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

Phase 2

Completed

• Conditions: Chronic Hepatitis C
• Interventions: Drug: SOF; Drug: LDV/SOF; Drug: VEL; Drug: GS-9669; Drug: RBV; Drug: Peg-IFN

• Registration Number: NCT01826981
• Lead Sponsor: Gilead Sciences

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-04
• Study First Submitted: 2013-04-01
• Study First Submitted QC: 2013-04-04
• Study First Posted: 2013-04-09
• Primary Completion: 2015-03
• Study Completion: 2015-05
• Disposition First Submitted: 2016-01-22
• Disposition First Submitted QC: 2016-01-22
• Disposition First Posted: 2016-02-15
• Results First Submitted: 2016-07-28
• Results First Submitted QC: 2016-07-28
• Status Verified: 2016-09
• Results First Posted: 2016-09-16
• Last Update Submitted: 2018-10-19
• Last Update Posted: 2018-11-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 359

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1,Group 2:SOF+Peg-IFN+RBV 12 wk (GT2,3 SOF retreatment)	SOF	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
Cohort 2,Group 1: LDV/SOF+RBV 12 wk (GT 1 TE, liver disease)	LDV/SOF	LDV/SOF+RBV for 12 weeks in treatment-experienced participants with genotype 1 HCV infection and advanced liver fibrosis or compensated liver fibrosis
Cohort 1,Group 1: LDV/SOF + RBV 12 wk (GT1 SOF retreatment)	LDV/SOF	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
Cohort 1,Group 2:SOF+Peg-IFN+RBV 12 wk (GT2,3 SOF retreatment)	Peg-IFN	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
Cohort 4,Group 3: SOF+VEL 100mg 8 wk (GT3 TN noncirrhotic)	VEL	SOF+VEL (100 mg) for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection
Cohort 2,Group 2: LDV/SOF+GS-9669 12wk (GT1 TE, liver disease)	LDV/SOF	LDV/SOF + GS-9669 for 12 weeks in treatment-experienced participants with genotype 1 HCV infection and advanced liver fibrosis or compensated liver fibrosis
Cohort 2,Group 2: LDV/SOF+GS-9669 12wk (GT1 TE, liver disease)	GS-9669	LDV/SOF + GS-9669 for 12 weeks in treatment-experienced participants with genotype 1 HCV infection and advanced liver fibrosis or compensated liver fibrosis
Cohort 2,Group 5: LDV/SOF 12 wk (GT6 TE/TN)	LDV/SOF	LDV/SOF for 12 weeks in treatment-naive or treatment-experienced participants with genotype 6 HCV infection
Cohort 4,Group 2:SOF+VEL 25mg+RBV 8 wk (GT3 TN noncirrhotic)	VEL	SOF+VEL(25 mg)+RBV for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection
Cohort 4,Group 4: SOF+VEL 100mg+RBV 8 wk (GT3 TN noncirrhotic)	SOF	SOF+VEL (100 mg)+RBV for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection
Cohort 5,Group 1: LDV/SOF + RBV 24 wk (SOF retreatment)	LDV/SOF	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
Cohort 2,Group 3: LDV/SOF 12 wk (GT3 TN)	LDV/SOF	LDV/SOF for 12 weeks in treatment-naive participants with genotype 3 HCV infection
Cohort 4,Group 1: SOF+VEL 25mg 8 wk (GT3 TN noncirrhotic)	VEL	SOF+VEL (25 mg) for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection
Cohort 4,Group 3: SOF+VEL 100mg 8 wk (GT3 TN noncirrhotic)	SOF	SOF+VEL (100 mg) for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection
Cohort 4,Group 2:SOF+VEL 25mg+RBV 8 wk (GT3 TN noncirrhotic)	SOF	SOF+VEL(25 mg)+RBV for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection
Cohort 4,Group 4: SOF+VEL 100mg+RBV 8 wk (GT3 TN noncirrhotic)	VEL	SOF+VEL (100 mg)+RBV for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection
Cohort 2,Group 4: LDV/SOF+RBV 12 wk (GT3 TN)	LDV/SOF	LDV/SOF + RBV for 12 weeks in treatment-naive participants with genotype 3 HCV infection
Cohort 2,Group 6: LDV/SOF+RBV 12 wk (GT3 TE)	LDV/SOF	LDV/SOF + RBV for 12 weeks in treatment-experienced participants with genotype 3 HCV infection
Cohort 3,Group 1: LDV/SOF 12 wk (GT1 cirrhotic CPT B)	LDV/SOF	LDV/SOF for 12 weeks in participants with genotype 1 HCV infection and Child-Pugh Turcotte (CPT) B cirrhosis
Cohort 4,Group 1: SOF+VEL 25mg 8 wk (GT3 TN noncirrhotic)	SOF	SOF+VEL (25 mg) for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection
Cohort 6,Group 1: LDV/SOF 12 wk (GT1, HBV coinfection)	LDV/SOF	LDV/SOF for 12 weeks in participants with genotype 1 HCV and hepatitis B virus (HBV) coinfection
Cohort 1,Group 1: LDV/SOF + RBV 12 wk (GT1 SOF retreatment)	RBV	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
Cohort 1,Group 2:SOF+Peg-IFN+RBV 12 wk (GT2,3 SOF retreatment)	RBV	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
Cohort 2,Group 1: LDV/SOF+RBV 12 wk (GT 1 TE, liver disease)	RBV	LDV/SOF+RBV for 12 weeks in treatment-experienced participants with genotype 1 HCV infection and advanced liver fibrosis or compensated liver fibrosis
Cohort 2,Group 4: LDV/SOF+RBV 12 wk (GT3 TN)	RBV	LDV/SOF + RBV for 12 weeks in treatment-naive participants with genotype 3 HCV infection
Cohort 2,Group 6: LDV/SOF+RBV 12 wk (GT3 TE)	RBV	LDV/SOF + RBV for 12 weeks in treatment-experienced participants with genotype 3 HCV infection
Cohort 4,Group 2:SOF+VEL 25mg+RBV 8 wk (GT3 TN noncirrhotic)	RBV	SOF+VEL(25 mg)+RBV for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection
Cohort 4,Group 4: SOF+VEL 100mg+RBV 8 wk (GT3 TN noncirrhotic)	RBV	SOF+VEL (100 mg)+RBV for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection
Cohort 5,Group 1: LDV/SOF + RBV 24 wk (SOF retreatment)	RBV	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

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)	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)	Up to 24 weeks plus 30 days

Secondary Outcome Measures

Name	Time	Method
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	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)
Percentage of Participants Experiencing Viral Relapse	Up to Posttreatment Week 24	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.

Trial Locations

Locations (2)

Auckland Clinical Studies Ltd.; 🇳🇿 Auckland, New Zealand

Christchurch Clinical Studies Trust; 🇳🇿 Christchurch, New Zealand