Background
Calcific uremic arteriolopathy (calciphylaxis) is a rare disease seen predominantly in patients receiving dialysis. Calciphylaxis is characterised by poorly healing or nonhealing wounds, and is associated with mortality, substantial morbidity related to infection, and typically severe pain. In an open-label Phase 2 clinical trial, SNF472, a selective inhibitor of vascular calcification, was well-tolerated and associated with improvement in wound healing, reduction of wound-related pain, and improvement in wound-related quality of life. Those results informed the design of the CALCIPHYX trial, an ongoing, randomised, placebo-controlled, Phase 3 trial of SNF472 for treatment of calciphylaxis.
Methods
In CALCIPHYX, 66 patients receiving haemodialysis who have an ulcerated calciphylaxis lesion will be randomised 1:1 to double-blind SNF472 (7 mg/kg intravenously) or placebo three times weekly for 12 weeks (Part 1), then receive open-label SNF472 for 12 weeks (Part 2). All patients will receive stable background care, which may include pain medications and sodium thiosulphate, in accordance with the clinical practices of each site. A statistically significant difference between the SNF472 and placebo groups for improvement of either primary endpoint at Week 12 will demonstrate efficacy of SNF472: change in BWAT-CUA (a quantitative wound assessment tool for evaluating calciphylaxis lesions) or change in pain visual analogue scale score. Additional endpoints will address wound-related quality of life, qualitative changes in wounds, wound size, analgesic use, and safety.
Conclusions
This randomised, placebo-controlled Phase 3 clinical trial will examine the efficacy and safety of SNF472 in patients who have ulcerated calciphylaxis lesions. Patient recruitment is ongoing.