Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 DeficiencyNCT06302439
PROPEL - A Prospective Observational Patient Registry to Evaluate ENPP1 and ABCC6 Deficiency
An observational study of Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 Deficiency and ATP-Binding Cassette Subfamily C Member 6 Deficiency, run by Inozyme Pharma at 14 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 Deficiency, ATP-Binding Cassette Subfamily C Member 6 Deficiency
- How many people
- 54 participants
- Where
- 14 sitesin 9 countries
- Study dates
- 25 Jul 2024to 28 Aug 2026
- How long will I take part?
- 10 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- 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
Show all 17Show fewer
- Monoallelic ENPP1 mutation confirmed by a certified CAP/CLIA laboratory or regional equivalent and any of the following clinical symptoms:
- ≥ 1 traumatic vertebral fracture
- ≥ 2 fractures as an adult (eg, long-bones, digits, vertebrae)
- Low bone mineral density (dual-energy X-ray absorptiometry [DXA] Z-score <1.5) and <55 years of age
- Bone or joint pain interfering with movement or daily activities
- History of myocardial infarction (MI), unstable angina, transient ischemic attack (TIA) or low cardiac output before the age of 40 yrs.
- History of rickets or bone deformity
- Diagnosis of ossification of the posterior longitudinal ligament (OPLL)
- Other clinical symptoms, with approval by Inozyme
- OR
- 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
Who cannot join
- 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
Trial locations and contacts
14 sites in 9 countries.
14 sites in 9 countries
United States5 sites
Boston Children's Hospital
Boston, Massachusetts, 02115
Ann and Robert H. Lurie Children's Hospital
Chicago, Illinois, 60611
CLINILABS Drug Development Corp
Eatontown, New Jersey, 07724
The Children's Hospital of Philadelphia (CHOP)
Philadelphia, Pennsylvania, 19104
Mayo Clinic
Rochester, Minnesota, 55905
Spain2 sites
EU Hub - VCTC
Barcelona, 08029
Hospital Sant Joan de Deu
Barcelona, 08950
Turkey (Türkiye)1 site
Umraniye Training and Research Hospital
Istanbul, 34764
About this study
Official title: 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.
Read the 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.
- Conditions
- Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 Deficiency, ATP-Binding Cassette Subfamily C Member 6 Deficiency
- Being tested
- No Intervention for this observational study
- 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
- Medical subject headings
- Arterial calcification of infancy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No Intervention for this observational studyOther
No Intervention for this observational study
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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.
Measured: 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
Measured: Annually up to 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2024
- Study start25 Jul 2024
- Primary completion28 Aug 2026
- Study completion28 Aug 2026
Why it stopped: The study was terminated by the sponsor prior to planned completion based on a review of the data across indications and overall program considerations. Study termination was not related to participant safety.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 54 participants (actual)
- Target duration
- 10 Years
Sponsor and investigators
- Lead sponsor
- Inozyme Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- GACI Global
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06302439
- Sponsor's protocol ID
- INZ701-007
- Status last verified
- Sep 2026
- First submitted
- 16 Feb 2024
- Last updated
- 1 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Observational Patient Registry to Evaluate Disease Progression in Patients With ENPP1 Deficiency and Infantile-Onset ABCC6 Deficiency (GACI Type 2)
- ClinicalTrials.gov ID
- NCT06302439
- Acronym / sponsor ID
- INZ701-007
- 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
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: The study was terminated by the sponsor prior to planned completion based on a review of the data across indications and overall program considerations. Study termination was not related to participant safety.
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Inozyme PharmaIndustry (pharma, biotech, devices)
- Collaborators
- GACI Global
- Study start
- 25 Jul 2024 (actual)
- Primary completion
- 28 Aug 2026 (actual)
- Study completion
- 28 Aug 2026 (actual)
- First posted
- 8 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Case only
- Time perspective
- Prospective
- Target follow-up
- 10 Years
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (17 listed)
- 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
- OR
- ≥ 2 fractures as an adult (eg, long-bones, digits, vertebrae)
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No Intervention for this observational studyNo Intervention for this observational study | Other | – |
Primary outcome
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.
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
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.
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
Results and safety
The study was stopped early (reason given: The study was terminated by the sponsor prior to planned completion based on a review of the data across indications and overall program considerations. Study termination was not related to participant safety.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2026.
- Individual participant dataSharing planned: Undecided
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
14 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 Deficiency and ATP-Binding Cassette Subfamily C Member 6 Deficiency, run by Inozyme Pharma at 14 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States, Spain, Canada, Germany, Italy and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: The study was terminated by the sponsor prior to planned completion based on a review of the data across indications and overall program considerations. Study termination was not related to participant safety.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Characterization of the natural history of ENPP1 Deficiency and the infantile-onset form of ABCC6 Deficiency longitudinally (time frame: Annually up to 10 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2026.