two-sided test with a 
type I error rate of 0.05.
The primary analysis will be carried out in the ITT_A1 Population and the PP_A1 
Population.  Non-responder imputation will be used as the primary approach for missing 
values.  LOCF and MI will be performed as sensitivity analyses.
10.2.2
Primary Efficacy Analysis in Part B
Achievement of an sPGA of clear or almost clear (0 or 1) at Week 52 is the primary 
endpoint for Part B under re-randomization.  This endpoint will be tested independently 
with a type I error rate of 0.05, for the ITT_B_R Population.  A sensitivity analysis will 
also be performed on the same endpoint for the PP_B_R Population.
10.3
Secondary Efficacy Analyses
10.3.1
Ranked Secondary Efficacy Analysis 
10.3.1.1
Ranked Secondary Efficacy Analysis in Part A
The ranked secondary endpoints in Part A are in ranked order as follows:
1.
Achievement of ≥ 75% reduction from baseline PASI score (PASI 75) at Week 16
2.
Achievement of 100% reduction from baseline PASI score (PASI 100) at Week 16
3.
Achievement of sPGA of clear at Week 16
4.
Achievement of DLQI score of 0 or 1 at Week 16


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Ranked secondary endpoints above will be analyzed for the ITT_A1 Population.  The 
same methods as discussed for the primary analyses will be used.  The following null 
hypotheses will be tested in a hierarchical order using two-sided tests with a type I error 
of 0.05 only if the null hypothesis for the co-primary endpoints in Part A1 has been 
rejected:
1.
Risankizumab is not different from placebo with respect to PASI 75 response at 
Week 16
2.
Risankizumab is not different from placebo with respect to PASI 100 response at 
Week 16
3.
Risankizumab is not different from placebo with respect to achieving an sPGA of 
clear at Week 16
4.
Risankizumab is not different from placebo with respect to achieving a DLQI score 
of 0 or 1 at Week 16.
10.3.1.2
Ranked Secondary Efficacy Analysis in Part B
The ranked secondary endpoint for Part B is the achievement of sPGA of clear or almost 
clear (0 or 1) at Week 104.
This ranked secondary endpoint will be analyzed for the ITT_B_R Population.  The same 
methods as discussed for the primary analyses will be used.
The null hypotheses below will be tested in a hierarchical order in the final analysis only, 
using two-sided tests with a type I error of 0.05 only if the null hypothesis for the primary 
endpoint in Part B has been rejected:
●
Continuation of risankizumab is not different from switching to placebo with 
respect to sPGA of clear or almost clear (0 or 1) response at Week 104.


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10.3.2
Other Secondary Efficacy Analysis
The other secondary endpoints are as follows:
●
Achievement of PASI 75 at Week 52
●
Achievement of PASI 90 at Week 52
●
Achievement of PASI 100 at Week 52
Other secondary endpoints will be analyzed among the ITT_B_R Population.  
10.3.3
Further Efficacy Endpoints 
The further endpoints are as follows:
●
Achievement of PASI 50 at all visits collected
●
Achievement of PASI 75 at all visits collected
●
Achievement of PASI 90 at all visits collected
●
Achievement of PASI 100 at all visits collected
●
Time to the first achievement of PASI 50, PASI 75, PASI 90, and PASI 100
●
Time to loss of PASI 50, PASI 75, PASI 90, and PASI 100 response for 
subjects re-randomized at Week 28
●
Change and percent change from baseline in PASI at all visits collected
●
Achievement of PASI < 3 at all visits collected
●
Proportion of subjects with at least 25% increase in PASI from baseline within 
60 days after re-randomization for subjects re-randomized to placebo at 
Week 28
●
Achievement of sPGA of clear or almost clear at all visits collected
●
Achievement of sPGA of clear at all visits collected
●
Time to the first achievement of sPGA of clear or almost clear
●
Time to loss of sPGA of clear or almost clear response for subjects 
re-randomised at Week 28
●
Time to  sPGA of ≥ 3 (relapse) for subjects re-randomised at Week 28
●
Change from baseline in DLQI at all visits collected


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●
Achievement of a DLQI score of 0 or 1 at all visits collected
●
Achievement of a reduction of 5 or more points from baseline in DLQI score 
at all visits collected, among subjects with baseline DLQI ≥ 5
●
Change from baseline in HAQ-DI at all visits collected, among subjects with 
PsA confirmed via ClASsification of Psoriatic Arthritis (CASPAR) and had 
baseline value > 0
●
Achievement of a reduction of 0.3 or more from baseline HAQ-DI at all visits 
collected, among subjects with PsA confirmed via CASPAR and had baseline 
value ≥ 0.3
●
Change and percent change from baseline on patient Pain VAS, among 
subjects with PsA confirmed via CASPAR and had baseline value > 0
●
Achievement of a reduction of 10 or more from baseline Pain VAS at all visits 
collected, among subjects with PsA confirmed via CASPAR and had baseline 
value ≥ 10
●
Change and percent change from baseline on patient Global Assessment VAS, 
among subjects with PsA confirmed via CASPAR and had baseline value > 0
●
Change from baseline in Swollen or Tender Joint Count (28 joints) at all visits 
collected, among subjects with PsA confirmed via CASPAR and had baseline 
value > 0
●
Change from baseline in DAS28 at all visits collected, among subjects with 
PsA confirmed via CASPAR and had baseline value > 0
●
Change and percent change from baseline in Nail Psoriasis Severity Index 
(NAPSI) at all visits collected, in subjects with baseline NAPSI > 0
●
Change and percent change from baseline in Palmoplantar Psoriasis Severity 
Index (PPASI) at all visits collected, in subjects with baseline PPASI > 0
●
Change and percent change from baseline in Psoriasis Scalp Severity Index 
(PSSI) at all visits collected, in subjects with baseline PSSI > 0
10.4
Handling of Multiplicity
The statistical comparisons for the primary efficacy variable and the ranked secondary 
variables will be carried out in the hierarchical order.  This means that statistically 


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significant results (P value ≤ 0.05) for the comparison in the higher rank (primary, then 
ranked secondary variables) are necessary to initiate the testing of the next comparison in 
the lower rank.  Since a step-down procedure is used, each comparison will be tested at a 
significance level of 0.05 and overall alpha level of 0.05 will be preserved.
10.5
Efficacy Subgroup Analysis
To evaluate the consistency of the efficacy over demographic and other baseline 
characteristics, summaries and analyses will be performed for selected subgroups for the 
primary efficacy endpoints in Part A and the primary efficacy endpoint in Part B.
●
Age group (< 40 years, ≥ 40 – < 65 years, ≥ 65 years)
●
Sex (male, female)
●
Race (white, non-white)
●
Smoking (current, ex or never)
●
BMI (normal:  < 25, over weight:  ≥ 25 – < 30, obese:  ≥ 30)
●
Region (US, Asia, Other)
●
Baseline PASI score (by median)
●
Baseline sPGA (3, 4)
●
Psoriatic arthritis (yes [diagnosed or suspected], no)
●
Ps Therapy History (Phototherapy or Photochemotherapy, TNF Antagonist, 
Other biologics, Non-biologic systemic therapy, All biologics, Naïve to all)
11.0
Safety Analysis
11.1
General Considerations
Safety analyses will include adverse events, laboratory, local tolerability, ECG, and vital 
sign measurements.  Safety summaries will be provided using the safety population in 
each period as defined in Section 5.1.  Comparison between risankizumab group and 
placebo group will be performed in the Safety Population in Safety_A1 and Safety_B_R 
populations.  Continuous variables will be analyzed using one-way ANOVA and 


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categorical variables will be analyzed using Fisher's exact test.  For analyses of AEs, only 
P values ≤ 0.100 when rounded to three digits will be presented.
Missing safety data will not be imputed.
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 study drug and with an onset date within 105 days after the last 
dose of study drug in the analysis period, or prior to the first dose in the subsequent period 
for subjects who entered in to the subsequent 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 with the following exception:
●
If an AE onset date is the same as the first dose of Part B and the AE time is 
missing, the AE is considered TEAE for the Part A2.  
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).
Treatment-emergent adverse events (TEAE) for each safety population are defined as 
follows:
TEAEs of Safety_A1:
For subjects who do not enter Part A2, TEAEs are defined as any event with an onset after 
the first dose of study drug and no more than 105 days after the last dose of study drug.
For subjects who enter Part A2, TEAEs are defined as any event with an onset after the 
first dose of study drug and before the first dose of study drug in Part A2.


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TEAEs of Safety_A2 for Subjects from ARM 1:
For subjects who do not enter Part B, TEAEs are defined as any event with an onset after 
the first dose of study drug in Part A2 and no more than 105 days after the last dose of 
study drug in Part A2.
For subjects who enter Part B, TEAEs are defined as any event with an onset after the 
first dose of study drug in Part A2 and prior to the first dose of study drug in Part B. 
TEAE of Safety_ARM2:
TEAEs are defined as any event with an onset after the first dose of study drug in Part A2 
or Part B and no more than 105 days after the last dose of study drug in the study.
TEAEs of Safety_B_NR:
TEAEs are defined as any event with an onset after the first dose of study drug in Part B 
and no more than 105 days after the last dose of study drug in the study.
TEAEs of Safety_B_R:
For subjects who do not receive retreatment with risankimumab, TEAEs are defined as 
any event with an onset after the first dose of study drug in Part B and no more than 
105 days after the last dose of study drug in Part B.
For subjects who receive retreatment with risankimumab, TEAEs are defined as any event 
with an onset after the first dose of study drug in Part B and before the first dose of 
retreatment with risankimumab.
TEAEs of Safety_B_PBO_RT and Safety_B_RZB_RT:
TEAEs are defined as any event with an onset that is after the first dose of retreatment and 
no more than 105 days after the last dose of study drug.


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TEAE of ALL_RZB:
TEAEs are defined as any event with an onset after the first dose of risankizumab through 
105 days after the last dose of risankizumab, except for AEs with an onset during 
protocol-designed treatment gaps (i.e., placebo period) that was more than 105 days from 
the last dose of the previous risankizumab treatment and before the first dose of 
retreatment.
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 AE
●
Any AE that was assessed as related to study drug by the investigator
●
Any severe AE
●
Any serious AE (SAE)
●
Any serious AE that was assessed as related to study drug by the investigator
●
Any AE leading to discontinuation of study drug
●
Any AE leading to death
●
Any deaths
●
Areas of Safety Interest
2.
Adverse Events by System Organ Class and Preferred Term
TEAEs will 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 


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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 with causal relationship 
between the events and the study drug will be summarized using the same 
conventions described above. 
3.
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.
4.
Adverse Events by Maximum Relationship
Adverse events will be summarized by maximum relationship to study drug, as 
assessed by the investigator.  Relationship of an AE to study drug is assessed by 
the investigator and collected in the CRF as 'Yes' or 'No.'  If a subject has an 
adverse event with unknown relationship, the subject will be counted in the 
relationship category of "unknown," even if the subject has another occurrence of 
the same event with a relationship of "No."  If the subject has another occurrence 


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of the same adverse event with a relationship assessment of "Yes," the subject will 
be counted under the "yes" category. 
A listing of all pretreatment (i.e., events start prior to the first study drug injection) serious 
adverse events will be provided. 
The following tables are planned.
Treatment-emergent adverse events will be summarized as follows:
●
Grouped by SOC and PT
●
Grouped by SOC, PT and maximum relationship to study drug
●
Grouped by SOC, PT and maximum severity
Treatment-emergent serious adverse events will be summarized as follows:
●
Grouped by SOC and PT
●
A by-subject listing will be provided
Pre-treatment serious adverse events will be summarized as follows:
●
A by-subject listing will be provided
Treatment-emergent adverse events leading to death or premature discontinuation 
of study drug will be summarized as follows:
●
Grouped by SOC and PT
●
Separate listings by subject for deaths and premature terminations of study 
drug due to adverse events will be provided.
Treatment-emergent areas of safety interest will be summarized as follows:
●
Grouped by SOC and PT
●
A listing by subject will be provided.


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Areas of Safety Interest:
Areas of Safety Interest groupings are listed in Table 23.  These events are of interest due 
to a higher rate in the moderate to severe psoriasis population, or of interest for all Ig 
products or products in general.
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.
Table 23.
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/
Thromboembolism, 
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


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Table 23.
Areas of Safety Interest (Continued)
ASI Grouping
Categories 
(ASI)
Search Criteria
Terms to Display
Include 
in AE 
Overview 
(Y/N)
Adjudicated 
CV Events 
(continued)
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/
Thromboembolism, 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
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


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Table 23.
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) 
(continued)
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 23.
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


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Adverse Event per 100 Patient-Years of Exposure
Adverse events occurring during the entire study will be presented by event rate per 
100 patient-years.  These will be presented for any TEAEs, serious adverse events, and 
Areas of Special Interest. 
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.
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.
11.2.2
SAEs (Including Deaths) and Adverse Events Leading to 
Study Drug Discontinuation
Deaths and all SAEs will be presented in listing format.  In addition, SAEs and AE 
leading to study drug discontinuation will be summarized by System Organ Class and 
MedDRA Preferred Term.
11.2.3
Safety Subgroup Analysis
The AE overview and AE by SOC and PT in Safety_A1 and Safety_B_R populations will 
also be analyzed with respect to the actual values of stratification factors:
●
Dichotomous weight (≤ 100 kg vs. > 100 kg)
●
Prior exposure to TNF antagonists (0 versus ≥ 1)
Years
Patient 
Total
TEAEs
of
Number 
100 ∀


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11.3
Analysis of Laboratory Data
For the assessments of laboratory data, values observed more than 105 days after the last 
dose of study drug will be excluded.
Listing and descriptive statistics of laboratory values over time, changes from baseline, 
and extreme abnormal value on treatment will be provided.  Extreme abnormal value is 
the 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.
Analyses will be conducted in the Safety_A1 Population, the Safety_B_R Population, and 
the ALL_RZB Population.
For subjects who were re-randomized to placebo in Part B, laboratory values evaluated 
after 105 days from the last dose of risankizumab in Part A and before the first dose of 
retreatment will not be included in the summaries for the ALL_RZB Population.
11.3.1
Variables and Criteria Defining Abnormality
Clinical laboratory tests conducted in the study are listed in Table 24.


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Table 24.
Clinical Laboratory Tests
Category
Test Name
Haematology
Hematocrit (Hct)
Hemoglobin (Hb)
Glycosylated Hb (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)
Enzymes
AST (GOT)
ALT (GPT)
Alkaline Phosphatase (AP)
Creatine Kinase (CK)
Gamma-Glutamyl Transferase (GGT/γ-GT)
Lactic Dehydrogenase (LDH)
Amylase
Lipase
Electrolytes
Calcium
Sodium
Potassium
Substrates
Glucose
BUN
Uric acid
Creatinine
eGFR (estimated by CKD-EPI formula)
Bilirubin Total
Albumin
C-Reactive Protein (high sensitivity)
Cholesterol, total
Triglycerides
LDL-Cholesterol (calculated)
HDL-Cholesterol
Urinalysis (Stix)
Urine Protein
Urine Glucose


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11.3.2
Statistical Methods
Analysis of Quantitative Laboratory Parameters (Hematology and Chemistry)
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 lab analyses based on the NCI CTCAE scale 
will be presented.  Changes from Baseline to each scheduled visit and to the final value in 
continuous laboratory parameters will be summarized with the mean, standard deviation 
and median.  The Baseline and visit/final value means will also be presented for subjects 
who have both the Baseline and visit/final values (see Section 6.0 for the definition of 
Baseline and final values). 
If there are multiple post-baseline measurements on the same day, average value will be 
used.
Shift Tables
Shift tables for changes from Baseline according to the normal range will be provided for 
each hematology, and clinical chemistry parameter.  Shifts from Baseline to the following 
endpoints will be considered:  minimum value, maximum value and final value.  
Categories of "low or normal" and "high or normal" will be included at Baseline in 
addition to the categories of "low," "normal," "high" and "missing." 
If there are multiple post-baseline measurements on the same day, the last value will be 
used.
Potentially Clinically Important Laboratory Values
Frequencies and percentages of subjects with post Baseline lab values meeting the 
following criteria in Table 25 and Table 26 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 25.
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
TBL
mcmol/L
> 3.0 × ULN
SGOT/AST
U/L
> 5.0 × ULN
SGPT/ALT
U/L
> 5.0 × ULN
Albumin
g/L
< 20
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
CPK
U/L
> 5.0 × ULN
Total Cholesterol
mmol/L
> 10.34
GGT
> 5.0 × ULN
ALP
> 5.0 × ULN
Note:
A post baseline value must be more extreme than the baseline value to be considered a potentially clinically 
important finding.
Table 26.
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
WBC count
109/L
< 2.0
Neutrophils
109/L
< 1.0
Lymphocytes
109/L
< 0.5
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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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.  The NCI CTCAE grading is shown in Table 27
below:
Table 27.
NCI CTCAE Grading
Test
Grade 1
Grade 2
Grade 3
Grade 4
SGPT/ALT 
increased
> ULN – 3.0 × ULN
> 3.0 – 5.0 × ULN
> 5.0 – 20.0 × ULN
> 20.0 × ULN
SGOT/AST 
increased
> ULN – 3.0 × ULN
> 3.0 – 5.0 × ULN
> 5.0 – 20.0 × ULN
> 20.0 × ULN
GGT increased
> ULN – 2.5 × ULN
> 2.5 – 5.0 × ULN
> 5.0 – 20.0 × ULN
> 20.0 × ULN
ALP increased
> ULN – 3.0 × ULN
> 3.0 – 5.0 × ULN
> 5.0 – 20.0 × ULN
> 20.0 × ULN
TBL increased
> ULN – 1.5 × ULN
> 1.5 – 3.0 × ULN
> 3.0 – 10.0 × ULN
> 10.0 × ULN
Creatinine 
increased
> ULN – 1.5 × ULN
> 1.5 – 3.0 × ULN
> 3.0 – 6.0 × ULN
> 6.0 × ULN
CPK increased
> ULN – 2.5 × ULN
> 2.5 – 5.0 × ULN
> 5.0 – 10.0 × ULN
> 10.0 × ULN
Hemoglobin 
decreased
< LLN – 100.0 g/L
< 100.0 – 80.0 g/L
< 80.0
Neutrophil count 
decreased
< LLN – 1.5 × 109/L
< 1.5 – 1.0 × 109/L
< 1.0 – 0.5 × 109/L
< 0.5 × 109/L
WBC decreased
< LLN – 3.0 × 109/L
< 3.0 – 2.0 × 109/L
< 2.0 – 1.0 × 109/L
< 1.0 × 109/L
Lymphocyte 
count decreased
< LLN – 0.8 × 109/L
< 0.8 – 0.5 × 109/L
< 0.5 – 0.2 × 109/L
< 0.2 × 109/L
If there are multiple post-baseline measurements on the same day, the worst value will be 
used.
Liver Function Tests
Additional summaries will be presented for liver function tests including ALT or serum 
glutamic-pyruvic transaminase (SGPT), AST or serum glutamic-oxaloacetic transaminase 
(SGOT), alkaline phosphatase, and total bilirubin.  Each laboratory value will be 
categorized as follows:


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●
< 1.5 × ULN
●
≥ 1.5 × ULN – < 3.0 × ULN
●
≥ 3.0 × ULN – < 5.0 × ULN
●
≥ 5.0 × ULN – < 10.0 × ULN
●
≥ 10.0 × ULN – < 20.0 × ULN
●
≥ 20.0 × ULN
Shift tables of Baseline to the maximum (relative to the normal range, i.e., the largest 
multiple relative to the upper limit of normal) values, and from Baseline to final value will 
be presented using these categories.  A listing of potentially clinically important liver 
function laboratory values will be provided.  The listing will include all subjects who met 
any of the following four criteria:
●
ALT ≥ 3 × ULN, or
●
AST ≥ 3 × ULN, or
●
Alkaline phosphatase ≥ 1.5 × ULN, or
●
Total bilirubin ≥ 2 × ULN.
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
Analyses will be conducted in the Safety_A1 Population, the Safety_B_R Population, and 
the ALL_RZB Population.


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For subjects who were re-randomized to placebo in Part B, vital sign values evaluated 
after 105 days from the last dose of risankizumab in Part A and before the first dose of 
retreatment will not be included in the summaries for the ALL_RZB Population.
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 presents the Criteria for 
Potentially Clinically Important 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 28.
Criteria for Potentially Clinically Important Vital Sign Findings
Vital Sign
Category
Criteria for Potential Clinically Important 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
Note:
A post baseline value must be more extreme than the baseline value to be considered a potentially clinically 
important finding.
11.4.2
Statistical Methods
Changes from Baseline to each visit and to the final value in vital sign parameters will be 
summarized with the mean, standard deviation and median.  The Baseline and final value 
means will also be presented for subjects who have both the Baseline and final values (see 
Section 6.0 for the definition of Baseline and final values).


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For baseline, if there are multiple measurements on the same day, the last measurement 
prior to the first dose of study drug will be used as the Baseline vital sign value.  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 selected vital 
sign parameter.
11.5
Analysis of ECG Parameters
The ECG parameters will be assessed as scheduled in the study protocol.
Summary statistics for mean change from baseline for corrected QT interval (QTc) using 
Bazett (QTcB) and Fridericia (QTcF) corrections, aggregated, will be provided by 
analysis visits.
●
Values for both QTcF and QTcB interval measurements will be categorized 
into the following:  ≤ 450 ms, > 450 ms, > 480 ms, > 500 ms, or missing.  For 
the scheduled visits, as well as baseline, the number and percentage of subjects 
within each category will be presented.  Additionally, for each category, the 
number and percentage of subjects with a maximum QTcF interval falling into 
the category will be presented; a similar summary will be presented for QTcB 
intervals.
●
For QTcF and QTcB intervals, the changes from baseline will be categorized 
into the following:  < 30 ms, 30 ≤ – < 60 ms, ≥ 60 ms, or missing.  For the 
scheduled visits, the number and percentage of subjects within each category 
will be presented.  Additionally, for each category, the number and percentage 
of subjects with a maximum change from baseline in the QTcF interval falling 
into the category will be presented; a similar summary will be presented for 
QTcB intervals.


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Analyses will be conducted in the Safety_A1 Population, the Safety_B_R Population, and 
the ALL_RZB Population.  
11.6
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.  
Proportion of subjects reporting each condition will be summarized.
Local tolerability will be summarized in the Safety_A1 Population and the Safety_B_R 
Population.  In addition, the overall rate (with at least one occurrence) during the study 
will also be presented in the ALL_RZB Population.
12.0
Pharmacokinetic Analysis
Pharmacokinetic analysis is not covered in this SAP.
13.0
Biomarkers Analysis
Biomarker Analysis is not covered in this SAP.
14.0
Summary of Changes
14.1
Summary of Changes Between the Latest Version of 
Protocol and the Current SAP
●
Defined analysis populations (including the Per-protocol population) in detail.
●
Clarified independent null hypothesis test hierarchy in the ITT Population in 
Part B consisting re-randomized subjects.
●
Added additional ranked secondary endpoint to the ITT Population in Part B 
consisting re-randomized subjects:  achievement of sPGA of clear or almost 
clear (0 or 1) at Week 104.
●
Pre-specified Areas of Safety Interest.


Risankizumab
1311.4 – Statistical Analysis Plan
Version 2.0 – 12 Sep 2017
64
14.2
Summary of Changes Between the Previous Version and the 
Current Version of the SAP
Updated Table 25, Table 27, and Table 28 based on Integrated Summary of Safety SAP.
Updated the end day for inclusion concomitant medications, based on Integrated 
Summary of Safety SAP.
15.0
Appendix
None.
16.0
References
None.
17.0
List of Tables, Figures and Data Listings That are to 
Be Programmed
To be provided in a separate document.