A Phase II Trial of Sofosbuvir (SOF) and GS-5816 for People With Chronic Hepatitis C Virus Infection and Recent Injection Drug Use

Study Overview
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Brief Summary
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To evaluate the proportion of patients with undetectable HCV RNA at 12 weeks post end of treatment (SVR12) following sofosbuvir/GS-5816 therapy for 12 weeks in people with chronic HCV infection and recent injection drug use.

Official Title
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A Phase II, Open-label, Single Arm, Multicentre, International Trial of Sofosbuvir (SOF) and GS-5816 for People With Chronic Hepatitis C Virus Infection and Recent Injection Drug Use

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Sofosbuvir (SOF)/GS-5816


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants have voluntarily signed the informed consent form. 18 years of age or older. Chronic HCV infection as defined by anti-HCV antibody or HCV RNA detection for greater than 6 months. HCV RNA plasma ≥ 1000 IU/ml at Screening. HCV genotypes 1-6. Recent injecting drug use (previous 6 months). Compensated liver disease. Participants with Fibroscan >12 KPa or AFP >50 ng/mL must have an abdominal ultrasound or CT scan without evidence of hepatocellular carcinoma within 2 months prior to screening. Negative pregnancy test at baseline (females of childbearing potential only). All fertile males and females must be using effective contraception during treatment and during the 30 days after treatment end. Exclusion Criteria: History of any of the following: Clinically significant illness (other than HCV) or any other major medical disorder that may interfere with the participant treatment, assessment or compliance with the protocol; participants currently under evaluation for a potentially clinically significant illness (other than HCV) are also excluded. Clinical hepatic decompensation (i.e. ascites, encephalopathy or variceal haemorrhage) Solid organ transplant Malignancy within 5 years prior to screening, with exception of specific cancers that may have been cured by surgical resection (basal cell skin cancer, etc.). Subjects under evaluation for possible malignancy are also excluded. Significant drug allergy (such as anaphylaxis or hepatotoxicity). Screening ECG with clinically significant abnormalities Any of the following lab parameters at screening: ALT > 10 x ULN AST > 10 x ULN Direct bilirubin > 1.5 x ULN Platelets < 50,0000/μL HbA1c > 8.5% Creatinine clearance (CLcr) < 60 mL/min Haemoglobin < 11 g/dL for females ; < 12 g/dL for males Albumin < 30g/L INR > 1.5 ULN unless subject has known haemophilia or is stable on an anticoagulant regimen affecting INR Pregnant or nursing female. HIV infection or HBV infection (HBcAb and HBsAg positive) Use of prohibited concomitant medications as described in section 5.2 Chronic use of systemically administered immunosuppressive agents (e.g. prednisone equivalent > 10 mg/day) Known hypersensitivity to GS-5816, sofosbuvir (SOF) or formulation excipients. Therapy with any anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) ≤6 months prior to the first dose of study drug. Any investigational drug ≤6 weeks prior to the first dose of study drug. Previous therapy with sofosbuvir (SOF) or an NS5A inhibitor prior to the first dose of study drug. Ongoing severe psychiatric disease as judged by the treating physician. Frequent injecting drug use that is judged by the treating physician to compromise treatment safety. Inability or unwillingness to provide informed consent or abide by the requirements of the study.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sofosbuvir (SOF)/GS-5816<br>12 weeks of Sofosbuvir (SOF)/GS-5816 (400mg/100mg) in an oral once-daily fixed dose combination | Drug: Sofosbuvir (SOF)/GS-5816<br>* 12 weeks of Sofosbuvir (SOF)/GS-5816 (400mg/100mg) in an oral once-daily fixed dose<br>* Other names: SOF/GS-5816;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Virological Response (SVR12) | To evaluate the proportion of patients with undetectable HCV RNA at 12 weeks post end of treatment (SVR12) following sofosbuvir (SOF)/GS-5816 therapy for 12 weeks in people with chronic HCV infection and recent injection drug use. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment adherence | To evaluate the proportion of patients adherent to therapy (both on-treatment adherence and treatment discontinuation) | Baseline to Week 12 | 
| Impact of adherence on therapy (association between adherence and response to treatment ) | To evaluate the association between adherence and response to treatment [including an evaluation of the impact of early (0-3 weeks), mid (4-7 weeks) and late (8-11 weeks) missed doses on response to therapy]; Adehernce will be measure via a self report quesitonanire and pill counts via return of the weeekly blister packs. The impact of the number and timing of missed pills will be evaluated. | early (0-3 weeks), mid (4-7 weeks) and late (8-11 weeks) during therapy | 
| Factors associated with on-treatment adherence | To evaluate factors associated with on-treatment adherence >90% and treatment discontinuation. Demographic and behavioural factors will be examined. | Baseline to Week 12 | 
| End of Treatment Response (ETR) (proportion of participants with undetectable HCV RNA at the end of treatment (ETR) | To evaluate the proportion of participants with undetectable HCV RNA at the end of treatment (ETR) | Week 12 | 
| Safety and tolerability (number and type of adverse events and serious adverse events) | To evaluate the number and type of adverse events and serious adverse events on treament and for 12 weeks post end of treatment | Baseline to Week 24 | 
| Change in drug use | To evaluate the change in drug use during treatment | Baseline to Week 12 | 
| Change in mental health | To evaluate the change in mental health during treatment | Basleine to Week 12 | 
| Change in health related quality of life | To evaluate the change in health-related quality of life during treatment | Baseline to Week 12 | 
| Impact of mixed infection on treatment response | To evaluate the rate of mixed HCV infection at baseline and among those with treatment non-response | Baseline to Week 24 | 
| Reinfection Rate | To evaluate the rate of HCV reinfection during and up to two years following treatment | Week 108 | 
| Immunovirological factors associated with treatment clearance | To evaluate immunovirological factors associated with treatment clearance. We will evaluate cytokines and chemokines (e.g. interferon inducible protein 10), T-cell responses, viral evolution and genetic markers (e.g. inteferon lambda 4) that are potentially associated with treatment induced clearance | Week 24 | 
| Utility of Dried Blood Spot (DBS) (method for monitoring HCV including treatment response) | To evaluate the utility of dried blood spot (DBS) as a simple method for monitoring HCV including treatment response. HCV RNA will be measured from DBS samples and then compared to HCV RNA levels measured using standard methods (EDTA Plasma samples and Roche Taqman) | Week 108 |