Clinical trial NCT01965535: Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination ± Ribavirin in Cirrhotic Subjects With Chronic Genotype 1 HCV Infection
Official title: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination for 12 Weeks With Ribavirin or for 24 Weeks Without Ribavirin in Treatment-Experienced Cirrhotic Subjects With Chronic Genotype 1 HCV Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HCV Infection
Keywords: Hepatitis C
HCV
Cirrhosis
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2013-10-18
Enrollment: 155
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
timeFrame: Posttreatment Week 12
Secondary outcomes:
measure: Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
timeFrame: Posttreatment Weeks 4 and 24
measure: Percentage of Participants With HCV RNA < LLOQ (ie, < 25 IU/mL) at Weeks 1, 2, 4, 8, 12, and 24
timeFrame: Weeks 1, 2, 4, 8, 12, and 24
measure: Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, and 12
timeFrame: Baseline; Weeks 1, 2, 4, 8, and 12
measure: Percentage of Participants With Virologic Failure
timeFrame: Baseline to Posttreatment Week 24
Other outcomes:
Locations:
city: Clermont Ferrand
country: France
city: Clichy
country: France
city: Creteil
country: France
city: Grenoble
country: France
city: Lille
country: France
city: Limoges
country: France
city: Lyon
country: France
city: Marseille
country: France
city: Montpelier
country: France
city: Nancy
country: France
city: Nice
country: France
city: Paris
country: France
city: Paris
country: France
city: Paris
country: France
city: Paris
country: France
city: Pessac
country: France
city: Rennes
country: France
city: Strasbourg
country: France
city: Toulouse
country: France
Study officials:
affiliation: Gilead Sciences
name: Robert H Hyland, DPhil
role: STUDY_DIRECTOR
References:
citation: 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.