A Phase 2, Multicenter, Open-Label Study to Assess the Efficacy and Safety of Sofosbuvir Containing Regimens for the Treatment of Chronic HCV Infection
Overview
- Phase
- Phase 2
- Intervention
- LDV/SOF
- Conditions
- Chronic Hepatitis C
- Sponsor
- Gilead Sciences
- Enrollment
- 359
- Locations
- 2
- Primary Endpoint
- Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
Cohort 1,Group 1: LDV/SOF + RBV 12 wk (GT1 SOF retreatment)
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
Intervention: LDV/SOF
Cohort 1,Group 1: LDV/SOF + RBV 12 wk (GT1 SOF retreatment)
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
Intervention: RBV
Cohort 1,Group 2:SOF+Peg-IFN+RBV 12 wk (GT2,3 SOF retreatment)
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
Intervention: SOF
Cohort 4,Group 3: SOF+VEL 100mg 8 wk (GT3 TN noncirrhotic)
SOF+VEL (100 mg) for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection
Intervention: VEL
Cohort 1,Group 2:SOF+Peg-IFN+RBV 12 wk (GT2,3 SOF retreatment)
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
Intervention: RBV
Cohort 1,Group 2:SOF+Peg-IFN+RBV 12 wk (GT2,3 SOF retreatment)
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
Intervention: Peg-IFN
Cohort 2,Group 1: LDV/SOF+RBV 12 wk (GT 1 TE, liver disease)
LDV/SOF+RBV for 12 weeks in treatment-experienced participants with genotype 1 HCV infection and advanced liver fibrosis or compensated liver fibrosis
Intervention: LDV/SOF
Cohort 2,Group 1: LDV/SOF+RBV 12 wk (GT 1 TE, liver disease)
LDV/SOF+RBV for 12 weeks in treatment-experienced participants with genotype 1 HCV infection and advanced liver fibrosis or compensated liver fibrosis
Intervention: RBV
Cohort 2,Group 2: LDV/SOF+GS-9669 12wk (GT1 TE, liver disease)
LDV/SOF + GS-9669 for 12 weeks in treatment-experienced participants with genotype 1 HCV infection and advanced liver fibrosis or compensated liver fibrosis
Intervention: LDV/SOF
Cohort 2,Group 2: LDV/SOF+GS-9669 12wk (GT1 TE, liver disease)
LDV/SOF + GS-9669 for 12 weeks in treatment-experienced participants with genotype 1 HCV infection and advanced liver fibrosis or compensated liver fibrosis
Intervention: GS-9669
Cohort 2,Group 3: LDV/SOF 12 wk (GT3 TN)
LDV/SOF for 12 weeks in treatment-naive participants with genotype 3 HCV infection
Intervention: LDV/SOF
Cohort 2,Group 4: LDV/SOF+RBV 12 wk (GT3 TN)
LDV/SOF + RBV for 12 weeks in treatment-naive participants with genotype 3 HCV infection
Intervention: LDV/SOF
Cohort 2,Group 4: LDV/SOF+RBV 12 wk (GT3 TN)
LDV/SOF + RBV for 12 weeks in treatment-naive participants with genotype 3 HCV infection
Intervention: RBV
Cohort 2,Group 5: LDV/SOF 12 wk (GT6 TE/TN)
LDV/SOF for 12 weeks in treatment-naive or treatment-experienced participants with genotype 6 HCV infection
Intervention: LDV/SOF
Cohort 2,Group 6: LDV/SOF+RBV 12 wk (GT3 TE)
LDV/SOF + RBV for 12 weeks in treatment-experienced participants with genotype 3 HCV infection
Intervention: LDV/SOF
Cohort 2,Group 6: LDV/SOF+RBV 12 wk (GT3 TE)
LDV/SOF + RBV for 12 weeks in treatment-experienced participants with genotype 3 HCV infection
Intervention: RBV
Cohort 3,Group 1: LDV/SOF 12 wk (GT1 cirrhotic CPT B)
LDV/SOF for 12 weeks in participants with genotype 1 HCV infection and Child-Pugh Turcotte (CPT) B cirrhosis
Intervention: LDV/SOF
Cohort 4,Group 1: SOF+VEL 25mg 8 wk (GT3 TN noncirrhotic)
SOF+VEL (25 mg) for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection
Intervention: SOF
Cohort 4,Group 1: SOF+VEL 25mg 8 wk (GT3 TN noncirrhotic)
SOF+VEL (25 mg) for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection
Intervention: VEL
Cohort 4,Group 2:SOF+VEL 25mg+RBV 8 wk (GT3 TN noncirrhotic)
SOF+VEL(25 mg)+RBV for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection
Intervention: SOF
Cohort 4,Group 2:SOF+VEL 25mg+RBV 8 wk (GT3 TN noncirrhotic)
SOF+VEL(25 mg)+RBV for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection
Intervention: RBV
Cohort 4,Group 2:SOF+VEL 25mg+RBV 8 wk (GT3 TN noncirrhotic)
SOF+VEL(25 mg)+RBV for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection
Intervention: VEL
Cohort 4,Group 3: SOF+VEL 100mg 8 wk (GT3 TN noncirrhotic)
SOF+VEL (100 mg) for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection
Intervention: SOF
Cohort 4,Group 4: SOF+VEL 100mg+RBV 8 wk (GT3 TN noncirrhotic)
SOF+VEL (100 mg)+RBV for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection
Intervention: SOF
Cohort 4,Group 4: SOF+VEL 100mg+RBV 8 wk (GT3 TN noncirrhotic)
SOF+VEL (100 mg)+RBV for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection
Intervention: RBV
Cohort 4,Group 4: SOF+VEL 100mg+RBV 8 wk (GT3 TN noncirrhotic)
SOF+VEL (100 mg)+RBV for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection
Intervention: VEL
Cohort 5,Group 1: LDV/SOF + RBV 24 wk (SOF retreatment)
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
Intervention: LDV/SOF
Cohort 5,Group 1: LDV/SOF + RBV 24 wk (SOF retreatment)
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
Intervention: RBV
Cohort 6,Group 1: LDV/SOF 12 wk (GT1, HBV coinfection)
LDV/SOF for 12 weeks in participants with genotype 1 HCV and hepatitis B virus (HBV) coinfection
Intervention: LDV/SOF
Outcomes
Primary Outcomes
Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)
Time Frame: Posttreatment Week 12
SVR12 is defined as HCV RNA \< lower limit of quantification (LLOQ) at 12 weeks after stopping study treatment.
Percentage of Participants With Adverse Events Leading to Permanent Discontinuation of Study Drug(s)
Time Frame: Up to 24 weeks plus 30 days
Secondary Outcomes
- 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(Up to Posttreatment Week 24)
- Percentage of Participants Experiencing Viral Relapse(Up to Posttreatment Week 24)