Safety and Efficacy of Simtuzumab (SIM, GS-6624) in Adults With Advanced Liver Fibrosis But Not Cirrhosis Secondary to Non-Alcoholic Steatohepatitis (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

NCT01672866

2012-002488-88 (EudraCT Number)

GS-US-321-0105

Details and patient eligibility

About

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)

Enrollment: 222 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• 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 Exclusion Criteria:

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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222 participants in 3 patient groups, including a placebo group

SIM 75 mg

Experimental group

Description:

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.

Treatment:

Biological: SIM

SIM 125 mg

Experimental group

Description:

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.

Treatment:

Biological: SIM

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Biological: Placebo

Biological: SIM