A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Oral Dose Study of Mocravimod: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics in Healthy Participants

Mocravimod (KRP203) is a selective sphingosine 1-phosphate (S1P) receptor modulator currently in development for patients with haematological malignancies undergoing allogenic haematopoietic cell transplantation (HCT). This first-in-human, randomised, double-blind, placebo-controlled, single ascending oral dose study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of mocravimod in 136 healthy adult participants (EudraCT No. 2006-006814-13). Participants received single doses ranging from 0.01 to 40 mg or placebo, with a cohort dedicated to studying food-effect at 3 mg. Mocravimod demonstrated slow absorption (mean Tmax 6-11 hrs), extensive distribution, and a long terminal half-life (91-132 hrs). Exposure increased dose-proportionally for doses [≥]2 mg. The most common adverse events were headache, dizziness, and fatigue, all graded as mild or moderate; no serious adverse events or deaths occurred. Mocravimod-phosphate induced robust, dose-dependent reductions in lymphocyte counts, with significant decreases at doses [≥]2 mg and recovery to baseline observed in all but the highest dose groups. Cardiac effects included transient bradycardia and benign second-degree atrioventricular (AV) block at higher doses, without clinically significant arrhythmias. Food intake had minimal impact on PK. No clinically meaningful changes in pulmonary function or laboratory safety signals were detected. These results indicate that single oral doses of mocravimod up to 40 mg are safe and well tolerated in healthy adults, with predictable PK and expected PD effects. The findings support further clinical development of mocravimod as a targeted immunomodulator in settings such as allogeneic HCT for haematological malignancies.