Study of Tilpisertib Fosmecarbil in Participants With Moderately to Severely Active Ulcerative Colitis
ConditionUlcerative Colitis
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorGilead Sciences
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
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.
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).
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.
Disqualifiers
Current diagnosis of Crohn's Disease (CD) or diagnosis of indeterminate colitis due to an enteric pathogen, lymphocytic or collagenous colitis.
Individuals with disease limited to the rectum (ulcerative proctitis) during screening endoscopy.
Requirement for ongoing therapy with or prior use of any prohibited medications.
Active clinically significant infection, or any infection requiring hospitalization or treatment with intravenous anti-infectives within 8 weeks.
Trial design
Design model
Parallel
Treatments tested in this trial
Tilpisertib Fosmecarbil
DrugTablets administered orally
Placebo
DrugTablets administered orally
Treatment groups
176 Participants
are divided into 4 treatment groupsGroup A: Tilpisertib Fosmecarbil Dose AExperimental treatment 1 intervention
Group B: Tilpisertib Fosmecarbil Dose BExperimental treatment 1 intervention
Group C: Tilpisertib Fosmecarbil Dose CExperimental treatment 1 intervention
Group D: Tilpisertib Fosmecarbil PlaceboPlacebo comparator 2 interventions
Trial outcomes
Primary outcomes
1
Proportion of Participants Achieving Clinical Response Per Modified Mayo Clinic Score at 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.
Time frame
Week 12Secondary outcomes
1
Proportion of Participants Achieving Clinical Remission Per Modified Mayo Clinic Score at 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.
Time frame
Week 122
Proportion of Participants Achieving Endoscopic Response at 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.
Time frame
Week 123
Proportion of Participants Achieving Histologic Endoscopic Mucosal Improvement at 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.
Time frame
Week 124
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 daysSponsors and contacts
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Source ClinicalTrials.gov