Safety and Efficacy of Sofosbuvir Plus Velpatasvir With or Without Ribavirin in Treatment-experienced Subjects With Chronic HCV Infection

Study Overview
=================
Brief Summary
-----------------
The primary objectives of this study are to evaluate the antiviral efficacy, safety, and tolerability of sofosbuvir (SOF) + velpatasvir (VEL; GS-5816) with or without ribavirin (RBV) in treatment-naive adults with chronic genotype (GT) 1 or 3 hepatitis C virus (HCV) infection.

Official Title
-----------------
A Phase 2, Multicenter, Randomized, Open-Label Study to Investigate the Safety and Efficacy of Sofosbuvir + GS-5816 for 12 Weeks in Treatment-Experienced Subjects With Chronic HCV Infection

Conditions
-----------------
Hepatitis C

Intervention / Treatment
-----------------
* Drug: SOF
* Drug: VEL
* Drug: RBV


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Body mass index (BMI) ≥ 18 kg/m^2 HCV RNA ≥ 10000 IU/mL at screening Prior treatment failure to a regimen including interferon with or without RBV HCV genotype 1 or 3 Chronic HCV infection Cirrhosis determination Use of highly effective contraception methods if female of childbearing potential or sexually active male Exclusion Criteria: Current or prior history of clinically significant illness other than HCV Screening ECG with clinically significant abnormalities Prior exposure to HCV specific direct acting antiviral agent Pregnant or nursing female or male with pregnant female partner Chronic liver disease of non-HCV etiology Hepatitis B Active drug abuse Use of any prohibited concomitant medications

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+VEL 25 mg (GT3) without cirrhosis<br>Participants with genotype 3 HCV infection without cirrhosis will receive SOF+VEL 25 mg for 12 weeks. | Drug: SOF<br>* 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;|
| Experimental: SOF+VEL 25mg+RBV (GT3) without cirrhosis<br>Participants with genotype 3 HCV infection without cirrhosis will receive SOF+VEL 25 mg plus RBV for 12 weeks. | Drug: SOF<br>* 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;Drug: VEL<br>* Tablet administered orally once daily<br>* Other names: GS-5816;Drug: RBV<br>* 200 mg tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)<br>* Other names: Ribasphere®;|
| Experimental: SOF+VEL 100 mg (GT3) without cirrhosis<br>Participants with genotype 3 HCV infection without cirrhosis will receive SOF+VEL 100 mg for 12 weeks. | Drug: SOF<br>* 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;Drug: VEL<br>* Tablet administered orally once daily<br>* Other names: GS-5816;|
| Experimental: SOF+VEL 100 mg+RBV (GT3) without cirrhosis<br>Participants with genotype 3 HCV infection without cirrhosis will receive SOF+VEL 100 mg plus RBV for 12 weeks. | Drug: SOF<br>* 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;Drug: VEL<br>* Tablet administered orally once daily<br>* Other names: GS-5816;Drug: RBV<br>* 200 mg tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)<br>* Other names: Ribasphere®;|
| Experimental: SOF+VEL 25 mg (GT3) with cirrhosis<br>Participants with genotype 3 HCV infection with cirrhosis will receive SOF+VEL 25 mg for 12 weeks. | Drug: SOF<br>* 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;Drug: VEL<br>* Tablet administered orally once daily<br>* Other names: GS-5816;|
| Experimental: SOF+VEL 25 mg+RBV (GT3) with cirrhosis<br>Participants with genotype 3 HCV infection with cirrhosis will receive SOF+VEL 25 mg plus RBV for 12 weeks. | Drug: SOF<br>* 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;Drug: RBV<br>* 200 mg tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)<br>* Other names: Ribasphere®;|
| Experimental: SOF+VEL 100 mg (GT3) with cirrhosis<br>Participants with genotype 3 HCV infection with cirrhosis will receive SOF+VEL 100 mg for 12 weeks. | Drug: SOF<br>* 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;Drug: VEL<br>* Tablet administered orally once daily<br>* Other names: GS-5816;|
| Experimental: SOF+VEL 100 mg+RBV (GT3) with cirrhosis<br>Participants with genotype 3 HCV infection with cirrhosis will receive SOF+VEL 100 mg plus RBV for 12 weeks. | Drug: SOF<br>* 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;Drug: VEL<br>* Tablet administered orally once daily<br>* Other names: GS-5816;Drug: RBV<br>* 200 mg tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)<br>* Other names: Ribasphere®;|
| Experimental: SOF+VEL 25 mg (GT1)<br>Participants with genotype 1 HCV infection will receive SOF+VEL 25 mg for 12 weeks. | Drug: SOF<br>* 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;Drug: VEL<br>* Tablet administered orally once daily<br>* Other names: GS-5816;|
| Experimental: SOF+VEL 25 mg+RBV (GT1)<br>Participants with genotype 1 HCV infection will receive SOF+VEL 25 mg plus RBV for 12 weeks. | Drug: SOF<br>* 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;Drug: VEL<br>* Tablet administered orally once daily<br>* Other names: GS-5816;Drug: RBV<br>* 200 mg tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)<br>* Other names: Ribasphere®;|
| Experimental: SOF+VEL 100 mg (GT1)<br>Participants with genotype 1 HCV infection will receive SOF+VEL 100 mg for 12 weeks. | Drug: SOF<br>* 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;Drug: VEL<br>* Tablet administered orally once daily<br>* Other names: GS-5816;|
| Experimental: SOF+VEL 100 mg+RBV (GT1)<br>Participants with genotype 1 HCV infection will receive SOF+VEL 100 mg plus RBV for 12 weeks. | Drug: SOF<br>* 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;Drug: VEL<br>* Tablet administered orally once daily<br>* Other names: GS-5816;Drug: RBV<br>* 200 mg tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)<br>* Other names: Ribasphere®;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment. | Posttreatment Week 12 | 
| Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event |  | Up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 and SVR 24 were defined as HCV RNA < LLOQ at 4 and 24 weeks after stopping study treatment, respectively. | Posttreatment Weeks 4 and 24 | 
| Percentage of Participants With Virologic Failure | Virologic failure was defined as: On-treatment virologic failure: Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment) Virologic relapse: Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit. | Up to Posttreatment Week 24 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hepatitis, Genotype 1, Genotype 3, Treatment experienced