Ledipasvir/Sofosbuvir Fixed-Dose Combination for 12 Weeks in Participants With Chronic Genotype 2 HCV Infection

Study Overview
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Brief Summary
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The primary objectives of this study are to evaluate the antiviral efficacy of therapy with ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) and to evaluate the safety and tolerability of LDV/SOF FDC and sofosbuvir (SOF) + ribavirin (RBV) in participants with chronic genotype 2 hepatitis C virus (HCV) infection.

Official Title
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A Phase 3b, Multicenter, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination for 12 Weeks in Subjects With Chronic Genotype 2 HCV Infection

Conditions
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Hepatitis C Virus Infection

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


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Chronic genotype 2 HCV-infected males and non-pregnant/non-lactating females Aged 20 years or older Treatment naive or treatment experienced At least 20 subjects will have Child-Pugh-A compensated cirrhosis. In Cohort 2, participants must be ineligible or intolerant of RBV. Key Exclusion Criteria: Previous exposure to an NS5A or NS5B inhibitor Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) Pregnant or nursing female or male with pregnant female partner Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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 (Cohort 1)<br>LDV/SOF FDC for 12 weeks | Drug: LDV/SOF<br>* 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;|
| Experimental: SOF+RBV (Cohort 1)<br>SOF+RBV for 12 weeks | Drug: SOF<br>* 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;Drug: RBV<br>* Capsules 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: REBETOL®;|
| Experimental: LDV/SOF (Cohort 2)<br>Participants who are ineligible for or intolerant to RBV therapy will receive LDV/SOF FDC for 12 weeks. | Drug: LDV/SOF<br>* 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;|

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) 12 Weeks After Discontinuation of Therapy (SVR12) | SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 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 SVR at 4 Weeks After Discontinuation of Therapy (SVR4) | SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment. | Posttreatment Week 4 | 
| Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) | SVR 24 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment. | Posttreatment Week 24 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 1 |  | Week 1 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 2 |  | Week 2 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 3 |  | Week 3 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 4 |  | Week 4 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 5 |  | Week 5 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 6 |  | Week 6 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 8 |  | Week 8 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 10 |  | Week 10 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 12 |  | Week 12 | 
| Change From Baseline in HCV RNA at Week 1 |  | Baseline; Week 1 | 
| Change From Baseline in HCV RNA at Week 2 |  | Baseline; Week 2 | 
| Change From Baseline in HCV RNA at Week 3 |  | Baseline; Week 3 | 
| Change From Baseline in HCV RNA at Week 4 |  | Baseline; Week 4 | 
| Change From Baseline in HCV RNA at Week 5 |  | Baseline; Week 5 | 
| Change From Baseline in HCV RNA at Week 6 |  | Baseline; Week 6 | 
| Change From Baseline in HCV RNA at Week 8 |  | Baseline; Week 8 | 
| Change From Baseline in HCV RNA at Week 10 |  | Baseline; Week 10 | 
| Change From Baseline in HCV RNA at Week 12 |  | Baseline; Week 12 | 
| Percentage of Participants With Overall 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 |