The ENERGY Study: Evaluation of Safety and Tolerability of INZ-701 in Infants With ENPP1 Deficiency (ENERGY)

The ENERGY Study: An Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INZ-701 in Infant Subjects With Ectonucleotide Pyrophosphatase/ Phosphodiesterase 1 (ENPP1) Deficiency

The primary purpose of Study INZ701-104 (the ENERGY study) is to assess the safety and tolerability of INZ-701 in infants with ENPP1 Deficiency.

Study Overview

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

Detailed Description

INZ-701 is an ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) enzyme replacement therapy in development for the treatment of the ultra rare genetic disorder, ENPP1 Deficiency.

Study INZ701-104 (the ENERGY study) is a Phase 1b, open-label study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of INZ-701 in infant study participants with ENPP1 Deficiency.

The study will consist of up to a 60-day Screening Period, a 52-week Treatment Period during which study participants will receive INZ-701, an Extension Period during which study participants may continue to receive INZ-701, and an End of Treatment (EOT) visit 30 days after the last dose of INZ-701. Upon treatment discontinuation, study participants may continue to be followed for their ongoing disposition for survival outcome at least quarterly, if feasible through the end of the study. If the study site is not able to complete the survival outcome follow-up for up to 26 weeks post-treatment discontinuation, then the study participant can be considered "lost to follow up.

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Inozyme Clinical Trial Information; Phone Number: +1 857 330 4340; Email: clinicaltrials@inozyme.com

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123
      • Recruiting
      • Rady Children's Hospital
      • Contact: Nathaly Sweeney, MD; Phone Number: 858-966-5818; Email: nsweeney@rchsd.org
      • Contact: Sarah Lazar, MPH; Phone Number: 8585761700; Email: slazar@health.ucsd.edu
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
      • Contact: Alayna Dutcher; Phone Number: 617-355-0741; Email: Alayna.dutcher@childrens.harvard.edu
      • Contact: Andrea Hale, RN, MPH; Phone Number: 617-919-2867; Email: andrea.hale@childrens.harvard.edu
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Recruiting
      • Nationwide Children's Hospital
      • Contact: Bimal Chaudhari, MD; Phone Number: 614-722-3535; Email: bimal.chaudhari@nationwidechildrens.org
      • Contact: Marina Artemova, PhD; Phone Number: 614-722-2655; Email: marina.artemova@nationwidechildrens.org
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • The Children's Hospital of Philadelphia
      • Contact: Rachel Walega; Phone Number: 267-586-5969; Email: WALEGAR1@chop.edu
      • Contact: Maximilian Krumpholz; Phone Number: 267-432-0511; Email: krumpholm1@chop.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 1 year (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Caregiver(s) must provide written or electronic 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 must have a confirmed post-natal 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 local equivalent.
3. Study participant must be male or female from birth (newborn) to <1 year of age at Baseline (Day 1).
4. Study participant must weigh ≥ 0.5 kg at the time of the first dose of INZ-701
5. In the opinion of the Investigator, the subject must be able to complete all aspects of the study
6. Study participant's caregiver(s) must agree to provide access to their child's relevant medical records

Exclusion Criteria:

1. In the opinion of the Investigator, presence of any clinically significant disease or laboratory abnormality (outside of those considered associated with the diagnosis of ENPP1 Deficiency) that precludes study participation or may confound interpretation of study results, including known uncontrolled thyroid disease or unrelated connective tissue, bone, mineral, or muscle disease
2. Care has been withdrawn or subject is receiving end of life care or hospice only
3. Known malignancy
4. Known intolerance to INZ-701 or any of its excipients
5. Concurrent participation in another non-Inozyme interventional study and/or receipt of any other investigational new drug within 5 half-lives of the last dose of the other investigational product or from 4 weeks prior to the first dose of INZ-701, whichever is longer, or use of an investigational device, through completion of participation in the study

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; The first 2 study participants will receive a single 0.2 mg/kg dose of INZ-701 on Day 1. On Day 8, they will commence receiving Dose Level A (0.2 mg/kg twice weekly). After the second study participant completes Day 32, the DRC will perform a cumulative review of safety and PK/PD data and will make dosing recommendations, for example, modifying the dose of the ongoing study participants and/or changing the starting dose for future participants to Dose Levels B, C, D, E, or F. Each study participant's safety and PK/PD data will also be reviewed by the DRC during its quarterly review, based upon which the participant's dose may be modified to Dose Levels B, C, D, E, or F as specified in the protocol. Dose Level A: 0.2 mg/kg twice weekly Dose Level B: 0.6 mg/kg twice weekly Dose Level C: 0.2 mg/kg once weekly Dose Level D: 0.6 mg/kg once weekly Dose Level E: 1.8 mg/kg once weekly Dose Level F: 3.0 mg/kg once weekly

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
Number of Treatment Emergent Adverse Events (TEAEs)	Treatment-emergent AEs are defined as any AE occurring from the first dose of INZ-701 through 30 days after the last dose of INZ-701.	52 weeks (Treatment Period)
Incidence of Anti-Drug Antibodies (ADA)	For each participant, the presence of ADAs will be assessed and, if present, further evaluation will determine specificity and subtypes.	52 weeks (Treatment Period)
Left Ventricular Ejection Fraction	For each participant, an echocardiogram will be collected, and used to assess heart function. (Including measurement of left ventricular ejection fraction), and to identify any other abnormalities, for example, calcification of heart valves.	52 weeks (Treatment Period)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) Levels	For each participant, plasma PPi will be measured via a series of blood samples obtained throughout the study, comparing the participant's baseline value over time.	52 weeks (Treatment Period)
Area under the Plasma Concentration versus Time Curve (AUC) of INZ-701	For each participant, variation of concentration of INZ-701 in the plasma will be measured via a series of blood samples obtained throughout the study, comparing the participant's baseline value over time.	52 weeks (Treatment Period)
Maximum Plasma Concentration (Cmax) of INZ-701	For each participant, the maximum concentration of INZ-701 in the plasma will be measured via a series of blood samples obtained throughout the study, comparing the participant's baseline value over time.	52 weeks (Treatment Period)
ENPP1 Activity	For each participant, the activity of INZ-701 in the serum will be measured via a series of blood samples obtained throughout the study, comparing the participant's baseline value over time.	52 weeks (Treatment Period)

Collaborators and Investigators

• Sponsor: Inozyme Pharma
• Investigators: Study Director: Alex Lai, MD, Inozyme Pharma

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2023
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: January 26, 2023
• First Submitted That Met QC Criteria: February 15, 2023
• First Posted (Actual): February 17, 2023

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Generalized Arterial Calcification of Infancy; ENPP1; GACI; Autosomal Recessive Hypophosphatemic Rickets Type 2; ARHR2; hypopyrophosphatemia; ectonucleotide pyrophosphatase/phosphodiesterase1 deficiency
• 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: INZ701-104

Drug and device information, study documents

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