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

Primary Purpose

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

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
INZ-701
Sponsored by
Inozyme Pharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency focused on measuring ectonucleotide pyrophosphatase/phosphodiesterase1 deficiency, hypopyrophosphatemia, ENPP1, Generalized Arterial Calcification of Infancy, GACI, Autosomal Recessive Hypophosphatemic Rickets Type 2, ARHR2

Eligibility Criteria

1 Month - 1 Year (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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). Subject must have a post-natal confirmed 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 equivalent. Subject must be male or female ages ≥ 1 month to <1 year of age at Baseline Subject must weigh ≥ 0.5 kg at the time of the first dose of INZ-701 In the opinion of the Investigator, the subject must be able to complete all aspects of the study Subject's caregiver(s) must agree to provide access to their child's relevant medical records Exclusion Criteria: 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known uncontrolled thyroid disease or unrelated connective tissue, bone, mineral, or muscle disease Care has been withdrawn or subject is receiving end of life care or hospice only Known malignancy Known intolerance to INZ-701 or any of its excipients Concurrent participation in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

Sites / Locations

  • Boston Children's Hospital
  • The Children's Hospital of PhiladelphiaRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

INZ-701

Arm Description

The first two infant subjects will receive a single dose of 0.2 mg/kg on Day 1 and start at Dose Level A (0.2 mg/kg twice weekly) on Day 8. After the second subject completes Day 32, the Data Review Committee (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 subjects and/or changing the starting dose for future subjects to Dose Levels B, C, or D. Each subject's safety and PK/PD data will also be reviewed by the DRC during its quarterly review, based upon which, the subject's dose may be modified to Dose Levels B, C, or D, 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

Outcomes

Primary Outcome Measures

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.
Incidence of Anti-Drug Antibodies (ADA)
For each subject, the presence of ADAs will be assessed and, if present, further evaluation will determine specificity and subtypes.
Left Ventricular Ejection Fraction
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.

Secondary Outcome Measures

Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) Levels
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
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
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
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.

Full Information

First Posted
January 26, 2023
Last Updated
September 26, 2023
Sponsor
Inozyme Pharma
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1. Study Identification

Unique Protocol Identification Number
NCT05734196
Brief Title
The ENERGY Study: Evaluation of Safety and Tolerability of INZ-701 in Infants With ENPP1 Deficiency
Acronym
ENERGY
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 25, 2023 (Actual)
Primary Completion Date
March 1, 2025 (Anticipated)
Study Completion Date
April 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Inozyme Pharma

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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 subjects with ENPP1 Deficiency. The study will consist of up to a 60-day Screening Period, a 52-week Treatment Period during which subjects will receive INZ-701, an Extension Period during which subjects 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, they will continue to be followed for their ongoing disposition for survival outcome at least quarterly, if feasible, through the end of the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency, Autosomal Recessive Hypophosphatemic Rickets, Generalized Arterial Calcification of Infancy
Keywords
ectonucleotide pyrophosphatase/phosphodiesterase1 deficiency, hypopyrophosphatemia, ENPP1, Generalized Arterial Calcification of Infancy, GACI, Autosomal Recessive Hypophosphatemic Rickets Type 2, ARHR2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
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 subjects with ENPP1 Deficiency.
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
INZ-701
Arm Type
Experimental
Arm Description
The first two infant subjects will receive a single dose of 0.2 mg/kg on Day 1 and start at Dose Level A (0.2 mg/kg twice weekly) on Day 8. After the second subject completes Day 32, the Data Review Committee (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 subjects and/or changing the starting dose for future subjects to Dose Levels B, C, or D. Each subject's safety and PK/PD data will also be reviewed by the DRC during its quarterly review, based upon which, the subject's dose may be modified to Dose Levels B, C, or D, 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
Intervention Type
Drug
Intervention Name(s)
INZ-701
Other Intervention Name(s)
(rhENPP1-Fc).
Intervention Description
Recombinant fusion protein that contains the extracellular domains of human ENPP1 coupled with an Fc fragment from an immunoglobulin gamma-1 (IgG1) antibody.
Primary Outcome Measure Information:
Title
Number of Treatment Emergent Adverse Events (TEAEs)
Description
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.
Time Frame
52 weeks (Treatment Period)
Title
Incidence of Anti-Drug Antibodies (ADA)
Description
For each subject, the presence of ADAs will be assessed and, if present, further evaluation will determine specificity and subtypes.
Time Frame
52 weeks (Treatment Period)
Title
Left Ventricular Ejection Fraction
Description
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.
Time Frame
52 weeks (Treatment Period)
Secondary Outcome Measure Information:
Title
Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) Levels
Description
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.
Time Frame
52 weeks (Treatment Period)
Title
Area under the Plasma Concentration versus Time Curve (AUC) of INZ-701
Description
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.
Time Frame
52 weeks (Treatment Period)
Title
Maximum Plasma Concentration (Cmax) of INZ-701
Description
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.
Time Frame
52 weeks (Treatment Period)
Title
ENPP1 Activity
Description
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.
Time Frame
52 weeks (Treatment Period)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
1 Year
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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). Subject must have a post-natal confirmed 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 equivalent. Subject must be male or female ages ≥ 1 month to <1 year of age at Baseline Subject must weigh ≥ 0.5 kg at the time of the first dose of INZ-701 In the opinion of the Investigator, the subject must be able to complete all aspects of the study Subject's caregiver(s) must agree to provide access to their child's relevant medical records Exclusion Criteria: 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 Care has been withdrawn or subject is receiving end of life care or hospice only Known malignancy Known intolerance to INZ-701 or any of its excipients 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Inozyme Clinical Trial Information
Phone
+1 857 330 4340
Email
clinicaltrials@inozyme.com
Facility Information:
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alayna Dutcher
Phone
617-355-0741
Email
Alayna.dutcher@childrens.harvard.edu
First Name & Middle Initial & Last Name & Degree
Andrea Hale, RN, MHP
Phone
617-919-2867
Email
andrea.hale@childrens.harvard.edu
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maximilian Krumpholz
Phone
267-432-0511
Email
krumpholm1@chop.edu
First Name & Middle Initial & Last Name & Degree
Rachel Walega
Phone
267-586-5969
Email
WALEGAR1@chop.edu

12. IPD Sharing Statement

Learn more about this trial

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

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