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

Gilead Sciences

Status and phase: Terminated; Phase 2

Conditions: Ulcerative Colitis

Treatments: Drug: Placebo; Drug: Tilpisertib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04130919

2019-001430-33 (EudraCT Number)

GS-US-365-4237

Details and patient eligibility

About

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).

Enrollment: 19 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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19 participants in 4 patient groups, including a placebo group

Tilpisertib 300 mg

Experimental group

Description:

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.

Treatment:

Drug: Tilpisertib

Tilpisertib 100 mg

Experimental group

Description:

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.

Treatment:

Drug: Tilpisertib

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Open-label Tilpisertib 300 mg

Experimental group

Description:

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.

Treatment:

Drug: Tilpisertib