Merck announced results from the company's Phase 3 C-EDGE CO-STAR clinical trial evaluating the efficacy and safety of the investigational once-daily tablet elbasvir/grazoprevir (50mg/100mg) in patients with chronic hepatitis C virus (HCV) genotypes (GT) 1, 4 or 6 infection who inject drugs and are receiving opioid agonist therapy (OAT). 95% (189/198) of patients treated with elbasvir/grazoprevir for 12 weeks in the pre-specified primary efficacy analysis population achieved sustained virologic response 12 weeks after the completion of treatment (SVR12, considered virologic cure). Adherence to treatment was high, with 97% of patients taking at least 95% of their study medication over the 12 weeks of therapy.

C-EDGE CO-STAR is a Phase 3 randomized, double-blind, placebo-controlled study evaluating treatment with elbasvir/grazoprevir in patients with chronic HCV GT1, 4 or 6 infection who are on OAT (e.g., methadone, buprenorphine). The study randomized 301 patients to one of two study arms: an immediate treatment group (ITG) that received elbasvir/grazoprevir (blinded) for 12 weeks (n=201), and a deferred treatment group (DTG) that received 12 weeks of placebo (control arm) followed by a four-week follow-up period and then elbasvir/grazoprevir (open-label) for 12 weeks (n=100). The primary efficacy analysis – or modified full analysis set (mFAS) – excluded patients who discontinued treatment for reasons unrelated to study drug (n=3) and classified patients who had cleared their baseline infection but subsequently acquired a new infection as treatment successes (n=5).

In the mFAS, 96% of GT1a patients (147/153), 97% of GT1b patients (28/29), 100% of GT4 patients (11/11) and 60% of GT6 patients (3/5) achieved virologic cure when treated with elbasvir/grazoprevir for 12 weeks. Results for patients with GT6 infection were limited by the small number of GT6 patients enrolled. In a supportive efficacy analysis based on the full analysis set (FAS), which included all subjects with HCV GT1, 4 or 6 infection who received at least one dose of study drug, the overall SVR12 rate in the ITG was 92% (184/201).

Of the 301 patients evaluated across both treatment groups, 76% had GT1a infection, 21% had cirrhosis and 7% had HIV/HCV co-infection. All patients were on OAT at baseline. The use of non-prescribed drugs, such as cocaine and/or amphetamines, was observed in 59% of patients at baseline and remained steady throughout the trial; however, adherence to treatment with elbasvir/grazoprevir was high.

In the mFAS, virologic failures occurred in nine patients in the ITG, including seven relapses and two discontinuations for reasons deemed related to study drug; in the FAS, an additional five reinfections and three discontinuations for non-treatment related reasons were counted as treatment failures. Across the ITG on active study medication and DTG on placebo, four patients (1%) discontinued treatment due to adverse events (AE), including two patients (1%) in the ITG and two (2%) in the DTG. Two patients (1% across both groups) reported a serious drug-related AE (0.5% in the ITG, 1% in the DTG).

The most common AEs in the ITG versus the DTG, respectively, were fatigue (16% versus 20%), headache (13% versus 14%), nausea (11% versus 9%) and diarrhea (10% versus 9%). One patient receiving placebo died for reasons unrelated to the study drug.