Triple DAAs Regimen in Treating Non-cirrhotic HCV GT1b Subjects

Study Overview
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Brief Summary
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The study is designed to test the hypothesis that the addition of a protease inhibitor to dual NS5a-NS5B nucleoside prodrug analog will enhance antiviral efficacy and hence shorten the treatment duration to 3 weeks.

Official Title
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Effect of Triple Direct Acting Antiviral Agents (DAAs) for Non-cirrhotic Subjects With Chronic HCV G1b Infection

Conditions
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Chronic Hepatitis C Infection

Intervention / Treatment
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* Drug: LDV/SOF+ASV
* Drug: SOF+DCV+SMV
* Drug: SOF+DCV+ASV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age equal to or greater than 18 years, with chronic genotype 1b HCV infection; HCV RNA level > 10,000 and < 10,000,000 IU/ml at Screening; Rapid response to triple DAAs therapy with less than 500 IU/ml plasma HCV RNA level at Day 2; No evidence of cirrhosis. Cirrhosis defined as any 1 of the following, within 6 months of study entry: Liver biopsy showing cirrhosis; Fibroscan showing cirrhosis or results>12.5 kPa ; FibroTest® score >0.75 and an aspartate aminotransferase (AST): platelet ratio index (APRI) >2 during screening. Exclusion Criteria: Pregnant or nursing female or male with pregnant female partner; HIV or chronic hepatitis B virus (HBV) infection; Hematologic or biochemical parameters at Screening outside the protocol-specified requirements; Active or recent history (≤ 1 year) of drug or alcohol abuse; Hepatocellular carcinoma or other malignancy (with exception of certain resolved skin cancers); History or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the subject's participation for the full duration of the study, such that it is not in the best interest of the subject to participate.

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LDV/SOF+ASV<br>Participants with genotype 1b HCV infection will receive LDV/SOF FDC + ASV 3 weeks. | Drug: LDV/SOF+ASV<br>* Ledipasvir/sofosbuvir (LDV/SOF) 90 mg/400 mg fixed-dose combination (FDC) tablet; administered orally once daily; Asunaprevir (ASV) 200mg, administered orally twice daily.<br>* Other names: Sunvepra®;|
| Experimental: SOF+DCV+SMV<br>Participants with genotype 1b HCV infection will receive SOF + DCV + SMV for 3 weeks. | Drug: SOF+DCV+SMV<br>* Sofosbuvir (SOF) 400 mg tablet administered orally once daily; Daclatasvir (DCV) 60 mg tablet administered orally once daily; Simeprevir (SMV) 150 mg tablet orally once daily.<br>* Other names: OLYSIO®;|
| Experimental: SOF+DCV+ASV<br>Participants with genotype 1b HCV infection will receive SOF + DCV + ASV for 3 weeks | Drug: SOF+DCV+ASV<br>* Sofosbuvir (SOF) 400 mg tablet administered orally once daily; Daclatasvir (DCV) 60 mg tablet administered orally once daily; Asunaprevir (ASV) 200mg, administered orally twice daily.<br>* Other names: Sunvepra®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with sustained virologic response 12 weeks after discontinuation of therapy (SVR12) | SVR12 is defined as HCV RNA < lower limit of quantification (LLOQ) 12 weeks after last dose of study drug. | Post treatment Week 12 | 
| Proportion of participants with adverse events leading to permanent discontinuation of study drug(s) |  | Baseline up to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with unquantifiable HCV viral load at specified time points during and after treatment. |  | Baseline up to Week 24 | 
| HCV RNA levels and change during and after treatment. |  | Baseline up to Week 24 | 
| Proportion of participants with on-treatment virologic breakthrough and relapse | Viral breakthrough is defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) during treatment, but did not achieve a sustained virologic response (SVR). Viral relapse is defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) within 4 weeks of end of treatment, but did not achieve an SVR. | Baseline up to Week 24 |