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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3, Randomized, Open-Label, Study to Evaluate the Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination, With or Without Ribavirin, in Egyptian Adults With Chronic Genotype 4 HCV Infection

Conditions
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Hepatitis C Virus Infection

Intervention / Treatment
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* Drug: LDV/SOF
* Drug: RBV


Participation Criteria
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Eligibility Criteria
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Key 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.

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: LDV/SOF 8 wk TN (Cohort 1, Group 1)<br>LDV/SOF for 8 weeks (treatment-naive (TN)) | Drug: LDV/SOF<br>* 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;|
| Experimental: LDV/SOF+RBV 8 wk TN (Cohort 1, Group 2)<br>LDV/SOF+RBV for 8 weeks (treatment-naive) | Drug: LDV/SOF<br>* 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;Drug: RBV<br>* Tablets administered orally in a divided daily dose based on weight (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)<br>|
| Experimental: LDV/SOF 12 wk TN (Cohort 1, Group 3)<br>LDV/SOF for 12 weeks (treatment-naive) | Drug: LDV/SOF<br>* 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;|
| Experimental: LDV/SOF+RBV 12 wk TN (Cohort 1, Group 4)<br>LDV/SOF+RBV for 12 weeks (treatment-naive) | Drug: LDV/SOF<br>* 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;Drug: RBV<br>* Tablets administered orally in a divided daily dose based on weight (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)<br>|
| Experimental: LDV/SOF+RBV 12 wk TE (Cohort 2)<br>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. | Drug: LDV/SOF<br>* 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;Drug: RBV<br>* Tablets administered orally in a divided daily dose based on weight (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)<br>|
| Experimental: LDV/SOF 12 wk TE (Cohort 3, Group 1)<br>LDV/SOF for 12 weeks (treatment-experienced) | Drug: LDV/SOF<br>* 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;|
| Experimental: LDV/SOF+RBV 12 wk TE (Cohort 3, Group 2)<br>LDV/SOF+RBV for 12 weeks (treatment-experienced) | Drug: LDV/SOF<br>* 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;Drug: RBV<br>* Tablets administered orally in a divided daily dose based on weight (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)<br>|

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 was defined as HCV RNA < the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug. | Posttreatment Week 12 | 
| Percentage of Participants Who Discontinued LDV/SOF Drug Due to an Adverse Event (AE) |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 and SVR24 were defined as HCV RNA < LLOQ 4 and 24 weeks after the last dose of study drug, respectively. | Posttreatment Weeks 4 and 24 | 
| Percentage of Participants With Overall Virologic Failure | 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 | Up to Posttreatment Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sofosbuvir, HCV genotype 4 (GT-4), HCV, Sustained Virologic Response, Direct Acting Antiviral, Combination Therapy, GS-7977, GS-5885, Ribavirin, ledipasvir, Hepatitis C, Hepatitis C, Chronic, Liver Diseases, Virus Diseases, Antiviral Agents