3 out of ~45(?)in high dose arm with Grade 4 ALT elevations.
InterMune Announces Modification to On-Going Phase 2b Study of ITMN-191 in Patients with Chronic HCV Infection
BRISBANE, Calif., Nov. 17 /PRNewswire-FirstCall/ -- InterMune, Inc. (Nasdaq: ITMN - News) today announced that the on-going Phase 2b study conducted by Roche of ITMN-191 (RG7227) combined with standard of care (SOC) PEGASYS® (peginterferon alfa-2a) and COPEGUS® (ribavirin) in HCV treatment-naive patients has been modified.
The Phase 2b study has four dosage cohorts: SOC; 300mg q8h plus SOC; 600mg q12h plus SOC and 900mg q12h plus SOC. To date, approximately 175 patients have been enrolled in the study.
Three patients in the blinded 900 mg q12h dosage cohort experienced a Grade 4 elevation in ALT levels, one of whom experienced an elevation of total bilirubin while also receiving concomitant allopurinol. After their review of the un-blinded data from all cohorts, the study's independent Data Monitoring Committee (DMC) recommended that the 900mg q12h cohort be discontinued and that all other cohorts of the study continue. The companies accepted the DMC's recommendations. The on-going Phase 2b study is blinded and consequently, additional details will not be provided.
As previously disclosed, the company anticipates the results of blinded rapid virologic response (RVR) data from the 12-week treatment duration cohorts in the first quarter of 2010. The company also reported that the on-going ritonavir boosting study of low-dose ITMN-191 continues to enroll patients and that guidance for INFORM-2 and for a longer duration Phase 2 study of the combination of direct acting antivirals to evaluate sustained virologic response (SVR) is not expected to change at this time.
About the Phase 2b Study
The objective of the Phase 2b randomized, double-blind, placebo-controlled study is to further characterize the safety, tolerability, and antiviral effects of ITMN-191 in triple combination, compared with standard of care (PEGASYS plus COPEGUS).
The two-part study will evaluate treatment regimens of both 12 and 24 weeks. In Part 1 of the original study design, approximately 210 patients will be randomized to one of four study arms - three of which will receive a 12-week regimen of ITMN-191 at either 300 mg every 8 hours, 600 mg every 12 hours or 900 mg every 12 hours, in combination with PEGASYS and COPEGUS, followed by 12 weeks of therapy with PEGASYS and COPEGUS. The fourth group will be a control arm receiving PEGASYS and COPEGUS dosed for 48 weeks. As reported above, the third arm involving 900 mg every 12 hours, in combination with PEGASYS and COPEGUS, followed by 12 weeks of therapy with PEGASYS and COPEGUS is being discontinued at the recommendation of the independent DMC.
Part 2 of the study, is designed to further evaluate RG7227/ ITMN-191 in a 24-week triple combination regimen with PEGASYS and COPEGUS. Patients will be randomized to one of two study arms in Part 2, either a 24-week regimen of ITMN-191 in combination with PEGASYS and COPEGUS, or a control arm of PEGASYS and COPEGUS dosed for 48 weeks. Dose selection for Part 2 will be informed by week 4 results generated in Part 1.
About ITMN-191 / RG7227
ITMN-191 / RG7227 is a potent, macrocyclic inhibitor of HCV NS3/4A protease activity, and has produced multi-log10 reductions in levels of HCV in chronic HCV patients, when administered for 14 days as monotherapy and when combined with PEGASYS® (peginterferon alfa-2a) and COPEGUS® (ribavirin, USP). ITMN-191 was safe and well-tolerated in these studies. |
