ENERGY 2: Evaluation of the Efficacy and Safety of INZ-701 in Infants With ENPP1 Deficiency

The ENERGY 2 Study: An Open-Label Phase 3 Study to Evaluate the Efficacy and Safety of INZ-701 in Infants With Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1) Deficiency

The primary purpose of ENERGY 2 (Study INZ701-105) is to assess the efficacy and safety of INZ-701 in infants with ENPP1 Deficiency.

Study Overview

• Status: Recruiting
• Conditions: Autosomal Recessive Hypophosphatemic Rickets; Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency; Generalized Arterial Calcification of Infancy 1
• Intervention / Treatment: Drug: INZ-701

Detailed Description

ENPP1 Deficiency is an ultra-rare genetic disorder in which inactivating mutations in the ENPP1 gene lead to a deficiency in the ENPP1 enzyme.

ENERGY 2 (Study INZ701-105) is a multicenter, single-arm, open-label Phase 3 study to assess the efficacy and safety of INZ-701 in infants with ENPP1 Deficiency.

The study will consist of a Screening Period of up to 60 days, a Treatment Period of 52 weeks, a 52-week Extension Period, and an End of Treatment (EOT) Visit 30 days after the last dose of INZ-701.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 3

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

• Brazil
  • Rio de Janeiro, Brazil, 20551-030
    • Recruiting
    • Hospital Universitario Pedro Ernesto/Rio de Janeiro
• France
  • Paris, France, 75015
    • Recruiting
    • Hopital Necker - Enfants Malades
• Hungary
  • Debrecen, Hungary
    • Recruiting
    • Gyermekgyogyaszat, DE
• Italy
  • Florence, Italy, 50139
    • Recruiting
    • Azienda Ospedaliera Universitaria Meyer
• Saudi Arabia
  • Riyadh, Saudi Arabia, 12713
    • Recruiting
    • King Faisal Specialist Hospital and Research Center
• Spain
  • Esplugues de Llobregat
    • Barcelona, Esplugues de Llobregat, Spain, 08950
      • Recruiting
      • Hospital Sant Joan de Deu Edificio Consultas Externas. Unitat de Recerca
• Turkey (Türkiye)
  • Istanbul, Turkey (Türkiye)
    • Recruiting
    • Umraniye Traiing and Research Hospital
• United Kingdom
  • Manchester, United Kingdom, M13 9WL
    • Recruiting
    • Royal Manchester Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Participants must meet all of the following:

Inclusion Criteria:

1. Infant aged ≤ 1 year at the time of enrollment.
2. Confirmed diagnosis of ENPP1 deficiency, based on genetic testing.
3. Clinical features consistent with generalized arterial calcification of infancy (GACI) (e.g., vascular calcification or cardiac involvement).
4. Medically stable to participate in a 52-week treatment study.
5. Written informed consent provided by a parent or legal guardian.

Exclusion Criteria

Participants will not be eligible if any of the following apply:

1. Receiving end-of-life or hospice care.
2. Prior treatment with INZ-701, unless received through an approved expanded access program.
3. Concurrent participation in another interventional clinical trial.
4. Planned major surgery during the study period that would interfere with 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; Participants receive INZ-701 (rhENPP1-Fc) administered by subcutaneous injection once weekly at the protocol-specified dose. The visit final volume to administer (mL) is determined using protocol-defined parameters.	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
To determine if INZ-701 increases inorganic pyrophosphate (PPi) levels	For each subject, their change from baseline in Plasma Inorganic Pyrophosphate (PPi) concentration will be assessed.	52 weeks (Baseline through Week 52)
To determine if INZ-701 increases overall survival	For each subject, their change in overall survival based on time from date of birth to event of all-cause mortality will be assessed.	52 weeks (Baseline through Week 52)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine if INZ-701 prevents decline in cardiac ejection fraction	For each subject, their change from baseline in left ventricular ejection fraction will be assessed via echocardiography.	52 weeks (Baseline through Week 52)
To determine if INZ-701 prevents heart failure	For each subject, their incidence of heart failure will be assessed.	52 weeks (Baseline through Week 52)
To determine if INZ-701 attenuates progression of arterial calcification	For each subject, their change from baseline in vascular calcification in the coronary arteries and aorta will be examined via CT scan.	52 weeks (Baseline through Week 52)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2025
• Primary Completion (Estimated): September 11, 2028
• Study Completion (Estimated): November 7, 2028

Study Registration Dates

• First Submitted: March 11, 2026
• First Submitted That Met QC Criteria: March 11, 2026
• First Posted (Actual): March 16, 2026

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Generalized Arterial Calcification of Infancy; GACI; Autosomal Recessive Hypophosphatemic Rickets Type 2; ARHR2
• Additional Relevant MeSH Terms: Arterial calcification of infancy; Hypophosphatemic Rickets, Autosomal Recessive, 1
• Other Study ID Numbers: INZ701-105

Drug and device information, study documents

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