Sofosbuvir Containing Regimens for the Treatment of Chronic HCV GT2 Infected Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the safety, tolerability, and efficacy of Sofosbuvir containing regimens in treatment-naive or treatment-experienced patients with HCV genotypes 2 infection.

Official Title
-----------------
Efficacy and Safety Study of Sofosbuvir Containing Regimens in Subjects With Chronic Hepatitis C Virus Genotype 2 Infection

Conditions
-----------------
Chronic Hepatitis C Infection

Intervention / Treatment
-----------------
* Drug: SOF+RBV
* Drug: SOF+DCV
* Drug: LDV/SOF


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age equal to or greater than 18 years, with chronic genotype 2 HCV infection; Documented HCV treatment-naïve or treatment-experienced subjects who failed previous PEG+RBV regimen; HCV RNA > 10,000 IU/mL at Screening; Screening laboratory values within defined thresholds Use of two effective contraception methods if female of childbearing potential or sexually active male 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).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SOF+RBV 8 wk<br>Participants will receive SOF+RBV for 8 weeks. | Drug: SOF+RBV<br>* Sofosbuvir (SOF) 400 mg tablet administered orally once daily. Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg).<br>* Other names: Copegus®;|
| Experimental: SOF+RBV 12 wk<br>Participants will receive SOF+RBV for 12 weeks. | Drug: SOF+RBV<br>* Sofosbuvir (SOF) 400 mg tablet administered orally once daily. Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg).<br>* Other names: Copegus®;|
| Experimental: SOF+DCV 8 wk<br>Participants will receive SOF+DCV for 8 weeks. | Drug: SOF+DCV<br>* Sofosbuvir (SOF) 400 mg tablet administered orally once daily. Daclatasvir (DCV) 60mg tablet administered once daily.<br>* Other names: Daklinza®;|
| Experimental: SOF+DCV 12 wk<br>Participants will receive SOF+DCV for 12 weeks. | Drug: SOF+DCV<br>* Sofosbuvir (SOF) 400 mg tablet administered orally once daily. Daclatasvir (DCV) 60mg tablet administered once daily.<br>* Other names: Daklinza®;|
| Experimental: LDV/SOF 8 wk<br>Participants will receive LDV/SOF for 8 weeks. | Drug: LDV/SOF<br>* Ledipasvir 90 mg /Sofosbuvir 400 mg (LDV/SOF) FDC tablet administered orally once daily<br>* Other names: Harvoni®;|
| Experimental: LDV/SOF 12 wk<br>Participants will receive LDV/SOF for 12 weeks. | Drug: LDV/SOF<br>* Ledipasvir 90 mg /Sofosbuvir 400 mg (LDV/SOF) FDC tablet administered orally once daily<br>* Other names: Harvoni®;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with sustained virologic response 12 weeks after discontinuation of therapy | 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 |