Preclinical studies suggest a role for lysophosphatidic acid (LPA) in the pathogenesis of systemic sclerosis (SSc). We undertook this study to assess SAR100842, a potent selective oral antagonist of the LPA
An 8-week double-blind, randomized, placebo-controlled study followed by a 16-week open-label extension with SAR100842 was performed in patients with early dcSSc who had a baseline modified Rodnan skin thickness score (MRSS) of at least 15. The primary end point was safety during the double-blind phase of the trial. Exploratory end points included the identification of an LPA-induced gene signature in patients' skin.
Seventeen of 32 patients were randomly assigned to receive placebo and 15 to receive SAR100842; 30 patients participated in the open-label extension study. The most frequent adverse events reported for SAR100842 during the blinded phase were headache, diarrhea, nausea, and falling, and the safety profile was acceptable during the open-label extension. At week 8, the reduction in MRSS was numerically greater in the SAR100842 group than in the placebo group (mean ± SD change -3.57 ± 4.18 versus -2.76 ± 4.85; treatment effect -1.2 [95% confidence interval -4.37, 2.02]; P = 0.46). A greater reduction of LPA-related genes was observed in skin samples from the SAR100842 group at week 8, indicating LPA
SAR100842, a selective orally available LPA