Efficacy and Safety of Sofosbuvir Containing Regimens for the Treatment of Chronic HCV Infection in Participants With Chronic Genotype 1, 2, 3, or 6 HCV Infection

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the antiviral efficacy, safety, tolerability of combination therapy with sofosbuvir (SOF) containing regimens for the treatment of chronic hepatitis C virus (HCV) infection.

Official Title
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A Phase 2, Multicenter, Open-Label Study to Assess the Efficacy and Safety of Sofosbuvir Containing Regimens for the Treatment of Chronic HCV Infection

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Drug: LDV/SOF
* Drug: SOF
* Drug: RBV
* Drug: Peg-IFN
* Drug: GS-9669
* Drug: VEL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic genotype 1, 2, 3, or 6 HCV infection Cirrhosis determination; a liver biopsy may be required 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 Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain resolved skin cancers) Chronic use of systemic immunosuppressive agents History of clinically significant illness or any other medical disorder that may interfere with the individual's treatment, assessment or compliance with the protocol

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: Cohort 1,Group 1: LDV/SOF + RBV 12 wk (GT1 SOF retreatment)<br>LDV/SOF + RBV for 12 weeks in participants with genotype 1 HCV infection and who failed to achieve sustained virologic response (SVR) in a previous Gilead sofosbuvir study | Drug: LDV/SOF<br>* Ledipasvir/sofosbuvir (LDV/SOF) (90 /400 mg) fixed-dose combination (FDC) tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;Drug: RBV<br>* Ribavirin (RBV) 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>|
| Experimental: Cohort 1,Group 2:SOF+Peg-IFN+RBV 12 wk (GT2,3 SOF retreatment)<br>SOF + PEG + RBV for 12 weeks in participants with genotype 2 or 3 HCV infection and who failed to achieve SVR in a previous Gilead sofosbuvir study | Drug: SOF<br>* SOF 400 mg tablet administered orally once daily<br>* Other names: Sovaldi®;Drug: RBV<br>* Ribavirin (RBV) 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>Drug: Peg-IFN<br>* pegylated interferon (Peg-IFN) 180 µg administered subcutaneously once weekly<br>* Other names: Pegasys®;|
| Experimental: Cohort 2,Group 1: LDV/SOF+RBV 12 wk (GT 1 TE, liver disease)<br>LDV/SOF+RBV for 12 weeks in treatment-experienced participants with genotype 1 HCV infection and advanced liver fibrosis or compensated liver fibrosis | Drug: LDV/SOF<br>* Ledipasvir/sofosbuvir (LDV/SOF) (90 /400 mg) fixed-dose combination (FDC) tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;Drug: RBV<br>* Ribavirin (RBV) 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>|
| Experimental: Cohort 2,Group 2: LDV/SOF+GS-9669 12wk (GT1 TE, liver disease)<br>LDV/SOF + GS-9669 for 12 weeks in treatment-experienced participants with genotype 1 HCV infection and advanced liver fibrosis or compensated liver fibrosis | Drug: LDV/SOF<br>* Ledipasvir/sofosbuvir (LDV/SOF) (90 /400 mg) fixed-dose combination (FDC) tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;Drug: GS-9669<br>* GS-9669 500 mg (2 × 250 mg tablet) administered orally once daily<br>|
| Experimental: Cohort 2,Group 3: LDV/SOF 12 wk (GT3 TN)<br>LDV/SOF for 12 weeks in treatment-naive participants with genotype 3 HCV infection | Drug: LDV/SOF<br>* Ledipasvir/sofosbuvir (LDV/SOF) (90 /400 mg) fixed-dose combination (FDC) tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;|
| Experimental: Cohort 2,Group 4: LDV/SOF+RBV 12 wk (GT3 TN)<br>LDV/SOF + RBV for 12 weeks in treatment-naive participants with genotype 3 HCV infection | Drug: LDV/SOF<br>* Ledipasvir/sofosbuvir (LDV/SOF) (90 /400 mg) fixed-dose combination (FDC) tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;Drug: RBV<br>* Ribavirin (RBV) 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>|
| Experimental: Cohort 2,Group 5: LDV/SOF 12 wk (GT6 TE/TN)<br>LDV/SOF for 12 weeks in treatment-naive or treatment-experienced participants with genotype 6 HCV infection | Drug: LDV/SOF<br>* Ledipasvir/sofosbuvir (LDV/SOF) (90 /400 mg) fixed-dose combination (FDC) tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;|
| Experimental: Cohort 2,Group 6: LDV/SOF+RBV 12 wk (GT3 TE)<br>LDV/SOF + RBV for 12 weeks in treatment-experienced participants with genotype 3 HCV infection | Drug: LDV/SOF<br>* Ledipasvir/sofosbuvir (LDV/SOF) (90 /400 mg) fixed-dose combination (FDC) tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;Drug: RBV<br>* Ribavirin (RBV) 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>|
| Experimental: Cohort 3,Group 1: LDV/SOF 12 wk (GT1 cirrhotic CPT B)<br>LDV/SOF for 12 weeks in participants with genotype 1 HCV infection and Child-Pugh Turcotte (CPT) B cirrhosis | Drug: LDV/SOF<br>* Ledipasvir/sofosbuvir (LDV/SOF) (90 /400 mg) fixed-dose combination (FDC) tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;|
| Experimental: Cohort 4,Group 1: SOF+VEL 25mg 8 wk (GT3 TN noncirrhotic)<br>SOF+VEL (25 mg) for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection | Drug: SOF<br>* SOF 400 mg tablet administered orally once daily<br>* Other names: Sovaldi®;Drug: VEL<br>* Velpatasvir (VEL) tablet(s) administered orally once daily<br>* Other names: GS-5816;|
| Experimental: Cohort 4,Group 2:SOF+VEL 25mg+RBV 8 wk (GT3 TN noncirrhotic)<br>SOF+VEL(25 mg)+RBV for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection | Drug: SOF<br>* SOF 400 mg tablet administered orally once daily<br>* Other names: Sovaldi®;Drug: RBV<br>* Ribavirin (RBV) 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>Drug: VEL<br>* Velpatasvir (VEL) tablet(s) administered orally once daily<br>* Other names: GS-5816;|
| Experimental: Cohort 4,Group 3: SOF+VEL 100mg 8 wk (GT3 TN noncirrhotic)<br>SOF+VEL (100 mg) for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection | Drug: SOF<br>* SOF 400 mg tablet administered orally once daily<br>* Other names: Sovaldi®;Drug: VEL<br>* Velpatasvir (VEL) tablet(s) administered orally once daily<br>* Other names: GS-5816;|
| Experimental: Cohort 4,Group 4: SOF+VEL 100mg+RBV 8 wk (GT3 TN noncirrhotic)<br>SOF+VEL (100 mg)+RBV for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection | Drug: SOF<br>* SOF 400 mg tablet administered orally once daily<br>* Other names: Sovaldi®;Drug: RBV<br>* Ribavirin (RBV) 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>Drug: VEL<br>* Velpatasvir (VEL) tablet(s) administered orally once daily<br>* Other names: GS-5816;|
| Experimental: Cohort 5,Group 1: LDV/SOF + RBV 24 wk (SOF retreatment)<br>LDV/SOF+RBV for 24 weeks in participants with genotype 1, 2, 3, or 6 HCV infection and who failed to achieve SVR in a previous Gilead sofosbuvir study | Drug: LDV/SOF<br>* Ledipasvir/sofosbuvir (LDV/SOF) (90 /400 mg) fixed-dose combination (FDC) tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;Drug: RBV<br>* Ribavirin (RBV) 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>|
| Experimental: Cohort 6,Group 1: LDV/SOF 12 wk (GT1, HBV coinfection)<br>LDV/SOF for 12 weeks in participants with genotype 1 HCV and hepatitis B virus (HBV) coinfection | Drug: LDV/SOF<br>* Ledipasvir/sofosbuvir (LDV/SOF) (90 /400 mg) fixed-dose combination (FDC) tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) | SVR12 is defined as HCV RNA < lower limit of quantification (LLOQ) at 12 weeks after stopping study treatment. | Posttreatment Week 12 | 
| Percentage of Participants With Adverse Events Leading to Permanent Discontinuation of Study Drug(s) |  | Up to 24 weeks plus 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With HCV RNA < LLOQ (15 IU/mL) While on Treatment |  | Weeks 1 and 2 | 
| Percentage of Participants With HCV RNA < LLOQ (15 IU/mL) While on Treatment |  | Weeks 4, 6, and 8 | 
| Percentage of Participants With HCV RNA < LLOQ (15 IU/mL) While on Treatment |  | Week 10 | 
| Percentage of Participants With HCV RNA < LLOQ (15 IU/mL) While on Treatment |  | Week 12 | 
| Percentage of Participants With HCV RNA < LLOQ (15 IU/mL) While on Treatment |  | Weeks 16, 20, and 24 | 
| Percentage of Participants With HCV RNA < LLOQ (15 IU/mL) at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR 24) |  | Posttreatment Weeks 2, 4, 8, and 24 | 
| For Cohort 6, Percentage of Participants With HCV RNA < LLOQ (15 IU/mL) at 16 and 20 Weeks After Discontinuation of Therapy (SVR16 and SVR 20) |  | Posttreatment Weeks 16 and 20 | 
| Percentage of Participants With On-treatment Virologic Failure | On-treatment virologic failure was defined as: 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) | Up to Posttreatment Week 24 | 
| Percentage of Participants Experiencing Viral Relapse | Viral relapse is defined as HCV RNA ≥ LLOQ during the post-treatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available post-treatment measurement. | Up to Posttreatment Week 24 |