Clinical trial NCT04130919: Study to Evaluate the Efficacy and Safety of Tilpisertib in Adults With Moderately to Severely Active Ulcerative Colitis
Official title: A Phase 2, Blinded, Randomized, Placebo-Controlled Study Evaluating the Efficacy and Safety of GS-4875 in Subjects With Moderately to Severely Active Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ulcerative Colitis
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2019-10-18
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Key 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)

Key Exclusion Criteria:

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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants Who Achieved Clinical Remission Per Modified Mayo Clinic Score (MCS) at Week 10
timeFrame: Week 10
Secondary outcomes:
measure: Percentage of Participants Who Achieved Endoscopic Response at Week 10
timeFrame: Week 10
measure: Percentage of Participants Who Achieved MCS Response at Week 10
timeFrame: Week 10
measure: Percentage of Participants Who Achieved MCS Remission at Week 10
timeFrame: Week 10
measure: Percentage of Participants Who Achieved Histologic Remission Based Upon the Geboes Scale at Week 10
timeFrame: Week 10
measure: Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
timeFrame: 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
measure: Percentage of Participants Who Experienced Laboratory Abnormalities
timeFrame: 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
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Gut P.C., dba Digestive Health Specialists of the Southeast
state: Alabama
city: Lancaster
country: United States
facility: Om Research LLC
state: California
city: Murrieta
country: United States
facility: United Medical Doctors
state: California
city: Poway
country: United States
facility: Alliance Clinical Research
state: California
city: Coral Springs
country: United States
facility: Alliance Medical Research
state: Florida
city: Jacksonville
country: United States
facility: Encore Borland-Groover Clinical Research
state: Florida
city: Miami
country: United States
facility: A Plus Research, Inc
state: Florida
city: Plantation
country: United States
facility: BRCR Medical Center Inc.
state: Florida
city: Port Orange
country: United States
facility: Advanced Medical Research Center
state: Florida
city: Marietta
country: United States
facility: Gastrointestinal Specialists of Georgia
state: Georgia
city: Suwanee
country: United States
facility: Atlanta Gastroenterology Specialists, PC
state: Georgia
city: Shreveport
country: United States
facility: Louisiana Research Center, LLC
state: Louisiana
city: Kansas City
country: United States
facility: Kansas City Research Institute
state: Missouri
city: Las Vegas
country: United States
facility: Advanced Biomedical Research of America
state: Nevada
city: Cincinnati
country: United States
facility: Consultants for Clinical Research
state: Ohio
city: Orangeburg
country: United States
facility: Gastroenterology Associates of Orangeburg
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center - IBD Clinic
state: Tennessee
city: Cypress
country: United States
facility: Allied Digestive Disease Center
state: Texas
city: Houston
country: United States
facility: Southwest Clinical Trials
state: Texas
city: San Antonio
country: United States
facility: Clinical Associates in Research Therapeutics of America, LLC
state: Texas
city: San Marcos
country: United States
facility: Texas Digestive Disease Consultants
state: Texas
city: Southlake
country: United States
facility: Texas Digestive Disease Consultants
state: Texas
city: Wauwatosa
country: United States
facility: Allegiance Research Specialists, LLC
state: Wisconsin
city: Maroochydore
country: Australia
facility: Coastal Digestive Health
state: Queensland
city: Woodville
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
state: Victoria
city: Melbourne
country: Australia
facility: Emeritus Research
state: Victoria
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck, Universitätsklinik für Innere Medizin I
city: Vienna
country: Austria
facility: Medizinische Universitat Wien Klinik fur Innere Medizin III/Abt. fur Gastroenterologie and Hepatologie
city: Vancouver
country: Canada
facility: Vancouver General Hospital - The Gordon and Leslie Diamond Health Care Centre
state: British Columbia
city: Clichy
country: France
facility: Hopital Beaujon
city: Dijon
country: France
facility: CHU de Dijon Bourgogne
city: Grenoble
country: France
facility: Centre Hospitalier Universitaire de Grenoble Alpes
city: Lille
country: France
facility: CHRU de Lille - Hôpital Claude Huriez
city: Pierre-Benite
country: France
facility: CHU de Lyon Sud
city: Rennes
country: France
facility: CHRU Pontchaillou
city: Saint-Etienne
country: France
facility: CHU de Saint Etienne
city: Toulouse
country: France
facility: Hopital Rangueil
city: Vandoeuvre-les-Nancy Cedex
country: France
facility: CHRU de Nancy
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik fur Innere Medizin I, Haus C, Haus K3
city: Leipzig
country: Germany
facility: Eugastro GmbH
city: Minden
country: Germany
facility: Gastroenterologische Gemeinschaftspraxis Minden
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Szczecin
country: Poland
facility: Twoja Przychodnia - Szczecinskie Centrum Medyczne
city: Torun
country: Poland
facility: "GASTROMED" Kopon, Zmudzinski i Wsp. Sp. J. Spec. Centrum Gastrologii i Endoskopii, Spec. Gabinety Lekarskie
city: Wroclaw
country: Poland
facility: Centrum Medyczne Melita Medical
city: Bern
country: Switzerland
facility: Gastroenterologische Praxis Balsiger, Seibold & Partner/Crohn-Colitis-Zentrum
city: Bern
country: Switzerland
facility: Inselspital Bern/Klinik fur Viszerale Chirurgie und Medizin/Bauchzentrum
city: Zurich
country: Switzerland
facility: Universitätsspital Zürich/Klinik für Gastroenterologie und Hepatologie
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: