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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-003716-27 | EudraCT Number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| INZ-701 | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| INZ-701 | Drug | INZ701-101 is a recombinant fusion protein that contains the extracellular domains of human ENPP1 coupled with an Fc fragment from an immunoglobulin gamma-1 (IgG1) antibody. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 32 days (Dose Evaluation Period) |
| 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 (Day 1 through Safety Follow-up Visit) |
| Incidence of Anti-Drug Antibodies (ADA) | For each subject, the presence of ADAs will be assessed and, if present, further evaluation will determine specificity and subtypes. | 32 days (Dose Evaluation Period) |
| Incidence of Anti-Drug Antibodies (ADA) | For each subject, the presence of ADAs will be assessed and, if present, further evaluation will determine specificity and subtypes. | 52 weeks (Baseline through Safety Follow-up Visit) |
| Area under the Plasma Concentration versus Time Curve (AUC) of INZ-701 | 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. | 32 days (Dose Evaluation Period) |
| Maximum Plasma Concentration (Cmax) of INZ-701 | 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. |
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Individuals eligible to participate must meet all of the following inclusion criteria:
Individuals who meet any of the following exclusion criteria will not be eligible to participate:
In the opinion of the Investigator, presence of any clinically significant disease (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 cardiovascular, thyroid disease, or unrelated connective tissue, bone, mineral, lipid, or muscle disease
Clinically significant abnormal laboratory result at Screening in the opinion of the Investigator, including but not limited to screening laboratory results demonstrating
Known active fungal, bacterial, and/or viral infection including human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or COVID-19 virus. In Germany and France, a negative COVID-19 test result is required within 5 days prior to the first dose of INZ-701.
Malignancy within the last 5 years, except non-melanoma skin cancers or cervical carcinoma in situ
Known intolerance to INZ-701 or any of its excipients
Unable or unwilling to discontinue the use of any prohibited medication (examples include 1,25-dihydroxy vitamin D, phosphate, anti-FGF23 [eg, burosumab], calcimimetics, calcium-containing antacids, systemic corticosteroids, PTH suppressors). Discontinuation should be undertaken only if considered not detrimental and indicated by the subject's treating physician.
Concurrent participation in another non-Inozyme interventional clinical 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
Subjects who are pregnant, trying to become pregnant, or breastfeeding
Subjects who are trying to father a child
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| Name | Affiliation | Role |
|---|---|---|
| Kurt Gunter, MD | Inozyme Pharma, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic | Rochester | Minnesota | 55905 | United States | ||
| Clinilabs Drug Development Corporation |
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Study INZ701-101 is a Phase 1/2, multi-center, open-label, first-in-human (FIH), multiple ascending dose (MAD) study followed by a long-term open-label extension period conducted in adults with ENPP1 Deficiency. The study design during the Dose Evaluation Period is a MAD 3+3 with 3 dose cohorts.
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| 32 days (Dose Evaluation Period) |
| Systemic Clearance of INZ-701 | 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. | 32 days (Dose Evaluation Period) |
| Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) Levels | 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. | 32 days (Dose Evaluation Period) |
| Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) Levels | 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. | 52 weeks (Baseline through Safety Follow-up Visit) |
| Eatontown |
| New Jersey |
| 07724 |
| United States |
| University of Saskatchewan | Saskatoon | Saskatchewan | S7N 0W8 | Canada |
| Necker University Hospital-Sick Children | Paris | 75015 | France |
| Parexel International GmbH | Berlin | 14050 | Germany |
| University of Hamburg (Universitatklinikum Hamburg-Eppendorf) | Hamburg | 22529 | Germany |
| Richmond Pharmacology (RPL) | London | London Bridge | SE1 1YR | United Kingdom |
| ID | Term |
|---|---|
| C562792 | Hypophosphatemic Rickets, Autosomal Recessive, 1 |
| C537440 | Arterial calcification of infancy |
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