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

• ClinicalTrials.gov Identifier: NCT05734196
• Recruitment Status: Recruiting
• First Posted: February 17, 2023
• Last Update Posted: April 22, 2024
• Sponsor: Inozyme Pharma
• Information provided by (Responsible Party): Inozyme Pharma

Tracking Information

• First Submitted Date: January 26, 2023
• First Posted Date: February 17, 2023
• Last Update Posted Date: April 22, 2024
• Actual Study Start Date: May 25, 2023
• Estimated Primary Completion Date: March 1, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 5, 2024)

• Number of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 52 weeks (Treatment Period) ]
  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.
• Incidence of Anti-Drug Antibodies (ADA) [ Time Frame: 52 weeks (Treatment Period) ]
  For each participant, the presence of ADAs will be assessed and, if present, further evaluation will determine specificity and subtypes.
• Left Ventricular Ejection Fraction [ Time Frame: 52 weeks (Treatment Period) ]
  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.

Original Primary Outcome Measures (submitted: February 15, 2023)

• Number of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 52 weeks (Treatment Period) ]
  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.
• Incidence of Anti-Drug Antibodies (ADA) [ Time Frame: 52 weeks (Treatment Period) ]
  For each subject, the presence of ADAs will be assessed and, if present, further evaluation will determine specificity and subtypes.
• Left Ventricular Ejection Fraction [ Time Frame: 52 weeks (Treatment Period) ]
  For each subject, 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.

Current Secondary Outcome Measures (submitted: March 5, 2024)

• Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) Levels [ Time Frame: 52 weeks (Treatment Period) ]
  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.
• Area under the Plasma Concentration versus Time Curve (AUC) of INZ-701 [ Time Frame: 52 weeks (Treatment Period) ]
  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.
• Maximum Plasma Concentration (Cmax) of INZ-701 [ Time Frame: 52 weeks (Treatment Period) ]
  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.
• ENPP1 Activity [ Time Frame: 52 weeks (Treatment Period) ]
  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.

Original Secondary Outcome Measures (submitted: February 15, 2023)

• Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) Levels [ Time Frame: 52 weeks (Treatment Period) ]
  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.
• Area under the Plasma Concentration versus Time Curve (AUC) of INZ-701 [ Time Frame: 52 weeks (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.
• Maximum Plasma Concentration (Cmax) of INZ-701 [ Time Frame: 52 weeks (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.
• ENPP1 Activity [ Time Frame: 52 weeks (Treatment Period) ]
  For each subject, the activity of INZ-701 in the serum will be measured via a series of blood samples obtained throughout the study, comparing the subject's baseline value over time. efficacy of INZ701 treatment.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The ENERGY Study: Evaluation of Safety and Tolerability of INZ-701 in Infants With ENPP1 Deficiency
• Official Title: 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
• Brief Summary: 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.

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
• Study Phase: Phase 1

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

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

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency
• Autosomal Recessive Hypophosphatemic Rickets
• Generalized Arterial Calcification of Infancy

Intervention

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 Name: (rhENPP1-Fc).

Study Arms

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

Intervention: Drug: INZ-701

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 15, 2023): 8
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 1, 2025
• Estimated Primary Completion Date: March 1, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 1 Year (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Inozyme Clinical Trial Information; +1 857 330 4340; clinicaltrials@inozyme.com

• Listed Location Countries: United Kingdom, United States

Administrative Information

• NCT Number: NCT05734196
• Other Study ID Numbers: INZ701-104
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Inozyme Pharma
• Original Responsible Party: Same as current
• Current Study Sponsor: Inozyme Pharma
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Alex Lai, MD; Inozyme Pharma

• PRS Account: Inozyme Pharma
• Verification Date: April 2024