Selonsertib in Combination With Prednisolone Versus Prednisolone Alone in Participants With Severe Alcoholic Hepatitis (AH)
A Phase 2, Double-Blind, Randomized Study Evaluating the Safety, Tolerability, and Efficacy of GS-4997 in Combination With Prednisolone Versus Prednisolone Alone in Subjects With Severe Alcoholic Hepatitis (AH)
2 other identifiers
interventional
104
7 countries
44
Brief Summary
The primary objective of this study is to evaluate the safety and tolerability of selonsertib (GS-4997) in combination with prednisolone versus prednisolone alone in participants with severe alcoholic hepatitis (AH).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Sep 2016
44 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 29, 2016
CompletedFirst Posted
Study publicly available on registry
August 3, 2016
CompletedStudy Start
First participant enrolled
September 1, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 16, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
May 31, 2018
CompletedResults Posted
Study results publicly available
February 6, 2019
CompletedFebruary 6, 2019
February 1, 2019
1.5 years
July 29, 2016
December 21, 2018
February 5, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants With Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Grade 3 or 4 Laboratory Abnormalities
An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. Laboratory toxicity grading was based on Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.
Up to Day 28 plus 30 days
Secondary Outcomes (26)
Percentage of Participants Who Died by Day 28
Day 28
Percentage of Participants Who Died by Week 8
Week 8
Percentage of Participants Who Died by Week 12
Week 12
Percentage of Participants Who Died by Week 24
Week 24
Percentage of Participants With Survival at Day 28 Using Kaplan-Meier
Day 28
- +21 more secondary outcomes
Study Arms (2)
Selonsertib + Prednisolone
EXPERIMENTALSelonsertib + prednisolone for 28 days
Prednisolone
PLACEBO COMPARATORSelonsertib placebo + prednisolone for 28 days
Interventions
18 mg tablet administered orally once daily
40 mg (4 x 10 mg tablets) administered orally once daily
Eligibility Criteria
You may qualify if:
- Willing and able to give informed consent prior to any study specific procedures being performed. In individuals with hepatic encephalopathy (HE) which may impair decision-making, consent will be obtained per hospital procedures (eg, by Legally Authorized Representative)
- Clinical diagnosis of severe AH
- Maddrey's Discriminant Function (DF) ≥ 32 at screening
You may not qualify if:
- Pregnant or lactating females;
- Other causes of liver disease including chronic hepatitis B (hepatitis B surface antigen \[HBsAg\] positive), chronic hepatitis C (HCV RNA positive), acetaminophen hepatotoxicity, biliary obstruction, and autoimmune liver disease;
- Serum aspartate aminotransferase (AST) \>400 U/L or alanine aminotransferase (ALT) \>300 U/L;
- Model for End Stage Liver Disease (MELD) \>30 at screening;
- Maddrey's DF \>60 at screening;
- Grade 4 Hepatic Encephalopathy (HE) by West Haven criteria;
- Concomitant or previous history of hepatocellular carcinoma;
- History of liver transplantation;
- HIV Ab positive;
- Clinical suspicion of pneumonia;
- Uncontrolled sepsis;
- Uncontrolled gastrointestinal (GI) bleeding or controlled GI bleeding within 7 days of screening that was associated with shock or required transfusion of more than 3 units of blood;
- Type 1 hepatorenal syndrome (HRS) or renal failure defined as a serum creatinine \>221 μmol/L (\>2.5 mg/dL) or the requirement for renal replacement therapy;
- Individuals dependent on inotropic (eg, epinephrine or norepinephrine) or ventilatory support (ie, endotracheal intubation or positive-pressure ventilation);
- Portal vein thrombosis;
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Gilead Scienceslead
Study Sites (44)
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Southern California Research Centers
Coronado, California, United States
Cedars Sinai Medical Center
Los Angeles, California, 90048, United States
Cleveland Clinic Florida
Weston, Florida, United States
Oschner Medical Center
New Orleans, Louisiana, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
University of Michigan
Ann Arbor, Michigan, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Methodist Healthcare Dallas - The Liver Institute
Dallas, Texas, United States
Liver Institute of Virginia
Newport News, Virginia, United States
University of Washington
Seattle, Washington, United States
Medizinische Universitat Graz
Graz, Austria
Universitätsklinik für Innere Medizin I
Innsbruck, Austria
Medical University Vienna
Vienna, Austria
Cliniques Universitaires UCL Saint-Luc
Brussels, Belgium
CUB Hopital Erasme
Brussels, Belgium
Ghent University Hospital
Ghent, Belgium
Universitair Ziekenhuis Leuven
Leuven, Belgium
Centre Hospitalier Universitaire de Liege
Liège, Belgium
University of Calgary
Calgary, Alberta, Canada
University of Manitoba
Winnipeg, Manitoba, Canada
Toronto General Hospital
Toronto, Ontario, Canada
CHU Amiens Picardie
Amiens, France
CHU Angers
Angers, France
Hôpital Jean Minjoz
Besançon, France
C.H.U. de Caen
Caen, France
CHU henri Mondor
Créteil, France
CHU de Grenoble- Hopital Michallon
La Tronche, France
CHRU de Lille
Lille, France
Hôpital de la Croix Rousse
Lyon, France
Hopital La Pitie Salpetriere
Paris, France
Hopital Paul Brousse
Villejuif, France
University of Zurich
Zurich, Switzerland
Brighton & Sussex University Hospitals NHS Trust
Brighton, United Kingdom
Hull and East Yorkshire Hospitals NHS Trust
Hull, United Kingdom
Royal Liverpool & Broadgreen University Hospitals NHS Trust
Liverpool, United Kingdom
Barts Health NHS Trust
London, United Kingdom
Chelsea and Westminster Hospital
London, United Kingdom
Imperial College
London, United Kingdom
Kings College Hospital NHS Trust
London, United Kingdom
Freeman Hospital
Newcastle, United Kingdom
Nottingham University Hospitals NHS Trust
Nottingham, United Kingdom
Derriford Hospital
Plymouth, United Kingdom
Portsmouth Hospitals NHS Trust
Portsmouth, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Gilead Clinical Study Information Center
- Organization
- Gilead Sciences
Study Officials
- STUDY DIRECTOR
Gilead Study Director
Gilead Sciences
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 29, 2016
First Posted
August 3, 2016
Study Start
September 1, 2016
Primary Completion
February 16, 2018
Study Completion
May 31, 2018
Last Updated
February 6, 2019
Results First Posted
February 6, 2019
Record last verified: 2019-02