ATP-Binding Cassette Subfamily C Member 6 Deficiency, Autosomal Recessive Hypophosphatemic Rickets, Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency, Generalized Arterial Calcification of Infancy, Pseudoxanthoma Elasticum
Conditions
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
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.
Interventions
DRUGINZ-701
Recombinant fusion protein that contains the extracellular domains of human ENPP1 coupled with an Fc fragment from an immunoglobulin gamma-1 (IgG1) antibody.
Sponsors
Inozyme Pharma
BioMarin Pharmaceutical
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
No minimum to 1 Years
Healthy volunteers
No
Inclusion criteria
1. Infant aged ≤ 1 year at the time of enrollment 2. Study participant must have a confirmed post-natal molecular genetic diagnosis of ENPP1 Deficiency or ABCC6 Deficiency 3. Study participants must have clinical manifestations of generalized arterial calcification of infancy (GACI) or GACI-2, which must include at least one of the following: ectopic calcification, heart failure, respiratory distress, edema, cyanosis, hypertension, and cardiomegaly. 4. Study participant must weigh ≥0.5 kg at the time of the first dose of INZ-701 in this study 5. Written informed consent provided by a parent or legal guardian
Exclusion criteria
1. In the opinion of the Investigator, presence of any clinically significant disease or laboratory abnormality that precludes study participation or may confound interpretation of study result 2. Receiving end of life or hospice care 3. Known malignancy 4. Concurrent participation in another non-Inozyme interventional study 5. Treatment with any non-Inozyme product or investigational device during study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment Emergent Adverse Events (TEAEs) | 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) | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) Levels | 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 | 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 | 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 | 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. |
Countries
Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director, MD, MD
BioMarin Pharmaceutical
Outcome results
None listed