Ulcerative Colitis
Tilpisertib Fosmecarbil for Moderately to Severely Active Ulcerative Colitis
This Phase 2 study is testing whether different oral doses of tilpisertib fosmecarbil are effective and safe compared with placebo in adults with moderately to severely active ulcerative colitis.
Registry title: Study of Tilpisertib Fosmecarbil in Participants With Moderately to Severely Active Ulcerative Colitis
38 recruiting U.S. sites ↓Study at a glance
- Age
- 18 Years–75 Years
- Treatment
- Tilpisertib Fosmecarbil or Placebo
- Design
- Randomized · Double
- Central study contact
- Gilead Clinical Study Information Center1-833-445-3230 (GILEAD-0)GileadClinicalTrials@gilead.com
- Sponsor
- Gilead Sciences
Research question
Compared with placebo, do different doses of tilpisertib fosmecarbil produce a clinical response by Week 12, and what safety findings occur, in people with moderately to severely active ulcerative colitis?
Participant snapshot
Who the study is looking for
- The study is looking for adults ages 18 to 75.
- The study is looking for people with ulcerative colitis diagnosed at least 90 days before randomization and previously confirmed by endoscopy and histology.
- The study is looking for people whose ulcerative colitis is moderately to severely active during screening, according to specified modified Mayo Clinic Score and endoscopy thresholds.
- The study is looking for people who have not responded, or have lost response, to at least one advanced ulcerative colitis therapy mechanism.
Participation overview
What participation may involve
Participants receive oral tilpisertib fosmecarbil or placebo during an initial blinded phase lasting up to 12 weeks. Treatment after Week 12 depends on clinical response, with an optional non-responder phase for those without a response. What participation may involve: - Take study tablets by mouth. - Complete an efficacy assessment at Week 12 of the initial blinded phase. - If there is no clinical response at Week 12, participants may choose to enter a 12-week non-responder treatment phase and complete another efficacy assessment. - The study evaluates stool frequency, rectal bleeding, endoscopic findings, tissue histology, adverse events, and laboratory abnormalities. The initial blinded treatment lasts up to 12 weeks. Participants with a clinical response may receive tilpisertib fosmecarbil through Week 52; nonresponders may enter another 12-week treatment phase, after which further treatment depends on response.
Study interventions
What participants may receive or do
- Tilpisertib Fosmecarbil: Tilpisertib fosmecarbil, formerly called GS-5290, is given as tablets taken by mouth. The study compares three blinded dose groups with placebo during the first 12 weeks and may provide additional tilpisertib fosmecarbil treatment according to clinical response.
- Placebo: The placebo is given as tablets taken by mouth in the placebo-comparator group during the blinded 12-week phase.
Study design
How the comparison works
This is a Phase 2, parallel-group study in which participants are assigned at random to one of three tilpisertib fosmecarbil dose groups or a placebo group. Treatment assignment is hidden from participants and investigators during the blinded phase. Participants are assigned randomly among parallel treatment groups; the registry does not report the assignment ratio. The study is double-blinded: both participants and investigators are masked to treatment assignment. The three tilpisertib fosmecarbil dose groups are compared with a placebo group during the initial blinded treatment phase. One of the four listed groups receives oral placebo for up to 12 weeks, but the registry does not state the randomization ratio or an individual's probability of receiving placebo.
Reported activities
Procedures and tests
- Efficacy assessment at Week 12, and another Week 12 assessment for participants entering the non-responder phase.
- Modified Mayo Clinic Score assessments covering stool frequency, rectal bleeding, and endoscopic findings.
- Endoscopic assessment of ulcerative colitis activity.
- Histologic assessment of tissue using the Geboes score.
- Monitoring and recording of treatment-emergent adverse events.
- Laboratory testing to identify clinically significant abnormalities.
- A surveillance colonoscopy for dysplasia before randomization when regional guidelines indicate it.
Eligibility highlights
Details that may affect whether you contact the study
These are selected highlights, not a complete eligibility check. Exact criteria remain in the full registry record below.
Common requirements
- Participants must be 18 to 75 years old at the screening visit.
- Individuals assigned female at birth must be neither pregnant nor breastfeeding.
- Ulcerative colitis must have been present for at least 90 days before randomization and previously confirmed by both endoscopy and histology, with supporting records available before screening.
- Disease must extend at least 15 cm from the anal verge.
- Screening must show moderately to severely active ulcerative colitis, with a modified Mayo Clinic Score of 5 to 9 and a centrally read endoscopic subscore of 2 to 3.
- Participants must have failed, through lack or loss of response, at least one approved advanced ulcerative colitis therapy mechanism, but no more than three different advanced therapy mechanisms.
- A surveillance colonoscopy for dysplasia is required before randomization when regional guidelines indicate one.
Possible reasons someone may not be able to join
- People with a current Crohn's disease diagnosis or indeterminate colitis caused by an enteric pathogen, lymphocytic colitis, or collagenous colitis are excluded.
- People whose disease is limited to the rectum during screening endoscopy are excluded.
- Ongoing use or prior use of protocol-prohibited medications is exclusionary.
- An active clinically significant infection excludes participation.
- An infection requiring hospitalization or intravenous anti-infective treatment within eight weeks before randomization is exclusionary.
- An infection requiring oral anti-infective therapy within six weeks before randomization is exclusionary.
- A history of an opportunistic infection is exclusionary.
- People currently diagnosed with acute severe colitis, fulminant colitis, or toxic megacolon are excluded.
Important unknowns
What the record does not make clear
- The registry identifies Week 12 efficacy assessments but does not provide the number, timing, or length of study visits.
- Treatment pathways through Week 52 are described, and safety outcomes mention Week 52 for responders or Week 64 for nonresponders plus 30 days, but the total commitment for each pathway is not stated clearly.
- Four groups are listed, including one placebo group, but the allocation ratio is not reported.
- The registry does not say which current ulcerative colitis treatments may continue during the study.
- The criteria mention prohibited medications but do not name them or provide required stopping intervals.
- The registry does not describe what treatment is available if ulcerative colitis worsens during the study.
- Endoscopic findings are used for screening and Week 12 outcomes, and surveillance colonoscopy may be required, but the total number and timing of endoscopies are not stated.
- The registry does not explain which study-related or routine-care costs are covered or billed to insurance.
- The registry does not report compensation or reimbursement.
- The registry does not state whether transportation, lodging, or other travel support is available.
- The registry does not say whether any visits or assessments may be completed remotely.
- The registry does not describe access to tilpisertib fosmecarbil after study treatment ends.
- The study is recruiting overall, but individual locations have recruiting, not-yet-recruiting, active-not-recruiting, or withdrawn statuses.
Before contacting the site
Questions for the study team
- How many visits, endoscopies, biopsies, blood draws, and stool assessments are required in each study phase?
- What is the randomization ratio, and what is the chance of receiving placebo during the first 12 weeks?
- Which current ulcerative colitis treatments can continue, and which prohibited medicines require a washout?
- What happens if symptoms worsen or there is no clinical response, including what rescue treatments are permitted?
- What is the full time commitment for each response pathway, including screening and safety follow-up?
- Which study-related costs are covered, and are compensation, travel reimbursement, or lodging support available?
- Is the nearest listed site currently enrolling, and can any assessments be completed remotely or locally?
Before changing care
Questions for your gastroenterologist
- How stable is my ulcerative colitis now, and what concerns would you have about entering a placebo-controlled study?
- Which of my current treatments could be interrupted or changed by the protocol, and what risks would those changes create for me?
- What approved treatment alternatives are available to me now, and how do their known benefits and risks compare with the uncertainties of this study?
- Would the required endoscopic assessments or biopsies pose any special concerns in my clinical situation?
- If I contact the study team, how should you and the research clinicians coordinate monitoring, medication decisions, and care if my symptoms worsen?
This plain-language digest is provided by the Aidy clinical trials API. It may omit details and is not medical advice or an eligibility decision. Review the full registry record and confirm details with the study team.
Source record
Full registry record
The sections below preserve the study information supplied through ClinicalTrials.gov, including complete descriptions, criteria, outcomes, and locations.
About this study
The goal of this study is to learn if tilpisertib fosmecarbil (formerly known as GS-5290) is effective and safe in treating participants with moderate to severe ulcerative colitis. The study will compare participants in different treatment groups treated with tilpisertib fosmecarbil with participants treated with placebo. The primary objective of this study is to demonstrate the efficacy of tilpisertib fosmecarbil, compared to placebo control, in achieving Clinical Response at Week 12.
Study design and administration
- Organization
- Gilead Sciences
- Organization class
- Industry
- Organization study ID
- GS-US-457-6411
- Lead sponsor
- Gilead Sciences
- Sponsor class
- Industry
- Enrollment type
- Estimated
- Allocation
- Randomized
- Intervention model
- Parallel
- Primary purpose
- Treatment
- Masking
- Double
- Who is masked
- Participant, Investigator
- Standard age groups
- Adult, Older Adult
Study arms
Experimental
Tilpisertib Fosmecarbil Dose A
Blinded Treatment Phase: Participants will receive tilpisertib fosmecarbil Dose A for up to 12 weeks. An efficacy assessment will be performed at Week 12. • Participants who achieve clinical response will receive tilpisertib fosmecarbil Dose B for up to Week 52. Non-responder Treatment Phase: • Participants who do not achieve clinical response at Week 12 will discontinue the Blinded Treatment Phase and have the option to enter into the Non-responder Treatment Phase. Participants will receive tilpisertib fosmecarbil Dose A for another 12 weeks. An efficacy assessment will be performed at Week 12 of the Non-responder Treatment Phase. Participants who achieved clinical response will receive tilpisertib fosmecarbil Dose B for up to Week 52. Participants who do not achieve clinical response at Non-responder Treatment Phase Week 12 will discontinue study drug.
Interventions: Drug: Tilpisertib Fosmecarbil
Experimental
Tilpisertib Fosmecarbil Dose B
Blinded Treatment Phase: Participants will receive tilpisertib fosmecarbil Dose B for up to 12 weeks. An efficacy assessment will be performed at Week 12. • Participants who achieve clinical response will receive tilpisertib fosmecarbil Dose B for up to Week 52. Non-responder Treatment Phase: • Participants who do not achieve clinical response at Week 12 will discontinue the Blinded Treatment Phase and have the option to enter into the Non-responder Treatment Phase. Participants will receive tilpisertib fosmecarbil Dose B for another 12 weeks. An efficacy assessment will be performed at Week 12 of the Non-responder Treatment Phase. Participants who achieved clinical response will receive tilpisertib fosmecarbil Dose B for up to Week 52. Participants who do not achieve clinical response at Non-responder Treatment Phase Week 12 will discontinue study drug.
Interventions: Drug: Tilpisertib Fosmecarbil
Experimental
Tilpisertib Fosmecarbil Dose C
Blinded Treatment Phase: Participants will receive tilpisertib fosmecarbil Dose C for up to 12 weeks. An efficacy assessment will be performed at Week 12. • Participants who achieve clinical response will receive tilpisertib fosmecarbil Dose C for up to Week 52. Non-responder Treatment Phase: • Participants who do not achieve clinical response at Week 12 will discontinue the Blinded Treatment Phase and have the option to enter into the Non-responder Treatment Phase. Participants will receive tilpisertib fosmecarbil Dose B for another 12 weeks. An efficacy assessment will be performed at Week 12 of the Non-responder Treatment Phase. Participants who achieved clinical response will receive tilpisertib fosmecarbil Dose B for up to Week 52. Participants who do not achieve clinical response at Non-responder Treatment Phase Week 12 will discontinue study drug.
Interventions: Drug: Tilpisertib Fosmecarbil
Placebo Comparator
Tilpisertib Fosmecarbil Placebo
Blinded Treatment Phase: Participants will receive tilpisertib fosmecarbil placebo for up to 12 weeks. An efficacy assessment will be performed at Week 12. • Participants who achieve clinical response will receive tilpisertib fosmecarbil Dose C for up to Week 52. Non-responder Treatment Phase: • Participants who do not achieve clinical response at Week 12 will discontinue the Blinded Treatment Phase and have the option to enter into the Non-responder Treatment Phase. Participants will receive tilpisertib fosmecarbil Dose A for another 12 weeks. An efficacy assessment will be performed at Week 12 of the Non-responder Treatment Phase. Participants who achieved Clinical Response will receive tilpisertib fosmecarbil Dose B for up to Week 52. Participants who do not achieve Clinical Response at Non-responder Treatment Phase Week 12 will discontinue study drug.
Interventions: Drug: Tilpisertib Fosmecarbil, Drug: Placebo
Interventions
Drug
Tilpisertib Fosmecarbil
Tablets administered orally
Drug
Placebo
Tablets administered orally
Eligibility
18 Years–75 Years
All
Not accepted
Inclusion criteria (5)
- Individuals assigned male at birth, or nonpregnant, nonlactating individuals assigned female at birth, 18 to 75 years of age based on the date of the screening visit.Registry-derived · unreviewed
- Ulcerative colitis (UC) of at least 90-day duration before randomization confirmed by endoscopy and histology at any time in the past AND a minimum disease extent of 15 cm from the anal verge. Documentation of endoscopy and histology consistent with the diagnosis of UC must be available in the source documents prior to the initiation of screening.Registry-derived · unreviewed
- Moderately to severely active UC as determined during screening with a modified Mayo Clinic Score based on the sum of Stool Frequency, Rectal Bleeding, and Endoscopic Finding of 5 to 9 points and an endoscopic subscore of 2 to 3 (determined by central reader).Registry-derived · unreviewed
- Previous treatment history of approved UC therapy with at least one advanced therapy mechanisms of action but failure (ie, loss of response or lack of response) of no more than 3 different advanced therapy mechanisms of action.Registry-derived · unreviewed
- A surveillance colonoscopy for dysplasia is required prior to randomization if indicated by regional guidelines for individuals with UC.Registry-derived · unreviewed
Exclusion criteria (7)
- Current diagnosis of Crohn's Disease (CD) or diagnosis of indeterminate colitis due to an enteric pathogen, lymphocytic or collagenous colitis.Registry-derived · unreviewed
- Individuals with disease limited to the rectum (ulcerative proctitis) during screening endoscopy.Registry-derived · unreviewed
- Requirement for ongoing therapy with or prior use of any prohibited medications.Registry-derived · unreviewed
- Active clinically significant infection, or any infection requiring hospitalization or treatment with intravenous anti-infectives within 8 weeks.Registry-derived · unreviewed
- of randomization; or any infection requiring oral anti-infective therapy within 6 weeks of randomization.Registry-derived · unreviewed
- History of opportunistic infection.Registry-derived · unreviewed
- Current diagnosis of acute severe colitis, fulminant colitis, or toxic megacolon.Registry-derived · unreviewed
This information can identify a possible match, conflict, or item needing confirmation. Only the study team can determine eligibility.
Study outcomes
Primary outcome
Proportion of Participants Achieving Clinical Response Per Modified Mayo Clinic Score at Week 12
Time frame: Week 12
Clinical Response is defined as a decrease from baseline of ≥ 2 points and at least 30% in 3 components of the modified Mayo Clinic Score, Stool Frequency, Rectal Bleeding, and Endoscopic Findings, in addition to a ≥ 1 point decrease from baseline in the Rectal Bleeding subscore or Rectal Bleeding subscore of ≤ 1. The modified Mayo Clinic Score 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 modified Mayo Clinic Score ranges from 0 to 9 (sum of all subscores), with higher scores indicating higher disease activity.
Secondary outcome
Proportion of Participants Achieving Clinical Remission Per Modified Mayo Clinic Score at Week 12
Time frame: Week 12
Clinical Remission is defined as a Stool Frequency subscore ≤ 1 and not greater than baseline, Rectal Bleeding subscore of 0, and Endoscopic Findings subscore ≤ 1 at Week 12. The modified Mayo Clinic Score 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), 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.
Secondary outcome
Proportion of Participants Achieving Endoscopic Response at Week 12
Time frame: Week 12
Endoscopic Response is defined as an Endoscopic Findings subscore ≤ 1 at Week 12. 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). Higher scores indicate higher disease activity.
Secondary outcome
Proportion of Participants Achieving Histologic Endoscopic Mucosal Improvement at Week 12
Time frame: Week 12
Histologic Endoscopic Mucosal Improvement is defined as an Endoscopic Findings subscore ≤ 1 and Geboes score ≤ 3.1 (indicating neutrophil infiltration in \< 5% of crypts, no crypt destruction and no erosions, ulcerations, or granulation tissue). 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). Geboes histologic remission is assessed using the Geboes histologic scores to identify histologic changes in ulcerative colitis. Possible scores are graded as Grade 0 to Grade 5, with higher grade representing higher levels of disease activity.
Secondary outcome
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Time frame: First dose date up to Week 52 (responders) or Week 64 (non-responders) plus 30 days
Secondary outcome
Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities
Time frame: First dose date up to Week 52 (responders) or Week 64 (non-responders) plus 30 days
Recruiting locations in the United States
GI Alliance
RecruitingSun City, Arizona, 85351, United States
GastroSb Weight Loss Clinic
RecruitingChula Vista, California, 91910, United States
Southern California Research Centers
RecruitingCoronado, California, 92118, United States
VVCRD Research
RecruitingGarden Grove, California, 92845, United States
UC San Diego Health System
RecruitingLa Jolla, California, 92037, United States
Gastro Care Institute
RecruitingLancaster, California, 93534, United States
Om Research LLC
RecruitingLancaster, California, 93534, United States
University of California, Davis
RecruitingSacramento, California, 95817, United States
University of California San Francisco
RecruitingSan Francisco, California, 94115, United States
Luna Research
RecruitingCoral Gables, Florida, 33134, United States
University of Florida
RecruitingGainesville, Florida, 32610, United States
The Medici Medical Research
RecruitingHollywood, Florida, 33021, United States
Clinical Research of Osceola
RecruitingKissimmee, Florida, 34741, United States
Florida Research Institute
RecruitingLargo, Florida, 33771, United States
GI PROS Research
RecruitingNaples, Florida, 34102, United States
Clinical One Research
RecruitingOrlando, Florida, 32807, United States
Digestive and Liver Center of Florida, LLC
RecruitingOrlando, Florida, 32825, United States
Advanced Medical Research Center
RecruitingPort Orange, Florida, 32127, United States
Corewell Health
RecruitingGrand Rapids, Michigan, 49546, United States
Mayo Clinic
RecruitingRochester, Minnesota, 55905, United States
Gastroenterology Associates of North Mississippi
RecruitingOxford, Mississippi, 38655, United States
Digestive Health Specialists
RecruitingTupelo, Mississippi, 38801, United States
St. Charles Clinical Research
RecruitingSt Louis, Missouri, 63141, United States
NYU Langone Long Island Clinical Research Associates
RecruitingGreat Neck, New York, 11021, United States
Gastroenterology & Hepatology Specialists Inc
RecruitingCanton, Ohio, 44718, United States
The Ohio State University Wexner Medical Centre
RecruitingColumbus, Ohio, 43210, United States
Dayton Gastroenterology, LLC
RecruitingDayton, Ohio, 45145, United States
Great Lakes Gastroenterology Research, LLC
RecruitingMentor, Ohio, 44060, United States
Skyline Gastroenterology of West Tennessee
Not Yet RecruitingJackson, Tennessee, 38301, United States
Gastroenterology Research of Hill Country
RecruitingBoerne, Texas, 78006, United States
GI Alliance
RecruitingLubbock, Texas, 79410, United States
GI Associates and Endoscopy Center - GI Alliance
RecruitingMansfield, Texas, 76063, United States
Clinical Associates in Research Therapeutics of America
RecruitingSan Antonio, Texas, 78212, United States
Gastroenterology Research of San Antonio
RecruitingSan Antonio, Texas, 78229, United States
Tyler Research Institute, LLC
RecruitingTyler, Texas, 75701, United States
Gastroenterology Associates of Tidewater
RecruitingChesapeake, Virginia, 23320, United States
Emeritas Group Research
RecruitingLansdowne Town Center, Virginia, 20176, United States
Gastroenterology Consultants of Southwest Virginia
RecruitingRoanoke, Virginia, 24014, United States
This study also lists 76 locations outside the United States. They are not shown here.
Central study contacts
Gilead Clinical Study Information Center
Contact
Registry dates
- First posted
- Sep 8, 2023
- Primary completion
- Jan 2027
- Overall completion
- Feb 2028
Trial information comes from ClinicalTrials.gov and may change. Confirm current status, eligibility, and site details with the study team. Aidy does not provide medical advice or determine eligibility.