Study to Evaluate the Efficacy and Safety of Tilpisertib in Adults With Moderately to Severely Active Ulcerative Colitis

NCT ID: NCT04130919

Last Updated: 2022-08-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-20
• Study Completion Date: 2021-12-14

Brief Summary

The primary objective of this study is to demonstrate the efficacy of tilpisertib (formerly GS-4875) compared with placebo control in achieving clinical remission per modified Mayo Clinic Score (MCS) in adults with moderately to severely active ulcerative colitis (UC).

Conditions

Ulcerative Colitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Tilpisertib 300 mg

Participants will receive blinded tilpisertib 300 mg for up to 10 weeks. An efficacy assessment will be performed at Week 10. Participants who achieve MCS response will continue on the blinded treatment for up to 50 weeks.

Group Type: EXPERIMENTAL

Tilpisertib

Intervention Type: DRUG

Tablets administered orally once daily

Tilpisertib 100 mg

Participants will receive blinded tilpisertib 100 mg for up to 10 weeks. An efficacy assessment will be performed at Week 10. Participants who achieve MCS response will continue on the blinded treatment for up to 50 weeks.

Group Type: EXPERIMENTAL

Tilpisertib

Intervention Type: DRUG

Tablets administered orally once daily

Placebo

Participants will receive blinded tilpisertib matching placebo for up to 10 weeks. An efficacy assessment will be performed at Week 10. Participants who achieve MCS response will continue on the blinded treatment for up to 50 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Tablets administered orally once daily

Open-label Tilpisertib 300 mg

Based on the efficacy assessment results at Week 10, participants who do not achieve MCS response will have the option to receive open-label tilpisertib 300 mg for up to 50 weeks.

Group Type: EXPERIMENTAL

Tilpisertib

Intervention Type: DRUG

Tablets administered orally once daily

Interventions

Tilpisertib

Tablets administered orally once daily

Intervention Type: DRUG

Placebo

Tablets administered orally once daily

Intervention Type: DRUG

Other Intervention Names

GS-4875

Eligibility Criteria

Inclusion Criteria

• Males, or non-pregnant, non-lactating females, at least 18 years of age based on the date of the screening visit.
• UC of at least 3 months duration before randomization confirmed by endoscopy and histology at any time in the past AND a minimum disease extent of 15 centimeter (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 by a centrally read endoscopy score ≥ 2, a Rectal Bleeding subscore ≥ 1, a Stool Frequency subscore ≥ 1 and Physicians Global Assessment (PGA) of ≥ 2 as defined by the Mayo Clinic Score; total MCS must be between 6 and 12, inclusive.
• Previously demonstrated an inadequate response (primary non-response) or loss of response (secondary non-response) to a tumor necrosis factor-alpha (TNFα) inhibitor (ie, infliximab, adalimumab, golimumab, or biosimilars). The induction treatment regimen resulting in inadequate response or loss of response should have been in accordance with local prescribing information/guidelines or as outlined below.

• Infliximab: 5 mg/kg at Weeks 0, 2, and 6
• Adalimumab: 160 mg on Day 1 (given in 1 day or split over consecutive days), followed by 80 mg 2 weeks later (Day 15), 40 mg 2 weeks later (Day 29) and every 2 weeks thereafter until Day 57
• Golimumab: 200 mg on Day 1 followed by 100 mg at Week 2
• May be receiving concomitant therapy for UC at the time of enrollment as specified in the protocol, provided the dose prescribed has been stable as indicated prior to randomization.
• Meet the following Tuberculosis (TB) screening criteria:

• No evidence of active TB, latent TB, or inadequately treated TB as evidenced by 1 of the following:

• A negative QuantiFERON test or equivalent assay reported by the central lab at screening or within 90 days prior to randomization date. OR
• A history of fully treated active or latent TB according to local standard of care. Investigator must verify adequate previous anti-TB treatment and provide documentation; these individuals do not require QuantiFERON testing and eligibility must be approved by the sponsor prior to enrollment in the study. AND
• A chest radiograph (views as per local guidelines with the report or films available for investigator review) taken at screening or within the 4 months prior to randomization without evidence of active or latent TB infection.
• Laboratory assessments at screening within the following parameters:

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and total bilirubin ≤ 2 X upper limit of normal (ULN)
• Estimated glomerular filtration rate (eGFR) ≥ 60 ml/min (1.0 mL/sec) as calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Cystatin C formula as described in protocol.
• Hemoglobin ≥ 8 g/dL (≥ 80 g/L)
• Absolute neutrophil count (ANC) ≥ 1.5 × 10^3/μL (≥ 1.5 GI/L)
• Platelets ≥ 100 × 10^3/μL (≥ 100 GI/L)
• White blood cells (WBC) ≥ 3 × 10^3/μL (≥ 3 GI/L)
• Absolute lymphocyte count ≥ 0.75 × 10^3/μL (≥ 0.75 GI/L)

Exclusion Criteria

• Currently displaying clinical signs of acute severe colitis, fulminant colitis, or toxic megacolon.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Gut P.C., dba Digestive Health Specialists of the Southeast

Dothan, Alabama, United States

Om Research LLC

Lancaster, California, United States

United Medical Doctors

Murrieta, California, United States

Alliance Clinical Research

Poway, California, United States

Alliance Medical Research

Coral Springs, Florida, United States

Encore Borland-Groover Clinical Research

Jacksonville, Florida, United States

A Plus Research, Inc

Miami, Florida, United States

BRCR Medical Center Inc.

Plantation, Florida, United States

Advanced Medical Research Center

Port Orange, Florida, United States

Gastrointestinal Specialists of Georgia

Marietta, Georgia, United States

Atlanta Gastroenterology Specialists, PC

Suwanee, Georgia, United States

Louisiana Research Center, LLC

Shreveport, Louisiana, United States

Kansas City Research Institute

Kansas City, Missouri, United States

Advanced Biomedical Research of America

Las Vegas, Nevada, United States

Consultants for Clinical Research

Cincinnati, Ohio, United States

Gastroenterology Associates of Orangeburg

Orangeburg, South Carolina, United States

Vanderbilt University Medical Center - IBD Clinic

Nashville, Tennessee, United States

Allied Digestive Disease Center

Cypress, Texas, United States

Southwest Clinical Trials

Houston, Texas, United States

Clinical Associates in Research Therapeutics of America, LLC

San Antonio, Texas, United States

Texas Digestive Disease Consultants

San Marcos, Texas, United States

Texas Digestive Disease Consultants

Southlake, Texas, United States

Allegiance Research Specialists, LLC

Wauwatosa, Wisconsin, United States

Coastal Digestive Health

Maroochydore, Queensland, Australia

The Queen Elizabeth Hospital

Woodville, South Australia, Australia

St Vincent's Hospital Melbourne

Fitzroy, Victoria, Australia

Emeritus Research

Melbourne, Victoria, Australia

Medizinische Universität Innsbruck, Universitätsklinik für Innere Medizin I

Innsbruck, , Austria

Medizinische Universitat Wien Klinik fur Innere Medizin III/Abt. fur Gastroenterologie and Hepatologie

Vienna, , Austria

Vancouver General Hospital - The Gordon and Leslie Diamond Health Care Centre

Vancouver, British Columbia, Canada

Hopital Beaujon

Clichy, , France

CHU de Dijon Bourgogne

Dijon, , France

Centre Hospitalier Universitaire de Grenoble Alpes

Grenoble, , France

CHRU de Lille - Hôpital Claude Huriez

Lille, , France

CHU de Lyon Sud

Pierre-Bénite, , France

CHRU Pontchaillou

Rennes, , France

CHU de Saint Etienne

Saint-Etienne, , France

Hopital Rangueil

Toulouse, , France

CHRU de Nancy

Vandœuvre-lès-Nancy, , France

Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik fur Innere Medizin I, Haus C, Haus K3

Kiel, , Germany

Eugastro GmbH

Leipzig, , Germany

Gastroenterologische Gemeinschaftspraxis Minden

Minden, , Germany

Istituto Clinico Humanitas

Rozzano, , Italy

Twoja Przychodnia - Szczecinskie Centrum Medyczne

Szczecin, , Poland

"GASTROMED" Kopon, Zmudzinski i Wsp. Sp. J. Spec. Centrum Gastrologii i Endoskopii, Spec. Gabinety Lekarskie

Torun, , Poland

Centrum Medyczne Melita Medical

Wroclaw, , Poland

Gastroenterologische Praxis Balsiger, Seibold & Partner/Crohn-Colitis-Zentrum

Bern, , Switzerland

Inselspital Bern/Klinik fur Viszerale Chirurgie und Medizin/Bauchzentrum

Bern, , Switzerland

Universitätsspital Zürich/Klinik für Gastroenterologie und Hepatologie

Zurich, , Switzerland

Countries

United States; Australia; Austria; Canada; France; Germany; Italy; Poland; Switzerland

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-001430-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-365-4237

Identifier Type: -

Identifier Source: org_study_id