Efficacy and Safety of Sofosbuvir/Velpatasvir ± Ribavirin for 12 Weeks in Adults With Chronic HCV Infection and Decompensated Cirrhosis

Study Overview
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Brief Summary
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The primary objectives of this study are to evaluate the antiviral efficacy, safety, and tolerability of sofosbuvir/velpatasvir (SOF/VEL) fixed-dose combination (FDC) with or without ribavirin (RBV) for 12 weeks in adults with chronic hepatitis C virus (HCV) infection and decompensated cirrhosis.

Official Title
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A Multicenter, Randomized, Phase 3, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/Velpatasvir ± Ribavirin for 12 Weeks in Subjects With Chronic HCV Infection and Decompensated Cirrhosis

Conditions
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Hepatitis C Virus Infection

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


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Chronic HCV-infected males and non-pregnant/non-lactating females Treatment naive or treatment experienced individuals Child-Pugh-Turcotte Score 7-12 at screening 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: SOF/VEL<br>SOF/VEL for 12 weeks | Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily<br>* Other names: Epclusa®;|
| Experimental: SOF/VEL + RBV<br>SOF/VEL + RBV for 12 weeks | Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily<br>* Other names: Epclusa®;Drug: RBV<br>* Capsules administered orally in a divided daily dose<br>* Other names: Rebetol®;|

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 Discontinued Treatment (SOF/VEL or RBV) Early 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) | SVR24 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment. | Posttreatment Week 24 | 
| Percentage of Participants Who Had HCV RNA < LLOQ by Visit While on Treatment |  | Up to 12 weeks | 
| Change From Baseline in HCV RNA |  | Baseline and up to 12 weeks | 
| Percentage of Participants With a Decrease, No Change, or Increase in Model for End Stage Liver Disease (MELD) Score | MELD score is a chronic liver disease severity scoring system. Scores can range from 6 to 40, with higher scores indicating greater disease severity. No change was assigned for differences (posttreatment visits minus baseline score) of -1, 0 or 1; Decrease was assigned for differences that were less than or equal to -2; and Increase was assigned for values that were greater than or equal to 2. | Baseline to Posttreatment Week 24 | 
| Percentage of Participants With Improved and Worsened Child-Pugh-Turcotte (CPT) Class | CPT is a chronic liver disease classification system. Classes include CPT Class A, CPT Class B, and CPT Class C, in order of greater disease severity. Participants with improved CPT class was defined as having Class C at Baseline and Class B or A at Posttreatment Week 24 or Class B at Baseline and Class A at Posttreatment Week 24. Participants with worsened CPT class was defined as having Class A at Baseline and Class B or C at Posttreatment Week 24 or Class B at Baseline and Class C at Posttreatment Week 24. CPT scores were calculated using prothrombin activation percentage for the coagulation parameter per Japan's standard. | Baseline to Posttreatment Week 24 | 
| Percentage of Participants With Virologic Failure | Virologic failure was defined as: 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 during the post-treatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available post-treatment measurement). | Up to Posttreatment Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Communicable Diseases, Hepatitis, Hepatitis C, Virus Diseases, Liver Diseases, Digestive System Diseases, Hepatitis, Viral, Human, Velpatasvir, RNA Virus Infections, Ribavirin, Sofosbuvir, Antiviral Agents, Antimetabolites, Molecular Mechanisms of Pharmacological Action, Anti-Infective Agents, Decompensated Cirrhosis