Study of Tilpisertib Fosmecarbil in Participants With Moderately to Severely Active Ulcerative Colitis
- Conditions
- Ulcerative Colitis
- Interventions
- Drug: Placebo
- Registration Number
- NCT06029972
- Lead Sponsor
- Gilead Sciences
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 176
- 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.
- A surveillance colonoscopy for dysplasia is required prior to randomization if indicated by regional guidelines for individuals with UC.
Key
- 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.
of randomization; or any infection requiring oral anti-infective therapy within 6 weeks of randomization.
- History of opportunistic infection.
- Current diagnosis of acute severe colitis, fulminant colitis, or toxic megacolon.
Note: Other protocol-defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tilpisertib Fosmecarbil Placebo Tilpisertib Fosmecarbil 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. Tilpisertib Fosmecarbil Placebo 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. Tilpisertib Fosmecarbil Dose C Tilpisertib Fosmecarbil 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. Tilpisertib Fosmecarbil Dose A Tilpisertib Fosmecarbil 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. Tilpisertib Fosmecarbil Dose B Tilpisertib Fosmecarbil 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.
- Primary Outcome Measures
Name Time Method Proportion of Participants Achieving Clinical Response Per Modified Mayo Clinic Score at Week 12 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 Measures
Name Time Method Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) First dose date up to Week 52 (responders) or Week 64 (non-responders) plus 30 days Proportion of Participants Achieving Clinical Remission Per Modified Mayo Clinic Score at Week 12 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.
Proportion of Participants Achieving Histologic Endoscopic Mucosal Improvement at Week 12 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.
Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities First dose date up to Week 52 (responders) or Week 64 (non-responders) plus 30 days Proportion of Participants Achieving Endoscopic Response at Week 12 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.
Trial Locations
- Locations (123)
Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
Azienda Sanitaria Universitaria Friuli Centrale
🇮🇹Udine, Italy
Hyogo Medical University Hospital
🇯🇵Hyogo, Japan
Nzoz Vivamed
🇵🇱Warszawa, Poland
Fairfield General Hospital
🇬🇧Bury, United Kingdom
Cambridge University Hospitals NHS Foundation Trust
🇬🇧Cambridge, United Kingdom
Barts Health NHS Trust
🇬🇧London, United Kingdom
Norfolk and Norwich University Hospital Nhs Foundation Trust
🇬🇧Norwich, United Kingdom
Amicis Research Center
🇺🇸Valencia, California, United States
Arizona Digestive Health
🇺🇸Sun City, Arizona, United States
GastroSb Weight Loss Clinic
🇺🇸Chula Vista, California, United States
Southern California Research Centers
🇺🇸Coronado, California, United States
VVCRD Research
🇺🇸Garden Grove, California, United States
UC San Diego Health System
🇺🇸La Jolla, California, United States
Gastro Care Institute
🇺🇸Lancaster, California, United States
Om Research LLC
🇺🇸Lancaster, California, United States
United Medical Doctors
🇺🇸Murrieta, California, United States
University of California, Davis
🇺🇸Sacramento, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Luna Research
🇺🇸Coral Gables, Florida, United States
University of Florida
🇺🇸Gainesville, Florida, United States
The Medici Medical Research
🇺🇸Hollywood, Florida, United States
Encore Medical Research, LLC
🇺🇸Hollywood, Florida, United States
Florida Research Institute
🇺🇸Largo, Florida, United States
Wellness Research Center
🇺🇸Miami, Florida, United States
IMIC Inc
🇺🇸Miami, Florida, United States
Reserka LLC
🇺🇸Miami, Florida, United States
GI PROS Research
🇺🇸Naples, Florida, United States
Revival Clinical Research
🇺🇸Orlando, Florida, United States
Digestive and Liver Center of Florida, LLC
🇺🇸Orlando, Florida, United States
Advanced Medical Research Center
🇺🇸Port Orange, Florida, United States
Gastroenterology Associates of Florida - GI Alliance
🇺🇸Wellington, Florida, United States
Atlanta Center For Gastroenterology P.C.
🇺🇸Decatur, Georgia, United States
Corewell Health
🇺🇸Grand Rapids, Michigan, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Gastroenterology Associates of North Mississippi
🇺🇸Oxford, Mississippi, United States
Digestive Health Specialists
🇺🇸Tupelo, Mississippi, United States
St. Charles Clinical Research
🇺🇸Saint Louis, Missouri, United States
Ellipsis Research Group
🇺🇸Brooklyn, New York, United States
NYU Langone Long Island Clinical Research Associates
🇺🇸Great Neck, New York, United States
Gastroenterology & Hepatology Specialists Inc
🇺🇸Canton, Ohio, United States
Ohio Gastroenterology & Liver Institute
🇺🇸Cincinnati, Ohio, United States
The Ohio State University Wexner Medical Centre
🇺🇸Columbus, Ohio, United States
Dayton Gastroenterology, LLC
🇺🇸Dayton, Ohio, United States
Great Lakes Gastroenterology Research, LLC
🇺🇸Mentor, Ohio, United States
Skyline Gastroenterology of West Tennessee
🇺🇸Jackson, Tennessee, United States
Hill Country Digestive Health
🇺🇸Boerne, Texas, United States
Gastroenterology Research of America
🇺🇸El Paso, Texas, United States
DHAT Research Institute
🇺🇸Garland, Texas, United States
Southwest Clinical Trials
🇺🇸Houston, Texas, United States
Lubbock Digestive Disease Associates
🇺🇸Lubbock, Texas, United States
GI Associates and Endoscopy Center - GI Alliance
🇺🇸Mansfield, Texas, United States
Gastroenterology Research of San Antonio
🇺🇸San Antonio, Texas, United States
Tyler Research Institute, LLC
🇺🇸Tyler, Texas, United States
LinQ Research LLC
🇺🇸Pearland, Texas, United States
Clinical Associates in Research Therapeutics of America
🇺🇸San Antonio, Texas, United States
Queen Elizabeth Hospital
🇦🇺Woodville, South Australia, Australia
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
Northern Health
🇦🇺Epping, Victoria, Australia
Gastroenterology Associates of Tidewater
🇺🇸Chesapeake, Virginia, United States
Emeritas Group Research
🇺🇸Lansdowne Town Center, Virginia, United States
Gastroenterology Consultants of Southwest Virginia
🇺🇸Roanoke, Virginia, United States
Swedish Medical Center
🇺🇸Seattle, Washington, United States
Mater Adult Hospital
🇦🇺South Brisbane, Queensland, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Footscray Hospital
🇦🇺Footscray, Victoria, Australia
Medical University of Innsbruck
🇦🇹Innsbruck, Austria
University of Salzburg, Universitätsklinik für Innere Medizin III
🇦🇹Salzburg, Austria
Universitätsklinikum St. Pölten
🇦🇹St. Pölten, Austria
Medical University Vienna, Department of Internal Medicine III, Division Gastroenterology and Hepatology
🇦🇹Vienna, Austria
Universitaire Ziekenhuis Leuven
🇧🇪Leuven, Belgium
London Health Sciences Centre-University Hospital
🇨🇦London, Canada
Physician's Clinical Research, Inc. (PCRI)
🇨🇦Toronto, Canada
Mount Sinai Hospital
🇨🇦Toronto, Canada
TDDA Speciality Research
🇨🇦Vaughan, Canada
Centre Hospitalier Universitaire Grenoble
🇫🇷Grenoble Cedex 9, France
Hôpital Claude Huriez
🇫🇷Little Cedex, France
Hopital Saint Eloi
🇫🇷Montpellier, France
Centre Hospitalier Universitaire de Nantes
🇫🇷Nantes, France
Institut des MICI
🇫🇷Neuilly Sur Seine, France
CHU de Saint Etienne - Hopital Nord
🇫🇷Saint-Etienne, France
Hopital Rangueil
🇫🇷Toulouse, France
CHRU Nancy
🇫🇷Vandoeuvre Les Nancy, France
Charite Universitaetsmedizin Berlin Campus CVK, Department of Hepatology and Gastroenterology
🇩🇪Berlin, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Universitatsklinikum Schleswig-Holstein
🇩🇪Kiel, Germany
Eugastro Gmbh
🇩🇪Liepzig, Germany
Universitaetsklinikum Ulm Klinik fur Innere Medizin I CED Studien Ambulanz
🇩🇪Ulm, Germany
Tolna Megye Balassa Janos Korhaz
🇭🇺Beri Balogh, Hungary
Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak
🇭🇺Budapest, Hungary
AZIENDA UNICA OSPEDALIERO-UNIVERSITARIA"RENATO DULBECCO" - AOU"Mater Domini"
🇮🇹Catanzaro, Italy
IRCCS Istituto Clinico Humanitas
🇮🇹Milano, Italy
Azienda Ospedaliera San Camillo Forlanini
🇮🇹Roma, Italy
Fukuoka University Hospital
🇯🇵Jonan-ku, Japan
The Jikei University Hospital
🇯🇵Minato-ku, Japan
Kitasato University Kitasato Institute Hospital
🇯🇵Minato-ku, Japan
Kyorin University Hospital
🇯🇵Mitaka-shi, Japan
Nagasaki University Hospital
🇯🇵Nagasaki, Japan
Ishida Clinic of IBD and Gastroenterology
🇯🇵Oita-shi, Japan
Saga University Hospital
🇯🇵Sagaken, Japan
Kitasato University Hospital
🇯🇵Sagamihara, Japan
Sapporo Medical University Hospital
🇯🇵Sapporo, Japan
Tokyo Medical And Dental University Hospital
🇯🇵Toukiyouto, Japan
Yonsei University Severance Hospital
🇰🇷Seodaemun-Gu, VIC, Korea, Republic of
Inje University
🇰🇷Busan, Korea, Republic of
Yeungnam University Hospital
🇰🇷Daegu, Korea, Republic of
Kyungpook National University Hospital
🇰🇷Jung-gu, Korea, Republic of
Kyung Hee University Medical Center
🇰🇷Seoul, Korea, Republic of
Kangbuk Samsung Hospital
🇰🇷Seoul, Korea, Republic of
Hanyang University Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Wonju Severance Christian Hospital
🇰🇷Wonju, Korea, Republic of
Economicus Sp. z o.o., Niepubliczny Zakład Opieki Zdrowotnej (NZOZ) ALL-MEDICUS
🇵🇱Katowice, Poland
Gabinet Endoskopii Przewodu Pokarmowego
🇵🇱Krakow, Poland
Kliniczny Szpital Wojewódzki Nr 2 im. Sw. Jadwigi Królowej w Rzeszowie
🇵🇱Rzeszów, Poland
Specjalistyczna Praktyka Lekarska Leszek Bryniarski
🇵🇱Sopot, Poland
GASTROMED Kopon, Zmudzinski i wspolnicy Sp. J. Specialized Center of Gastroenterology and Endoscopy
🇵🇱Torun, Poland
Medical Network Sp. z o.o. WIP Warsaw IBD Point Profesor Kierkus
🇵🇱Warszawa, Poland
Specjalistyczne Gabinety Lekarskie Body Clinic
🇵🇱Warszawa, Poland
Centrum Medyczne Oporow
🇵🇱Wroclaw, Poland
Intesto, Gastroenterologische Praxis Crohn-Colitis-Zentrum
🇨🇭Bern, Switzerland
University Hospital Southampton Nhs Foundation Trust
🇬🇧Southampton, United Kingdom