Natural History Study of ENPP1 Deficiency and and the Early-onset Form of ABCC6 Deficiency

Conditions: Generalized Arterial Calcification of Infancy
Autosomal Recessive Hypophosphatemic Rickets
ATP-Binding Cassette Subfamily C Member 6 Deficiency
Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency

Brief Summary: The purpose of this prospective study is to characterize the natural history of ENPP1 Deficiency (including Generalized Arterial Calcification of Infancy Type 1 \[GACI\] and Autosomal Recessive Hypophosphatemic Rickets Type 2 \[ARHR2\]) and the early-onset form of ABCC6 Deficiency (Generalized Arterial Calcification of Infancy Type 2 \[GACI-2\]) longitudinally.

Detailed Description: Study INZ701-003 is a multicenter, prospective, longitudinal, observational study to evaluate disease presentation and progression in infant, pediatric, and adult subjects with ENPP1 Deficiency and the early-onset form of ABCC6 Deficiency. The study will gather information about the biochemical, physiological, anatomic, radiographic, and functional manifestations (including patient reported outcomes \[PROs\]) of each disease.

Subjects will receive the current standard of care available at the clinical site along with additional assessments administered by the study team.

Subject participation will consist of a Screening Period and an Observational Period.

During the Screening Period, eligibility will be determined. A subject will be enrolled into the study if they meet all eligibility criteria.

During the Observational Period, subjects will be assessed for changes in their disease in the following areas: measurements of physiological function (including laboratory testing, anatomical and radiographical assessment of calcification and bone mineralization, performance outcomes, patient, caregiver, and physician reported outcomes) and healthcare utilization.

The type and timing of assessments will be based on the age of the subject at the time of testing.

Recruitment & Eligibility

Inclusion Criteria

Individuals eligible to participate must meet all of the following inclusion criteria:

Must provide written or electronic consent (if able) and/or the consent of the legally authorized representative/caregiver and assent for subjects <18 years of age after the nature of the study has been explained and prior to any research-related procedures, following the policies of the clinical site
Clinical diagnosis of ENPP1 Deficiency or the early-onset form of ABCC6 Deficiency (GACI 2) based on clinical, radiological, or biochemical evidence and confirmed by prior or concurrent genetic testing. The early-onset form of ABCC6 Deficiency is defined as diagnosis of GACI 2 before 5 years of age for subjects of any age at enrollment.
Male or female, birth through adulthood
In the opinion of the Investigator, must be willing and able to complete all aspects of the study
Agree to provide access to relevant medical records.

Exclusion Criteria

Individuals who meet the following exclusion criterion will not be eligible to participate:

In the opinion of the Investigator and/or Sponsor, presence of any clinically significant disease (outside of those considered associated with the diagnosis of ENPP1 Deficiency or the early-onset form of ABCC6 Deficiency [GACI 2]) that precludes study participation or may confound interpretation of study results, such as an unrelated bone, mineral, or muscle disease or genetic connective tissue disease
Receiving any investigational new drug or device or plans to do so before completion of participation in the study. Participation in an interventional trial of an approved drug or device being used in an investigational manner is allowed, depending on review and approval of the Sponsor

Primary Outcome Measures

Name	Time	Method
Measurement of Plasma Inorganic Pyrophosphate (PPi) in Plasma	Up to 12 months	For each subject, blood plasma will be assayed for Plasma Inorganic Pyrophosphate (PPi), comparing the subjects baseline value over time
Determination of Arterial Calcification	Up to 12 months	For each subject, occurrence of arterial calcification will be examined
Determination of Organ Calcification	Up to 12 months	For each subject, occurrence of organ calcification will be examined
Determination of skeletal radiographs	Up to 12 months	For each subject, skeletal radiographs will be obtained to determine skeletal abnormalities and will be compared to baseline
Determination of range of motion	Up to 12 months	For each subject, aged 4 to \<18 years, range of motion will be assessed comparing to subjects baseline over time

Secondary Outcome Measures

Name	Time	Method

Locations (5): Boston Children's Hospital
🇺🇸
Boston, Massachusetts, United States
CHOP - Robers Center for Pediatric Research
🇺🇸
Philadelphia, Pennsylvania, United States
Cook Children's Hospital
🇺🇸
Fort Worth, Texas, United States
CHU Sainte-Justine
🇨🇦
Montréal, Quebec, Canada
Royal Manchester University Hospital
🇬🇧
Manchester, United Kingdom