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

NCT06046820 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: INZ701-106
• Study Type: interventional
• Target: 27
• Locations: 8 countries
• Sites: 11

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.

Conditions

Autosomal Recessive Hypophosphatemic Rickets; Generalized Arterial Calcification of Infancy; Ectonucleotide Pyrophosphatase/Phosphodiesterase1 Deficiency

Keywords

Ectonucleotide Pyrophosphatase/Phosphodiesterase1 Deficiency; Hypopyrophosphatemia; ENPP1; Autosomal Recessive Hypophosphatemic Rickets Type 2; ARHR2; Generalized Arterial Calcification of Infancy; GACI

Outcome Measures

Primary Outcomes (2)

• Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) concentration through Week 52

  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 (Baseline through Week 52)

• Change from Baseline in skeletal abnormalities as measured by the Radiographic Global Impression of Change (RGI-C) global score through Week 52

  The RGI-C is an overall radiographic score which can be used to monitor response to a therapeutic intervention comparing scores from 2 time points. A determination of healing on a scale of 0 to +3 with 0 being no change or healing and +3 being complete healing; worsening is also measured on a scale of 0 to -3 with 0 being no change and -3 being severe worsening.

  52 weeks (Baseline through Week 52)

Secondary Outcomes (5)

• Change from Baseline in rickets as measured by Rickets Severity Score (RSS) total score through Week 52

  Baseline, Week 26, Week 52

• Change from Baseline in growth Z-score (height/body length and weight) through Week 52

  Baseline, Day 29, Week 8, Week 13, Week 26, Week 39, Week 52

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

  52 weeks (Randomized Treatment Period)

• Maximum Plasma Concentration (Cmax) of INZ-701

  52 weeks (Randomized Treatment Period)

• Change from Baseline in ENPP1 activity (µM/min) through week 52

  52 weeks (Randomized Treatment Period)

Study Arms (2)

INZ-701

EXPERIMENTAL

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 (RTP). RTP will be followed by a Low-dose Open-label Extension Period during which all study participants will receive INZ-701 at a dose of 2.4 mg/kg QW while the primary analysis is pending. If dose escalation criteria are met, all participants will transition to the Randomized Extension Period (REP) where participants who were originally randomized to INZ-701 during RTP will transition to a higher dose regimen of INZ-701 at 1.8 mg/kg twice weekly. Participants who were originally randomized to the active control arm during RTP will continue receiving INZ-701 at 2.4 mg/kg QW in the REP.

Drug: INZ-701

Control Arm (Conventional Therapy)

ACTIVE COMPARATOR

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.

Drug: Control Arm (Conventional Therapy)

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

Control Arm (Conventional Therapy) 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.

Control Arm (Conventional Therapy)

Eligibility Criteria

• Age: 1 Year - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Caregiver's written 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)
• Study participant's assent in accordance with local regulations
• 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
• Males and females ≥1 year and \<13 years of age at Study Day 1
• Open growth plates of the distal femur and proximal tibia in both legs
• Plasma PPi concentration of \<1400 nM at Screening
• (OH)D levels of ≥12 ng/mL at Screening
• Radiographic evidence of skeletal abnormalities based on an RSS ≥2
• Women of childbearing potential (WOCBP, as defined in Clinical Trials Coordination Group \[CTCG 2024\]) must have a negative serum pregnancy test at Screening and must not be breastfeeding
• Males who are sexually active must agree to use condoms from the period following first dose of INZ-701 through 30 days after the last dose of INZ-701
• WOCBP and partners of fertile males who are WOCBP must be using or must agree to use a highly effective form of (as per CTCG) from at least 1 month before the first dose of INZ-701 through 30 days after the last dose of INZ-701 (greater than 5 half-lives of INZ-701)
• In the opinion of the Investigator, able to complete all aspects of the study

You may not qualify if:

• 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
• If receiving any of the following prohibited medications as indicated in the protocol: systemic corticosteroids (\>5 mg prednisone equivalent per day), anti-FGF23 and oral and/or IV bisphosphonates
• 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
• Planned orthopedic surgery or other procedures that may confound the interpretation of study results during the 52-week RTP
• Known intolerance to INZ-701 or any of its excipients
• A positive COVID-19 test within 5 days prior to Randomization, only if required as per local regulations or institutional policy
• Previous treatment with INZ-701
• 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 the first dose of INZ-701, whichever is longer, or use of an investigational device

Sponsors & Collaborators

• BioMarin Pharmaceutical: collaborator
• Inozyme Pharma: lead

Study Sites (11)

Ann & Robert H. Lurie Children's Hospital

Chicago, Illinois, 60611, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Queensland Children's Hospital

South Brisbane, 4101, Australia

Location

Centre Hospitalier Universitaire (CHU) Sainte-Justine

Montreal, H3T 1C5, Canada

Location

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

Le Kremlin-Bicêtre, 94270, France

Location

King Faisal Specialist Hospital and Research Centre

Riyadh, 12713, Saudi Arabia

Location

Umraniye Training and Research Hospital

Istanbul, 34764, Turkey (Türkiye)

Location

Cukurova Universitesi Tip Fakultesi

Sarıçam, 01330, Turkey (Türkiye)

Location

Al Jalila Children's Specialty Hospital

Dubai, 30726, United Arab Emirates

Location

Royal Manchester Children's Hospital

Manchester, M13 9WL, United Kingdom

Location

MeSH Terms

Conditions

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Study INZ701-106 (ENERGY 3) is a multicenter, 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.

Study Record Dates

• First Submitted: August 28, 2023
• First Posted: September 21, 2023
• Study Start: November 5, 2023
• Primary Completion: January 29, 2026
• Study Completion: August 19, 2026
• Last Updated: October 1, 2026

Record last verified: 2026-09

Locations

TU (2); FR (1); CA (1); GB (1); AE (1); AU (1); US (3); SA (1)