Registry to evaluate ENPP1 and ABCC6 deficiencies

A Prospective Observational Patient Registry to Evaluate Disease Progression in Patients With ENPP1 Deficiency and Infantile-Onset ABCC6 Deficiency (GACI Type 2)

This study is collecting information from kids with ENPP1 and ABCC6 deficiencies to better understand how these rare genetic conditions affect their health over time.

Quick facts

• Study type: Observational
• Enrollment: 1000 (estimated)
• Sex: All
• Sponsor: Inozyme Pharma (Industry-sponsored)
• Locations: 14 sites (Chicago, Illinois and 13 other locations)
• Trial ID: NCT06302439 on ClinicalTrials.gov

What this trial studies

This prospective observational registry aims to characterize the natural history of ENPP1 and ABCC6 deficiencies by collecting data on genetic, biochemical, physiological, anatomic, radiographic, and functional manifestations during routine care visits. It will include patients with confirmed genetic diagnoses of ENPP1 deficiency and symptomatic patients with ABCC6 deficiency under 18 years of age. The registry seeks to develop a comprehensive understanding of the burden of illness and the progressive nature of these rare genetic disorders.

Who should consider this trial

Good fit: Ideal candidates include individuals with confirmed genetic diagnoses of ENPP1 deficiency or symptomatic ABCC6 deficiency who are under 18 years of age.

Not a fit: Patients who do not have a genetic diagnosis of ENPP1 or ABCC6 deficiencies or those participating in an interventional clinical study for INZ-701 will not benefit from this registry.

Why it matters

Potential benefit: If successful, this registry could provide valuable insights into the management and treatment of patients with ENPP1 and ABCC6 deficiencies.

How similar studies have performed: While this registry approach is observational, similar studies have successfully characterized rare genetic disorders, providing a foundation for understanding these conditions.

Eligibility criteria

Inclusion Criteria:

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

1. Must provide written or electronic consent after the nature of the registry has been explained, and prior to any research-related procedures, per International Council for Harmonisation (ICH) Good Clinical Practice (GCP)
2. Agree to provide access to relevant medical records
3. One of the following genetic or clinical criteria

   1. A confirmed prenatal or postnatal molecular genetic diagnosis of ENPP1 Deficiency with biallelic mutations (ie, homozygous or compound heterozygous) performed by a College of American Pathologists/Clinical Laboratory Improvement Amendments (CAP/CLIA) certified laboratory or regional equivalent

      OR
   2. Monoallelic ENPP1 mutation confirmed by a certified CAP/CLIA laboratory or regional equivalent and any of the following clinical symptoms:

   i. ≥ 1 traumatic vertebral fracture

ii. ≥ 2 fractures as an adult (eg, long-bones, digits, vertebrae)

iii. Low bone mineral density (dual-energy X-ray absorptiometry \[DXA\] Z-score \<1.5) and \<55 years of age

iv. Bone or joint pain interfering with movement or daily activities

v. History of myocardial infarction (MI), unstable angina, transient ischemic attack (TIA) or low cardiac output before the age of 40 yrs.

vi. History of rickets or bone deformity

vii. Diagnosis of ossification of the posterior longitudinal ligament (OPLL)

viii. Other clinical symptoms, with approval by Inozyme

OR

c. A confirmed prenatal or postnatal molecular genetic diagnosis of ABCC6 Deficiency with biallelic mutations confirmed by a certified CAP/CLIA laboratory or regional equivalent, and \<18 years of age

Exclusion Criteria:

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

1. Participant or their legally designated representative does not have the cognitive capacity to provide informed consent
2. Patients who are currently participating in an INZ-701 interventional clinical study, with the exception of expanded access programs and long-term safety follow-up studies

   1. Participants in interventional studies may be approached for inclusion in the registry once their involvement in the treatment period of the clinical study has been completed

Where this trial is running

Chicago, Illinois and 13 other locations

• Ann and Robert H. Lurie Children's Hospital — Chicago, Illinois, United States (Recruiting)
• Boston Children's Hospital — Boston, Massachusetts, United States (Recruiting)
• Mayo Clinic — Rochester, Minnesota, United States (Recruiting)
• CLINILABS Drug Development Corp — Eatontown, New Jersey, United States (Recruiting)
• The Children's Hospital of Philadelphia (CHOP) — Philadelphia, Pennsylvania, United States (Recruiting)
• CHU Sainte-Justine Research Centre — Montreal, Quebec, Canada (Recruiting)
• Universitätsklinikum Hamburg-Eppendorf — Hamburg, Germany (Recruiting)
• IRCCS San Raffaele Hospital - Main — Milan, Italy (Recruiting)
• The University of Tokyo Hospital — Tokyo, Japan (Recruiting)
• Royal Hospital Muscat — Muscat, Oman (Recruiting)
• EU Hub - VCTC — Barcelona, Spain (Recruiting)
• Hospital Sant Joan de Deu — Barcelona, Spain (Recruiting)
• Umraniye Training and Research Hospital — Istanbul, Turkey (Türkiye) (Recruiting)
• Vctc — Derby, United Kingdom (Recruiting)

Study contacts

• Study coordinator: Jelena Garafalo, Ph.D

Conditions Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 Deficiency; ATP-Binding Cassette Subfamily C Member 6 Deficiency; Ectonucleotide pyrophosphatase; ENPP1; Generalized Arterial Calcification of Infancy; GACI; Autosomal Recessive Hypophosphatemic Rickets Type 2; ARHR2