Treatment of patients with ABCC6 Deficiency Manifesting as Pseudoxanthoma elasticum (PXE) MedDRA version: 20.0 Level: PT Classification code 10037150 Term: Pseudoxanthoma elasticum System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: INZ-701
Product Code: INZ-701
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: RECOMBINANT HUMAN ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE 1 FUSED
Sponsors
Inozyme Pharma, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Must provide written or electronic consent after the nature of the study has been explained, and prior to any research-related procedures, following International Conference on Harmonisation (ICH) Good Clinical Practice (GCP). 2. Clinical diagnosis of PXE supported by prior or concurrent genetic identification of biallelic Abcc6 mutations 3. Male or female, ages 18 to =65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. In the opinion of the Investigator and/or Sponsor, presence of any clinically significant disease (outside of those considered associated with the diagnosis of ABCC6 Deficiency) that precludes study participation or may confound interpretation of study results, including uncontrolled thyroid disease or unrelated connective tissue, bone, mineral, ophthalmologic, or muscle disease 2. Advanced eye disease requiring anti-VEGF treatment at Screening 3. Clinically significant abnormal laboratory result at screening, including but not limited to elevations of aspartate aminotransferase, alanine aminotransferase, bilirubin, or creatinine greater than 2 times the upper limit of normal, 25 (OH) Vitamin D levels <20 ng/mL, parathyroid hormone (PTH) more than 20% above the upper limit of normal, and hyper- or hypocalcemia 4. Known active fungal, bacterial, and/or viral infection including human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or COVID-19 virus. A negative COVID-19 test result is required within 5 days of first dose of INZ-701 5. Known intolerance to any INZ-701 excipient 6. Unable or unwilling to discontinue the use of any prohibited medication (examples include bisphosphonates, calcimimetics, antacids, systemic corticosteroids, pyrophosphate containing medications), as provided in protocol Section 9.4 7. Receipt of any other investigational new drug within 5 half-lives of the last dose of the other investigational drug 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 8. Last symptoms from a COVID-19 vaccination within 14 days prior to the first dose of INZ-701 or as described in the Inozyme COVID-19 Vaccine Guidance Document 9. Women who are breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Safety and Immunogenicity: Safety assessments will be summarized at Baseline and at each observed time point. Safety variables include: • Changes from baseline in the terminal elimination half-life (clearance) of INZ701 • Changes from baseline in the ENPP1 enzyme activity and mass ratio (neutralizing anti-drug antibodies [ADA]) • Incidence, frequency, and severity of adverse events (AEs), treatment-related AEs, and serious adverse events (SAEs) • Vital signs and weight • Physical examinations • Estimated glomerular filtration rate (eGFR) • Laboratory tests including chemistry, hematology, and urinalysis, including additional biochemical parameters of interest • Anti-INZ-701 antibody testing and dose-limiting toxicities (DLTs) • Incidence of any anti-drug antibodies (ADA) • Incidence of treatment emergent adverse events (TEAEs) associated with hypersensitivity reactions • Concomitant medications • Electrocardiogram (ECG) Pharmacokinetic Endpoints: • INZ-701 plasma concentration-time profiles and determination of noncompartmental PK parameters (including Tmax, Cmax, AUClast, AUCtau, AUCinf, T1/2, Cmin, Cl/F, and V/F) • Assess linearity between ascending INZ-701 SC doses and PK parameters Pharmacodynamic Endpoints: • Change from baseline for plasma PPi levels • Changes from baseline for renal clearance of PPi, Pi, calcium normalized to blood and urine creatinine • Changes from baseline for blood and urine biomarkers - Serum 1,25(OH)2D, plasma ionized and total calcium, parathyroid hormone - Bone biomarkers: serum alkaline phosphatase (ALP), bone specific alkaline phosphatase (BALP), carboxy terminal cross-linked telopeptide of type I collagen (CTX), and procollagen type 1 N-terminal propeptide (P1NP), serum phosphate, plasma intact fibroblast growth factor 23 (FGF23), tubular maximum reabsorption rate of phosphate adjusted for glomerular filtration rate(TmP/GFR) Efficacy Endpoints: Skeletal, calcification, and hearing evaluations that | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Please see above. ;Timepoint(s) of evaluation of this end point: Please see above. | — |
Countries
France
Contacts
Public ContactClinical Trial Information Desk
Inozyme Pharma, Inc.
Outcome results
None listed