Ectonucleotide Pyrophosphatase/Phosphodiesterase1 DeficiencyPhase 3NCT06046820
The ENERGY 3 Study: Evaluation of Efficacy and Safety of INZ-701 in Children With ENPP1 Deficiency
A Phase 3 study testing INZ-701 in people with Ectonucleotide Pyrophosphatase/Phosphodiesterase1 Deficiency and Autosomal Recessive Hypophosphatemic Rickets, run by Inozyme Pharma at 11 sites in 8 countries.
Trial summary
The primary purpose of Study INZ701-106 (The ENERGY 3 Study) is to assess the efficacy and safety of INZ-701 in children with ENPP1 Deficiency. Read more about this study
- Who is it for?
- Ages 1 year to 12 years
- Conditions the study is for
- Ectonucleotide Pyrophosphatase/Phosphodiesterase1 Deficiency, Autosomal Recessive Hypophosphatemic Rickets, Generalized Arterial Calcification of Infancy
- What is being tested?
- INZ-701
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 11 sitesin 8 countries
- Study dates
- 5 Nov 2023to 19 Aug 2026
- Phase
- Phase 3
- 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 year to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Study participants must meet all of the following inclusion criteria:
- Caregiver's written informed consent after the nature of the study has been explained, and prior to any research-related procedures, per International Conference on Harmonisation (ICH) Good Clinical Practice (GCP)
- Study participant's assent in accordance with local regulations
- A confirmed 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
- Males and females ≥1 year and <13 years of age at Study Day 1
- Open growth plates of the distal femur and proximal tibia in both legs
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- Plasma PPi concentration of <1400 nM at Screening
- 25(OH)D levels of ≥12 ng/mL at Screening
- Radiographic evidence of skeletal abnormalities based on an RSS ≥2
- Women of childbearing potential (WOCBP, as defined in Clinical Trials Coordination Group [CTCG 2024]) must have a negative serum pregnancy test at Screening and must not be breastfeeding
- Males who are sexually active must agree to use condoms from the period following first dose of INZ-701 through 30 days after the last dose of INZ-701
- WOCBP and partners of fertile males who are WOCBP must be using or must agree to use a highly effective form of (as per CTCG) from at least 1 month before the first dose of INZ-701 through 30 days after the last dose of INZ-701 (greater than 5 half-lives of INZ-701)
- In the opinion of the Investigator, able to complete all aspects of the study
Who cannot join
- Study participants meeting any of the following exclusion criteria will not be eligible to participate in the study:
- In the opinion of the Investigator, has clinically significant disease or laboratory abnormality not associated with ENPP1 Deficiency that will preclude study participation and/or may confound the interpretation of study results
- If receiving any of the following prohibited medications as indicated in the protocol: systemic corticosteroids (>5 mg prednisone equivalent per day), anti-FGF23 and oral and/or IV bisphosphonates
- Unable or unwilling to discontinue calcitriol or other active forms of vitamin D3 (or analogs) within 7 days prior to Study Day 1 and/or oral phosphate supplements within 36 hours prior to Study Day 1 if randomized to the INZ-701 arm
- Planned orthopedic surgery or other procedures that may confound the interpretation of study results during the 52-week RTP
- Known intolerance to INZ-701 or any of its excipients
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- A positive COVID-19 test within 5 days prior to Randomization, only if required as per local regulations or institutional policy
- Previous treatment with INZ-701
- Concurrent participation in another interventional clinical study and/or has received an investigational drug within 5 half-lives of the last dose or within 4 weeks prior to the first dose of INZ-701, whichever is longer, or use of an investigational device
Trial locations and contacts
11 sites in 8 countries.
11 sites in 8 countries
United States3 sites
Ann & Robert H. Lurie Children's Hospital
Chicago, Illinois, 60611
Cook Children's Medical Center
Fort Worth, Texas, 76104
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Turkey (Türkiye)2 sites
Umraniye Training and Research Hospital
Istanbul, 34764
Cukurova Universitesi Tip Fakultesi
Sarıçam, 01330
Canada1 site
Centre Hospitalier Universitaire (CHU) Sainte-Justine
Montreal, H3T 1C5
France1 site
Hôpital Bicêtre, Service d'endocrinologie et diabète de l'enfant (Childhood Endocrinology and Diabetes Department)
Le Kremlin-Bicêtre, 94270
Saudi Arabia1 site
King Faisal Specialist Hospital and Research Centre
Riyadh, 12713
United Arab Emirates1 site
Al Jalila Children's Specialty Hospital
Dubai, 30726
United Kingdom1 site
Royal Manchester Children's Hospital
Manchester, M13 9WL
About this study
Official title: The ENERGY 3 Study: A Randomized, Controlled, Open-Label, Phase 3 Study to Evaluate the Efficacy and Safety of INZ-701 in Children With Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1) Deficiency
The primary purpose of Study INZ701-106 (The ENERGY 3 Study) is to assess the efficacy and safety of INZ-701 in children with ENPP1 Deficiency.
Read the detailed description
INZ-701 is an ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) enzyme replacement therapy (ERT) in development for the treatment of ENPP1 Deficiency, an ultra-rare genetic disorder with an incidence of 1 in 64,000 pregnancies.
Study INZ701-106 (The ENERGY 3 Study) is a multi-center, randomized in a 2:1 ratio, controlled, open-label Phase 3 study to evaluate the efficacy and safety of INZ-701 in children with ENPP1 Deficiency.
The study will consist of a Screening Period of up to 52 days (including a washout period of up to 7 days for prohibited medications post-Randomization) and a Randomized Treatment Period (INZ-701 or control) of 52 weeks, followed by an Open-label Extension Period during which all study participants may receive INZ-701, and an End of Study (EOS) Safety visit 30 days after the last dose of INZ-701.
- Conditions
- Ectonucleotide Pyrophosphatase/Phosphodiesterase1 Deficiency, Autosomal Recessive Hypophosphatemic Rickets, Generalized Arterial Calcification of Infancy
- Being tested
- INZ-701, Control Arm (Conventional Therapy)
- Keywords
- Ectonucleotide Pyrophosphatase/Phosphodiesterase1 Deficiency, Hypopyrophosphatemia, ENPP1, Autosomal Recessive Hypophosphatemic Rickets Type 2, ARHR2, Generalized Arterial Calcification of Infancy, GACI
- Medical subject headings
- Hypophosphatemic Rickets, Autosomal Recessive, 1, Arterial calcification of infancy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INZ-701Drug
Also called (rhENPP1-Fc).
Recombinant fusion protein that contains the extracellular domains of human ENPP1 coupled with an Fc fragment from an immunoglobulin gamma-1 (IgG1) antibody.
Control Arm (Conventional Therapy)Drug
Conventional therapy is defined as oral phosphate supplements and calcitriol or other active forms of vitamin D3 (or analogs). No other agents for treatment of ENPP1 Deficiency are allowed in the control arm.
| Study group | Role | What they receive |
|---|---|---|
| INZ-701 | Experimental | Subjects randomized to the INZ-701 arm will be administered a 2.4 mg/kg once weekly dose by subcutaneous (SC) injection for the duration of the 52-week Randomized Treatment Period (RTP). RTP will be followed by a Low-dose Open-label Extension Period during which all study participants will receive INZ-701 at a dose of 2.4 mg/kg QW while the primary analysis is pending. If dose escalation criteria are met, all participants will transition to the Randomized Extension Period (REP) where participants who were originally randomized to INZ-701 during RTP will transition to a higher dose regimen of INZ-701 at 1.8 mg/kg twice weekly. Participants who were originally randomized to the active control arm during RTP will continue receiving INZ-701 at 2.4 mg/kg QW in the REP. Receives: Drug: INZ-701 |
| Control Arm (Conventional Therapy) | Active comparator | Subjects randomized to the control arm will continue taking their conventional therapy as clinically indicated by their treating physician for the duration of the 52-week Randomized Treatment Period. Receives: Drug: Control Arm (Conventional Therapy) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) concentration through Week 52
For each subject, plasma PPi will be measured via a series of blood samples obtained throughout the study, comparing the subject's baseline value over time.
Measured: 52 weeks (Baseline through Week 52)
Change from Baseline in skeletal abnormalities as measured by the Radiographic Global Impression of Change (RGI-C) global score through Week 52
The RGI-C is an overall radiographic score which can be used to monitor response to a therapeutic intervention comparing scores from 2 time points. A determination of healing on a scale of 0 to +3 with 0 being no change or healing and +3 being complete healing; worsening is also measured on a scale of 0 to -3 with 0 being no change and -3 being severe worsening.
Measured: 52 weeks (Baseline through Week 52)
Secondary outcomes (5)
Change from Baseline in rickets as measured by Rickets Severity Score (RSS) total score through Week 52
The RSS assesses rickets severity by utilizing a scoring system that uses a scale from 0 to 4 for the wrists and 0 to 6 for the knees, to generate a total score of 0 to 10, where 0 is normal and 10 is the worst score possible ie, most severe skeletal abnormalities observed radiographically.
Measured: Baseline, Week 26, Week 52
Change from Baseline in growth Z-score (height/body length and weight) through Week 52
A Z-score represents the degree to which that particular measurement for that individual differs from the reference value in the general population.
(height/body length and weight) through Week 52
Measured: Baseline, Day 29, Week 8, Week 13, Week 26, Week 39, Week 52
Area under the Plasma Concentration versus Time Curve (AUC) of INZ-701
For each subject, variation of concentration of INZ-701 in the plasma will be measured via a series of blood samples obtained throughout the study, comparing the subject's baseline value over time.
Measured: 52 weeks (Randomized Treatment Period)
Maximum Plasma Concentration (Cmax) of INZ-701
For each subject, the maximum concentration of INZ-701 in the plasma will be measured via a series of blood samples obtained throughout the study, comparing the subject's baseline value over time.
Measured: 52 weeks (Randomized Treatment Period)
Change from Baseline in ENPP1 activity (µM/min) through week 52
For each subject, the activity of INZ-701 (µM/min) in the serum will be assessed through hydrolysis of a substrate to the enzyme, via a series of blood samples obtained throughout the study, comparing the subject's baseline value over time.
Measured: 52 weeks (Randomized Treatment Period)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2023
- Study start5 Nov 2023
- Primary completion29 Jan 2026
- Study completion19 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/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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Study INZ701-106 (ENERGY 3) is a multicenter, randomized in a 2:1 ratio, controlled, open-label Phase 3 study to evaluate the efficacy and safety of INZ-701 in children with ENPP1 Deficiency.
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Inozyme Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- BioMarin Pharmaceutical
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06046820
- Sponsor's protocol ID
- INZ701-106
- Status last verified
- Sep 2026
- First submitted
- 28 Aug 2023
- Last updated
- 1 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
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
- The ENERGY 3 Study: A Randomized, Controlled, Open-Label, Phase 3 Study to Evaluate the Efficacy and Safety of INZ-701 in Children With Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1) Deficiency
- ClinicalTrials.gov ID
- NCT06046820
- Acronym / sponsor ID
- INZ701-106
- Conditions
- Ectonucleotide Pyrophosphatase/Phosphodiesterase1 Deficiency, Autosomal Recessive Hypophosphatemic Rickets, Generalized Arterial Calcification of Infancy
- Keywords
- Ectonucleotide Pyrophosphatase/Phosphodiesterase1 Deficiency, Hypopyrophosphatemia, ENPP1, Autosomal Recessive Hypophosphatemic Rickets Type 2, ARHR2, Generalized Arterial Calcification of Infancy, GACI
- Phase
- Phase 3
- Study type
- Interventional
- 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
- 27 participants (actual)
- Lead sponsor
- Inozyme PharmaIndustry (pharma, biotech, devices)
- Collaborators
- BioMarin Pharmaceutical
- Study start
- 5 Nov 2023 (actual)
- Primary completion
- 29 Jan 2026 (actual)
- Study completion
- 19 Aug 2026 (actual)
- First posted
- 21 Sep 2023 (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 primary purpose of Study INZ701-106 (The ENERGY 3 Study) is to assess the efficacy and safety of INZ-701 in children with ENPP1 Deficiency.
Detailed description
INZ-701 is an ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) enzyme replacement therapy (ERT) in development for the treatment of ENPP1 Deficiency, an ultra-rare genetic disorder with an incidence of 1 in 64,000 pregnancies.
Study INZ701-106 (The ENERGY 3 Study) is a multi-center, randomized in a 2:1 ratio, controlled, open-label Phase 3 study to evaluate the efficacy and safety of INZ-701 in children with ENPP1 Deficiency.
The study will consist of a Screening Period of up to 52 days (including a washout period of up to 7 days for prohibited medications post-Randomization) and a Randomized Treatment Period (INZ-701 or control) of 52 weeks, followed by an Open-label Extension Period during which all study participants may receive INZ-701, and an End of Study (EOS) Safety visit 30 days after the last dose of INZ-701.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Study INZ701-106 (ENERGY 3) is a multicenter, randomized in a 2:1 ratio, controlled, open-label Phase 3 study to evaluate the efficacy and safety of INZ-701 in children with ENPP1 Deficiency.
| Arm | Type | Receives |
|---|---|---|
| INZ-701 | Experimental | Drug: INZ-701Subjects randomized to the INZ-701 arm will be administered a 2.4 mg/kg once weekly dose by subcutaneous (SC) injection for the duration of the 52-week Randomized Treatment Period (RTP). RTP will be followed by a Low-dose Open-label Extension Period during which all study participants will receive INZ-701 at a dose of 2.4 mg/kg QW while the primary analysis is pending. If dose escalation criteria are met, all participants will transition to the Randomized Extension Period (REP) where participants who were originally randomized to INZ-701 during RTP will transition to a higher dose regimen of INZ-701 at 1.8 mg/kg twice weekly. Participants who were originally randomized to the active control arm during RTP will continue receiving INZ-701 at 2.4 mg/kg QW in the REP. |
| Control Arm (Conventional Therapy) | Active comparator | Drug: Control Arm (Conventional Therapy)Subjects randomized to the control arm will continue taking their conventional therapy as clinically indicated by their treating physician for the duration of the 52-week Randomized Treatment Period. |
Who may qualify
- Ages
- 1 year to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (13 listed)
- Caregiver's written informed consent after the nature of the study has been explained, and prior to any research-related procedures, per International Conference on Harmonisation (ICH) Good Clinical Practice (GCP)
- Study participant's assent in accordance with local regulations
- A confirmed 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
- Males and females ≥1 year and <13 years of age at Study Day 1
- Open growth plates of the distal femur and proximal tibia in both legs
Key exclusion criteria (9 listed)
- Study participants meeting any of the following exclusion criteria will not be eligible to participate in the study:
- In the opinion of the Investigator, has clinically significant disease or laboratory abnormality not associated with ENPP1 Deficiency that will preclude study participation and/or may confound the interpretation of study results
- If receiving any of the following prohibited medications as indicated in the protocol: systemic corticosteroids (>5 mg prednisone equivalent per day), anti-FGF23 and oral and/or IV bisphosphonates
- Unable or unwilling to discontinue calcitriol or other active forms of vitamin D3 (or analogs) within 7 days prior to Study Day 1 and/or oral phosphate supplements within 36 hours prior to Study Day 1 if randomized to the INZ-701 arm
- Planned orthopedic surgery or other procedures that may confound the interpretation of study results during the 52-week RTP
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 |
|---|---|---|
| INZ-701Also: (rhENPP1-Fc).Recombinant fusion protein that contains the extracellular domains of human ENPP1 coupled with an Fc fragment from an immunoglobulin gamma-1 (IgG1) antibody. | Drug | INZ-701 |
| Control Arm (Conventional Therapy)Conventional therapy is defined as oral phosphate supplements and calcitriol or other active forms of vitamin D3 (or analogs). No other agents for treatment of ENPP1 Deficiency are allowed in the control arm. | Drug | Control Arm (Conventional Therapy) |
Primary outcome
Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) concentration through Week 52
Time frame: 52 weeks (Baseline through Week 52)
For each subject, plasma PPi will be measured via a series of blood samples obtained throughout the study, comparing the subject's baseline value over time.
Change from Baseline in skeletal abnormalities as measured by the Radiographic Global Impression of Change (RGI-C) global score through Week 52
Time frame: 52 weeks (Baseline through Week 52)
The RGI-C is an overall radiographic score which can be used to monitor response to a therapeutic intervention comparing scores from 2 time points. A determination of healing on a scale of 0 to +3 with 0 being no change or healing and +3 being complete healing; worsening is also measured on a scale of 0 to -3 with 0 being no change and -3 being severe worsening.
5 secondary outcomes
Change from Baseline in rickets as measured by Rickets Severity Score (RSS) total score through Week 52
Time frame: Baseline, Week 26, Week 52
Change from Baseline in growth Z-score (height/body length and weight) through Week 52
Time frame: Baseline, Day 29, Week 8, Week 13, Week 26, Week 39, Week 52
Area under the Plasma Concentration versus Time Curve (AUC) of INZ-701
Time frame: 52 weeks (Randomized Treatment Period)
Maximum Plasma Concentration (Cmax) of INZ-701
Time frame: 52 weeks (Randomized Treatment Period)
Change from Baseline in ENPP1 activity (µM/min) through week 52
Time frame: 52 weeks (Randomized Treatment Period)
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.
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.
11 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing INZ-701 in people with Ectonucleotide Pyrophosphatase/Phosphodiesterase1 Deficiency and Autosomal Recessive Hypophosphatemic Rickets, run by Inozyme Pharma at 11 sites in 8 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 13 inclusion and 9 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 11 sites in United States, Turkey (Türkiye), Australia, Canada, France and 3 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) concentration through Week 52 (time frame: 52 weeks (Baseline through Week 52)). 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 1 Oct 2026.