PROPEL - A Prospective Observational Patient Registry to Evaluate ENPP1 and ABCC6 Deficiency

December 15, 2025 updated by: Inozyme Pharma

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

The purpose of this prospective registry is to characterize the natural history of ectonucleotide pyrophosphatase/phosphodiesterase1(ENPP1) Deficiency and the infantile-onset form of adenosine triphosphate (ATP) binding cassette transporter protein subfamily C member 6 (ABCC6) Deficiency longitudinally. The registry will prospectively gather information about the genetic, biochemical, physiological, anatomic, radiographic, and functional manifestations (including patient reported outcomes [PROs]) of each disease during routine, standard-of-care visits, with the aim of developing a comprehensive understanding of the burden of illness and progressive nature of the disease.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

ENPP1 Deficiency is a rare, genetic disorder caused by inactivating mutations in the ENPP1 gene that encodes the ENPP1 enzyme. Infantile-onset ENPP1 Deficiency has a high mortality (approximately 50%) in the first 0 to 6 months of life, a result of downstream cardiopulmonary complications. Pediatric patients with ENPP1 Deficiency typically experience rickets, a condition also known as autosomal-recessive hypophosphatemic rickets type 2 (ARHR2), while adults experience osteomalacia (softened bones), and they can exhibit a range of signs and symptoms that include hearing loss, arterial calcification, and cardiac and/or neurological involvement.

Like ENPP1 Deficiency, infantile-onset ABCC6 Deficiency is a rare, genetic disorder caused by mutations in the ABCC6 gene. Infantile-onset of ABCC6 Deficiency resembles the acute infantile form of ENPP1 Deficiency. Pediatric patients with biallelic or monoallelic ABCC6 mutations can present with cerebrovascular disease.

This is an international, multicenter, prospective, non-interventional, observational registry of patients with biallelic variants in ENPP1, symptomatic patients with monoallelic ENPP1 variants and the infantile-onset form of ABCC6 Deficiency (<18 years of age). The registry will include patients with ENPP1 Deficiency or infantile-onset of ABCC6 Deficiency independent of treatment regimen. Note: patients participating in an INZ-701 interventional clinical study are not eligible.

Registry participation will consist of a Screening Period and an Observational Period. During the Screening Period, both retrospective data (past medical history) and data available at the time of consent (baseline visit) will be collected. Data collected will include standard of care assessments, which may consist of any or all of the following: laboratory testing, radiographical assessment of calcification and vascular stenosis, bone mineralization, with addition of performance outcomes, patient-, caregiver-, and physician-reported outcomes, and healthcare utilization. During the Observational Period, participants will be assessed during their routine visits for changes in their disease and PROs and data will be added periodically to the database. There will be an opportunity for an optional blood draw to assess levels of inorganic pyrophosphate (PPi) at each routine visit.

Study Type

Observational

Enrollment (Estimated)

1000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H3T1C5
  • Germany
      • Hamburg, Germany, 20251
        • Recruiting
        • Universitatsklinikum Hamburg-Eppendorf
        • Contact:
        • Principal Investigator:
          • Ralf Oheim, MD
  • Italy
      • Milan, Italy, 20132
        • Recruiting
        • IRCCS San Raffaele Hospital - Main
        • Contact:
        • Principal Investigator:
          • Giuseppe Vezzoli, MD
  • Japan
      • Tokyo, Japan, 113-8655
        • Recruiting
        • The University of Tokyo Hospital
        • Principal Investigator:
          • Nobuaki Ito, MD
  • Oman
      • Muscat, Oman
        • Recruiting
        • Royal Hospital Muscat
        • Principal Investigator:
          • Maryam AL Badi, MD
  • Spain
      • Barcelona, Spain, 08950
        • Recruiting
        • Hospital Sant Joan de Déu
        • Contact:
          • Paula Sanchez Ruiz
          • Phone Number: +34936009731
        • Principal Investigator:
          • Pedro Arango Sancho, MD
      • Barcelona, Spain, 08029
        • Recruiting
        • EU Hub - VCTC
        • Principal Investigator:
          • Victoria Aniyar Lopez-Abadia, MD
        • Contact:
  • Turkey (Türkiye)
      • Istanbul, Turkey (Türkiye), 34764
        • Recruiting
        • Umraniye Training and Research Hospital
        • Contact:
        • Principal Investigator:
          • Fatma Dursun, MD
  • United Kingdom
      • Derby, United Kingdom, DE11 7AQ
        • Recruiting
        • VCTC
        • Contact:
        • Principal Investigator:
          • Victoria Aniyar Lopez-Abadia, MD
  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Ann and Robert H. Lurie Children's Hospital
        • Contact:
        • Principal Investigator:
          • Jennifer Miller, MD
    • Massachusetts
    • Minnesota
      • Rochester, Minnesota, United States, 55905
    • New Jersey
      • Eatontown, New Jersey, United States, 07724
        • Recruiting
        • CLINILABS Drug Development Corp
        • Contact:
        • Principal Investigator:
          • Magdy Shenouda, MD
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • The Children's Hospital of Philadelphia (CHOP)
        • Contact:
        • Principal Investigator:
          • David Weber, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Evidence of biallelic ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) variants in ENPP1 Deficiency

or

Evidence of monoallelic ENPP1 variants and disease-related symptoms

or

Infantile onset with biallelic adenosine triphosphate (ATP) binding cassette transporter protein subfamily C member 6 (ABCC6) variants in participants aged <18 years.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Characterization of the natural history of ENPP1 Deficiency and the infantile-onset form of ABCC6 Deficiency longitudinally
Time Frame: Annually up to 10 years
Assessments will be collected during each subject's routine visit. The assessments will be done per local standard of care.
Annually up to 10 years
Assessment of Patient Functional changes through a validated Patient Reported Outcomes (PROs) tool
Time Frame: Annually up to 10 years

For each subject, patient function will be assessed using the appropriate Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaires. These may include: PROMIS Cognitive Function, PROMIS Fatigue, PROMIS Pain Intensity, PROMIS Pain Interference and PROMIS Physical Function. Each questionnaire is scored on a 5-point Likert scale ranging from 1 (never) to 5 (always). High scores indicate more of the domain being measured (eg, more fatigue, more physical function). Raw scores are converted to T-Scores based on a mean of 50 and a standard deviation of 10, allowing comparison of the sample to the general population.

Parent Proxy questionnaires will be used for children aged 5 to <18 years
Annually up to 10 years
Assessment of Health-Related Quality-of-Life (HRQoL) changes through validated Patient Reported Outcomes (PROs) tools
Time Frame: Annually up to 10 years

For each subject, HRQoL will be assessed using the following scales:

age 5 to <18 years: Pediatric QoL scales (Short Form [SF]-10, Caregiver Global Impression of Status/Severity [CaGI-S]);

age ≥18 years: Adult QoL scales (Short Form [SF]-36, Patient Global Impression of Status/Severity [PGI-S])

The SF-10 is a 10-item caregiver-completed questionnaire for assessment of physical and psychosocial HRQoL in children. Each question has 5 options ranging from "Excellent" to "Poor". Higher scores are associated with better HRQoL.

The SF-36 measures a broad spectrum of physical and mental health domains, including physical functioning, role limitations due to physical and emotional problems, bodily pain, general health perceptions, vitality, social functioning, and emotional well-being. The SF-36 generates scores ranging from 0-100 with higher scores associated with better HRQoL.

The CaGI-S and PGI-S will be scored across a 7-point scale with lower scores associated with better HRQoL.
Annually up to 10 years
Measurement of inorganic phosphate (PPi) levels in patients' venous blood
Time Frame: Annually up to 10 years
For each subject, QoL will be assessed using the following scales: global clinical impression of severity (GCI-S) and, short form 10 health survey for children and short form 36 health survey for adults short form 10 health survey for children and short form 36 health survey for adults
Annually up to 10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Inozyme Pharma

Collaborators

GACI Global

Investigators

  • Study Director: Petra Duda, MD, Inozyme Pharma, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 25, 2024

Primary Completion (Estimated)

May 1, 2034

Study Completion (Estimated)

May 1, 2034

Study Registration Dates

First Submitted

February 16, 2024

First Submitted That Met QC Criteria

March 4, 2024

First Posted (Actual)

March 8, 2024

Study Record Updates

Last Update Posted (Actual)

December 22, 2025

Last Update Submitted That Met QC Criteria

December 15, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INZ701-007

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on ATP-Binding Cassette Subfamily C Member 6 Deficiency

Clinical Trials on No Intervention for this observational study

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Uzbekistan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe