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Clinical Trial Results:
A Multicenter, Randomized, Double-Blind, Placebo Controlled Induction Study to Evaluate the Efficacy and Safety of Risankizumab in Subjects With Moderately to Severely Active Ulcerative Colitis

Summary
EudraCT number	2016-004677-40
Trial protocol	BE SK AT SE ES NL PT GR DK LT PL DE GB LV SI BG HR FR IT
Global end of trial date	11 May 2023

Results information
Results version number	v1(current)
This version publication date	25 May 2024
First version publication date	25 May 2024
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

M16-067

ISRCTN number

US NCT number

NCT03398148

WHO universal trial number (UTN)

Sponsor organisation name

AbbVie Deutschland GmbH & Co. KG

Sponsor organisation address

AbbVie House, Vanwall Business Park, Vanwall Road,, Maidenhead, Berkshire, United Kingdom, SL6 4UB

Public contact

Global Medical Services, AbbVie, AbbVie Deutschland GmbH & Co. KG, 001 8006339110, abbvieclinicaltrials@abbvie.com

Scientific contact

Global Medical Services, AbbVie, AbbVie Deutschland GmbH & Co. KG, 001 8006339110, abbvieclinicaltrials@abbvie.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

11 May 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

11 May 2023

Was the trial ended prematurely?

Main objective of the trial

This study comprises two sub-studies: The purpose of Substudy 1 (SS1) is to characterize the efficacy, safety, and pharmacokinetics of Risankizumab as induction treatment in subjects with moderately to severely active Ulcerative Colitis (UC) and to identify the appropriate induction dose of Risankizumab for further evaluation in Substudy 2 (SS2). The purpose of SS2 is to evaluate the efficacy and safety of Risankizumab compared to placebo in inducing clinical remission in subjects with moderately to severely active UC.

Protection of trial subjects

Subject and/or legal guardian read and understood the information provided about the study and gave written permission.

Background therapy

Evidence for comparator

Actual start date of recruitment

01 Apr 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Israel: 55

Country: Number of subjects enrolled

Argentina: 12

Country: Number of subjects enrolled

Netherlands: 20

Country: Number of subjects enrolled

Poland: 118

Country: Number of subjects enrolled

Portugal: 15

Country: Number of subjects enrolled

Slovakia: 37

Country: Number of subjects enrolled

Slovenia: 4

Country: Number of subjects enrolled

Spain: 38

Country: Number of subjects enrolled

United Kingdom: 28

Country: Number of subjects enrolled

Croatia: 20

Country: Number of subjects enrolled

Austria: 40

Country: Number of subjects enrolled

Belgium: 75

Country: Number of subjects enrolled

Bulgaria: 5

Country: Number of subjects enrolled

Czechia: 10

Country: Number of subjects enrolled

Denmark: 4

Country: Number of subjects enrolled

France: 17

Country: Number of subjects enrolled

Germany: 102

Country: Number of subjects enrolled

Greece: 26

Country: Number of subjects enrolled

Italy: 109

Country: Number of subjects enrolled

Latvia: 7

Country: Number of subjects enrolled

Lithuania: 15

Country: Number of subjects enrolled

Brazil: 29

Country: Number of subjects enrolled

Canada: 52

Country: Number of subjects enrolled

Chile: 19

Country: Number of subjects enrolled

Colombia: 2

Country: Number of subjects enrolled

China: 88

Country: Number of subjects enrolled

Egypt: 22

Country: Number of subjects enrolled

Japan: 207

Country: Number of subjects enrolled

Korea, Republic of: 39

Country: Number of subjects enrolled

Mexico: 1

Country: Number of subjects enrolled

New Zealand: 31

Country: Number of subjects enrolled

Romania: 15

Country: Number of subjects enrolled

Russian Federation: 20

Country: Number of subjects enrolled

Serbia: 37

Country: Number of subjects enrolled

Singapore: 2

Country: Number of subjects enrolled

South Africa: 22

Country: Number of subjects enrolled

Sweden: 3

Country: Number of subjects enrolled

Switzerland: 19

Country: Number of subjects enrolled

Taiwan: 15

Country: Number of subjects enrolled

Ukraine: 8

Country: Number of subjects enrolled

United States: 167

Country: Number of subjects enrolled

Türkiye: 3

Worldwide total number of subjects

1558

EEA total number of subjects

680

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

1451

From 65 to 84 years

107

85 years and over

Subject disposition

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Recruitment details

Induction study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). Both sub studies included Periods 1 and 2: S1P1 12 weeks-Double-Blind and Open-Label; S1P2 12 weeks for clinical non-responders in S1P1; S2P1: 12 weeks; S2P2 12 weeks for clinical non-responders from S2P1.

Screening details

In SS1 Double-blind (DB) Dose Finding Induction Period 1 (S1P1) (ITT1A), 240 subjects enrolled 180 received at least 1 dose of study drug ; Open-Label (ITT1B), 341 subjects enrolled 340 received drug. S1P2 (ITT1P2): 215 subjects enrolled 214 received drug. In S2P1 (ITT2), 977 randomized 650 received drug. S2P2 (ITT2P2), 384 enrolled and 382 treated

Period 1 title

S1P1 and S2P1

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Blinding implementation details

During Substudy 1, Induction Period 1 (S1P1), Participants received Risankizumab 1800mg administered by intravenous (IV) infusion in an Open-Label manner. All other Substudies were Double-Blinded.

Are arms mutually exclusive

Yes

S1P1: DB - Placebo IV

Arm description

Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Placebo for Risankizumab administered by intravenous (IV) infusion.

Arm type

Placebo

Investigational medicinal product name

Placebo for Risankizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Placebo for Risankizumab administered by intravenous (IV) infusion.

S1P1: DB - Risankizumab 600mg IV

Arm description

Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Risankizumab 600mg administered by intravenous (IV) infusion.

Arm type

Experimental

Investigational medicinal product name

Risankizumab

Investigational medicinal product code

Other name

ABBV-066, BI 655066

Pharmaceutical forms

Injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Risankizumab 600mg administered by intravenous (IV) infusion

S1P1: DB - Risankizumab 1200mg IV

Arm description

Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Risankizumab 1200mg administered by intravenous (IV) infusion.

Arm type

Experimental

Investigational medicinal product name

Risankizumab

Investigational medicinal product code

Other name

ABBV-066, BI 655066

Pharmaceutical forms

Injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Risankizumab 1200mg administered by intravenous (IV) infusion

S1P1: DB - Risankizumab 1800mg IV

Arm description

Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Risankizumab 1800mg administered by intravenous (IV) infusion.

Arm type

Experimental

Investigational medicinal product name

Risankizumab

Investigational medicinal product code

Other name

ABBV-066, BI 655066

Pharmaceutical forms

Injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Risankizumab 1800mg administered by intravenous (IV) infusion

S1P1: OL - Risankizumab 1800mg IV

Arm description

Substudy 1, Induction Period 1 (S1P1): Open-label (OL) Participants received Risankizumab 1800mg administered by intravenous (IV) infusion.

Arm type

Experimental

Investigational medicinal product name

Risankizumab

Investigational medicinal product code

Other name

ABBV-066, BI 655066

Pharmaceutical forms

Injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Risankizumab 1800mg administered by intravenous (IV) infusion

S2P1: DB – Placebo IV

Arm description

Substudy 2, Induction Period 1 (S2P1): Double-blind (DB) received placebo for risankizumab administered by intravenous (IV) infusion.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Placebo for risankizumab administered by intravenous (IV) infusion.

S2P1: DB Risankizumab 1200mg IV

Arm description

Substudy 2, Induction Period 1 (S2P1): Double-blind (DB) received risankizumab 1200mg administered by intravenous (IV) infusion.

Arm type

Experimental

Investigational medicinal product name

risankizumab

Investigational medicinal product code

Other name

ABBV-066, BI 655066

Pharmaceutical forms

Injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

risankizumab 1200mg administered by intravenous (IV) infusion.

Number of subjects in period 1 ^[1]	S1P1: DB - Placebo IV	S1P1: DB - Risankizumab 600mg IV	S1P1: DB - Risankizumab 1200mg IV	S1P1: DB - Risankizumab 1800mg IV	S1P1: OL - Risankizumab 1800mg IV	S2P1: DB – Placebo IV	S2P1: DB Risankizumab 1200mg IV
Started	60	61	61	58	340	325	650
Completed	53	55	58	57	306	297	637
Not completed	7	6	3	1	34	28	13
COVID-19 INFECTION	-	-	-	-	-	-	1
Consent withdrawn by subject	1	2	-	1	3	6	4
Adverse event, non-fatal	5	2	2	-	8	12	2
COVID-19 LOGISTICAL RESTRICTIONS	-	-	-	-	-	-	1
Not Specified	-	1	-	-	3	4	4
Lack of efficacy	1	1	1	-	20	6	1

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: In S1P1: Open-label Risankizumab 1800mg IV arm, a total of 341 subjects were enrolled, but only 340 subjects were treated. In the S2P1: Double-blind Risankizumab 1200mg IV arm, a total of 652 subjects were randomized, but only 650 subjects were treated.

Period 2 title

S1P2 and S2P2

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

S1P2: DB - Risankizumab 180mg SC

Arm description

Substudy 1, Induction Period 2 (S1P2): Double-blind (DB) Participants who received risankizumab with inadequate response in Induction 1 randomized to receive risankizumab 180mg administered by subcutaneous (SC) injection.

Arm type

Experimental

Investigational medicinal product name

Risankizumab

Investigational medicinal product code

Other name

ABBV-066, BI 655066

Pharmaceutical forms

Injection/infusion

Routes of administration

Subcutaneous use

Dosage and administration details

Risankizumab 180mg administered by subcutaneous (SC) injection.

S1P2: DB – Risankizumab 360mg SC

Arm description

Substudy 1, Induction Period 2 (S1P2): Double-blind (DB) Participants who received risankizumab with inadequate response in Induction 1 randomized to receive Risankizumab 360mg administered by subcutaneous (SC) injection.

Arm type

Experimental

Investigational medicinal product name

risankizumab

Investigational medicinal product code

Other name

ABBV-066, BI 655066

Pharmaceutical forms

Injection/infusion

Routes of administration

Subcutaneous use

Dosage and administration details

Risankizumab 360mg administered by subcutaneous (SC) injection

S1P2: DB – Risankizumab 1800mg IV

Arm description

Substudy 1, Induction Period 2 (S1P2): Double-blind (DB) Participants who received risankizumab with inadequate response in Induction 1 randomized to receive 1800mg administered by intravenous (IV) infusion

Arm type

Experimental

Investigational medicinal product name

risankizumab

Investigational medicinal product code

Other name

ABBV-066, BI 655066

Pharmaceutical forms

Injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Risankizumab 1800mg administered by intravenous (IV) infusion

S1P2: DB – Risankizumab 1800mg IV Pbo

Arm description

Substudy 1, Induction Period 2 (S1P2): Double-blind (DB) participants who received placebo with inadequate response in Induction 1 receive risankizumab 1800mg administered by intravenous (IV) infusion

Arm type

Experimental

Investigational medicinal product name

risankizumab

Investigational medicinal product code

Other name

ABBV-066, BI 655066

Pharmaceutical forms

Injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

risankizumab 1800mg administered by intravenous (IV) infusion

S2P2 DB – Risankizumab 180mg SC

Arm description

Substudy 2, Induction Period 2 (S2P2): Double-blind (DB) participants who received risankizumab with inadequate response in Induction 1 randomized to receive risankizumab 180mg administered by subcutaneous (SC) injection

Arm type

Experimental

Investigational medicinal product name

risankizumab

Investigational medicinal product code

Other name

ABBV-066, BI 655066

Pharmaceutical forms

Injection/infusion

Routes of administration

Subcutaneous use

Dosage and administration details

risankizumab 180mg administered by subcutaneous (SC) injection

S2P2 DB – Risankizumab 360mg SC

Arm description

Substudy 2, Induction Period 2 (S2P2): Double-blind (DB) participants who received risankizumab with inadequate response in Induction 1 randomized to receive risankizumab 360mg administered by subcutaneous (SC) injection.

Arm type

Experimental

Investigational medicinal product name

risankizumab

Investigational medicinal product code

Other name

ABBV-066, BI 655066

Pharmaceutical forms

Injection/infusion

Routes of administration

Subcutaneous use

Dosage and administration details

Risankizumab 360mg administered by subcutaneous (SC) injection.

S2P2 DB – Risankizumab 1200mg IV

Arm description

Substudy 2, Induction Period 2 (S2P2): Double-blind (DB) participants who received risankizumab with inadequate response in Induction 1 randomized to receive Risankizumab 1200mg administered by intravenous (IV) infusion.

Arm type

Experimental

Investigational medicinal product name

risankizumab

Investigational medicinal product code

Other name

ABBV-066, BI 655066

Pharmaceutical forms

Injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Risankizumab 1200mg administered by intravenous (IV) infusion.

S2P2 DB – Risankizumab 1200mg IV Pbo

Arm description

Substudy 2, Induction Period 2 (S2P2): Double-blind (DB) participants received placebo with inadequate response in Induction 1 randomized to receive risankizumab 1200mg administered by intravenous (IV) infusion.

Arm type

Experimental

Investigational medicinal product name

risankizumab

Investigational medicinal product code

Other name

ABBV-066, BI 655066

Pharmaceutical forms

Injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Risankizumab 1200mg administered by intravenous (IV) infusion.

Number of subjects in period 2 ^[2]	S1P2: DB - Risankizumab 180mg SC	S1P2: DB – Risankizumab 360mg SC	S1P2: DB – Risankizumab 1800mg IV	S1P2: DB – Risankizumab 1800mg IV Pbo	S2P2 DB – Risankizumab 180mg SC	S2P2 DB – Risankizumab 360mg SC	S2P2 DB – Risankizumab 1200mg IV	S2P2 DB – Risankizumab 1200mg IV Pbo
Started	72	69	36	37	71	70	68	173
Completed	65	57	34	35	65	65	61	164
Not completed	7	12	2	2	6	5	7	9
Consent withdrawn by subject	-	1	2	-	4	-	2	1
Adverse event, non-fatal	2	4	-	-	-	-	1	3
COVID-19 LOGISTICAL RESTRICTIONS	-	1	-	-	-	-	-	-
Not Specified	-	1	-	-	-	-	1	1
Lost to follow-up	-	-	-	-	1	1	-	-
Lack of efficacy	5	5	-	2	1	4	3	4

Notes
[2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). Both sub studies included a Period 1 followed by a Period 2. Within Substudy 1 and 2, subjects who did not achieve clinical response at Week 12 in the respective substudy were eligible to receive blinded risankizumab treatment in the study period 2.

Baseline characteristics

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Reporting group title

S1P1: DB - Placebo IV

Reporting group description

Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Placebo for Risankizumab administered by intravenous (IV) infusion.

Reporting group title

S1P1: DB - Risankizumab 600mg IV

Reporting group description

Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Risankizumab 600mg administered by intravenous (IV) infusion.

Reporting group title

S1P1: DB - Risankizumab 1200mg IV

Reporting group description

Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Risankizumab 1200mg administered by intravenous (IV) infusion.

Reporting group title

S1P1: DB - Risankizumab 1800mg IV

Reporting group description

Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Risankizumab 1800mg administered by intravenous (IV) infusion.

Reporting group title

S1P1: OL - Risankizumab 1800mg IV

Reporting group description

Substudy 1, Induction Period 1 (S1P1): Open-label (OL) Participants received Risankizumab 1800mg administered by intravenous (IV) infusion.

Reporting group title

S2P1: DB – Placebo IV

Reporting group description

Substudy 2, Induction Period 1 (S2P1): Double-blind (DB) received placebo for risankizumab administered by intravenous (IV) infusion.

Reporting group title

S2P1: DB Risankizumab 1200mg IV

Reporting group description

Substudy 2, Induction Period 1 (S2P1): Double-blind (DB) received risankizumab 1200mg administered by intravenous (IV) infusion.

Reporting group values	S1P1: DB - Placebo IV	S1P1: DB - Risankizumab 600mg IV	S1P1: DB - Risankizumab 1200mg IV	S1P1: DB - Risankizumab 1800mg IV	S1P1: OL - Risankizumab 1800mg IV	S2P1: DB – Placebo IV	S2P1: DB Risankizumab 1200mg IV	Total
Number of subjects	60	61	61	58	340	325	650	1555
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	44.4 ± 14.09	43.0 ± 14.90	41.8 ± 13.80	40.9 ± 13.73	40.4 ± 14.17	42.8 ± 14.30	41.8 ± 13.47	-
Gender categorical
Units: Subjects
Female	24	21	26	27	145	124	265	632
Male	36	40	35	31	195	201	385	923
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	3	2	6	1	21	20	44	97
Not Hispanic or Latino	57	59	55	57	319	305	606	1458
Unknown or Not Reported	0	0	0	0	0	0	0	0
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0	1	1
Asian	14	11	15	11	47	96	171	365
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0
Black or African American	2	1	1	2	3	7	12	28
White	44	49	45	45	290	218	461	1152
More than one race	0	0	0	0	0	4	5	9
Unknown or Not Reported	0	0	0	0	0	0	0	0
Adapted Mayo Score
Measure Description: The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: 1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal) 2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed) 3. Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration) The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease.
Units: Adapted Mayo Score 0 - 9
arithmetic mean (standard deviation)	7.012 ± 1.1645	6.929 ± 1.2240	7.011 ± 1.1288	7.15 ± 1.3908	7.179 ± 1.2279	7.052 ± 1.2800	7.068 ± 1.2173	-

End points

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Reporting group title

S1P1: DB - Placebo IV

Reporting group description

Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Placebo for Risankizumab administered by intravenous (IV) infusion.

Reporting group title

S1P1: DB - Risankizumab 600mg IV

Reporting group description

Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Risankizumab 600mg administered by intravenous (IV) infusion.

Reporting group title

S1P1: DB - Risankizumab 1200mg IV

Reporting group description

Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Risankizumab 1200mg administered by intravenous (IV) infusion.

Reporting group title

S1P1: DB - Risankizumab 1800mg IV

Reporting group description

Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Risankizumab 1800mg administered by intravenous (IV) infusion.

Reporting group title

S1P1: OL - Risankizumab 1800mg IV

Reporting group description

Substudy 1, Induction Period 1 (S1P1): Open-label (OL) Participants received Risankizumab 1800mg administered by intravenous (IV) infusion.

Reporting group title

S2P1: DB – Placebo IV

Reporting group description

Substudy 2, Induction Period 1 (S2P1): Double-blind (DB) received placebo for risankizumab administered by intravenous (IV) infusion.

Reporting group title

S2P1: DB Risankizumab 1200mg IV

Reporting group description

Substudy 2, Induction Period 1 (S2P1): Double-blind (DB) received risankizumab 1200mg administered by intravenous (IV) infusion.

Reporting group title

S1P2: DB - Risankizumab 180mg SC

Reporting group description

Reporting group title

S1P2: DB – Risankizumab 360mg SC

Reporting group description

Reporting group title

S1P2: DB – Risankizumab 1800mg IV

Reporting group description

Reporting group title

S1P2: DB – Risankizumab 1800mg IV Pbo

Reporting group description

Reporting group title

S2P2 DB – Risankizumab 180mg SC

Reporting group description

Reporting group title

S2P2 DB – Risankizumab 360mg SC

Reporting group description

Reporting group title

S2P2 DB – Risankizumab 1200mg IV

Reporting group description

Reporting group title

S2P2 DB – Risankizumab 1200mg IV Pbo

Reporting group description

Primary: Sub-Study 1: Percentage of Participants Achieving Clinical Remission Per Adapted Mayo Score

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End point title

Sub-Study 1: Percentage of Participants Achieving Clinical Remission Per Adapted Mayo Score ^[1]

End point description

The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: 1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal) 2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed) 3. Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration) The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. For Sub-Study 1, clinical remission was defined as SFS ≤ 1, and not greater than baseline, RBS of 0, and endoscopic subscore ≤ 1.

End point type

Primary

End point timeframe

Week 12

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S1P1: DB - Placebo IV	S1P1: DB - Risankizumab 600mg IV	S1P1: DB - Risankizumab 1200mg IV	S1P1: DB - Risankizumab 1800mg IV	S1P1: OL - Risankizumab 1800mg IV
Number of subjects analysed	60 ^[2]	61 ^[3]	61 ^[4]	58 ^[5]	340 ^[6]
Units: Participants	1	7	6	6	42

Notes
[2] - ITT1A randomized subjects who received at least 1 dose of drug during Induction Period 1 Substudy 1.
[3] - ITT1A randomized subjects who received at least 1 dose of drug during Induction Period 1 Substudy 1
[4] - ITT1A randomized subjects who received at least 1 dose of drug during Induction Period 1 Substudy 1
[5] - ITT1A randomized subjects who received at least 1 dose of drug during Induction Period 1 Substudy 1
[6] - ITT1B includes all the additional subjects who received at least one dose of risankizumab 1800 mg IV

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0324 ^[7]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

9.6

Confidence interval

level

90%

sides

2-sided

lower limit

2.2

upper limit

Notes
[7] - P-value ≤ 0.05. Based on Cochran-Mantel-Haenszel (CMH) test stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (≤ 7, > 7). Risk difference = (risankizumab – Placebo).

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.046 ^[8]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

8.4

Confidence interval

level

90%

sides

2-sided

lower limit

1.5

upper limit

15.3

Notes
[8] - P-value ≤ 0.05. Based on Cochran-Mantel-Haenszel (CMH) test stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (≤ 7, > 7). Risk difference = (risankizumab – Placebo).

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0397 ^[9]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

8.7

Confidence interval

level

90%

sides

2-sided

lower limit

1.7

upper limit

15.6

Notes
[9] - P-value ≤ 0.05. Based on Cochran-Mantel-Haenszel (CMH) test stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (≤ 7, > 7). Risk difference = (risankizumab – Placebo)

Primary: Sub-Study 2: Percentage of Participants Achieving Clinical Remission Per Adapted Mayo Score

Top of page

End point title

Sub-Study 2: Percentage of Participants Achieving Clinical Remission Per Adapted Mayo Score ^[10]

End point description

The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: 1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal) 2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed) 3. Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration) The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. For Sub-Study 2, clinical remission was defined as SFS ≤ 1, and not greater than baseline, RBS of 0, and endoscopic subscore ≤ 1. Evidence of friability during endoscopy in subjects with otherwise "mild" endoscopic activity will confer an endoscopic subscore of 2.

End point type

Primary

End point timeframe

Week 12

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S2P1: DB – Placebo IV	S2P1: DB Risankizumab 1200mg IV
Number of subjects analysed	325 ^[11]	650 ^[12]
Units: Percentage of Participants
arithmetic mean (confidence interval 95%)	6.2 (3.6 to 8.9)	20.3 (17.2 to 23.4)

Notes
[11] - ITT2 population.
[12] - ITT2 population.

Primary Analysis

Comparison groups

S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV

Number of subjects included in analysis

975

Analysis specification

Pre-specified

Analysis type

superiority ^[13]

P-value

< 0.0001 ^[14]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Notes
[13] - Stratified by Advanced Therapy-IR status (yes vs no), Baseline steroid use (yes vs. no) and Baseline Adapted Mayo Score (≤ 7, > 7).
[14] - Achieved statistical significance at the 2-sided α level of 0.05 under overall Type I error rate control.

Secondary: Sub-Study 1: Percentage of Participants Achieving Endoscopic Improvement

Top of page

End point title

Sub-Study 1: Percentage of Participants Achieving Endoscopic Improvement ^[15]

End point description

Endoscopic improvement is defined as endoscopy subscore of 0 or 1. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).

End point type

Secondary

End point timeframe

Week 12

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S1P1: DB - Placebo IV	S1P1: DB - Risankizumab 600mg IV	S1P1: DB - Risankizumab 1200mg IV	S1P1: DB - Risankizumab 1800mg IV	S1P1: OL - Risankizumab 1800mg IV
Number of subjects analysed	60 ^[16]	61 ^[17]	61 ^[18]	58 ^[19]	340 ^[20]
Units: Participants	3	15	8	9	61

Notes
[16] - Includes ITT1A population.
[17] - Includes ITT1A population.
[18] - Includes ITT1A population.
[19] - Includes ITT1A population.
[20] - Includes ITT1B population.

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0028 ^[21]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

18.7

Confidence interval

level

90%

sides

2-sided

lower limit

8.4

upper limit

Notes
[21] - P-value ≤ 0.01. Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab – Placebo).

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0968 ^[22]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

8.4

Confidence interval

level

90%

sides

2-sided

lower limit

0.1

upper limit

16.7

Notes
[22] - P-value ≤ 0.1. Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab – Placebo).

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0512 ^[23]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

10.5

Confidence interval

level

90%

sides

2-sided

lower limit

1.6

upper limit

19.3

Notes
[23] - P-value ≤ 0.1. Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab – Placebo).

Secondary: Sub-Study 1: Percentage of Participants Achieving Clinical Remission Per Full Mayo Score in Participants With a FullMayo Score of 6 to 12 at Baseline

Top of page

End point title

Sub-Study 1: Percentage of Participants Achieving Clinical Remission Per Full Mayo Score in Participants With a FullMayo Score of 6 to 12 at Baseline ^[24]

End point description

The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Full Mayo score (FMS) ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore > 1.

End point type

Secondary

End point timeframe

Week 12

Notes
[24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S1P1: DB - Placebo IV	S1P1: DB - Risankizumab 600mg IV	S1P1: DB - Risankizumab 1200mg IV	S1P1: DB - Risankizumab 1800mg IV	S1P1: OL - Risankizumab 1800mg IV
Number of subjects analysed	0 ^[25]	0 ^[26]	0 ^[27]	0 ^[28]	0 ^[29]
Units: Participants

Notes
[25] - Data could not be analyzed due to data gathering/validation issues.
[26] - Data could not be analyzed due to data gathering/validation issues.
[27] - Data could not be analyzed due to data gathering/validation issues.
[28] - Data could not be analyzed due to data gathering/validation issues.
[29] - Data could not be analyzed due to data gathering/validation issues.

No statistical analyses for this end point

Secondary: Sub-Study 1: Percentage of Participants Achieving Clinical Response Per Adapted Mayo Score

Top of page

End point title

Sub-Study 1: Percentage of Participants Achieving Clinical Response Per Adapted Mayo Score ^[30]

End point description

The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: 1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal) 2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed) 3. Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration) The overall Adapted Mayo Score ranges from 0 to 9 where higher scores represent more severe disease. Clinical response per Adapted Mayo Score was defined as decrease from baseline in Adapted Mayo Score ≥ 2 points and ≥ 30%, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1.

End point type

Secondary

End point timeframe

Week 12

Notes
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S1P1: DB - Placebo IV	S1P1: DB - Risankizumab 600mg IV	S1P1: DB - Risankizumab 1200mg IV	S1P1: DB - Risankizumab 1800mg IV	S1P1: OL - Risankizumab 1800mg IV
Number of subjects analysed	60 ^[31]	61 ^[32]	61 ^[33]	58 ^[34]	340 ^[35]
Units: Participants	12	26	28	31	157

Notes
[31] - Includes ITT1A population.
[32] - Includes ITT1A population.
[33] - Includes ITT1A population.
[34] - Includes ITT1A population.
[35] - Includes ITT1B population.

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0022 ^[36]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

23.9

Confidence interval

level

90%

sides

2-sided

lower limit

upper limit

36.7

Notes
[36] - P-value ≤ 0.01. Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002 ^[37]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

28.4

Confidence interval

level

90%

sides

2-sided

lower limit

15.7

upper limit

41.1

Notes
[37] - P-value ≤ 0.001. Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[38]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

33.8

Confidence interval

level

90%

sides

2-sided

lower limit

20.7

upper limit

46.9

Notes
[38] - P-value ≤ 0.001. Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).

Secondary: Sub-Study 1: Percentage of Participants Achieving Clinical Response Per Partial Adapted Mayo Score

Top of page

End point title

Sub-Study 1: Percentage of Participants Achieving Clinical Response Per Partial Adapted Mayo Score ^[39]

End point description

Clinical response per Partial Adapted Mayo Score (without endoscopy). The Partial Mayo Score is a composite score of UC disease activity based on the following 2 subscores: 1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal) 2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed) The overall Partial Mayo Score ranges from 0 to 6 with higher scores representing more severe disease. Clinical response per Partial Mayo Score is defined as a decrease in Partial Adapted Mayo score >= 1 point and ≥ 30% from Baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1.

End point type

Secondary

End point timeframe

Week 4

Notes
[39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S1P1: DB - Placebo IV	S1P1: DB - Risankizumab 600mg IV	S1P1: DB - Risankizumab 1200mg IV	S1P1: DB - Risankizumab 1800mg IV	S1P1: OL - Risankizumab 1800mg IV
Number of subjects analysed	60 ^[40]	61 ^[41]	61 ^[42]	58 ^[43]	340 ^[44]
Units: Participants	15	20	28	22	148

Notes
[40] - Includes ITT1A population.
[41] - Includes ITT1A population.
[42] - Includes ITT1A population.
[43] - Includes ITT1A population.
[44] - Includes ITT1B population.

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1842 ^[45]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

10.2

Confidence interval

level

90%

sides

2-sided

lower limit

-2.4

upper limit

22.9

Notes
[45] - Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0041 ^[46]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

23.2

Confidence interval

level

90%

sides

2-sided

lower limit

9.9

upper limit

36.4

Notes
[46] - P-value ≤ 0.01. Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1117 ^[47]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

13.1

Confidence interval

level

90%

sides

2-sided

lower limit

-0.4

upper limit

26.6

Notes
[47] - Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).

Secondary: Sub-Study 1: Percentage of Participants Achieving Endoscopic Remission

Top of page

End point title

Sub-Study 1: Percentage of Participants Achieving Endoscopic Remission ^[48]

End point description

Endoscopic remission was defined as endoscopy subscore of 0.

End point type

Secondary

End point timeframe

Week 12

Notes
[48] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S1P1: DB - Placebo IV	S1P1: DB - Risankizumab 600mg IV	S1P1: DB - Risankizumab 1200mg IV	S1P1: DB - Risankizumab 1800mg IV	S1P1: OL - Risankizumab 1800mg IV
Number of subjects analysed	60 ^[49]	61 ^[50]	61 ^[51]	58 ^[52]	340 ^[53]
Units: Participants	0	5	3	5	22

Notes
[49] - Includes ITT1A population.
[50] - Includes ITT1A population.
[51] - Includes ITT1A population.
[52] - Includes ITT1A population.
[53] - Includes ITT1B population.

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0192 ^[54]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

8.3

Confidence interval

level

90%

sides

2-sided

lower limit

2.5

upper limit

14.1

Notes
[54] - P-value ≤ 0.05. Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0706 ^[55]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

4.8

Confidence interval

level

90%

sides

2-sided

lower limit

0.4

upper limit

9.1

Notes
[55] - P-value ≤ 0.1. Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.017 ^[56]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

8.7

Confidence interval

level

90%

sides

2-sided

lower limit

2.7

upper limit

14.6

Notes
[56] - P-value ≤ 0.05. Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).

Secondary: Sub-Study 1: Percentage of Participants With Hospitalization

Top of page

End point title

Sub-Study 1: Percentage of Participants With Hospitalization ^[57]

End point description

Participants with an event that results in admission to the hospital.

End point type

Secondary

End point timeframe

Through Week 12

Notes
[57] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S1P1: DB - Placebo IV	S1P1: DB - Risankizumab 600mg IV	S1P1: DB - Risankizumab 1200mg IV	S1P1: DB - Risankizumab 1800mg IV	S1P1: OL - Risankizumab 1800mg IV
Number of subjects analysed	60 ^[58]	61 ^[59]	61 ^[60]	58 ^[61]	340 ^[62]
Units: Participants	5	6	4	3	19

Notes
[58] - Includes ITT1A population.
[59] - Includes ITT1A population.
[60] - Includes ITT1A population.
[61] - Includes ITT1A population.
[62] - Includes ITT1B population.

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7737 ^[63]

Method

Chi-squared

Confidence interval

Notes
[63] - P value for comparisons between treatment groups and placebo group using chi-square test or Fisher's exact test.

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7432 ^[64]

Method

Fisher exact

Confidence interval

Notes
[64] - P value for comparisons between treatment groups and placebo group using chi-square test or Fisher's exact test.

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7172 ^[65]

Method

Fisher exact

Confidence interval

Notes
[65] - P value for comparisons between treatment groups and placebo group using chi-square test or Fisher's exact test.

Secondary: Sub-Study 1: Percentage of Participants Achieving Histologic Endoscopic Mucosal Remission (HEMR)

Top of page

End point title

Sub-Study 1: Percentage of Participants Achieving Histologic Endoscopic Mucosal Remission (HEMR) ^[66]

End point description

Mucosal healing defined as endoscopic and histologic remission. Mucosal healing is defined as an endoscopic score of 0 and Geboes score < 2.0. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation;Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; andGrade 5, erosions or ulceration.

End point type

Secondary

End point timeframe

Week 12

Notes
[66] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S1P1: DB - Placebo IV	S1P1: DB - Risankizumab 600mg IV	S1P1: DB - Risankizumab 1200mg IV	S1P1: DB - Risankizumab 1800mg IV	S1P1: OL - Risankizumab 1800mg IV
Number of subjects analysed	60 ^[67]	61 ^[68]	61 ^[69]	58 ^[70]	340 ^[71]
Units: Participants	0	3	2	1	10

Notes
[67] - Includes ITT1A population.
[68] - Includes ITT1A population.
[69] - Includes ITT1A population.
[70] - Includes ITT1A population.
[71] - Includes ITT1B population.

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0722 ^[72]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

4.7

Confidence interval

level

90%

sides

2-sided

lower limit

0.4

upper limit

Notes
[72] - P-value ≤ 0.1. Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.148 ^[73]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

3.1

Confidence interval

level

90%

sides

2-sided

lower limit

-0.4

upper limit

6.6

Notes
[73] - Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3042 ^[74]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

1.7

Confidence interval

level

90%

sides

2-sided

lower limit

-1

upper limit

4.5

Notes
[74] - Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).

Secondary: Sub-Study 1: Change in Ulcerative Colitis Symptom Questionnaire (UC-SQ)

Top of page

End point title

Sub-Study 1: Change in Ulcerative Colitis Symptom Questionnaire (UC-SQ) ^[75]

End point description

The UC-SQ is a patient questionnaire to assess severity of Ulcerative Colitis Symptom

End point type

Secondary

End point timeframe

Baseline Through Week 12

Notes
[75] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S1P1: DB - Placebo IV	S1P1: DB - Risankizumab 600mg IV	S1P1: DB - Risankizumab 1200mg IV	S1P1: DB - Risankizumab 1800mg IV	S1P1: OL - Risankizumab 1800mg IV
Number of subjects analysed	50 ^[76]	52 ^[77]	56 ^[78]	53 ^[79]	286 ^[80]
Units: Units on a scale
least squares mean (standard error)	-7.4 ± 1.53	-13.8 ± 1.50	-15.6 ± 1.46	-15.1 ± 1.51	-17.1 ± 0.58

Notes
[76] - Includes ITT1A population.
[77] - Includes ITT1A population.
[78] - Includes ITT1A population.
[79] - Includes ITT1A population.
[80] - Includes ITT1B population.

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[81]

Method

Mixed-effect model repeated measurement

Parameter type

Least Squares (LS) Mean Difference

Point estimate

-6.4

Confidence interval

level

90%

sides

2-sided

lower limit

-9.94

upper limit

-2.89

Variability estimate

Standard error of the mean

Dispersion value

2.13

Notes
[81] - P-value ≤ 0.01.

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV

Number of subjects included in analysis

106

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001 ^[82]

Method

Mixed-effect model repeated measurement

Parameter type

Least Squares (LS) Mean Difference

Point estimate

-8.2

Confidence interval

level

90%

sides

2-sided

lower limit

-11.67

upper limit

-4.71

Variability estimate

Standard error of the mean

Dispersion value

2.11

Notes
[82] - P-value ≤ 0.001

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0004 ^[83]

Method

Mixed-effect model repeated measurement

Parameter type

Least Squares (LS) Mean Difference

Point estimate

-7.7

Confidence interval

level

90%

sides

2-sided

lower limit

-11.27

upper limit

-4.19

Variability estimate

Standard error of the mean

Dispersion value

2.14

Notes
[83] - P-value ≤ 0.001

Secondary: Sub-Study 1: Change in Inflammatory Bowel Disease Questionnaire (IBDQ)

Top of page

End point title

Sub-Study 1: Change in Inflammatory Bowel Disease Questionnaire (IBDQ) ^[84]

End point description

The IBDQ is used to assess the quality of life of patients with inflammatory bowel disease. The IBDQ is a 32-item (ranges 1 - 7) 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). The IBDQ total Score ranges from 32 to 224 with a higher score indicating better outcome.

End point type

Secondary

End point timeframe

Baseline Through Week 12

Notes
[84] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S1P1: DB - Placebo IV	S1P1: DB - Risankizumab 600mg IV	S1P1: DB - Risankizumab 1200mg IV	S1P1: DB - Risankizumab 1800mg IV	S1P1: OL - Risankizumab 1800mg IV
Number of subjects analysed	51 ^[85]	55 ^[86]	59 ^[87]	54 ^[88]	305 ^[89]
Units: Units on a scale
least squares mean (standard error)	20.1 ± 4.67	37.4 ± 4.56	40.3 ± 4.38	40.0 ± 4.55	49.5 ± 1.86

Notes
[85] - Includes ITT1A population.
[86] - Includes ITT1A population.
[87] - Includes ITT1A population.
[88] - Includes ITT1A population.
[89] - Includes ITT1B population.

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV

Number of subjects included in analysis

106

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0081 ^[90]

Method

Mixed-effect model repeated measurement

Parameter type

Least Squares (LS) Mean Difference

Point estimate

17.3

Confidence interval

level

90%

sides

2-sided

lower limit

6.61

upper limit

Variability estimate

Standard error of the mean

Dispersion value

6.47

Notes
[90] - P-value ≤ 0.01.

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV

Number of subjects included in analysis

110

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0017 ^[91]

Method

Mixed-effect model repeated measurement

Parameter type

Least Squares (LS) Mean Difference

Point estimate

20.3

Confidence interval

level

90%

sides

2-sided

lower limit

9.74

upper limit

30.79

Variability estimate

Standard error of the mean

Dispersion value

6.37

Notes
[91] - P-value ≤ 0.01

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0024 ^[92]

Method

Mixed-effect model repeated measurement

Parameter type

Least Squares (LS) Mean Difference

Point estimate

19.9

Confidence interval

level

90%

sides

2-sided

lower limit

9.22

upper limit

30.67

Variability estimate

Standard error of the mean

Dispersion value

6.49

Notes
[92] - P-value ≤ 0.01

Secondary: Sub-Study 1: Change in Short Form-36 (SF-36) - Physical Component

Top of page

End point title

Sub-Study 1: Change in Short Form-36 (SF-36) - Physical Component ^[93]

End point description

The SF-36 is an indicator of overall health status. The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health).

End point type

Secondary

End point timeframe

Baseline Through Week 12

Notes
[93] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S1P1: DB - Placebo IV	S1P1: DB - Risankizumab 600mg IV	S1P1: DB - Risankizumab 1200mg IV	S1P1: DB - Risankizumab 1800mg IV	S1P1: OL - Risankizumab 1800mg IV
Number of subjects analysed	51 ^[94]	54 ^[95]	59 ^[96]	54 ^[97]	298 ^[98]
Units: Units on a scale
least squares mean (standard error)	3.904 ± 0.8907	5.112 ± 0.8751	6.350 ± 0.8341	6.296 ± 0.8675	7.719 ± 0.3929

Notes
[94] - Includes ITT1A population.
[95] - Includes ITT1A population.
[96] - Includes ITT1A population.
[97] - Includes ITT1A population.
[98] - Includes ITT1B population.

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3315

Method

Mixed-effect model repeated measurement

Parameter type

Least Squares (LS) Mean Difference

Point estimate

1.208

Confidence interval

level

90%

sides

2-sided

lower limit

-0.8429

upper limit

3.2596

Variability estimate

Standard error of the mean

Dispersion value

1.2416

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV

Number of subjects included in analysis

110

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0451 ^[99]

Method

Mixed-effect model repeated measurement

Parameter type

Least Squares (LS) Mean Difference

Point estimate

2.447

Confidence interval

level

90%

sides

2-sided

lower limit

0.4415

upper limit

4.4519

Variability estimate

Standard error of the mean

Dispersion value

1.2137

Notes
[99] - P-value ≤ 0.05

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0543 ^[100]

Method

Mixed-effect model repeated measurement

Parameter type

Least Squares (LS) Mean Difference

Point estimate

2.392

Confidence interval

level

90%

sides

2-sided

lower limit

0.3498

upper limit

4.4352

Variability estimate

Standard error of the mean

Dispersion value

1.2364

Notes
[100] - P-value ≤ 0.1

Secondary: Sub-Study 1: Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)

Top of page

End point title

Sub-Study 1: Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) ^[101]

End point description

The FACIT-Fatigue Scale is a validated self-administered 13-item tool that measures an individual's level of fatigue during their usual daily activities over the past 7 days. Each of the fatigue and impact of fatigue items are measured on a four-point Likert scale. The FACIT Fatigue Scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better the quality of life. A positive change from baseline indicates improvement.

End point type

Secondary

End point timeframe

Baseline Through Week 12

Notes
[101] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S1P1: DB - Placebo IV	S1P1: DB - Risankizumab 600mg IV	S1P1: DB - Risankizumab 1200mg IV	S1P1: DB - Risankizumab 1800mg IV	S1P1: OL - Risankizumab 1800mg IV
Number of subjects analysed	51 ^[102]	54 ^[103]	59 ^[104]	54 ^[105]	298 ^[106]
Units: units on a scale
least squares mean (standard error)	3.7 ± 1.37	7.6 ± 1.35	9.0 ± 1.29	8.3 ± 1.33	10.7 ± 0.54

Notes
[102] - Includes ITT1A population.
[103] - Includes ITT1A population..
[104] - Includes ITT1A population.
[105] - Includes ITT1A population.
[106] - Includes ITT1B population.

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0422 ^[107]

Method

Mixed-effect model repeated measurement

Parameter type

Least Squares (LS) Mean Difference

Point estimate

3.9

Confidence interval

level

90%

sides

2-sided

lower limit

0.75

upper limit

7.06

Variability estimate

Standard error of the mean

Dispersion value

1.91

Notes
[107] - P-value ≤ 0.05

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV

Number of subjects included in analysis

110

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0049 ^[108]

Method

Mixed-effect model repeated measurement

Parameter type

Least Squares (LS) Mean Difference

Point estimate

5.3

Confidence interval

level

90%

sides

2-sided

lower limit

2.23

upper limit

8.42

Variability estimate

Standard error of the mean

Dispersion value

1.87

Notes
[108] - P-value ≤ 0.01

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0156 ^[109]

Method

Mixed-effect model repeated measurement

Parameter type

Least Squares (LS) Mean Difference

Point estimate

4.6

Confidence interval

level

90%

sides

2-sided

lower limit

1.5

upper limit

7.8

Variability estimate

Standard error of the mean

Dispersion value

1.91

Notes
[109] - P-value ≤ 0.05

Secondary: Sub-Study 1: Percentage of Participants Undergoing Ulcerative Colitis (UC)-Related Surgeries

Top of page

End point title

Sub-Study 1: Percentage of Participants Undergoing Ulcerative Colitis (UC)-Related Surgeries ^[110]

End point description

Participants who underwent surgery related to UC.

End point type

Secondary

End point timeframe

Through Week 12

Notes
[110] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S1P1: DB - Placebo IV	S1P1: DB - Risankizumab 600mg IV	S1P1: DB - Risankizumab 1200mg IV	S1P1: DB - Risankizumab 1800mg IV	S1P1: OL - Risankizumab 1800mg IV
Number of subjects analysed	60 ^[111]	61 ^[112]	61 ^[113]	58 ^[114]	340 ^[115]
Units: Participants	0	1	0	0	7

Notes
[111] - Includes ITT1A population.
[112] - Includes ITT1A population.
[113] - Includes ITT1A population.
[114] - Includes ITT1A population.
[115] - Includes ITT1B population.

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 1 ^[116]

Method

Fisher exact

Confidence interval

Notes
[116] - P-Value for comparisons between treatment groups and placebo group using Fisher's exact test.

Secondary: Sub-Study 2: Percentage of Participants Achieving Clinical Response Per Adapted Mayo Score

Top of page

End point title

Sub-Study 2: Percentage of Participants Achieving Clinical Response Per Adapted Mayo Score ^[117]

End point description

The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal) Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed) Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration) The overall Adapted Mayo Score ranges from 0 to 9 where higher scores represent more severe disease. Clinical Response is defined as a decrease from baseline in the Adapted Mayo Score ≥ 2 points and ≥ 30% from baseline, and a decrease in RBS ≥ 1 or an absolute RBS ≤ 1).

End point type

Secondary

End point timeframe

Week 12

Notes
[117] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S2P1: DB – Placebo IV	S2P1: DB Risankizumab 1200mg IV
Number of subjects analysed	325 ^[118]	650 ^[119]
Units: Participants	116	418

Notes
[118] - ITT2
[119] - ITT2

Primary Analysis

Comparison groups

S2P1: DB Risankizumab 1200mg IV v S2P1: DB – Placebo IV

Number of subjects included in analysis

975

Analysis specification

Pre-specified

Analysis type

superiority ^[120]

P-value

< 0.0001 ^[121]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

28.6

Confidence interval

level

95%

sides

2-sided

lower limit

22.3

upper limit

34.8

Notes
[120] - Between-group diff. and 95% CI calculated using Mantel-Haenszel common rate diff. (Greenland and Robins (1985)).
[121] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

Secondary: Sub-Study 2: Percentage of Participants Achieving Endoscopic Improvement

Top of page

End point title

Sub-Study 2: Percentage of Participants Achieving Endoscopic Improvement ^[122]

End point description

Endoscopic Improvement is defined as an endoscopic subscore of 0 or 1. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).

End point type

Secondary

End point timeframe

Week 12

Notes
[122] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S2P1: DB – Placebo IV	S2P1: DB Risankizumab 1200mg IV
Number of subjects analysed	325 ^[123]	650 ^[124]
Units: Participants	39	237

Notes
[123] - ITT2
[124] - ITT2

Primary Analysis

Comparison groups

S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV

Number of subjects included in analysis

975

Analysis specification

Pre-specified

Analysis type

superiority ^[125]

P-value

< 0.0001 ^[126]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

24.3

Confidence interval

level

95%

sides

2-sided

lower limit

19.3

upper limit

29.4

Notes
[125] - Between-group diff. and 95% CI calculated using Mantel-Haenszel common rate diff. (Greenland and Robins (1985)).
[126] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

Secondary: Sub-Study 2: Percentage of Participants Achieving Histologic Endoscopic Mucosal Improvement (HEMI)

Top of page

End point title

Sub-Study 2: Percentage of Participants Achieving Histologic Endoscopic Mucosal Improvement (HEMI) ^[127]

End point description

Histologic-Endoscopic Mucosal Improvement is defined as an endoscopic subscore of 0 or 1 without evidence of friability and a Geboes score ≤ 3.1. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.

End point type

Secondary

End point timeframe

Week 12

Notes
[127] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S2P1: DB – Placebo IV	S2P1: DB Risankizumab 1200mg IV
Number of subjects analysed	325 ^[128]	650 ^[129]
Units: Participants	25	159

Notes
[128] - ITT2
[129] - ITT2

Primary Analysis

Comparison groups

S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV

Number of subjects included in analysis

975

Analysis specification

Pre-specified

Analysis type

superiority ^[130]

P-value

< 0.0001 ^[131]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

16.6

Confidence interval

level

95%

sides

2-sided

lower limit

12.3

upper limit

Notes
[130] - Between-group diff. and 95% CI calculated using Mantel-Haenszel common rate diff. (Greenland and Robins (1985)).
[131] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level. Adjusted Risk Difference.

Secondary: Sub-Study 2: Percentage of Participants Achieving Endoscopic Remission

Top of page

End point title

Sub-Study 2: Percentage of Participants Achieving Endoscopic Remission ^[132]

End point description

Endoscopic remission per endoscopy subscore. Endoscopic Remission: SES-CD ≤ 4 and at least a 2-point reduction versus baseline and no subscore greater than 1 in any individual variable.

End point type

Secondary

End point timeframe

Week 12

Notes
[132] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S2P1: DB – Placebo IV	S2P1: DB Risankizumab 1200mg IV
Number of subjects analysed	325 ^[133]	650 ^[134]
Units: Participants	11	69

Notes
[133] - ITT2
[134] - ITT2

Primary Analysis

Comparison groups

S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV

Number of subjects included in analysis

975

Analysis specification

Pre-specified

Analysis type

superiority ^[135]

P-value

< 0.0001 ^[136]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

7.2

Confidence interval

level

95%

sides

2-sided

lower limit

4.2

upper limit

10.2

Notes
[135] - Between-group diff. and 95% CI calculated using Mantel-Haenszel common rate diff. (Greenland and Robins (1985)).
[136] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

Secondary: Sub-Study 2: Percentage of Participants Achieving Clinical Response Per Partial Adapted Mayo Score at Week 4

Top of page

End point title

Sub-Study 2: Percentage of Participants Achieving Clinical Response Per Partial Adapted Mayo Score at Week 4 ^[137]

End point description

Clinical response per Partial Adapted Mayo Score (without endoscopy). The Partial Mayo Score is a composite score of UC disease activity based on the following 2 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal) Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed) The overall Partial Mayo Score ranges from 0 to 6 with higher scores representing more severe disease. Clinical Response per Partial Mayo Score is defined as a decrease in Partial Adapted Mayo Score ≥ 1 points and ≥ 30% from Baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1.

End point type

Secondary

End point timeframe

Week 4

Notes
[137] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S2P1: DB – Placebo IV	S2P1: DB Risankizumab 1200mg IV
Number of subjects analysed	325 ^[138]	650 ^[139]
Units: Participants	99	339

Notes
[138] - ITT2
[139] - ITT2

Primary Analysis

Comparison groups

S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV

Number of subjects included in analysis

975

Analysis specification

Pre-specified

Analysis type

superiority ^[140]

P-value

< 0.0001 ^[141]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

21.8

Confidence interval

level

95%

sides

2-sided

lower limit

15.6

upper limit

28.1

Notes
[140] - Between-group diff. and 95% CI calculated using Mantel-Haenszel common rate diff. (Greenland and Robins (1985)).
[141] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

Secondary: Sub-Study 2: Percentage of Participants Achieving No Bowel Urgency

Top of page

End point title

Sub-Study 2: Percentage of Participants Achieving No Bowel Urgency ^[142]

End point description

Percentage of participants who reported no bowel urgency. Bowel urgency was assessed by participants in a subject diary completed once a day.

End point type

Secondary

End point timeframe

Week 12

Notes
[142] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S2P1: DB – Placebo IV	S2P1: DB Risankizumab 1200mg IV
Number of subjects analysed	325 ^[143]	650 ^[144]
Units: Participants	90	287

Notes
[143] - ITT2
[144] - ITT2

Primary Analysis

Comparison groups

S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV

Number of subjects included in analysis

975

Analysis specification

Pre-specified

Analysis type

superiority ^[145]

P-value

< 0.0001 ^[146]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

16.3

Confidence interval

level

95%

sides

2-sided

lower limit

10.3

upper limit

22.4

Notes
[145] - Between-group diff. and 95% CI calculated using Mantel-Haenszel common rate diff. (Greenland and Robins (1985)).
[146] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

Secondary: Sub-Study 2: Percentage of Participants Achieving No Abdominal Pain

Top of page

End point title

Sub-Study 2: Percentage of Participants Achieving No Abdominal Pain ^[147]

End point description

Percentage of participants who reported no abdominal pain. Abdominal pain was assessed by participants in a subject diary completed once a day.

End point type

Secondary

End point timeframe

Week 12

Notes
[147] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S2P1: DB – Placebo IV	S2P1: DB Risankizumab 1200mg IV
Number of subjects analysed	325 ^[148]	650 ^[149]
Units: Participants	86	232

Notes
[148] - ITT2
[149] - ITT2

Primary Analysis

Comparison groups

S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV

Number of subjects included in analysis

975

Analysis specification

Pre-specified

Analysis type

superiority ^[150]

P-value

= 0.0021 ^[151]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

9.3

Confidence interval

level

95%

sides

2-sided

lower limit

3.4

upper limit

15.3

Notes
[150] - Between-group diff. and 95% CI calculated using Mantel-Haenszel common rate diff. (Greenland and Robins (1985)).
[151] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

Secondary: Sub-Study 2: Percentage of Participants Achieving Histologic Endoscopic Mucosal Remission (HEMR): Endoscopy Subscore of 0 and Geboes Score < 2.0) at Week 12

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End point title

Sub-Study 2: Percentage of Participants Achieving Histologic Endoscopic Mucosal Remission (HEMR): Endoscopy Subscore of 0 and Geboes Score < 2.0) at Week 12 ^[152]

End point description

Mucosal healing defined as endoscopic and histologic remission. Mucosal healing is defined as an endoscopic score of 0 and Geboes score < 2.0. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.

End point type

Secondary

End point timeframe

Week 12

Notes
[152] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S2P1: DB – Placebo IV	S2P1: DB Risankizumab 1200mg IV
Number of subjects analysed	325 ^[153]	650 ^[154]
Units: Participants	2	41

Notes
[153] - ITT2
[154] - ITT2

Primary Analysis

Comparison groups

S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV

Number of subjects included in analysis

975

Analysis specification

Pre-specified

Analysis type

superiority ^[155]

P-value

< 0.0001 ^[156]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

5.6

Confidence interval

level

95%

sides

2-sided

lower limit

3.5

upper limit

7.7

Notes
[155] - Between-group diff. and 95% CI calculated using Mantel-Haenszel common rate diff. (Greenland and Robins (1985)).
[156] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

Secondary: Sub-Study 2: Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)

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End point title

Sub-Study 2: Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) ^[157]

End point description

End point type

Secondary

End point timeframe

Week 12

Notes
[157] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S2P1: DB – Placebo IV	S2P1: DB Risankizumab 1200mg IV
Number of subjects analysed	308 ^[158]	614 ^[159]
Units: Units on scale
least squares mean (confidence interval 95%)	3.3 (2.12 to 4.50)	7.9 (7.03 to 8.69)

Notes
[158] - ITT2
[159] - ITT2

Primary Analysis

Comparison groups

S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV

Number of subjects included in analysis

922

Analysis specification

Pre-specified

Analysis type

superiority ^[160]

P-value

< 0.0001 ^[161]

Method

ANCOVA

Parameter type

Least Squares (LS) Mean Difference

Point estimate

4.5

Confidence interval

level

95%

sides

2-sided

lower limit

3.13

upper limit

5.97

Variability estimate

Standard error of the mean

Dispersion value

0.72

Notes
[160] - Between-group diff. and 95% CI calculated using ANCOVA/MMRM with RTB-MI for continuous endpoints.
[161] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

Secondary: Sub-Study 2: Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score

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End point title

Sub-Study 2: Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score ^[162]

End point description

End point type

Secondary

End point timeframe

Baseline to Week 12

Notes
[162] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S2P1: DB – Placebo IV	S2P1: DB Risankizumab 1200mg IV
Number of subjects analysed	310 ^[163]	619 ^[164]
Units: Units on scale
least squares mean (confidence interval 95%)	24.3 (20.19 to 28.46)	42.6 (39.72 to 45.57)

Notes
[163] - ITT2
[164] - ITT2

Primary Analysis

Comparison groups

S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV

Number of subjects included in analysis

929

Analysis specification

Pre-specified

Analysis type

superiority ^[165]

P-value

< 0.0001 ^[166]

Method

ANCOVA

Parameter type

Least Squares (LS) Mean Difference

Point estimate

18.3

Confidence interval

level

95%

sides

2-sided

lower limit

13.38

upper limit

23.25

Variability estimate

Standard error of the mean

Dispersion value

2.52

Notes
[165] - Between-group diff. and 95% CI calculated using ANCOVA/MMRM with RTB-MI for continuous endpoints.
[166] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

Secondary: Sub-Study 2: Occurrence of UC-related Hospitalizations

Top of page

End point title

Sub-Study 2: Occurrence of UC-related Hospitalizations ^[167]

End point description

Participants with an UC-related event that results in admission to the hospital.

End point type

Secondary

End point timeframe

Baseline Through Week 12

Notes
[167] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S2P1: DB – Placebo IV	S2P1: DB Risankizumab 1200mg IV
Number of subjects analysed	325 ^[168]	650 ^[169]
Units: Count of participants
least squares mean (confidence interval 95%)	5.5 (3.1 to 8.0)	0.8 (0.1 to 1.4)

Notes
[168] - ITT2
[169] - ITT2

Primary Analysis

Comparison groups

S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV

Number of subjects included in analysis

975

Analysis specification

Pre-specified

Analysis type

superiority ^[170]

P-value

< 0.0001 ^[171]

Method

Chi-squared

Parameter type

Risk difference=(Risankizumab - Placebo)

Point estimate

-4.8

Confidence interval

level

95%

sides

2-sided

lower limit

-7.3

upper limit

-2.2

Notes
[170] - 95% CI for treatment differences is based on normal approximation of the binomial proportions
[171] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

Secondary: Sub-Study 2: Percentage of Participants Achieving No Nocturnal Bowel Movements

Top of page

End point title

Sub-Study 2: Percentage of Participants Achieving No Nocturnal Bowel Movements ^[172]

End point description

Percentage of participants who reported no nocturnal bowel movements.

End point type

Secondary

End point timeframe

Week 12

Notes
[172] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S2P1: DB – Placebo IV	S2P1: DB Risankizumab 1200mg IV
Number of subjects analysed	325 ^[173]	650 ^[174]
Units: Participants	140	437

Notes
[173] - ITT2
[174] - ITT2

Primary Analysis

Comparison groups

S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV

Number of subjects included in analysis

975

Analysis specification

Pre-specified

Analysis type

superiority ^[175]

P-value

< 0.0001 ^[176]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

24.2

Confidence interval

level

95%

sides

2-sided

lower limit

17.9

upper limit

30.5

Notes
[175] - Between-group diff. and 95% CI calculated using Mantel-Haenszel common rate difference. (Greenland and Robins (1985)).
[176] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

Secondary: Sub-Study 2: Percentage of Participants Achieving No Tenesmus

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End point title

Sub-Study 2: Percentage of Participants Achieving No Tenesmus ^[177]

End point description

Percentage of participants who reported no tenesmus.

End point type

Secondary

End point timeframe

Week 12

Notes
[177] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S2P1: DB – Placebo IV	S2P1: DB Risankizumab 1200mg IV
Number of subjects analysed	325 ^[178]	650 ^[179]
Units: Participants	98	317

Notes
[178] - ITT2
[179] - ITT2

Primary Analysis

Comparison groups

S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV

Number of subjects included in analysis

975

Analysis specification

Pre-specified

Analysis type

superiority ^[180]

P-value

< 0.0001 ^[181]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Risk Difference

Point estimate

18.6

Confidence interval

level

95%

sides

2-sided

lower limit

12.4

upper limit

24.8

Notes
[180] - Between-group diff. and 95% CI calculated using Mantel-Haenszel common rate diff. (Greenland and Robins (1985)).
[181] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

Secondary: Sub-Study 2: Change in Number of Fecal Incontinence Episodes Per Week

Top of page

End point title

Sub-Study 2: Change in Number of Fecal Incontinence Episodes Per Week ^[182]

End point description

Change in number of fecal incontinence episodes per week.

End point type

Secondary

End point timeframe

Baseline to Week 12

Notes
[182] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S2P1: DB – Placebo IV	S2P1: DB Risankizumab 1200mg IV
Number of subjects analysed	288	602
Units: Count of participants
least squares mean (confidence interval 95%)	-2.213 (-2.8526 to -1.5726)	-3.839 (-4.2687 to -3.4099)

Primary Analysis

Comparison groups

S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV

Number of subjects included in analysis

890

Analysis specification

Pre-specified

Analysis type

superiority ^[183]

P-value

< 0.0001 ^[184]

Method

Mixed-Effect Model Repeated Measures

Parameter type

Least Squares (LS) Mean Difference

Point estimate

-1.627

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3846

upper limit

-0.8689

Variability estimate

Standard error of the mean

Dispersion value

0.3865

Notes
[183] - Between-group diff. and 95% CI calculated using ANCOVA/MMRM with RTB-MI for continuous endpoints.
[184] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

Secondary: Sub-Study 2: Change in Number of Days Per Week With Sleep Interrupted Due to UC Symptoms

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End point title

Sub-Study 2: Change in Number of Days Per Week With Sleep Interrupted Due to UC Symptoms ^[185]

End point description

Change from baseline in number of days per week with sleep interrupted due to UC symptoms.

End point type

Secondary

End point timeframe

Baseline to Week 12

Notes
[185] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S2P1: DB – Placebo IV	S2P1: DB Risankizumab 1200mg IV
Number of subjects analysed	288 ^[186]	602 ^[187]
Units: Count of Participants
least squares mean (confidence interval 95%)	-1.505 (-1.7969 to -1.2122)	-2.485 (-2.6872 to -2.2831)

Notes
[186] - ITT2
[187] - ITT2

Primary Analysis

Comparison groups

S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV

Number of subjects included in analysis

890

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[188]

Method

Mixed-effect model repeated measurement

Parameter type

Least Squares (LS) Mean Difference

Point estimate

-0.981

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3285

upper limit

-0.6326

Variability estimate

Standard error of the mean

Dispersion value

0.1775

Notes
[188] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

Secondary: Sub-Study 1: Change From Baseline in Short Form-36 (SF-36) - Mental Component

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End point title

Sub-Study 1: Change From Baseline in Short Form-36 (SF-36) - Mental Component ^[189]

End point description

End point type

Secondary

End point timeframe

Baseline through Week 12

Notes
[189] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.

End point values	S1P1: DB - Placebo IV	S1P1: DB - Risankizumab 600mg IV	S1P1: DB - Risankizumab 1200mg IV	S1P1: DB - Risankizumab 1800mg IV	S1P1: OL - Risankizumab 1800mg IV
Number of subjects analysed	51 ^[190]	54 ^[191]	59 ^[192]	54 ^[193]	298 ^[194]
Units: Units on a scale
least squares mean (standard error)	3.094 ± 1.2533	6.756 ± 1.2319	7.284 ± 1.1739	5.442 ± 1.2185	7.777 ± 0.4777

Notes
[190] - Includes ITT1A population.
[191] - Includes ITT1A population.
[192] - Includes ITT1A population.
[193] - Includes ITT1A population.
[194] - Includes ITT1B population.

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0367 ^[195]

Method

Mixed-effect model repeated measurement

Parameter type

LS Mean of Difference

Point estimate

3.662

Confidence interval

level

90%

sides

2-sided

lower limit

0.7841

upper limit

6.5402

Notes
[195] - P-value for test of difference between each Risankizumab dose group and placebo for mean change from baseline using the mixed-effect repeated measure model The unstructured covariance structure was used to estimate within subject errors.

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV

Number of subjects included in analysis

110

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0151 ^[196]

Method

Mixed-effect model repeated measurement

Parameter type

LS Mean of Difference

Point estimate

4.19

Confidence interval

level

90%

sides

2-sided

lower limit

1.3656

upper limit

7.0144

Notes
[196] - P-value for test of difference between each Risankizumab dose group and placebo for mean change from baseline using the mixed-effect repeated measure model The unstructured covariance structure was used to estimate within subject errors.

Primary Analysis

Comparison groups

S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1795 ^[197]

Method

Mixed-effect model repeated measurement

Parameter type

LS Mean of Difference

Point estimate

2.348

Confidence interval

level

90%

sides

2-sided

lower limit

-0.5322

upper limit

5.2281

Notes
[197] - P-value for test of difference between each Risankizumab dose group and placebo for mean change from baseline using the mixed-effect repeated measure model The unstructured covariance structure was used to estimate within subject errors.

Adverse events

Top of page

Timeframe for reporting adverse events

All-cause mortality and Serious AE were reported from time of informed consent until 140 days following last dose of study drug, or the first dose of next period/study, whichever occurs first.

Adverse event reporting additional description

All other AE were reported from time of first dose until 140 days following last dose of study drug, or the first dose of next period/study, whichever occurs earlier.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

25.1

Reporting group title

SS1_P1_PlbIV

Reporting group description

Reporting group title

SS1_P1_Risa_1200mgIV

Reporting group description

Reporting group title

SS1_P1_Risa_600mgIV

Reporting group description

Reporting group title

SS1_P2_Risa_1800mgIV

Reporting group description

Reporting group title

SS1_P2_PlbIV_Risa_1800mgIV

Reporting group description

Reporting group title

SS1_P1_OL_Risa_1800mgIV

Reporting group description

Reporting group title

SS1_P1_DB_Risa_1800mgIV

Reporting group description

Reporting group title

SS1_P2_Risa_180mgSC

Reporting group description

Reporting group title

SS2_P2_PlbIV_Risa_1200mgIV

Reporting group description

Reporting group title

SS2_P1_Risa_1200mgIV

Reporting group description

Reporting group title

SS1_P2_Risa_360mgSC

Reporting group description

Reporting group title

SS2_P1_PlbIV

Reporting group description

Reporting group title

SS2_P2_Risa_180mgSC

Reporting group description

Reporting group title

SS2_P2_Risa_1200mgIV

Reporting group description

Reporting group title

SS2_P2_Risa_360mgSC

Reporting group description

SS1_P1_PlbIV

SS1_P1_Risa_1200mgIV

SS1_P1_Risa_600mgIV

SS1_P2_Risa_1800mgIV

SS1_P2_PlbIV_Risa_1800mgIV

SS1_P1_OL_Risa_1800mgIV

SS1_P1_DB_Risa_1800mgIV

SS1_P2_Risa_180mgSC

SS2_P2_PlbIV_Risa_1200mgIV

SS2_P1_Risa_1200mgIV

SS1_P2_Risa_360mgSC

SS2_P1_PlbIV

SS2_P2_Risa_180mgSC

SS2_P2_Risa_1200mgIV

SS2_P2_Risa_360mgSC

Total subjects affected by serious adverse events

subjects affected / exposed

6 / 59 (10.17%)

4 / 61 (6.56%)

6 / 62 (9.68%)

1 / 37 (2.70%)

3 / 36 (8.33%)

20 / 340 (5.88%)

3 / 58 (5.17%)

6 / 71 (8.45%)

4 / 173 (2.31%)

15 / 651 (2.30%)

7 / 70 (10.00%)

33 / 324 (10.19%)

4 / 71 (5.63%)

1 / 68 (1.47%)

1 / 70 (1.43%)

number of deaths (all causes)

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

BREAST CANCER

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

1 / 324 (0.31%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PITUITARY TUMOUR BENIGN

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

1 / 324 (0.31%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PROSTATE CANCER

subjects affected / exposed

1 / 59 (1.69%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

RENAL CANCER

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

1 / 324 (0.31%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

ARTERIAL OCCLUSIVE DISEASE

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

1 / 71 (1.41%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

DEEP VEIN THROMBOSIS

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

1 / 62 (1.61%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

1 / 651 (0.15%)

0 / 70 (0.00%)

1 / 324 (0.31%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HYPERTENSION

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

1 / 70 (1.43%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PERIPHERAL ARTERY OCCLUSION

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

1 / 71 (1.41%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

PYREXIA

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

1 / 62 (1.61%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

1 / 71 (1.41%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Immune system disorders

ANAPHYLACTIC REACTION

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

1 / 70 (1.43%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Reproductive system and breast disorders

UTERINE PROLAPSE

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

1 / 71 (1.41%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

PLEURAL EFFUSION

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

1 / 340 (0.29%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PULMONARY EMBOLISM

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

2 / 651 (0.31%)

0 / 70 (0.00%)

1 / 324 (0.31%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

RESPIRATORY DISTRESS

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

1 / 70 (1.43%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

ADJUSTMENT DISORDER

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

1 / 324 (0.31%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

GENERALISED ANXIETY DISORDER

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

1 / 324 (0.31%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

MAJOR DEPRESSION

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

1 / 651 (0.15%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SUICIDAL IDEATION

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

1 / 340 (0.29%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

HAEMOGLOBIN DECREASED

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

1 / 324 (0.31%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

ROAD TRAFFIC ACCIDENT

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

1 / 173 (0.58%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

1 / 71 (1.41%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SKELETAL INJURY

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

1 / 651 (0.15%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SKIN LACERATION

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

1 / 651 (0.15%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SUBDURAL HAEMATOMA

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

1 / 651 (0.15%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

ARTERIOSCLEROSIS CORONARY ARTERY

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

1 / 324 (0.31%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

TACHYCARDIA

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

1 / 70 (1.43%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

CEREBRAL MASS EFFECT

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

1 / 651 (0.15%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CEREBROVASCULAR ACCIDENT

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

1 / 70 (1.43%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

DIZZINESS

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

1 / 324 (0.31%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

ANAEMIA

subjects affected / exposed

0 / 59 (0.00%)

2 / 61 (3.28%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

2 / 651 (0.31%)

1 / 70 (1.43%)

2 / 324 (0.62%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 1

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Eye disorders

CATARACT

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

1 / 340 (0.29%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

ANAL FISTULA

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

2 / 324 (0.62%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

ANAL PROLAPSE

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

1 / 340 (0.29%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

COLITIS

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

1 / 62 (1.61%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

1 / 58 (1.72%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

COLITIS ULCERATIVE

subjects affected / exposed

3 / 59 (5.08%)

0 / 61 (0.00%)

1 / 62 (1.61%)

0 / 37 (0.00%)

1 / 36 (2.78%)

12 / 340 (3.53%)

0 / 58 (0.00%)

3 / 71 (4.23%)

1 / 173 (0.58%)

2 / 651 (0.31%)

2 / 70 (2.86%)

16 / 324 (4.94%)

1 / 71 (1.41%)

0 / 68 (0.00%)

1 / 70 (1.43%)

occurrences causally related to treatment / all

0 / 3

0 / 0

0 / 1

0 / 0

0 / 1

1 / 12

0 / 0

0 / 3

0 / 1

1 / 2

2 / 17

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

ENTERITIS

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

1 / 71 (1.41%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

GASTRITIS EROSIVE

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

1 / 651 (0.15%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HAEMATEMESIS

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

1 / 173 (0.58%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

NAUSEA

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

1 / 324 (0.31%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

HEPATIC CIRRHOSIS

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

1 / 324 (0.31%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin and subcutaneous tissue disorders

ERYTHEMA NODOSUM

subjects affected / exposed

1 / 59 (1.69%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PEMPHIGOID

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

1 / 36 (2.78%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

CALCULUS URINARY

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

1 / 71 (1.41%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

NEPHROLITHIASIS

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

1 / 71 (1.41%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

RENAL COLIC

subjects affected / exposed

0 / 59 (0.00%)

1 / 61 (1.64%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

RENAL FAILURE

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

1 / 340 (0.29%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

FLANK PAIN

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

1 / 340 (0.29%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

OSTEONECROSIS

subjects affected / exposed

1 / 59 (1.69%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

1 / 36 (2.78%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

1 / 651 (0.15%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

ABSCESS LIMB

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

1 / 651 (0.15%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ANAL ABSCESS

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

2 / 340 (0.59%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

APPENDICITIS

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

1 / 58 (1.72%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

1 / 324 (0.31%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CLOSTRIDIUM DIFFICILE INFECTION

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

1 / 173 (0.58%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

COVID-19

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

1 / 651 (0.15%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

1 / 68 (1.47%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

COVID-19 PNEUMONIA

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

1 / 651 (0.15%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

CYSTITIS

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

1 / 173 (0.58%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CYTOMEGALOVIRUS INFECTION

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

1 / 62 (1.61%)

0 / 37 (0.00%)

0 / 36 (0.00%)

1 / 340 (0.29%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

DEVICE RELATED SEPSIS

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

1 / 58 (1.72%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ENDOCARDITIS

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

1 / 324 (0.31%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ENTERITIS INFECTIOUS

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

1 / 324 (0.31%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ERYSIPELAS

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

1 / 36 (2.78%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

LARGE INTESTINE INFECTION

subjects affected / exposed

0 / 59 (0.00%)

1 / 61 (1.64%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

LUNG ABSCESS

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

1 / 36 (2.78%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PAROTID ABSCESS

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

1 / 324 (0.31%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PHARYNGEAL ABSCESS

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

1 / 324 (0.31%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PNEUMONIA

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

1 / 651 (0.15%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PNEUMONIA HAEMOPHILUS

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

1 / 62 (1.61%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PNEUMONIA MYCOPLASMAL

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

1 / 70 (1.43%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

POST PROCEDURAL INFECTION

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

1 / 340 (0.29%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

POSTOPERATIVE WOUND INFECTION

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

1 / 340 (0.29%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

RECTAL ABSCESS

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

1 / 340 (0.29%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SALMONELLOSIS

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

1 / 37 (2.70%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

0 / 70 (0.00%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SEPSIS

subjects affected / exposed

0 / 59 (0.00%)

0 / 61 (0.00%)

0 / 62 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 340 (0.00%)

0 / 58 (0.00%)

0 / 71 (0.00%)

0 / 173 (0.00%)

0 / 651 (0.00%)

1 / 70 (1.43%)

0 / 324 (0.00%)

0 / 71 (0.00%)

0 / 68 (0.00%)

0 / 70 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	SS1_P1_PlbIV	SS1_P1_Risa_1200mgIV	SS1_P1_Risa_600mgIV	SS1_P2_Risa_1800mgIV	SS1_P2_PlbIV_Risa_1800mgIV	SS1_P1_OL_Risa_1800mgIV	SS1_P1_DB_Risa_1800mgIV	SS1_P2_Risa_180mgSC	SS2_P2_PlbIV_Risa_1200mgIV	SS2_P1_Risa_1200mgIV	SS1_P2_Risa_360mgSC	SS2_P1_PlbIV	SS2_P2_Risa_180mgSC	SS2_P2_Risa_1200mgIV	SS2_P2_Risa_360mgSC
Total subjects affected by non serious adverse events
subjects affected / exposed	14 / 59 (23.73%)	12 / 61 (19.67%)	13 / 62 (20.97%)	6 / 37 (16.22%)	11 / 36 (30.56%)	75 / 340 (22.06%)	12 / 58 (20.69%)	4 / 71 (5.63%)	22 / 173 (12.72%)	100 / 651 (15.36%)	16 / 70 (22.86%)	63 / 324 (19.44%)	10 / 71 (14.08%)	9 / 68 (13.24%)	23 / 70 (32.86%)
Nervous system disorders
HEADACHE
subjects affected / exposed	3 / 59 (5.08%)	3 / 61 (4.92%)	2 / 62 (3.23%)	0 / 37 (0.00%)	2 / 36 (5.56%)	21 / 340 (6.18%)	4 / 58 (6.90%)	2 / 71 (2.82%)	3 / 173 (1.73%)	19 / 651 (2.92%)	5 / 70 (7.14%)	7 / 324 (2.16%)	1 / 71 (1.41%)	2 / 68 (2.94%)	6 / 70 (8.57%)
occurrences all number	4	3	2	0	2	24	5	2	3	25	5	8	1	4	6
Blood and lymphatic system disorders
ANAEMIA
subjects affected / exposed	2 / 59 (3.39%)	2 / 61 (3.28%)	0 / 62 (0.00%)	1 / 37 (2.70%)	0 / 36 (0.00%)	12 / 340 (3.53%)	1 / 58 (1.72%)	1 / 71 (1.41%)	4 / 173 (2.31%)	20 / 651 (3.07%)	1 / 70 (1.43%)	18 / 324 (5.56%)	2 / 71 (2.82%)	1 / 68 (1.47%)	6 / 70 (8.57%)
occurrences all number	2	3	0	1	0	12	1	1	4	20	1	20	2	1	6
Gastrointestinal disorders
COLITIS ULCERATIVE
subjects affected / exposed	4 / 59 (6.78%)	3 / 61 (4.92%)	1 / 62 (1.61%)	1 / 37 (2.70%)	1 / 36 (2.78%)	12 / 340 (3.53%)	1 / 58 (1.72%)	0 / 71 (0.00%)	3 / 173 (1.73%)	9 / 651 (1.38%)	3 / 70 (4.29%)	17 / 324 (5.25%)	3 / 71 (4.23%)	1 / 68 (1.47%)	0 / 70 (0.00%)
occurrences all number	5	3	1	1	1	12	1	0	3	9	3	17	3	1	0
HAEMORRHOIDS
subjects affected / exposed	3 / 59 (5.08%)	0 / 61 (0.00%)	0 / 62 (0.00%)	0 / 37 (0.00%)	1 / 36 (2.78%)	0 / 340 (0.00%)	0 / 58 (0.00%)	0 / 71 (0.00%)	0 / 173 (0.00%)	5 / 651 (0.77%)	1 / 70 (1.43%)	0 / 324 (0.00%)	1 / 71 (1.41%)	0 / 68 (0.00%)	1 / 70 (1.43%)
occurrences all number	3	0	0	0	1	0	0	0	0	6	1	0	1	0	1
Skin and subcutaneous tissue disorders
DRY SKIN
subjects affected / exposed	0 / 59 (0.00%)	0 / 61 (0.00%)	2 / 62 (3.23%)	0 / 37 (0.00%)	2 / 36 (5.56%)	4 / 340 (1.18%)	0 / 58 (0.00%)	0 / 71 (0.00%)	0 / 173 (0.00%)	3 / 651 (0.46%)	1 / 70 (1.43%)	2 / 324 (0.62%)	0 / 71 (0.00%)	0 / 68 (0.00%)	0 / 70 (0.00%)
occurrences all number	0	0	2	0	2	4	0	0	0	3	1	2	0	0	0
Infections and infestations
BRONCHITIS
subjects affected / exposed	0 / 59 (0.00%)	1 / 61 (1.64%)	4 / 62 (6.45%)	0 / 37 (0.00%)	0 / 36 (0.00%)	1 / 340 (0.29%)	0 / 58 (0.00%)	0 / 71 (0.00%)	1 / 173 (0.58%)	2 / 651 (0.31%)	0 / 70 (0.00%)	0 / 324 (0.00%)	0 / 71 (0.00%)	1 / 68 (1.47%)	1 / 70 (1.43%)
occurrences all number	0	1	4	0	0	1	0	0	1	3	0	0	0	1	1
COVID-19
subjects affected / exposed	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 62 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	1 / 340 (0.29%)	0 / 58 (0.00%)	0 / 71 (0.00%)	10 / 173 (5.78%)	30 / 651 (4.61%)	0 / 70 (0.00%)	19 / 324 (5.86%)	4 / 71 (5.63%)	4 / 68 (5.88%)	6 / 70 (8.57%)
occurrences all number	0	0	0	0	0	1	0	0	10	30	0	19	4	4	6
NASOPHARYNGITIS
subjects affected / exposed	4 / 59 (6.78%)	3 / 61 (4.92%)	5 / 62 (8.06%)	4 / 37 (10.81%)	2 / 36 (5.56%)	24 / 340 (7.06%)	5 / 58 (8.62%)	1 / 71 (1.41%)	3 / 173 (1.73%)	18 / 651 (2.76%)	6 / 70 (8.57%)	8 / 324 (2.47%)	1 / 71 (1.41%)	0 / 68 (0.00%)	4 / 70 (5.71%)
occurrences all number	5	5	5	5	2	26	6	1	3	18	6	9	1	0	4
PHARYNGITIS
subjects affected / exposed	1 / 59 (1.69%)	0 / 61 (0.00%)	1 / 62 (1.61%)	0 / 37 (0.00%)	2 / 36 (5.56%)	3 / 340 (0.88%)	0 / 58 (0.00%)	0 / 71 (0.00%)	1 / 173 (0.58%)	0 / 651 (0.00%)	1 / 70 (1.43%)	0 / 324 (0.00%)	0 / 71 (0.00%)	0 / 68 (0.00%)	0 / 70 (0.00%)
occurrences all number	1	0	1	0	2	3	0	0	1	0	1	0	0	0	0
SINUSITIS
subjects affected / exposed	0 / 59 (0.00%)	1 / 61 (1.64%)	0 / 62 (0.00%)	0 / 37 (0.00%)	2 / 36 (5.56%)	3 / 340 (0.88%)	1 / 58 (1.72%)	0 / 71 (0.00%)	0 / 173 (0.00%)	1 / 651 (0.15%)	2 / 70 (2.86%)	1 / 324 (0.31%)	0 / 71 (0.00%)	0 / 68 (0.00%)	0 / 70 (0.00%)
occurrences all number	0	1	0	0	3	3	1	0	0	1	2	1	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

18 Oct 2017

Global amendment 1 • Modified the number of days prior to each study visit needed to calculate the Subscores for Rectal Bleeding, Stool Frequency, and the Physician's Global Assessment. • Corrected typographical errors.

14 Feb 2018

Global Amendment 2 ● Added text that the subjects dosed in the Dose-analysis period will receive open-label risankizumab. ● Modify the adverse event follow-up time, duration of contraception use after last dose and time during which live or attenuated vaccines are not allowed. ● Add language to confirm that the dose and sample size will be reassessed after the completion of Sub-Study 1. ● To change the study duration up to 45 weeks. ● Correct typographical errors. ● Clarified when INR test is drawn. ● Modified the justification for the statistical methodology used for dose selection in Sub-Study 1. ● Updated Secondary Efficacy Variables, Sub-study 2. ● Modified the assumptions used for power calculation ● Corrected the study activities table.

01 Oct 2020

Global amendment 3: • Updated the Sponsor address text. • Modified Benefits and Risks text to include assessment of clinical data from Sub-study 1 (Phase 2b) of Study M16-067 and in the light of the COVID-19 pandemic. • Updated text throughout the protocol to include the dose selected based on completion of Sub-study 1. • Update study title, study population and eligibility criteria to include enrollment of non-bio-IR in Sub-study 2. • Update the number of subjects to be enrolled in Sub-study 2 and total number of subjects throughout the protocol. Update the randomization stratification factors for Sub-study 2. • Updated DMC text. • Specified the types of prohibited corticosteroids. • Clarified the types of biopsies collected during the study. • Removed the open label filler arm after Sub-study 2. • Clarified that anti-infectives used for TB prophylaxis are permissible. • Removed statistical tests for demographics and baseline characteristics. • Removed the missing imputation method LOCF and the analysis of continuous efficacy endpoint. • Changed CMH test to MN test in statistical analysis for binary endpoint. • Updated text for statistical testing procedures. • Addition of exclusion criteria to exclude subjects with active COVID-19 infection from enrollment into study. • modified study visits/protocol-specified procedures impacted by changes in local regulations due to the COVID-19 pandemic. • Clarified HIV results language throughout. • Clarifying text throughout. • Additions to the study activities table.

16 Dec 2022

Global amendment 4: • Updated Secondary Endpoints and Additional Endpoints for Sub-Study 2. • Clarified randomization stratification factors for Period 2 of Sub-Studies 1 and 2. • Clarified the safety analyses population text. • Replaced, added, edited text regarding handling of missing data in binary and in continuous endpoints. • Updated the language of baseline summary for clarity. • Updated CMH test as the primary method for binary endpoints instead of M-N test. • Advanced Therapy-IR status (yes vs no), in replacement of "number of prior failed biologics (0, 1, >1)", will be used as a stratification factor in the CMH test. • Updated multiple testing procedure language for Sub-Study 2. • Added RTB-MI analysis method for secondary efficacy endpoints. • Clarified efficacy analysis methods for secondary endpoints.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported.

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Clinical trials

Clinical Trial Results: A Multicenter, Randomized, Double-Blind, Placebo Controlled Induction Study to Evaluate the Efficacy and Safety of Risankizumab in Subjects With Moderately to Severely Active Ulcerative Colitis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Sub-Study 1: Percentage of Participants Achieving Clinical Remission Per Adapted Mayo Score

Primary: Sub-Study 1: Percentage of Participants Achieving Clinical Remission Per Adapted Mayo Score

Primary: Sub-Study 2: Percentage of Participants Achieving Clinical Remission Per Adapted Mayo Score

Primary: Sub-Study 2: Percentage of Participants Achieving Clinical Remission Per Adapted Mayo Score

Secondary: Sub-Study 1: Percentage of Participants Achieving Endoscopic Improvement

Secondary: Sub-Study 1: Percentage of Participants Achieving Endoscopic Improvement

Secondary: Sub-Study 1: Percentage of Participants Achieving Clinical Remission Per Full Mayo Score in Participants With a FullMayo Score of 6 to 12 at Baseline

Secondary: Sub-Study 1: Percentage of Participants Achieving Clinical Remission Per Full Mayo Score in Participants With a FullMayo Score of 6 to 12 at Baseline

Secondary: Sub-Study 1: Percentage of Participants Achieving Clinical Response Per Adapted Mayo Score

Secondary: Sub-Study 1: Percentage of Participants Achieving Clinical Response Per Adapted Mayo Score

Secondary: Sub-Study 1: Percentage of Participants Achieving Clinical Response Per Partial Adapted Mayo Score

Secondary: Sub-Study 1: Percentage of Participants Achieving Clinical Response Per Partial Adapted Mayo Score

Secondary: Sub-Study 1: Percentage of Participants Achieving Endoscopic Remission

Secondary: Sub-Study 1: Percentage of Participants Achieving Endoscopic Remission

Secondary: Sub-Study 1: Percentage of Participants With Hospitalization

Secondary: Sub-Study 1: Percentage of Participants With Hospitalization

Secondary: Sub-Study 1: Percentage of Participants Achieving Histologic Endoscopic Mucosal Remission (HEMR)

Secondary: Sub-Study 1: Percentage of Participants Achieving Histologic Endoscopic Mucosal Remission (HEMR)

Secondary: Sub-Study 1: Change in Ulcerative Colitis Symptom Questionnaire (UC-SQ)

Secondary: Sub-Study 1: Change in Ulcerative Colitis Symptom Questionnaire (UC-SQ)

Secondary: Sub-Study 1: Change in Inflammatory Bowel Disease Questionnaire (IBDQ)

Secondary: Sub-Study 1: Change in Inflammatory Bowel Disease Questionnaire (IBDQ)

Secondary: Sub-Study 1: Change in Short Form-36 (SF-36) - Physical Component

Secondary: Sub-Study 1: Change in Short Form-36 (SF-36) - Physical Component

Secondary: Sub-Study 1: Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)

Secondary: Sub-Study 1: Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)

Secondary: Sub-Study 1: Percentage of Participants Undergoing Ulcerative Colitis (UC)-Related Surgeries

Secondary: Sub-Study 1: Percentage of Participants Undergoing Ulcerative Colitis (UC)-Related Surgeries

Secondary: Sub-Study 2: Percentage of Participants Achieving Clinical Response Per Adapted Mayo Score

Secondary: Sub-Study 2: Percentage of Participants Achieving Clinical Response Per Adapted Mayo Score

Secondary: Sub-Study 2: Percentage of Participants Achieving Endoscopic Improvement

Secondary: Sub-Study 2: Percentage of Participants Achieving Endoscopic Improvement

Secondary: Sub-Study 2: Percentage of Participants Achieving Histologic Endoscopic Mucosal Improvement (HEMI)

Secondary: Sub-Study 2: Percentage of Participants Achieving Histologic Endoscopic Mucosal Improvement (HEMI)

Secondary: Sub-Study 2: Percentage of Participants Achieving Endoscopic Remission

Secondary: Sub-Study 2: Percentage of Participants Achieving Endoscopic Remission

Secondary: Sub-Study 2: Percentage of Participants Achieving Clinical Response Per Partial Adapted Mayo Score at Week 4

Secondary: Sub-Study 2: Percentage of Participants Achieving Clinical Response Per Partial Adapted Mayo Score at Week 4

Secondary: Sub-Study 2: Percentage of Participants Achieving No Bowel Urgency

Secondary: Sub-Study 2: Percentage of Participants Achieving No Bowel Urgency

Secondary: Sub-Study 2: Percentage of Participants Achieving No Abdominal Pain

Secondary: Sub-Study 2: Percentage of Participants Achieving No Abdominal Pain

Secondary: Sub-Study 2: Percentage of Participants Achieving Histologic Endoscopic Mucosal Remission (HEMR): Endoscopy Subscore of 0 and Geboes Score < 2.0) at Week 12

Secondary: Sub-Study 2: Percentage of Participants Achieving Histologic Endoscopic Mucosal Remission (HEMR): Endoscopy Subscore of 0 and Geboes Score < 2.0) at Week 12

Secondary: Sub-Study 2: Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)

Secondary: Sub-Study 2: Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)

Secondary: Sub-Study 2: Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score

Secondary: Sub-Study 2: Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score

Secondary: Sub-Study 2: Occurrence of UC-related Hospitalizations

Secondary: Sub-Study 2: Occurrence of UC-related Hospitalizations

Secondary: Sub-Study 2: Percentage of Participants Achieving No Nocturnal Bowel Movements

Secondary: Sub-Study 2: Percentage of Participants Achieving No Nocturnal Bowel Movements

Secondary: Sub-Study 2: Percentage of Participants Achieving No Tenesmus

Secondary: Sub-Study 2: Percentage of Participants Achieving No Tenesmus

Secondary: Sub-Study 2: Change in Number of Fecal Incontinence Episodes Per Week

Secondary: Sub-Study 2: Change in Number of Fecal Incontinence Episodes Per Week

Secondary: Sub-Study 2: Change in Number of Days Per Week With Sleep Interrupted Due to UC Symptoms

Secondary: Sub-Study 2: Change in Number of Days Per Week With Sleep Interrupted Due to UC Symptoms

Secondary: Sub-Study 1: Change From Baseline in Short Form-36 (SF-36) - Mental Component

Secondary: Sub-Study 1: Change From Baseline in Short Form-36 (SF-36) - Mental Component

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Multicenter, Randomized, Double-Blind, Placebo Controlled Induction Study to Evaluate the Efficacy and Safety of Risankizumab in Subjects With Moderately to Severely Active Ulcerative Colitis