The ENERGY 3 Study: Evaluation of Efficacy and Safety of INZ-701 in Children With ENPP1 Deficiency

NCT ID: NCT06046820

Last Updated: 2025-05-01

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-05
• Study Completion Date: 2026-02-28

Brief 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

INZ-701

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 and the Open-label Extension Period.

Group Type: EXPERIMENTAL

INZ-701

Intervention Type: DRUG

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)

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.

Group Type: ACTIVE_COMPARATOR

Control Arm (Conventional Therapy)

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

(rhENPP1-Fc).

Eligibility Criteria

Inclusion Criteria

1. Caregiver's written or electronic 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)

2. Study participant's assent in accordance with local regulations

3. 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

4. Males and females ≥1 year and <13 years of age at Study Day 1

5. Open growth plates of the distal femur and proximal tibia in both legs

6. Plasma PPi concentration of <1400 nM at Screening

7. 25-hydroxyvitamin D (25[OH]D) levels of ≥12 ng/mL at Screening

8. Radiographic evidence of skeletal abnormalities based on an RSS ≥2

9. Female participants of childbearing potential must have a negative serum pregnancy test at Screening and must not be breastfeeding

10. Study participants of childbearing potential who are sexually active must agree to use a highly effective form of contraception in accordance with Clinical Trials Facilitation and Coordination Group (CTFG) guidance and local guidelines for the duration of the study

11. In the opinion of the Investigator, able to complete all aspects of the study

Exclusion Criteria

1. 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

2. If receiving any of the following prohibited medications as indicated in the protocol: systemic corticosteroids (>5 mg prednisone equivalent per day), anti-fibroblast growth factor 23 (FGF23), and oral and/or IV bisphosphonates

3. 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

4. Planned orthopedic surgery that may confound the interpretation of study results during the 52-week Randomized Treatment Period

5. Known intolerance to INZ-701 or any of its excipients

6. A positive COVID-19 test within 5 days prior to Randomization, only if required as per local regulations or institutional policy

7. Previous treatment with INZ-701

8. 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 Randomization, whichever is longer, or use of an investigational device

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Inozyme Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kurt Gunter, MD

Role: STUDY_DIRECTOR

Inozyme Pharma, Inc.

Locations

Children's Hospital of Colorado

Aurora, Colorado, United States

Ann & Robert H. Lurie Children's Hospital

Chicago, Illinois, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

Queensland Children's Hospital

South Brisbane, , Australia

Centre Hospitalier Universitaire (CHU) Sainte-Justine

Montreal, , Canada

Hôpital Bicêtre, Service d'endocrinologie et diabète de l'enfant (Childhood Endocrinology and Diabetes Department)

Le Kremlin-Bicêtre, , France

King Faisal Specialist Hospital and Research Centre

Riyadh, , Saudi Arabia

Hospital San Joan de Deu

Barcelona, , Spain

Umraniye Training and Research Hospital

Istanbul, , Turkey (Türkiye)

Cukurova Universitesi Tip Fakultesi

Sarıçam, , Turkey (Türkiye)

Al Jalila Children's Specialty Hospital

Dubai, , United Arab Emirates

Royal Manchester Children's Hospital

Manchester, , United Kingdom

Countries

United States; Australia; Canada; France; Saudi Arabia; Spain; Turkey (Türkiye); United Arab Emirates; United Kingdom

Other Identifiers

INZ701-106

Identifier Type: -

Identifier Source: org_study_id