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

Phase 3

Recruiting

• Conditions: Ectonucleotide Pyrophosphatase/Phosphodiesterase1 Deficiency; Generalized Arterial Calcification of Infancy; Autosomal Recessive Hypophosphatemic Rickets
• Interventions: Drug: Control Arm (Conventional Therapy); Drug: INZ-701

• Registration Number: NCT06046820
• Lead Sponsor: Inozyme Pharma

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.

Study Timeline

• Study First Submitted: 2023-08-28
• Study First Submitted QC: 2023-09-18
• Study First Posted: 2023-09-21
• Study Start: 2023-11-05
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-24
• Last Update Posted: 2024-06-26
• Primary Completion: 2025-05
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 33

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control Arm (Conventional Therapy)	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.
INZ-701	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.

Primary Outcome Measures

Name	Time	Method
Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) concentration through Week 52	52 weeks (Baseline 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.

Secondary Outcome Measures

Name	Time	Method
Maximum Plasma Concentration (Cmax) of INZ-701	52 weeks (Randomized Treatment Period)	For each subject, the maximum concentration of INZ-701 in the plasma will be measured via a series of blood samples obtained throughout the study, comparing the subject's baseline value over time.
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	A Z-score represents the degree to which that particular measurement for that individual differs from the reference value in the general population.; (height/body length and weight) through Week 52
Change from Baseline in ENPP1 activity (µM/min) through week 52	52 weeks (Randomized Treatment Period)	For each subject, the activity of INZ-701 (µM/min) in the serum will be assessed through hydrolysis of a substrate to the enzyme, via a series of blood samples obtained throughout the study, comparing the subject's baseline value over time.
Change from Baseline in skeletal abnormalities as measured by the Radiographic Global Impression of Change (RGI-C) global score through Week 52	Baseline, Week 26, 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.
Area under the Plasma Concentration versus Time Curve (AUC) of INZ-701	52 weeks (Randomized Treatment Period)	For each subject, variation of concentration of INZ-701 in the plasma will be measured via a series of blood samples obtained throughout the study, comparing the subject's baseline value over time.
Change from Baseline in rickets as measured by Rickets Severity Score (RSS) total score through Week 52	Baseline, Week 26, Week 52	The RSS assesses rickets severity by utilizing a scoring system that uses a scale from 0 to 4 for the wrists and 0 to 6 for the knees, to generate a total score of 0 to 10, where 0 is normal and 10 is the worst score possible ie, most severe skeletal abnormalities observed radiographically.

Trial Locations

Locations (11)

Cook Children's Medical Center; 🇺🇸 Fort Worth, Texas, United States

Centre Hospitalier Universitaire (CHU) Sainte-Justine; 🇨🇦 Montréal, Canada

Hôpital Bicêtre, Service d'endocrinologie et diabète de l'enfant (Childhood Endocrinology and Diabetes Department); 🇫🇷 Le Kremlin-Bicêtre, France

Hospital San Joan de Deu; 🇪🇸 Barcelona, Spain

Royal Manchester Children's Hospital; 🇬🇧 Manchester, United Kingdom

Umraniye Training and Research Hospital; 🇹🇷 Istanbul, Turkey

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

Al Jalila Children's Specialty Hospital; 🇦🇪 Dubai, United Arab Emirates