Ectonucleotide Pyrophosphatase/phosphodiesterase1 DeficiencyNCT07745179
Natural History Study: ENPP1 Deficiency or the Early-Onset Form of ABCC6 Deficiency
An observational study of Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency and ATP-Binding Cassette Subfamily C Member 6 Deficiency, run by Inozyme Pharma at 8 sites in 4 countries.
Trial summary
The purpose of this study is to characterize the natural history of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) Deficiency and the early-onset form of adenosine triphosphate binding cassette transporter subfamily C member 6 (ABCC6) Deficiency through retrospective review of medical records and other… Read more about this study
- Who is it for?
- Ages 1 day and older
- Conditions the study is for
- Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency, ATP-Binding Cassette Subfamily C Member 6 Deficiency, Generalized Arterial Calcification of Infancy
- How many people
- 23 participants
- Where
- 8 sitesin 4 countries
- Study dates
- 5 Dec 2018to 14 Feb 2025
- 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 1 day and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Infant, pediatric, and adult participants with ENPP1 Deficiency or early-onset ABCC6 Deficiency, including participants with generalized arterial calcification of infancy (GACI), whose diagnoses were confirmed by genetic testing and/or clinical phenotype and who had medical records available for retrospective review.
Who may be able to join
- Participants were eligible for inclusion if they met at least one of the following criteria:
- Generalized arterial calcification of infancy (GACI) genotype, defined as two pathogenic mutations in ENPP1 and/or ABCC6, confirmed by mutational analysis, and a GACI phenotype confirmed by imaging or biopsy.
- GACI phenotype confirmed by imaging or biopsy, with mutational analysis demonstrating that each parent carried at least one mutation in ENPP1 and/or ABCC6.
- Biallelic mutations in ENPP1 and a clinical phenotype consistent with ENPP1 Deficiency.
- Mutational analysis demonstrating that each parent carried at least one mutation in ENPP1, together with clinical signs and symptoms consistent with ENPP1 Deficiency in the participant.
- Availability of medical records and source documentation sufficient for retrospective review.
Who cannot join
- Insufficient medical records, imaging studies, or source documentation to support retrospective data collection.
- Diagnosis not consistent with ENPP1 Deficiency, GACI, or early-onset ABCC6 Deficiency.
- Inability to obtain informed consent from the participant or legally authorized representative, as required by local regulations.
Trial locations and contacts
8 sites in 4 countries.
8 sites in 4 countries
France3 sites
Centre de References des Maladies Neuromusculaires (CRMN)
La Tronche
Hospices Civils de Lyon
Lyon
Hopital Necker-Enfants Malades
Paris
United Kingdom3 sites
Birmingham Children's Hospital
Birmingham
Evelina London Children's Hospital
London, 19104
Royal Manchester University Hospital
Manchester
United States1 site
Children's Hospital of Philadelpha
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Retrospective, Longitudinal Natural History Study of Subjects With ENPP1 Deficiency or the Early-Onset Form of ABCC6 Deficiency
The purpose of this study is to characterize the natural history of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) Deficiency and the early-onset form of adenosine triphosphate binding cassette transporter subfamily C member 6 (ABCC6) Deficiency through retrospective review of medical records and other available data sources. Information collected on medical history, clinical manifestations, radiographic imaging, and other disease-related assessments may be used to support the development of future therapies for these diseases.
Read the detailed description
Study INZ701-006 is a multicenter, retrospective, observational natural history study designed to evaluate disease presentation and progression in infant, pediatric, and adult subjects with ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) Deficiency and in subjects with the early-onset form of adenosine triphosphate-binding cassette transporter subfamily C member 6 (ABCC6) Deficiency.
The study will utilize data obtained from medical records, radiographic imaging, and other available sources to characterize the physiological, anatomical, and functional manifestations of ENPP1 Deficiency and early-onset ABCC6 Deficiency.
For eligible subjects, historical data will be retrospectively abstracted from medical records and other available sources from birth, or earlier when available, through the date of informed consent, loss to follow-up, death, or another defined data cutoff, as applicable.
No study intervention will be administered as part of this observational study.
- Conditions
- Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency, ATP-Binding Cassette Subfamily C Member 6 Deficiency, Generalized Arterial Calcification of Infancy, Autosomal Recessive Hypophosphatemic Rickets, PXE (Pseudoxanthoma Elasticum)
- Keywords
- Ectonucleotide pyrophosphatase/phosphodiesterase 1 deficiency, ENPP1, ATP-binding cassette subfamily C member 6 deficiency, ABCC6, Generalized Arterial Calcification of Infancy, GACI, Autosomal Recessive Hypophosphatemic Rickets Type 2, ARHR2, Hypopyrophosphatemia, PXE (Pseudoxanthoma Elasticum), ectopic calcification, Arterial calcification, Intraarticular calcification, Aortic calcification
- Medical subject headings
- Arterial calcification of infancy, Hypophosphatemic Rickets, Autosomal Recessive, 1, Pseudoxanthoma Elasticum
What is being measured
The primary outcome is the main question the study is designed to answer.
Participants with Ectopic Calcification
Assessment of the occurrence of ectopic calcification documented in available imaging records. Ectopic calcification was identified based on radiologist or investigator interpretation of imaging assessments. The measure was the number of participants with documented ectopic calcification.
Measured: Retrospective assessment of available historical records collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).
Participants With Disease-Related Skeletal Abnormalities
Assessment of the occurrence of disease-related skeletal abnormalities documented in available medical records and imaging reports. Skeletal abnormalities were identified based on clinical diagnoses and radiographic findings recorded by treating physicians. The measure was the number of participants with documented skeletal abnormalities.
Measured: Retrospective assessment of available historical records collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).
Secondary outcomes (7)
Global Rickets Severity Score
Assessment of rickets severity using the Global Rickets Severity Score (RSS), which was derived from radiographic evaluations. Score (0 to 10), with higher scores indicating greater severity of rickets.
Measured: Retrospective assessment of available radiographic evaluations collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).
Height Z-Score
Assessment of longitudinal growth using height measurements obtained from medical records. Height measurements were converted to age- and sex-adjusted height Z-scores using WHO and CDC growth standards. The measured variable was height Z-score, reported as standard deviations (SD) from the reference population mean.
Measured: Retrospective assessment of available height measurements collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).
Weight Z-Score
Assessment of longitudinal growth using weight measurements obtained from medical records. Weight measurements were converted to age- and sex-adjusted weight Z-scores using WHO and CDC growth standards. The measured variable was weight Z-score, reported as standard deviations (SD) from the reference population mean.
Measured: Retrospective assessment of available weight measurements collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).
Serum Phosphate Concentration
Assessment of serum phosphate concentration obtained from clinical laboratory evaluations documented in medical records. The measured variable was serum phosphate concentration, reported in milligrams per deciliter (mg/dL) or converted to a common unit for analysis where appropriate.
Measured: Retrospective assessment of available serum phosphate measurements collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).
Fibroblast Growth Factor 23 (FGF23) Concentration
Assessment of fibroblast growth factor 23 (FGF23) concentration obtained from clinical laboratory evaluations documented in medical records. The measured variable was FGF23 concentration, reported in picograms per milliliter (pg/mL) according to local laboratory methodology.
Measured: Retrospective assessment of available FGF23 measurements collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).
Parathyroid Hormone (PTH) Concentration
Assessment of parathyroid hormone (PTH) concentration obtained from clinical laboratory evaluations documented in medical records. The measured variable was serum PTH concentration, reported in picograms per milliliter (pg/mL) according to local laboratory methodology.
Measured: Retrospective assessment of available PTH measurements collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).
Inorganic Pyrophosphate (PPi) Concentration
Assessment of inorganic pyrophosphate (PPi) concentration obtained from clinical laboratory evaluations documented in medical records. The measured variable was PPi concentration, reported in micromoles per liter (µmol/L) according to local laboratory methodology.
Measured: Retrospective assessment of available PPi measurements collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2026
- Study start5 Dec 2018
- Primary completion8 Jun 2023
- Study completion14 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ectonucleotide Pyrophosphatase/phosphodiesterase1 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
- Retrospective
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Inozyme Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07745179
- Sponsor's protocol ID
- INZ701-006
- Status last verified
- Jul 2026
- First submitted
- 5 Nov 2021
- Last updated
- 4 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: This data was collected for clinical trial planning and publication purposes by the Sponsor
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Retrospective, Longitudinal Natural History Study of Subjects With ENPP1 Deficiency or the Early-Onset Form of ABCC6 Deficiency
- ClinicalTrials.gov ID
- NCT07745179
- Acronym / sponsor ID
- INZ701-006
- Conditions
- Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency, ATP-Binding Cassette Subfamily C Member 6 Deficiency, Generalized Arterial Calcification of Infancy, Autosomal Recessive Hypophosphatemic Rickets, PXE (Pseudoxanthoma Elasticum)
- Keywords
- Ectonucleotide pyrophosphatase/phosphodiesterase 1 deficiency, ENPP1, ATP-binding cassette subfamily C member 6 deficiency, ABCC6, Generalized Arterial Calcification of Infancy, GACI, Autosomal Recessive Hypophosphatemic Rickets Type 2, ARHR2
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Inozyme PharmaIndustry (pharma, biotech, devices)
- Study start
- 5 Dec 2018 (actual)
- Primary completion
- 8 Jun 2023 (actual)
- Study completion
- 14 Feb 2025 (actual)
- First posted
- 4 Aug 2026 (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 study is to characterize the natural history of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) Deficiency and the early-onset form of adenosine triphosphate binding cassette transporter subfamily C member 6 (ABCC6) Deficiency through retrospective review of medical records and other available data sources. Information collected on medical history, clinical manifestations, radiographic imaging, and other disease-related assessments may be used to support the development of future therapies for these diseases.
Detailed description
Study INZ701-006 is a multicenter, retrospective, observational natural history study designed to evaluate disease presentation and progression in infant, pediatric, and adult subjects with ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) Deficiency and in subjects with the early-onset form of adenosine triphosphate-binding cassette transporter subfamily C member 6 (ABCC6) Deficiency.
The study will utilize data obtained from medical records, radiographic imaging, and other available sources to characterize the physiological, anatomical, and functional manifestations of ENPP1 Deficiency and early-onset ABCC6 Deficiency.
For eligible subjects, historical data will be retrospectively abstracted from medical records and other available sources from birth, or earlier when available, through the date of informed consent, loss to follow-up, death, or another defined data cutoff, as applicable.
No study intervention will be administered as part of this observational study.
Study design
- Observational model
- Case only
- Time perspective
- Retrospective
Who may qualify
- Ages
- 1 day and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Infant, pediatric, and adult participants with ENPP1 Deficiency or early-onset ABCC6 Deficiency, including participants with generalized arterial calcification of infancy (GACI), whose diagnoses were confirmed by genetic testing and/or clinical phenotype and who had medical records available for retrospective review.
Key inclusion criteria (6 listed)
- Participants were eligible for inclusion if they met at least one of the following criteria:
- Generalized arterial calcification of infancy (GACI) genotype, defined as two pathogenic mutations in ENPP1 and/or ABCC6, confirmed by mutational analysis, and a GACI phenotype confirmed by imaging or biopsy.
- GACI phenotype confirmed by imaging or biopsy, with mutational analysis demonstrating that each parent carried at least one mutation in ENPP1 and/or ABCC6.
- Biallelic mutations in ENPP1 and a clinical phenotype consistent with ENPP1 Deficiency.
- Mutational analysis demonstrating that each parent carried at least one mutation in ENPP1, together with clinical signs and symptoms consistent with ENPP1 Deficiency in the participant.
Key exclusion criteria (3 listed)
- Insufficient medical records, imaging studies, or source documentation to support retrospective data collection.
- Diagnosis not consistent with ENPP1 Deficiency, GACI, or early-onset ABCC6 Deficiency.
- Inability to obtain informed consent from the participant or legally authorized representative, as required by local regulations.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Participants with Ectopic Calcification
Time frame: Retrospective assessment of available historical records collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).
Assessment of the occurrence of ectopic calcification documented in available imaging records. Ectopic calcification was identified based on radiologist or investigator interpretation of imaging assessments. The measure was the number of participants with documented ectopic calcification.
Participants With Disease-Related Skeletal Abnormalities
Time frame: Retrospective assessment of available historical records collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).
Assessment of the occurrence of disease-related skeletal abnormalities documented in available medical records and imaging reports. Skeletal abnormalities were identified based on clinical diagnoses and radiographic findings recorded by treating physicians. The measure was the number of participants with documented skeletal abnormalities.
7 secondary outcomes
Global Rickets Severity Score
Time frame: Retrospective assessment of available radiographic evaluations collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).
Height Z-Score
Time frame: Retrospective assessment of available height measurements collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).
Weight Z-Score
Time frame: Retrospective assessment of available weight measurements collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).
Serum Phosphate Concentration
Time frame: Retrospective assessment of available serum phosphate measurements collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).
Fibroblast Growth Factor 23 (FGF23) Concentration
Time frame: Retrospective assessment of available FGF23 measurements collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).
Parathyroid Hormone (PTH) Concentration
Time frame: Retrospective assessment of available PTH measurements collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).
Inorganic Pyrophosphate (PPi) Concentration
Time frame: Retrospective assessment of available PPi measurements collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2026.
- Individual participant dataSharing planned: No. This data was collected for clinical trial planning and publication purposes by the Sponsor
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.
8 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency and ATP-Binding Cassette Subfamily C Member 6 Deficiency, run by Inozyme Pharma at 8 sites in 4 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 6 inclusion and 3 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: finished, as of the sponsor's last update on 4 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in France, United Kingdom, United States, Germany. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Participants with Ectopic Calcification (time frame: Retrospective assessment of available historical records collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).). The study lists 2 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 4 Aug 2026.