Clinical trial NCT05734196: The ENERGY Study: Evaluation of Safety and Tolerability of INZ-701 in Infants With ENPP1 Deficiency or ABCC6 Deficiency
Official title: The ENERGY Study: An Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INZ-701 in Infants With Ectonucleotide Pyrophosphatase/ Phosphodiesterase 1 (ENPP1) Deficiency or ATP-binding Cassette Sub-family C Member 6 (ABCC6) Deficiency
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency
Autosomal Recessive Hypophosphatemic Rickets
Generalized Arterial Calcification of Infancy
ATP-Binding Cassette Subfamily C Member 6 Deficiency
Pseudoxanthoma Elasticum
Keywords: ectonucleotide pyrophosphatase/phosphodiesterase1 deficiency
hypopyrophosphatemia
ENPP1
Generalized Arterial Calcification of Infancy
GACI
Autosomal Recessive Hypophosphatemic Rickets Type 2
ARHR2
ATP-Binding Cassette Subfamily C Member 6 Deficiency
ABCC6
Pseudoxanthoma elasticum
PXE
Lead sponsor: Inozyme Pharma
Sponsor class: INDUSTRY
First posted: 2023-02-17
Enrollment: 16
Sex: ALL
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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 or with ABCC6 Deficiency.
Primary purpose: TREATMENT

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 or with ABCC6 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 or with ABCC6 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 or ABCC6 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 participants may continue to receive INZ-701 until it is commercially available in the country where the participant resides, or until an alternative study of INZ-701 is available, and an End of Treatment (EOT) visit 30 days after the last dose of INZ-701. Upon treatment discontinuation, participants will continue to be followed for their ongoing disposition for survival outcome at least quarterly through the end of the study.

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 Council for Harmonisation (ICH) Good Clinical Practice (GCP)
2. Study participant must have a confirmed post-natal molecular genetic diagnosis of ENPP1 Deficiency or ABCC6 Deficiency with biallelic mutations (ie, homozygous or compound heterozygous) performed by a College of American Pathologists/Clinical Laboratory Improvement Amendments (CAP/CLIA) certified laboratory
3. Study participants must have clinical manifestations of GACI or GACI-2, which may include, but are not limited to, pathologic ectopic calcification, heart failure, respiratory distress, edema, cyanosis, hypertension, and cardiomegaly
4. Study participant must be male or female from birth to \<1 year of age at Baseline (Day 1)
5. Study participant must weigh ≥0.5 kg at the time of the first dose of INZ-701 in this study
6. In the opinion of the Investigator, the study participant must be able to complete all aspects of the study
7. 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 or ABCC6 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 study participant 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
6. Receipt of any non-Inozyme investigational new drug within 5 half-lives of the last dose of the other investigational product or within 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

Primary outcomes:
measure: Number of Treatment Emergent Adverse Events (TEAEs)
timeFrame: 52 weeks (Treatment Period)
measure: Incidence of Anti-Drug Antibodies (ADA)
timeFrame: 52 weeks (Treatment Period)
measure: Left Ventricular Ejection Fraction
timeFrame: 52 weeks (Treatment Period)
Secondary outcomes:
measure: Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) Levels
timeFrame: 52 weeks (Treatment Period)
measure: Area under the Plasma Concentration versus Time Curve (AUC) of INZ-701
timeFrame: 52 weeks (Treatment Period)
measure: Maximum Plasma Concentration (Cmax) of INZ-701
timeFrame: 52 weeks (Treatment Period)
measure: ENPP1 Activity
timeFrame: 52 weeks (Treatment Period)
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Rady Children's Hospital
state: California
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Salt Lake City
country: United States
facility: The University of Utah
state: Utah
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Déu
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
Study officials:
affiliation: Inozyme Pharma
name: Alex Lai, MD
role: STUDY_DIRECTOR
References: