Simtuzumab (SIM, GS-6624) in the Treatment of Cirrhosis Due to NASH

Gilead Sciences

Status and phase: Terminated; Phase 2

Conditions: Liver Fibrosis Due to NASH

Treatments: Biological: SIM; Biological: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01672879

GS-US-321-0106

2012-002489-11 (EudraCT Number)

Details and patient eligibility

About

The primary objective of this study is to evaluate the safety and efficacy of SIM (formerly referred to as GS-6624) in adults with compensated cirrhosis due to Non-Alcoholic Steatohepatitis (NASH). It will consist of 2 phases:

• Randomized Double-Blind Phase
• Open-Label Phase (optional)

Enrollment: 259 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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259 participants in 3 patient groups, including a placebo group

SIM 200 mg

Experimental group

Description:

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.

Treatment:

Biological: SIM

SIM 700 mg

Experimental group

Description:

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.

Treatment:

Biological: SIM

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Biological: Placebo

Biological: SIM