This 12-week, four-arm, parallel group Phase II clinical trial will enroll 200 patients and is designed to provide a head-to-head comparison of the efficacy and tolerability of 0.25mg, 0.5mg and 1mg once daily oral doses of CH-1504 versus a 20mg once weekly oral dose of methotrexate (MTX) in an MTX naive rheumatoid arthritis (RA) patient population.
During their review of unblinded data, the data safety monitoring board (DSMB) evaluated all the safety and efficacy data related to the first 100 patients in the study and found both a sufficient efficacy signal and acceptable safety profile to recommend continuation of each arm of the trial.
The primary efficacy endpoint of this study is to determine the percent of patients with ACR 20 response at the end of 12 weeks. An ACR 20 response is a standard efficacy measure that requires at least a 20% improvement in a number of different measures of disease activity.
As the improved safety and tolerability of CH-1504 is expected to be a significant advantage over MTX, the trial will also compare a cluster of gastrointestinal system related adverse events, such as nausea, vomiting and diarrhea, frequently seen with MTX use as well as closely monitor the results of standard liver function tests across dose groups.
In parallel to its development of CH-1504, Chelsea has also begun validating the potency of additional compounds in its library of metabolically inert antifolates. In March 2008, the company reported significant efficacy of CH-4051, the second compound from this portfolio, in the reduction of collagen-induced arthritis in an animal model.
In light of the positive DSMB assessment of its Phase II trial of CH-1504, Chelsea intends to continue the current Phase II trial and to initiate its planned Phase I study of CH-4051 later this quarter.
Simon Pedder, president and CEO of Chelsea Therapeutics, said: “We believe this trial will validate earlier clinical findings by demonstrating CH-1504 has at least comparable efficacy to methotrexate while maintaining superior safety and tolerability and are eagerly looking forward to the full results of this trial early 2009.”