Abstract

ABSTRACT

Background

Calcific uraemic arteriolopathy (CUA; calciphylaxis) is a rare disease seen predominantly in patients receiving dialysis. Calciphylaxis is characterized by poorly healing or non-healing 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 (QoL). Those results informed the design of the CALCIPHYX trial, an ongoing, randomized, 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 randomized 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 Bates-Jensen Wound Assessment Tool-CUA (a quantitative wound assessment tool for evaluating calciphylaxis lesions) or change in pain visual analogue scale score. Additional endpoints will address wound-related QoL, qualitative changes in wounds, wound size, analgesic use and safety.

Conclusions

This randomized, 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.

Details

Title
The CALCIPHYX study: a randomized, double-blind, placebo-controlled, Phase 3 clinical trial of SNF472 for the treatment of calciphylaxis
Author
Sinha, Smeeta 1 ; Gould, Lisa J 2 ; Nigwekar, Sagar U 3 ; Serena, Thomas E 4 ; Brandenburg, Vincent 5 ; Moe, Sharon M 6 ; Aronoff, George 7 ; Chatoth, Dinesh K 8 ; Hymes, Jeffrey L 9 ; Miller, Stephan 10 ; Padgett, Claire 10 ; Carroll, Kevin J 11 ; Perelló, Joan 12 ; Gold, Alex 10 ; Chertow, Glenn M 13 

 Renal Medicine, Salford Royal NHS Foundation Trust , Salford, UK 
 South Shore Health Department of Surgery, South Shore Health Center for Wound Healing , Weymouth, MA, USA 
 Department of Medicine, Massachusetts General Hospital , Boston, MA, USA 
 SerenaGroup Research Foundation , Cambridge, MA, USA 
 Cardiology and Nephrology, Rhein-Maas Hospital , Würselen, Germany 
 Department of Medicine, Indiana University School of Medicine , Indianapolis, IN, USA 
 Clinical Affairs, DaVita Kidney Care , Naples, FL, USA 
 Fresenius Kidney Care , Waltham, MA, USA 
 Global Head of Clinical Affairs, Fresenius Kidney Care , Waltham, MA, USA 
10  Department of Clinical Development, Sanifit Therapeutics , San Diego, CA, USA 
11  KJC Statistics Ltd , Cheshire, UK 
12  University Institute of Health Sciences Research (IUNICS- IDISBA), University of the Balearic Islands , Palma, Spain 
13  Department of Medicine, Stanford University School of Medicine , Stanford, CA, USA 
Pages
136-144
Publication year
2022
Publication date
Jan 2022
Publisher
Oxford University Press
ISSN
20488505
e-ISSN
20488513
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3169586720
Copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. This work is published under https://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.