Pilot Study of Simtuzumab in the Treatment of Liver Fibrosis

A Phase 2a, Pilot, Open-Label Trial Evaluating the Safety, Tolerability and Pharmacodynamic Effects of GS-6624 in Subjects With Fibrosis of the Liver

This study will evaluate the safety and tolerability of simtuzumab (GS-6624) in patients with fibrosis of the liver.

Up to 20 participants will be enrolled into two sequential cohorts. Cohort 1 will consist of 10 participants who will receive simtuzumab every other week for a total of 3 infusions. Participants in Cohort 2 (10 subjects) will also receive simtuzumab every other week for a total of 3 infusions; the dose will depend on the safety and tolerability of simtuzumab seen in Cohort 1.

Participants from both cohorts who have completed the main study will be allowed to continue on simtuzumab treatment for an additional extension period, and will receive up to 13 additional infusions of simtuzumab at a fixed dose of 700 mg for an additional 24 weeks.

Inclusion Criteria:

• Males and females 18 - 65 years of age
• Chronic liver disease of any etiology
• Stage 1-3 fibrosis by Metavir score on a liver biopsy.
• Body mass index <36 kg/m2

Exclusion Criteria:

• Any evidence of hepatic decompensation past or present
• Subjects currently abusing amphetamines, cocaine, opiates, or alcohol
• Clinically significant cardiac disease
• History of cancer, other than non-melanomatous skin cancer, within 5 years prior to Screening
• Systemic fungal, bacterial, viral, or other infection that is not controlled
• Use of systemic immunosuppressants within 28 days of the Pre-treatment Phase
• Use of approved therapy for hepatitis C or hepatitis B virus within 28 days of the Pre-treatment Phase
• Pregnant or lactating
• History of bleeding diathesis within the last 6 months of study Day 1