Simtuzumab (SIM, GS-6624) in the Treatment of Cirrhosis Due to NASH (NASH)
Liver Fibrosis Due to NASH
About this trial
This is an interventional treatment trial for Liver Fibrosis Due to NASH focused on measuring NASH, cirrhosis, Compensated Liver disease, Monoclonal antibody, LOXL2, Simtuzumab, Nonalcoholic Steatohepatitis, Hepatic venous pressure gradient, HVPG, NAFLD, MRE, Liver biopsy, Liver fibrosis, Ishak
Eligibility Criteria
Key Inclusion Criteria:
- Adults with cirrhosis of the liver defined as an Ishak fibrosis stage ≥ 5
- Liver biopsy consistent with NASH or cryptogenic cirrhosis
- Exclusion of other causes of liver disease including viral hepatitis and alcoholic liver disease
- The liver biopsy sample must be determined to be adequate for evaluation by the Central pathologist
- Must have aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 10 x the upper limit of the normal range (ULN)
- Must have serum creatinine < 2.0 mg/dL
- A negative serum pregnancy test is required for female subjects of childbearing potential
- All sexually active female subjects of childbearing potential must agree to use a protocol recommended method of contraception during heterosexual 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
- Male subjects, 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 Exclusion Criteria:
- Pregnant or breast feeding
- Any history of hepatic decompensation including ascites, hepatic encephalopathy or variceal bleeding
- Weight reduction surgery in the past 5 year
- Child-Pugh-Turcotte (CPT) score >7; Model for End-Stage Liver Disease (MELD) score > 12 and Body Mass Index (BMI) <18kg/m2
- 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. Subjects on stable methadone or buprenorphine maintenance treatment for at least 6 months prior to screening may be included in the study. Subjects with a positive urine drug screen due to prescription opioid-based medication are eligible if the prescription and diagnosis are reviewed and approved by the investigator
- 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 subject's compliance with the protocol procedures;
- Participation in an investigational trial of a drug or device within 30 days prior to screening
- History of solid-organ transplant; poor venous access or requirement for permanent or semi-permanent central vein catheter such as portacath
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
- Mayo Clinic Hospital
- Southern California Liver Centers
- University of California, San Diego (UCSD)
- University of California San Francisco (UCSF)
- University of Colorado, Denver
- University of Miami
- Tampa General Hospital
- Northwestern University
- Indiana University School of Medicine, Division of Gastroenterology/Hepatology
- Iowa Digestive Disease Center
- University of Louisville
- Tulane University
- Mercy Medical Center
- Walter Reed National Military Medical Center
- Lahey Clinic
- University of Mississippi Medical Center
- Minnnesota Gastroenterology, PA
- Saint Louis University Hospital
- State University Of New York at Buffalo
- North Shore University Health System
- New York University
- Columbia University Medical Center
- Duke University Medical Center
- University Hospitals Case Medical Center
- University of Pennsylvania Hospital
- University Gastroenterology
- Medical University of South Carolina
- Methodist University Hospital
- Vanderbilt University Medical Center
- Texas Clinical Research Institute
- Brooke Army Medical Center
- St. Luke Episcopal Hospital
- Alamo Clinical Research Associates
- Intermountain Transplant Center
- University of Virginia Health Center
- Liver Institute of Virginia
- Digestive and Liver Disease Specialists
- Bucheon St. Marys Hospital
- Virginia Commonwealth University
- Virginia Mason Medical Center
- University of Washington
- University of Manitoba
- Dalhousie University
- Toronto Liver Centre
- Hôpital de la Croix Rousse
- Hospital Saint-Antoine
- CHU Pitié-Salpêtrière
- Fonds de Recherche Honoraires
- Gastroenterologisch-Hepatologisches Zentrum Kiel
- Eugastro Gmbh
- Istituto Clinico Humanitas
- Azienda Ospedaliero-Universitaria Policlinico di Modena
- Azienda Ospedaliera Città della Salute e della Scienza di Torino
- Fundacion De Investigacion
- Hospital Vall D´Hebron
- Hospital Universitario Puerta de Hierro
- Royal Free Hospital, Pond Street
- King's College Hospital NHS Trust
- Nottingham University Hospitals Queen's Medical Centre
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Placebo Comparator
SIM 200 mg
SIM 700 mg
Placebo
During the Randomized Double-Blind Phase, participants will receive SIM 200 mg via intravenous infusion every 2 weeks for up to 240 weeks. During the optional Open-Label Phase, participants will receive SIM 700 mg via intravenous infusion every 2 weeks for up to an additional 240 weeks.
During the Randomized Double-Blind Phase, participants will receive SIM 700 mg via intravenous infusion every 2 weeks for up to 240 weeks. During the optional Open-Label Phase, participants will receive SIM 700 mg via intravenous infusion every 2 weeks for up to an additional 240 weeks.
During the Randomized Double-Blind Phase, participants will receive placebo to match SIM administered via intravenous infusion every 2 weeks for up to 240 weeks. During the optional Open-Label Phase, participants will receive SIM 700 mg administered via intravenous infusion every 2 weeks for up to an additional 240 weeks.