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

NCT04130919 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: GS-US-365-42372019-001430-33
• Study Type: interventional
• Target: 19
• Locations: 8 countries
• Sites: 45

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved Clinical Remission Per Modified Mayo Clinic Score (MCS) at Week 10

  The modified MCS is a scoring system for assessment of ulcerative colitis (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), and physician's global assessment (PGA) (range: 0 to 3, where 0 = normal and 3 = severe disease). Total score for MCS ranges from 0 to 12 (sum of all subscores), with higher scores indicating higher disease activity. Clinical remission per modified MCS is defined as stool frequency subscore ≤ 1 and not greater than baseline, rectal bleeding subscore of 0, and endoscopic subscore ≤ 1 at Week 10.

  Week 10

Secondary Outcomes (6)

• Percentage of Participants Who Achieved Endoscopic Response at Week 10

  Week 10

• Percentage of Participants Who Achieved MCS Response at Week 10

  Week 10

• Percentage of Participants Who Achieved MCS Remission at Week 10

  Week 10

• Percentage of Participants Who Achieved Histologic Remission Based Upon the Geboes Scale at Week 10

  Week 10

• Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)

  Blinded Treatment phase: First dose date up to 50.6 weeks plus 30 days; Open-label phase: First dose date up to 50.7 weeks plus 30 days

Study Arms (4)

Tilpisertib 300 mg

EXPERIMENTAL

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.

Drug: Tilpisertib

Tilpisertib 100 mg

EXPERIMENTAL

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.

Drug: Tilpisertib

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Open-label Tilpisertib 300 mg

EXPERIMENTAL

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.

Drug: Tilpisertib

Interventions

Tilpisertib DRUG

Tablets administered orally once daily

Also known as: GS-4875

Open-label Tilpisertib 300 mg; Tilpisertib 100 mg; Tilpisertib 300 mg

Placebo DRUG

Tablets administered orally once daily

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (49)

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

Dothan, Alabama, 36305, United States

Location

Om Research LLC

Lancaster, California, 93534, United States

Location

United Medical Doctors

Murrieta, California, 92563, United States

Location

Alliance Clinical Research

Poway, California, 92064, United States

Location

Alliance Medical Research

Coral Springs, Florida, 33071, United States

Location

Encore Borland-Groover Clinical Research

Jacksonville, Florida, 32256, United States

Location

A Plus Research, Inc

Miami, Florida, 33144, United States

Location

BRCR Medical Center Inc.

Plantation, Florida, 33322, United States

Location

Advanced Medical Research Center

Port Orange, Florida, 32127, United States

Location

Gastrointestinal Specialists of Georgia

Marietta, Georgia, 30060, United States

Location

Atlanta Gastroenterology Specialists, PC

Suwanee, Georgia, 30024, United States

Location

Louisiana Research Center, LLC

Shreveport, Louisiana, 71105, United States

Location

Kansas City Research Institute

Kansas City, Missouri, 64131, United States

Location

Advanced Biomedical Research of America

Las Vegas, Nevada, 89123, United States

Location

Consultants for Clinical Research

Cincinnati, Ohio, 45219, United States

Location

Gastroenterology Associates of Orangeburg

Orangeburg, South Carolina, 29118, United States

Location

Vanderbilt University Medical Center - IBD Clinic

Nashville, Tennessee, 37212-1375, United States

Location

Allied Digestive Disease Center

Cypress, Texas, 77429, United States

Location

Southwest Clinical Trials

Houston, Texas, 77074, United States

Location

Clinical Associates in Research Therapeutics of America, LLC

San Antonio, Texas, 78212, United States

Location

Texas Digestive Disease Consultants

San Marcos, Texas, 78666, United States

Location

Texas Digestive Disease Consultants

Southlake, Texas, 76092, United States

Location

Allegiance Research Specialists, LLC

Wauwatosa, Wisconsin, 53225, United States

Location

Coastal Digestive Health

Maroochydore, Queensland, 4558, Australia

Location

The Queen Elizabeth Hospital

Woodville, South Australia, 5011, Australia

Location

St Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

Emeritus Research

Melbourne, Victoria, 3124, Australia

Location

Medizinische Universität Innsbruck, Universitätsklinik für Innere Medizin I

Innsbruck, 6020, Austria

Location

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

Vienna, 1090, Austria

Location

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

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Hopital Beaujon

Clichy, 92110, France

Location

CHU de Dijon Bourgogne

Dijon, 21079, France

Location

Centre Hospitalier Universitaire de Grenoble Alpes

Grenoble, 38043, France

Location

CHRU de Lille - Hôpital Claude Huriez

Lille, 59000, France

Location

CHU de Lyon Sud

Pierre-Bénite, 69495, France

Location

CHRU Pontchaillou

Rennes, 35033 Cedex 9, France

Location

CHU de Saint Etienne

Saint-Etienne, 42055, France

Location

Hopital Rangueil

Toulouse, 31059 cedex 9, France

Location

CHRU de Nancy

Vandœuvre-lès-Nancy, 54511, France

Location

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

Kiel, 24105, Germany

Location

Eugastro GmbH

Leipzig, 04103, Germany

Location

Gastroenterologische Gemeinschaftspraxis Minden

Minden, 32423, Germany

Location

Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

Twoja Przychodnia - Szczecinskie Centrum Medyczne

Szczecin, 71-434, Poland

Location

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

Torun, 87-100, Poland

Location

Centrum Medyczne Melita Medical

Wroclaw, 50-449, Poland

Location

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

Bern, 3012, Switzerland

Location

Inselspital Bern/Klinik fur Viszerale Chirurgie und Medizin/Bauchzentrum

Bern, CH-3010, Switzerland

Location

Universitätsspital Zürich/Klinik für Gastroenterologie und Hepatologie

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Limitations and Caveats

Gilead made the decision to discontinue the development of tilpisertib since a new molecular entity was able to achieve greater target coverage. The decision was not due to any safety concerns. Since only 19 participants were enrolled, none of the planned statistical analyses were performed. During the coronavirus disease 2019 (COVID-19) pandemic, there were changes to protocol visits and procedures where necessary to mitigate the impact of the pandemic to the study.

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2019
• First Posted: October 18, 2019
• Study Start: December 20, 2019
• Primary Completion: February 25, 2021
• Study Completion: December 14, 2021
• Last Updated: August 24, 2022
• Results First Posted: August 24, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); PL (3); AU (2); CH (3); FR (9); IT (1); US (23); DE (3)