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

NCT05734196 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: INZ701-104
• Study Type: interventional
• Target: 16
• Locations: 3 countries
• Sites: 7

Brief Summary

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.

Conditions

Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency; Autosomal Recessive Hypophosphatemic Rickets; Generalized Arterial Calcification of Infancy; ATP-Binding Cassette Subfamily C Member 6 Deficiency; Pseudoxanthoma Elasticum

Keywords

ectonucleotide pyrophosphatase/phosphodiesterase1 deficiency; hypopyrophosphatemia; ENPP1; Generalized Arterial Calcification of Infancy; GACI; Autosomal Recessive Hypophosphatemic Rickets Type 2; ARHR2; ATP-Binding Cassette Subfamily C Member 6 Deficiency; ABCC6; Pseudoxanthoma elasticum; PXE

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (4)

• Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) Levels

  52 weeks (Treatment Period)

• Area under the Plasma Concentration versus Time Curve (AUC) of INZ-701

  52 weeks (Treatment Period)

• Maximum Plasma Concentration (Cmax) of INZ-701

  52 weeks (Treatment Period)

• ENPP1 Activity

  52 weeks (Treatment Period)

Study Arms (1)

INZ-701

EXPERIMENTAL

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

Interventions

INZ-701 DRUG

Recombinant fusion protein that contains the extracellular domains of human ENPP1 coupled with an Fc fragment from an immunoglobulin gamma-1 (IgG1) antibody.

Also known as: (rhENPP1-Fc).

INZ-701

Eligibility Criteria

• Age: Up to 1 Year
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Infant aged ≤ 1 year at the time of enrollment
• Study participant must have a confirmed post-natal molecular genetic diagnosis of ENPP1 Deficiency or ABCC6 Deficiency
• 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.
• Study participant must weigh ≥0.5 kg at the time of the first dose of INZ-701 in this study
• Written informed consent provided by a parent or legal guardian

You may not qualify if:

• 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
• Receiving end of life or hospice care
• Known malignancy
• Concurrent participation in another non-Inozyme interventional study
• Treatment with any non-Inozyme product or investigational device during study participation

Sponsors & Collaborators

• Inozyme Pharma: lead
• BioMarin Pharmaceutical: collaborator

Study Sites (7)

Rady Children's Hospital

San Diego, California, 92123, United States

RECRUITING

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

WITHDRAWN

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

The University of Utah

Salt Lake City, Utah, 84108, United States

WITHDRAWN

Hospital Sant Joan de Déu

Barcelona, Spain

TERMINATED

Royal Manchester Children's Hospital

Manchester, M13 9WL, United Kingdom

TERMINATED

MeSH Terms

Conditions

Hypophosphatemic Rickets, Autosomal Recessive, 1; Arterial calcification of infancy; Pseudoxanthoma Elasticum

Condition Hierarchy (Ancestors)

Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Medical Director, MD, MD

  BioMarin Pharmaceutical

  STUDY DIRECTOR

Central Study Contacts

Trial Specialist

CONTACT

+1 800-983-4587; medinfo@bmrn.com

Medical Director, MD

CONTACT

+1 800-983-4587; medinfo@bmrn.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Study INZ701-104 is a Phase 1b, open-label study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of INZ-701 in infant study participants with ENPP1 Deficiency or with ABCC6 Deficiency.

Study Record Dates

• First Submitted: January 26, 2023
• First Posted: February 17, 2023
• Study Start: June 25, 2023
• Primary Completion (Estimated): November 11, 2027
• Study Completion (Estimated): November 11, 2027
• Last Updated: March 24, 2026

Record last verified: 2026-03

Locations

GB (1); US (5); ES (1)