Experimental Drug for RA Enrolling Subjects in Phase II Trial

September 27, 2010

Chelsea Therapeutics initiated enrollment for a 12-week trial involving CH-4051 to treat rheumatoid arthritis.

Experimental drug CH-4051, designed to treat rheumatoid arthritis (RA), will be used in a double-blind phase II trial study, according to the drug manufacturer Chelsea Therapeutics International, Ltd.

Chelsea Therapeutics initiated enrollment for the multinational, 12-week trial, which is designed to compare the efficacy and tolerability of CH-4051 against methotrexate (MTX) in 250 patients with RA who are experiencing an adequate response to MTX treatment.

The experimental drug is an orally available, non-metabolized antifolate with potent anti-inflammatory properties. The drug is engineered to provide enhanced clinical benefits to patients without the associated liver toxicities or other side effects that often limit the use of chronic MTX therapy.

“There is a significant unmet medical need for safe and effective treatment options for RA patients who fail to achieve a good clinical outcome on methotrexate,” said Dr. Simon Pedder, president and CEO of Chelsea Therapeutics, in a press release. “Based on the available data, we believe that oral treatment with CH-4051 has the potential to significantly reduce joint pain and swelling as well as have disease-modifying effects in patients who have not responded well or have difficulty tolerating methotrexate and who might otherwise be moved onto more costly, biological injectable monoclonal therapies. We look forward to the outcome of this head-to-head comparison against methotrexate in this treatment refractory population.”

Patients in the five-arm phase II trial will be randomized to receive 0.3 mg, 1.0 mg, or 3.0 mg of CH-4051 daily in combination with a folate supplement or 20 mg MTX weekly with a folate supplement for 12 weeks following a two-week MTX-washout.

The hybrid American College of Rheumatology, or ACR, score (hACR), will be used to analyze the primary efficacy of the trial. The hACR allows for a more comprehensive assessment of treatment benefit across all seven symptomatic and functional components of the standard ACR 20/50/70 evaluations.

The trial is being conducted with a staggered start. The first patients will be randomized to receive either 0.3 mg or 1.0 mg of CH-4051 daily or 20 mg MTX weekly in combination with a folate supplement. After 10 patients in both the 0.3 mg and 1.0 mg CH-4051 cohorts complete treatment and assuming no safety concerns are observed, the study will begin randomizing patients into all five study cohorts.

Chelsea intends to conduct an un-blinded interim efficacy analysis after approximately 50% of patients in the two lower CH-4051 dose groups complete treatment. The company expects to report results from this analysis in the third quarter of 2011. Full study results, inclusive of all dose groups, are expected in mid-2012.