An investigational study to assess the safety and efficacy of a new investigational drug in subjects with Primary Sclerosing Cholangitis Without Cirrhosis

• Register: EUCTR
• Last refreshed on: 15 June 2020
• Main ID: EUCTR2016-002442-23-AT
• Date of registration: 21/12/2016
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc.
• Public title: An investigational study to assess the safety and efficacy of a new investigational drug in subjects with Primary Sclerosing Cholangitis Without Cirrhosis
• Scientific 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
• Date of first enrolment: 31/01/2017
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002442-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Canada, United Kingdom, United States

Contacts

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd.

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
-Diagnosis of PSC based on cholangiogram (magnetic resonance cholangiopancreatography [MRCP], endoscopic retrograde cholangiopancreatography [ERCP], or percutaneous transhepatic cholangiogram [PTC]) within the previous 12 months;

-Serum ALP > 1.67 x ULN;

-For subjects on ursodeoxycholic acid (UDCA), the dose of UDCA must have been stable for at least 12 months prior to screening through the end of treatment. For subjects not on UDCA, no UDCA use for at least 12 months before screening through the end of treatment;

-For subjects being administered biologic treatments (eg, antitumor necrosis factor [TNF] or anti-integrin monoclonal antibodies), immunosuppressants or systemic corticosteroids, the dose must have been stable at least 3 months prior to screening and anticipated to remain stable throughout the trial;

-Screening FibroSURE/FibroTest® <0.75 unless a historical liver biopsy within 12 months of screening does not reveal cirrhosis. In subjects with Gilbert's syndrome or hemolysis, FibroSURE/FibroTest® will be calculated using direct bilirubin instead of total bilirubin.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 43
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 7

Exclusion criteria:
-ALT > 10x ULN;
-Total bilirubin > 2x ULN;
-INR > 1.2 unless on anticoagulant therapy;
-Serum albumin < 3.3 g/dL;
-Cirrhosis of the liver as defined by any of the following:
a) Historical liver biopsy demonstrating stage 4 fibrosis (e.g. Ludwig stage 4 or Ishak stage =5);
b) History of decompensated liver disease, including ascites, hepatic encephalopathy or variceal bleeding;
c) Liver stiffness > 14.4 kPa by FibroScan®
-Small-duct PSC (histologic evidence of PSC with normal bile ducts on cholangiography);
-Other causes of liver disease including secondary sclerosing cholangitis and viral, metabolic, alcoholic, and other autoimmune conditions. Subjects with hepatic steatosis may be included if there is no evidence of nonalcoholic steatohepatitis (NASH) in the opinion of the investigator or on liver biopsy;
-Ascending cholangitis within 60 days of screening;
-Presence of a percutaneous drain or bile duct stent;
-Use of fibrates or obeticholic acid within 3 months prior to screening and through the end of treatment;
-Current, active inflammatory bowel disease (IBD) defined as a partial Mayo score of > 1 and/or a score on the Rectal Bleeding Domain > 0.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Primary Sclerosing Cholangitis
MedDRA version: 20.1 Level: LLT Classification code 10036732 Term: Primary sclerosing cholangitis System Organ Class: 100000004871

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Product Code: GS-9674
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Not available
CAS Number: 1418274-28-8
Current Sponsor code: GS-9674
Other descriptive name: GS-9674
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Code: GS-9674
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: not available
CAS Number: 1418274-28-8
Current Sponsor code: GS-9674
Other descriptive name: GS-9674
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Blinded phase: Baseline/Day 1 and at Weeks 1, 2, 4, 8, and 12
Open Label phase: Baseline/Day 1 and at Weeks 1, 2, 4, 8, 12 and every 12 weeks thereafter

Main Objective: The primary objective of this study is to evaluate the safety and tolerability of GS-9674 in subjects with primary sclerosing cholangitis (PSC).

Secondary Objective: The exploratory objectives of this study are as follows:
-To evaluate changes in serum alkaline phosphatase (ALP)
-To evaluate changes in serum bilirubin
-To assess changes in markers of liver injury and function: ALT, AST, GGT, albumin, and INR
-To assess changes in non-invasive markers of fibrosis including ELFTM test score and FibroSURE/FibroTest®
-To evaluate changes in liver stiffness as measured by FibroScan® and by Magnetic Resonance Elastography (MRE)
-To evaluate changes in biliary strictures as measured by Magnetic Resonance Cholangiopancreatography (MRCP)
-To determine the effect of GS-9674 on metabolism and cardiovascular risk factors (insulin resistance, hyperlipidemia, obesity and blood pressure)
-To evaluate the pharmacokinetics (PK) of GS-9674
-To evaluate the pharmacodynamic (PD) effects of GS-9674 as evidenced by changes in FGF19, C4, and bile acids
-To determine the effects of GS-9674 on quality of life as assessed by QoL questionnaires

Primary end point(s): To evaluate the safety and tolerability of GS-9674 in subjects with PSC

Secondary Outcome(s)

Secondary end point(s): -Change in serum ALP concentration
-Change in serum bilirubin concentration
-Change from baseline in markers of liver injury and function: ALT, AST, GGT, INR, and albumin
-Change from baseline in liver stiffness by FibroScan® and MRE
-Change from baseline in biliary strictures as assessed by MRCP
-Change from baseline in non-invasive markers of fibrosis including the ELF™ test score and FibroSURE/FibroTest®
-Change from baseline in Mayo Risk Score and UK-PSC Risk Score
-Change from baseline in health-related QoL measures
-Change from baseline in measures of pruritus
-Change from baseline in HOMA-IR, serum lipid profiles, and HbA1c levels
-Change from baseline in Pooled Cohort Risk Score

Timepoint(s) of evaluation of this end point: Blinded phase: Baseline/Day 1 and at Weeks 1, 2, 4, 8, and 12
Open Label phase: Baseline/Day 1 and at Weeks 1, 2, 4, 8, 12 and every 12 weeks thereafter

Secondary ID(s)

GS-US-428-4025

NCT02943460

2016-002442-23-GB

Source(s) of Monetary Support

Gilead Sciences, Inc.

Ethics review

Status: Approved
Approval date: 31/01/2017
Contact:

Results

• Results available: Yes
• Date Posted: 31/07/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-002442-23/results