In August 2012, Achillion initiated a Phase 1b clinical trial enrolling a total of 14 patients infected with GT 1a chronic HCV, of which 2 received placebo and 12 received a single dose of 50 mg, 150 mg or 300 mg ACH-3102. No serious adverse events were reported and there were no patient discontinuations.
The mean maximum HCV RNA decline for each dose group is provided below:
|Mean maximal||Range decline|
|Dose||decline HCV RVA||HCV RNA|
|50||4||3.78||3.35 – 4.16|
|1a||150||4||3.52||2.91 – 3.98|
|300||4||3.93||3.40 – 4.60|
An assessment of clinical virology was conducted on baseline samples from all 12 patients receiving a single-dose of ACH-3102. Sequencing revealed one patient had a baseline L31M mutation (300 mg dose group, maximum HCV RNA decline of 3.4 log 10) and another patient had a baseline Y93C mutation (300 dose group, maximum HCV RNA decline of 4.6 log 10). These mutations have been previously reported to convey a high level of resistance to first-generation NS5A inhibitors which was not observed following exposure to ACH-3102.
ACH-3102: All-oral, interferon-free pilot Phase 2 12-week trial of ACH-3102 and ribavirin for the treatment of HCV GT 1bAchillion has initiated patient enrollment in an open-label Phase 2 pilot trial evaluating 12-weeks of once-daily ACH-3102 in combination with ribavirin for the treatment of HCV GT 1b. This study will initially enroll up to 16 treatment-naïve patients with GT 1b IL28B CC HCV. Patients will receive 225 mg of ACH-3102 on day 1 followed by 75 mg of ACH-3102 once daily on subsequent days in combination with twice daily ribavirin. The primary objective of the trial is to determine the safety and sustained virologic response 12 weeks after the completion of treatment (SVR12) with secondary endpoints assessing safety, pharmacokinetics, pharmacodynamics, and virologic endpoints including rapid virologic response (RVR) and extended RVR (eRVR). Achillion expects to report initial RVR results from this study during the fourth quarter of 2012.