Study of GS-1427 in Participants With Moderately to Severely Active UC
- Conditions
- Ulcerative Colitis (UC)
- Interventions
- Drug: Placebo-to-match GS-1427
- Registration Number
- 2023-508304-38-00
- Lead Sponsor
- Gilead Sciences Inc.
- Brief Summary
To assess the efficacy of GS 1427, compared with placebo control, in achieving clinical response at Week 12
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised, recruiting
- Sex
- Not specified
- Target Recruitment
- 84
Participants have 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.
Participants have UC with minimum disease extent of 15 cm from the anal verge.
Participants have moderately to severely active UC as determined by endoscopy occurring during screening with a total mMCS of 5 to 9 points, including a centrally read endoscopic subscore of at least 2.
Participants have an inadequate response or loss of response or are intolerant to at least 1 of the following UC treatments: -Corticosteroids -Immunomodulators: azathioprine, 6-mercaptopurine (see full inclusion criteria for details) -Advanced therapy: have an inadequate response or loss of response or are intolerant to an advanced therapy (AT) for the treatment of UC: 1)Tumor necrosis factor-alpha (TNF-α) inhibitor: eg, infliximab, adalimumab, golimumab, or biosimilars 2)Interleukin-12/23 inhibitor: eg, ustekinumab 3)Sphingosine 1-phosphate receptor modulator: eg, ozanimod 4) Janus Kinase inhibitor: eg, tofacitinib, upadacitinib, filgotinibkinas
Participants 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):
Have a current diagnosis of Crohn’s disease (CD) or clinical findings suggestive of CD, diagnosis of indeterminate colitis due to causes 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.
Have any history of stroke, seizure disorder, multiple sclerosis, neurodegenerative disease of brain (such as Parkinson’s disease, dementias), or brain tumor.
Have a positive progressive multifocal leukoencephalopathy subjective checklist at screening or at randomization prior to the administration of the first dose of study drug.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A, Part B, Part C: GS-1427 Dose A GS-1427 Participants will receive GS-1427 Dose A Day 1 through Week 12 (Part A). Participants who complete the 12-week Part A treatment period will be eligible to continue and remain on the same dose of GS-1427 through Week 52 (Part B). Participants who complete Part B of the study will continue onto Part C: Blinded treatment extension for an additional 24 weeks (through Week 76). Part A, Part B, Part C: GS-1427 Dose B GS-1427 Participants will receive GS-1427 Dose B Day 1 through Week 12 (Part A). Participants who complete the 12-week Part A treatment period will be eligible to continue and remain on the same dose of GS-1427 through Week 52 (Part B). Participants who complete Part B of the study will continue onto Part C: Blinded treatment extension for an additional 24 weeks (through Week 76). Part A, Part B, Part C: GS-1427 Dose C GS-1427 Participants will receive GS-1427 Dose C Day 1 through Week 12 (Part A). Participants who complete the 12-week Part A treatment period will be eligible to continue and remain on the same dose of GS-1427 through Week 52 (Part B). Participants who complete Part B of the study will continue onto Part C: blinded treatment extension for an additional 24 weeks (through Week 76). Part A, Placebo; Part B, Part C: GS-1427 GS-1427 Participants will receive Placebo to match GS-1427 Day 1 through Week 12 (Part A). Part A placebo participants will be eligible to undergo re-randomization in a double-blind manner after endoscopy assessment at Week 12 to receive one of the GS-1427 dose A, B, or C treatments. Participants will be eligible to continue and remain on the new dose through Week 52 (Part B). Participants who complete Part B of the study will continue onto Part C: blinded treatment extension for an additional 24 weeks (through Week 76). Part A, Placebo; Part B, Part C: GS-1427 Placebo-to-match GS-1427 Participants will receive Placebo to match GS-1427 Day 1 through Week 12 (Part A). Part A placebo participants will be eligible to undergo re-randomization in a double-blind manner after endoscopy assessment at Week 12 to receive one of the GS-1427 dose A, B, or C treatments. Participants will be eligible to continue and remain on the new dose through Week 52 (Part B). Participants who complete Part B of the study will continue onto Part C: blinded treatment extension for an additional 24 weeks (through Week 76).
- Primary Outcome Measures
Name Time Method 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. 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.
- Secondary Outcome Measures
Name Time Method Incidence of treatment-emergent adverse events, serious adverse events, or deaths, and treatment-emergent laboratory abnormalities Incidence of treatment-emergent adverse events, serious adverse events, or deaths, and treatment-emergent laboratory abnormalities
Clinical remission at Week 12 Clinical remission at Week 12
Clinical remission at Week 52 Clinical remission is defined as an mMCS of ≤ 2 points, 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). Clinical remission at Week 52 Clinical remission is defined as an mMCS of ≤ 2 points, 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).
Histologic-endoscopic mucosal improvement at Week 12 Histologic-endoscopic mucosal improvement is defined as a Geboes score ≤ 3.1 and endoscopic subscore of ≤ 1. Histologic-endoscopic mucosal improvement at Week 12 Histologic-endoscopic mucosal improvement is defined as a Geboes score ≤ 3.1 and endoscopic subscore of ≤ 1.
Mucosal healing at Week 12 Mucosal healing is defined as a Geboes score ≤ 2B.1 and endoscopic subscore ≤ 1. Mucosal healing at Week 12 Mucosal healing is defined as a Geboes score ≤ 2B.1 and endoscopic subscore ≤ 1.
Endoscopic improvement at Week 12 Endoscopic improvement is defined as an endoscopic subscore ≤ 1. Endoscopic improvement at Week 12 Endoscopic improvement is defined as an endoscopic subscore ≤ 1.
Partial mMCS remission at Week 76 Partial mMCS remission is defined as a SFS ≤ 1 and rectal bleeding subscore of 0. Partial mMCS remission at Week 76 Partial mMCS remission is defined as a SFS ≤ 1 and rectal bleeding subscore of 0.
Trial Locations
- Locations (76)
Universitaetsklinikum Ulm AöR
🇩🇪Ulm, Germany
Studiengesellschaft BSF UG (haftungsbeschraenkt)
🇩🇪Halle (Saale), Germany
Universitaetsklinikum Schleswig-Holstein AöR
🇩🇪Kiel, Germany
Universitaetsklinikum Regensburg AöR
🇩🇪Regensburg, Germany
Technische Universitaet Dresden
🇩🇪Dresden, Germany
Universitaetsklinikum Brandenburg an der Havel GmbH
🇩🇪Brandenburg An Der Havel, Germany
Centrul Medical Monza S.R.L.
🇷🇴Bucharest, Romania
Spitalul Universitar De Urgenta Militar Central Dr. Carol Davila
🇷🇴Bucharest, Romania
Institutul Regional De Gastroenterologie Hepatologie Prof. Dr. Octavian Fodor Cluj
🇷🇴Cluj-Napoca, Romania
Spitalul Clinic Colentina Bucuresti
🇷🇴Bucharest, Romania
Scroll for more (66 remaining)Universitaetsklinikum Ulm AöR🇩🇪Ulm, GermanyJochen KlausSite contact+4973150044727jochen.klaus@uniklinik-ulm.de