Sofosbuvir/Velpatasvir Fixed-Dose Combination in Adults With Chronic HCV Infection and Child-Pugh Class B Cirrhosis

Study Overview
=================
Brief Summary
-----------------
The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of sofosbuvir (SOF)/velpatasvir (VEL) fixed dose combination (FDC) with and without ribavirin (RBV) for 12 weeks and SOF/VEL FDC for 24 weeks in adults with chronic hepatitis C virus (HCV) infection and Child-Pugh-Turcotte (CPT) class B cirrhosis.

Official Title
-----------------
A Phase 3, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/GS-5816 Fixed-Dose Combination in Subjects With Chronic HCV Infection and Child-Pugh Class B Cirrhosis

Conditions
-----------------
Hepatitis C Virus Infection

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Willing and able to provide written informed consent HCV RNA > 10^4 IU/mL at screening Chronic HCV infection (≥ 6 months) Confirmed CPT class B (7-9) at screening Exclusion Criteria: Current or prior history of solid organ transplantation, significant pulmonary disease, significant cardiac disease, or porphyria Inability to exclude hepatocellular carcinoma (HCC) by imaging within 6 months of baseline/Day 1 Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) Screening ECG with clinically significant abnormalities Prior exposure to SOF or any other nucleotide analogue HCV nonstructural protein 5B (NS5B) inhibitor or any HCV NS5A inhibitor Laboratory results outside of acceptable ranges at screening

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 12 weeks<br>Participants will receive SOF/VEL FDC for 12 weeks. | Drug: SOF/VEL<br>* 400/100 mg tablets administered orally once daily<br>* Other names: Epclusa®;|
| Experimental: SOF/VEL+RBV 12 weeks<br>Participants will receive SOF/VEL FDC plus RBV for 12 weeks. | Drug: SOF/VEL<br>* 400/100 mg tablets administered orally once daily<br>* Other names: Epclusa®;Drug: RBV<br>* Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)<br>|
| Experimental: SOF/VEL 24 weeks<br>Participants will receive SOF/VEL FDC for 24 weeks. | Drug: SOF/VEL<br>* 400/100 mg tablets administered orally once daily<br>* Other names: Epclusa®;|

What is the study measuring?
-----------------
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) 12 weeks following the last dose of study drug. | Posttreatment Week 12 | 
| Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event |  | Up to 24 weeks plus 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | 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 HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 |  | Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 | 
| Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 |  | Baseline; Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 | 
| Percentage of Participants With Virologic Failure | Virologic failure was defined as On-treatment virologic failure HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment, > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, HCV RNA persistently ≥ LLOQ through 8 weeks of treatment (ie nonresponse) Relapse HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement | Up to Posttreatment Week 24 | 
| Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in MELD Score | Model for End-Stage Liver Disease (MELD) scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40; higher scores/increased scores indicate greater severity of disease. | Baseline to Posttreatment Week 24 | 
| Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in Child-Pugh-Turcotte (CPT) Score | CPT scores grade the severity of cirrhosis and are used to determine the need for liver transplantation. Scores can range from 5 to 15; higher scores/increased scores indicate greater severity of disease. | Baseline to Posttreatment Week 24 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Sofosbuvir, Velpatasvir, SOF/VEL, GS-5816, Hepatitis C, HCV, Cirrhosis, CPT-B