Phase 2 study GS-9674 in Primary Biliary Cholangitis without cirrhosis

• Research type

  Research Study

• Full title

  A Phase 2, Randomized, Double-Blind, Placebo Controlled Study Evaluating the Safety, Tolerability, and Efficacy of GS-9674 in Subjects with Primary Biliary Cholangitis Without Cirrhosis

• IRAS ID

  217105

• Contact name

  Gideon Hirschfield

• Contact email

  g.hirschfield@bham.ac.uk

• Sponsor organisation

  Gilead Sciences, Inc.

• Eudract number

  2016-002443-42

• Clinicaltrials.gov Identifier

  NCT02943447, IND number: 131032

• Duration of Study in the UK

  0 years, 2 months, 0 days

• Research summary

  Primary Biliary Cholangitis (PBC) is an autoimmune disorder which is characterised by infiltration of the liver with inflammatory cells and bile duct destruction that result in impairment of bile flow. Excess bile acid accumulation causes liver cell death that may lead to progressive liver fibrosis, including cirrhosis (or liver scarring) in some patients. The study medication known as GS-9674 has demonstrated an anti-scarring effect in rodent models. Clinical data with obeticholic acid, an analog of bile acid chenodeoxycholic acid (CDCA) which activates the FXR(a bile acid receptor), has shown liver biochemistry improvements in patients with PBC supporting the potential of FXR agonists in this condition. Thus, FXR agonist,GS-9674 is postulated to be beneficial in participants with PBC.
  This study will evaluate the safety, tolerability,and efficacy of 30mg and 100mg of GS-9674 administered in participants with PBC. The doses were selected based on short-term safety, pharmacodynamic and pharmacokinetic (PD and PK)results from Study in healthy participants.
  Participants will be randomly assigned to one of the following treatment groups:
  -GS-9674 30mg + Placebo-to-match (PTM) GS-9674 100mg orally once daily
  -GS-9674 100mg + PTM GS-9674 30mg orally once daily
  -PTM GS-9674 30 mg + PTM GS-9674 100mg orally once daily

  In this study approximately 75 participants will be enrolled at multiple sites globally. Eligible participants will attend a 4 week screening period, a blinded treatment period of 12 weeks, and a follow-up visit 4 weeks after completion of blinded treatment. Participants completing the Blinded Study Phase without permanently discontinuing study medication will be eligible to participate in the Open Label Extension (OLE) Phase of the study. This includes a 96 week OLE and a follow-up visit 4 weeks after completion of treatment. Participation in the Blinded Study Phase can last up to 20 weeks and OLE Phase can last up to 100 weeks, thus total study duration can be up to 120 weeks.

• REC name

  South Central - Berkshire Research Ethics Committee

• REC reference

  16/SC/0677

• Date of REC Opinion

  9 Jan 2017

• REC opinion

  Favourable Opinion