Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination ± Ribavirin in Cirrhotic Subjects With Chronic Genotype 1 HCV Infection

NCT ID: NCT01965535

Last Updated: 2018-11-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 155 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2014-11-30

Brief Summary

This study is to determine the antiviral efficacy of sofosbuvir (SOF)/ledipasvir (LDV) fixed-dose combination (FDC) with and without ribavirin (RBV), and to evaluate the safety and tolerability of each regimen as assessed by review of the accumulated safety data. Approximately 150 participants with genotype 1 HCV infection, who have previously received treatment for HCV, and who have a diagnosis for cirrhosis will be enrolled. Participants will be randomized to 1 of 2 groups.

Group 1: SOF/LDV FDC tablet plus placebo to match RBV for 24 weeks

Group 2: Delayed treatment group: placebo to match SOF/LDV FDC plus placebo to match RBV for 12 weeks, followed by SOF/LDV FDC once daily plus RBV in a divided daily dose for 12 weeks

Randomization will 1:1 to the two groups and will be stratified by HCV genotype (1a, 1b; mixed or other genotype 1 results will be stratified as genotype 1a), and prior HCV therapy treatment response (never achieved HCV RNA < the lower limit of quantitation (LLOQ), or achieved HCV RNA < LLOQ).

Conditions

HCV Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

LDV/SOF

LDV/SOF FDC tablet plus placebo to match RBV for 24 weeks

Group Type: EXPERIMENTAL

LDV/SOF

Intervention Type: DRUG

LDV/SOF (90/400 mg) FDC tablet administered orally once daily

Placebo to match RBV

Intervention Type: DRUG

Placebo to match RBV administered orally in a divided daily dose

LDV/SOF + RBV

Placebo to match SOF/LDV FDC plus placebo to match RBV for 12 weeks, followed by LDV/SOF FDC plus RBV for 12 weeks.

Group Type: EXPERIMENTAL

LDV/SOF

Intervention Type: DRUG

LDV/SOF (90/400 mg) FDC tablet administered orally once daily

RBV

Intervention Type: DRUG

RBV (200 mg tablets) administered orally in a divided daily dose based on weight (1000 mg per day for participants weighing \< 75 kg; 1200 mg per day for participants weighing ≥ 75 kg)

Placebo to match LDV/SOF

Intervention Type: DRUG

Placebo to match LDV/SOF administered orally once daily

Placebo to match RBV

Intervention Type: DRUG

Placebo to match RBV administered orally in a divided daily dose

Interventions

LDV/SOF

LDV/SOF (90/400 mg) FDC tablet administered orally once daily

Intervention Type: DRUG

RBV

RBV (200 mg tablets) administered orally in a divided daily dose based on weight (1000 mg per day for participants weighing \< 75 kg; 1200 mg per day for participants weighing ≥ 75 kg)

Intervention Type: DRUG

Placebo to match LDV/SOF

Placebo to match LDV/SOF administered orally once daily

Intervention Type: DRUG

Placebo to match RBV

Placebo to match RBV administered orally in a divided daily dose

Intervention Type: DRUG

Other Intervention Names

Harvoni®; GS-5885/GS-7977

Eligibility Criteria

Inclusion Criteria

• Age equal to or greater than 18 years, with chronic genotype 1 HCV infection
• HCV RNA ≥ 10,000 IU/mL at screening
• Prior virological failure after treatment with pegylated interferon (PEG-IFN), RBV and a protease inhibitor following documented prior virology failure after treatment with a PEG-IFN + RBV regimen
• Evidence of cirrhosis
• Screening laboratory values within defined thresholds
• Use of two effective contraception methods if female of childbearing potential or sexually active male

Exclusion Criteria

• Pregnant or nursing female or male with pregnant female partner
• Current or prior history of clinical hepatic decompensation
• Prior exposure to approved or experimental HCV specific direct-acting antivirals other than a nonstructural protein (NS)3/4A protease inhibitor
• History of solid organ transplantation, including liver transplant
• Hepatocellular carcinoma or other malignancy (with exception of certain resolved skin cancers)
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert H Hyland, DPhil

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Clermont-Ferrand, , France

Clichy, , France

Créteil, , France

Grenoble, , France

Lille, , France

Limoges, , France

Lyon, , France

Marseille, , France

Montpelier, , France

Nancy, , France

Nice, , France

Paris, , France

Paris, , France

Paris, , France

Paris, , France

Pessac, , France

Rennes, , France

Strasbourg, , France

Toulouse, , France

Countries

France

References

Bourliere M, Bronowicki JP, de Ledinghen V, Hezode C, Zoulim F, Mathurin P, Tran A, Larrey DG, Ratziu V, Alric L, Hyland RH, Jiang D, Doehle B, Pang PS, Symonds WT, Subramanian GM, McHutchison JG, Marcellin P, Habersetzer F, Guyader D, Grange JD, Loustaud-Ratti V, Serfaty L, Metivier S, Leroy V, Abergel A, Pol S. Ledipasvir-sofosbuvir with or without ribavirin to treat patients with HCV genotype 1 infection and cirrhosis non-responsive to previous protease-inhibitor therapy: a randomised, double-blind, phase 2 trial (SIRIUS). Lancet Infect Dis. 2015 Apr;15(4):397-404. doi: 10.1016/S1473-3099(15)70050-2. Epub 2015 Mar 13.

Reference Type: DERIVED

PMID: 25773757 (View on PubMed)

Other Identifiers

2013-002296-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-337-0121

Identifier Type: -

Identifier Source: org_study_id