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

Phase 3

Completed

• Conditions: Hepatitis C Virus Infection
• Interventions: Drug: SOF/VEL; Drug: RBV

• Registration Number: NCT02201901
• Lead Sponsor: Gilead Sciences

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-07
• Study First Submitted: 2014-07-24
• Study First Submitted QC: 2014-07-24
• Study First Posted: 2014-07-28
• Primary Completion: 2015-08
• Study Completion: 2015-11
• Results First Submitted: 2016-08-24
• Status Verified: 2016-10
• Results First Submitted QC: 2016-10-24
• Results First Posted: 2016-12-14
• Last Update Submitted: 2018-10-19
• Last Update Posted: 2018-11-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 268

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SOF/VEL 12 weeks	SOF/VEL	Participants will receive SOF/VEL FDC for 12 weeks.
SOF/VEL+RBV 12 weeks	SOF/VEL	Participants will receive SOF/VEL FDC plus RBV for 12 weeks.
SOF/VEL+RBV 12 weeks	RBV	Participants will receive SOF/VEL FDC plus RBV for 12 weeks.
SOF/VEL 24 weeks	SOF/VEL	Participants will receive SOF/VEL FDC for 24 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)	Posttreatment Week 12	SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event	Up to 24 weeks plus 30 days

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)	Posttreatment Weeks 4 and 24	SVR4 and SVR24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
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	Up to Posttreatment Week 24	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
Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in MELD Score	Baseline to Posttreatment Week 24	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.
Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in Child-Pugh-Turcotte (CPT) Score	Baseline to Posttreatment Week 24	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.