Phase 2
Completed N=155
Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination ± Ribavirin in Cirrhotic Subjects With Chronic Genotype 1 HCV Infection
HCV Infection
Source: ClinicalTrials.gov NCT01965535 ↗
Enrolled (actual)
155
Serious AEs
7.7%
Results posted
Sep 2015
Primary outcomePrimary: Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) — 97.4; 96.1 percentage of participants
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).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) |
97.4; 96.1 | — |
| SECONDARY Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) |
97.4; 97.4; 97.4; 96.1 | — |
| SECONDARY Percentage of Participants With HCV RNA < LLOQ (ie, < 25 IU/mL) at Weeks 1, 2, 4, 8, 12, and 24 |
7.8; 9.1; 50.6; 59.7; 97.4; 97.4 | — |
| SECONDARY Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, and 12 |
-4.10; -4.27; -4.74; -4.94; -5.10; -5.19 | — |
| SECONDARY Percentage of Participants With Virologic Failure |
0; 0; 2.6; 3.9 | — |
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
Data sourced from ClinicalTrials.gov (NCT01965535). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.