Interim data from the ongoing C-WORTHY study, a phase II clinical trial evaluating the efficacy and safety of an all-oral regimen combining once-daily MK-5172, an investigational hepatitis C virus ( HCV ) NS3/4A protease inhibitor, and MK-8742, an investigational HCV NS5A replication complex inhibitor, with or without twice-daily Ribavirin, administered for 12 weeks to treatment-naïve, non-cirrhotic patients with HCV genotype 1a and 1b infection, were presented at the 2013 American Association for the Study of Liver Diseases ( AASLD ) Annual Meeting. Br> The interim data have shown that the administration of MK-5172 and MK-8742 in combination is associated with a sustained virologic response ( lack of detectable and quantifiable HCV ) 12 weeks following the end of study therapy ( SVR12 ).
In the C-WORTHY study, 65 patients ( 45% male, 11% African American, and 58% genotype 1a infection ) were enrolled in one of three 12-week treatment arms.
The Ribavirin arms were stratified by genotype 1a versus genotype 1b. The Ribavirin-free arm included only genotype 1b-infected patients.
Virologic response was assessed each week during treatment and at 2, 4, 8, 12 and 24 weeks after the end of treatment.
The primary efficacy endpoint of the trial was the proportion of patients who achieved sustained virologic response at post-treatment follow-up week 12 ( SVR12 ).
The primary analysis population was per protocol, including patients who did not have protocol violations and had received the correct study medications. A total of 58/65 enrolled patients met these criteria: Arm 1: MK-5172 ( 100 mg ) + MK-8742 ( 20 mg ) + Ribavirin ( 22 patients ) SVR4: 100%; SVR12: 100% - Arm 2: MK-5172 ( 100 mg ) + MK-8742 ( 50 mg ) + Ribavirin ( 24 patients ) SVR4: 96%; SVR12: 96% - Arm 3: MK-5172 ( 100 mg ) + MK-8742 ( 50 mg ) ( 12 patients ) SVR4: 100%; SVR12: 100%.
Of the seven patients who were not in the per-protocol population, four achieved SVR12 and three discontinued early for reasons other than adverse experiences or virologic failure.
Among the entire study population of 65 patients, one patient ( 1.5% ) experienced a relapse with detectable HCV RNA at follow-up week 4 and 12.
The most frequently reported adverse events occurring in the study were fatigue ( 26% ), headache ( 22% ), nausea ( 18% ), diarrhea ( 12% ), dizziness ( 11% ) and rash ( 11% ). The incidence of anemia ( less than 10 mg/dL haemoglobin ) and elevated total bilirubin levels to 2 times the upper limit of normal was 19% and 4%, respectively, in the Ribavirin-containing arms ( combined arms 1 and 2 ), and 0% and 0%, respectively, in the Ribavirin-free arm. No grade 3 or 4 laboratory abnormalities were observed. There were eight cases of rash. Seven cases of rash were observed in the Ribavirin-containing arms; half of these cases were attributed to Ribavirin. The single case in the Ribavirin-free arm was not study drug related and was mild in intensity. No early discontinuations due to drug-related adverse events were recorded.
The C-WORTHY trial has been expanded to evaluate the safety and efficacy of MK-5172 and MK-8742, with or without Ribavirin, in difficult-to-cure HCV genotype 1-infected patient populations. Approximately 400 additional HCV genotype 1-infected patients have been enrolled in this trial. The expanded C-WORTHY study is testing: 8 week regimen of MK-5172/MK-8742 + RBV in treatment naïve non-cirrhotic patients; 12 week regimen of MK-5172/MK-8742 without RBV in treatment-naïve non-cirrhotic patients; 12 week regimens ( MK-5172/MK-8742 with or without RBV ) among HIV co-infected patients; 12 or 18 week regimens ( MK-5172/MK-8742 with or without RBV ) in patients with cirrhosis; 12 or 18 week regimens ( MK-5172/MK-8742 with or without RBV ) in patients who had failed to respond to prior Peginterferon and Ribavirin therapy ( null responders ). ( Xagena )
Source: Merck, 2013