Efficacy and Safety of Ledipasvir/Sofosbuvir, With or Without Ribavirin, in HCV Infected Participants Who Have Failed Prior Treatment With Sofosbuvir-based Therapies

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed dose combination (FDC) for 12 weeks with or without ribavirin (RBV) in participants without cirrhosis, and LDV/SOF FDC for 12 weeks with RBV or LDV/SOF FDC for 24 weeks without RBV in participants with cirrhosis.

Official Title
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A Phase 3b, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Ledipasvir/Sofosbuvir, With or Without Ribavirin, in HCV Infected Subjects Who Have Failed Prior Treatment With Sofosbuvir-based Therapies

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: HCV RNA > 15 IU/mL at screening HCV genotype 1 or 4 Chronic HCV infection (≥ 6 months) Prior virologic failure after treatment with SOF in combination with simeprevir (SMV) ± RBV or with RBV ± pegylated interferon (PEG) Cirrhotic and non-cirrhotic as determined by standard methods Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception Key Exclusion Criteria: Prior exposure to approved or experimental non-structural protein (NS5A) inhibitors Prior exposure to nucleos(t)ide polymerase inhibitors, other than SOF Pregnant or nursing female or male with pregnant female partner Coinfection with HIV or hepatitis B virus Current or prior history of clinical hepatic decompensation Hepatocellular carcinoma or other malignancy (with exception of certain resolved skin cancers) Chronic use of systemic immunosuppressive agents History of clinically significant illness or any other medical disorder that may interfere with individual's treatment, assessment or compliance with the protocol 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 12 weeks, without cirrhosis<br>LDV/SOF for 12 weeks | 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 weeks, without cirrhosis<br>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 according to weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)<br>|
| Experimental: LDV/SOF + RBV 12 weeks, with compensated cirrhosis<br>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 according to weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)<br>|
| Experimental: LDV/SOF 24 weeks, with compensated cirrhosis<br>LDV/SOF for 24 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 12 Weeks After Cessation 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 Discontinued From Study Treatment for an Adverse Event |  | Up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With HCV RNA < the Lower Limit of Quantitation (LLOQ) at 4 and 24 Weeks Posttreatment | SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively. | Posttreatment Weeks 4 and 24 | 
| Percentage of Participants With Viral Breakthrough | Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while receiving treatment. | Up to 24 weeks | 
| Percentage of Participants With Viral Relapse | Viral relapse was defined as confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA <LLOQ at last on-treatment visit. | Up to Posttreatment Week 24 | 
| Number of Participants With Emerging Resistance | The full-length NS3, NS5A, and NS5B coding regions were deep sequenced at pretreatment (baseline) for all participants included in the Full Analysis Set, and at posttreatment for all participants who relapsed. | Up to Posttreatment Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ribavirin, Hepatitis C Virus (HCV), Ledipasvir/Sofosbuvir