Clinical trial NCT05025722: Pseudoxanthoma Elasticum (PXE) Natural History Biomarkers in PXE Individuals and Their Biological Non-PXE Siblings
Official title: An Evaluation of Pseudoxanthoma Elasticum (PXE) Natural History Biomarkers in PXE Individuals and Their Biological Non-PXE Siblings
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pseudoxanthoma Elasticum
Keywords: Pseudoxanthoma Elasticum
Bone turnover biomarkers
Tissue mineralization biomarkers
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: PXE International
name: Thomas Jefferson University
First posted: 2021-08-27
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: PXE probands with identified ABCC6 mutations and non-PXE biological siblings will be invited for study participation.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Plasma Levels of Inorganic Pyrophosphate (PPi)
timeFrame: Study visit (0 up to 2 hours)
measure: Mean Plasma Levels of Pyridoxal 5´-Phosphate (PLP)
timeFrame: Study visit (0 up to 2 hours)
measure: Mean Serum Enzyme Activity Levels of Alkaline Phosphatase (ALP)
timeFrame: Study visit (0 up to 2 hours)
measure: Mean Serum Enzyme Activity Levels of Bone-specific Alkaline Phosphatase (BSAP)
timeFrame: Study visit (0 hours)
Secondary outcomes:
measure: Percent Change from Baseline in Plasma Levels of PPi and PLP, by Sex
timeFrame: Study visit (0 to 2 hours)
measure: Percent Change from Baseline in Serum Enzyme Activity of ALP, by Sex
timeFrame: Study visit (0 to 2 hours)
measure: Percent Change from Baseline and Variability in Plasma Levels of PPi and PLP
timeFrame: Study visit (0 to 2 hours)
measure: Percent Change from Baseline and Variability in Serum Enzyme Activity of ALP
timeFrame: Study visit (0 to 2 hours)
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: