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)

Genentech, Inc.195 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

195

Conditions

Ulcerative Colitis

Interventions

UTTR1147ADRUG

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.

UTTR1147A PlaceboDRUG

The matching placebo to UTTR1147A (UTTR1147A Placebo) will be administered IV.

VedolizumabDRUG

Vedolizumab will be administered IV, as specified in the prescribing information.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Locations (72)

Outcomes

Primary Outcomes

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.

Time frame: 8 weeks

Secondary Outcomes

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

Time frame: At Weeks 8 and 30

Maximum Serum Concentration (Cmax) of UTTR1147A

Time frame: Days 1 - 29, Visit: Day 57

Minimum Serum Concentration (Cmin) of UTTR1147A

Time frame: 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.

Time frame: At Week 8

Percentage of Participants With Clinical Response at Week 30

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

The matching placebo to vedolizumab (Vedolizumab Placebo) will be administered IV.

Carolina Digestive Diseases

Greenville, North Carolina, United States

University of Utah School of Medicine; Gastroenterology Division

Salt Lake City, Utah, United States

MHAT Saint Karidad EAD

Plovdiv, Bulgaria

Multiprofile Hospital for Active Treatment Hadji Dimitar OOD

Sliven, Bulgaria

LLC ARENSIA Exploratory Medicine

Tbilisi, Georgia

Gastroenterologische Spezialpraxis-Berlin-Karlshorst

Berlin, Germany

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, Germany

St. Marien Krankenhaus; Med. Klinik

Ludwigshafen, Germany

Universitatsklinikum Schleswig-Holstein

Lübeck, Germany

Universitätsklinikum Ulm; Klinik für Innere Medizin II

Ulm, Germany

...and 62 more locations

Time frame: 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.

Time frame: At Week 8

Percentage of Participants With Endoscopic Healing at Week 30

Time frame: 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.

Time frame: At Week 8

Percentage of Participants With Endoscopic Remission at Week 30

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: At Week 30

Percentage of Participants With Adverse Events

Time frame: Up to 30 weeks

Percentage of Participants With Presence of Anti-Drug Antibodies (ADA) at Baseline and After Drug Administration

Time frame: Baseline up to 30