Clinical trial NCT02513459
Conditions: Crohn Disease
Keywords: ABBV-066 BI 655066 Risankizumab
Sponsor: AbbVie
Start date: 2015-09-16; Completion date: 2019-06-19
Enrollment: 65 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The primary objective of the study was to investigate long-term safety of risankizumab (BI 655066/ABBV-066) in participants with moderately to severely active Crohn's disease who showed a clinical response or remission on previous treatment with risankizumab in Study NCT02031276 (BI trial 1311.6/ AbbVie M15-993) and were now receiving long-term treatment. Additional objectives of this study were to further investigate long-term efficacy, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of risankizumab.

Detailed description:
This was a single group, open-label long-term extension study that assessed the long-term safety, efficacy, and pharmacokinetics of risankizumab in participants with moderately to severely active Crohn's disease. This study was terminated early by AbbVie to enable participants who completed the study to rollover into Study NCT03105102 (AbbVie M16-000 Sub-Study 3 \[Phase 3 OLE study\]) for further OLE treatment within the Phase 3 program, which allows for risankizumab dose escalation if needed.

Arms: arm 1: Maintenance treatment with risankizumab 180 mg administered subcutaneously (SC) every 8 weeks (q8w) from Visit 2 through the end of trial (EOT) visit. Participants who re-gained their clinical response following the re-induction treatment could continue with maintenance treatment beginning at Visit 5.
Interventions: intervention 1: Risankizumab 600 mg IV intervention 2: Risankizumab 180 mg SC
Intervention descriptions: intervention 1: Re-induction treatment; 3 infusions every 4 weeks, after which eligibility was assessed if clinical response was re-gained intervention 2: Maintenance treatment every 8 weeks (q8w) from Visit 2 through the end of trial (EOT) visit. Participants who re-gained their clinical response following the re-induction treatment could continue with maintenance treatment beginning at Visit 5.

Protocol documents:
Prot_000.pdf: 
Risankizumab
1311.20/M15-989 Protocol Amendment 4
EudraCT 2015-001834-15
1
Title Page
Clinical Study Protocol 1311.20/M15-989
An Open Label, Single Group, Long Term Safety 
Extension Trial of BI 655066/ABBV-066 
(Risankizumab), in Patients with Moderately to 
Severely Active Crohn's Disease
Amendment 4
AbbVie Investigational
  Product:
BI 655066/ABBV-066 (risankizumab)
Date:
25 July 2018
Development Phase:
II
EudraCT Number:
2015-001834-15
Investigator:
Multicenter Study (Investigator information is on file at AbbVie)
Sponsor:
Non-European Countries:
AbbVie
1 North Waukegan Road
North Chicago, IL 60064 USA
European Countries:*
AbbVie Deutschland GmbH & 
Co KG
Knollstrasse 50
Ludwigshafen 67061
Germany
Sponsor/Emergency 
  Contact:
* The specific contact details of the AbbVie legal/regulatory entity (person) within the relevant country are 
provided within the clinical trial agreement with the Investigator/Institution and in the Clinical Trial 
Application with the Competent Authority.
This study will be conducted in compliance with the protocol, Good Clinical Practice and all other 
applicable regulatory requirements, including the archiving of essential documents.
Confidential Information
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
NCT02513459


Risankizumab
1311.20/M15-989 Protocol Amendment 4
EudraCT 2015-001834-15
2
CLINICAL TRIAL PROTOCOL SYNOPSIS
Name of company:
Tabulated
Trial Protocol
AbbVie, Inc.
Name of finished product:
NA
Name of active ingredient:
BI 655066/ABBV-066 (risankizumab)
Protocol date:
Trial number:
Revision date:
25 July 2018
28 Apr 2017
1311.20/M15-989
Title of trial:
An open label, single group, long term safety extension trial of 
BI-655066/ABBV-066 (risankizumab), in patients with moderately to severely 
active Crohn's disease 
Co-ordinating 
Investigator:
Trial sites:
Multi-centre trial
Clinical phase:
II
Objectives:
Primary objective:
To investigate long-term safety of BI 655066/ABBV-066 (risankizumab), in 
patients with moderately to severely active Crohn`s disease, who showed a clinical 
response or remission on previous treatment with BI 655066/ABBV-066 
(risankizumab) and are now receiving long term treatment.
Additional objectives:
To further investigate long-term efficacy, tolerability, pharmacokinetics, 
pharmacodynamics and immunogenicity of BI 655066/ABBV-066 (risankizumab).
Methodology:
Open label, single group, roll-over
No. of patients: 
60 (estimated)
total entered:
60 (estimated)
each treatment:
All patients will receive 180 mg of BI 655066/ABBV-066 (risankizumab) every 
8 weeks (q8w) as subcutaneous injection.
Patients who lost clinical response or remission after end of treatment in 1311.6 
and/or at screening for 1311.20/M15-989 will receive open label i.v.  re-induction 
treatment with three infusions of 600 mg each every 4 weeks 
Diagnosis:
Moderate to severe active Crohn`s disease with clinical response or remission after 
previous treatment with BI 655066/ABBV-066 (risankizumab)


Risankizumab
1311.20/M15-989 Protocol Amendment 4
EudraCT 2015-001834-15
3
Name of company:
Tabulated
Trial Protocol
AbbVie, Inc.
Name of finished product:
NA
Name of active ingredient:
BI 655066/ABBV-066 (risankizumab)
Protocol date:
Trial number:
Revision date:
25 July 2018
28 Apr 2017
1311.20/M15-989
Main criteria
for inclusion:
1.
Patients with Crohn`s disease, who have successfully completed the preceding 
trial 1311.6. Successful treatment is defined as:
Completion of period 2 in 1311.6 with a clinical response (drop in CDAI from 
baseline by ≥100) but no remission (CDAI < 150) at Visit E1; or
Completion of period 3 in 1311.6 with a clinical response (drop in CDAI from 
baseline by ≥100) or remission (CDAI < 150) at Visit E5.
2.
Female patients:
a. Women of childbearing potential (not surgically sterilized and between 
menarche and 1 year postmenopause), that, if sexually active agree to use 
one of the appropriate medically accepted methods of birth control in 
addition to the consistent and correct use of a condom from date of 
screening until 20 weeks after last administration of study medication. 
Medically accepted methods of contraception are: ethinyl estradiol 
containing contraceptives, diaphragm with spermicide substance, and intra-
uterine-device, or
b. Surgically sterilized female patients with documentation of prior 
hysterectomy, tubal ligation or complete bilateral oophorectomy, or
c. Postmenopausal women with postmenopausal is defined as permanent 
cessation ≥ 1 year of previously occurring menses, and
d. Negative urine pregnancy test at screening.  Serum ß-Human Chorionic 
Gonadotrophin (ß-HCG) pregnancy test will be done at screening  only in 
case when urine pregnancy test is positive.
Male patients:
a. Who are documented to be sterile, or
b. Who consistently and correctly use effective method of contraception (i.e. 
condoms) during the study and 20 weeks after last administration of study 
medication.
3.
Be able to adhere to the study visit schedule and other protocol requirements.


Risankizumab
1311.20/M15-989 Protocol Amendment 4
EudraCT 2015-001834-15
4
Name of company:
Tabulated
Trial Protocol
AbbVie, Inc.
Name of finished product:
NA
Name of active ingredient:
BI 655066/ABBV-066 (risankizumab)
Protocol date:
Trial number:
Revision date:
25 July 2018
28 Apr 2017
1311.20/M15-989
Test products:
BI 655066/ABBV-066 (risankizumab)
dose:
180 mg every 8 weeks
mode of admin.:
Subcutaneous injection (maintenance treatment)
dose:
600 mg every 4 weeks
mode of admin.:
Intravenous infusion (re- induction treatment)
Comparator products:
NA
dose:
NA
mode of admin.:
NA
Duration of treatment: Approximately 4 years
Extension of Treatment 
Following Study
Patients who complete the study, including all study procedures for end of trial 
(EoT), may continue in M16-000 Sub-Study 3.


Risankizumab
1311.20/M15-989 Protocol Amendment 4
EudraCT 2015-001834-15
5
Name of company:
Tabulated
Trial Protocol
AbbVie, Inc.
Name of finished product:
NA
Name of active ingredient:
BI 655066/ABBV-066 (risankizumab)
Protocol date:
Trial number:
Revision date:
25 July 2018
28 Apr 2017
1311.20/M15-989
Criteria for efficacy:
! Clinical remission by visit, defined as a CDAI score of < 150.
! Clinical response by visit, defined by either a CDAI score of < 150 or a CDAI 
reduction from baseline of at least 100 points.
! PRO-2 remission by visit, defined by a PRO-2 score of < 75
! PRO-2 response by visit, defined as a decrease from baseline of 50 points or 
more.
! CDEIS remission by visit, defined as a score of 4 or less (for patients with initial 
isolated ileitis a score of 2 or less)
! CDEIS response by visit, defined as a score of 7 or less (for patients with initial 
isolated ileitis > 50% reduction from baseline).
! Mucosal healing by visit, defined as the absence of mucosal ulceration.
! Deep remission by visit, defined as clinical remission and endoscopic remission 
(CDEIS).  Change from baseline in CDAI scores by visit.
! Change from baseline in PRO-2 scores by visit.
! Change in CDEIS by visit.
! Change in SES-CD by visit.
! CDEIS percentage change from baseline by visit.
! SES-CD percentage change from baseline by visit.
! Reduction of 75% in CDEIS scores from baseline by visit.
! Reduction of 75% in SES-CD scores from baseline by visit.
!Change from baseline in stool frequency by visit based on patient diary.


Risankizumab
1311.20/M15-989 Protocol Amendment 4
EudraCT 2015-001834-15
6
Name of company:
Tabulated
Trial Protocol
AbbVie, Inc.
Name of finished product:
NA
Name of active ingredient:
BI655066/ABBV-066 (risankizumab)
Protocol date:
Trial number:
Revision date:  
25 July 2018
28 Apr 2017
1311.20/M15-989
Criteria for efficacy:
! Stool consistency by visit based on patient diary.
! Change from baseline in abdominal pain score by visit based on patient diary, with 
possible answers none, mild, moderate and severe.
! Change from baseline in IBDQ scores by visit.
! Change from baseline in CRP and fecal calprotectin profile by visit.
! Reduction in the number of draining fistulas in patients with draining fistulas at 
baseline.
Criteria for safety:
Criteria for 
pharmacokinetics:
Physical examination, vital signs (BP, HR, oral body temperature), 12-lead ECG, 
laboratory tests (haematology, clinical chemistry and urinalysis), adverse events, 
immunogenicity.
Pharmacokinetic parameters of BI 655066/ABBV-066 (risankizumab): PK 
concentrations, trough levels, descriptive statistics and pharmacokinetic parameters as 
appropriate.
Statistical methods:
Endpoints will be summarized descriptively, there is no statistical model.








Risankizumab
1311.20/M15-989 Protocol Amendment 4
EudraCT 2015-001834-15
10
FLOW CHART 1: PATIENTS (1) ROLLING-OVER AT WEEK 26 FROM PRECEDING TRIAL 1311.6 
(WITH CLINICAL RESPONSE BUT NOT REMISSION AT VISIT E1); OR (2) WHO 
MAINTAINED RESPONSE AFTER COMPLETION OF TRIAL 1311.6, 
VISITS 19-EOT
Trial Period
Treatment period
Visit
19
20
21
22
23
24
25
26
27
EoT3
Week
140
148
156
164
172
180
188
196
204
Time window (days)
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
LABS/SAFETY 
ASSESSMENTS
Detailed physical 
examination
X
Targeted physical
examination (incl. vital 
signs)
X
X
X
X
X
X
X
X
X
Weight
X
X
X
X
X
X
X
X
X
X
12 Lead Resting-ECG
X
X
X
Urine Pregnancy test4
X
X
X
X
X
X
X
X
X
Laboratory tests (serum 
chemistry, hematology, 
urinalysis)9
X
X
X
X
X
X
X
X
X
X
QuantiFERON-TB Gold In-
Tube test5
X
X
EFFICACY 
ASSESSMENTS
Crohn's Disease Activity 
Index (CDAI), PRO-2
X
X
X
X
X
X
X
X
X
X
Review patient diary
X
X
X
X
X
X
X
X
X
X


Risankizumab
1311.20/M15-989 Protocol Amendment 4
EudraCT 2015-001834-15
11
Trial Period
Treatment period
Visit
19
20
21
22
23
24
25
26
27
EoT3
Week
140
148
156
164
172
180
188
196
204
Time window (days)
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
Fistula exam
X
X
X
X
X
X
X
X
X
X
Inflammatory Bowel 
Disease Questionnaire 
(IBDQ)12
X
X
X
X
Ileocolonoscopy (CDEIS)
X
X10
X11
OTHER ASSESSMENTS
Pharmacokinetics13
X
X
X
X
X
X
Anti-drug antibodies13
X
X
X
X
X
X
CRP9
X
X
X
X
X
X
X
Fecal calprotectin
X
X
X
X
Soluble protein biomarkers 
in serum 9
X
X
X
X
Previous and concomitant 
therapy
X
X
X
X
X
X
X
X
X
X
Adverse events6
X
X
X
X
X
X
X
X
X
X
TRIAL MEDICATION
Contact IRT
X
X
X
X
X
X
X
X
X
X8
Administration of trial 
medication7
X
X
X
X
X
X
X
X
X


Risankizumab
1311.20/M15-989 Protocol Amendment 4
EudraCT 2015-001834-15
12
1.
Visit 1 of this LT extension study should preferably be performed in one visit combined with the last visit of the preceding trial 1311.6 or during the interim 
period of maximum 5 days after completion of the last visit in 1311.6. If an EoT colonoscopy has not been performed during E1 within 1311.6, it must be 
performed between V1 and V2 in 1311.20/M15-989.
2.
Assessments performed at the last visit in the previous trial do not have to be repeated at visit 1 in this trial.  Assessments scheduled but not performed at the 
last visit in the previous trial should be repeated at Visit 1 in this trial, and the results entered into the CRFs of both trials 1311.6 and 1311.20/M15-989.
3.
For patients who discontinue study medication before scheduled EoT visit, an early EoT visit should be performed.  After last dose of study medication, a 
140 day follow-up call should be scheduled. Upon EC/CA approvals of Study M16-000 protocol amendment 4, patients receiving treatment in M15-989 will 
have the option to enroll into M16-000 Sub-Study 3 after completing the EoT visit.
4.
Must be performed at Visit 1 and starting from Visit 2 prior to each study drug administration in females of childbearing potential. In case of positive result, 
serum pregnancy test will be performed. Study drug will only be administered if pregnancy is ruled out.
5.
Positive QuantiFERON-TB Gold In-Tube tests need not to be repeated. If TB or infection is suspected at any time during the study, a routine work up 
including chest x-ray and a QuantiFERON-TB Gold In-Tube test or an infection assessment must be performed at investigator's discretion and according to 
local guidelines. 
6.
Assessment of AE after subcutaneous injections will also include assessment of local tolerability.  The assessment of local tolerability should be done just 
before the patient leaves the investigator site.
7.
All assessments are to be completed prior to study drug administration, unless otherwise specified.
8.
An end of trial call should be performed for both patients that agree to enroll into M16-000 Sub-Study 3 OLE or those that do not choose to participate.
9.
For details of laboratory tests see Section 5.2.3, Table 5.2.3:1and Table 5.2.3:2.
10. Every effort should be made for the patient to perform a final ileocolonoscopy at the study visit where the last dose of study medication is administered.  For 
patients with early EoT, every effort should be made to perform a final ileocolonoscopy within 2 weeks following the early EoT visit.
11. Colonoscopy is not to be repeated if done at preceding visit.
12. IBDQ should be completed before site staff interaction and study drug administration.
13. Blood samples for PK and ADA will be drawn BEFORE drug administration, i.e. pre-dose, whenever visits coincide.
14. Visit 1.1 is applicable only for those patients that had visit E1 more than 5 days before Visit 1.  Visit 1.1 can be performed by phone, fax or email.
15. IRT has to be called only once at V1 or V1.1 after assessment if s.c or i.v. re-induction is needed.
16. In case patient had visit E1 less than 5 days before Visit 1, CDAI assessment and new patient diary dispense should be done at Visit 1.






Risankizumab
1311.20/M15-989 Protocol Amendment 4
EudraCT 2015-001834-15
15
FLOW CHART 2: PATIENTS (1) ROLLING-OVER AT WEEK 52 FROM PRECEDING TRIAL 1311.6 
(WITH CLINICAL RESPONSE OR REMISSION AT VISIT E5); VISITS 19-EOT 
Trial Period
Treatment period
Visit
19
20
21
22
23
24
25
26
27
EoT3
Week
142
150
158
166
174
182
190
198
206
Time window (days)
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
LABS/SAFETY 
ASSESSMENTS
Detailed physical 
examination
X
Targeted physical 
examination (incl. vital 
signs)
X
X
X
X
X
X
X
X
X
Weight
X
X
X
X
X
X
X
X
X
X
12 Lead Resting-ECG
X
X
X
Urine Pregnancy test4
X
X
X
X
X
X
X
X
X
Laboratory tests (serum 
chemistry, hematology, 
urinalysis)9
X
X
X
X
X
X
X
X
X
X
QuantiFERON-TB Gold In-
Tube test5
X
X
EFFICACY 
ASSESSMENTS
Crohn's Disease Activity 
Index (CDAI), PRO-2
X
X
X
X
X
X
X
X
X
X
Review patient diary
X
X
X
X
X
X
X
X
X
X


Risankizumab
1311.20/M15-989 Protocol Amendment 4
EudraCT 2015-001834-15
16
Trial Period
Treatment period
Visit
19
20
21
22
23
24
25
26
27
EoT3
Week
142
150
158
166
174
182
190
198
206
Time window (days)
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
Fistula exam
X
X
X
X
X
X
X
X
X
X
Inflammatory Bowel 
Disease Questionnaire 
(IBDQ)12
X
X
X
X
Ileocolonoscopy (CDEIS)
X
X10
X11
OTHER ASSESSMENTS
Pharmacokinetics13
X
X
X
X
X
X
Anti-drug antibodies13
X
X
X
X
X
X
CRP9
X
X
X
X
X
X
X
Fecal calprotectin
X
X
X
X
Soluble protein biomarkers 
in serum 9
X
X
X
X
Previous and concomitant 
therapy
X
X
X
X
X
X
X
X
X
X
Adverse events6
X
X
X
X
X
X
X
X
X
X
TRIAL MEDICATION
Contact IRT
X
X
X
X
X
X
X
X
X
X8
Administration of trial 
medication7
X
X
X
X
X
X
X
X
X


Risankizumab
1311.20/M15-989 Protocol Amendment 4
EudraCT 2015-001834-15
17
1.
Visit 1 of this LT extension study should preferably be performed in one visit combined with the last visit of the preceding trial 1311.6 or during the interim 
period of maximum 5 days after completion of the last visit in 1311.6. If an EoT colonoscopy has not been performed during E5 within 1311.6, it must be 
performed between V1 and V2 in 1311.20/M15-989. 
2.
Assessments performed at the last visit in the previous trial do not have to be repeated at visit 1 in this trial.  Assessments scheduled but not performed at the 
last visit in the previous trial should be repeated at visit 1 in this trial, and the results entered into the CRFs of both trials 1311.6 and 1311.20/M15-989.
3.
For patients who discontinue study medication before scheduled EoT visit, an early EoT visit should be performed.  After last dose of study medication, a 
140 day follow-up call should be scheduled.  Upon EC/CA approvals of Study M16-000 protocol amendment 4, patients receiving treatment in M15-989 
will have the option to enroll into M16-000 Sub-Study 3 after completing the EoT visit.
4.
Must be performed at Visit 1 and starting from Visit 2 prior to each study drug administration in females of childbearing potential.  In case of positive result, 
serum pregnancy test will be performed.  Study drug will only be administered if pregnancy is ruled out.
5.
Positive QuantiFERON-TB Gold In-Tube tests need not to be repeated.  If TB or infection is suspected at any time during the study, a routine work up 
including chest x-ray and a QuantiFERON-TB Gold In-Tube test or an infection assessment must be performed at investigator's discretion and according to 
local guidelines.
6.
Assessment of AE after subcutaneous injections will also include assessment of local tolerability.  The assessment of local tolerability should be done just 
before the patient leaves the investigator site.
7.
All assessments are to be completed prior to study drug administration, unless otherwise specified.
8.
An end of trial call should be performed for both patients that agree to enroll into M16-000 Sub-Study 3 OLE or those that do not choose to participate.
9.
For details of laboratory tests see Section 5.2.3, Table 5.2.3:1 and Table 5.2.3:2
10. Every effort should be made for the patient to perform a final ileocolonoscopy at the study visit where the last dose of study medication is administered.  For 
patients with early EoT, every effort should be made to perform a final ileocolonoscopy within 2 weeks following the early EoT visit.
11. Colonoscopy is not to be repeated if done at preceding visit.
12. IBDQ should be completed before site staff interaction and study drug administration.
13. Blood samples for PK and ADA will be drawn BEFORE drug administration, i.e. pre-dose, whenever the visits coincide.
14. Visit 1.1 is applicable only for those patients that had visit E5 more than 5 days before Visit 1.  Visit 1.1 can be performed by phone, fax or email.
15. In case patient had visit E5 less than 5 days before Visit 1, CDAI assessment and new patient diary dispense should be done at Visit 1.


Risankizumab
1311.20/M15-989 Protocol Amendment 4
EudraCT 2015-001834-15
18
FLOW CHART 3: PATIENTS ROLLING-OVER WHO HAVE LOST RESPONSE OR REMISSION
AFTER COMPLETION OF TRIAL 1311.6 EITHER AT VISIT E1 OR E5, VISITS 1-18 
Trial Period
Screening
Re-induction
Treatment period
Visit
11, 2
1.115
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Week
0
1
4
8
12
16
24
32
40
48
56
64
72
80
88
96
104
112
120
128
Time window (days)
+5
+5
± 7
±5
±5
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
Informed consent
X
Assessment of eligibility 
X
X14
LABS/SAFETY 
ASSESSMENTS
Detailed physical 
examination
X
Targeted physical 
examination (incl. vital 
signs)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
12 Lead Resting-ECG
X
X
X
Urine Pregnancy test4
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory tests (serum 
chemistry, hematology, 
urinalysis)9
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
QuantiFERON-TB Gold In-
Tube test5
X
X
X


Risankizumab
1311.20/M15-989 Protocol Amendment 4
EudraCT 2015-001834-15
19
Trial Period
Screening
Re-induction
Treatment period
Visit
11,2
1.115
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Week
0
1
4
8
12
16
24
32
40
48
56
64
72
80
88
96
104
112
120
128
Time window (days)
+5
+5
± 7
±5
±5
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
EFFICACY ASSESSMENTS
Dispense patient diary for 
screening
X
Crohn's Disease Activity 
Index (CDAI), PRO-2
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Review patient diary
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Fistula exam
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Inflammatory Bowel 
Disease Questionnaire 
(IBDQ)12
X
X
X
X
X
Ileocolonoscopy (CDEIS)
X1
X
X
OTHER ASSESSMENTS
Pharmacokinetics13
X
X
X
X
X
X
X
X
Anti-drug antibodies13
X
X
X
X
X
X
X
X
CRP9
X
X
X
X
X
X
X
X
Fecal calprotectin
X
X
X
X
X
Soluble protein biomarkers 
in serum9
X
X
X
X
X
Previous and concomitant 
therapy
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse events6
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
TRIAL MEDICATION
Contact IRT
X16
X16
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Administration of trial i.v. 
medication7
X
X
X
Administration of trial s.c. 
medication7
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X


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FLOW CHART 3: PATIENTS ROLLING-OVER WHO HAVE LOST RESPONSE OR REMISSION
AFTER COMPLETION OF TRIAL 1311.6 EITHER AT VISIT E1 OR E5, VISITS 19-
EOT 
Trial Period
Treatment period
Visit
20
219
22
23
24
25
26
27
28
29
30
EoT3
Week
136
144
152
160
168
176
184
192
200
208
216
Time window (days)
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
LABS/SAFETY 
ASSESSMENTS
Detailed physical 
examination
X
Targeted physical 
examination (incl. vital 
signs)
X
X
X
X
X
X
X
X
X
X
X
Weight
X
X
X
X
X
X
X
X
X
X
X
X
12 Lead Resting-ECG
X
X
X
Urine Pregnancy test4
X
X
X
X
X
X
X
X
X
X
X
Laboratory tests (serum 
chemistry, hematology, 
urinalysis)9
X
X
X
X
X
X
X
X
X
X
X
X
QuantiFERON-TB Gold In-
Tube test5
X
X
EFFICACY 
ASSESSMENTS
Crohn's Disease Activity 
Index (CDAI), PRO-2
X
X
X
X
X
X
X
X
X
X
X
X
Review patient diary
X
X
X
X
X
X
X
X
X
X
X
X


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Trial Period
Treatment period
Visit
20
219
22
23
24
25
26
27
28
29
30
EoT3
Week
136
144
152
160
168
176
184
192
200
208
216
Time window (days)
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
Fistula exam
X
X
X
X
X
X
X
X
X
X
X
X
Inflammatory Bowel 
Disease Questionnaire 
(IBDQ)12
X
X
X
X
X
Ileocolonoscopy (CDEIS)
X
X10
X11
OTHER ASSESSMENTS
Pharmacokinetics13
X
X
X
X
X
X
X
Anti-drug antibodies13
X
X
X
X
X
X
X
CRP 9
X
X
X
X
X
X
X
X
X
Fecal calprotectin  
X
X
X
X
X
Soluble protein biomarkers 
in serum 9
X
X
X
X
X
Previous and concomitant 
therapy
X
X
X
X
X
X
X
X
X
X
X
X
Adverse events6
X
X
X
X
X
X
X
X
X
X
X
X
TRIAL MEDICATION
Contact IRT
X
X
X
X
X
X
X
X
X
X
X
X8
Administration of trial i.v.
medication7
Administration of trial s.c. 
medication7
X
X
X
X
X
X
X
X
X
X
X


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1.
If an EoT colonoscopy has not been performed during E1/E5 within 1311.6, or if the patient had a treatment interruption followed by a clinical relapse, it 
must be performed between V1 and V2 in 1311.20/M15-989.
2.
Assessments performed at visit E1/E5 in the previous trial do not have to be repeated at Visit 1 in this trial.  Assessments scheduled but not performed at 
Visit E1/E5 in the previous trial should be repeated at visit 1 in this trial, and the results entered into the CRFs of both trials, 1311.6 and 1311.20/M15-989.
3.
For patients who discontinue study medication before scheduled EoT visit, an early EoT visit should be performed.  After last dose of study medication, a 
140 day follow-up call should be scheduled.  Upon EC/CA approvals of Study M16-000 protocol amendment 4, patients receiving treatment in M15-989 
will have the option to enroll into M16-000 Sub-Study 3 after completing the EoT visit.
4.
Must be performed at Visit 1 and starting from Visit 2 prior to each study drug administration in females of childbearing potential.  In case of positive result, 
serum pregnancy test will be performed.  Study drug will only be administered if pregnancy is ruled out.
5.
Positive QuantiFERON-TB Gold In-Tube tests need not to be repeated. If TB or infection is suspected at any time during the study, a routine work up 
including chest x-ray and a QuantiFERON-TB Gold In-Tube test or an infection assessment must be performed at investigator's discretion and according to 
local guidelines.
6.
Assessment of AE after intravenous infusions and subcutaneous injections will also include assessment of local tolerability. The assessment of local 
tolerability should be done just before the patient leaves the investigator site.
7.
All assessments are to be completed prior to study drug administration, unless otherwise specified.
8.
An end of trial call should be performed for both patients that agree to enroll into M16-000 Sub-Study 3 OLE or those that do not choose to participate.
9.
For details of laboratory tests see Section 5.2.3, Table 5.2.3:1 and Table 5.2.3:2.
10. Every effort should be made for the patient to perform a final ileocolonoscopy at the study visit where the last dose of study medication is administered.  For 
patients with early EoT, every effort should be made to perform a final ileocolonoscopy within 2 weeks following the early EoT visit.
11. Colonoscopy is not to be repeated if done at preceding visit.
12. IBDQ should be completed before site staff interaction and study drug administration.
13. Blood samples for PK and ADA will be drawn BEFORE drug administration, i.e. pre-dose, whenever the visits coincide.
14. Clinical response or remission will be compared to 1311.6 baseline (Visit 2), to continue SC medication patients should have response.
15. Visit can be performed by phone, fax or email.
16. IRT has to be called only once at V1 or V1.1 after assessment if s.c or i.v. re-induction is needed.


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TABLE OF CONTENTS
Clinical Trial Protocol Synopsis .................................................................2
Flow Chart 1: Patients (1) rolling-over at WEEK 26 from 
preceding Trial 1311.6 (with Clinical Response but 
not remission at Visit E1); or (2) who maintained 
response OR REMISSION After completion of Trial 
1311.6, Visits 1-18..................................................................7
Flow Chart 1: Patients (1) rolling-over at WEEK 26 from 
preceding Trial 1311.6 (with Clinical Response but 
not remission at Visit E1); or (2) who maintained 
response after completion of Trial 1311.6, 
Visits 19-EoT .......................................................................10
Flow Chart 2: Patients (1) rolling-over at WEEK 52 from 
preceding Trial 1311.6 (with Clinical Response or 
remission at Visit E5) Visits 1-18........................................ 13
Flow Chart 2: Patients (1) rolling-over at WEEK 52 from 
preceding Trial 1311.6 (with Clinical Response or 
remission at Visit E5); Visits 19-EoT ................................. 15
Flow Chart 3: Patients rolling-over who have lost response or 
remission after completion of Trial 1311.6 either at 
visit e1 or e5, Visits 1-18......................................................18
Flow Chart 3: Patients rolling-over who have lost response OR 
Remission after completion of Trial 1311.6 either at 
visit e1 or e5, Visits 19-EoT.................................................20
TABLE OF CONTENTS.......................................................................... 23
ABBREVIATIONS ................................................................................... 28
1.
INTRODUCTION............................................................... 31
1.1
MEDICAL BACKGROUND ............................................................... 31
1.2
DRUG PROFILE ................................................................................. 32
2.
Rationale, objectives, and Benefit - Risk Assessment........36
2.1
RationalE for Performing the Trial ....................................................... 36
2.2
Trial Objectives.................................................................................... 36
2.3
Benefit - Risk Assessment .................................................................... 37
3.
DESCRIPTION OF DESIGN AND TRIAL 
POPULATION.................................................................... 40


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3.1
OVERALL TRIAL DESIGN AND PLAN ........................................... 40
3.1.1
Administrative structure of the trial ...................................................... 42
3.1.1.1 
Data Monitoring Committee (DMC)..................................................... 43
3.2
DISCUSSION OF TRIAL DESIGN, INCLUDING THE 
CHOICE OF CONTROL GROUP(S)................................................... 43
3.3
SELECTION OF TRIAL POPULATION............................................. 44
3.3.1
Main diagnosis for study entry.............................................................. 44
3.3.2
Inclusion criteria................................................................................... 44
3.3.3
Exclusion criteria.................................................................................. 45
3.3.4
Removal of patients from therapy or assessments ................................. 46
3.3.4.1
Removal of individual patients ............................................................. 46
3.3.4.2
Discontinuation of the trial by the sponsor............................................ 47
4.
TREATMENTS...................................................................48
4.1
TREATMENTS TO BE ADMINISTERED.......................................... 48
4.1.1
Identity of investigational product and comparator product(s)............... 48
4.1.2
Method of assigning patients to treatment groups ................................. 49
4.1.3
Selection of doses in the trial................................................................ 50
4.1.4
Drug assignment and administration of doses for each patient .............. 50
4.1.5
Blinding and procedures for unblinding................................................ 51
4.1.5.1
Blinding ............................................................................................... 51
4.1.5.2
Procedures for emergency unblinding................................................... 51
4.1.6
Packaging, labelling, and re-supply ...................................................... 51
4.1.7
Storage conditions................................................................................ 52
4.1.8
Drug accountability .............................................................................. 52
4.2
CONCOMITANT THERAPY, RESTRICTIONS, AND rescue 
treatment .............................................................................................. 53
4.2.1
Rescue medication, emergency procedures, and additional 
treatment(s) .......................................................................................... 53
4.2.2
Restrictions .......................................................................................... 54
4.2.2.1
Restrictions regarding concomitant treatment ....................................... 54
4.3
TREATMENT COMPLIANCE............................................................ 57
5.
Variables and their assessment...........................................58
5.1
EFFICACY - pharmacodynamics......................................................... 58


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5.1.1
Endpoint of efficacy ............................................................................. 58
5.1.2
Assessment of efficacy......................................................................... 59
5.2
SAFETY .............................................................................................. 60
5.2.1
Endpoint(s) of safety ............................................................................ 60
5.2.2
Assessment of adverse events............................................................... 61
5.2.2.1
Definitions of adverse events................................................................ 61
5.2.2.2
Adverse event and serious adverse event reporting ............................... 64
5.2.3
Assessment of safety laboratory parameters.......................................... 67
5.2.4
Medical examination ............................................................................ 71
5.2.5
Local tolerability .................................................................................. 71
5.2.6
Infusion reaction................................................................................... 71
5.2.7
Electrocardiogram................................................................................ 71
5.3
OTHER................................................................................................ 72
5.3.1
Other endpoint(s).................................................................................. 72
5.3.2
Other assessment(s).............................................................................. 72
5.3.3
Pharmacogenomic evaluation ............................................................... 72
5.4
APPROPRIATENESS OF MEASUREMENTS ................................... 72
5.5
DRUG CONCENTRATION MEASUREMENTS AND 
PHARMACOKINETICS ..................................................................... 73
5.5.1
Pharmacokinetic endpoint(s) ................................................................ 73
5.5.2
Methods of sample collection ............................................................... 73
5.5.2.1
Plasma sampling for pharmacokinetic analysis ..................................... 73
5.5.2.2
Plasma sampling for assessment of anti-drug antibody ......................... 74
5.5.3
Analytical determinations..................................................................... 75
5.6
BIOMARKER(S)................................................................................. 75
5.6.1
Endpoints based on biomarker(s).......................................................... 75
5.6.2
Methods of sample collection ............................................................... 75
5.6.3
Analytical determinations..................................................................... 76
5.7
Pharmacodynamics............................................................................... 76
5.7.1
Pharmacodynamic endpoints ................................................................ 76
5.7.2 
Methods of sample collection ............................................................... 76
5.8
PHARMACOKINETIC - PHARMACODYNAMIC 
RELATIONSHIP ................................................................................. 76


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6.
INVESTIGATIONAL PLAN ............................................. 77
6.1
VISIT SCHEDULE.............................................................................. 77
6.2
Details of TRIAL PROCEDURES AT selected VISITs........................ 77
6.2.1
Screening period................................................................................... 77
6.2.2
Treatment periods................................................................................. 78
6.2.3
End of trial and follow-up period.......................................................... 78
7.
STATISTICAL METHODS AND 
DETERMINATION OF SAMPLE SIZE .......................... 79
7.1
STATISTICAL DESIGN - MODEL .................................................... 79
7.2
NULL AND ALTERNATIVE HYPOTHESES.................................... 79
7.3
PLANNED ANALYSES...................................................................... 79
7.3.1
Primary analyses .................................................................................. 79
7.3.2
Secondary analyses............................................................................... 79
7.3.3
Safety analyses..................................................................................... 79
7.3.4
Interim analyses ................................................................................... 80
7.3.5
Pharmacokinetic analyses..................................................................... 80
7.3.6
Pharmacodynamic analyses .................................................................. 81
7.3.7
Pharmacogenomic analyses .................................................................. 81
7.4
HANDLING OF MISSING DATA ...................................................... 82
7.5
Randomisation ..................................................................................... 82
7.6
DETERMINATION OF SAMPLE SIZE.............................................. 82
8.
Informed Consent, Data Protection, Trial records............83
8.1
STUDY APPROVAL, Patient Information, and Informed Consent ...... 83
8.2
DATA QUALITY ASSURANCE ........................................................ 84
8.3
RECORDS........................................................................................... 84
8.3.1
Source documents ................................................................................ 84
8.3.2
Direct access to source data and documents.......................................... 84
8.4
listedness and expedited reporting of Adverse Events........................... 85
8.4.1
Listedness............................................................................................. 85
8.4.2
Expedited reporting to health authorities and IECs/IRBs ...................... 85
8.5
STATEMENT OF CONFIDENTIALITY ............................................ 85
8.6
COMPLETION OF TRIAL.................................................................. 85
9.
REFERENCES....................................................................86


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9.1
PUBLISHED REFERENCES............................................................... 86
9.2
UNPUBLISHED REFERENCES......................................................... 89
10.
APPENDICES.....................................................................90
10.1
Clinical Evaluation of Liver Injury ....................................................... 90
10.1.1
Introduction.......................................................................................... 90
10.1.2
Procedures............................................................................................ 90
10.2
Equivalent doses of corticosteroids....................................................... 91
10.3
SEVERITY OF AE AS DESCRIBED IN THE 
RHEUMATOLOGY COMMON TOXICITY CRITERIA 
(OMERACT) ....................................................................................... 92
10.4
Investigator's Agreement .....................................................................119
10.5
PROTOCOL SIGNATORIES .............................................................120
11.
Description of global Amendment(s)................................ 121


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ABBREVIATIONS
ADA
AE
AESI
ALT
AP/ALP
AST
Anti-drug antibody
Adverse Event
Adverse Events of Special Interest
Alanine aminotransferase
Alkaline Phosphatase
Aspartate aminotransferase
AUC
BI
BCG
BP
ß-HCG
CAC
CD
CDAI
CDEIS
CHO
Area under the Curve
Boehringer Ingelheim
Bacille Calmette-Guérin
blood pressure
ß-Human Chorionic Gonadotrophin
Cardiovascular Adjudication Committee
Crohn's Disease
Crohn's Disease Activity Index
Crohn's Disease Endoscopic Index of Severity
Chinese Hamster Ovary
CI
CK
Confidence Interval
Creatine Kinase
CML
Local Clinical Monitor
CRA
CRO
Clinical Research Associate
Contract Research Organisation
CRF
CRP
Case Report Form
C-reactive protein
CTCAE
Common Terminology Criteria for Adverse Events
CTMF
Clinical Trial Master File
CTP
Clinical Trial Protocol
CTR
Clinical Trial Report
DMC
Data Monitoring Committee
eCRF
Electronic Case Report Form
EDC
EDTA
ELISA
EOT
Electronic Data Capture
ethylenediaminetetraacetic acid
Enzyme Linked Immunosorbent Assay
End of Trial
EudraCT
European Clinical Trials Database
FAS
Full Analysis Set
GCP
GGT/γ-GT
Hb
Good Clinical Practice
Gamma-Glutamyl Transferase
Hemoglobin


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Hct
HDL
Hematocrit
High density lipoprotein
HPC
HR
Human Pharmacology Centre
heart rate
IB
IBDQ
IEC
IFN-γ
Ig
Investigator's Brochure
Inflammatory Bowel Disease Questionnaire
Independent Ethics Committee
Interferon gamma
Immunglogulin
IRB
IRT
Institutional Review Board
Interactive Response Tool
ISF
Investigator Site File
i.v.
intravenous
IVRS
Interactive Voice Response System
IWRS
LDH
LDL
LT
MACE
Interactive Web-based Response System
Lactic Dehydrogenase
Low Density Lipoprotein
Long term
Major Adverse Cardiovascular Events
MedDRA
mg
mL
MRI
Medical Dictionary for Drug Regulatory Activities
milligram
milliliter
Magnetic Resonance Imaging
MST
Medical Subteam
p.o.
per os (oral)
PCC
PMN
PRO-2
PTT
Protocol Challenge Committee
Polymorphonuclear
Patient reported outcome-2
Partial Thromboplastin Time
q4w
RBC
RCTC
REP
RSI
quaque 4 weeks (once in 4 week)
Red Blood Cell
Rheumatology Common Toxicity Criteria
Residual Effect Period
Reference Safety Information
SAE
Serious Adverse Event
s.c.
SES-CD
SOP
subcutaneous
Simple Endoscopic Score in Crohn`s Disease
Standard Operating Procedures
SPC
TB
Summary of Product Characteristics
Tuberculosis


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TCM
Trial Clinical Monitor
TDMAP
Trial Data Management and Analysis Plan
TMM
Team Member Medicine
TMW
Trial Medical Writer
TSAP
ULN
xg
WBC
Trial Statistical Analysis Plan
Upper limit of normal
times gravity
White Blood Cells


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1.
INTRODUCTION
1.1
MEDICAL BACKGROUND
Crohn's Disease (CD) is a chronic relapsing, remitting inflammatory disease of the 
gastrointestinal tract characterized by abdominal pain, fever, and bloody or mucus-
containing diarrhea (R13-2231). The disease affects the gastrointestinal tract 
discontinuously from mouth to anus, but most commonly the ileum and colon (40%), 
followed by the small bowel only (30%), and the colon only (25%) (R13-2232, 
R13-2233). It occurs in a relatively young population and there is no marked sex 
difference. 
The annual incidence of CD seems to be increasing with more recent estimates varying 
from 7.9 to 20.2 cases/100,000, and a prevalence of 161 to 319 cases/100,000 in North 
America and Europe (R13-2231). Mucosal lesions may be complicated by perforation and 
fistula formation, which may require hospitalization for medical or surgical management.
Because of myriad symptoms, clinical status is measured using clinical indexes. The most 
widely used, in clinical trials, is the Crohn's Disease Activity Index (CDAI) (R97-2689). 
At the mucosal level, the extent of disease can be graded following ileocolonoscopy 
according to the Crohn's Disease Endoscopic Index of Severity (CDEIS). 
Remission of clinical symptoms and endoscopic mucosal healing are predictors of long 
term improved clinical outcomes, including sustained steroid-free clinical remission, 
decreased need for surgical intervention, reduction in hospital admissions, improvement 
in quality of life, and increased work productivity (R13-2413). There is a poor correlation 
between CDAI and CDEIS. It has been reported that mucosal healing may be better than 
CDAI for the prediction of long term prognosis (R13-2295, R13-2294).
The mainstay of treatment of moderate to severe CD has been with glucocorticoid 
therapy, azathioprine, or 6-mercaptopurine (R13-2269). More recently, biologics 
consisting of monoclonal antibodies directed at cytokines, thought to mediate the 
pathology, have been used extensively for this indication. In clinical studies of infliximab, 
adalimumab, and certolizumab pegol, induction of CDAI remission at 4 weeks were in the 
range of 25 to 35% in contrast to placebo rates of 4 to 12%. At six months, response rates 
were of approximately 60% and remission rates of 40-50%, compared with 20% in 
placebo-treated patients. Adverse events reported with these agents include drug-induced 
lupus, lymphoma, demyelinating diseases, and serious and opportunistic infections, 
including tuberculosis and systemic fungal infections. Many patients lose response to 
TNF inhibitors over time, in part due to development of neutralizing or depleting anti-
drug antibodies (ADA). Overall, one third of patients fail to respond to initial anti-TNF 


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therapy (primary non-response), and another third lose their response over time 
(secondary non-response) (R13-2268, R13-2267, P13-05746, R13-2264, R13-2266, 
R13-2265). Thus, there remains a significant unmet medical need for better treatments of 
this disease.
BI 655066/ABBV-066 (risankizumab) is a humanized antibody that is directed against 
IL-23 p19. Although the etiology of Crohn's Disease (CD) is unknown, data suggest that 
there is altered immune regulation at the epithelial barrier, leading to overproduction of 
inflammatory cytokines, tissue destruction, and aberrant tissue repair. Among the 
cytokines implicated in CD pathogenesis, data at the genetic, human biology and clinical 
level strongly implicate IL-23 in this disease. In a Phase II placebo-controlled trial of the 
IL-12/IL-23 antagonist mAb ustekinumab in Crohn's Disease, 34.1 to 39.7% of patients 
receiving single doses of ustekinumab (1 mg/kg, 3 mg/kg, or 6 mg/kg) had a CDAI
response at 6 weeks, compared to 23.5% of patients receiving placebo (R12-5152). In a 
recent Phase II placebo-controlled trial of the specific IL-23p19 antagonistic mAb 
MEDI-2070 in moderate to severe Crohn's Disease, 46% of exclusively anti-TNF 
pretreated patients achieved a clinical response (vs. 25% on placebo) while 27% achieved 
a clinical remission (vs 15% on placebo) (R15-1973). Therefore, an IL-23 antagonist, 
whether directed against the p40 or p19 subunit, is likely to be an effective treatment for 
CD.
1.2
DRUG PROFILE
Preclinical summary
BI 655066/ABBV-066 (risankizumab) binds with high affinity to human and cynomolgus 
monkey IL-23, but it does not bind to rat or murine IL-23. There was no binding to IL-12 
at the highest concentration (100 nM) tested. Binding to human IL-23 was analyzed in the 
presence of 50% human serum to assess the potential for non-specific binding. BI 
655066/ABBV-066 (risankizumab) does not display interference to binding in the 
presence of 50% serum.
The primary functional cell assay for the IL-23 antibodies measures their ability to inhibit 
IL-23 stimulated IL-17 production from mononuclear cells isolated from mouse spleens.
Human, cynomologus, rat and mouse recombinant IL-23 are all capable of stimulating 
IL-17 release from mouse splenocytes with similar EC50 values. The ability of 
BI 655066/ABBV-066 (risankizumab)  to functionally inhibit both a recombinant and 
natural form of IL-23 was measured in this system. IC50 values for 


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BI 655066/ABBV-066 (risankizumab) were equivalently low against recombinant (6 pM) 
and naturally occurring (1 pM) forms of human IL-23 and lower than the IC50 observed 
with ustekinumab of 167 pM.
BI 655066/ABBV-066 (risankizumab) did not affect IL-12 at a maximum concentration tested 
of 33 nM and it did not inhibit IL-12 stimulated IFN-γ production, in contrast to a control 
antibody against IL-12 p70 that completely inhibited IFN-γ output.
A mouse ear inflammation model (R11-1273) of in vivo efficacy of 
BI 655066/ABBV-066 (risankizumab)  demonstrated 71% inhibition of ear skin 
thickness, 100% inhibition of ear tissue IL-17 and 94% inhibition of ear tissue IL-22 after 
1 mg/kg of BI 655066/ABBV-066. When ustekinumab was studied in the same model, 
similar levels of inhibition in IL-17 and IL-22 levels were seen at a dose of 1 mg/kg of 
ustekinumab as with 0.1 mg/kg of BI 655066/ABBV-066. These results suggest that 
BI 655066/ABBV-066 (risankizumab) may have higher potency than ustekinumab.
Toxicology summary
No adverse findings have been identified in any of the toxicology studies using 
BI 655066/ABBV-066 (risankizumab).
In the 26 week monkey toxicity study, marginal but transient test article-related decreases 
in B lymphocytes were noted only at Month 1 in ≥5mg/kg/week animals (both sexes), but 
this change was not noted at 3 or 6 month time points.  Given the small magnitude of 
change and the transient nature of the decrease in B lymphocytes, this is not considered an 
adverse change.  Also in the 26 week study, hypospermatogenesis was observed at a low 
incidence in the testes of ≥ 5 mg/kg/week males and correlated with a reduction in testes 
weights only in 50 mg/kg/week males. Following 8 weeks of recovery, there was no 
testicular pathology or testis weight effect in 50 mg/kg/week males.  The 
hypospermatogenesis was not considered as an adverse event given the small magnitude 
of change and no corresponding decrease of epididymal sperm. In contrast, an external 
expert panel interpreted these findings as normal variations associated with the onset of 
puberty that were not considered to represent testicular toxicity related to treatment with 
BI 655066/ABBV-066 (risankizumab). Moreover, a repeat 26 week male fertility study in 
sexually mature monkeys demonstrated that weekly subcutaneous administration of BI 
655066/ABBV-066 (risankizumab) at 50 mg/kg/week for 26 weeks to sexually mature 
male cyno monkeys produced no BI 655066/ABBV-066 (risankizumab) related effects on 
reproductive parameters. 
The toxicology data suggest BI 655066/ABBV-066 (risankizumab) can be safely 
administered to humans, as supported by chronic administration to monkeys for up to 


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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 μg/mL 
for the Cmax and 86,250 μg.h/mL for AUC0-168, respectively.
Clinical summary
BI 655066/ABBV-066 (risankizumab) has been studied in a randomized, double blind, 
single dose trial in a total of 39 patients with moderate to severe psoriasis (Study 1311.1). 
BI 655066/ABBV-066 (risankizumab) was administered i.v. in ascending doses ranging 
0.01 mg/kg to 5 mg/kg i.v., or s.c. in doses of 0.25 mg/kg or 1 mg/kg. After a single i.v. 
administration, exposure (Cmax and AUC) to BI 655066/ABBV-066 (risankizumab)
increased with dose in an approximately dose-proportional manner. The variability and 
the estimates of the pharmacokinetic parameters after i.v. dosing of BI 655066/ABBV-
066 (risankizumab)  appears to be in line with other mAbs binding a soluble target. The 
geometric mean half-life of BI 655066/ABBV-066 (risankizumab) ranged from 
approximately 20-28 days. The Tmax occurred at approximately 1 to 2 h from start of i.v. 
infusion in all patients given BI 655066/ABBV-066 (risankizumab).
Mean Psoriasis Area and Severity Index (PASI) scores showed no relevant change over 
time among placebo treated patients, but showed marked improvements among the 
BI 655066/ABBV-066 (risankizumab) treatment groups in Study 1311.1. At doses of 
0.25 mg/kg and above, all dose groups showed improvement in mean PASI scores of at 
least 75% from baseline by week 12, which lasted at least until week 20. Similar 
improvements were observed in both of the BI 655066/ABBV-066 (risankizumab) 
subcutaneous dose groups.
In a subsequent randomized double-dummy design phase IIb trial, 166 patients with 
moderate or severe plaque psoriasis were randomly assigned to one of three dose 
regimens of BI 655066/ABBV-066 (risankizumab)  (18/0, 90/90 or 180/180 mg s.c. at 
weeks 0 and 4) or ustekinumab (45 or 90 mg, per weight, s.c. at weeks 0 and 4). The 
primary endpoint was PASI 90 at week 12, comparing BI 655066/ABBV-066 
(risankizumab) with ustekinumab. In the pre-specified primary analysis of the 90 and 
180 mg BI 655066/ABBV-066 (risankizumab) doses (pooled), BI 655066/ABBV-066 
(risankizumab) was superior to ustekinumab (PASI 90 77.1% for BI 655066/ABBV-066 
(risankizumab) vs 40.0% for ustekinumab [p<0.0001]). Ninety percent of BI 
655066/ABBV-066 (risankizumab) patients had sPGA of clear or almost clear compared 
with 67.5% for ustekinumab. Forty-six percent of BI 655066/ABBV-066 (risankizumab)
patients had complete clearing of lesions (PASI 100) compared with 17.5% for 
ustekinumab. AEs were similar across treatment groups with no drug-related severe or 
serious AEs. Thus, selective blockade of IL-23p19 with BI 655066/ABBV-066 


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(risankizumab) was associated with clinical responses superior to ustekinumab in patients 
with moderate-to-severe plaque psoriasis.
The overall safety profile of risankizumab is consistent with its mechanism of action. 
Across all indications and doses, the most frequently reported AEs (AEs or serious AEs 
that received at least 1 dose of risankizumab) were nasopharyngitis, upper respiratory tract 
infection, headache, and arthralgia. Based on the review of all the risankizumab safety 
data to date, there are no important identified risks.
For further details see the Investigators Brochure.


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2.
RATIONALE, OBJECTIVES, AND BENEFIT - RISK 
ASSESSMENT
2.1
RATIONALE FOR PERFORMING THE TRIAL
The etiology of CD is unknown but data suggests altered immune regulation at the 
epithelial barrier leading to overproduction of inflammatory cytokines, tissue destruction 
and aberrant tissue repair (R13-2231). 
Biologic agents targeting TNFα, a cytokine thought to mediate the pathology of CD, have 
been used extensively for this indication. However, one-third of patients do not respond to 
anti-TNF agents, and another third of patients have only a transient response (R13-2268, 
R13-2267, P13-05746, R13-2264, R13-2266, R13-2265). There remains a high unmet 
medical need for effective therapies for CD, particularly with a different mode of action 
that overcomes current treatment limitations.
Among the cytokines involved in CD pathogenesis, data at the genetic, human biology 
and clinical level strongly suggests the role of IL-23 in this disease (R13-2625;
R12-5152). Analysis of tissue obtained from surgical biopsies or endoscopies has shown 
that IL-23 and IL-23R are upregulated in the inflamed mucosa of CD (R12-1009). Data 
from T cell-driven murine models of colitis support the role of IL-23 in gut pathology 
(R11-1269; R11-1271). Ustekinumab, an IL-12/IL-23 p40 antagonist mAb, has shown 
clinical efficacy in Phase II studies of CD (R12-5152). Furthermore, the IL-23 p19 
antibody MEDI-2070 has shown very promising activity in patients with CD who have 
failed one or more anti-TNF treatments before (R15-1973). Finally, BI 655066/ABBV-
066 (risankizumab) has shown superior clinical efficacy with comparable safety 
compared to ustekinumab in a phase II trial in chronic plaque psoriasis, another disease 
associated with dysregulation of the IL-23 pathway (P15-03262).
Together, these observations suggest that BI 655066/ABBV-066 (risankizumab) may
demonstrate efficacy in this disease.
2.2
TRIAL OBJECTIVES
The purpose of this long term safety extension trial is to provide subjects who responded 
to treatment with BI 655066/ABBV-066 (risankizumab) in a preceding trial with a 
long-term treatment option.


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The primary objective of the study is to investigate long-term safety of 
BI 655066/ABBV-066 (risankizumab), in patients with moderately to severely active 
Crohn`s disease, who showed a clinical response or remission on previous treatment with 
BI 655066/ABBV-066 (risankizumab) and are now receiving long term treatment.
Additional objectives of this study are to further investigate long-term efficacy, 
tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of 
BI 655066/ABBV-066 (risankizumab).
Study endpoints are listed in Section 5.1.1.
2.3
BENEFIT - RISK ASSESSMENT
The preclinical and clinical profiles of BI 655066/ABBV-066 (risankizumab) suggest that 
it profoundly inhibits IL-23 in patients with psoriasis and thus has the potential to address 
unmet medical need in Crohn's disease, as shown for other IL23 inhibitors before (see 
Section 1.2) (R15-1973). Since Crohn's disease is a chronic disease that typically requires 
long-term treatment, a direct benefit for the individual participants in this study can be 
assumed, since only such patients will be enrolled that have achieved a clinical response 
to this compound in the preceding trial 1311.6.
In addition, participation in this study may help to generate a group benefit by providing a 
new treatment modality for the population of patients with moderate or severe Crohn's 
disease if BI 655066/ABBV-066 (risankizumab) proves to be successful in treating this 
disease.
Though there are no serious adverse drug reactions known to be associated with 
risankizumab therapy, risks of participating in this study include risk of infection and risks 
related to the trial specific procedures blood sampling, infusion and injection of study 
medication, and ileocolonoscopy.
Blood sampling, intravenous infusions and subcutaneous injections can cause local 
bruising, inflammation, and pain. Ileocolonoscopy although generally well tolerated, can 
be associated with diarrhoea, abdominal pain, perforation, bleeding, effects from 
anaesthetic medications and infection.
As with any immune modulating agent, BI 655066/ABBV-066 (risankizumab) has the 
potential to impair immune function resulting in an increased risk of infections. This will 
be addressed by clinical monitoring for AEs during the treatment and observation periods. 


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Interferon gamma (IFN-γ) release assay to M. tuberculosis will be obtained at visit 1, to 
exclude or discontinue patients with untreated active or latent TB infection. All patients 
with negative TB screening at baseline will be re-tested once per year in order to exclude 
possible active or latent TB infection. Patients having current signs or symptoms of 
infection or history of serious infection will not be included in the study.
Major adverse cardiovascular events, including myocardial infarction, cerebrovascular 
accident, and cardiovascular death, have been reported in patients with Psoriasis treated 
with the anti-IL-12/23 agents, ustekinumab and briakinumab, based on their frequent co-
morbidities associated with cardiovascular risk. Such an association has not been reported 
in other diseases and the causal relationship of MACE to treatment with these agents is 
unclear. The overall risk of MACE in the present study is considered to be low. However, 
all suspected cardio- and cerebro-vascular events (serious or nonserious) observed in this 
study will be adjudicated by an independent cardiovascular adjudication committee 
(CAC) during long-term treatment.
Local reactions to s.c. administered biologic agents are uncommon, and are usually 
limited to redness, swelling or induration at the injection site. Manifestations of systemic 
infusion reactions include anaphylaxis, pruritus, hypotension, and respiratory distress. 
Both local and systemic hypersensitivity reactions were rare in phase II, readily 
detectable, transient in nature, and manageable with standard medical treatment. No 
systemic hypersensitivity reactions have been reported with BI 655066/ABBV-066 
(risankizumab) to date. Patients will be closely monitored for at least 2 to 3 hours after 
start of i.v. drug administration whereas 30 minutes to 1 hour after s.c. drug 
administration for signs of redness, swelling or hardness at the injection site or 
generalized itching, dizziness or difficulty breathing.
The role of IL-23 in tumor immunity is not well established at this time, but an increased 
risk of cancer from an IL-23 antagonist, though considered small, cannot be excluded.
Although rare, a potential for drug-induced liver injury is under constant surveillance by 
sponsors and regulators. Therefore, this study requires timely detection, evaluation, and 
follow-up of laboratory alterations of selected liver laboratory parameters to ensure 
patients' safety.
Summary of benefit-risk assessment
The benefit-risk profile is considered appropriate for an experimental therapy at this stage 
of clinical development. In order to mitigate any safety signals as early as possible, an 
independent DMC will oversee this study.


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The independent external CAC will be adjudicating observed cardio- and cerebro-vascular 
events.  The events that are adjudicated and the adjudication process will be detailed in 
the Cardiovascular Adjudication Committee Charter. Dedicated eCRFs will be used for 
events of myocardial infarction-unstable angina, stroke-transient ischemic attack, and 
death. In addition, the site may be contacted for additional source documentation for 
relevant events.


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3.
DESCRIPTION OF DESIGN AND TRIAL POPULATION
3.1
OVERALL TRIAL DESIGN AND PLAN
This open label long term extension trial investigates the long term safety and efficacy of 
BI 655066/ABBV-066 (risankizumab). Approximately 60 patients who meet the entry 
criteria are planned for inclusion in this trial, rolling over from preceding trial 1311.6. The 
treatment will be open label.
The treatment period will be 204 (Flow chart 1), 206 (Flow chart 2) or 216 (Flow chart 3) 
weeks, followed by a 140 day follow up period.
Patients rolling over from preceding trial 1311.6 will have to complete period 2 or 3 in 
that trial and either demonstrate a clinical response without remission at Visit E1 or a 
clinical response or remission at Visit E5 as defined by that protocol (see Figure 3.1:1).
Figure 3.1:1
Guideline for roll over of patients from 1311.6 to long term extension 
study 1311.20/M15-989
All patients directly rolled over from 1311.6 into 1311.20/M15-989 will receive 180 mg 
BI 655066/ABBV-066 (risankizumab) subcutaneously from visit 2 onwards every 


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8 weeks, until the EoT visit is performed. Patients who complete this study may elect to 
continue in M16-000 Sub-Study 3 (Phase 3 open label extension study).
Patients who have completed 1311.6 qualifying for roll-over into 1311.20/M15-989 
before availability of this study, can be enrolled depending on their clinical remission or 
response. If patients were treated between finishing 1311.6 and entering 
1311.20/M15-989 with anti-TNF therapy or any biologic agent an 8 weeks or 5 times the 
half-life (whichever is longer), wash-out period will be needed before administration of 
first i.v or s.c. study medication. Patients must maintain their best response status (clinical 
response or remission) post 1311.6. Patients who dropped from 1311.6 with remission 
must maintain remission or undergo re-induction while responders will have to maintain 
their response.
!
If clinical response or remission (CDAI drop >100 from baseline of 1311.6 or 
CDAI < 150) was maintained after end of treatment and is confirmed at screening for 
1311.20/M15-989, patients can directly be assigned to open label s.c. maintenance 
treatment with 180 mg every 8 weeks (FLOW CHART 1) ( visit window between last 
IMP dose in 1311.6 and first IMP dose in 1311.20/M15-989 should be at least 
8 weeks).
!
If clinical remission (achieved at E5 1311.6) has been lost after end of treatment in 
1311.6 and/or at screening for 1311.20/M15-989, patients will receive open label i.v. 
re-induction treatment with three infusions of 600 mg each every 4 weeks after which 
eligibility will be re-assessed. If clinical remission or at least response compared to 
1311.6 study baseline (V2) is achieved patients will switch to s.c. maintenance 
treatment with 180 mg s.c. every 8 weeks (Flow chart 3), otherwise an EoT visit has 
to be performed. After last administration of trial drug in 1311.20/M15-989 trial, a 
140 day follow up call should be scheduled for patients who do not elect to enroll in 
Study M16-000.
!
If clinical response (achieved at E1 or E5 1311.6) has been lost after end of treatment 
in 1311.6 and/or at screening for 1311.20/M15-989, patients will receive open label 
i.v. re-induction treatment with three infusions of 600 mg each every 4 weeks after 
which eligibility will be re-assessed. If clinical response or remission compared to 
1311.6 study baseline (V2 1311.6) is achieved patients will switch to s.c. maintenance 
treatment with 180 mg s.c. every 8 weeks (Flow chart 3), otherwise an EoT visit has 
to be performed. After last administration of trial drug in 1311.20/M15-989 trial, a 
140 day follow up call should be scheduled for patients who do not elect to enroll in 
Study M16-000.
The results from the last colonoscopy done in 1311.6 will serve as baseline for 
1311.20/M15-989. A colonoscopy at screening is only required for patients who lost 


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response or remission during extended follow-up phase after completion of 1311.6. 
Colonoscopies are repeated once per year to assess the effect of continued treatment on 
endoscopic response and mucosal healing.
The end of study is defined as the date the last subject completes the End of trial visit
The primary analysis will be performed after all patients have completed their EoT visit. 
The reference values for the efficacy endpoints clinical or endoscopic response will be the 
baseline values in 1311.6.
For details regarding Adverse event and serious adverse event reporting, see 
Section 5.2.2.2
3.1.1
Administrative structure of the trial
The trial is sponsored by AbbVie, Inc.
A Co-ordinating Investigator will be nominated to coordinate investigators at different 
sites participating in this multicentre trial. Tasks and responsibilities for the Co-ordinating 
Investigators will be defined in a contract filed before initiation of the trial.
Documents on participating (Principal) investigators and other important participants, 
especially their curricula vitae, will be filed in the CTMF.
All documentation collected during the trial and filed in the CTMF will be transitioned to 
AbbVie, Inc.
Details of the trial supplies including responsible institutions are given in Section 4 of this 
protocol.
Details regarding Interactive Response Tool (IRT) used in this trial are provided in the 
ISF.
Details regarding procedures pertaining to central laboratory will be provided in the 
Laboratory Manual in ISF.
External vendors will be contracted to centrally manage videotapes of ileocolonoscopies. 
Details regarding the procedures pertaining to the central image managing system will be 
provided in the ISF.


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The Investigator Site File (ISF) will be maintained at the sites as required by local 
regulations. A copy of the ISF documents will be kept as an electronic CTMF document 
and the CTMF will be transitioned to AbbVie, Inc.
3.1.1.1 Data Monitoring Committee (DMC)
The study will have a DMC independent from the sponsor. The purpose of the DMC is to 
ensure that the welfare of patients participating in this trial is maintained by:
!
Monitoring the trial for possible untoward harmful effects or unexpected frequency of 
adverse safety events of study drugs;
!
Assessing whether the goals of the trial are quite unlikely to be achieved, based on 
emerging data.
The DMC will perform an evaluation of the accrued patient data in order to recommend 
whether the trial or program should continue, be modified or stopped for safety concerns 
or ethical reasons. The DMC will review pertinent trial data, including deaths, SAEs and 
AEs, laboratory data and efficacy. All materials provided to the DMC are confidential. 
The tasks and responsibilities of the DMC will be filed in a contract before initiation of 
the trial and will contain written operating procedures. The DMC will maintain written 
records of all its meetings. Sponsor will remain blinded to these ongoing data reviews.
Details on the DMC, including the analyses, the composition of the DMC, the procedures, 
roles, responsibilities and regular meeting planner are provided in the DMC charter in the 
Investigator Site File (ISF).
3.2
DISCUSSION OF TRIAL DESIGN, INCLUDING THE CHOICE OF 
CONTROL GROUP(S)
Study 1311.20/M15-989 is designed as an open label, single group trial and is expected to 
generate long term safety information to support the submission for registration. As noted 
in Section 4.1.3 below, the s.c. dose (180 mg every 8 weeks) from the study 1311.6 will 
be used in all patients for the maintenance treatment. Since study 1311.6 has not been 
completed and analysed at the time this study has been designed, the highest induction 
schedule of three 600 mg infusions every 4 weeks that was found safe in 1311.6 will serve 
as re-induction dose for patients who lost their response or remission between completion 
of 1311.6 and enrolment in 1311.20/M15-989. 


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The goal of this study is to obtain initial on-drug, long-term safety data together with early 
evidence on the durability of the clinical response, that both will be essential for the 
licensing authorization application. As typical for an open-label, single-group study, 
neither powered nor controlled analyses can be obtained. However, the study may yield 
initial tendencies and at the same time permit early study participants to continue a 
successful therapy.
3.3
SELECTION OF TRIAL POPULATION
Eligible patients from preceding 1311.6 trial will be offered participation in this long term 
extension trial based on their achievement of clinical response. The check for patient
eligibility will be based upon a successful treatment (Section 3.3.2) of the preceding trial 
and on signing the Informed Consent for the long term extension trial.
Based on the results for the MEDI-2070 compound with identical mode-of-action, it is 
expected that up to 50 % of patients in 1311.6 will achieve a clinical response after 
induction treatment. Assuming a 100% maintenance rate of their response, up to 
60 patients may be entered in this trial.
A log of all patients included into the study (i.e. having given informed consent) will be 
maintained in the ISF at the investigational site irrespective of whether they have been 
treated with investigational drug or not.
3.3.1
Main diagnosis for study entry
3.3.2
Inclusion criteria
1. Patients with Crohn's disease, who have successfully completed the preceding trial 
1311.6. Successful treatment is defined as:
!
Completion of period 2 in 1311.6 with a clinical response (drop in CDAI from 
baseline by ≥100) but no remission (CDAI < 150) at Visit E1; or
!
Completion of period 3 in 1311.6 with a clinical response (drop in CDAI from 
baseline by ≥100) and / or remission (CDAI < 150) at Visit E5; or 
!
Completion of period 2 or 3 in 1311.6 per protocol with a clinical response or 
remission before initiation of 1311.20/M15-989 may roll-over either directly if that 
response/remission is maintained or through an open-label i.v. re-induction phase if 
they have lost their previous response/remission.(for more details see Section 3.1)


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2. Female patients:
a. Women of childbearing potential (not surgically sterilized and between menarche 
and 1 year postmenopause), that, if sexually active agree to use one of the 
appropriate medically accepted methods of birth control in addition to the 
consistent and correct use of a condom from date of screening until 20 weeks after 
last administration of study medication. Medically accepted methods of 
contraception are: ethinyl estradiol containing contraceptives, diaphragm with 
spermicide substance, and intra-uterine-device, or
b. Surgically sterilized female patients with documentation of prior hysterectomy, 
tubal ligation or complete bilateral oophorectomy, or
c. Postmenopausal women with postmenopausal is defined as permanent cessation ≥ 
1 year of previously occurring menses, and
d. Negative serum ß-Human Chorionic Gonadotrophin (ß-HCG) test at screening and 
urine pregnancy test prior to randomization.
Male patients: 
a.  Who are documented to be sterile, or 
b.  Who consistently and correctly use effective method of contraception 
(i.e., condoms) during the study and 20 weeks after last administration of study 
medication.
3.   Be able to adhere to the study visit schedule and other protocol requirements.
3.3.3
Exclusion criteria
Patients meeting any of the following criteria cannot roll over.
1. Patients who were not compliant with key study procedures (colonoscopy, 
treatment compliance, endpoint assessment, contraception measures) in preceding 
trial 1311.6
2. Patients who could not tolerate BI 655066/ABBV-066 (risankizumab) treatment 
for tolerability or safety reasons in the preceding trial
3. Are pregnant, nursing, or planning pregnancy while enrolled in the study, or within 
20 weeks after receiving the last dose of study medication.
4. Patients must agree not to receive a live virus or bacterial or BCG vaccination 
during the study or up to 12 months after the last administration of study drug.


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5. Patients who have developed malignancy, or suspicion of active malignant disease 
during the preceding trial.
6. Are intending to participate in any other study using an investigational agent or 
procedure during participation in this study.
7. Cannot adhere to the concomitant medication requirements mentioned in 
Section 4.2.2.
3.3.4
Removal of patients from therapy or assessments
3.3.4.1
Removal of individual patients
An excessive rate of withdrawals may render the study results uninterpretable; therefore 
unnecessary withdrawal of patients must be avoided. Patients who discontinue their 
treatment early should undergo all study required procedures including an early EoT visit 
and colonoscopy, as defined in Section 6.
Patients have the right to withdraw from the study at any time without the need to justify 
the decision.
The sponsor reserves the right to terminate a patient from the trial for non-compliance.
The investigator has the right to remove patients from the study for non-compliance.
Furthermore, patients' treatment must be discontinued early due to lack of efficacy 
(defined as an endoscopically confirmed CDAI re-increase to >100 points above baseline 
in 1311.6 and a CDEIS >4), or for other reasons (as described below). If, in the 
investigator's opinion, such a patient requires alternative medical therapy for their Crohn's 
disease, the study treatment must be stopped and patients may receive conventional 
treatment for active disease as per investigator's judgment.
Criteria and rules for stopping patient treatment due to reasons other than lack of efficacy 
include:
!
Development of a toxicity or adverse event which warrants drug discontinuation.
!
Development of any potentially life-threatening toxicity.
!
Any concomitant illness that prevents compliance.
!
The patient is unwilling to continue in the trial.


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!
Pregnancy in a female participant.
!
Patient lost to follow-up despite reasonable efforts to make contact with the patient.
!
Patient is no longer able to participate for other medical reasons (e.g., surgery, adverse 
events or other diseases).
!
The DMC may recommend termination or re-design of the trial for other relevant 
issues of safety.
Patients who discontinue from the study after Visit 2 will be considered as "early 
discontinuations" and the reason for premature discontinuation must be recorded in the 
eCRFs. The data will be included in the trial database and will be reported. 
3.3.4.2
Discontinuation of the trial by the sponsor
Abbvie Inc., 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,
2. Emergence of any efficacy/safety information that could significantly affect 
continuation of the trial, or any other administrative reasons, i.e. termination of 
clinical development of BI655066 in Crohn's disease,
3. Violation of GCP, the CTP, or the contract by a trial site or investigator, disturbing the 
appropriate conduct of the trial.
The investigator / the trial site will be reimbursed for reasonable expenses incurred in case 
of trial termination (except in case of the third reason).


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4.
TREATMENTS
4.1
TREATMENTS TO BE ADMINISTERED
BI 655066/ABBV-066 (risankizumab) will be administered intravenously and/or 
subcutaneously.
4.1.1
Identity of investigational product and comparator product(s)
The characteristics of the test product for i.v. administration are below.
Substance:
BI 655066/ABBV-066 (risankizumab):  
Anti-human IL-23p19 mAb
Pharmaceutical formulation:
Chemical name:
Anti-human IL-23p19 mAb
Molecular weight:
Approximately 148 kDa
Source:
Boehringer Ingelheim Pharma GmbH & Co. 
KG
Unit strength:
Dose (per infusion)
600 mg
Posology
3 infusions separated by 4 weeks
Route of administration:
i.v. infusions
The characteristics of the test product for s.c. administration are below.


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Substance:
BI 655066/ABBV-066 (risankizumab):  
Anti-human IL-23p19 mAb
Pharmaceutical formulation:
Chemical name:
Anti-human IL-23p19 mAb
Molecular weight:
Approximately 148 kDa
Source:
Boehringer Ingelheim Pharma GmbH & Co. 
KG
Unit strength:
Dose (per injection)
180 mg
Posology
Every 8 weeks
Route of administration:
s.c.
4.1.2
Method of assigning patients to treatment groups
Patients directly rolled over from 1311.6 into this study will be assigned to open label s.c. 
treatment via IRT.
For early completers of 1311.6,i.e. patients who have completed 1311.6 qualifying for 
roll-over into 1311.20/M15-989 before availability of this study and not treated otherwise, 
will be assigned per clinical response post study treatment and at screening in 
1311.20/M15-989 either to i.v. re-induction treatment or directly to open label s.c. 
treatment via IRT (as described earlier in Section 3.1)


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4.1.3
Selection of doses in the trial
Direct roll-over patients from 1311.6 will receive open label treatment with 180 mg s.c. 
q8w, representing the maintenance dose tested in phase II, that was found safe and 
effective in preceding study 1311.6.
Early completers of 1311.6 dependent on clinical response post study treatment and at 
screening in 1311.20/M15-989 will receive either 180 mg s.c. q8w maintenance treatment 
or re-induction with 3 infusions of 600 mg i.v. q4w followed by180 mg s.c. q8w 
maintenance treatment.
4.1.4
Drug assignment and administration of doses for each patient
The dose of BI 655066/ABBV-066 (risankizumab) for s.c. and i.v. injections will be fixed.
The subcutaneous study drug will be administered as an injection in the abdomen, thighs, 
gluteal region, or upper arms. Injections being given in the same area should be at least 
2 cm apart and should not be close to a vein. The injection site should avoid sites where 
the skin is tender, bruised, erythematous, or indurated, and should be alternated to other 
areas for subsequent doses.
Supplied BI 655066/ABBV-066 (risankizumab) solution for i.v. administration 
(concentration 10.0 mg/mL) will be injected into a 100 mL i.v. infusion bag of 5% 
dextrose in water (D5W) and administered as described in detail in the Investigator Site 
File (Instructions for Preparation and Handling of BI 655066/ABBV-066 (risankizumab)).
Subcutaneous administration of biologic agents involves the risk of local (injection site) 
or systemic hypersensitivity reactions. Therefore patients should be closely monitored for 
signs and symptoms of hypersensitivity reactions for approximately 30 minutes following 
study drug administration. Study personnel should observe the injection site for signs of 
redness, swelling or hardness. They should also ask subjects about itching, dizziness or 
shortness of breath. Patients should be advised that if they experience redness, swelling or 
other changes at the injection site, they should notify site personnel. They should further 
be advised that if they experience itching all over or a feeling of being swollen, dizzy or 
short of breath, they should notify site personnel or their own healthcare provider 
immediately.
The i.v. study drug will be administered under immediate supervision of the physician 
investigator or a designee with a minimum of a nursing degree. In all cases a physician 


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investigator must be on-site during administration and until at least 2 hours after the start 
of drug administration. Patients will remain at the trial center for approximately 1 hour 
following the end of i.v. administration (2 hours after the first administration)
Detailed procedures for preparing and handling of the study drug are provided in 
the ISF.
4.1.5
Blinding and procedures for unblinding
4.1.5.1
Blinding
Since this is a single group, open label study, there are no blinding issues and the dose 
received will be visible in the database.
4.1.5.2
Procedures for emergency unblinding
Not applicable.
4.1.6
Packaging, labelling, and re-supply
The clinical trial supply consists of containers (cartons) with trial- identification that hold 
the trial medication and is labelled as required per country requirements with the 
following:
!
Trial number
!
Name of product and strengths or identification code
!
Pharmaceutical form
!
Route and mode of administration
!
Term "for clinical trial use" (domestic language)
!
Sponsor name and address
!
Storage conditions
!
Medication number
!
Batch number
!
Expiry date (use-by-date)
Labels must remain affixed to the kits.


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Drug supply and inventory will be controlled by IRT. Each kit label will contain a unique 
kit number. The kit is assigned to a subject via IRT at each dispensing visit. For details of 
packaging and the description of the label, refer to the ISF.
4.1.7
Storage conditions
Both i.v. and s.c. drug supplies will be kept refrigerated (the recommended storage 
conditions is +2 - +8°C or 36-46°F) in their original packaging. The trial medication must 
be stored securely, e.g., in a locked refrigerator or at a pharmacy and must be kept 
protected from light as well as must not be frozen at any time.
The refrigerator temperature must be recorded each business day. Malfunctions or any 
temperature excursion must be reported to the Sponsor immediately.
Study drug should be quarantined and not dispensed until AbbVie or AbbVie 
Temperature Excursion Management System (ATEMS) deems the drug as acceptable.
4.1.8
Drug accountability
Drug supplies, which will be provided by the sponsor, must be kept in a secure, limited 
access storage area under the storage conditions defined by the sponsor. Where necessary, 
a temperature log must be maintained to make certain that the drug supplies are stored at 
the correct temperature.
All unused medication must be returned to the sponsor. Receipt, usage and return must be 
documented on the respective forms in the ISF. An account must be given for any 
discrepancies.
The investigator / pharmacist / investigational drug storage manager will receive the 
investigational drugs delivered by the sponsor when the following requirements are 
fulfilled:
!
approval of the study protocol by the IRB / ethics committee,
!
availability of a signed and dated clinical trial contract between the sponsor and the 
Head of Trial Centre,
!
approval/notification of the regulatory authority, e.g. competent authority,
!
availability of the curriculum vitae of the principal investigator,


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!
availability of a signed and dated clinical trial protocol or immediately imminent 
signing of the clinical trial protocol, (in exceptional cases, medication could already 
be sent to the site, before its activation via IRT)
!
if applicable availability of the proof of a medical licence for the principal 
investigator, 
!
for USA availability of the Form 1572.
The investigator / pharmacist / investigational drug storage manager must maintain 
records of the product's delivery to the trial site, the inventory at the site, the use by each 
patient, and the return to the sponsor or alternative disposition of unused product(s).
These records will include dates, quantities, batch/serial numbers, expiry ('use by') dates, 
and the unique code numbers assigned to the investigational product(s) and trial patients. 
The investigator / pharmacist / investigational drug storage manager will maintain records 
that document adequately that the patients were provided the doses specified by the CTP 
and reconcile all investigational product(s) received from the sponsor. At the time of 
return to the sponsor or appointed CRO, the investigator / pharmacist / investigational 
drug storage manager must verify that no remaining supplies are in the investigator's 
possession.
4.2
CONCOMITANT THERAPY, RESTRICTIONS, AND RESCUE 
TREATMENT
4.2.1
Rescue medication, emergency procedures, and additional treatment(s)
Concomitant therapies should be limited to those essential for the non-gastrointestinal 
care of the patient. All concomitant medications and the reason(s) for use will be 
documented throughout the course of the study.
In case of infusion reactions emerging during or after infusion of BI 655066/ABBV-066 
(risankizumab), the investigator should consider in accordance with severity of the 
reaction and local standard of care to
!
immediately interrupt the infusion
!
treat with systemic anti-histamines and intravenous steroids
Based on patient's clinical course and medical judgment, the infusion may be re-initiated 
in case of mild or moderate reactions (according to RCTC grading in Appendix 10.3) at 


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lower speed with gradual increase to complete the infusion as detailed in the Instructions 
for Preparation and Handling of BI 655066/ABBV-066 (risankizumab) in the Investigator 
Site File.
In case of adverse events in need of treatment, symptomatic therapy according to the 
judgment of the investigator will be permitted. All concomitant and/or rescue therapies 
will be recorded on the appropriate pages of the eCRF.
There are no special emergency procedures to be followed.
4.2.2
Restrictions
4.2.2.1
Restrictions regarding concomitant treatment
Medications
Restriction time period
Investigational 
products
4 weeks or 5 half-lives, whichever is greater
5-ASA compounds.
!
Rectal 5-ASA compounds are not permitted during 
the study and must have been discontinued at least 
4 weeks prior to visit 2.
!
Oral 5-ASA compounds must have been at a stable 
dose for at least 4 weeks prior to visit 2.
!
If oral 5-ASA compounds were recently 
discontinued, they must have been discontinued at 
least 4 weeks prior to visit 2.


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Immunomodulators
Patients receiving chronic (i.e., ≥ 12 weeks) treatment 
with AZA, 6-MP, or MTX prior to visit 2 must have been 
on a stable dose for at least 4 weeks prior to visit 2 and 
must continue on this same dose during the study. 
Patients who have discontinued therapy with AZA, 6-MP, 
or MTX must have stopped the medication at least 
4 weeks prior to visit 2 to be considered eligible for 
randomisation.
Patients must not have received therapy with other known 
immunomodulators (e.g., 6-thioguanine [6-TG], 
cyclosporine, tacrolimus, sirolimus, pentoxifylline, or 
mycophenolate mofetil) or experimental agents 
(e.g., granulocyte macrophage – colony stimulating factor 
[GM-CSF]) within 8 weeks or 5 half-lives of agent from 
visit 2, whichever is longer.
monoclonal antibodies 
or anti-TNF agents
Patients must not have received therapy ≤ 8 weeks or 
5 half-lives (whichever is longer) from visit 2 and during 
study treatment period.
4.2.2.1
Restrictions regarding concomitant treatment (cont.)
Medications
Restriction time period
Systemic 
corticosteroids (eg, 
prednisone, 
budesonide)
!
Parenteral (SC, IM, or IV) or rectal corticosteroids 
are not permitted during the study and must not have 
been used within a 4-week period prior to visit 2.
!
Oral corticosteroids must be at a prednisone-
equivalent dose of ≤ 20 mg/day, or ≤ 6 mg/day of 
budesonide, and have been at a stable dose for at 
least 4 weeks prior to visit 2.
!
If oral corticosteroids were recently discontinued, 
discontinuation must have been completed at least 
3 weeks prior to visit 2.


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Crohn's disease-
specific antibiotics
If using a Crohn's disease-specific antibiotic for treatment 
of Crohn's disease, patients must have been using the 
antibiotic for at least 4 weeks before visit 2 at a stable 
dose. If not currently using a Crohn's disease-specific 
antibiotic, the stop date must have been at least 4 weeks 
prior to visit 2.
Opioids
Patients with regular daily opioid use over the past 3 
months before screening are excluded due to the 
interference of such medication with key efficacy 
endpoints (CDAI)
Live or attenuated 
vaccines (during study 
or 140 days after last 
dose of study drug)
!
live attenuated influenza (intranasal)
!
herpes zoster
!
rotavirus
!
varicella (chicken pox)
!
measles-mumps-rubella (MMR) or measles mumps 
rubella varicella
!
(MMRV)
!
oral polio vaccine (OPV)
!
smallpox
!
yellow fever
!
Bacille Calmette-Guérin (BCG)
!
oral typhoid
Tapering of corticosteroids
The tapering of prednisone dosage or equivalent (see Appendix 10.2) of other systemic 
corticosteroids is requested for patients achieving clinical remission the first time while on 
treatment with BI 655066. In such patients steroids must be tapered at a maximum rate of 
2.5 mg per week to a dosage of 0. If a patient experiences a loss of clinical response 
(decrease in CDAI < 100 points from baseline on 2 consecutive visits) during steroid 
tapering, the dosage of prednisone may be increased back to the dosage used at study 
entry.


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


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5.
VARIABLES AND THEIR ASSESSMENT
5.1
EFFICACY - PHARMACODYNAMICS
5.1.1
Endpoint of efficacy
Efficacy endpoints are:
!
Clinical remission by visit, defined as a CDAI score of < 150.
!
Clinical response by visit, defined by either a CDAI score of < 150 or a CDAI 
reduction from baseline of at least 100 points.
!
PRO-2 remission by visit, defined by a PRO-2 score of < 75
!
PRO-2 response by visit, defined as a decrease from baseline of 50 points or more.
!
CDEIS remission by visit, defined as a score of 4 or less (for patients with initial 
isolated ileitis a score of 2 or less)
!
CDEIS response by visit, defined as a score of 7 or less (for patients with initial 
isolated ileitis > 50% reduction from baseline).
!
Mucosal healing by visit, defined as the absence of mucosal ulceration.
!
Deep remission by visit, defined as clinical remission and endoscopic remission 
(CDEIS).
!
Change from baseline in CDAI scores by visit.
!
Change from baseline in PRO-2 scores by visit.
!
Change in CDEIS by visit.
!
Change in SES-CD by visit.
!
CDEIS percentage change from baseline by visit.
!
SES-CD percentage change from baseline by visit.
!
Reduction of 75% in CDEIS scores from baseline by visit.
!
Reduction of 75% in SES-CD scores from baseline by visit.
!
Change from baseline in stool frequency by visit based on patient diary.
!
Stool consistency by visit based on patient diary.
!
Change from baseline in abdominal pain score by visit based on patient diary and 
scored, with possible answers none, mild, moderate and severe.
!
Change from baseline in IBDQ scores by visit.
!
Change from baseline in CRP and fecal calprotectin profile by visit.
!
Reduction in the number of draining fistulas in patients with draining fistulas at 
baseline.


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5.1.2
Assessment of efficacy
CDAI, PRO-2
The investigator will determine and record the CDAI score throughout the study, as 
denoted (see Flow chart 1, Flow chart 2 and Flow chart 3). Hematocrit evaluations will be 
made at each visit by the central laboratory as they are integral to the CDAI calculation.
The Patient reported outcome-2 (PRO-2) includes only the two CDAI items stool 
frequency and abdominal pain and will be analyzed based on the CDAI responses 
recorded by the investigator for these two dimensions.
Inflammatory Bowel Disease Questionnaire (IBDQ)
The IBDQ (R97-3472) is a 32-item self-report questionnaire for patients with IBD to 
evaluate the patient reported outcomes across 4 dimensions: bowel symptoms (loose 
stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social 
function (work attendance, need to cancel social events), and emotional function (anger, 
depression, irritability). Scores range from 32 to 224 with higher scores indicating better 
outcomes.
The patient will complete the IBDQ before site staff interaction and study drug 
administration as noted in the Flow chart 1, Flow chart 2 and Flow chart 3.
Tapering of corticosteroids
Any change in the corticosteroid co-medication has to be recorded on the appropriate 
eCRF page for Crohn's disease specific co-medication. The dose of corticosteroid 
co-medication should remain stable prior to achieving clinical remission.
CRP and Fecal Calprotectin
Concentration of serum CRP and fecal calprotectin will be measured by the central 
laboratory, and if necessary by additional specialist laboratories.
Ileocolonoscopy, SES-CD and CDEIS
Every effort should be made for the patient to perform a final ileocolonoscopy at the study 
visit where the last dose of study medication is administered or within 2 weeks following 
the premature discontinuation visit.


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Lesions detected by ileocolonoscopy will be scored by means of the validated Crohn's 
Disease Endoscopic Index of Severity (CDEIS). The same endoscopist at the study site 
will complete the CDEIS for each ileocolonoscopy immediately after the procedure. 
Investigators will record endoscopies and send the videos to the central imaging 
laboratory. A central reading of endoscopies will be performed by independent blinded 
reviewer(s) and the findings will be scored using both, the CDEIS and the SES-CD 
scores. In case of discrepancies between the local endoscopic and central blinded 
reviewer, the centrally read scores will be used for efficacy assessments and the trial 
report.
Fistula response
A fistula response is defined as a ≥ 50% reduction in the number of draining fistulas.
Enterocutaneous fistulas (e.g., perianal and abdominal) will be considered no longer 
draining (i.e., closed) when there is absence of drainage despite gentle compression. 
Rectovaginal fistulas will be considered closed based on either physical examination, 
appropriate MRI imaging or absence of relevant symptoms (e.g., passage of rectal 
material or flatus from the vagina).
5.2
SAFETY
5.2.1
Endpoint(s) of safety
There is no primary endpoint in a statistical sense in this study (see Section 7.2). Instead, 
safety and tolerability will be assessed in a descriptive way based on:
!
Physical examination
!
Vital signs (blood pressure (BP), heart rate (HR) and oral body temperature)
!
12-lead ECG (electrocardiogram)
!
Clinical laboratory tests (haematology, clinical chemistry and urinalysis)
!
Adverse events
!
Immunogenicity


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5.2.2
Assessment of adverse events
5.2.2.1
Definitions of adverse events
Adverse event
An adverse event (AE) is defined as any untoward medical occurrence in a patient or 
clinical investigation subject administered a medicinal product and which does not 
necessarily have to have a causal relationship with this treatment.  An AE can therefore be 
any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom or disease temporally associate with the use of a medicinal (investigational) 
product, whether or not the event is considered causally related to the use of the product.
Such an event can result from use of the drug as stipulated in the protocol or labeling, as 
well as from accidental or intentional overdose, drug abuse, or drug withdrawal. Any 
worsening of a pre-existing condition or illness is considered an AE.  Laboratory 
abnormalities and changes in vital signs are considered to be AEs only if they result in 
discontinuation from the study drug, necessitate therapeutic medical intervention, and/or 
if the investigator considers them to be AEs.
An elective surgery/procedure scheduled to occur during a study will not be considered an 
adverse event if the surgery/procedure is being performed for a pre-existing condition and 
the surgery/procedure has been pre-planned prior to study entry.  However, if the 
pre-existing condition deteriorates unexpectedly during the study (e.g., surgery performed 
earlier than planned), then the deterioration of the condition for which the elective 
surgery/procedure is being done will be considered an adverse event.
Adverse reaction
An adverse reaction is defined as a response to a medicinal product which is noxious and 
unintended. Response in this context means that a causal relationship between a medicinal 
product and an adverse event is at least a reasonable possibility. Adverse reactions may 
arise from use of the product within or outside the terms of the marketing authorisation or 
from occupational exposure. Conditions of use outside the marketing authorization 
include off label use, overdose, misuse, abuse and medication errors.
Serious adverse event
A serious adverse event (SAE) is defined as any AE which results in death, is life-
threatening, results in persistent or significant disability  or incapacity, requires inpatient 
hospitalisation or prolongation of existing hospitalisation, is a congenital anomaly / birth 


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defect, or is to be deemed serious for any other reason if it is an important medical event 
when based upon appropriate medical judgement which may jeopardise the patient and 
may require medical or surgical intervention to prevent one of the other outcomes listed in 
the above definitions.
Medical and scientific judgment should be exercised in deciding whether other situations 
should be considered serious reactions, such as important medical events that might not be 
immediately life threatening or result in death or hospitalisation but might jeopardise the 
patient or might require intervention to prevent one of the other outcomes listed above.
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm, blood dyscrasias or convulsions that do not result in 
hospitalisation or development of dependency or abuse. Any suspected transmission via a 
medicinal product of an infectious agent is also considered a serious adverse reaction.
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.
Adverse Events of Special Interest (AESI)
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 5.2.2.2.
The following are considered as AESI:
!
Hepatic injury defined by the following alterations of liver parameters:
o
For patients with normal liver function at baseline:
an elevation of aspartate aminotransferase (AST) and/or alanine 
aminotransferase (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.
o
Hepatic injury defined by the following alterations of liver parameters (for 
patients with impaired liver function tests at baseline): an elevation of AST 
and/or ALT ≥ 3 times the baseline value combined with an elevation of 
bilirubin ≥ 2 times the baseline value measured in the same blood draw 
sample.


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Patients showing these lab abnormalities need to be followed up according to 
Section 10.1.2 of this clinical trial protocol and the hepatic injury adverse event form 
provided via EDC system.  These lab findings constitute a hepatic injury alert and the 
patients showing these lab abnormalities need to be followed up according to the hepatic 
injury AE form via the EDC-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 laboratory results meet the definition of hepatic 
injury, the investigator will complete the supplemental form.Cardiac Events/Procedures
In the case of any of the following reported major cardiovascular adverse events (MACE), 
the appropriate supplemental eCRFs should be completed:
●
Cardiac events;
●
Myocardial infarction or unstable angina;
●
Cerebral vascular accident and transient ischemic attack;
●
Cardiovascular procedures
Tuberculosis (TB)
In the case of any positive TB test or diagnosis of active TB, the appropriate supplemental 
eCRF should be completed.
Intensity of adverse event
The intensity grading of AEs will be performed according to Rheumatology Common 
Toxicity Criteria (RCTC) Version 2.0 developed by OMERACT (R13-3515). See 
Appendix 10.3 for intensity/severity classification.
Causal relationship of adverse event
The definition of an adverse reaction implies at least a reasonable possibility of a causal 
relationship between a suspected medicinal product and an adverse event. An adverse 
reaction, in contrast to an adverse event, is characterised by the fact that a causal 
relationship between a medicinal product and an occurrence is suspected.
Medical judgment should be used to determine the relationship, considering all relevant 
factors, including pattern of reaction, temporal relationship, de-challenge or re-challenge, 


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confounding factors such as concomitant medication, concomitant diseases and relevant 
history.
Arguments that may suggest that there is a reasonable possibility of a causal relationship 
could be:
!
The event is consistent with the known pharmacology of the study drug.
!
The event is known to be caused by or attributed to the drug class.
!
A plausible time to onset of the event relative to the time of drug exposure.
!
Evidence that the event is reproducible when the drug is re-introduced.
!
No medically sound alternative aetiologies that could explain the event 
(e.g. pre-existing or concomitant diseases, or co-medications).
!
The event is typically drug-related and infrequent in the general population not 
exposed to drugs (e.g. Stevens-Johnson syndrome).
!
An indication of dose-response (i.e. greater effect size if the dose is increased, 
smaller effect size if dose is diminished).
Arguments that may suggest that there is no reasonable possibility of a causal relationship 
could be:
!
No plausible time to onset of the event relative to the time of drug exposure is 
evident (e.g. pre-treatment cases, diagnosis of cancer or chronic disease within days 
/ weeks of drug administration; an allergic reaction weeks after discontinuation of 
the drugconcerned)
!
Continuation of the event despite the withdrawal of the medication, taking into 
account the pharmacological properties of the compound (e.g. after 5 half-lives). Of 
note, this criterion may not be applicable to events whose time course is prolonged 
despite removing the original trigger
!
Additional arguments amongst those stated before, like alternative explanation 
(e.g. situations where other drugs or underlying diseases appear to provide a more 
likely explanation for the observed event than the drug concerned).
!
Disappearance of the event even though the study drug treatment continues or 
remains unchanged.
The reason for the decision on causal relationship for unlisted AEs needs to be provided in 
the (e)CRF.
5.2.2.2
Adverse event and serious adverse event reporting
AE Collection


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The Investigator shall maintain and keep detailed records of all AEs in their patient files.
The following must be collected and documented on the appropriate CRF(s) / eCRF by 
the Investigator:
!
From signing the informed consent onwards through the Residual Effect Period 
(REP), until individual patient's end of trial: all AEs (serious and non-serious) and all 
AESIs.
The residual effect period (REP) for BI 655066/ABBV-066 (risankizumab) is defined as 
20 weeks after the last trial medication application. Therefore, all AEs which occurred 
through the treatment phase and throughout the REP will be considered as on treatment 
(see Section 7.3.3). Events which occurred after the REP will be considered as post 
treatment events.
AE reporting to sponsor and timelines
In the event of an SAE, whether associated with study drug or not, the Investigator will 
notify Clinical Pharmacovigilance within 24 hours the site being made aware of the SAE 
by entering the SAE data into the electronic data capture (EDC) system.  SAEs that occur 
prior to the site having access to the RAVE system, or if RAVE is not operable, should be 
documented on the SAE Non-CRF forms and emailed (preferable route) or faxed to 
Clinical Pharmacovigilance within 24 hours of the site being made aware of the SAE.
Email:  PPDINDPharmacovigilance@abbvie.com
FAX to: +1(847) 938-0660




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RSI in place at the time of occurrence of the 'suspected' Serious Adverse Reaction will be 
used to assess expectedness.
Information required
The following should also be recorded as an (S)AE in the (e)CRF 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 to a satisfactory conclusion or no further information can be obtained.
Pregnancy
Pregnancy in a study subject must be reported to AbbVie within 1 working day of the site 
becoming aware of the pregnancy. Subjects who become pregnant during the study must 
be discontinued from study drug.
Information regarding a pregnancy occurrence in a study subject and the outcome of the 
pregnancy will be collected.
Pregnancy in a study subject is not considered an AE.  However, the medical outcome of 
an elective or spontaneous abortion, stillbirth, or congenital anomaly is considered an 
SAE and must be reported to AbbVie within 24 hours of the site becoming aware of the 
event.
5.2.3
Assessment of safety laboratory parameters
The laboratory tests will be performed as listed in Table 5.2.3: 1and Table 5.2.3: 2. 
Instructions on sample collection, sample handling/ processing, and sample shipping will 
be provided to the investigator site file by the central laboratory. For time points of 
laboratory sampling, see Flow chart 1, Flow chart 2 and Flow chart 3.


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Laboratory results of the patients will be available in real time to the respective 
investigator and to the clinical monitor of each country (central laboratory website), and 
selected abnormal laboratory alerts will be sent automatically to the sites and to the 
sponsor in real time. PK, PD and biomarker data will not be available to the investigators 
or local clinical monitors but the Trial Team (sponsor) in a blinded manner and when 
relevant, in an unblinded manner to the DMC. Laboratory results will be reported as the 
absolute value of the measurement obtained on a study patient.
Clinically relevant laboratory values will be commented on in the eCRF. A clinically 
relevant value may be either in- or outside the reference range. Clinically relevant 
abnormal laboratory test results must be repeated using an unscheduled visit lab kit and 
must be repeated until normalisation or stabilisation or until an alternative explanation has 
been found. Clinically relevant abnormal laboratory values will be also graded for 
intensity by using RCTC Version 2.0 criteria.


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Table 5.2.3: 1 Laboratory tests
Category
Test name
Haematology
Hematocrit (Hct)
Hemoglobin (Hb)
Red Blood Cell Count / Erythrocytes
Reticulocyte Count
White Blood Cells / Leucocytes
Platelet Count
Differential automatic 
(relative
and absolute count)
Neutrophils
Eosinophils
Basophils
Monocytes
Lymphocytes
Differential manual 
(relative and
absolute count)
(if differential automatic is
abnormal)
Neutrophils, Bands
Neutrophils, Polymorphonuclear (PMN)
Eosinophils
Basophils
Monocytes
Lymphocytes
Coagulation
Partial Thromboplastin Time (PTT)
Prothrombin Time (Quick / INR)
Fibrinogen
Enzymes
AST/GOT, SGOT
ALT/GPT, SGPT
Alkaline Phosphatase (AP/ALP)
Creatine Kinase (CK)
CK-MB if CK is elevated
Gamma-Glutamyl Transferase (GGT/γ-GT)
Lactic Dehydrogenase (LDH)
Lipase
Amylase
Specific gamma-globulin 
quantification
IgE1, IgG
1 only in case of allergic reaction


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Table 5.2.3: 1 Laboratory tests (con't)
Category
Test name
Substrates
Glucose
Creatinine and Creatinine Clearance
Blood urea nitrogen
Bilirubin Total
Bilirubin Direct
Protein, Total
Albumin
hsC-Reactive Protein
Uric Acid
Cholesterol, Total
High density lipoprotein (HDL) Cholesterol
Calculated Low Density Lipoprotein (LDL) Cholesterol
Triglycerides
Electrolytes
Calcium
Sodium
Potassium
Chloride 
Bicarbonate
Hormones
Thyroid stimulating hormone (screening visit only)
Free T3, Free T4 if TSH <LLN or >ULN
Urinalysis (Stix)
Urine Nitrite
Urine Protein
Urine Glucose
Urine Ketone
Urobilinogen
Urine Bilirubin
Urine RBC/Erythrocyte
Urine WBC/Leukocytes
Urine pH
Urine sediment
(microscopic examination)
(if urine analysis abnormal)
Urine Sediment Bacteria
Urine Casts in Sediment
Urine Squamous Epithelial Cells
Urine Sediment Crystals, Unspecified
Urine Sediment RBC/Erythrocytes
Urine Sediment WBC/Leucocytes


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Table 5.2.3: 2 Other sampling and testing
Autoantibodies
Human Anti-BI 655066/ABBV-066 
(risankizumab) Antibodies (ADA)
Serum Sample for Biomarkers
Refer to Section 5.6
Fecal sample
Calprotectin
5.2.4
Medical examination
Complete physical examination will include vital sign assessment and general appearance 
as well as evaluation for fistulas and of all organ systems (eyes, ears, nose, mouth, and 
throat, neck, respiratory, cardiovascular, chest, gastrointestinal, lymphatic, 
musculoskeletal, skin, neurologic and psychiatric). Targeted physical examination will 
include vital sign assessment and evaluation for fistulas and of organ systems associated 
with AE(s) symptoms or laboratory abnormalities.
The medical examination will be carried out at screening. It will include documentation of 
patient information, informed consent, demographics including height, weight and 
smoking and alcohol history, relevant medical history and concomitant medication, 
review of inclusion/exclusion criteria, review of vital signs, 12-lead ECG and laboratory, 
and a complete physical examination.
5.2.5
Local tolerability
Local tolerability at the administration site of the subcutaneous injection will be assessed 
by the investigator according to "swelling", "induration", "heat", "redness", "pain", or 
"other findings".
5.2.6
Infusion reaction
In case of an infusion reaction monitor the patient per standard of care, grade the intensity 
of the reaction according to RCTC grading (Appendix 10.3) and proceed as described in 
Section 4.2.2.1. Also draw plasma sample for IgE and ADA (anti-drug antibodies), as 
detailed in the CTP Section 5.5.2.2. and the Lab Manual.
5.2.7
Electrocardiogram
The 12-lead ECGs will be performed as scheduled in the Flow chart 1, Flow chart 2 and 
Flow chart 3.


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It will be recorded after the patients have rested for at least 5 minutes in supine position at 
Visit 1. 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. The 
investigator or a designate will evaluate whether the ECG is normal or abnormal and 
whether it is clinically significant, if abnormal. Additionally, any occurrence of re- or 
depolarization disorders, arrhythmic disorders or other abnormalities will be assessed.
The electronic version of the ECG is regarded as source data. Dated and signed printouts 
will be stored in the patient's medical file.
ECGs may be repeated for quality reasons and the repeat used for analysis. Additional 
ECGs may be collected by the investigator for safety reasons. All clinically-significant 
abnormalities, even transient, must be followed by ECG performed at every subsequent 
visit.
Clinically relevant abnormal findings will be reported as adverse events.
5.3
OTHER
5.3.1
Other endpoint(s)
Not applicable
5.3.2
Other assessment(s)
Not applicable
5.3.3
Pharmacogenomic evaluation
Not applicable
5.4
APPROPRIATENESS OF MEASUREMENTS
All measurements performed during this trial are standard measurements and will be 
performed in order to monitor patients'/patients' safety and to determine pharmacokinetic 
and pharmacodynamic parameters in an appropriate way.


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The scheduled measurements are appropriate to see drug induced changes in vital signs, 
standard laboratory values and ECG. These endpoints are standard and accepted for 
evaluation of safety and tolerability of a biologic drug and are widely used in this kind of 
study.
The pharmacokinetic parameters and measurements outlined in Section 5.5 are generally 
used assessments of drug exposure. The biomarkers and pharmacodynamic parameters 
and measurements outlined in Section 5.6 and 5.7 are of an exploratory nature only.
5.5
DRUG CONCENTRATION MEASUREMENTS AND 
PHARMACOKINETICS
Detailed information on timings for dosing, PK and ADA sampling are listed in 
Flow chart 1, Flow chart 2 and Flow chart 3. Date and exact clock time of administration 
as well as of PK sampling times will be recorded.
They will be documented in the CRFs by the medical personnel or sent as electronic files.
These actual sampling times will be used for determination of PK parameters. If the 
sampling visit represents a drug administration visit, sampling for PK will occur prior to 
the drug administration.
5.5.1
Pharmacokinetic endpoint(s)
The collected concentrations from all patients will be summarized through descriptive 
statistics. If data allow, steady state pharmacokinetic parameters of BI 655066/ABBV-066 
(risankizumab) will be evaluated as appropriate using non-compartmental analysis 
methods according to sponsor's standard
Pharmacokinetic data may additionally be analysed using population pharmacokinetic 
approaches. For this purpose data may also be combined with data from other trials. 
Modelling activities will be planned and documented separately according to internal and 
external guidelines and SOPs.
5.5.2
Methods of sample collection
5.5.2.1
Plasma sampling for pharmacokinetic analysis
For the quantification of analyte plasma concentrations, approximately 2.5 mL of blood 
will be taken from a forearm vein into a K3EDTA (ethylenediaminetetraacetic acid) 


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anticoagulant blood-drawing tube at the time points listed in the Flow chart 1, 
Flow chart 2 and Flow chart 3 under PK sampling.
The blood samples must be taken from the forearm vein that is not receiving the i.v. 
infusion.
Mix the K3EDTA-anticoagulated blood samples gently and place on ice until 
centrifugation at approximately +4°C. The blood will be centrifuged to produce plasma as 
soon as possible after collection, but not later than 30 minutes after withdrawal. 
Centrifugation will last for approximately 10 minutes (at 2000 x g to 4000 x g) at 
approximately +4°C. Two aliquots of EDTA plasma samples will be obtained in two 
labelled (label to include: trial number, patient number, visit, PTM, aliquot 1 or 2, plasma, 
and PK) polypropylene cryotubes. The two aliquots should contain approximately 0.5 mL 
of plasma each. The plasma samples will be stored in a freezer set to -20°C or below at 
the clinical site(s) until shipment on dry ice to the central lab (with dry ice sufficient for 
3 days transit), then stored in a freezer set to –70°C or below at the central lab until 
shipment to the analytical laboratory.  Both aliquots will be shipped (in separate 
shipments with dry ice sufficient for 3 days transit) to the analytical laboratory for the 
determination of BI 655066/ABBV-066 (risankizumab).  Both aliquots will be stored in in 
a freezer set to –70°C or below at the analytical laboratory until the finalization of the 
clinical trial report.
5.5.2.2
Plasma sampling for assessment of anti-drug antibody
For the assessment of anti-drug antibody, approximately 2.5 mL of blood will be taken 
from a forearm vein into a K3EDTA (ethylendiaminetetraacetic acid) anticoagulant blood-
drawing tube at the time points listed in the Flow chart 1, Flow chart 2 and Flow chart 3
under anti-drug antibody (ADA).
Mix the K3EDTA-anticoagulated blood samples gently and place on ice until 
centrifugation at approximately +4°C. The blood will be centrifuged to produce plasma as 
soon as possible after collection, but not later than 30 minutes after withdrawal. 
Centrifugation will last for approximately 10 minutes (at 2000 x g to 4000 x g) at 
approximately +4°C. Two aliquots of EDTA plasma samples will be obtained in two 
labelled (label to include: trial number, patient number, visit, PTM, aliquot 1 or 2, plasma, 
and ADA) polypropylene cryotubes. Both aliquots will contain approximately 0.5 mL of 
plasma each. The plasma samples will be stored in a freezer set to -20°C or below at the 
clinical site(s) until shipment on dry ice to the central lab (with dry ice sufficient for 
3 days transit), then stored in a freezer set to -70°C or below at the central lab until 
shipment to the analytical laboratory.  Both aliquots will be shipped (in separate 


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shipments with dry ice sufficient for 3 days transit) to the analytical laboratory for 
assessment of potential ADA to BI 655066/ABBV-066 (risankizumab).  Following the 
finalization of the ADA bioanalytical report, selected ADA aliquots will be transferred to 
long term storage for possible/ additional ADA characterization in the future.
5.5.3
Analytical determinations
BI 655066/ABBV-066 (risankizumab) concentrations will be determined by a validated 
Enzyme Linked Immunosorbent Assay (ELISA).
The presence of ADA to BI 655066/ABBV-066 (risankizumab) will be assessed via a 
tiered approach using a validated electrochemiluminescence assay (screening, 
confirmatory, and titration analysis as appropriate). Samples that are confirmed positive 
will then be characterized in a validated neutralizing antibody (Nab) assay.
5.6
BIOMARKER(S)
5.6.1
Endpoints based on biomarker(s)
Biomarkers associated with Crohn's disease and the IL-23 pathway will be assessed in 
serum from patients' pre and post treatment with BI 655066/ABBV-066 (risankizumab). 
Changes in protein levels of disease specific markers such as but not limited to 
β defensin 2, neutrophil gelatinase associated lipocalin (NGAL), and S-100 proteins (A7, 
A8, A12) pre and post treatment with BI 655066/ABBV-066 (risankizumab) will be 
assessed. These biomarkers are considered exploratory and respective assays will be 
qualified to meet the required performance criteria.
Serum samples will be collected at time points indicated in Flow chart 1, Flow chart 2 and 
Flow chart 3 for the analysis of biomarkers. After completion of the study these samples 
may be used for not yet specified non-genetic biomarker analyses associated with 
autoimmune diseases as well as method development and evaluation. Samples will be 
stored for a maximum of 3 years (under consideration of local legislation) upon signature 
of the final study report.
5.6.2
Methods of sample collection
For the assessment of soluble biomarkers in serum, approximately 8.5 ml of blood will be 
collected from a forearm vein into a serum separation tube at time points indicated in 
Flow chart 1, Flow chart 2 and Flow chart 3. The blood will be thoroughly mixed with 
clotting activation agent by gently inverting the tube not less than five times and will be 
allowed to clot for at least 30 mins, but for a maximum of 60 mins, with the tube standing 


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upright. The tube is then centrifuged at 1500 to 2000 xg for 15 mins until clot and serum 
are separated by a well formed barrier. The serum will then be divided into at least 
6 aliquots (in polypropylene tubes) of at least 500 μl and will be frozen immediately at 
approximately -20°C or below until shipment on dry ice.
5.6.3
Analytical determinations
Characteristics of the analytical methods for the analysis of serum biomarkers will be 
given in detail in the clinical trial report.
5.7
PHARMACODYNAMICS
5.7.1
Pharmacodynamic endpoints
Serum will be collected to assess changes in the levels of IL-23 pathway and disease 
specific markers as stated in Section 5.6.1.
5.7.2 
Methods of sample collection
See Section 5.6.2
5.8
PHARMACOKINETIC - PHARMACODYNAMIC RELATIONSHIP
No formal analysis of pharmacokinetic/pharmacodynamic relationships is planned. If the 
data suggest a pharmacokinetic/pharmacodynamic relationship of special parameters, eg., 
CDAI, an exploratory analysis may be performed.
Correlation between drug concentration and response may be made if adequate data are 
available. In addition, exploratory correlations may also be made between drug 
concentration and AEs.
Data may also be used to develop pharmacokinetic/pharmacodynamic models using 
nonlinear mixed effect modeling techniques, if feasible. For this purpose data may also be 
combined with data from other trials. Modeling activities will be planned and documented 
separately according to internal and external guidelines and SOP.


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6.
INVESTIGATIONAL PLAN
6.1
VISIT SCHEDULE
All patients are to adhere to the visit schedule as specified in the Flow chart 1, 
Flow chart 2 and Flow chart 3. Additional unscheduled 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 further trial procedures, please refer to the Flow chart 1, 
Flow chart 2 and Flow chart 3.
6.2
DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS
6.2.1
Screening period
After patients have been informed about the study, written informed consent in 
accordance with GCP and local legislation must be obtained prior to any study related 
procedures taking place. Patients will be assigned a number and enrolment must be 
recorded in eCRF pages.
Visit 1 of this study should preferably be performed in one visit combined with the last 
visit of preceding trial 1311.6 or during the interim period of maximum 5 days after 
completion of the last visit in 1311.6.
Patients rolling-over directly from preceding 1311.6 trial eligibility will be assessed based 
on the patient diary dispensed earlier at the 1311.6 trial containing symptoms over 7 days. 
Investigators will review the diary in order to assess the CDAI score. The hematocrit 
result to calculate the CDAI score must be used from visit 1. If an EoT (or at the last 
preceding trial visit E1 or E5) colonoscopy has not been performed during 1311.6, it must 
be performed between V1 and V2 in 1311.20/M15-989.
Patients successfully completing the 1311.6 trial before initiation of the 1311.20/M15-989 
trial, will be assessed for eligibility based on a newly dispensed patient diary at visit 1. At 
the following 1.1 visit the investigator will review the diary in order to assess the CDAI 
score. The hematocrit result to calculate the CDAI score must be used from visit 1. If an 
EoT colonoscopy has not been performed during 1311.6 or if the patient had a treatment 
interruption followed by a clinical relapse, it must be performed between V1 and V2 in 
1311.20/M15-989.


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For detailed description of the trial procedures at screening please refer to Flow chart 1, 
Flow chart 2 and Flow chart 3.
6.2.2
Treatment periods
If upon completion of screening patient eligibility was confirmed by maintaining clinical 
response or remission (CDAI drop ≥100 from baseline of 1311.6 or CDAI < 150) patients 
can directly be assigned to open label s.c. maintenance treatment (see Flow charts 1 and 
Flow chart 2).
However, if clinical response or remission has been lost after end of treatment in 1311.6 
and/or at screening for 1311.20/M15-989, patients will receive open label i.v. re-induction 
treatment with three infusions of 600 mg each every 4 weeks. After re-induction 
eligibility will be re-assessed. If clinical response or remission compared to 
1311.20/M15-989 study entry is achieved patients will switch to s.c. maintenance 
treatment (see Flow chart 3).
During the s.c. maintenance treatment patients will be administered BI 655066/ABBV-066 
(risankizumab) 180 mg every 8 weeks. Medication will be assigned by IRT. All study 
medication will be stored and administered on site by authorized study staff only.
For details on the study assessments refer to Flow chart 1, Flow chart 2 and Flow chart 3.
6.2.3
End of trial and follow-up period
The follow up period is 20 weeks after the last administration of study medication. Refer 
to Flow chart 1, Flow chart 2 and Flow chart 3 for further details.


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7.
STATISTICAL METHODS AND DETERMINATION OF
SAMPLE SIZE
7.1
STATISTICAL DESIGN - MODEL
This trial is a single group, open label extension study of BI 655066/ABBV-066 
(risankizumab) in patients with moderately to severely active CD. The patients enrolled in 
this study are those that achieved clinical response to previous treatment with 
BI 655066/ABBV-066 (risankizumab). There will be no statistical testing performed.
7.2
NULL AND ALTERNATIVE HYPOTHESES
There is no formal statistical hypothesis test planned.
7.3
PLANNED ANALYSES
Descriptive analyses will be used to analyse the proportion of participants achieving the 
efficacy endpoints. The study is designed to gain extensive documentation of safety and 
efficacy.
7.3.1
Primary analyses
There are no primary analyses for efficacy.
7.3.2
Secondary analyses
There is no secondary analyse for efficacy.
Other efficacy endpoints will be summarized descriptively by visit. They will be tabulated 
and descriptive statistics will be provided.
Additional further endpoints may be defined in the Trial Statistical Analysis Plan (TSAP).
7.3.3
Safety analyses
Since the main objective of this study is long term safety, the primary focus would be on 
incidence of drug-related AE and serious infection.


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Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) coding dictionary. 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 20 weeks 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.
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). 
Safety analyses will focus on adverse events related to early discontinuation, immune 
suppression and injection site effects.
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. Analysis of laboratory measures will focus 
on haemotologic measures of immune suppression.
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.
7.3.4
Interim analyses
No formal interim analyses are planned. However since this is an open label study, 
interim analyses may be performed as needed after approximately 20 patients complete 
the study.
7.3.5
Pharmacokinetic analyses
Refer to Section 5.5.1 for pharmacokinetic parameters to be calculated using 
noncompartmental analysis (NCA). The derivation of pharmacokinetic parameter is 
described in sponsor's standard operating procedure.


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All evaluable patients who received at least one dose of BI 655066/ABBV-066 
(risankizumab) will be included in the pharmacokinetic analysis. Patients who are 
considered as not evaluable will be listed with their individual plasma concentrations and 
individual pharmacokinetic parameters, however, will not be included in descriptive 
statistics for plasma concentrations, pharmacokinetic parameters or other statistical 
assessment.
Concentrations will be used for graphs and calculations in the format that is reported in 
the bioanalytical report. Noncompartmental pharmacokinetic analyses of the plasma 
concentration-time data will be performed using a validated software program. Only 
concentrations within the validated concentration range will be used for the calculation of 
pharmacokinetic parameters.
Plasma concentrations will be plotted graphically versus time for all evaluable patients as 
listed in the drug plasma concentration-time tables. The actual sampling times will be 
used for individual drug plasma concentration-time plots. For the presentation of the mean 
profiles, the arithmetic mean and the planned blood sampling times will be used.
The following descriptive statistics will be calculated for BI 655066/ABBV-066 
(risankizumab) concentrations as well as for all pharmacokinetic parameters:  N, 
arithmetic mean, standard deviation, minimum, median, maximum, arithmetic coefficient 
of variation, geometric mean, and geometric coefficient of variation. The data format for 
descriptive statistics of concentrations will be identical with the data format of the 
respective concentrations. The descriptive statistics of pharmacokinetic parameters will be 
calculated using the individual values with the number of decimal places as provided by 
the evaluation program. Then the individual values as well as the descriptive statistics will 
be reported with three significant digits in the clinical trial report.
7.3.6
Pharmacodynamic analyses
Baseline levels and changes from baseline in serum protein biomarkers will be described 
over time. Correlations between change from baseline in CDAI scores, endoscopic scores 
and biomarker levels will be explored. In addition, the relationships, between drug 
concentrations, clinical efficacy, and selected biomarkers will be explored. The details of 
these analyses will be included in the SAP.
7.3.7
Pharmacogenomic analyses
Not applicable.


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7.4
HANDLING OF MISSING DATA
No imputation will be performed for missing data. 
7.5
RANDOMISATION
There is no randomisation for this study. All patients will be assigned to the same regimen 
and dose of BI 655066/ABBV-066 (risankizumab) , regardless of the treatment and dose 
received in the 1311.6 trial.
7.6
DETERMINATION OF SAMPLE SIZE
The sample size is determined by the completion of previous trial and the consenting for 
the extension.


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


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The patient must be informed that his / her medical records may be examined by 
authorised monitors (CML/CRA) or Clinical Quality Assurance auditors appointed by 
AbbVie by appropriate IRB / IEC members, and by inspectors from regulatory authorities.
8.2
DATA QUALITY ASSURANCE
A quality assurance audit/inspection of this trial may be conducted by the sponsor or 
sponsor's designees or by IRBs/IECs or by regulatory authorities. The quality assurance 
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. For drug accountability, refer to Section 4.1.8.
8.3.1
Source documents
Source documents provide evidence for the existence of the patient and substantiate the 
integrity of the data collected. Source documents are filed at the investigator's site.
Data entered in the eCRFs that are transcribed from source documents must be consistent 
with the source documents or the discrepancies must be explained. The investigator may 
need to request previous medical records or transfer records, depending on the trial; also 
current medical records must be available.
For eCRFs all data must be derived from source documents.
8.3.2
Direct access to source data and documents
The investigator / institution will permit trial-related monitoring, audits, IRB / IEC review 
and regulatory inspection, providing direct access to all related source data / documents. 
CRFs/eCRFs and all source documents, including progress notes and copies of laboratory 
and medical test results must be available at all times for review by the sponsor's clinical 
trial monitor, auditor and inspection by health authorities (e.g. FDA). The Clinical 
Research Associate (CRA) / on site monitor and auditor may review all CRFs/eCRFs, and 
written informed consents. The accuracy of the data will be verified by reviewing the 
documents described in Section 8.3.1.


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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. The current versions of the Investigator's Brochure reference documents are to 
be provided in the ISF. No AEs are classified as listed for study design, or invasive 
procedures.
8.4.2
Expedited reporting to health authorities and IECs/IRBs
Expedited reporting of serious adverse events, e.g. suspected unexpected serious adverse 
reactions (SUSARs) to health authorities and IECs/IRBs, will be done according to local 
regulatory requirements. Further details regarding this reporting procedure are provided in 
the Investigator Site File.
8.5
STATEMENT OF CONFIDENTIALITY
Individual patient medical information obtained as a result of this trial is considered 
confidential and disclosure to third parties is prohibited with the exceptions noted below. 
Patient confidentiality will be ensured by using patient identification code numbers.
Treatment data may be given to the patient's personal physician or to other appropriate 
medical personnel responsible for the patient's welfare. Data generated as a result of the 
trial need to be available for inspection on request by the participating physicians, the 
sponsor's representatives, by the IRB / IEC and the regulatory authorities i.e. the CA.
8.6
COMPLETION OF TRIAL
The EC/competent authority in each participating EU member state needs to be notified 
about the end of the trial (last patient/patient out, unless specified differently in 
Section 6.2.3 of the CTP) or early termination of the trial.


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9.
REFERENCES
9.1
PUBLISHED REFERENCES
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Colombel JF, Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB, Panaccione 
R, Schreiber S, Byczkowski D, Li J, Kent JD, Pollack PF. Adalimumab for 
maintenance of clinical response and remission in patients with Crohn's 
disease: the CHARM trial. Gastroenterology 132 (1), 52 - 65 (2007)
P15-03262
Papp KA, Menter A, Sofen H, Tyring S, Lacour JP, Berner B, Bennett N, 
Flack M, Scholl P. Efficacy and safety of different dose regimens of a 
novel selective IL-23p19 inhibitor (BI 655066) compared with 
ustekinumab in patients with moderate-to-severe plaque psoriasis. 73rd 
Ann Mtg of the American Academy of Dermatology (AAD), San 
Francisco, 21 - 24 Mar 2015 (Oral Presentation)
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Best WR, Becktel JM, Singleton JW, Kern F. Development of a Crohn's 
disease activity index: National Cooperative Crohn's Disease Study. 
Gastroenterology 70, 439 - 444 (1976)
R97-3472
Irvine EJ, Feagan B, Rochon J, Archambault A, Fedorak RN, Groll A, 
Kinnear D, Saibil F, McDonald JWD, Quality of life: A valid and reliable 
measure of therapeutic efficacy in the treatment of inflammatory bowel 
disease. Gastroenterology 106, 287 - 296 (1994)
R11-1269
Yen D, Cheung J, Scheerens H, Poulet F, McClanahan T, Mckenzie B, 
Kleinschek MA, Owyang A, Mattson J, Blumenschein W, Murphy E, 
Sathe M, Cua DJ, Kastelein RA, Rennick D. IL-23 is essential for T cell-
mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin 
Invest 116 (5), 1310 - 1316 (2006)
R11-1271
Elson CO, Cong Y, Weaver CT, Schoeb TR, McClanahan TK, Fick RB, 
Kastelein RA. Monoclonal anti-interleukin 23 reverses active colitis in a T 
cell-mediated model in mice. Gastroenterology 132 (7), 2359 - 2370 
(2007)
R11-1273
Chan JR, Blumenschein W, Murphy E, Diveu C, Wiekowski M, 
Abbondanzo S, Lucian L, Geissler R, Brodie S, Kimball AB, Gorman DM, 
Smith K, Waal Malefyt R de, Kastelein RA, McClanahan TK, Bowman EP
IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent 


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mechanisms with implications for psoriasis pathogenesis.
J Exp Med 203 (12), 2577 - 2587 (2006)
R12-1009
Liu Z, Yadav PK, Xu X, Su J, Chen C, Tang M, Lin H, Yu J, Qian J, Yang 
PC, Wang X. The increased expression of IL-23 in inflammatory bowel 
disease promotes intraepithelial and lamina propria lymphocyte 
inflammatory responses and cytotoxicity. J Leukocyte Biol 89, 597 - 606 
(2011)
R12-5152 
Sandborn WJ, Gasink C, Gao LL, Blank MA, Johanns J, Guzzo C, Sands 
BE, Hanauer SB, Targan S, Rutgeerts P, Ghosh S, Villiers WJS de, 
Panaccione R, Greenberg G, Schreiber S, Lichtiger S, Feagan BG, 
CERTIFI Study Group. Ustekinumab induction and maintenance therapy 
in refractory Crohn's disease. N Engl J Med 367 (16), 1519 - 1528 (2012)
R15-1973
Sands BE, Chen J, Penney M, Newbold P, Faggioni R, Merwe R van der, 
Patra K, Klekotka P, Pulkstenis E, Drappa J, Gasser RA. A randomized, 
double-blind placebo-controlled phase 2a induction study of MEDI2070 
(anti-p19 antibody) in patients with active Crohn's disease who have failed 
anti-TNF antibody therapy. ECCO 2015, 10th Cong of the European 
Crohn's and Colitis Organisation, Barcelona, 18 - 21 Feb 2015. J Crohns 
Colitis 9 (Suppl 1), S15 - S16, Abstr OP025 (2015) 
R13-2231
Baumgart DC, Sandborn WJ. Crohn's disease.Lancet 380, 1590 - 1605 
(2012)
R13-2232 
Latella G, Papi C. Crucial steps in the natural history of infammatory 
bowel disease. World J Gastroenterol 18 (29), 3790 - 3799 (2012)
R13-2233 
Cosnes J, Gower-Rousseau C, Seksik P, Cortot A. Epidemiology and 
natural history of inflammatory bowel diseases. Gastroenterology 140 (6), 
1785 - 1794 (2011)
R13-2264 
Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB, Colombel JF, Panaccione 
R, D'Haens G, Rosenfeld MR, Kent JD, Pollack PF. Adalimumab 
induction therapy for Crohn disease previously treated with infliximab: a 
randomized trial. Ann Intern Med 146 (12), 829 - 838 (2007)
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Rutgeerts P, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, 
Colombel JF, Rachmilewitz D, Wolf DC, Olson A, Bao W, Hanauer SB. 


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Comparison of scheduled and episodic treatment strategies of infliximab in 
Crohn's disease. Gastroenterology 126 (2), 402 - 413 (2004)
R13-2266 
Schreiber S, Khaliq-Kareemi M, Lawrance IC, Thomsen OO, Hanauer SB, 
McColm J, Bloomfield R, Sandborn WJ, PRECISE 2 Study Investigators. 
Maintenance therapy with certolizumab pegol for Crohn's disease. N Engl
J Med 357 (3), 239 - 250 (2007)
R13-2267 
Hanauer SB, Sandborn WJ, Rutgeerts P, Fedorak RN, Lukas M, Macintosh 
D, Panaccione R, Wolf D, Pollack P. Human anti-tumor necrosis factor 
monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I 
trial. Gastroenterology 130 (2), 323 - 332 (2006)
R13-2268 
Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, 
Colombel JF, Rachmilewitz D, Wolf DC, Olson A, Bao W, Rutgeerts P, 
ACCENT I Study Group Maintenance infliximab for Crohn's disease: the 
ACCENT I randomised trial. Lancet 359, 1541 - 1549 (2002)
R13-2269 
Sandborn WJ. State-of-the-art: immunosuppression and biologic therapy. 
Dig Dis 28, 536 - 542 (2010)
R13-2294 
Cruz P de, Kamm MA, Prideaux L, Allen PB, Moore G. Mucosal healing 
in Crohn's disease: a systematic review. Inflamm Bowel Dis 19 (2), 429 -
444 (2013)
R13-2295 
Schnitzler F, Fidder H, Ferrante M, Noman M, Arijs I, Assche G van, 
Hoffman I, Steen K van, Vermeire S, Rutgeerts P. Mucosal healing 
predicts long-term outcome of maintenance therapy with infliximab in 
Crohn's disease. Inflamm Bowel Dis 15 (9), 1295 - 1301 (2009)
R13-2413 
Neurath MF, Travis SPL. Mucosal healing in inflammatory bowel 
diseases: a systematic review. Gut 61, 1619 - 1635 (2012)
R13-2625
Abraham C, Cho J. lnterleukin-23/Th17 pathways and inflammatory bowel 
disease. Inflamm Bowel Dis 15 (7), 1090 - 1100 (2009)
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 34 (6), 1401 - 1414 (2007)


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9.2
UNPUBLISHED REFERENCES
AbbVie Inc. Edition 1 Investigator's Brochure, December 22, 2016
AbbVie Inc. Edition 2 Investigator's Brochure, October 25, 2017
AbbVie Inc. Edition 3 Investigator's Brochure, May 10, 2018


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10.
APPENDICES
Appendix 10.1
Clinical evaluation of liver injury
Appendix 10.2
Equivalent doses of corticosteroids
Appendix 10.3
Severity of AE as described in the Rheumatology Common Toxicity 
Criteria (RCTC) Version 2.0 (OMERACT)
10.1
CLINICAL EVALUATION OF LIVER INJURY
10.1.1
Introduction
Alterations of liver laboratory parameters, as described in Section 5.2.2.1 (Adverse Events 
of Special Interest), are to be further evaluated using the following procedures: 
10.1.2
Procedures
Repeat the following laboratory tests: ALT, AST, and bilirubin (total and direct) - within 
48 to 72 hours and provide additional blood sample to the central laboratory for automatic 
reflex testing of the below listed laboratory parameters. Only in case whereby the central 
laboratory is not immediately available (e.g. if the logistics are such that the patient's 
repeat specimen would not reach the central laboratory in a reasonable timeframe), ALT, 
AST, and bilirubin (total and direct) will be evaluated by local laboratory and results are 
made available to the investigator and to BI as soon as possible. If in such a case ALT 
and/or AST > 3 fold ULN combined with an elevation of total bilirubin > 2 fold ULN are 
confirmed, results of the laboratory parameters described below must be made available to 
the investigator and to BI as soon as possible.
Clinical chemistry
alkaline phosphatase, albumin, PT or INR, CK, CK-MB, coeruloplasmin, α-1 antitrypsin, 
transferin, amylase, lipase, fasting glucose, cholesterol, triglycerides
Serology
Hepatitis A (Anti-IgM, Anti-IgG), Hepatitis B (HbsAg, Anti-HBs, DNA), Hepatitis C 
(Anti-HCV, RNA if Anti-HCV positive), Hepatitis D (Anti-IgM, Anti-IgG), Hepatitis E 
(Anti-HEV, Anti-HEV IgM, RNA if Anti-HEV IgM positive), Anti-Smooth Muscle 
antibody (titer), Anti-nuclear antibody (titer), Anti-LKM (liver-kidney microsomes) 
antibody, Anti-mitochondrial antibody
<project dependent:> Epstein Barr Virus (VCA IgG, VCA IgM), cytomegalovirus (IgG, 
IgM), herpes simplex virus (IgG, IgM), varicella (IgG, IgM), parvovirus (IgG, IgM), 
toxoplasmosis (IgG, IgM)>


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Hormones, tumormarker
TSH
Haematology
Thrombocytes, eosinophils
!
Provide abdominal ultrasound to rule out biliary tract, pancreatic or intrahepatic 
pathology, e.g. bile duct stones or neoplasm.
!
Initiate close observation of subjects by repeat testing of ALT, AST, and total 
bilirubin (with fractionation by total and direct) at least weekly until the laboratory 
ALT and / or AST abnormalities stabilize or return to normal, then according to the 
protocol. Depending on further laboratory changes, additional parameters identified 
e.g. by reflex testing will be followed up based on medical judgement and Good 
Clinical Practices (GCP).
10.2
EQUIVALENT DOSES OF CORTICOSTEROIDS
Drug
Equivalent dose (mg)
Conversion factor
Prednisone
5
X 1
Prednisolone
5
X 1
Triamcinolone
4
X 1.25
6-Methylprednisolone
4
X 1.25
Dexamethasone
1
X 5
Betamethasone
0,75
X 6.7
16-Methylprednisolone
6
X 0.8
Fluocortalon
5
X 1
Cloprednol
3,75-5
X 1.0-1.5
Deflazacort
6
X 0.8
Cortisol (hydrocortisone)
20
X 0.25
Cortisone
25
X 0.20


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10.3
SEVERITY OF AE AS DESCRIBED IN THE RHEUMATOLOGY COMMON TOXICITY CRITERIA 
(OMERACT)
1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
Asymptomatic, or 
transient
Short duration 
(< 1 week)
No change in life style
No medication or OTC 
Symptomatic
Duration (1–2 weeks)
Alter lifestyle 
occasionally
Meds relieve. (may be 
prescription),
Study drug continued
Prolonged symptoms, 
reversible, major 
functional impairment
Prescription meds/partial 
relief
May be hospitalized 
< 24h
Temporary study drug 
discontinuation, or/and 
dose reduced
At risk of death
Substantial disability, 
especially if permanent.
Multiple meds
Hospitalised > 24h
Study drug discontinued
A. ALLERGIC/IMMUNOLOGIC
A1. Allergic reaction/ 
hypersensitivity 
(including drug fever)
Transient rash; drug 
fever < 38° C, transient 
asymptomatic 
bronchospasm
Generalized urticaria 
responsive to meds; or 
drug fever > 38° C, or 
reversible bronchospasm
Symptomatic 
bronchospasm, requiring 
meds; symptomatic 
urticaria persisting with 
meds, allergy related 
oedema/angioedema
Anaphylaxis, laryngeal/ 
pharyngeal edema, 
requiring resuscitation


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10.3
SEVERITY OF AE AS DESCRIBED IN THE RHEUMATOLOGY COMMON TOXICITY CRITERIA 
(OMERACT) (CON'T)
1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
A. ALLERGIC/IMMUNOLOGIC
A2. Autoimmune 
reaction
Serologic or other 
evidence of 
autoimmune reaction 
but patient 
asymptomatic: all organ 
function normal and no 
treatment is required 
(e.g., vitiligo)
Evidence of autoimmune 
reaction involving a non-
essential organ or 
functions, requiring 
treatment other than 
immunosuppressive 
drugs (e.g., 
hypothyroidism)
Reversible autoimmune 
reaction involving 
function of a major organ 
or toxicity requiring short 
term immunosuppressive 
treatment (e.g., transient 
colitis or anemia)
Causes major organ 
dysfunction, or 
progressive, not 
reversible, or requires 
long term administration 
of high dose 
immunosuppressive 
therapy
A3. Rhinitis (includes 
sneezing, nasal 
stuffiness, post nasal 
discharge)
Transient, non-
prescription meds 
relieve
Prescription med 
required, slow 
Corticosteroids or other 
prescription med. with 
persistent disabling 
symptoms such as 
impaired exercise 
tolerance
NA


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10.3
SEVERITY OF AE AS DESCRIBED IN THE RHEUMATOLOGY COMMON TOXICITY CRITERIA 
(OMERACT) (CON'T)
1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
A. ALLERGIC/IMMUNOLOGIC
A4. Serum sickness
Transient, non-
prescription meds 
relieve
Symptomatic, slow 
response to meds (e.g. 
oral corticosteroids)
Prolonged; symptoms 
only partially relieved by 
meds; parenteral 
corticosteroids required
Major organ dysfunction, 
requires long-term high-
dose immunosuppressive 
therapy
A5. Vasculitis
Localized, not requiring 
treatment; or rapid 
response to meds; 
cutaneous
Symptomatic, slow 
response to meds (e.g. 
oral corticosteroids)
Generalized, parenteral 
corticosteroids required 
or/and short duration 
hospitalization 
Prolonged 
hospitalization, ischemic 
changes, amputation
B. CARDIAC
B1. Arrhythmia 
Transient, 
asymptomatic
Transient, but 
symptomatic or 
recurrent, responds to 
meds
Recurrent/persistent; 
maintenance prescription
Unstable, hospitalization 
required; parenteral meds


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10.3
SEVERITY OF AE AS DESCRIBED IN THE RHEUMATOLOGY COMMON TOXICITY CRITERIA 
(OMERACT) (CON'T)
1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
B. CARDIAC
B2. Cardiac function 
decreased
Asymptomatic decline 
in resting ejection 
fraction by > 10%, but 
< 20% of baseline value
Asymptomatic decline of 
resting ejection fraction 
≥20% of baseline value
CHF responsive to
treatment
Severe or refractory CHF
B3. Edema 
Asymptomatic 
(e.g., 1+ feet/calves), 
self-limited, no therapy 
required
Symptomatic 
(e.g., 2+ feet/calves), 
requires therapy
Symptoms limiting 
function 
(e.g., 3+ feet/calves, 
2+ thighs), partial relief 
with treatment; 
prolonged
Anasarca; no response to 
treatment
B4. Hypertension 
(new onset or 
worsening)
Asymptomatic, 
transient, increase by 
> 20 mm Hg 
(diastolic),or to 
> 150/100 if previously 
normal, no therapy 
required
Recurrent or persistent 
increase > 150/100, or by 
> 10 mmHg (diastolic), 
requiring and responding 
readily to treatment
Symptomatic increase 
> 150/100, > 20 mm Hg, 
persistent, requiring 
multi-agent therapy, 
difficult to control
Hypertensive crisis


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10.3
SEVERITY OF AE AS DESCRIBED IN THE RHEUMATOLOGY COMMON TOXICITY CRITERIA 
(OMERACT) (CON'T)
1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
B. CARDIAC
B5. Hypotension 
(without underlying 
diagnosis)
Transient, intermittent, 
asymptomatic 
orthostatic decrease in 
blood pressure 
> 20 mmHg
Symptomatic, without 
interference with 
function, recurrent or 
persistent > 20 mmHg 
decrease, responds to 
treatment
Syncope, or 
symptomatic, interferes 
with function, requiring 
therapy and sustained 
medical attention, dose 
adjustment or drug 
discontinuation
Shock
B6. Myocardial 
ischemia 
Transient chest 
pain/ECG changes; 
rapid relief with nitro
Recurring chest pain, 
transient ECG ST-T 
changes; treatment 
relieves
Angina with infarction, 
no or minimal functional 
compromise, reduce dose 
or discontinue study drug
Acute myocardial 
infarction, arrthymia 
or/and CHF
B7. 
Pericarditis/pericardial 
effusion
Rub heard, 
asymptomatic
Detectable effusion by 
echocardiogram, 
symptomatic, NSAID 
required
Detectable on chest 
X-ray, dyspnea; or 
pericardiocentesis; 
requires corticosteroids
Pulsus alternates with 
low cardiac output; 
requires surgery


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10.3
SEVERITY OF AE AS DESCRIBED IN THE RHEUMATOLOGY COMMON TOXICITY CRITERIA 
(OMERACT) (CON'T)
1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
B. CARDIAC
B8. 
Phlebitis/thrombosis/ 
embolism (excludes 
injection site reaction)
Asymptomatic, 
superficial, transient, 
local, or no treatment 
required
Symptomatic, recurrent, 
deep vein thrombosis, no 
anticoagulant therapy 
required 
Deep vein thrombosis 
requiring anticoagulant 
therapy
Pulmonary embolism
C. GENERAL (constitutional)
C1. Fatigue/malaise 
(asthenia)
Increase over baseline; 
most usual daily 
functions maintained, 
short term
Limits daily function 
intermittently over time
Interferes with basic 
ADL, persistent
Unable to care for self, 
bed or wheelchair bound 
> 50% of day 
debilitating, 
hospitalization
C2. Fever (pyrexia) 
(note: fever due to 
drug allergy should be 
coded as allergy)
Transient, few 
symptoms 37.7–38.5°C
Symptomatic, recurrent, 
38.6-39.9°C. Relieved by 
meds. 
≥ 40°C; ≤ 24h, persistent 
symptoms; partial 
response to meds
≥ 40°C, debilitating, 
> 24h, hospitalisation; no 
relief with meds
C3. Headache
Transient or 
intermittent, no meds or 
relieved with OTC 
Persistent, recurring, 
non- narcotic analgesics
relieve
Prolonged, with limited 
response to narcotic 
medicine
Intractable, debilitating, 
requires parenteral meds.


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10.3
SEVERITY OF AE AS DESCRIBED IN THE RHEUMATOLOGY COMMON TOXICITY CRITERIA 
(OMERACT) (CON'T)
1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
C. GENERAL (constitutional)
C4. Insomnia
Difficulty sleeping, 
short term, not 
interfering with 
function
Difficulty sleeping, 
interfering with function, 
use of prescription med
Prolonged symptoms, 
with limited response to 
narcotic meds
Debilitating, 
hospitalization; no relief 
with meds
C5. Rigors, chills
Asymptomatic, 
transient, no meds, or 
non-narcotic meds 
relieve
Symptomatic, narcotic 
meds relieve
Prolonged symptoms, 
with limited response to 
narcotic meds
Debilitating, 
hospitalization; no relief 
with meds
C6. Sweating 
(diaphoresis)
Episodic, transient
Frequent, short term
Frequent, drenching, 
disabling
Dehydration, requiring 
i.v. fluids/hospitalization 
> 24hr
C7. Weight gain
5–9.9% 
10–19.9% 
20–30%
NA
C8. Weight loss
5–9.9% 
10–19.9% 
20–30%
NA


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10.3
SEVERITY OF AE AS DESCRIBED IN THE RHEUMATOLOGY COMMON TOXICITY CRITERIA 
(OMERACT) (CON'T)
1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
D. DERMATOLOGIC
D1. Alopecia 
Subjective, transient 
Objective, fully 
reversible 
Patchy, wig used, partly 
reversible 
Complete or irreversible 
even if patchy
D2. Bullous eruption
Localized, 
asymptomatic
Localized, symptomatic, 
requiring treatment
Generalized, responsive 
to treatment; reversible
Prolonged, generalized, 
or requiring 
hospitalization for 
treatment
D3. Dry skin 
Asymptomatic, 
controlled with 
emollients
Symptoms eventually 
(1-2 wks) controlled with 
emollients
Generalized, interfering 
with ADL > 2 wks, 
persistent pruritus, 
partially responsive to
treatment
Disabling for extended 
period, unresponsive to 
ancillary therapy and 
requiring study drug 
discontinuation for relief
D4. Injection site 
reaction
Local erythema, pain 
pruritus, < few days
Erythema, pain, oedema, 
may include superficial 
phlebitis, 1-2 wks
Prolonged induration, 
superficial ulceration; 
includes thrombosis
Major ulceration necrosis 
requiring surgery
D5. Petechiae 
(without vasculitis)
Few, transient, 
asymptomatic
Dependent areas, 
persistent up to 2 wks
Generalized, responsive 
to treatment; reversible
Prolonged, irreversible, 
disabling


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10.3
SEVERITY OF AE AS DESCRIBED IN THE RHEUMATOLOGY COMMON TOXICITY CRITERIA 
(OMERACT) (CON'T)
1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
D. DERMATOLOGIC
D6. Photosensitivity 
Transient erythema 
Painful erythema and 
oedema requiring topical 
treatment
Blistering or 
desquamation, requires 
systemic corticosteroids
Generalized exfoliation, 
or hospitalization
D7. Pruritis 
Localized, 
asymptomatic, 
transient, local 
treatment
Intense, or generalized, 
relieved by systemic 
medication
Intense or generalized; 
poorly controlled despite 
treatment
Disabling, irreversible
D8. Rash (not bullous) Erythema, scattered 
macular/ papular 
eruption; pruritus 
transient, OTC or no 
meds
Diffuse macular/papular 
eruption or erythema 
with pruritus; dry 
desquamation; treatment 
required
Generalized, moist 
desquamation, requires 
systemic corticosteroids; 
responsive to treatment; 
reversible
Exfoliative or ulcerating; 
or requires 
hospitalization; or 
parenteral corticosteroids
D9. 
Induration/fibrosis/ 
Thickening (not 
sclerodermal)
Localized, high density 
on palpation, reversible, 
no effect on ADL and 
no disfiguring
Local areas < 50% body 
surface, not disfiguring, 
transient interference 
with ADL, reversible
Generalized, disfiguring, 
interferes with ADL, 
reversible
Disabling, irreversible, 
systemic symptoms


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SEVERITY OF AE AS DESCRIBED IN THE RHEUMATOLOGY COMMON TOXICITY CRITERIA 
(OMERACT) (CON'T)
1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
E. EAR/NOSE/THROAT
E1. Hearing loss
Transient, intermittent, 
no interference with 
function
Symptomatic, treatment 
required, reversible
Interferes with function; 
incomplete response to 
treatment
Irreversible deafness
E2. Sense of smell
Slightly altered
Markedly altered
Complete loss, reversible
Complete loss, without 
recovery
E3. Stomatitis
Asymptomatic
Painful, multiple, can eat
Interferes with nutrition, 
slowly reversible
Requires enteral support, 
residual dysfunction
E4. Taste disturbance 
(dysgeusia)
Transiently altered; 
metallic
Persistently altered; 
limited effect on eating
Disabling, effect on 
nutrition
NA
E5. Tinnitus
Intermittent, transient, 
no interference with 
function
Requires treatment, 
reversible
Disabling, or associated 
with hearing loss
Irreversible deafness
E6. Voice changes 
(includes hoarseness, 
loss of voice, 
laryngitis
Intermittent hoarseness, 
able to vocalize
Persistent hoarseness, 
able to vocalize
Whispered speech, slow 
return of ability to 
vocalize
Unable to vocalize for 
extended


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


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(OMERACT) (CON'T)
F4. Retinopathy
Asymptomatic, non-
progressive, no 
treatment
Reversible change in 
vision; readily responsive 
to treatment
Disabling change in 
vision ophthalmological 
findings reversible, sight 
improves over time
Loss of sight
F5. Vision changes 
(e.g., blurred, 
photophobia, night 
blindness, reversible 
vitreous floaters)
Asymptomatic, 
transient, no treatment 
required
Symptomatic, vision 
changes not interfering 
with function, reversible
Symptomatic, vision 
changes interfering with 
function
Loss of sight
F6. Xerophthalmia 
(dry eyes)
Mild scratchiness
Symptomatic without 
interfering with function, 
requires artificial tears
Interferes with 
vision/function, corneal 
ulceration
Loss of sight


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
G. GASTROINTESTINAL
G1. Anorexia
Adequate food intake, 
minimal weight loss
Symptoms requiring oral 
nutritional 
supplementation
Prolonged, requiring i.v. 
support
Requires hospitalization 
for nutritional support
G2. Constipation
Asymptomatic, 
transient, responds to 
stool softener, OTC 
laxatives
Symptomatic, requiring 
prescription laxatives, 
reversible
Obstipation, requiring 
medical intervention 
Bowel obstruction. 
Surgery required.
G3. Diarrhea
Transient, increase of 
2–3 stools/day over pre-
treatment (no blood or 
mucus), OTC agents 
relieve
Symptomatic, increase 
4–6 stools/day, nocturnal 
stools, cramping, 
requires treatment with 
prescription meds.
Increase > 6 stools/day, 
associated with disabling 
symptoms, e.g. severe 
cramping, partial 
response to treatment.
Prolonged, dehydration, 
unresponsive to 
treatment,  requires 
hospitalization
G4. Dyspepsia 
(heartburn) 
Transient, intermittent, 
responds to OTC 
antacids, H-2 blockers
Prolonged, recurrent, 
requires prescription 
meds, relieved by meds
Persistent despite 
treatment, interferes with 
function, associated with 
GI bleeding
NA


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


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
G. GASTROINTESTINAL
G9. Pancreatitis 
Amylase elevation, 
intermittent 
nausea/vomiting, 
transient, responds 
rapidly to treatment
Amylase elevation with 
abdominal pain, nausea, 
occasional vomiting, 
responsive to treatment
Severe, persistent 
abdominal pain with 
pancreatic enzyme 
elevation, incomplete or 
slow response to 
treatment
Complicated by shock, 
hemorrhage (acute 
circulatory failure)
G10. Proctitis
Perianal pruritus, 
hemorrhoids(new 
onset), transient, or 
intermittent, relieved by 
OTC meds
Tenesmus or ulcerations, 
anal fissure, responsive 
to treatment, minimal 
interference with 
function
Unresponsive to 
treatment, marked 
interference with 
function
Mucosal necrosis with 
hemorrhage, infection, 
surgery required.


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1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
H. MUSCULOSKELETAL
H1. Avascular 
necrosis
Asymptomatic MRI 
changes, non-
progressive
MRI changes and 
symptoms responsive to 
rest and analgesia
MRI changes, symptoms 
requiring surgical 
intervention
Wheelchair bound; 
surgical repair not 
possible
H2. Arthralgia
Intermittent transient 
symptoms, no meds, or 
relieved by OTC meds
Persistent or recurrent 
symptoms, resolve with 
meds, little effect on 
function
Severe symptoms despite 
meds impairs function
Debilitating, 
hospitalization required 
for treatment
H3. Leg cramps
Transient, intermittent, 
does not interfere with 
function
Recurrent symptoms, 
minimally interferes with 
function or sleep, 
respond to meds
Persistent, prolonged 
interference with 
function or sleep, partial 
or no response to meds
NA


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SEVERITY OF AE AS DESCRIBED IN THE RHEUMATOLOGY COMMON TOXICITY CRITERIA 
(OMERACT) (CON'T)
1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
H. MUSCULOSKELETAL
H4. Myalgia
Occasional; does not 
interfere with function
Frequent, requires meds 
(non- narcotic); minor 
effect on function
Major change in 
function/lifestyle, 
narcotic pain meds
Debilitating, profound 
weakness, requires 
wheelchair, unresponsive 
to meds
I. NEUROPSYCHIATRIC
I1. Anxiety or 
Depression(mood 
alteration)
Symptomatic, does not 
interfere with function; 
no meds
Frequent symptoms, 
responds to meds; 
interferes with ADL at 
times
Persistent, prolonged 
symptoms, partial or no 
response to meds, limits 
daily function
Suicidal ideation, or 
danger to self
I2. Cerebrovascular 
ischemia
NA
Single transient ischemic 
event, responsive to 
treatment
Recurrent transient 
ischemic events
Cerebrovascular vascular 
accident with permanent 
disability


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(OMERACT) (CON'T)
1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
I. NEUROPSYCHIATRIC
I3. Cognitive 
disturbance 
Subjective symptoms, 
transient, intermittent, 
not interfering with 
function
Objective symptoms, 
persisting, interferes with 
daily function 
occasionally
Persistent, or worsening 
objective symptoms; 
interferes with routine 
daily function
Debilitating/disabling 
and permanent; toxic 
psychosis
I4. Depressed 
consciousness 
(somnolence)
Observed, transient, 
intermittent, not 
interfering with 
function
Somnolence or sedation, 
interfering with function
Persistent, progressive, 
obtundation, stupor
Coma
I5. Inability to 
concentrate
Subjective symptoms, 
does not interfere with 
function
Objective findings, 
interferes with function
Persistent, prolonged 
objective findings; or 
organic cause
NA
I6. Insomnia (in 
absence of pain)
Occasional difficulty 
sleeping, transient, 
intermittent, not 
interfering with 
function
Recurrent difficulty 
sleeping; requires meds 
for relief; occasional 
interference with 
function
Persistent or worsening 
difficulty sleeping; 
severely interferes with 
routine daily function
NA


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SEVERITY OF AE AS DESCRIBED IN THE RHEUMATOLOGY COMMON TOXICITY CRITERIA 
(OMERACT) (CON'T)
1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
I. NEUROPSYCHIATRIC
I7. Libido decreased
Decrease in interest
Loss of interest; 
influences relationship
Persistent, prolonged, 
interfering with 
relationship
NA
I8. Peripheral motor 
neuropathy
Subjective, or transient 
loss of deep tendon 
reflexes; function 
maintained
Objective weakness, 
persistent, no significant 
impairment of daily 
function
Objective weakness with 
substantial impairment of 
function
Paralysis
I9. Peripheral sensory 
(sensory disturbance)
Subjective symptoms 
without objective 
findings, transient, not 
interfering with 
function
Objective sensory loss, 
persistent, not interfering 
with function
Prolonged sensory loss or 
paresthesias interfering 
with function
NA
I10. Seizure
NA
Recurrence of old 
seizures, controlled with 
adjustment of medication
Recurrence/exacerbation 
with partial response to 
medication
Recurrence not 
controlled, requiring 
hospitalization; new 
seizures


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(OMERACT) (CON'T)
1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
I. NEUROPSYCHIATRIC
I11. Vertigo 
(dizziness)
Subjective symptoms, 
transient, intermittent, 
no treatment
Objective findings, 
recurrent, meds relieve, 
occasionally interfering 
with function
Persistent, prolonged, 
interfering with daily 
function; partial response 
to medication 
Debilitating, without 
response to medication, 
hospitalization


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SEVERITY OF AE AS DESCRIBED IN THE RHEUMATOLOGY COMMON TOXICITY CRITERIA 
(OMERACT) (CON'T)
1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
J. PULMONARY
J1. Asthma
Occasional wheeze, no 
interference with 
activities
Wheezing, requires oral 
meds, occasional 
interference with 
function
Debilitating, requires 
nasal O2
Requires ventilator 
assistance
J2. Cough
Transient, intermittent, 
occasional OTC meds 
relieve
Persistent, requires 
narcotic or other 
prescription meds for 
relief
Recurrent, persistent 
coughing spasms without 
consistent relief by meds, 
interferes with function
Interferes with
oxygenation; debilitating
J3. Dyspnea
Subjective, transient, no 
interference with 
function
Symptomatic, 
intermittent or recurring, 
interferes with exertional 
activities
Symptomatic during 
daily routine activities, 
interferes with function, 
treatment with
intermittent nasal O2
relieves
Symptomatic at rest, 
debilitating, requires 
constant nasal O2
J4. Pleuritic pain 
(pleurisy)
Transient, intermittent 
symptoms, no treatment 
or OTC meds relieve
Persistent symptoms, 
requires prescription 
meds for relief
Prolonged symptoms, 
interferes with function, 
requires frequent narcotic 
pain relief
Debilitating, requiring 
hospitalisation


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SEVERITY OF AE AS DESCRIBED IN THE RHEUMATOLOGY COMMON TOXICITY CRITERIA 
(OMERACT) (CON'T)
1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
J. PULMONARY
J5. Pneumonitis 
(pulmonary infiltrates)
Asymptomatic 
radiographic changes, 
transient, no treatment 
required
Symptomatic, persistent, 
requiring corticosteroids
Symptomatic, requiring 
treatment including O2
Debilitating, not 
reversible; or requiring 
assisted ventilation
J6. Pulmonary 
function decreased 
(FVC or carbon 
monoxide diffusion 
capacity— DLCO)
76–90% of pre-
treatment value 
51–75% of pre-treatment 
value 
26–50% of pre-treatment 
value 
≤ 25% of pre-treatment 
value
LABORATORY DATA
K. HEMATOLOGY
K1. Hgb (g/dl) 
decrease from pre-
treatment
1.0–1.4 
1.5–2.0 
2.1–2.9; or Hgb< 8.0, > 
7.0
≥3.0; or Hgb < 7.0
K2. Leukopenia (total 
WBC) x 1000
3.0–3.9 
2.0–2.9 
1.0–1.9 
< 1.0


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(OMERACT) (CON'T)
1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
LABORATORY DATA
K. HEMATOLOGY
K3. Neutropenia 
(x 1000) 
1.5–1.9
1.0–1.4
0.5–0.9
< 0.5
K4. Lymphopenia 
(x 1000) 
1.5–1.9
1.0–1.4
0.5–0.9
< 0.5
K5. Platelets (x 1000)
75–LLN
50–74.9 
20–49.9; platelet 
transfusion required
< 20; recurrent platelet 
transfusions
L. CHEMISTRY
L1. Hypercalcemia 
(mg/dl)
1.1 x ULN–11.5
11.6–12.5
12.6–13.5; or symptoms 
present
> 13.5; or associated 
coma
L2. Hyperglycemia 
(mg/dl) Fasting
140–160
161–250
251–500
> 500, or associated with 
ketoacidosis


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(OMERACT) (CON'T)
1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
LABORATORY DATA
L. CHEMISTRY
L3. Hyperkalemia 
(mg/dl)
5.5–5.9 
6.0–6.4 
6.5–7.0 or any ECG 
change
> 7.0 or any arrhythmia
L4. Hypocalcaemia 
(mg/dl)
0.9 x LLN–7.8
7.7–7.0 
6.9–6.5; or associated 
with symptoms
< 6.5, or occurrence of 
tetany
L5. Hypoglycemia 
(mg/dl)
55–64 (no symptoms)
40–54 (or symptoms 
present) 
30–39 (symptoms impair 
function) 
< 30, or coma
L6. Hyponatremia 
(mg/dl)
NA
125–129
120–124
< 120
L7. Hypokalemia 
(mg/dl)
NA
3.0–3.4
2.5–2.9
< 2.5


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SEVERITY OF AE AS DESCRIBED IN THE RHEUMATOLOGY COMMON TOXICITY CRITERIA 
(OMERACT) (CON'T)
1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
LABORATORY DATA
L. CHEMISTRY
L8. CPK (also if 
polymyositis-disease
1.2–1.9 x ULN
2.0–4.0 x ULN
> 4.0 x ULN with 
weakness but without 
life-threatening signs or 
symptoms
> 4.0 x ULN with signs 
or symptoms of 
rhabdomyolysis or life-
threatening
L9.Serum uric acid
1.2–1.6 x ULN
1.7–2.9 x ULN
3.0–5.0 x ULN or gout
NA
L10. Creatinine 
(mg/dl)
1.1–1.3 x ULN
1.3–1.8 x ULN
1.9–3.0 x ULN
> 3.0 x ULN
L11. SGOT (AST)
1.2–1.5 x ULN
1.6–3.0 x ULN
3.1–8.0 x ULN
> 8.0 x ULN
L12. SGPT (ALT)
1.2–1.5 x ULN
1.6–3.0 x ULN
3.0–8.0 x ULN
> 8.0 x ULN
L13. Alkaline 
phosphatase
1.1–2.0 x ULN
1.6–3.0 x ULN
3.0–5.0 x ULN
> 5.0 x ULN


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(OMERACT) (CON'T)
1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
LABORATORY DATA
L. CHEMISTRY
L14. T. bilirubin
1.1–1.4 x ULN
1.5–1.9 x ULN
2.0–3.0 x ULN
> 3.0 x ULN
L15. LDH
1.3–2.4 x ULN
2.5–5.0 x ULN
5.1–10 x ULN
> 10 x ULN
M. URINALYSIS
M1. Hematuria
Micro only
Gross, no clots
Clots, transfusion 
< 2 units 
Transfusions required
M2. Proteinuria (per 
24 h)
300–500 g (tr/1+)
501–1999 g (2+)
2–5.0 g (3+) nephrotic 
syndrome
> 5.0 g (4+) anasarca
M3. WBC in urine
NA
NA
Indicating acute 
interstitial nephritis
Associated with acute 
renal failure


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SEVERITY OF AE AS DESCRIBED IN THE RHEUMATOLOGY COMMON TOXICITY CRITERIA 
(OMERACT) (CON'T)
1 - Mild
2 - Moderate
3 - Severe
4 - Includes Life 
Threatening
LABORATORY DATA
M. URINALYSIS
M4. Uric acid crystals
Present without 
symptoms
NA
With stones or symptoms 
of stones (e.g., renal 
colic)
Causing renal outflow 
obstruction and 
hospitalization


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10.4
INVESTIGATOR'S AGREEMENT
1.
I have received and reviewed the Investigator's Brochure for 
BI 655066/ABBV-066 (Risankizumab).
2.
I have read this protocol and agree that the study is ethical.
3.
I agree to conduct the study as outlined and in accordance with all applicable 
regulations and guidelines.
4.
I agree to maintain the confidentiality of all information received or developed in 
connection with this protocol.
5.
I agree that all electronic signatures will be considered the equivalent of a 
handwritten signature and will be legally binding.
Protocol Title:
An Open Label, Single Group, Long Term Safety Extension Trial of 
BI 655066/ABBV-066 (Risankizumab), in Patients with Moderately 
to Severely Active Crohn's Disease
Protocol Date:
25 July 2018
Signature of Principal Investigator
Date
Name of Principal Investigator (printed or typed)


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PROTOCOL SIGNATORIES
Name
Title
Functional Area
Clinical
Clinical
Bioanalysis
Clinical Pharmacology and Pharmacometrics
Clinical
Statistics
Pharma Development


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11.
DESCRIPTION OF GLOBAL AMENDMENT(S)
Number of global amendment
1.0
Date of CTP revision
15-Oct-2015
EudraCT number
2015-001834-15
BI Trial number
1311.20
BI Investigational Product(s)
BI 655066
Title of protocol
An open label, single group, long term safety extension 
trial of BI 655066, in patients with moderately to severely 
active Crohn's disease
To be implemented only after 
approval of the IRB/IEC/Competent 
Authorities
To be implemented immediately in 
order to eliminate hazard –
IRB / IEC / Competent Authority to 
be notified of change with request 
for approval
Can be implemented without 
IRB/IEC/ Competent Authority 
approval as changes involve 
logistical or administrative aspects 
only
Section to be changed
CTP Title 
Description of change
Rationale for change
Change of TCM
Section to be changed
Main Criteria for Inclusion
Description of change
1. Deleted: Completion of period 2 or 3 in 1311.6 per 
protocol with a clinical response or remission before 
initiation of 1311.20 can roll-over either directly or 
through an open-label i.v. re-induction phase.
2.
d. Deleted: and urine pregnancy test prior to 
randomization , added: Serum ß-Human Chorionic 
Gonadotrophin (ß-HCG) pregnancy test will be done at 
screening  only in case when urine pregnancy test is 
positive
Rationale for change
1.
Not a criteria of successful treatment, this statement 
will remain in section 3.3.2
2.
Additional information about serum pregnancy test 
requirement at screening


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Number of global amendment
1.0
Section to be changed
Criteria for Efficacy
Description of change
1. Change from baseline in abdominal pain score by 
visit based on patient diary, with possible answers none, 
mild, moderate and severe.
2. Change from baseline in CRP and fecal calprotectin 
profile by visit
Rationale for change
1.
Numeric rating scale was replaced by patient diary 
with pain scale as none, mild, moderate and severe as 
numeric scale was mistakenly taken from previous 
protocol 
2.
Lactoferin will not be analysed and was removed
Section to be changed
Flowchart 1 (including footnotes)
Description of change
1. Added: who maintained response OR REMISSION  
after completion of Trial 1311.6,
2. 2 additional ECG procedures added at V20 and V26
3. Visit 1.1: footnote mark 16 deleted (2x)
4. Footnote 3: added: starting from EoT visit
5. Footnote 4: added: "at Visit 1 and starting from 
Visit 2"
6. Footnote 15: deleted "completed 1311.6 qualifying 
for roll-over … this study"; added: Visit 1.1 is applicable 
only for those patients that had visit E1 more than 
5 days before Visit 1. Visit 1.1 can be performed by 
phone, fax or email
7. Footnote 16 ( new one): IRT has to be called only 
once at V1 or V1.1 after  assessment if s.c or i.v. re-
induction is needed
8. Visit window for V2 changed to ±7
9. IRT added at visit 1.1
Rationale for change
1. OR REMISSION was added as it was omitted by 
mistake
2. ECG omitted by mistake in previous version at V20 
and V26
3. Visit 1.1. footnote not applicable
4. Footnote 3: additional explanation for VS collection 
starting point
5. Footnote 4: additional explanation regarding serum 
pregnancy test
6. Footnote 15: additional explanation needed regarding 
V 1.1. Footnotes 15 and 16 were joined together.
7. If there is a gap between last visit in 1311.6 trial and 
first visit in 1311.20 IRT has to be contacted only after 
assessment if patient kept his best response or not
8. To allow more flexibility to plan V2
9. IRT has to be called first time to register the patient at 


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Number of global amendment
1.0
V1.1. in case patient has completed trial 1311.6 before 
availability of trial 1311.20 after assessment if s.c or i.v. 
re-induction is needed
Section to be changed
Flowchart 2 (including footnotes)
Description of change
1.
Title: deleted  "or (2) who maintained response 
after successful completion of Trial 1311.6,"
2. Visit 1.1: footnote mark 16 deleted (2x)
3. 12 Lead Resting-ECG: footnote mark 12 deleted (2x)
4. 2 additional ECG procedures added at V20 and V26
5. Footnote 3: added: starting from EoT visit
6. Footnote 4: added: "at Visit 1 and starting from 
Visit 2"
7. Footnote 15: Added: Visit 1.1 is applicable only for 
those patients that had visit E1 more than 5 days 
before Visit 1. Visit 1.1 can be performed by phone, fax 
or email. Footnote 15: deleted "completed 1311.6 
qualifying for roll … this study"
8. Footnote 16: deleted
9. Visit window for V2 changed to ±7
Rationale for change
1. Additional text was removed because this group of pts 
will follow Flowchart 1
2. Visit 1.1. footnote is not applicable
3. Footnote mark 12 mistakenly entered to ECG
4. ECG omitted by mistake in previous version at V20 
and V26
5. Footnote 3: additional explanation for VS collection 
starting point
6. Footnote 4: additional explanation regarding serum 
pregnancy test
7. Footnote 15: additional explanation needed regarding 
V 1.1
8. Footnotes 15 and 16 were joined together. 
9. To allow more flexibility to plan V2


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Number of global amendment
1.0
Section to be changed
Flowchart 3 (including footnotes)
Description of change
1.
Title: added "lost response OR REMISSION after" 
(2x)
2.
Visit 1.1: footnote mark 15 deleted (2x)
3.
Visit 30: footnote mark 12 added, footnote mark 11 
deleted
4.
2 additional ECG procedures added at V23 and V29
5.
12 Lead Resting-ECG: footnote mark 12 deleted
6.
Footnote 4: added: "at Visit 1 and starting from Visit 
2"
7.
Footnote 15: added "1311.6 baseline (visit 2), to 
continue SC medication  patients should have response"
8.
Footnote 17 added: IRT has to be called only once at 
V1 or V1.1 after assessment, if s.c or i.v. re-induction is 
needed.
9.
Visit window for V2 changed to ±7
10. Dispense patient diary for screening: footnote mark 
15 deleted
Rationale for change
1. OR REMISSION was added as it was omitted by 
mistake in previous versions
2. Visit 1.1. footnote 16 not applicable
3. Updated according to Protocol section 3.1
4. ECG omitted by mistake in previous version at V20 
and V26 
5. 12 Lead Resting-ECG: footnote mark 12 is not 
applicable
6. Footnote 4: additional explanation regarding serum 
pregnancy test
7. Footnote 15: additional explanation needed regarding 
V 1.1
8. If there is a gap between last visit in 1311.6 trial and 
first visit in 1311.20 IRT has to be contacted only after 
assessment if patient kept his best response or not.
9. To allow more flexibility to plan V2
10. Dispense patient diary for screening footnote 15 not 
applicable
Section to be changed
Table of Contents
Description of change
Flowchart 1 added: "who maintained response OR 
REMISSION  after completion of Trial 1311.6"
Flow chart 2: removed: " or (2) who maintained response 
after successful completion of Trial 1311.6,"
Flow chart 3: added "…OR REMISSION after…" (2x)
Rationale for change
Omitted by mistake in previous version, needed to include 
all possible patient population
Section to be changed
Section 3.1 Overall Trial Design and Plan


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Number of global amendment
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Description of change
1.
Figure 3.1:1: Legend: "1311.6" changed to "1311.20" 
2.
Added: "… an 8 weeks OR 5 times the half-life 
(whichever is longer) wash-out period…"
3.
Added: If clinical response or remission ( CDAI drop 
≥100 from baseline of 1311.6 or CDAI < 159 ) was 
maintained after end of treatment  … (FLOW CHART  
1)  ( visit window between last IMP dose in 1311.6 and 
first IMP dose in 1311.2 should be at least 8 weeks), 
deleted: "Flow Chart 2"
4.
Added: "If clinical response or remission compared to 
1311.20 study entry …, OTHERWISE VISIT EoT HAS 
TO BE COMPLETED 15 WEEKS after last 
administration of trial drug…
5.
Deleted: "response or" 2x
6.
Added : "(achieved at E5 1311.6)", "or at least 
response compared to 1311.6  study entry baseline (V2)"
7.
Replaced "1311.20 study entry" to "1311.6 study 
baseline (1311.6 V2)"
8.
Added: "If clinical response (achieved at E1 or E5 
1311.6) has been lost after end of treatment in 1311.6 
and/or at screening for 1311.20, patients will receive open 
label i.v. re-induction treatment with three infusions of 
600 mg each every 4 weeks after which eligibility will be 
re-assessed. If clinical response or remission compared to 
1311.6  study baseline (V2 1311.6)  is achieved patients 
will switch to s.c. maintenance treatment with 180 mg s.c. 
every 8 weeks (Flow chart 3), otherwise visit EoT has to 
be completed  15 weeks  after  last administration of trial 
drug in 1311.20 trial."
Rationale for change
1.
Typos
2.
Typos
3.
Change of Flowchart number for and additional 
explanation regarding treatment visit window added.
4.
Additional explanations regarding eligibility of 
patients
5.
Additional statement about patient who lost response 
was added
6.
Additional clarifications on eligibility reassessment 
were added
7.
More broad criteria for eligibility reassement at Visit 
5
8.
Additional clarification added for patients who lost 
response
Section to be changed
Section 3.3.2 Inclusion Criteria
Description of change
1.
Added: "… (drop in CDAI from baseline by ≥100) 
AND/or remission…"


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2.
Added: "… with a clinical response AND/or 
remission…"
3.
Added: "…may roll-over either directly IF THAT 
RESPONSE / REMISSION  IS MAINTAINED or …"
4.
Added: "… i.v. re-induction phase IF THEY HAVE 
LOST THEIR PREVIOUS RESPONSE / REMISSION"
5.
Added reference to Section 3.1
Rationale for change
1.
AND omitted in previous version by mistake
2.
AND omitted in previous version by mistake
3.
Additional explanation needed regarding inclusion of 
patients that have completed trial 1311.6 before initiation 
of trial 1311.6
4.
Additional explanation needed regarding inclusion of 
patients that have completed trial 1311.6 before initiation 
of trial 1311.6
5.
Reference added for easier handling
Section to be changed
Section 4.1.3 Selection of doses in the trial
Description of change
Changed: "…with 3 infusions OF 600mg i.v…."
Rationale for change
Typo
Section to be changed
Section 4.1.4 Drug assignment and administration of doses 
for each patient
Description of change
1. Deleted: "Placebo"
2. Added: "2 hours after the first administration"
Rationale for change
1. Mistakenly entered in previous version
2. Additional clarification on patient stay at the site after 
first i.v. IP administration were added
Section to be changed
Section 4.1.7 Storage conditions
Description of change
Added: "…in THE ISF"
Added: "…AN account"
Rationale for change
Typos
Section to be changed
Section 4.2.1
Description of change
Deleted: "Placebo"
Rationale for change
Mistakenly entered in previous version
Section to be changed
Section 4.2.2.1
Description of change
Table substantially revised
Rationale for change
Restricted medication table was not complete in previous 
version in line with restrictions in 1311.6 trial
Section to be changed
Section 4.2.2.1: Tapering of corticosteroids
Description of change
Changed: "…decrease in CDAI <100 points…"
Rationale for change
Typo


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Number of global amendment
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Section to be changed
Section 5.1.1 Endpoint(s) efficacy
Description of change
1.
Endpoint(s)  (s) removed 
2.
Added:  "… WITH POSSIBLE ANSWERS NONE, 
MILD, MODERATE AND SEVERE"
3.
Deleted: "on a numeric rating … pain)"
4.
Added: "Change from baseline in CRP AND fecal
calprotectin …", deleted: " … and lactoferin"
5.
Change from baseline in CDAI scores  by visit moved 
as separate endpoint
Rationale for change
1.
Typo
2.
Numeric rating scale was be replaced by patient diary 
with pain scale as none, mild, moderate and severe 
3.
Numeric rating scale was be replaced by patient diary 
with pain scale as none, mild, moderate and severe
4.
Lactoferin will not be analysed and was removed,  
fecal forgotten by mistake
5.
Clarity
Section to be changed
Section 5.1.2  Assessment of Efficacy
Description of change
1.
Deleted:" The procedure for handling biopsies will be 
provided in the laboratory manual."
2.
Added fecal to calprotectin
Rationale for change
1.
Biopsy is not planned as a part of colonoscopy and 
was present in the text mistakenly from previous protocol.
2.
Fecal forgotten by mistake
Section to be changed
Section 5.2.2.1 Definition of Adverse Events
Description of change
1.
Definition of adverse event rephrased
2.
Definition of adverse reaction added and 
additional explanation  that medical and scientific 
judgement should be exercised in deciding 
whether other situations
should be considered serious reactions
Rationale for change
Adaptation to new Protocol template
Section to be changed
Section 5.2.2.1 Definition of Serious adverse event
Description of change
1.
Definition of serious adverse reaction added and 
also additional explanation what should be 
considered as serious adverse event. 
2.
AE considered "Always Serious" rephrased
Rationale for change
Adaptation to new Protocol template


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Number of global amendment
1.0
Section to be changed
Section 5.2.2.1 Causal Relationship of AE
Description of change
1.
Added Arguments that may suggest that there is / 
is not a reasonable possibility of a causal 
relationship
2.
Removed statement: the reason for the decision 
on causal relationship for unlisted AEs needs to 
be provided in the (e)CRF.
Rationale for change
Adaptation to new Protocol template
Section to be changed
Section 5.2.2.2 Adverse event and serious adverse events 
reporting
Description of change
Added: The Investigator shall maintain and keep detailed 
records of all AEs in their patient files.
Rationale for change
Adaptation to new Protocol template
Section to be changed
Section 5.2.2.2 AE Reporting
Description of change
1.
Removed: reporting obligations after patient`s 
individual end of trial
2.
Added wording for VS data collection
Rationale for change
Adaptation to new Protocol template
Section to be changed
Section 5.2.2.2  AE Reporting
Description of change
1.
Added: After the individual patient's end of the 
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.
2.
Figure updated accordingly.
3.
Added: Events which occurred after the REP will 
be considered as post treatment events.
Rationale for change
Adaptation to new Protocol template
Section to be changed
Section 5.2.2.2 Information required
Description of change
Details of AE CRF pages and SAE form as e.g. onset date, 
end date, intensity, treatment required, outcome, 
seriousness and action taken with the investigational 
drug(s)  removed
Rationale for change
Adaptation to new Protocol template
Section to be changed
Section 5.2.2.2 AE Reporting / Pregnancy
Description of change
Rephrasing the whole paragraph
Rationale for change
Adaptation to new Protocol template
Section to be changed
Section 5.2.4 Medical examination
Description of change
Changed: "FISTULAS" (2x)


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Number of global amendment
1.0
Rationale for change
typo
Section to be changed
Section 5.7.2 Methods of sample collection
Description of change
Deleted: "Not applicable"
Added: "SEE SECTION 5.6.2"
Rationale for change
Missing reference to Section 5.6.2
Section to be changed
Section 6.2.1 Screening period
Description of change
1.
Several typos/grammar in the paragraph "Patient 
rolling-over directly …", changed: "…will be assessed 
FOR ELIGIBILITY"
2.
Deleted paragraph: "Demographics and medical 
history … be recorded in eCRF"
3. Added: "(or at the last preceding trial visit E1 or E5)"
Rationale for change
1. Typos
2. Additional explanation needed for collection of 
information in eCRF
3. Additional clarifications on colonoscopy requirements 
between V1 and V2 are added.
Section to be changed
Section 6.2.2 Treatment periods
Description of change
Changed: "(CDAI drop ≥ 100 from baseline…"
Rationale for change
typo
Section to be changed
Section 6.2.3 End of trial and follow-up period
Description of change
Changed: "THE follow up period …"
Rationale for change
Grammar corrected
Section to be changed
Section 7.3.4 Interim analyses
Description of change
Added: However since this is an open label study, interim 
analyses may be performed as needed after approximately 
20 patients complete the study.
Rationale for change
Trial team decision


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Number of global amendment
1.0
Section to be changed
Section 8.0
Description of change
Statement: The terms and conditions of the insurance 
cover are made available to the investigator and the 
patients via documentation in the ISF (Investigator Site 
File)
Was replaced by:
Insurance certificates are made available to the 
investigator and the patients via documentation in the ISF 
(Investigator Site File).
Rationale for change
Adaptation to new Protocol template
Number of global amendment
2.0
Date of CTP revision
13 October 2016
EudraCT number
2015-001834-15
BI Trial number
1311.20
BI Investigational Product(s)
BI 655066/ABBV-066 (risankizumab)
Title of protocol
An open label, single group, long term safety extension 
trial of BI BI 655066/ABBV-066 (risankizumab), in 
patients with moderately to severely active Crohn's disease
To be implemented only after 
approval of the IRB/IEC/Competent 
Authorities
To be implemented immediately in 
order to eliminate hazard –
IRB / IEC / Competent Authority to 
be notified of change with request 
for approval
Can be implemented without 
IRB/IEC/ Competent Authority 
approval as changes involve 
logistical or administrative aspects 
only
Section to be changed
Title page
Description of change 1
The name of TCM changed to 
Rationale for change
Change of TCM, Study handover from 
 
Section to be changed
Whole document
Description of change 2
Changed "Boehringer Ingelheim" into 
"AbbVie/Boehringer Ingelheim"


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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
Whole document
Description of change 3
Added ABBV-066 (risankizumab) after BI 655066
Rationale for change
Refer to rational for first change listed
Section to be changed
Section 3.1.1 Administrative structure of the trial
Description of change 4
"The trial is sponsored by Boehringer Ingelheim (BI)" was 
changed to "The trial is sponsored by AbbVie in the US 
and Boehringer Ingelheim (BI) ex-US.
Rationale for change
Refer to rational for first change listed
Section to be changed
Section 3.1.1 Administrative structure of the trial
Description of change 5
"Data Management and Statistical Evaluation will be done 
by BI according to BI SOPs" was changed to "Data 
Management will be done by BI according to BI SOPs and 
the Statistical Evaluation will be done by AbbVie 
according to their SOPs."
Rationale for change
Refer to rational for first change listed
Number of global amendment
3.0
Date of CTP revision
28 April 2017
EudraCT number
2015-001834-15
BI Trial number
1311.20/M15-989
BI Investigational Product(s)
BI 655066/ABBV-066 (risankizumab)
Title of protocol
An open label, single group, long term safety extension 
trial of ABBV-066 (risankizumab) in patients with 
moderately to severely active Crohn's disease
To be implemented only after 
approval of the IRB/IEC/Competent 
Authorities


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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
Cover page
Description of change 1
AbbVie will add their cover page once completed 
document has been modified by BI.  All headers and 
footers will be changed to reflect AbbVie language and a 
signature/approval page will be added for AbbVie 
signatories.
Rationale for change
Change in contact details will be needed for sites.
Section to be changed
Whole document
Description of change 2
Removed reference to Boehringer Ingelheim or BI as 
sponsor and changed to AbbVie Inc.  Added M15-989 
after 1311.20.
Rationale for change
At end of June of 2017, AbbVie, Inc will take full 
sponsorship of this study.  Added Abbvie study number 
for site awareness.
Section to be changed
Abbreviations
Description of change 3
DILI - Drug Induced Liver Injury checklist and OPU -
Operative Unit have been deleted
Rationale for change
Abbvie does not follow this checklist for reporting hepatic 
injury details and does not use OPU terminology.
Section to be changed
Section 1.2 Drug Profile, Section 8.4 Listedness and 
Expedited reporting of AEs, and Section 9.2 Unpublished 
References
Description of change 4
Removed link and reference number to the last BI 
Investigator Brochure.
Rationale for change
AbbVie has written a new version which is now 
referenced in the unpublished references section.
Section to be changed
Section 3.1.1 Administrative structure of the trial
Description of change 5
Removed reference to BI team structure and their tasks 
and functions, activities performed by DM and Stats, and 
reference to BI SOPs.
Added a statement that the clinical trial master file 
(CTMF) documents will be transitioned to AbbVie.


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Rationale for change
Team structure and their responsibilities and BI SOPs do 
not apply to AbbVie.  Confirmed that all clinical 
documents will be transitioned to AbbVie.
Section to be changed
Section 4.1 Treatments to be Administered
Description of change 6
Removed drug to be supplied by BI, added ABBV-066 
drug number to substance and removed substance 
language.
Rationale for change
Supplied by BI removed as part of the sponsor change, 
Abbvie drug number was missed to be added at last update 
and substance row is removed as it is duplicate 
information.
Section to be changed
Section 5.2.2 Assessment of adverse events
Description of change 7
Adverse event definition has been added, AEs considered 
always serious has been removed, hepatic injury adverse 
event form has replaced the drug induced liver injury 
checklist "DILI", adverse event reporting to sponsor and 
timelines has been modified, emergency contact details 
have been added and pregnancy language and reporting 
expectations were changed.
Rationale for change
These changes have been made to follow Abbvie standard 
language and reporting expectations.  The always serious 
AE list is used for Post Marketing Observational Studies 
and is not used in clinical trials.
Section to be changed
Safety analyses 7.3.3
Description of change 8
Removed standard BI language for tables and listings and 
the how safety analyses will be performed.
Rationale for change
BI standards to do not apply to AbbVie.
Number of global amendment
4.0
Date of CTP revision
25 July 2018
EudraCT number
2015-001834-15
BI Trial number
1311.20/M15-989
BI Investigational Product(s)
BI 655066/ABBV-066 (risankizumab)
Title of protocol
An open label, single group, long term safety extension 
trial of ABBV-066 (risankizumab) in patients with 
moderately to severely active Crohn's disease
To be implemented only after 
approval of the IRB/IEC/Competent 
Authorities


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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
Synopsis, page 3
Description of change 1
Changed 15 to 20 weeks duration to remain on effective 
birth control after last dose of medication.
Rationale for change
To reflect updated safety risk language.
Section to be changed
Synopsis, page 4
Description of change 2
Added option for patients to enroll, into M16-000 Sub-
Study 3 for those who complete the EoT visit.
Rationale for change
As this study will be terminated, we are allowing patients 
to enroll into the M16-000 Sub-Study 3 which has similar 
long-term extension design.
Section to be changed
Synopsis, page 5
Description of change 3
Efficacy endpoints changed from Week 204/206/216 into 
‘by visit’ time points.
Rationale for change
This study will be terminated and not all patients will have 
the same treatment duration.  Using ‘by visit’ will allow 
for the different time points when the patient will end 
treatment.
Section to be changed
Synopsis, page 6
Description of change 4
Removed annual vital status for criteria for long-term 
safety evaluation of completed patients.
Rationale for change
AbbVie standard does not require and annual vital status 
or follow up visit to occur after premature discontinuation.
Section to be changed
Synopsis, pages 7-23 flowcharts 1 through 3.
Description of change 5
Removed Week number in EoT flowcharts.
Footnote was removed regarding study being conducted 
until study drug registration, as a result, some footnotes 
needed to be renumbered.
Language was added to accommodate patients that will be 
allowed to enroll into M16-000 Sub-Study 3.
Modified premature discontinuation to early EoT.
Removed Vital Status from list of assessments.


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Rationale for change
Patients will be ending participation at different weeks so 
this Week number no longer applies.
Study will be terminated and will not continue until study 
drug registration.
Patients will be asked to come in for their EoT visit and 
provide the option to enroll into the M16-000 Sub-Study 3.
Administrative change from premature discontinuation to 
early EoT to be consistent within the entire document.
Vital Status no longer being completed, it is not an 
AbbVie standard to follow patients annually.
Section to be changed
Abbreviations
Description of change 6
Added Cardiovascular Adjudication Committee (CAC), 
End Of Trial (EoT), and Reference Safety Information 
(RSI). 
Rationale for change
Language was added to the body of the protocol that 
included these abbreviations.
Section to be changed
Section 1.2
Description of change 7
Added Clinical summary subheading and provided 
summary of safety profile.
Rationale for change
To clarify where clinical information begins and to update 
the safety profile with current information.
Section to be changed
Section 2.3 – Benefit Risk Assessment
Description of change 8
Added clarity on known risks and added a statement about 
tumor immunity risk.
Added the CAC will adjudicate all suspected cardio-and 
cerebrovascular events.
Rationale for change
To provide the most current safety profile updates.
To allow for adjudication of events (aligns with other 
risankizumab studies) until the study is terminated.
Section to be changed
Section 3.1 – Overall Trial Design and Plan
Description of change 9
Changed the duration of time from 15 weeks to 140 days 
for follow up period after last dose of study drug.
Removed language regarding study being conducted until 
study drug registration.
Added option for patients who complete the EoT visit to 
enroll into M16-000 Sub-Study 3.


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Rationale for change
Change made as a result of IB update and updated RZB 
half–life of 28 days.
Study will be terminated and will not continue until study 
drug registration.
To create efficiencies by moving patients from this study 
into Study M16-000 Sub-Study 3 (OLE Phase 3), e.g. 
ensuring long term continuation of all patients within one 
OLE trial which will minimize the burden on participating 
sites and patients as well as allow obtaining more robust 
OLE safety analysis. In addition, the OLE design of M16-
000 Sub-Study 3 OLE gives an option of RZB dose 
escalation if needed.
Section to be changed
Sections 3.3.2 – Inclusion Criteria and 3.3.3 - Exclusion 
Criteria
Description of change 10
Changed 15 to 20 weeks duration to remain on effective 
birth control after last dose of medication.
Rationale for change
To reflect updated safety risk language.
Section to be changed
Sections 4.1.6 – Packaging, labelling, and resupply
Description of change 11
Removed drug supplies being provided by BI.
Added description of supplies.
Rationale for change
BI no longer provides the drug supplies.
Other changes provided for clarity.
Section to be changed
Section 4.1.7 - Storage conditions
Description of change 12
Added language on proper storage and assessing any 
temperature excursions.
Rationale for change
Changes were made to provide more clarity. 
Section to be changed
Section 4.1.8 - Drug accountability
Description of change 13
Added paragraph regarding unused medication.
Rationale for change
Moved paragraph from storage conditions to 
accountability as this is the proper section.
Section to be changed
Section 4.2.2.1 – Restrictions regarding concomitant 
treatment
Description of change 14
Added Live or attenuated vaccines 140 days after last 
study drug dose.
Rationale for change
Added to align with phase 3 protocols and due to product 
risk language.
Section to be changed
Section 5.1.1 – Efficacy endpoints
Description of change 15
Efficacy endpoints changed from Week 204/206/216 into 
‘by visit’ time points.


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Rationale for change
This study will be terminated and not all patients will have 
the same treatment duration.  Using “by visit” will allow 
for the different time points when the patient will end 
treatment.
Section to be changed
Section 5.2.1 – Endpoints of safety
Description of change 16
Removed annual vital status for criteria for safety 
evaluation
Rationale for change
AbbVie standard does not require an annual vital status or 
follow up visit to occur after premature discontinuation.
Section to be changed
Section 5.2.2.1 – Adverse Event and Adverse Event of 
Special Interest
Description of change 17
Added language to define reporting elective
surgery/procedures and language regarding cardiac events 
and procedures and TB.
Rationale for change
To capture further information on reporting requirements 
and for suspected cardiac events and TB.
Section to be changed
Section 5.2.2.2 – AE collection
Description of change 18
Removed language regarding annual vital status and 
reporting of SAEs and AESIs.
Rationale for change
AbbVie standard does not require and annual vital status 
or follow up visit to occur after premature discontinuation.
Section to be changed
Section 5.2.2.2 – AE collection
Description of change 19
Modified language regarding SUSAR reporting.
Rationale for change
Modified to align with new protocol template language.
Section to be changed
Section 6.2.3 – End of trial and follow-up period
Description of change 20
Changed the duration of time from 15 to 20 weeks for 
follow up period after last dose of study drug.
Rationale for change
Change made as a result of IB update and updated RZB 
half–life of 28 days.
Section to be changed
Section 7.3.3 – Safety analysis
Description of change 22
Changed the duration of time from 15 to 20 weeks for 
follow up period after last dose of study drug.
Rationale for change
Change made as a result of IB update and updated RZB 
half–life of 28 days.
Section to be changed
Section 9.2 – Unpublished references
Description of change 20
Added versions of the Investigators Brochure that have 
been approved.
Rationale for change
To ensure complete list of IBs were noted.



SAP_001.pdf: