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

NCT01965535 | Completed Phase 2 Results DMC

• 2 other identifiers: GS-US-337-01212013-002296-17
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 19

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

Keywords

Hepatitis C; HCV; Cirrhosis

Outcome Measures

Primary Outcomes (1)

• 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, \< 25 IU/mL) 12 weeks following the last dose of study drug. * 1 participant who was randomized to the LDV/SOF + RBV group who received placebo discontinued prior to receiving LDV/SOF + RBV and is excluded from the Full Analysis Set. * 1 participant who was randomized to the LDV/SOF + RBV group received LDV/SOF + placebo, and is counted in the LDV/SOF group for the safety analysis, and in the LDV/SOF+RBV group for the efficacy analysis (ie, in the Full Analysis Set).

  Posttreatment Week 12

Secondary Outcomes (4)

• Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)

  Posttreatment Weeks 4 and 24

• Percentage of Participants With HCV RNA < LLOQ (ie, < 25 IU/mL) at Weeks 1, 2, 4, 8, 12, and 24

  Weeks 1, 2, 4, 8, 12, and 24

• Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, and 12

  Baseline; Weeks 1, 2, 4, 8, and 12

• Percentage of Participants With Virologic Failure

  Baseline to Posttreatment Week 24

Study Arms (2)

LDV/SOF

EXPERIMENTAL

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

Drug: LDV/SOF; Drug: Placebo to match RBV

LDV/SOF + RBV

EXPERIMENTAL

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

Drug: LDV/SOF; Drug: RBV; Drug: Placebo to match LDV/SOF; Drug: Placebo to match RBV

Interventions

LDV/SOF DRUG

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

Also known as: Harvoni®, GS-5885/GS-7977

LDV/SOF; LDV/SOF + RBV

RBV 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)

LDV/SOF + RBV

Placebo to match LDV/SOF DRUG

Placebo to match LDV/SOF administered orally once daily

LDV/SOF + RBV

Placebo to match RBV DRUG

Placebo to match RBV administered orally in a divided daily dose

LDV/SOF; LDV/SOF + RBV

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (19)

Unknown Facility

Clermont-Ferrand, 63003, France

Location

Unknown Facility

Clichy, 92110, France

Location

Unknown Facility

Créteil, 94000, France

Location

Unknown Facility

Grenoble, 38043, France

Location

Unknown Facility

Lille, 57037, France

Location

Unknown Facility

Limoges, 87042, France

Location

Unknown Facility

Lyon, 69317, France

Location

Unknown Facility

Marseille, 13285, France

Location

Unknown Facility

Montpelier, 34295, France

Location

Unknown Facility

Nancy, 54500, France

Location

Unknown Facility

Nice, 06202, France

Location

Unknown Facility

Paris, 75012, France

Location

Unknown Facility

Paris, 75013, France

Location

Unknown Facility

Paris, 75014, France

Location

Unknown Facility

Paris, 75020, France

Location

Unknown Facility

Pessac, 33604, France

Location

Unknown Facility

Rennes, 35033, France

Location

Unknown Facility

Strasbourg, 67091, France

Location

Unknown Facility

Toulouse, 31059, France

Location

Related Publications (1)

• 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.

  PMID: 25773757 DERIVED

MeSH Terms

Conditions

Hepatitis C; Fibrosis

Interventions

ledipasvir, sofosbuvir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

There were no limitations affecting the analysis or results.

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences

ClinicalTrialDisclosures@gilead.com

Study Officials

• Robert H Hyland, DPhil

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2013
• First Posted: October 18, 2013
• Study Start: October 1, 2013
• Primary Completion: August 1, 2014
• Study Completion: November 1, 2014
• Last Updated: November 16, 2018
• Results First Posted: September 28, 2015

Record last verified: 2016-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

FR (19)