Safety and Efficacy of Simtuzumab (SIM, GS-6624) in Adults With Advanced Liver Fibrosis But Not Cirrhosis Secondary to Non-Alcoholic Steatohepatitis (NASH)
- Conditions
- Liver Fibrosis Due to NASH
- Interventions
- Biological: SIMBiological: Placebo
- Registration Number
- NCT01672866
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The primary objective of this study is to evaluate whether SIM (formerly referred to as GS-6624) is effective at preventing the histologic progression of liver fibrosis and the clinical progression to cirrhosis in participants with NASH.
It will consist of 2 phases:
* Randomized Double-Blind Phase
* Open-Label Phase (optional)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 222
- Adults with chronic liver disease due to NASH defined as macrovesicular steatosis involving > 5% of hepatocytes on a liver biopsy with associated lobular inflammation
- Stage 3-4 fibrosis by Ishak score on a liver biopsy
- Exclusion of other causes of liver disease including viral hepatitis and alcoholic liver disease
- Must have aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 10 x Central Laboratory Upper Limit of Normal (clULN)
- Must have serum creatinine < 2.0 mg/dL
- A negative serum pregnancy test is required for females of childbearing potential
- All sexually active females of childbearing potential must agree to use a protocol recommended method of contraception during intercourse throughout the study and for 90 days following the last dose of study medication
- Lactating females must agree to discontinue nursing before starting study treatment
- Males, if not vasectomized, are required to use barrier contraception (condom plus spermicide) during heterosexual intercourse from the screening through the study completion and for 90 days following the last dose of study drug.
Key
- Pregnant or breast feeding
- Cirrhosis of the liver
- Any history of hepatic decompensation including ascites, hepatic encephalopathy or variceal bleeding
- Weight reduction surgery in the past 5 years
- Positive for hepatitis C virus (HCV) RNA
- Positive for HBsAg
- Alcohol consumption greater than 21oz/week for males or 14oz/week for females
- Positive urine screen for amphetamines, cocaine or opiates (i.e. heroin, morphine) at screening.
- Clinically significant cardiac disease
- History of malignancy, other than non-melanomatous skin cancer, within 5 years prior to screening
- Major surgical procedure within 30 days prior to screening or the presence of an open wound
- Known hypersensitivity to the investigation product or any of its formulation excipients
- History of bleeding diathesis within 6 months of screening
- Unavailable for follow-up assessment or concern for individual's compliance with the protocol procedures;
- Participation in an investigational trial of a drug or device within 30 days prior to screening
- BMI < 18 kg/m^2
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SIM 75 mg SIM During the Randomized Double-Blind Phase, participants will receive SIM 75 mg via subcutaneous injection once weekly for up to 240 weeks. During the optional Open-Label Phase, participants will receive SIM 125 mg via subcutaneous injection once weekly for up to an additional 240 weeks. SIM 125 mg SIM During the Randomized Double-Blind Phase, participants will receive SIM 125 mg via subcutaneous injection once weekly for up to 240 weeks. During the optional Open-Label Phase, participants will receive SIM 125 mg via subcutaneous injection once weekly for up to an additional 240 weeks. Placebo SIM During the Randomized Double-Blind Phase, participants will receive placebo to match SIM via subcutaneous injection once weekly for up to 240 weeks. During the optional Open-Label Phase, participants will receive SIM 125 mg via subcutaneous injection once weekly for up to an additional 240 weeks. Placebo Placebo During the Randomized Double-Blind Phase, participants will receive placebo to match SIM via subcutaneous injection once weekly for up to 240 weeks. During the optional Open-Label Phase, participants will receive SIM 125 mg via subcutaneous injection once weekly for up to an additional 240 weeks.
- Primary Outcome Measures
Name Time Method Event Free Survival (EFS) Using Kaplan-Meier Baseline up to the time of progression to cirrhosis or last dose date (maximum: 240 weeks in the Blinded Phase), which ever occurred first The EFS was the primary clinical efficacy endpoint and was assessed by the time to progression to cirrhosis. Participants were considered to have become cirrhotic if they had a post-baseline biopsy consistent with cirrhosis or developed overt signs and symptoms of cirrhosis. All overt signs and symptoms went through an adjudication process and were confirmed before they were considered for the EFS analysis.
Change From Baseline in MQC on Liver Biopsy Baseline to Week 96
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (68)
University Hospitals Case Medical Center
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
John Radcliffe Hospital
🇬🇧Headington, United Kingdom
Indianapolis Gastroenterology Research Foundation
🇺🇸Indianapolis, Indiana, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
University of Washington
🇺🇸Seattle, Washington, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Hôpital Erasme
🇧🇪Brussels, Belgium
Iowa Digestive Disease Center
🇺🇸Clive, Iowa, United States
Tulane University
🇺🇸New Orleans, Louisiana, United States
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Mercy Medical Center
🇺🇸Baltimore, Maryland, United States
Lahey Clinic
🇺🇸Burlington, Massachusetts, United States
Minnnesota Gastroenterology, PA
🇺🇸Saint Paul, Minnesota, United States
State University Of New York
🇺🇸Buffalo, New York, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
Walter Reed National Military Medical Center
🇺🇸Bethesda, Maryland, United States
Saint Louis University Hospital
🇺🇸Saint Louis, Missouri, United States
Texas Clinical Research Institute, LLC
🇺🇸Arlington, Texas, United States
University Gastroenterology
🇺🇸Providence, Rhode Island, United States
St. Luke's Episcopal Hospital
🇺🇸Houston, Texas, United States
Université Catholique de Louvain
🇧🇪Bruxelles, Belgium
Hopital Beaujon
🇫🇷Clichy, France
Azienda Ospedaliera San Camillo Forlanini
🇮🇹Roma, Italy
Fundacion De Investigacion
🇵🇷San Juan, Puerto Rico
Hospital Donostia
🇪🇸San Sebastian, Spain
Gastroenterologisch-Hepatologisches Zentrum Kiel
🇩🇪Kiel, Germany
Hospital Universitario Puerta de Hierro
🇪🇸Majadahonda, Spain
The Royal London Hospital
🇬🇧London, United Kingdom
Hospital Saint-Antoine
🇫🇷Paris, France
Duke University
🇺🇸Durham, North Carolina, United States
University of California, San Diego (UCSD)
🇺🇸San Diego, California, United States
Southern California Liver Centers
🇺🇸Coronado, California, United States
University of California San Francisco (UCSF)
🇺🇸San Francisco, California, United States
Tampa General Hospital
🇺🇸Tampa, Florida, United States
Miami Veterans Administration Healthcare System
🇺🇸Miami, Florida, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Mount Sinai Hospital
🇺🇸New York, New York, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Brooke Army Medical Center
🇺🇸Fort Sam Houston, Texas, United States
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
Alamo Clinical Research Associates
🇺🇸San Antonio, Texas, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Digestive and Liver Disease Specialists
🇺🇸Norfolk, Virginia, United States
Bucheon St. Marys Hospital
🇺🇸Richmond, Virginia, United States
Virginia Commonwealth University Health System
🇺🇸Richmond, Virginia, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
UZ Ghent
🇧🇪Gent, Belgium
University of Calgary
🇨🇦Calgary, Alberta, Canada
University of Manitoba
🇨🇦Winnipeg, Manitoba, Canada
London Health Science Center
🇨🇦London, Ontario, Canada
Toronto Liver Centre
🇨🇦Toronto, Ontario, Canada
Azienda Ospedaliera Città della Salute e della Scienza di Torino
🇮🇹Torino, Italy
CHU Strasbourg Hôpital Civil
🇫🇷Strasbourg, France
Groupe Hospitalier Pitié- Salpétrière
🇫🇷Paris, France
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Azienda Ospedaliero-Universitaria di Modena Policlinico
🇮🇹Modena, Italy
EUGASTRO GmbH
🇩🇪Leipzig, Germany
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Royal Free Hospital, Pond Street
🇬🇧London, United Kingdom
King's College Hospital NHS Foundation Trust No. 1 Account
🇬🇧London, United Kingdom
Nottingham University Hospitals Queens Medica
🇬🇧Nottingham, United Kingdom
Liver Institute of Virginia
🇺🇸Newport News, Virginia, United States