PROPEL: un registro prospettico osservazionale dei pazienti per valutare il deficit di ENPP1 e ABCC6
Un registro prospettico osservazionale dei pazienti per valutare la progressione della malattia nei pazienti con deficit di ENPP1 e deficit di ABCC6 a esordio infantile (GACI tipo 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.
Panoramica dello studio
Stato
Stato
Condizioni
Condizioni
Intervento / Trattamento
Intervento / Trattamento
Descrizione dettagliata
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.
Tipo di studio
Tipo di studio
Iscrizione (Effettivo)
Iscrizione
Contatti e Sedi
Luoghi di studio
-
-
Quebec
-
Montreal, Quebec, Canada, H3T1C5
- CHU Sainte-Justine Research Centre
-
-
-
-
-
Hamburg, Germania, 20251
- Universitätsklinikum Hamburg-Eppendorf
-
-
-
-
-
Tokyo, Giappone, 113-8655
- The University of Tokyo Hospital
-
-
-
-
-
Milan, Italia, 20132
- IRCCS San Raffaele Hospital - Main
-
-
-
-
-
Muscat, Oman
- Royal Hospital Muscat
-
-
-
-
-
Derby, Regno Unito, DE11 7AQ
- VCTC
-
-
-
-
-
Barcelona, Spagna, 08029
- EU Hub - VCTC
-
Barcelona, Spagna, 08950
- Hospital Sant Joan de Deu
-
-
-
-
Illinois
-
Chicago, Illinois, Stati Uniti, 60611
- Ann and Robert H. Lurie Children's Hospital
-
-
Massachusetts
-
Boston, Massachusetts, Stati Uniti, 02115
- Boston Children's Hospital
-
-
Minnesota
-
Rochester, Minnesota, Stati Uniti, 55905
- Mayo Clinic
-
-
New Jersey
-
Eatontown, New Jersey, Stati Uniti, 07724
- CLINILABS Drug Development Corp
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, Stati Uniti, 19104
- The Children's Hospital of Philadelphia (CHOP)
-
-
-
-
-
Istanbul, Turchia (Türkiye), 34764
- Umraniye Training and Research Hospital
-
-
Criteri di partecipazione
Criteri di ammissibilità
Criteri di ammissibilità
Età idonea allo studio
- Bambino
- Adulto
- Adulto più anziano
Accetta volontari sani
Sessi ammissibili allo studio
Metodo di campionamento
Popolazione di studio
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.
Descrizione
Inclusion Criteria:
Individuals eligible to participate must meet all the following inclusion criteria:
-
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
OR
-
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:
-
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
- 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
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Modelli osservazionali: CASE_ONLY
- Prospettive temporali: PROSPECTIVE
Cosa sta misurando lo studio?
Misure di risultato primarie
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Characterization of the natural history of ENPP1 Deficiency and the infantile-onset form of ABCC6 Deficiency longitudinally
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
|
Collaboratori e investigatori
Sponsor
Sponsor
Collaboratori
Collaboratori
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Inizio studio
Completamento primario (Effettivo)
Completamento primario
Completamento dello studio (Effettivo)
Completamento dello studio
Date di iscrizione allo studio
Primo inviato
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Primo Inserito
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento pubblicato
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
Altri numeri di identificazione dello studio
- INZ701-007
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .