Lysophosphatidic Acid Receptor 1 Antagonist SAR100842 for Patients With Diffuse Cutaneous Systemic Sclerosis: A Double-Blind, Randomized, Eight-Week Placebo-Controlled Study Followed by a Sixteen-Week Open-Label Extension Study
Abstract
Objective: Preclinical studies advise a role for lysophosphatidic acidity (LPA) within the pathogenesis of systemic sclerosis (SSc). We began this research to evaluate SAR100842, a powerful selective dental antagonist from the LPA1 receptor, for safety, biomarkers, and clinical effectiveness in patients with diffuse cutaneous SSc (dcSSc).
Methods: An 8-week double-blind, randomized, placebo-controlled study adopted with a 16-week open-label extension with SAR100842 was performed in patients with early dcSSc who’d set up a baseline modified Rodnan skin thickness score (MRSS) with a minimum of 15. The main finish point was safety throughout the double-blind phase from the trial. Exploratory finish points incorporated the identification of the LPA-caused gene signature in patients’ skin.
Results: 17 of 32 patients were at random allotted to receive placebo and 15 to get SAR100842 30 volunteers participated on view-label extension study. The commonest adverse occasions reported for SAR100842 throughout the blinded phase were headache, diarrhea, nausea, and falling, and also the safety profile was acceptable throughout the open-label extension. At week 8, the decrease in MRSS was numerically greater within the SAR100842 group compared to 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 = .46). A larger decrease in LPA-related genes was noticed in skin samples in the SAR100842 group at week 8, indicating LPA1 target engagement.
Conclusion: SAR100842, a selective orally available LPA1 receptor antagonist, was well tolerated in patients with dcSSc. The MRSS improved throughout the study even though the difference wasn’t significant, and extra gene signature analysis recommended target engagement. These results have to be confirmed inside a bigger controlled BMS-986020 trial.