Study of Simtuzumab in HIV and/or Hepatitis C- Infected Adults With Liver Fibrosis

Phase 2

Completed

Brief Summary: The primary objective of this study is to assess the safety and tolerability of simtuzumab (formerly GS-6624) in HIV and/or hepatitis C virus (HCV)-infected adults with evidence of liver fibrosis.

Recruitment & Eligibility

Inclusion Criteria

HIV-infected individuals must have positive serologies with viral load suppressed below 400 copies/mL
HCV-infected individuals must have:
- Chronic HCV infection with HCV RNA ≥ 2000 IU/ml AND at least 1 of the following:
- Been null responder to previous pegylated interferon and ribavirin therapy OR
- Failed to achieve sustained virologic response (SVR) on a regimen containing a direct-acting antiviral (DAA) in addition to pegylated interferon and ribavirin OR
- Are unwilling to receive or have contraindications to interferon therapy for HCV
HIV/HCV co-infected individuals must have:
- Positive HIV serologies with viral load suppressed below 400 copies/mL
- Chronic HCV infection with HCV RNA ≥ 2000 IU/ml AND at least 1 of the following:
- Been null responder to previous pegylated interferon and ribavirin therapy OR
- Failed to achieve SVR on a regimen containing a direct-acting antiviral (DAA) in addition to pegylated interferon and ribavirin OR
- Are unwilling to receive or have contraindications to interferon therapy for HCV
Willing to allow blood and tissue samples to be stored for future use to study HIV infection, immune function, liver disease and additional mechanisms involved in liver fibrosis among patients with HIV and/or HCV, which may not be related directly to the specific objectives of this study protocol
Have a primary care physician

Key

Exclusion Criteria

Cause of liver fibrosis other than HCV or long-term antiretroviral therapy (ART) treatment for HIV
Currently being treated for HCV
Evidence of active Hepatitis A, B or D infections
History or evidence of hepatocellular carcinoma
Unwillingness to undergo a liver biopsy pre-treatment and post-treatment, or to undergo all other protocol required tests/procedures or return to the site for required visits
Presence of contraindications to magnetic resonance imaging (e.g., presence of any metal in the body, cardiac or neural pacemaker, aneurysm clip, cochlear implant, claustrophobia)

Arm && Interventions

Group	Intervention	Description
Simtuzumab in HIV Patients	Simtuzumab	HIV-infected participants will receive simtuzumab every 2 weeks for 24 weeks while continuing on standard therapy for HIV.
Simtuzumab in HCV Patients	Simtuzumab	HCV-infected participants will receive simtuzumab every 2 weeks for 24 weeks.
Simtuzumab in HIV/HCV Co-Infected Patients	Simtuzumab	HIV/HCV co-infected participants will receive simtuzumab every 2 weeks for 24 weeks while continuing on standard therapy for HIV.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Experiencing Treatment-Emergent Adverse Events	First dose date up to Week 24 plus 30 days

Secondary Outcome Measures

Name	Time	Method
Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24	Baseline; Week 24	The Ishak fibrosis score measures the degree of liver fibrosis (scarring) and ranges from 0 (best) to 6 (worst). A negative value in change from baseline indicates an improvement and a positive value indicates worsening.
Change From Baseline in HVPG at Week 24	Baseline; Week 24
Change From Baseline in MQC at Week 24	Baseline; Week 24
Change From Baseline in Alpha SMA at Week 24	Baseline; Week 24
Change From Baseline in Liver Fibrosis as Estimated by MRE at Week 24	Baseline; Week 24