Chelsea initiates enrollment in Phase II arthritis trial

CH-1504, a non-metabolized antifolate, is said to be engineered to provide the same potent efficacy as methotrexate (MTX) but without the side effects caused by the metabolic breakdown of MTX into by-products that are believed to play a significant role in the liver and kidney toxicities and tolerability related side effects associated with chronic therapy. In order to accurately compare the efficacy and tolerability profile and assess the suitability of CH-1504 as a first-line treatment alternative to MTX, the Phase II trial will be conducted in a MTX naive rheumatoid arthritis (RA) patient population.

The 4-arm, parallel group trial will enroll 200 patients and compare 0.25mg, 0.5mg and 1mg once daily oral doses of CH-1504 to a 20mg once weekly oral dose of MTX. 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.

Simon Pedder, president and CEO of Chelsea, said: “This proof-of-concept trial represents an opportunity for us to not only demonstrate CH-1504’s significant advantages over MTX but to also differentiate our compound from other disease modifying drugs, both approved and under development, whose safety and tolerability are limited by their combination use with MTX.”