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

A Prospective Observational Study to Evaluate Disease Presentation and Progression in Subjects With ENPP1 Deficiency and the Early-Onset Form of ABCC6 Deficiency

The purpose of this prospective study is to characterize the natural history of ENPP1 Deficiency and the early-onset form of ABCC6 Deficiency longitudinally. The study will prospectively gather information about the biochemical, physiological, anatomic, radiographic, and functional manifestations (including patient reported outcomes) of each disease.

Study Overview

• Status: Completed
• Conditions: Generalized Arterial Calcification of Infancy; Autosomal Recessive Hypophosphatemic Rickets; Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency; Adenosine Triphosphate Binding Cassette Transporter Protein Subfamily C Member 6
• Intervention / Treatment: Other: No Intervention for this observational study

Detailed Description

Study INZ701-003 is a multicenter, prospective, longitudinal, observational study to evaluate disease presentation, progression, and burden of illness in pediatric subjects aged 2 to <18 years with ENPP1 Deficiency and the early-onset form of ABCC6 Deficiency. Subjects will receive care available at the clinical site along with additional assessments administered by the study team.

To participate in this study, subjects will give informed assent and parents/guardians will provide informed consent.

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

Assessments will be performed at each visit as indicated in the Schedule of Events.

During the Screening Period, assessments will be performed to determine eligibility.

Screening and Baseline assessments may be conducted on the same day if the Investigator determines that the patient can successfully complete all study procedures in one day due to their age. If not, sites may schedule additional visits, as needed. A subject will be enrolled into the study if they meet all eligibility criteria.

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

• Study Type: Observational
• Enrollment (Actual): 12

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • CHU Sainte-Justine
• United Kingdom
  • Manchester
    • Manchester, Manchester, United Kingdom, M13 9WL
      • Royal Manchester University Hospital
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19146
      • CHOP - Roberts Center for Pediatric Research
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years and older (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study will enroll all eligible subjects aged 2 to <18 years with ENPP1 Deficiency and the early-onset form of ABCC6 Deficiency who consent to participate, with the goal of recruiting up to 20 subjects.

Description

Inclusion Criteria:

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

1. Must provide written consent of the legally authorized representative/caregiver and assent for subjects after the nature of the study has been explained and prior to any research-related procedures, following the policies of the clinical site
2. Genetic confirmation of ENPP1 Deficiency or ABCC6 Deficiency
3. Male or female, aged 2 to <18 years
4. In the opinion of the Investigator, must be willing and able to complete all aspects of the study
5. Agree to provide access to relevant medical records

Exclusion Criteria:

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

1. 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) 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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Inozyme Pharma
• Investigators: Study Director: Deborah Wenkert, MD, Inozyme Pharma, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2022
• Primary Completion (Actual): May 31, 2024
• Study Completion (Actual): June 26, 2024

Study Registration Dates

• First Submitted: September 10, 2021
• First Submitted That Met QC Criteria: September 10, 2021
• First Posted (Actual): September 20, 2021

Study Record Updates

• Last Update Posted (Actual): July 6, 2026
• Last Update Submitted That Met QC Criteria: July 1, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Generalized Arterial Calcification of Infancy; ABCC6; ectonucleotide pyrophosphatase/phosphodiesterase 1 deficiency; ENPP1; ATP-binding cassette subfamily C member 6 deficiency; GACI; Autosomal Recessive Hypophosphatemic Rickets Type 2; ARHR2; hypopyrophosphatemia; Early Onset Form
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Skin Diseases; Kidney Diseases; Urologic Diseases; Congenital Abnormalities; Hematologic Diseases; Nutrition Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Musculoskeletal Diseases; Connective Tissue Diseases; Hemostatic Disorders; Skin Diseases, Genetic; Avitaminosis; Deficiency Diseases; Malnutrition; Bone Diseases; Metabolism, Inborn Errors; Bone Diseases, Metabolic; Skin Abnormalities; Renal Tubular Transport, Inborn Errors; Calcium Metabolism Disorders; Metal Metabolism, Inborn Errors; Phosphorus Metabolism Disorders; Vitamin D Deficiency; Hypophosphatemia, Familial; Hypophosphatemia; Arterial calcification of infancy; Hypophosphatemic Rickets, Autosomal Recessive, 1
• Other Study ID Numbers: INZ701-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No