Evaluation of Safety, Tolerability, and Efficacy of INZ-701 in Adults With ENPP1 Deficiency
- Conditions
- Ectonucleotide Pyrophosphatase/phosphodiesterase1 DeficiencyAutosomal Recessive Hypophosphatemic RicketsGeneralized Arterial Calcification of Infancy
- Interventions
- Registration Number
- NCT04686175
- Lead Sponsor
- Inozyme Pharma
- Brief Summary
The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of multiple ascending doses of INZ-701, an ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) enzyme replacement therapy, for the treatment of ENPP1 Deficiency. The goal of the study is to identify a dose regimen for further clinical development in the treatment of ENPP1 Deficiency.
- Detailed Description
INZ-701 is an ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) enzyme replacement therapy (ERT) in development for the treatment of ENPP1 Deficiency, an ultra-rare genetic disorder with an incidence of 1 in 64,000 pregnancies.
Study INZ701-101 is a Phase 1/2, multicenter, open-label, FIH, MAD, dose-finding study followed by a long-term open-label Extension Period conducted in adults with ENPP1 Deficiency. This study is designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of multiple ascending doses of INZ-701. The goal of the study is to identify a dose and dose schedule (number of doses per week) for further clinical development. No placebo will be used in the study. Subjects will be 18 to \<65 years of age, with a confirmed genetic diagnosis of ENPP1 Deficiency and biochemical evidence of hypopyrophosphatemia (ie, PPi \<1300 nM). Exploratory endpoints for the Extension Period of the study include evaluations of skeletal assessment (X-ray and DEXA), arterial and organ calcification (either Na18F-PET/CT or low dose CT \[full body\] without contrast, echocardiogram, and renal ultrasound), and cardiovascular function (echocardiogram) as well as patient reported outcomes.
Subject participation consists of a Screening Period of up to 30 days, a 32-day Dose Evaluation Period, and an Extension Period during which subjects may continue to receive INZ-701 (with options for self-, caregiver-, or healthcare provider administration) until INZ-701 is approved and available in the country where the subject resides or until an alternative study for subjects to continue receiving study drug is available. During the Extension Period, follow-up visits will be conducted every 4 weeks until Week 48, followed by every 12 weeks until the subject leaves the study.
Subjects will complete an End of Study (EOS) Visit (Safety Follow-Up Visit) 30 days after their last dose of INZ-701.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 9
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description INZ-701 INZ-701 The study design of the Dose Evaluation Period is a MAD 3 + 3 with 3 dose cohorts. Additional cohorts may be added to evaluate an intermediate dose and/or an alternative dosing regimen of an existing dose level. Based on nonclinical findings and nonclinical pharmacology modeling, the initial planned doses will be 0.2 mg/kg, 0.6 mg/kg, and 1.8 mg/kg all twice weekly, not to exceed 3.6 mg/kg weekly. During the Extension Period, visits will be every 4 weeks until Week 48 and then every 12 weeks until the subject leaves the study. Subjects will complete an End of Study (EOS) Visit (Safety Follow-up Visit) 30 days after their last dose of INZ-701 (greater than 5 half-lives of INZ-701) for all subjects.
- Primary Outcome Measures
Name Time Method Number of Treatment Emergent Adverse Events (TEAEs) 52 weeks (Day 1 through Safety Follow-up Visit) 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 (Baseline through Safety Follow-up Visit) For each subject, the presence of ADAs will be assessed and, if present, further evaluation will determine specificity and subtypes.
Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) Levels 52 weeks (Baseline through Safety Follow-up Visit) 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.
Maximum Plasma Concentration (Cmax) of INZ-701 32 days (Dose Evaluation Period) 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.
Area under the Plasma Concentration versus Time Curve (AUC) of INZ-701 32 days (Dose Evaluation Period) 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.
Systemic Clearance of INZ-701 32 days (Dose Evaluation Period) For each subject, clearance of INZ-701 from the body will be measured via a series of blood samples obtained throughout the study, comparing the subject's baseline value over time.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (7)
Parexel International GmbH
🇩🇪Berlin, Germany
Necker University Hospital-Sick Children
🇫🇷Paris, France
University of Saskatchewan
🇨🇦Saskatoon, Saskatchewan, Canada
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
University of Hamburg (Universitatklinikum Hamburg-Eppendorf)
🇩🇪Hamburg, Germany
Clinilabs Drug Development Corporation
🇺🇸Eatontown, New Jersey, United States
Richmond Pharmacology (RPL)
🇬🇧London, London Bridge, United Kingdom