Ledipasvir/Sofosbuvir Fixed-Dose Combination and Vedroprevir With or Without Ribavirin in Treatment-Experienced Participants With Chronic Genotype 1 HCV Infection and Cirrhosis

A Phase 2, Randomized, Open-Label Study of Ledipasvir/Sofosbuvir Fixed-Dose Combination and Vedroprevir With or Without Ribavirin in Treatment-Experienced Subjects With Chronic Genotype 1 HCV Infection and Cirrhosis

This study is to evaluate the antiviral efficacy, safety, and tolerability of combination therapy with ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) + vedroprevir (VDV) ± ribavirin (RBV) for 8 weeks in treatment-experienced adults with chronic genotype 1 hepatitis C virus (HCV) infection and cirrhosis.

Study Overview

• Status: Completed
• Conditions: Hepatitis C Virus Infection
• Intervention / Treatment: Drug: LDV/SOF; Drug: RBV; Drug: VDV

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years, with chronic HCV genotype 1 infection
• Documentation as treatment-experienced having received pegylated interferon (Peg-IFN) + RBV ≥ 4 weeks of duration without an additional agent in the regimen without achieving sustained viral response (SVR)
• Presence of compensated cirrhosis
• Screening laboratory values within defined thresholds
• Must use specific contraceptive methods if female of childbearing potential or sexually active male
• Not pregnant or a nursing female

Exclusion Criteria:

• Co-infection with HIV or hepatitis B virus (HBV)
• Current or prior history of clinical hepatic decompensation
• Chronic use of systemic immunosuppressive agents
• History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LDV/SOF+VDV; Participants will receive LDV/SOF+VDV for 8 weeks.	Drug: LDV/SOF; LDV/SOF (90/400 mg) FDC tablet administered orally once daily; Other Names: Harvoni®; GS-5885/GS-7977; Drug: VDV; VDV 80 mg tablet administered orally once daily; Other Names: GS-9451
Experimental: LDV/SOF+VDV+RBV; Participants will receive LDV/SOF+VDV+RBV for 8 weeks.	Drug: LDV/SOF; LDV/SOF (90/400 mg) FDC tablet administered orally once daily; Other Names: Harvoni®; GS-5885/GS-7977; Drug: RBV; 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); Drug: VDV; VDV 80 mg tablet administered orally once daily; Other Names: GS-9451

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; ie, 15 IU/mL) at 12 weeks after stopping study treatment.	Posttreatment Week 12
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event		Up to 8 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

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Robert Hyland, DPhil, Gilead Sciences

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: August 25, 2014
• First Submitted That Met QC Criteria: August 25, 2014
• First Posted (Estimate): August 27, 2014

Study Record Updates

• Last Update Posted (Actual): November 16, 2018
• Last Update Submitted That Met QC Criteria: October 19, 2018
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: hepatitis C; Gilead; GS-9451
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Disease Attributes; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Infections; Communicable Diseases; Hepatitis; Hepatitis C; Anti-Infective Agents; Antiviral Agents; Sofosbuvir; Ledipasvir, sofosbuvir drug combination; Ledipasvir
• Other Study ID Numbers: GS-US-337-1512

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)