The ENERGY Study: Evaluation of Safety and Tolerability of INZ-701 in Infants With ENPP1 Deficiency or ABCC6 Deficiency (ENERGY)

The ENERGY Study: An Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INZ-701 in Infants With Ectonucleotide Pyrophosphatase/ Phosphodiesterase 1 (ENPP1) Deficiency or ATP-binding Cassette Sub-family C Member 6 (ABCC6) Deficiency

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 or with ABCC6 Deficiency.

Study Overview

• Status: Recruiting
• Conditions: Pseudoxanthoma Elasticum; Generalized Arterial Calcification of Infancy; Autosomal Recessive Hypophosphatemic Rickets; Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency; ATP-Binding Cassette Subfamily C Member 6 Deficiency
• Intervention / Treatment: Drug: INZ-701

Detailed Description

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 or with ABCC6 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 study participants with ENPP1 Deficiency or ABCC6 Deficiency.

The study will consist of up to a 60-day Screening Period, a 52-week Treatment Period during which study participants will receive INZ-701, an Extension Period during which participants may continue to receive INZ-701 until it is commercially available in the country where the participant resides, or until an alternative study of INZ-701 is available, and an End of Treatment (EOT) visit 30 days after the last dose of INZ-701. Upon treatment discontinuation, participants will continue to be followed for their ongoing disposition for survival outcome at least quarterly through the end of the study.

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Trial Specialist; Phone Number: +1 800-983-4587; Email: medinfo@bmrn.com
• Study Contact Backup: Name: Medical Director, MD; Phone Number: +1 800-983-4587; Email: medinfo@bmrn.com

Study Locations

• Spain
  • Barcelona, Spain
    • Terminated
    • Hospital Sant Joan de Déu
• United Kingdom
  • Manchester, United Kingdom, M13 9WL
    • Terminated
    • Royal Manchester Children's Hospital
• United States
  • California
    • San Diego, California, United States, 92123
      • Recruiting
      • Rady Children's Hospital
      • Contact: Sarah Lazar, MPH; Phone Number: 8585761700; Email: slazar@health.ucsd.edu
      • Contact: Nathaly Sweeney, MD; Phone Number: 8589665818; Email: nsweeney@rchsd.org
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Withdrawn
      • Boston Children's Hospital
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Recruiting
      • Nationwide Children's Hospital
      • Contact: Bimal Chaudhari, MD; Phone Number: 614-722-3535; Email: bimal.chaudhari@nationwidechildrens.org
      • Contact: Marina Artemova, PhD; Phone Number: 614-722-2655; Email: marina.artemova@nationwidechildrens.org
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • The Children's Hospital of Philadelphia
      • Contact: Olivia Lucas; Phone Number: 267-995-0907; Email: lucaso@chop.edu
      • Contact: Emily McCoy; Phone Number: 267-251-4268; Email: mccoye3@chop.edu
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • Withdrawn
      • The University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 1 year (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Infant aged ≤ 1 year at the time of enrollment
2. Study participant must have a confirmed post-natal molecular genetic diagnosis of ENPP1 Deficiency or ABCC6 Deficiency
3. Study participants must have clinical manifestations of generalized arterial calcification of infancy (GACI) or GACI-2, which must include at least one of the following: ectopic calcification, heart failure, respiratory distress, edema, cyanosis, hypertension, and cardiomegaly.
4. Study participant must weigh ≥0.5 kg at the time of the first dose of INZ-701 in this study
5. Written informed consent provided by a parent or legal guardian

Exclusion Criteria:

1. In the opinion of the Investigator, presence of any clinically significant disease or laboratory abnormality that precludes study participation or may confound interpretation of study result
2. Receiving end of life or hospice care
3. Known malignancy
4. Concurrent participation in another non-Inozyme interventional study
5. Treatment with any non-Inozyme product or investigational device during study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: INZ-701; The first 2 study participants will receive 1 dose of 0.2 mg/kg on Day 1 and start at Dose Level A (0.2 mg/kg twice weekly) on Day 8. The Data Review Committee (DRC) comprised of representatives of the Sponsor, the study Investigators, and a physician who is a subject matter expert not affiliated with the study or Sponsor, will review the safety data of the first study participant through Day 8. Contingent upon this review, the Sponsor will decide if additional study participants can begin receiving INZ-701. After the second study participant completes Day 32, the 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 study participants and/or changing the starting dose for future participants. 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 Dose Level E: 1.8 mg/kg once weekly

Drug: INZ-701; Recombinant fusion protein that contains the extracellular domains of human ENPP1 coupled with an Fc fragment from an immunoglobulin gamma-1 (IgG1) antibody.; Other Names: (rhENPP1-Fc).

What is the study measuring?

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 participant, 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 participant, 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 participant, plasma PPi will be measured via a series of blood samples obtained throughout the study, comparing the participant's baseline value over time.	52 weeks (Treatment Period)
Area under the Plasma Concentration versus Time Curve (AUC) of INZ-701	For each participant, variation of concentration of INZ-701 in the plasma will be measured via a series of blood samples obtained throughout the study, comparing the participant's baseline value over time.	52 weeks (Treatment Period)
Maximum Plasma Concentration (Cmax) of INZ-701	For each participant, the maximum concentration of INZ-701 in the plasma will be measured via a series of blood samples obtained throughout the study, comparing the participant's baseline value over time.	52 weeks (Treatment Period)
ENPP1 Activity	For each participant, the activity of INZ-701 in the serum will be measured via a series of blood samples obtained throughout the study, comparing the participant's baseline value over time.	52 weeks (Treatment Period)

Collaborators and Investigators

• Sponsor: Inozyme Pharma
• Collaborators: BioMarin Pharmaceutical
• Investigators: Study Director: Medical Director, MD, MD, BioMarin Pharmaceutical

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2023
• Primary Completion (Estimated): November 11, 2027
• Study Completion (Estimated): November 11, 2027

Study Registration Dates

• First Submitted: January 26, 2023
• First Submitted That Met QC Criteria: February 15, 2023
• First Posted (Actual): February 17, 2023

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Generalized Arterial Calcification of Infancy; PXE; ABCC6; ENPP1; GACI; Autosomal Recessive Hypophosphatemic Rickets Type 2; ARHR2; hypopyrophosphatemia; ectonucleotide pyrophosphatase/phosphodiesterase1 deficiency; ATP-Binding Cassette Subfamily C Member 6 Deficiency; Pseudoxanthoma elasticum
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Connective Tissue Diseases; Hematologic Diseases; Skin Diseases; Congenital Abnormalities; Hemostatic Disorders; Hemorrhagic Disorders; Skin Diseases, Genetic; Skin Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Hemic and Lymphatic Diseases; Pseudoxanthoma Elasticum; Arterial calcification of infancy; Hypophosphatemic Rickets, Autosomal Recessive, 1
• Other Study ID Numbers: INZ701-104

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No