Ledipasvir/Sofosbuvir in Adults With Chronic Hepatitis C Virus (HCV) Infection Who Are on Dialysis for End Stage Renal Disease

Study Overview
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Brief Summary
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The primary objectives of this study are to evaluate the safety, efficacy and tolerability of treatment with ledipasvir/sofosbuvir (LDV/SOF) in adults with chronic HCV infection who are on dialysis for ESRD.

Official Title
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A Phase 2, Multicenter, Open-Label Study to Evaluate the Efficacy and Safety of Ledipasvir/Sofosbuvir in Subjects With Genotype 1, 4, 5 and 6 Chronic HCV Infection Who Are on Dialysis for End Stage Renal Disease

Conditions
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Hepatitis C Virus Infection

Intervention / Treatment
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* Drug: LDV/SOF


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Chronic HCV infected genotype 1, 2 (Taiwan only), 4, 5, or 6 male and nonpregnant/ nonlactating females aged 18 years or older who are on dialysis for ESRD, including adults with HIV coinfection if they are suppressed on a stable, protocol-approved antiretroviral (ARV) regimens for ≥8 weeks prior to 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LDV/SOF for 8 weeks<br>Treatment-naive participants with genotype 1 without cirrhosis will receive LDV/SOF for 8 weeks | Drug: LDV/SOF<br>* 90/400 mg fixed- dose combination (FDC) tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;|
| Experimental: LDV/SOF for 12 weeks<br>Treatment-experienced participants with genotype 1 and treatment-naive or treatment-experienced participants with genotype 2 (Taiwan only), 4, 5 and 6 without cirrhosis will receive LDV/SOF for 12 weeks | Drug: LDV/SOF<br>* 90/400 mg fixed- dose combination (FDC) tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;|
| Experimental: LDV/SOF for 24 weeks<br>Participants with compensated cirrhosis will receive LDV/SOF for 24 weeks | Drug: LDV/SOF<br>* 90/400 mg fixed- dose combination (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 hepatitis C virus ribonucleic acid (HCV RNA) < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment. The exact 95% confidence interval (CI) for the percentage within treatment group was based on the Clopper-Pearson method. | Posttreatment Week 12 | 
| Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event |  | First dose date up to Week 24 | 

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 (ie, 15 IU/mL) at 4 weeks after stopping study treatment. The exact 95% CI for the percentage within treatment group was based on the Clopper-Pearson method. | Posttreatment Week 4 | 
| Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) | SVR24 was defined as HCV RNA < LLOQ (ie, 15 IU/mL) at 24 weeks after stopping study treatment. The exact 95% CI for the percentage within treatment group was based on the Clopper-Pearson method. | Posttreatment Week 24 | 
| Percentage of Participants With HCV RNA < LLOQ on Treatment | The total number of participants with HCV RNA < LLOQ was the sum of the number of participants with HCV RNA < LLOQ detected plus the number of participants with HCV RNA < LLOQ target not detected (TND). LLOQ was 15 IU/mL. The exact 95% CI for the percentage within treatment group was based on the Clopper-Pearson method. | Weeks 2, 4, 6, 8, 12, 16, 20, 24 | 
| HCV RNA |  | Weeks 2, 4, 6, 8, 12, 16, 20, 24 | 
| Change From Baseline in HCV RNA |  | Weeks 2, 4, 6, 8, 12, 16, 20, 24 | 
| Percentage of Participants With 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. | Baseline up to Posttreatment Week 24 | 
| Percentage of Participants Who Developed Resistance to LDV and SOF |  | Baseline up to Posttreatment Week 24 | 
| Pharmacokinetics (PK) Parameter: AUCtau of LDV | AUCtau is defined as the population PK derived area under the concentration versus time curve of the drug over the dosing interval. | Sparse PK Samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2)) | 
| PK Parameter: AUCtau of SOF | AUCtau is defined as the population PK derived area under the concentration versus time curve of the drug over the dosing interval. | Sparse PK Samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2)) | 
| PK Parameter: AUCtau of GS-331007 (Metabolite of SOF) | AUCtau is defined as the population PK derived area under the concentration versus time curve of the drug over the dosing interval. | Sparse PK Samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2)) | 
| PK Parameter: Cmax of LDV | Cmax is defined as the population PK derived maximum concentration of the drug. | Sparse PK Samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2)) | 
| PK Parameter: Cmax of SOF | Cmax is defined as the population PK derived maximum concentration of the drug. | Sparse PK Samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2)) | 
| PK Parameter: Cmax of GS-331007 (Metabolite of SOF) | Cmax is defined as the population PK derived maximum concentration of the drug. | Sparse PK Samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2)) |