Natural History Study of ENPP1 Deficiency and 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 (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.

Study Overview

• Status: Not yet recruiting
• Conditions: Generalized Arterial Calcification of Infancy; Autosomal Recessive Hypophosphatemic Rickets; Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency; ATP-Binding Cassette Subfamily C Member 6 Deficiency
• 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 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.

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

• Study Contact: Name: Inozyme Clinical Trial Information; Phone Number: +1 857 330 4340; Email: clinicaltrials@inozyme.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This study will enroll all eligible subjects, from birth through adulthood (infant, pediatric, and adult populations), with ENPP1 Deficiency and the early-onset form of ABCC6 Deficiency who consent to participate.

Description

Inclusion Criteria:

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

1. 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
2. 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.
3. Male or female, birth through adulthood
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 [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
2. 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

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 22 months
Determination of Arterial Calcification	For each subject, occurrence of arterial calcification will be examined	Up to 22 months
Determination of Organ Calcification	For each subject, occurrence of organ calcification will be examined	Up to 22 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 22 months
Determination of range of motion	For each subject, range of motion will be assessed using goniometer, comparing to subjects baseline over time	Up to 22 months
Determination of infant and toddler development	In infants and Toddlers up to 42 months of age, development will be assessed using Bayley scale of infant and toddler development	22 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2022
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

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): January 27, 2022
• Last Update Submitted That Met QC Criteria: January 12, 2022
• Last Verified: September 1, 2021

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
• 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; Rickets; Pseudoxanthoma Elasticum; Familial Hypophosphatemic Rickets; Rickets, Hypophosphatemic; Calcinosis
• Other Study ID Numbers: INZ701-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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