Clinical Trials

Date: 2017-04-22

Type of information: Presentation of results at a congress

phase: 2

Announcement: presentation of results at The International Liver Congress™ 2017

Company: Merck&Co (USA - NJ)

Product: MK-3682B (uprifosbuvir/grazoprevir/rusazvir)

Action mechanism: direct-acting antiviral agent/nucleotide analog/NS5B polymerase inhibitor/nonstructural protein 5A (NS5A) inhibitor/ NS3/4A protease inhibitor. MK-3682B  is an investigational triple-combination therapy. It combines an HCV nucleotide analogue NS5B polymerase inhibitor (MK-3682 - uprifosbuvir)), an HCV NS3/4A protease inhibitor (grazoprevir, MK-5172) and an HCV NS5A inhibitor (ruzasvir, MK-8408). Uprifosbuvir) is a uridine nucleotide analog developed by Idenix Pharmaceuticals. Merck&Co has acquired this company in 2014.  

Disease: hepatitis C

Therapeutic area: Infectious diseases

Country: France, Germany, Spain, Sweden, USA

Trial details: This is a randomized, multicenter, open-label trial of the combination regimen of MK-5172 (grazoprevir [GZR]) (100 mg), MK-3682 (450 mg) and MK-8408 (ruzasvir) (60 mg) for 16 weeks with ribavirin (RBV) or 24 weeks without RBV in cirrhotic (C) or non-cirrhotic (NC) hepatitis C virus (HCV) genotype 1 or genotype 3-infected participants who have previously failed a direct-acting antiviral regimen (DAA). The combination regimen will be administered as two fixed-dose combination tablets, referred to as MK-3682B, given once-daily. The study will evaluate the efficacy of the combination regimen of MK-5172 (GZR), MK-3682 and MK-8408 (ruzasvir) with or without ribavirin as assessed by the proportion of participants achieving Sustained Virologic Response 12 weeks (SVR12) after the end of all study therapy. (NCT02613403)

Latest news:

• • On April 22, 2017, Merck&Co announced the first sustained virologic response1 (SVR) results 12 weeks after completion of therapy (SVR12, considered virologic cure) from C-SURGE, an ongoing, open label Phase 2 clinical trial evaluating MK-3682B [uprifosbuvir (MK-3682)/grazoprevir/rusazvir], in treatment-experienced patients with hepatitis C virus genotype 1 infection for whom treatment with approved direct-acting antiviral regimens had failed. The study showed that 100 percent (43/43) of patients who completed 16 weeks of treatment plus ribavirin achieved SVR12 and 100 percent (49/49) of patients who completed 24 weeks of treatment achieved SVR12 (abstract PS-159). These results will be presented at The International Liver Congress™ 2017.
• The Phase 2 C-SURGE study enrolled 94 patients who were randomized to receive a once-daily regimen of MK-3682B for either 16 weeks with ribavirin (n=45) or 24 weeks without RBV (n=49); one patient in the 16-week arm withdrew prior to starting treatment. Of the 93 patients who received treatment (full analysis set), 57 had previously received a regimen of ledipasvir/sofosbuvir (LDV/SOF) for 12 to 24 weeks, 14 had previously received LDV/SOF for 8 weeks and 22 had previously received Zepatier® (elbasvir and grazoprevir) for 12 weeks. Seventy-eight patients who received treatment had at least one baseline NS5A resistance-associated substitution (RAS) at positions 28, 30, 31 or 93. Eighty patients who received treatment in C-SURGE had GT1a infection, and 40 patients had compensated cirrhosis. In the full analysis set, 98 percent of patients who received MK-3682B for 16 weeks with RBV (43/44) and 100 percent of patients who received MK-3682B for 24 weeks without ribavirin (49/49) achieved SVR12.
• Results from the modified full analysis set, which excludes one patient in the 16-week arm who withdrew after three doses of treatment, show that 100 percent of patients receiving treatment with MK-3682B for 16 weeks with ribavirin (43/43) and 100 percent of patients receiving treatment with MK-3682B for 24 weeks without ribavirin (49/49) achieved SVR12.
• Across the combined treatment arms, the most common adverse events (AEs) reported in the full analysis set were fatigue (35%), headache (13%), diarrhea (9%), rash (9%) and pruritus (5%). There were no drug-related serious AEs, and no patients discontinued treatment due to a drug-related AE. SVR8 results from the C-SURGE study were previously presented at The Liver Meeting® 2016.

 

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