Pseudoxanthoma Elasticum (PXE) Natural History Biomarkers in PXE Individuals and Their Biological Non-PXE Siblings

Completed

• Conditions: Pseudoxanthoma Elasticum
• Interventions: Other: Non Interventional

• Registration Number: NCT05025722
• Lead Sponsor: Daiichi Sankyo

Brief Summary

This PXE biomarker study aims to characterize the levels of inorganic pyrophosphate (PPi), pyridoxal 5´-phosphate (PLP), and other biomarkers relevant to PXE and ectopic calcification in both PXE patients and their biological siblings who are PXE carriers or normal non-PXE individuals.

Detailed Description

This non-interventional PXE study is designed to assess differences in circulation levels of selective biomarkers related to PXE and tissue-nonspecific alkaline phosphatase (TNAP) inhibition, between PXE patients, PXE carriers, and non-PXE normal individuals.

Study Timeline

• Study First Submitted: 2021-07-30
• Study First Submitted QC: 2021-08-23
• Study First Posted: 2021-08-27
• Study Start: 2021-08-30
• Primary Completion: 2022-08-11
• Study Completion: 2022-08-11
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-02
• Last Update Posted: 2022-09-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

• Male or female participants aged 18 to 75 years

• Participants (approximately 1 carrier and 1 normal to match proband)

  • Confirmed PXE participants: index PXE/proband with established PXE and ABCC6 mutations identified
  • PXE carrier participants: biological sibling of the PXE index case and confirmed as PXE carrier
  • Non-PXE normal participants: biological sibling of PXE index case and confirmed as non-PXE normal

Exclusion Criteria

• Unconfirmed ABCC6 mutation status
• Use of bisphosphonate in the preceding 12 months and during the study
• Use of Vitamin B6 and/or Vitamin D supplement in the preceding 1 month and during the study (if the total Vitamin B6 supplementation is >5 mg/day)
• Recent initiation or dose change of Vitamin D and/or multivitamin supplement in the preceding 1 month and during the study
• Bone fracture within 3 months prior to Screening or active bone disease (excluding osteopenia or osteoporosis)
• History of hyperparathyroidism
• History of moderate to severe renal impairment
• History of hypophosphatasia
• Known history of uncorrected abnormality in calcium (Ca), phosphate, alkaline phosphatase (ALP) or parathyroid hormone
• Other significant condition (medical, psychiatric, social, or medication) that, in the judgment of the Investigator, would prevent full participation or would be inappropriate for the study

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Confirmed PXE participants	Non Interventional	Participants who have index PXE/proband with established PXE and ABCC6 mutations identified.
PXE carrier participants	Non Interventional	Participants who are biological siblings of the PXE index case and confirmed as PXE carrier.
Non-PXE normal participants	Non Interventional	Participants who are biological siblings of PXE index case and confirmed as non-PXE normal.

Primary Outcome Measures

Name	Time	Method
Mean Plasma Levels of Pyridoxal 5´-Phosphate (PLP)	Study visit (0 up to 2 hours)	PLP will be assessed by study group and by timepoint where applicable.
Mean Serum Enzyme Activity Levels of Bone-specific Alkaline Phosphatase (BSAP)	Study visit (0 hours)	BSAP will be measured using the standard clinical chemistry assays, by study group and by timepoint where applicable.
Mean Serum Enzyme Activity Levels of Alkaline Phosphatase (ALP)	Study visit (0 up to 2 hours)	ALP will be measured using the standard clinical chemistry assays, by study group and by timepoint where applicable.
Mean Plasma Levels of Inorganic Pyrophosphate (PPi)	Study visit (0 up to 2 hours)	PPi will be assessed by study group and by timepoint where applicable.

Secondary Outcome Measures

Name	Time	Method
Percent Change from Baseline in Serum Enzyme Activity of ALP, by Sex	Study visit (0 to 2 hours)	Blood samples will be assessed by sex group.
Percent Change from Baseline and Variability in Serum Enzyme Activity of ALP	Study visit (0 to 2 hours)	Variability of ALP will be assessed.
Percent Change from Baseline in Plasma Levels of PPi and PLP, by Sex	Study visit (0 to 2 hours)	Blood samples will be assessed by sex group.
Percent Change from Baseline and Variability in Plasma Levels of PPi and PLP	Study visit (0 to 2 hours)	Variability of PPi and PLP will be assessed.

Trial Locations

Locations (1)

Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States