- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06046820
The ENERGY 3 Study: Evaluation of Efficacy and Safety of INZ-701 in Children With ENPP1 Deficiency
The ENERGY 3 Study: A Randomized, Controlled, Open-Label, Phase 3 Study to Evaluate the Efficacy and Safety of INZ-701 in Children With Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1) Deficiency
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Inozyme Clinical Trial Information
- Phone Number: +1 857 330 4340
- Email: clinicaltrials@inozyme.com
Study Locations
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Montréal, Canada, H3T 1C5
- Recruiting
- Centre Hospitalier Universitaire (CHU) Sainte-Justine
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Contact:
- Nathalie Alos, MD
- Email: nathalie.alos.med@ssss.gouv.qc.ca
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Contact:
- Michna Alphonse, MSc
- Phone Number: 514-345-4931
- Email: kenny-michna.alphonse.hsj@ssss.gouv.qc.ca
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Manchester, United Kingdom, M13 9WL
- Recruiting
- Royal Manchester Children's Hospital
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Contact:
- Amish Chinoy, MD
- Phone Number: 0161 701 7901
- Email: amish.chinoy@mft.nhs.uk
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Illinois
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Chicago, Illinois, United States, 60611
- Recruiting
- Ann & Robert H. Lurie Children's Hospital
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Contact:
- Jennifer Miller, MD
- Phone Number: 312-227-6090
- Email: JLMiller@luriechildrens.org
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Contact:
- Sarayu Ratnam, PhD
- Phone Number: 312-227-6617
- Email: SRatnam@luriechildrens.org
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Recruiting
- The Children's Hospital of Philadelphia
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Contact:
- Rachel Walega
- Phone Number: 267-586-5969
- Email: WALEGAR1@chop.edu
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Contact:
- Maximilian Krumpholz
- Phone Number: 267-432-0511
- Email: krumpholm1@chop.edu
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Texas
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Fort Worth, Texas, United States, 76104
- Recruiting
- Cook Children's Medical Center
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Contact:
- Joel Steelman, MD
- Phone Number: 682-885-7960
- Email: joel.steelman@cookchildrens.org
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Contact:
- Tiffany Skrodzki, RN
- Phone Number: 682-885-7960
- Email: Tiffany.skrodzki@cookchildrens.org
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
Accepts Healthy Volunteers
Description
Inclusion Criteria
Study participants must meet all of the following inclusion criteria:
- 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)
- 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
- 25-hydroxyvitamin D (25[OH]D) levels of ≥12 ng/mL at Screening
- Radiographic evidence of skeletal abnormalities based on an RSS ≥2
- Female participants of childbearing potential must have a negative serum pregnancy test at Screening and must not be breastfeeding
- 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
- In the opinion of the Investigator, able to complete all aspects of the study
Exclusion Criteria
Study participants meeting any of the following exclusion criteria will not be eligible to participate in the study:
- 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-fibroblast growth factor 23 (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 that may confound the interpretation of study results during the 52-week Randomized Treatment Period
- 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 Randomization, whichever is longer, or use of an investigational device
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: 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.
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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:
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Active Comparator: 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.
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) concentration through Week 52
Time Frame: 52 weeks (Baseline through Week 52)
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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.
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52 weeks (Baseline through Week 52)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change from Baseline in skeletal abnormalities as measured by the Radiographic Global Impression of Change (RGI-C) global score through Week 52
Time Frame: Baseline, Week 26, Week 52
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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.
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Baseline, Week 26, Week 52
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Change from Baseline in rickets as measured by Rickets Severity Score (RSS) total score through Week 52
Time Frame: Baseline, Week 26, Week 52
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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.
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Baseline, Week 26, Week 52
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Change from Baseline in growth Z-score (height/body length and weight) through Week 52
Time Frame: Baseline, Day 29, Week 8, Week 13, Week 26, Week 39, Week 52
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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 |
Baseline, Day 29, Week 8, Week 13, Week 26, Week 39, Week 52
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Area under the Plasma Concentration versus Time Curve (AUC) of INZ-701
Time Frame: 52 weeks (Randomized Treatment Period)
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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.
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52 weeks (Randomized Treatment Period)
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Maximum Plasma Concentration (Cmax) of INZ-701
Time Frame: 52 weeks (Randomized Treatment Period)
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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.
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52 weeks (Randomized Treatment Period)
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Change from Baseline in ENPP1 activity (µM/min) through week 52
Time Frame: 52 weeks (Randomized Treatment Period)
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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.
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52 weeks (Randomized Treatment Period)
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Alex Lai, MD, Inozyme Pharma, Inc.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Metabolic Diseases
- Kidney Diseases
- Urologic Diseases
- Nutrition Disorders
- Genetic Diseases, Inborn
- Musculoskeletal Diseases
- Avitaminosis
- Deficiency Diseases
- Malnutrition
- Bone Diseases
- Metabolism, Inborn Errors
- Bone Diseases, Metabolic
- Renal Tubular Transport, Inborn Errors
- Calcium Metabolism Disorders
- Metal Metabolism, Inborn Errors
- Phosphorus Metabolism Disorders
- Vitamin D Deficiency
- Hypophosphatemia, Familial
- Hypophosphatemia
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Rickets
- Familial Hypophosphatemic Rickets
- Rickets, Hypophosphatemic
- Calcinosis
- Vascular Calcification
Other Study ID Numbers
- INZ701-106
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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