Efficacy and Safety of Oral Regimens for the Treatment of Chronic HCV Infection

Phase 2

Completed

• Conditions: Chronic Hepatitis C
• Interventions: Drug: LDV/SOF; Drug: SOF/VEL; Drug: RBV; Drug: VOX

• Registration Number: NCT02202980
• Lead Sponsor: Gilead Sciences

Brief Summary

This study will evaluate the antiviral efficacy, safety, and tolerability of combination therapy with oral regimens for the treatment of chronic hepatitis C virus (HCV) infection.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-07-25
• Study First Submitted QC: 2014-07-25
• Study First Posted: 2014-07-29
• Study Start: 2014-08-04
• Primary Completion: 2016-03-16
• Study Completion: 2016-05-09
• Results First Submitted: 2017-03-15
• Status Verified: 2017-11
• Results First Submitted QC: 2017-11-06
• Results First Posted: 2017-11-17
• Last Update Submitted: 2018-10-19
• Last Update Posted: 2018-11-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 273

Inclusion Criteria

• Willing and able to provide written informed consent
• Chronic HCV infection
• Cirrhosis determination (liver biopsy may be required)
• Screening laboratory values within specified limits
• Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
• Specific genotype, prior medical history, or concurrent disease as required by the specific study group

Key

Exclusion Criteria

• History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol
• Pregnant or nursing female, or male with pregnant female partner
• Clinical hepatic decompensation (ie, ascites, encephalopathy or variceal hemorrhage)
• Use of any prohibited concomitant medications

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LDV/SOF+RBV 12 Weeks (Cohort 1 Group 2)	LDV/SOF	Participants who previously received a sofosbuvir-based regimen without achieving SVR12 were initially enrolled to receive LDV/SOF+RBV for 12 weeks (excluding participants who previously received LDV/SOF+RBV for ≥ 12 weeks). Participants who did not achieve sustained virologic response at 12 weeks were then moved to Cohort 1 Group 1.
LDV/SOF+RBV 12 Weeks (Cohort 1 Group 2)	RBV	Participants who previously received a sofosbuvir-based regimen without achieving SVR12 were initially enrolled to receive LDV/SOF+RBV for 12 weeks (excluding participants who previously received LDV/SOF+RBV for ≥ 12 weeks). Participants who did not achieve sustained virologic response at 12 weeks were then moved to Cohort 1 Group 1.
LDV/SOF 12 Weeks GT2 (Cohort 2 Group 1)	LDV/SOF	Participants with genotype 2 (GT2) HCV infection will receive LDV/SOF FDC for 12 weeks.
LDV/SOF 8 Weeks GT2 (Cohort 2 Group 2)	LDV/SOF	Participants with GT2 HCV infection will receive LDV/SOF FDC for 8 weeks.
LDV/SOF 12 Weeks GT1/GT2/GT4 (Cohort 3 Group 1)	LDV/SOF	Participants with genotypes 1 (GT1), 2 (GT2), or 4 (GT4) HCV infection and extrahepatic manifestations of chronic HCV infection will receive LDV/SOF FDC for 12 weeks.
LDV/SOF+RBV 24 Weeks (Cohort 1 Group 1)	LDV/SOF	Participants who previously received ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) plus ribavirin (RBV) for ≥ 12 weeks without achieving sustained virologic response at 12 weeks following treatment (SVR12) will receive LDV/SOF+RBV for 24 weeks.
LDV/SOF+RBV 24 Weeks (Cohort 1 Group 1)	RBV	Participants who previously received ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) plus ribavirin (RBV) for ≥ 12 weeks without achieving sustained virologic response at 12 weeks following treatment (SVR12) will receive LDV/SOF+RBV for 24 weeks.
LDV/SOF+RBV 12 Weeks GT3 (Cohort 3 Group 2)	LDV/SOF	Participants with genotype 3 (GT3) HCV infection and extrahepatic manifestations of chronic HCV infection will receive LDV/SOF FDC plus RBV for 12 weeks.
LDV/SOF+RBV 12 Weeks GT3 (Cohort 3 Group 2)	RBV	Participants with genotype 3 (GT3) HCV infection and extrahepatic manifestations of chronic HCV infection will receive LDV/SOF FDC plus RBV for 12 weeks.
SOF/VEL+VOX 6 Weeks GT1 (Cohort 4)	VOX	Treatment-naive participants with GT1 HCV infection without cirrhosis will receive VOX only on Day 1 followed by sofosbuvir/velpatasvir (SOF/VEL) + voxilaprevir (VOX) for 6 weeks.
SOF/VEL+VOX 4 Weeks GT1 (Cohort 5 Group 1)	SOF/VEL	Treatment-naive participants with GT1 HCV infection without cirrhosis will receive SOF/VEL+VOX for 4 weeks.
SOF/VEL+VOX 4 Weeks GT1 (Cohort 5 Group 1)	VOX	Treatment-naive participants with GT1 HCV infection without cirrhosis will receive SOF/VEL+VOX for 4 weeks.
SOF/VEL+VOX 8 Weeks GT1 (Cohort 5 Group 4)	VOX	Treatment-experienced participants with GT1 HCV infection with cirrhosis who were previously treated with pegylated interferon (Peg-IFN)+RBV will receive SOF/VEL+VOX for 6 weeks.
SOF/VEL+VOX 6 Weeks GT1 (Cohort 5 Group 2)	SOF/VEL	Treatment-naive participants with GT1 HCV infection with cirrhosis will receive SOF/VEL+VOX for 6 weeks.
SOF/VEL+VOX 6 Weeks GT1 (Cohort 5 Group 2)	VOX	Treatment-naive participants with GT1 HCV infection with cirrhosis will receive SOF/VEL+VOX for 6 weeks.
SOF/VEL+VOX 6 Weeks GT3 (Cohort 5 Group 3)	SOF/VEL	Treatment-naive participants with GT3 HCV infection with cirrhosis will receive SOF/VEL+VOX for 6 weeks.
SOF/VEL+VOX 6 Weeks GT3 (Cohort 5 Group 3)	VOX	Treatment-naive participants with GT3 HCV infection with cirrhosis will receive SOF/VEL+VOX for 6 weeks.
SOF/VEL+VOX 8 Weeks GT1 (Cohort 5 Group 4)	SOF/VEL	Treatment-experienced participants with GT1 HCV infection with cirrhosis who were previously treated with pegylated interferon (Peg-IFN)+RBV will receive SOF/VEL+VOX for 6 weeks.
SOF/VEL+VOX 8 Weeks GT3 (Cohort 5 Group 5)	VOX	Treatment-experienced participants with GT3 HCV infection with cirrhosis who were previously treated with Peg-IFN+RBV will receive SOF/VEL+VOX for 6 weeks.
SOF/VEL+VOX 8 Weeks GT1 (Cohort 5 Group 6)	SOF/VEL	Treatment-experienced participants with GT1 HCV infection with or without cirrhosis who were previously treated with non-structural protein (NS3/4A) protease inhibitor (PI) will receive SOF/VEL+VOX for 6 weeks.
SOF/VEL+VOX 8 Weeks GT1 (Cohort 5 Group 6)	VOX	Treatment-experienced participants with GT1 HCV infection with or without cirrhosis who were previously treated with non-structural protein (NS3/4A) protease inhibitor (PI) will receive SOF/VEL+VOX for 6 weeks.
SOF/VEL+VOX 6 Weeks GT1 (Cohort 5 Group 7)	SOF/VEL	Treatment-experienced participants with GT1 HCV infection with or without cirrhosis who were previously treated with direct-acting antivirals (DAA) will receive SOF/VEL+VOX for 6 weeks.
SOF/VEL+VOX 6 Weeks GT1 (Cohort 5 Group 7)	VOX	Treatment-experienced participants with GT1 HCV infection with or without cirrhosis who were previously treated with direct-acting antivirals (DAA) will receive SOF/VEL+VOX for 6 weeks.
SOF/VEL+VOX 8 Weeks GT3 (Cohort 5 Group 8)	SOF/VEL	Treatment-experienced participants with GT3 HCV infection with or without cirrhosis who were previously treated with DAA will receive SOF/VEL+VOX for 8 weeks.
SOF/VEL+VOX 8 Weeks GT3 (Cohort 5 Group 8)	VOX	Treatment-experienced participants with GT3 HCV infection with or without cirrhosis who were previously treated with DAA will receive SOF/VEL+VOX for 8 weeks.
SOF/VEL+VOX 8 Weeks GT3 (Cohort 5 Group 5)	SOF/VEL	Treatment-experienced participants with GT3 HCV infection with cirrhosis who were previously treated with Peg-IFN+RBV will receive SOF/VEL+VOX for 6 weeks.
SOF/VEL+VOX 6 Weeks GT1 (Cohort 4)	SOF/VEL	Treatment-naive participants with GT1 HCV infection without cirrhosis will receive VOX only on Day 1 followed by sofosbuvir/velpatasvir (SOF/VEL) + voxilaprevir (VOX) for 6 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event	Up to 24 weeks
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)	Posttreatment Week 12	SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)	Posttreatment Weeks 4 and 24	SVR4 and SVR 24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks after stopping study treatment, respectively.
Percentage of Participants With Virologic Failure	Up to Posttreatment Week 24	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.
Percentage of Participants With HCV RNA < LLOQ While on Treatment by Study Visit	Weeks 1, 2, 4, 6, 8, 12, 16, 20, and 24 (depending on treatment duration; Week 6 data was not collected for Cohorts 1-3)