Phase 2 study GS-9674 in Primary Sclerosing Cholangitis w/o Cirrohsis

• 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 Sclerosing Cholangitis Without Cirrhosis

• IRAS ID

  217183

• Contact name

  Gideon Hirschfield

• Contact email

  g.hirschfield@bham.ac.uk

• Sponsor organisation

  Gilead Sciences, Inc.

• Eudract number

  2016-002442-23

• Clinicaltrials.gov Identifier

  NCT02943460

• Clinicaltrials.gov Identifier

  NCT02943460, IND number – 131031

• Duration of Study in the UK

  2 years, 6 months, 0 days

• Research summary

  Primary Sclerosing Cholangitis (PSC) is a disorder of unknown cause characterised by inflammation and fibrosis of the liver bile ducts that results in the impairment of bile flow (cholestasis). Accumulation of excess bile acid causes liver cell death that leads to progressive liver fibrosis and cirrhosis (scarring). In pre-clinical and clinical studies, FXR (bile acid receptor) agonists have been shown to reduce bile acid levels.

  This study will evaluate the safety, tolerability, and efficacy of 30 mg and 100 mg GS-9674 administered with food for 12 weeks in participants with PSC. The doses were selected based on short-term safety, PD and PK results from Study GS-US-402-1851 in healthy participants.

  Globally, approximately 50 participants will be randomly assigned in a 2:2:1 ratio to 1 of 3 different treatment groups during the Blinded Study Phase:
  - Group A: 20 participants taking GS-9674 30mg + PTM GS-9674 100mg orally once daily
  - Group B: 20 participants taking GS-9674 100mg + PTM GS-9674 30mg orally once daily
  - Group C: 10 participants taking PTM GS-9674 30mg + PTM GS-9674 100mg orally once daily

  To assess the safety and effectiveness of GS-9674 participants will attend a 4 week screening period, 12 weeks of blinded treatment and a Blinded Study Phase follow-up visit 4 weeks after completion of blinded treatment.
  Participants completing the Blinded Study Phase can participate in the OLE Phase of the study. All participants will receive 100mg GS-9674 orally once daily in the Open Label Extension (OLE) phase.
  There will be an option to enrol in a pharmacokinetic/pharmacodynamics (PK/PD) sub study to measure concentrations of GS-9674 (and its metabolites) and biomarkers.

  The treatment period is a total of 120 weeks .

• REC name

  South Central - Berkshire Research Ethics Committee

• REC reference

  16/SC/0676

• Date of REC Opinion

  9 Jan 2017

• REC opinion

  Favourable Opinion