Massachusetts General Hospital received a USD 2.46 million grant from the US FDA to support a four-year project involving a Phase II randomized, double-blind, placebo-controlled trial of EPN-701, a highly purified form of menaquinone-7 (vitamin K2), in dialysis-dependent patients with calciphylaxis, a rare, potentially life-threatening vascular calcification disorder with no approved treatment.
Calciphylaxis predominantly affects dialysis-dependent patients, producing painful ischemic skin lesions through microvessel occlusion in the dermis and subcutaneous tissue, and is associated with high morbidity and mortality. EPN-701 is hypothesized to act by enhancing carboxylation and activation of matrix Gla protein (MGP), which the grant application describes as a potent inhibitor of vascular calcification.
The double-blind, randomized, placebo-controlled trial will enroll 60 patients in a 1:1 allocation, with participants in the treatment arm receiving EPN-701 at 10 mg/day orally for 24 weeks, and it uses alternate primary endpoints of change in pain intensity and change in total calciphylaxis lesion surface area from baseline to Week 24, while exploratory measures include lesion healing, hospitalization, infection, mortality, and whether novel proteomic biomarkers of calciphylaxis improve with treatment.
The trial is led by Rajeev Malhotra, Sagar Nigwekar, and Karin Rosen at MGH, with the team drawing on academic and industry expertise as well as patient advisor input. The project period runs through August 2030, and the findings are intended to inform endpoint selection for a future Phase III trial.