Sofosbuvir/Velpatasvir in Adults With Chronic Hepatitis C Virus 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 safety, efficacy, and tolerability of treatment with sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks in adults on dialysis for end stage renal disease (ESRD) with chronic hepatitis C virus (HCV) infection of any genotype.

Official Title
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A Phase 2, Multicenter, Open-Label Study to Evaluate the Efficacy and Safety of Sofosbuvir/Velpatasvir for 12 Weeks in Subjects With Chronic HCV Infection Who Are on Dialysis for End Stage Renal Disease

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Drug: SOF/VEL


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Chronic HCV infected, male and non-pregnant/non-lactating females aged 18 years or older who are on dialysis for ESRD, including adults with HIV co-infection if they are suppressed on a stable, protocol-approved antiretroviral (ARV) regimen 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SOF/VEL<br>SOF/VEL for 12 weeks | Drug: SOF/VEL<br>* 400/100 mg fixed-dose combination (FDC) tablet(s) administered orally once daily<br>* Other names: Epclusa®;|

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 Discontinuation of Therapy (SVR12) | SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) 12 weeks after stopping the study treatment. | Posttreatment Week 12 | 
| Percentage of Participants Who Permanently Discontinued the Study Drug Due to an Adverse Event |  | First dose date up to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Therapy (SVR4) | SVR4 was defined as HCV RNA < LLOQ 4 weeks after stopping study treatment. | Posttreatment Week 4 | 
| Percentage of Participants With Sustained Virologic Response 24 Weeks After Discontinuation of Therapy (SVR24) | SVR24 was defined as HCV RNA < LLOQ 24 weeks after stopping study treatment. | Posttreatment Week 24 | 
| Change From Baseline in HCV RNA |  | Baseline; Weeks 2, 4, 6, 8, and 12 | 
| Percentage of Participants With HCV RNA < LLOQ on Treatment |  | Weeks 2, 4, 6, 8, and 12 | 
| 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 to Posttreatment Week 24 | 
| Number of Participants Who Develop Viral Resistance (as Assessed by Presence of HCV NS5A and NS5B Genes) to SOF and VEL During Treatment and After Discontinuation of Treatment | Baseline deep sequencing of the HCV NS5A and NS5B genes was performed for all participants. For all participants with virologic failure, deep sequencing was performed at the first time point after virologic failure if the plasma or serum sample was available and HCV RNA was > 1000 IU/mL. | First dose date up to Posttreatment Week 24 | 
| Pharmacokinetic (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 Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1)) | 
| 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 Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1)) | 
| PK Parameter: AUCtau of VEL | AUCtau is defined as the population PK derived area under the concentration verses 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 Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1)) | 
| 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 Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1)) | 
| 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 Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1)) | 
| PK Parameter: Cmax of VEL | 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 Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1)) | 
| PK Parameter: Ctau of VEL | Ctau is defined as the population PK derived concentration of the drug at the end of a 24 hour dosing interval. The 24 hour Ctau is estimated based on the combination of sparse PK samples collected at random times across the dosing interval as well as intensive PK samples collected for up to 12 hours post-dose. | 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 Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1)) |