Study of GS-1427 in Participants With Moderately to Severely Active Ulcerative Colitis
Purpose
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
Condition
- Ulcerative Colitis
Eligibility
- Eligible Ages
- Between 18 Years and 75 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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
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
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Part 1A, Part 1B: GS-1427 Dose A |
Participants will receive GS-1427 Dose A Day 1 through Week 12 (Part 1A). Participants will be eligible to continue and remain on the same dose of GS-1427 through Week 52 (Part 1B). |
|
|
Experimental Part 1A, Part 1B: GS-1427 Dose B |
Participants will receive GS-1427 Dose B Day 1 through Week 12 (Part 1A). Participants will be eligible to continue and remain on the same dose of GS-1427 through Week 52 (Part 1B). |
|
|
Experimental Part 1A, Part 1B: GS-1427 Dose C |
Participants will receive GS-1427 Dose C Day 1 through Week 12 (Part 1A). Participants will be eligible to continue and remain on the same dose of GS-1427 through Week 52 (Part 1B). |
|
|
Experimental Part 1A, Placebo; Part 1B, GS-1427 |
Participants will receive Placebo to match GS-1427 Day 1 through Week 12 (Part 1A). Participants will be eligible to be re-randomized to receive one of the GS-1427 dose A, B, or C treatment after Week 12 through Week 52 (Part 1B). |
|
|
Experimental Part 2: GS-1427 Monotherapy |
Participants will receive GS-1427 (at a dose determined based in Part 1A) Day 1 through Week 12. Participants will be eligible to continue and remain on the same dose of GS-1427 through Week 24. |
|
|
Experimental Part 2: Ustekinumab Monotherapy |
Participants will receive ustekinumab, initial dose determined by body weight: 260 to 520 mg intravenous (IV), then subsequent dose: 90 mg subcutaneous (SC) 8 weeks after the initial IV dose, and every 8 weeks up to week 16 ( total of 2 subcutaneous injections after initial IV ustekinumab). Participants will be eligible to continue and remain on the ustekinumab through Week 24. |
|
|
Experimental Part 2: GS-1427 + Ustekinumab Combination Therapy |
Participants will receive GS-1427 (dose determined based on Part 1A) and ustekinumab, initial dose determined by body weight: 260 to 520 mg IV, then subsequent dose: 90 mg SC 8 weeks after the initial IV dose, and every 8 weeks up to week 16 ( total of 2 subcutaneous injections after initial IV ustekinumab). Participants will be eligible to continue and remain on the same dose of GS-1427 and ustekinumab combination therapy through Week 24. |
|
|
Experimental Part 2: Open-label GS-1427 |
Participants who complete Part 2 Week 24, will be eligible to continue and and receive open-label GS-1427 through Week 52 at a dose to be determined in Part 1A. |
|
Recruiting Locations
Vanderbilt Inflammatory Bowel Disease Clinic
Nashville, Tennessee 37232
Nashville, Tennessee 37232
More Details
- Status
- Recruiting
- Sponsor
- Gilead Sciences
Study Contact
Gilead Clinical Study Information Center1-833-445-3230 (GILEAD-0)
GileadClinicalTrials@gilead.com