A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of UTTR1147A Compared With Placebo and With Vedolizumab in Participants With Moderate to Severe Ulcerative Colitis (UC)

Study Overview
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Brief Summary
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This study is designed to evaluate the efficacy, safety, and pharmacokinetics of UTTR1147A compared with vedolizumab and with placebo in the treatment of participants with moderate to severe UC. This study will consist of two parts, Part A and Part B. Part A will test the induction of clinical remission and Part B will test the durability of clinical remission.

Official Title
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A Phase II, Randomized, Parallel-Group, Double-Blind, Double-Dummy, Placebo-Controlled, Multicenter Study To Evaluate the Efficacy, Safety, and Pharmacokinetics of UTTR1147A Compared With Placebo and Compared With Vedolizumab in Patients With Moderate to Severe Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: UTTR1147A
* Drug: UTTR1147A Placebo
* Drug: Vedolizumab
* Drug: Vedolizumab Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of UC Confirmation of moderately to severely active UC, defined by the Mayo Clinic Score Inadequate response, loss of response, or intolerance to prior immunosuppressant treatment (i.e., azathioprine, 6-mercaptopurine, methotrexate, or tumor necrosis factor [TNF] inhibitors [maximum of 2 prior TNF inhibitors]) and/or corticosteroid treatment Use of highly effective contraception as defined by the protocol Exclusion Criteria: History of psoriasis or psoriatic arthritis; any other inflammatory skin disorders requiring oral corticosteroids, immunosuppressants, or biological therapy within the previous year; or primary sclerosing cholangitis History of cancer as defined by the protocol Significant uncontrolled comorbidity, such as cardiac, pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders (excluding UC) Prior extensive colonic resection, subtotal or total colectomy, or proctocolectomy, or planned surgery for UC Diagnosis of indeterminate colitis or granulomatous (Crohn's) colitis or toxic megacolon within 12 months prior to screening Suspicion of ischemic colitis, radiation colitis, or microscopic colitis Current fistula or history of fistula, pericolonic abscess and stricture (stenosis) of the colon History or current evidence of unresectable colonic mucosal dysplasia or history of high-grade colonic mucosal dysplasia Prior treatment with UTTR1147A Prior treatment with vedolizumab, etrolizumab, natalizumab, efalizumab, or any other anti-integrin agents Prior treatment with rituximab Use of prohibited therapies, as defined by the protocol, prior to randomization Congenital or acquired immune deficiency Evidence or treatment of infections or history of infections, as defined by the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1a: UTTR1147A Dose Level 1 (Part A) + UTTR1147A (Part B)<br>Part A: UTTR1147A dose level 1 and Vedolizumab Placebo. Part B: UTTR1147A maintenance dose and Vedolizumab Placebo. | Drug: UTTR1147A<br>* UTTR1147A will be administered intravenously (IV) at dose levels 1, 2, or 3 in Part A, and at the maintenance dose level in Part B, per the respective arm descriptions.<br>* Other names: IL-22Fc;Drug: Vedolizumab Placebo<br>* The matching placebo to vedolizumab (Vedolizumab Placebo) will be administered IV.<br>|
| Experimental: Arm 1b: UTTR1147A Dose Level 1 (Part A) + Placebo (Part B)<br>Part A: UTTR1147A dose level 1 and Vedolizumab Placebo. Part B: UTTR1147A Placebo and Vedolizumab Placebo. | Drug: UTTR1147A<br>* UTTR1147A will be administered intravenously (IV) at dose levels 1, 2, or 3 in Part A, and at the maintenance dose level in Part B, per the respective arm descriptions.<br>* Other names: IL-22Fc;Drug: UTTR1147A Placebo<br>* The matching placebo to UTTR1147A (UTTR1147A Placebo) will be administered IV.<br>Drug: Vedolizumab Placebo<br>* The matching placebo to vedolizumab (Vedolizumab Placebo) will be administered IV.<br>|
| Experimental: Arm 2a: UTTR1147A Dose Level 2 (Part A) + UTTR1147A (Part B)<br>Part A: UTTR1147A dose level 2 and Vedolizumab Placebo. Part B: UTTR1147A maintenance dose and Vedolizumab Placebo. | Drug: UTTR1147A<br>* UTTR1147A will be administered intravenously (IV) at dose levels 1, 2, or 3 in Part A, and at the maintenance dose level in Part B, per the respective arm descriptions.<br>* Other names: IL-22Fc;Drug: Vedolizumab Placebo<br>* The matching placebo to vedolizumab (Vedolizumab Placebo) will be administered IV.<br>|
| Experimental: Arm 2b: UTTR1147A Dose Level 2 (Part A) + Placebo (Part B)<br>Part A: UTTR1147A dose level 2 and Vedolizumab Placebo. Part B: UTTR1147A Placebo and Vedolizumab Placebo. | Drug: UTTR1147A<br>* UTTR1147A will be administered intravenously (IV) at dose levels 1, 2, or 3 in Part A, and at the maintenance dose level in Part B, per the respective arm descriptions.<br>* Other names: IL-22Fc;Drug: UTTR1147A Placebo<br>* The matching placebo to UTTR1147A (UTTR1147A Placebo) will be administered IV.<br>Drug: Vedolizumab Placebo<br>* The matching placebo to vedolizumab (Vedolizumab Placebo) will be administered IV.<br>|
| Experimental: Arm 3a: UTTR1147A Dose Level 3 (Part A) + UTTR1147A (Part B)<br>Part A: UTTR1147A dose level 3 and Vedolizumab Placebo. Part B: UTTR1147A maintenance dose and Vedolizumab Placebo. | Drug: UTTR1147A<br>* UTTR1147A will be administered intravenously (IV) at dose levels 1, 2, or 3 in Part A, and at the maintenance dose level in Part B, per the respective arm descriptions.<br>* Other names: IL-22Fc;Drug: Vedolizumab Placebo<br>* The matching placebo to vedolizumab (Vedolizumab Placebo) will be administered IV.<br>|
| Experimental: Arm 3b: UTTR1147A Dose Level 3 (Part A) + Placebo (Part B)<br>Part A: UTTR1147A dose level 3 and Vedolizumab Placebo. Part B: UTTR1147A Placebo and Vedolizumab Placebo. | Drug: UTTR1147A<br>* UTTR1147A will be administered intravenously (IV) at dose levels 1, 2, or 3 in Part A, and at the maintenance dose level in Part B, per the respective arm descriptions.<br>* Other names: IL-22Fc;Drug: UTTR1147A Placebo<br>* The matching placebo to UTTR1147A (UTTR1147A Placebo) will be administered IV.<br>Drug: Vedolizumab Placebo<br>* The matching placebo to vedolizumab (Vedolizumab Placebo) will be administered IV.<br>|
| Active Comparator: Arm 4: Vedolizumab<br>Parts A and B: Vedolizumab and UTTR1147A Placebo. | Drug: UTTR1147A Placebo<br>* The matching placebo to UTTR1147A (UTTR1147A Placebo) will be administered IV.<br>Drug: Vedolizumab<br>* Vedolizumab will be administered IV, as specified in the prescribing information.<br>* Other names: Entyvio;|
| Placebo Comparator: Arm 5: Placebo<br>Parts A and B: UTTR1147A Placebo and Vedolizumab Placebo. | Drug: UTTR1147A Placebo<br>* The matching placebo to UTTR1147A (UTTR1147A Placebo) will be administered IV.<br>Drug: Vedolizumab Placebo<br>* The matching placebo to vedolizumab (Vedolizumab Placebo) will be administered IV.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinical Remission at Week 8 | Clinical remission is defined as modified Mayo Clinic Score (mMCS) <= 2 with Mayo rectal bleeding subscore = 0, Mayo stool frequency subscore <=1 and Centrally read endoscopic score <= 1. Patients were classified as Non-Remitters if Week 8 assessments were missing or patient received permitted/ prohibited Rescue Therapy prior to assessment. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Remission | Sustained remission is defined as clinical remission at both Week 8 and Week 30, where clinical remission is defined as modified Mayo Clinic Score (mMCS) <= 2 with Mayo rectal bleeding subscore = 0, Mayo stool frequency subscore <=1 and Centrally read endoscopic score <= 1. Patients were classified as Non-Remitters at Week 8 or at Week 30 if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment | At Weeks 8 and 30 | 
| Maximum Serum Concentration (Cmax) of UTTR1147A |  | Days 1 - 29, Visit: Day 57 | 
| Minimum Serum Concentration (Cmin) of UTTR1147A |  | Days 1 - 29, Visit: Day 57 | 
| Percentage of Participants With Clinical Response at Week 8 | Clinical response is defined as achieving clinical remission or as meeting both of the following criteria: A >= 3-point decrease from baseline in modified Mayo Clinic Score (mMCS); A >= 1-point decrease from baseline in rectal bleeding subscore or a rectal bleeding subscore of 0 or 1. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment. NOTE: An Outcome Measure Description has not been entered. | At Week 8 | 
| Percentage of Participants With Clinical Response at Week 30 | Clinical response is defined as achieving clinical remission or as meeting both of the following criteria: A >= 3-point decrease from baseline in modified Mayo Clinic Score (mMCS); A >= 1-point decrease from baseline in rectal bleeding subscore or a rectal bleeding subscore of 0 or 1. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment. | At Week 30 | 
| Percentage of Participants With Endoscopic Healing at Week 8 | Endoscopic healing is defined as a Mayo endoscopic subscore <= 1. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment. | At Week 8 | 
| Percentage of Participants With Endoscopic Healing at Week 30 | Endoscopic healing is defined as a Mayo endoscopic subscore <= 1. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment. | At Week 30 | 
| Percentage of Participants With Endoscopic Remission at Week 8 | Endoscopic remission is defined as a Mayo endoscopic subscore of 0. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment. | At Week 8 | 
| Percentage of Participants With Endoscopic Remission at Week 30 | Endoscopic remission is defined as a Mayo endoscopic subscore of 0. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment. | At Week 30 | 
| Change From Baseline in UC Bowel Movement Signs and Symptoms at Week 8, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The bowel domain score ranges from 0-27, with a higher score indicating a worse disease state. | At Week 8 | 
| Change From Baseline in UC Bowel Movement Signs and Symptoms at Week 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The bowel domain score ranges from 0-27, with a higher score indicating a worse disease state. | At Week 30 | 
| Change From Baseline in UC Abdominal Signs and Symptoms at Week 8, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The functional (abdominal symptoms) domain score ranges from 0-12, with a higher score indicating a worse disease state. | At Week 8 | 
| Change From Baseline in UC Abdominal Signs and Symptoms at Week 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The functional (abdominal symptoms) domain score ranges from 0-12, with a higher score indicating a worse disease state. | At Week 30 | 
| Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 8 | The IBDQ score is a Total Score summed up from across all 32 questions on the questionnaire. The Total Score range is from 32 to 224 with higher scores representing a better quality of life. | At Week 8 | 
| Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 30 | The IBDQ score is a Total Score summed up from across all 32 questions on the questionnaire. The Total Score range is from 32 to 224 with higher scores representing a better quality of life. | At Week 30 | 
| Percentage of Participants With Adverse Events |  | Up to 30 weeks | 
| Percentage of Participants With Presence of Anti-Drug Antibodies (ADA) at Baseline and After Drug Administration |  | Baseline up to 30 |