TOUCHSTONE, the phase 2 trial of RPC1063 in ulcerative colitis ( UC ), met its primary endpoint and all secondary endpoints with statistical significance in patients on the 1 mg dose of RPC1063 in the 8-week induction period. The overall safety and tolerability profile of RPC1063 was consistent with the results of the recent phase 2 trial in relapsing multiple sclerosis, and continues to support the potential for orally administered RPC1063 to significantly improve the treatment paradigm for patients with ulcerative colitis.
The maintenance period of the TOUCHSTONE trial is currently ongoing.
This randomized, double-blind, placebo-controlled trial assessed the efficacy, safety and tolerability of two orally administered doses ( 0.5 mg and 1 mg ) of RPC1063 in patients with ulcerative colitis across 57 sites in 13 countries.
The trial enrolled 199 patients, approximately 10% higher than planned, due to a strong interest among investigators and patients to participate in the study.
The primary endpoint of the trial, the proportion of patients in clinical remission at week 8 as defined by the industry standard Mayo scoring criteria, was achieved by 16.4% of patients on the 1 mg dose of RPC1063, as compared to 6.2% of patients on placebo, which was statistically significant ( p less than 0.05 ).
In the low dose group of 0.5 mg, 13.8% of patients achieved clinical remission, which was not statistically significantly different from the placebo group.
All secondary endpoints at week 8, including clinical response, change in the Mayo score and mucosal improvement on endoscopy were also positive and statistically significant for the 1 mg dose.
Notably, 58.2% of patients on the 1 mg dose of RPC1063 achieved clinical response, as compared to 36.9% of patients on placebo ( p less than 0.05 ).
Trends were observed for all secondary efficacy endpoints for the 0.5 mg dose group that appear to demonstrate evidence of a dose response.
RPC1063 was generally well tolerated, and the incidence of adverse events across the active treatment groups and placebo appeared to be similar.
Most adverse events were either mild or moderate in nature, and there appeared to be no concerning signals in the adverse events of special interest, including the cardiac and hepatic safety profiles.
With regard to the cardiovascular profile, first dose mean changes in heart rate in patients receiving RPC1063 were generally modest during the first six hours after administration, which is consistent with the findings of the earlier phase 2 trial in relapsing multiple sclerosis and thorough QT study.
Rates of liver transaminase elevations observed in patients receiving RPC1063 were low and consistent with the earlier phase 2 trial in relapsing multiple sclerosis.
RPC1063 is a sphingosine 1-phosphate 1 receptor ( S1P1R ) small molecule modulator candidate for immune indications, including relapsing multiple sclerosis ( RMS ) and inflammatory bowel disease ( IBD ). ( Xagena )
Source: Receptos, 2014