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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2a Study of an Anti-LOXL2 Monoclonal Antibody (GS-6624) in HIV and/or Hepatitis C- Infected Subjects With Liver Fibrosis

Conditions
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Hepatitis C, HIV, Liver Fibrosis, HIV/HCV Co-infection

Intervention / Treatment
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* Biological: Simtuzumab


Participation Criteria
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Eligibility Criteria
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Key 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simtuzumab in HIV Patients<br>HIV-infected participants will receive simtuzumab every 2 weeks for 24 weeks while continuing on standard therapy for HIV. | Biological: Simtuzumab<br>* 700 mg intravenously for a total of 12 infusions.<br>* Other names: GS-6624;|
| Experimental: Simtuzumab in HCV Patients<br>HCV-infected participants will receive simtuzumab every 2 weeks for 24 weeks. | Biological: Simtuzumab<br>* 700 mg intravenously for a total of 12 infusions.<br>* Other names: GS-6624;|
| Experimental: Simtuzumab in HIV/HCV Co-Infected Patients<br>HIV/HCV co-infected participants will receive simtuzumab every 2 weeks for 24 weeks while continuing on standard therapy for HIV. | Biological: Simtuzumab<br>* 700 mg intravenously for a total of 12 infusions.<br>* Other names: GS-6624;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events |  | First dose date up to Week 24 plus 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at 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. | Baseline; Week 24 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver Fibrosis, Fibrosis, HIV, HCV, GS-6624, Hepatitis, Hepatitis C