The ENERGY Study: Evaluation of Safety and Tolerability of INZ-701 in Infants With ENPP1 Deficiency

Study Overview
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Brief Summary
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The primary purpose of Study INZ701-104 (the ENERGY study) is to assess the safety and tolerability of INZ-701 in infants with ENPP1 Deficiency.

Detailed Description
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INZ-701 is an ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) enzyme replacement therapy in development for the treatment of the ultra rare genetic disorder, ENPP1 Deficiency. Study INZ701-104 (the ENERGY study) is a Phase 1b, open-label study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of INZ-701 in infant subjects with ENPP1 Deficiency. The study will consist of up to a 60-day Screening Period, a 52-week Treatment Period during which subjects will receive INZ-701, an Extension Period during which subjects may continue to receive INZ-701, and an End of Treatment (EOT) visit 30 days after the last dose of INZ-701. Upon treatment discontinuation, they will continue to be followed for their ongoing disposition for survival outcome at least quarterly, if feasible, through the end of the study.

Official Title
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The ENERGY Study: An Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INZ-701 in Infant Subjects With Ectonucleotide Pyrophosphatase/ Phosphodiesterase 1 (ENPP1) Deficiency

Conditions
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Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency, Autosomal Recessive Hypophosphatemic Rickets, Generalized Arterial Calcification of Infancy

Intervention / Treatment
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* Drug: INZ-701


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Caregiver(s) must provide written or electronic 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). Subject must have a post-natal confirmed 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 equivalent. Subject must be male or female ages ≥ 1 month to <1 year of age at Baseline Subject must weigh ≥ 0.5 kg at the time of the first dose of INZ-701 In the opinion of the Investigator, the subject must be able to complete all aspects of the study Subject's caregiver(s) must agree to provide access to their child's relevant medical records Exclusion Criteria: In the opinion of the Investigator, presence of any clinically significant disease or laboratory abnormality (outside of those considered associated with the diagnosis of ENPP1 Deficiency) that precludes study participation or may confound interpretation of study results, including known uncontrolled thyroid disease or unrelated connective tissue, bone, mineral, or muscle disease Care has been withdrawn or subject is receiving end of life care or hospice only Known malignancy Known intolerance to INZ-701 or any of its excipients Concurrent participation in another non-Inozyme interventional study and/or receipt of any other investigational new drug within 5 half-lives of the last dose of the other investigational product or from 4 weeks prior to the first dose of INZ-701, whichever is longer, or use of an investigational device, through completion of participation in the study

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Study INZ701-104 is a Phase 1b, open-label study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of INZ-701 in infant subjects with ENPP1 Deficiency.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INZ-701<br>The first two infant subjects will receive a single dose of 0.2 mg/kg on Day 1 and start at Dose Level A (0.2 mg/kg twice weekly) on Day 8. After the second subject completes Day 32, the Data Review Committee (DRC) will perform a cumulative review of safety and PK/PD data and will make dosing recommendations, for example, modifying the dose of the ongoing subjects and/or changing the starting dose for future subjects to Dose Levels B, C, or D. Each subject's safety and PK/PD data will also be reviewed by the DRC during its quarterly review, based upon which, the subject's dose may be modified to Dose Levels B, C, or D, as specified in the protocol. Dose Level A: 0.2 mg/kg twice weekly Dose Level B: 0.6 mg/kg twice weekly Dose Level C: 0.2 mg/kg once weekly Dose Level D: 0.6 mg/kg once weekly | Drug: INZ-701<br>* Recombinant fusion protein that contains the extracellular domains of human ENPP1 coupled with an Fc fragment from an immunoglobulin gamma-1 (IgG1) antibody.<br>* Other names: (rhENPP1-Fc).;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Treatment Emergent Adverse Events (TEAEs) | Treatment-emergent AEs are defined as any AE occurring from the first dose of INZ-701 through 30 days after the last dose of INZ-701. | 52 weeks (Treatment Period) | 
| Incidence of Anti-Drug Antibodies (ADA) | For each subject, the presence of ADAs will be assessed and, if present, further evaluation will determine specificity and subtypes. | 52 weeks (Treatment Period) | 
| Left Ventricular Ejection Fraction | For each subject, an echocardiogram will be collected, and used to assess heart function. (including measurement of left ventricular ejection fraction), and to identify any other abnormalities, for example, calcification of heart valves. | 52 weeks (Treatment Period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) Levels | 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. | 52 weeks (Treatment Period) | 
| 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. | 52 weeks (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. | 52 weeks (Treatment Period) | 
| ENPP1 Activity | For each subject, the activity of INZ-701 in the serum will be measured via a series of blood samples obtained throughout the study, comparing the subject's baseline value over time. | 52 weeks (Treatment Period) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GACI, ARHR2, ectonucleotide pyrophosphatase/phosphodiesterase1 deficiency, hypopyrophosphatemia, ENPP1, Generalized Arterial Calcification of Infancy, Autosomal Recessive Hypophosphatemic Rickets Type 2