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

Generalized Arterial Calcification of Infancy Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05734196
• Other study ID #: INZ701-104
• Status: Recruiting
• Phase: Phase 1
• Start date: May 25, 2023
• Est. completion date: April 1, 2025

Study information

• Verified date: April 2024
• Source: Inozyme Pharma
• Contact: Inozyme Clinical Trial Information
• Phone: +1 857 330 4340
• Email: clinicaltrials[@]inozyme.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 8
• Est. completion date: April 1, 2025
• Est. primary completion date: March 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 1 Year

Eligibility

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

Related Conditions & MeSH terms

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

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.

Locations

Country	Name	City	State
United Kingdom	Royal Manchester Children's Hospital	Manchester
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	The University of Utah	Salt Lake City	Utah
United States	Rady Children's Hospital	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Inozyme Pharma

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)