Clotaire Laetitia, Rubera Isabelle, Duranton Christophe, Gal Jocelyn, Chamorey Emmanuel, Humeau Hélène, Yamani Samir, Chiaverini Christine, Willoteaux Serge, Padovani Bernard, Mourozeau Laurie, Mainguy Adam, Baillif Stéphanie, Martin Ludovic, Leftheriotis Georges
Université Côte d'Azur, CNRS, LP2M, Nice, France.
Research and Development Department, Laboratoires ProNutri, Carros, France.
Trials. 2025 Jan 29;26(1):30. doi: 10.1186/s13063-024-08666-w.
/aims. Pseudoxanthoma Elasticum (PXE, OMIM 264800) is an autosomal, recessive, metabolic disorder characterized by progressive ectopic calcification in the skin, the vasculature and Bruch's membrane. Variants in the ABCC6 gene are associated with low plasma pyrophosphate (PPi) concentration. There is currently no reference treatment for this chronic debilitating disease.
PROPHECI (PyROphosPHate supplementation to fight ECtopIc calcification in PseudoXanthoma Elasticum) is the first phase II, randomized, double-blind, placebo-controlled clinical trial (NTC 04868578) to evaluate the efficacy and safety of a daily oral PPi salt supplementation to attenuate and/or stabilize the progression of ectopic calcification in PXE patients. The primary endpoint is the change in arterial calcification volume quantified by non-contrast CT scan between baseline and 12 months of treatment. Secondary endpoints include the safety and efficacy of daily oral PPi administration on ocular and skin lesions and the evaluation of patients' quality of life.
The PROPHECI trial aims to provide safety and efficacy data on the use of daily oral PPi to reduce or stabilize ectopic calcification in PXE. It also aims to validate the best markers to include in the design of future trials for the treatment of PXE and other parent diseases.
Trial registration number: NCT04868578. References can be found on the ClinicalTrials.gov website: https://clinicaltrials.gov/study/NCT04868578?cond=Pseudoxanthoma%20Elasticum&intr=pyrophosphate&rank=2.
/目的。弹性假黄瘤（PXE，OMIM 264800）是一种常染色体隐性代谢紊乱疾病，其特征为皮肤、脉管系统和布鲁赫膜中出现进行性异位钙化。ABCC6基因的变异与血浆焦磷酸盐（PPi）浓度降低有关。目前尚无针对这种慢性致残性疾病的标准治疗方法。
PROPHECI（补充焦磷酸盐以对抗弹性假黄瘤中的异位钙化）是第一项II期随机双盲安慰剂对照临床试验（NTC 04868578），旨在评估每日口服PPi盐补充剂减轻和/或稳定PXE患者异位钙化进展的疗效和安全性。主要终点是通过非增强CT扫描量化的治疗12个月时与基线相比动脉钙化体积的变化。次要终点包括每日口服PPi对眼部和皮肤病变的安全性和疗效以及患者生活质量的评估。
PROPHECI试验旨在提供关于每日口服PPi用于减少或稳定PXE中异位钙化的安全性和疗效数据。它还旨在验证在未来治疗PXE和其他相关疾病的试验设计中应纳入的最佳标志物。
试验注册号：NCT04868578。可在ClinicalTrials.gov网站上找到参考文献：https://clinicaltrials.gov/study/NCT04868578?cond=Pseudoxanthoma%20Elasticum&intr=pyrophosphate&rank=2 。
