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

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.

For Sub-Study 1, clinical remission was defined as SFS ≤ 1, and not greater than baseline, RBS of 0, and endoscopic subscore ≤ 1.

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.

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.

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).

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.

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 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.

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.

Endoscopic remission was defined as endoscopy subscore of 0.

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

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.

The US-SQ is a patient questionnaire to assess severity of Ulcerative Colitis (UC) related gastrointestinal symptoms (e.g., frequent bowel movements, abdominal pain, cramping) and non-gastrointestinal symptoms (e.g., joint pain and sleep difficulties).

It consists of 17 questions and each question is answered on a scale from can be answered on a scale from 1 (Not at all/ never) to 5 (Very much/Always) with overall symptom score range from 17 to 85. A lower score indicates lower UC severity.

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.

The SF-36 (Version 2) is a self-administered, health-related survey that measures the impact of disease on overall quality of life during the past 4 weeks. SF-36 consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and 2 component scores (mental [MCS] and physical [PCS]). MCS consisted of social functioning, vitality, mental health, and role-emotional scales. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. Each domain is scored by summing the individual items and transforming the scores into a 0 (poorest health) to 100 (best health) scale with higher scores indicating better health status or functioning.

The SF-36 (Version 2) is a self-administered, health-related survey that measures the impact of disease on overall quality of life during the past 4 weeks. SF-36 consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and 2 component scores (mental [MCS] and physical [PCS]). MCS consisted of social functioning, vitality, mental health, and role-emotional scales. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. Each domain is scored by summing the individual items and transforming the scores into a 0 (poorest health) to 100 (best health) scale with higher scores indicating better health status or functioning.

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.

0 = not at all

• = a little bit
• = somewhat
• = quite a bit
• = very much

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.

Participants who underwent surgery related to UC.

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).

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).

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.

Endoscopic remission per endoscopy subscore.

Endoscopic Remission: endoscopic subscore = 0.

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.

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

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

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.

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.

0 = not at all

• = a little bit
• = somewhat
• = quite a bit
• = very much

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.

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.

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

Percentage of participants who reported no nocturnal bowel movements.

Percentage of participants who reported no tenesmus.

Change in number of fecal incontinence episodes per week.

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