Study of GS-1427 in Participants With Moderately to Severely Active Ulcerative Colitis

Phase 2Active Not RecruitingNCT06290934

Gilead Sciences228 enrolled

Overview

The goal of this study is to learn if GS-1427 is effective in treating participants with moderate to severe ulcerative colitis. The study will compare participants in different treatment groups treated with GS-1427 with participants treated with placebo. The primary objective of this study is to assess the efficacy of GS-1427, compared with placebo control, in achieving clinical response at Week 12.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

228

Conditions

Ulcerative Colitis

Interventions

GS-1427DRUG

Administered orally

Placebo-to-match GS-1427DRUG

Administered orally

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Individuals have Ulcerative Colitis (UC) with symptoms of at least 90 days duration before randomization, with the diagnosis confirmed by endoscopy and histology at any time prior to randomization. Documentation of endoscopy and histology consistent with the diagnosis of UC must be available in the source documents. * Individuals have UC with minimum disease extent of 15 cm from the anal verge. * Individuals have moderately to severely active UC as determined by endoscopy occurring during screening with a total modified Mayo Clinic Score (mMCS) of 5 to 9 points, including a centrally read endoscopic subscore of at least 2. * Individuals have an inadequate response or loss of response or are intolerant to at least 1 of the following UC treatments: corticosteroids, immunomodulators, or advanced therapy. * Individuals have an inadequate response or loss of response or are intolerant to \< 3 AT mechanisms of action for UC (use of 2 or more AT with the same mechanism of action, eg, 2 TNF-α inhibitors, counts as 1 mechanism of action) Key Exclusion Criteria: * Have a current diagnosis of Crohn's Disease (CD) or clinical findings suggestive of CD, diagnosis of indeterminate colitis due to etiologies such as an enteric pathogen, or lymphocytic or collagenous colitis. * Have a current diagnosis of toxic megacolon, symptomatic colonic stricture, acute severe colitis, fulminant colitis, or abdominal abscess at screening or randomization. * Have any history of exposure to vedolizumab or other integrin antagonists * Requirement for ongoing therapy with or use of any prohibited medication as specified in the protocol Note: Other protocol defined Inclusion/Exclusion criteria may apply

Locations (182)

Outcomes

Primary Outcomes

Proportion of Participants Achieving Clinical Response at Week 12

Clinical response is defined as a decrease from baseline in the modified Mayo Clinic Score (mMCS) of ≥ 2 points and at least a 30% reduction from baseline, and a decrease in rectal bleeding subscore of ≥ 1 from baseline or an absolute rectal bleeding subscore of 0 or 1. The mMCS is a scoring system for assessment of Ulcerative Colitis (UC) activity and is composed of subscores from endoscopy (range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease (spontaneous bleeding, ulceration)), rectal bleeding (range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes), and stool frequency (range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 or more stools more than normal). Total score for mMCS ranges from 0 to 9 (sum of all subscores), with higher scores indicating higher disease activity.

Time frame: Week 12

Secondary Outcomes

Incidence of Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Deaths.

Time frame: First dose date up to 76 weeks plus 28 days

Incidence of Treatment-emergent Lab Abnormalities

Time frame: First dose date up to 76 weeks plus 28 days

Proportion of Participants Achieving Clinical Remission at Week 12

Clinical remission is defined as a mMCS of ≤ 2, including a stool frequency subscore (SFS) ≤ 1 and not greater than baseline, rectal bleeding subscore of 0, and centrally read endoscopic subscore ≤ 1 (score of 1 modified to exclude friability).The mMCS is a scoring system for assessment of UC activity and is composed of subscores from endoscopy (range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease (spontaneous bleeding, ulceration)), rectal bleeding (range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes), and stool frequency (range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 or more stools more than normal). Total score for mMCS ranges from 0 to 9 (sum of all subscores), with higher scores indicating higher disease activity.

Data from ClinicalTrials.gov

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Onyx Clinical Research (Clinic Location)

Peoria, Arizona, United States

Om Research LLC

Camarillo, California, United States

VVCRD Research

Garden Grove, California, United States

310 Clinical Research

Inglewood, California, United States

US San Diego Health System

La Jolla, California, United States

Om Research LLC

Lancaster, California, United States

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

University Of California, Davis

Sacramento, California, United States

SDG Clinical Research, LLC

San Diego, California, United States

Acclaim Clinical Research

San Diego, California, United States

...and 172 more locations

Proportion of Participants Achieving Clinical Remission at Week 52

Clinical remission is defined as a mMCS of ≤ 2, including a stool frequency subscore (SFS) ≤ 1 and not greater than baseline, rectal bleeding subscore of 0, and centrally read endoscopic subscore ≤ 1 (score of 1 modified to exclude friability). The mMCS is a scoring system for assessment of UC activity and is composed of subscores from endoscopy (range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease (spontaneous bleeding, ulceration)), rectal bleeding (range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes), and stool frequency (range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 or more stools more than normal). Total score for mMCS ranges from 0 to 9 (sum of all subscores), with higher scores indicating higher disease activity.

Time frame: Week 52

Proportion of Participants Achieving Histologic-endoscopic Mucosal Improvement at Week 12

Histologic-endoscopic mucosal improvement is a composite endpoint that uses different units of measure for histologic and endoscopic activities.Histologic activity is measured by the Geboes score with 6 grades:0,structural change(sub-grade:0.0-0.3);1,chronic inflammatory infiltrate(sub-grade:1.0-1.3);2,lamina propria neutrophils \& eosinophils(sub-grade:2A.0-2B.3);3,neutrophils in epithelium(sub-grade:3.0-3.3);4,crypt destruction(sub-grade:4.0-4.3); and 5,erosion or ulceration(sub-grade:5.0-5.4);final score range 0.0-5.4;higher scores indicate more severe inflammation.Endoscopic activity is measured by the Mayo Clinic Score Endoscopic subscores(range 0-3):0,normal or inactive disease;1,mild disease(erythema,decreased vascular pattern);2,moderate disease(marked erythema,lack of vascular pattern,friability,erosions), and 3,severe disease(spontaneous bleeding,ulceration).Histologic-endoscopic mucosal improvement is defined as achieving both Geboes score ≤ 3.1 and endoscopic subscore ≤ 1

Time frame: Week 12

Proportion of Participants Achieving Mucosal Healing at Week 12

Mucosal healing is a composite endpoint that uses different units of measure for histologic and endoscopic activities. Histologic activity is measured by the Geboes score with 6 grades:0,structural change(sub-grade:0.0-0.3);1,chronic inflammatory infiltrate(sub-grade:1.0-1.3);2,lamina propria neutrophils \& eosinophils(sub-grade:2A.0-2B.3);3,neutrophils in epithelium(sub-grade:3.0-3.3);4,crypt destruction(sub-grade:4.0-4.3); and 5,erosion or ulceration(sub-grade:5.0-5.4);final score range 0.0-5.4;higher scores indicate more severe inflammation.Endoscopic activity is measured by the Mayo Clinic Score Endoscopic subscores(range 0-3):0,normal or inactive disease;1,mild disease(erythema,decreased vascular pattern);2,moderate disease(marked erythema,lack of vascular pattern,friability,erosions), and 3,severe disease(spontaneous bleeding,ulceration).Mucosal healing is defined as achieving both Geboes score ≤ 2B.1 and endoscopic subscore ≤ 1.

Time frame: Week 12

Proportion of Participants Achieving Endoscopic Improvement at Week 12

Endoscopic improvement is defined as an endoscopic subscore of ≤ 1. Endoscopic subscore is a part of the modified Mayo Clinic Score which is a scoring system for assessment of UC activity. Endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease, 1 = mild disease (erythema, decreased vascular pattern), 2 = moderate disease (marked erythema, lack of vascular pattern, friability, erosions), and 3 = severe disease (spontaneous bleeding, ulceration).

Time frame: Week 12

To Assess the Efficacy of GS-1427 in Achieving Partial Modified Mayo Clinic Score (mMCS) remission at Week 76

Time frame: Week 76