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

NCT06302439 | Recruiting

• 1 other identifier: INZ701-007
• Study Type: observational
• Target: 1,000
• Locations: 9 countries
• Sites: 14

Brief Summary

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.

Conditions

Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 Deficiency; ATP-Binding Cassette Subfamily C Member 6 Deficiency

Keywords

Ectonucleotide pyrophosphatase; ENPP1; Generalized Arterial Calcification of Infancy; GACI; Autosomal Recessive Hypophosphatemic Rickets Type 2; ARHR2; Observational; Registry; ATP-Binding Cassette Subfamily C Member 6 Deficiency; ABCC6; PROPEL; Phosphodiesterase 1

Outcome Measures

Primary Outcomes (4)

• Characterization of the natural history of ENPP1 Deficiency and the infantile-onset form of ABCC6 Deficiency longitudinally

  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

  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

  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

  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

Interventions

No Intervention for this observational study OTHER

No Intervention for this observational study

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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)
• Agree to provide access to relevant medical records
• One of the following genetic or clinical criteria
• 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
• 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
• 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

You may not qualify if:

• Participant or their legally designated representative does not have the cognitive capacity to provide informed consent
• 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

Sponsors & Collaborators

• GACI Global: collaborator
• Inozyme Pharma: lead

Study Sites (14)

Ann and Robert H. Lurie Children's Hospital

Chicago, Illinois, 60611, United States

RECRUITING

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

CLINILABS Drug Development Corp

Eatontown, New Jersey, 07724, United States

RECRUITING

The Children's Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

CHU Sainte-Justine Research Centre

Montreal, Quebec, H3T1C5, Canada

RECRUITING

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20251, Germany

RECRUITING

IRCCS San Raffaele Hospital - Main

Milan, 20132, Italy

RECRUITING

The University of Tokyo Hospital

Tokyo, 113-8655, Japan

RECRUITING

Royal Hospital Muscat

Muscat, Oman

RECRUITING

EU Hub - VCTC

Barcelona, 08029, Spain

RECRUITING

Hospital Sant Joan de Deu

Barcelona, 08950, Spain

RECRUITING

Umraniye Training and Research Hospital

Istanbul, 34764, Turkey (Türkiye)

RECRUITING

VCTC

Derby, DE11 7AQ, United Kingdom

RECRUITING

MeSH Terms

Conditions

Arterial calcification of infancy

Central Study Contacts

Jelena Garafalo, Ph.D

CONTACT

(857) 330-4340; jelena.garafalo@inozyme.com

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Target Duration: 10 Years
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2024
• First Posted: March 8, 2024
• Study Start: July 25, 2024
• Primary Completion (Estimated): May 1, 2034
• Study Completion (Estimated): May 1, 2034
• Last Updated: December 22, 2025

Record last verified: 2025-12

Locations

JP (1); CA (1); IT (1); US (5); TU (1); GB (1); DE (1); OM (1); ES (2)