Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination in Treatment-Naive and Treatment-Experienced Subjects With Chronic Genotype 4 or 5 HCV Infection

Study Overview
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Brief Summary
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This study is to evaluate the efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) in participants with chronic genotype 4 or 5 hepatitis C virus (HCV) infection as measured by the proportion of subjects with sustained virologic response (SVR12), defined as HCV RNA < lower limit of quantification (LLOQ) 12 weeks after discontinuation of therapy.

Official Title
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A Phase 2, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination in Treatment-Naive and Treatment-Experienced Subjects With Chronic Genotype 4 or 5 HCV Infection

Conditions
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Chronic Genotype 4 HCV, Chronic Genotype 5 HCV

Intervention / Treatment
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* Drug: LDV/SOF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HCV RNA ≥ 10^4 IU/mL at screening Chronic genotype 4 or 5 HCV Infection Individuals may be treatment naive or treatment experienced Presence or absence of cirrhosis, a liver biopsy may be required Healthy according to medical history and physical examination with the exception of HCV diagnosis Agree to use two forms of highly effective contraception for the duration of the study Exclusion Criteria: History or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the individual's participation for the full duration of the study or not be in the best interest of the individual in the opinion of the investigator Prior exposure to approved or experimental HCV specific direct acting antiviral(s) (DAA) other than NS3/4A protease inhibitors History of any other clinically significant chronic liver disease Evidence of or history of decompensated liver disease HIV or chronic hepatitis B (HBV) infection Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain resolved skin cancers) Chronic use of immunosuppressive agents or immunomodulatory agents

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Genotype 4<br>LDV/SOF for up to 12 weeks in treatment-naive and treatment-experienced participants with genotype 4 hepatitis C virus (HCV) infection | Drug: LDV/SOF<br>* LDV/SOF (90/400 mg) FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;|
| Experimental: Genotype 5<br>LDV/SOF for up to 12 weeks in treatment-naive and treatment-experienced participants with genotype 5 hepatitis C virus (HCV) infection | Drug: LDV/SOF<br>* LDV/SOF (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 LDV/SOF 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 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 Patients With Virologic Failure | Virologic failure was defined as either: 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); or Relapse: HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while receiving treatment | Up to posttreatment Week 24 | 
| Change From Baseline in HCV RNA at Weeks 2, 4, 8, and 12 |  | Baseline; Weeks 2, 4, 8, and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCV GT 4, HCV GT 5