Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination, With or Without Ribavirin, in Egyptian Adults With Chronic Genotype 4 HCV Infection

Phase 3

Completed

Brief Summary: The primary objective of this study was to evaluate the efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed dose combination (FDC) with or without ribavirin (RBV) in Egyptian adults with chronic genotype 4 hepatitis C virus (HCV) infection.

Recruitment & Eligibility

Inclusion Criteria

Willing and able to provide written informed consent
Chronic HCV infection (≥ 6 months) documented by medical history or liver biopsy
HCV genotype 4 at screening
HCV treatment naive or prior participation in this study or study GS-US-334-0138 (Cohorts 1 and 2 only)
Cohort 3 only: HCV treatment-experienced (previously received therapy for HCV infection with an interferon (IFN)-containing regimen, with or without RBV and/or an HCV NS3/NS4A protease inhibitor (PI)
Body mass index (BMI) ≥ 18 kg/m^2
Screening laboratory values within defined thresholds
Use of effective protocol-approved contraception methods

Key

Exclusion Criteria

History of clinically-significant illness or any other major medical disorder that may interfere with treatment, assessment or compliance with the protocol
Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
Pregnant or nursing females or male with pregnant female partner
Clinically-relevant drug or alcohol abuse within 12 months of screening

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

Arm && Interventions

Group	Intervention	Description
LDV/SOF+RBV 8 wk TN (Cohort 1, Group 2)	LDV/SOF	LDV/SOF+RBV for 8 weeks (treatment-naive)
LDV/SOF 8 wk TN (Cohort 1, Group 1)	LDV/SOF	LDV/SOF for 8 weeks (treatment-naive (TN))
LDV/SOF+RBV 8 wk TN (Cohort 1, Group 2)	RBV	LDV/SOF+RBV for 8 weeks (treatment-naive)
LDV/SOF 12 wk TN (Cohort 1, Group 3)	LDV/SOF	LDV/SOF for 12 weeks (treatment-naive)
LDV/SOF+RBV 12 wk TN (Cohort 1, Group 4)	LDV/SOF	LDV/SOF+RBV for 12 weeks (treatment-naive)
LDV/SOF+RBV 12 wk TN (Cohort 1, Group 4)	RBV	LDV/SOF+RBV for 12 weeks (treatment-naive)
LDV/SOF+RBV 12 wk TE (Cohort 2)	LDV/SOF	Treatment-experienced (TE) participants who completed treatment in Gilead sponsored study GS-US-334-0138 or in Cohort 1 of this study and did not achieve SVR12 will receive LDV/SOF+RBV for 12 weeks.
LDV/SOF+RBV 12 wk TE (Cohort 2)	RBV	Treatment-experienced (TE) participants who completed treatment in Gilead sponsored study GS-US-334-0138 or in Cohort 1 of this study and did not achieve SVR12 will receive LDV/SOF+RBV for 12 weeks.
LDV/SOF 12 wk TE (Cohort 3, Group 1)	LDV/SOF	LDV/SOF for 12 weeks (treatment-experienced)
LDV/SOF+RBV 12 wk TE (Cohort 3, Group 2)	LDV/SOF	LDV/SOF+RBV for 12 weeks (treatment-experienced)
LDV/SOF+RBV 12 wk TE (Cohort 3, Group 2)	RBV	LDV/SOF+RBV for 12 weeks (treatment-experienced)

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)	Posttreatment Week 12	SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.
Percentage of Participants Who Discontinued LDV/SOF Drug Due to an Adverse Event (AE)	12 weeks

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)	Posttreatment Weeks 4 and 24	SVR4 and SVR24 were defined as HCV RNA \< LLOQ 4 and 24 weeks after the last dose of study drug, respectively.
Percentage of Participants With Overall Virologic Failure	Up to Posttreatment Week 24	Virologic failure was defined as * On-treatment virologic failure * confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ, while on treatment (ie, breakthrough), * confirmed \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment (ie, rebound), * HCV RNA persistently ≥ LLOQ through 8 weeks of treatment (ie, nonresponse) * Relapse * HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement