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

Ulcerative Colitis Clinical Trial

— SWIFT  

Official title:

A Multicenter, Randomized, Double-blind, 2-Part Phase 2 Study to Evaluate the Efficacy and Safety of GS-1427 in Adult Participants With Moderately to Severely Active Ulcerative Colitis (UC) Part 1: Placebo-Controlled, Dose-Ranging Study of GS-1427; Part 2: Active-Controlled, Combination Study Evaluating the Efficacy and Safety of GS-1427 in Combination With Ustekinumab Versus GS-1427 or Ustekinumab Monotherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06290934
• Other study ID #: GS-US-409-5704
• Secondary ID: 2023-508304-38
• Status: Recruiting
• Phase: Phase 2
• Start date: March 27, 2024
• Est. completion date: March 2028

Study information

• Verified date: April 2024
• Source: Gilead Sciences
• Contact: Gilead Clinical Study Information Center
• Phone: 1-833-445-3230 (GILEAD-0)
• Email: GileadClinicalTrials[@]gilead.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this study is to learn if GS-1427 is effective and safe 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 (Part 1), and participants treated with GS-1427 or ustekinumab alone with participants treated with GS-1427 in combination with ustekinumab (Part 2). The primary objectives of this study are: Part 1: To assess the efficacy of GS-1427, compared with placebo control, in achieving clinical response at Week 12 Part 2: To assess the efficacy of combination therapy with GS-1427 and ustekinumab, compared with GS-1427 and ustekinumab monotherapies, in achieving clinical response at Week 12

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 423
• Est. completion date: March 2028
• Est. primary completion date: May 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Key Inclusion Criteria:

• Individuals have Ulcerative Colitis (UC) of at least 90-days duration before randomization confirmed by endoscopy and histology at any time in the past. 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 is intolerant to at least 1 of the following conventional UC treatments
• Individuals have an inadequate response or loss of response or are intolerant to:
• At least one of these conventional UC treatments: Corticosteroids, azathioprine or 6-mercaptopurine (6-MP) OR
• No more than two advanced therapies: Tumor necrosis factor-alpha inhibitors, interleukin (IL)-12/23 inhibitors (Part 1 only; no prior use in Part 2), sphingosine 1-phosphate receptor modulators, and Janus kinase inhibitors

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.
• Part 1 and 2; have any history of exposure to vedolizumab
• Part 2 only: have any history of exposure to interleukin - 12/23 or 23 inhibitor (eg ustekinumab)
• 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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• GS-1427
Administered orally
• Ustekinumab
Administered intravenously and subcutaneously
• Placebo-to-match GS-1427
Administered orally

Locations

Country	Name	City	State
United States	Om Research LLC	Camarillo	California
United States	Clinical Research Institute of Michigan, LLC.	Chesterfield	Michigan
United States	VVCRD Research	Garden Grove	California
United States	Encore Medical Research. LLC	Hollywood	Florida
United States	Southwest Clinical Trials	Houston	Texas
United States	Om Research LLC	Lancaster	California
United States	United Medical Doctors	Murrieta	California
United States	Quality Medical Research	Nashville	Tennessee
United States	Southern Star Research Institute, LLC.	San Antonio	Texas
United States	Tyler Research Institute, LLC.	Tyler	Texas
United States	Encore Medical Research of Weston, LLC	Weston	Florida
United States	Gastroenterology Associates of Western Michigan, PLC d.b.a. West Michigan Clinical Research Center.	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Parts 1 and 2: 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.	Week 12
Secondary	Part 2: Proportion of Participants Achieving Clinical Response at Week 24	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 modified Mayo Clinic Score ranges from 0 to 9 (sum of all subscores), with higher scores indicating higher disease activity.	Week 24
Secondary	Parts 1 and 2: Incidence of Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Deaths.		First dose date up to 52 weeks plus 28 days
Secondary	Parts 1 and 2: Incidence of Treatment-emergent Lab Abnormalities		First dose date up to 52 weeks plus 28 days
Secondary	Parts 1 and 2: 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.	Week 12
Secondary	Part 1: 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.	Week 52
Secondary	Part 2: Proportion of Participants Achieving Clinical Remission at Week 24	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.	Week 24
Secondary	Part 2: Proportion of Participants Achieving Partial Modified Mayo Score Remission at Week 52	Partial modified Mayo score remission is defined as a SFS of = 1 and rectal bleeding subscore of 0. The SFS ranges from 0 to 3, with 0 = normal number of stools and 3 = at least 5 or more stools more than normal. The rectal bleeding subscore ranges from 0 to 3, where 0 = no blood seen and 3 = blood alone passes. Higher scores indicate higher disease activity.	Week 52
Secondary	Parts 1 and 2: 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	Week 12
Secondary	Part 2: Proportion of Participants Achieving Histologic-endoscopic Mucosal Improvement at Week 24	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	Week 24
Secondary	Parts 1 and 2: 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.	Week 12
Secondary	Part 2: Proportion of Participants Achieving Mucosal Healing at Week 24	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.	Week 24
Secondary	Parts 1 and 2: 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).	Week 12
Secondary	Part 2: Proportion of Participants Achieving Endoscopic Improvement at Week 24	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).	Week 24

External Links

•   Gilead Clinical Trials Website