Efficacy and Safety of Sofosbuvir/Ledipasvir ± Ribavirin in Japanese Participants With Chronic Genotype 1 HCV Infection

Study Overview
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Brief Summary
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This study will evaluate the antiviral efficacy of sofosbuvir (SOF)/ledipasvir (LDV) fixed-dose combination (FDC) tablet with or without ribavirin (RBV) in treatment-naive or treatment-experienced Japanese participants with chronic genotype 1 HCV infection. Participants receive 12 weeks of treatment and continue assessments during a 24-week posttreatment follow-up period.

Official Title
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A Phase 3b, Randomized, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination ± Ribavirin in Treatment-Naïve and Treatment-Experienced Japanese Subjects With Chronic Genotype 1 HCV Infection

Conditions
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Chronic HCV Infection

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body weight ≥ 40 kg HCV RNA ≥ 10^5 IU/mL at screening Exclusion Criteria: Current or prior history of any clinically-significant illness (other than HCV) Pregnant or nursing female or male with pregnant female partner Chronic liver disease of a non-HCV etiology Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)

Ages Eligible for Study
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Minimum Age: 20 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 (treatment naive)<br>Treatment-naive participants will receive LDV/SOF for 12 weeks. | Drug: LDV/SOF<br>* LDV/SOF 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885;|
| Experimental: LDV/SOF+RBV (treatment naive)<br>Treatment-naive participants will receive LDV/SOF plus RBV for 12 weeks. | Drug: LDV/SOF<br>* LDV/SOF 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885;Drug: RBV<br>* RBV tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (≤ 60 kg = 600 mg, > 60 kg to ≤ 80 kg = 800 mg, and ≥ 80 kg = 1000 mg)<br>* Other names: Copegus®;|
| Experimental: LDV/SOF (treatment experienced)<br>Treatment-experienced participants will receive LDV/SOF for 12 weeks. | Drug: LDV/SOF<br>* LDV/SOF 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885;|
| Experimental: LDV/SOF+RBV (treatment experienced)<br>Treatment-experienced participants will receive LDV/SOF plus RBV for 12 weeks. | Drug: LDV/SOF<br>* LDV/SOF 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885;Drug: RBV<br>* RBV tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (≤ 60 kg = 600 mg, > 60 kg to ≤ 80 kg = 800 mg, and ≥ 80 kg = 1000 mg)<br>* Other names: Copegus®;|

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 (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12), Treatment-naive, Noncirrhotic Participants | SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment. | Posttreatment Week 12 | 
| Percentage of Participants With Sustained Virologic Response at 12 Weeks After Discontinuation of Therapy (SVR12) | SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment. | Posttreatment Week 12 | 
| Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event |  | Up to 12 weeks | 

Secondary Outcome Measures

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