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PROPEL - Un registre observationnel prospectif de patients pour évaluer les déficits ENPP1 et ABCC6

28 septembre 2026 mis à jour par: Inozyme Pharma

Un registre observationnel prospectif de patients pour évaluer la progression de la maladie chez les patients présentant un déficit en ENPP1 et un déficit en ABCC6 infantile (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.

Aperçu de l'étude

Statut

Résilié

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Observationnel

Inscription (Réel)

54

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Allemagne
      • Hamburg, Allemagne, 20251
        • Universitätsklinikum Hamburg-Eppendorf
  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H3T1C5
        • CHU Sainte-Justine Research Centre
  • Espagne
      • Barcelona, Espagne, 08029
        • EU Hub - VCTC
      • Barcelona, Espagne, 08950
        • Hospital Sant Joan de Deu
  • Italie
      • Milan, Italie, 20132
        • IRCCS San Raffaele Hospital - Main
  • Japon
      • Tokyo, Japon, 113-8655
        • The University of Tokyo Hospital
  • Oman
      • Muscat, Oman
        • Royal Hospital Muscat
  • Royaume-Uni
      • Derby, Royaume-Uni, DE11 7AQ
        • VCTC
  • Turquie (Türkiye)
      • Istanbul, Turquie (Türkiye), 34764
        • Umraniye Training and Research Hospital
  • États-Unis
    • Illinois
      • Chicago, Illinois, États-Unis, 60611
        • Ann and Robert H. Lurie Children's Hospital
    • Massachusetts
      • Boston, Massachusetts, États-Unis, 02115
        • Boston Children's Hospital
    • Minnesota
      • Rochester, Minnesota, États-Unis, 55905
        • Mayo Clinic
    • New Jersey
      • Eatontown, New Jersey, États-Unis, 07724
        • CLINILABS Drug Development Corp
    • Pennsylvania
      • Philadelphia, Pennsylvania, États-Unis, 19104
        • The Children's Hospital of Philadelphia (CHOP)

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Enfant
  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

Méthode d'échantillonnage

Échantillon non probabiliste

Population étudiée

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.

La 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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Modèles d'observation: CASE_ONLY
  • Perspectives temporelles: PROSPECTIVE

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Characterization of the natural history of ENPP1 Deficiency and the infantile-onset form of ABCC6 Deficiency longitudinally
Délai: 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
Délai: 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
Délai: 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
Délai: 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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Inozyme Pharma

Collaborateurs

GACI Global

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

25 juillet 2024

Achèvement primaire (Réel)

28 août 2026

Achèvement de l'étude (Réel)

28 août 2026

Dates d'inscription aux études

Première soumission

16 février 2024

Première soumission répondant aux critères de contrôle qualité

4 mars 2024

Première publication (Réel)

8 mars 2024

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

1 octobre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

28 septembre 2026

Dernière vérification

1 septembre 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • INZ701-007

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

INDÉCIS

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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