- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05030831
Evaluation of Safety, Tolerability, and Efficacy of INZ-701 in Adults With ABCC6 Deficiency Causing PXE
A Phase 1/2, Open-Label, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INZ-701 Followed by an Open-Label Long-Term Extension Period in Adults With ABCC6 Deficiency Manifesting as Pseudoxanthoma Elasticum (PXE)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
INZ-701 is an ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) recombinant fusion protein in development for the treatment of ABCC6 Deficiency, a rare genetic disorder.
Study INZ701-201 is a Phase 1/2, multicenter, open-label, multiple ascending dose (MAD), dose-finding study followed by a long-term open-label Extension Period conducted in adults with ABCC6 Deficiency manifesting as Pseudoxanthoma elasticum (PXE). 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. Exploratory endpoints for the Extension Period of the study include evaluations of arterial and organ calcification, ophthalmologic, cardiac and renal parameters, and physical function as well as patient reported outcomes.
Subject participation consists of a Screening Period of up to 60 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 a follow up visit 30 days after their last dose of INZ-701.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Inozyme Clinical Trial Information
- Phone Number: +1 857 330 4340
- Email: clinicaltrials@inozyme.com
Study Locations
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London, United Kingdom, SE1 1YR
- Richmond Pharmacology Ltd (RPL)
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New Jersey
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Eatontown, New Jersey, United States, 07724
- Clinilabs
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New York
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New York, New York, United States, 10029
- Icahn School of Medicine at Mount Sinai
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria
Individuals eligible to participate must meet all of the following inclusion criteria:
- 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)
- Clinical diagnosis of pseudoxanthoma elasticum (PXE) supported by prior genetic identification of biallelic ABCC6 mutations (ie, homozygous or compound heterozygous)
- Male or female, ages 18 to <70 years of age at Screening
- PPi <1300 nM at Screening
- Subjects who are being treated with statins or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors must have been on treatment for at least 6 months prior to Screening and no new anti-lipid therapy can be introduced within 6 months of Screening
- Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test at Screening
- WOCBP and partners of fertile males who are WOCBP must be using or agree to use one highly effective form of contraception (per CTFG 2020) and a barrier method from at least 1 month before the first dose of INZ-701 through 30 days after the last dose of INZ-701 (greater than 5 half-lives of INZ-701). WOCBP and partners of fertile males who are WOCBP must also agree to not donate ova from the period following the first dose of INZ-701 through 30 days after last dose of INZ-701.
- Males who are sexually active must agree to use condoms from the period following first dose of INZ-701 through 30 days after the last dose of INZ-701. Males must also agree to not donate sperm from the period following the first dose of INZ-701 through 30 days after last dose of INZ-701.
- In the opinion of the Investigator, must be willing and able to complete all aspects of the study
- Agree to provide access to relevant medical records
Exclusion 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 ABCC6 Deficiency) that precludes study participation or may confound interpretation of study results, including known uncontrolled thyroid, or unrelated connective tissue, bone, mineral, lipid, ophthalmologic, or muscle disease
- Active retinal bleeding in both eyes during Screening
- Clinically significant abnormal laboratory result at Screening, including but not limited to, eGFR <60 mL/min/1.73m2 (Chronic Kidney Disease-Epidemiology Collaboration equation) and 25-hydroxyvitamin D levels <12 ng/mL
- Known active fungal, bacterial, and/or viral infection including human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, or COVID-19 virus
- 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. 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 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
- Subjects who are pregnant, trying to become pregnant, or breastfeeding
- Subjects who are trying to father a child
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: INZ-701
The study design during the Dose Evaluation Period is a MAD 3+3 with 3 dose cohorts. The planned doses will be 0.2 mg/kg, 0.6 mg/kg, and 1.8 mg/kg administered via subcutaneous injection twice weekly. During the Extension Period, subjects will be administered INZ-701 at the dose and dose schedule assigned in the Dose Evaluation Period. However, the administered dose and dose schedule for a subject may change once the selected dosing regimen has been determined upon completion of the Dose Evaluation Period, at which time all subjects will be assigned to the selected dosing regimen. |
INZ-701 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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Treatment Emergent Adverse Events (TEAEs)
Time Frame: 32 days (Dose Evaluation Period)
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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.
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32 days (Dose Evaluation Period)
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Number of Treatment Emergent Adverse Events (TEAEs)
Time Frame: 52 weeks (Day 1 through Safety Follow-up Visit)
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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.
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52 weeks (Day 1 through Safety Follow-up Visit)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Incidence of Anti-Drug Antibodies (ADAs)
Time Frame: 32 days (Dose Evaluation Period)
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The presence of ADAs will be assessed and, if present, further evaluation will determine specificity and subtypes.
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32 days (Dose Evaluation Period)
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Area under the Plasma Concentration versus Time Curve (AUC) of INZ-701
Time Frame: 32 days (Dose Evaluation Period)
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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.
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32 days (Dose Evaluation Period)
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Maximum Plasma Concentration (Cmax) of INZ-701
Time Frame: 32 days (Dose Evaluation Period)
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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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32 days (Dose Evaluation Period)
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Systemic Clearance of INZ-701
Time Frame: 32 days (Dose Evaluation Period)
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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.
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32 days (Dose Evaluation Period)
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Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) Levels
Time Frame: 32 days (Dose Evaluation Period)
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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.
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32 days (Dose Evaluation Period)
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Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) Levels
Time Frame: 52 weeks (Baseline through Safety Follow-up Visit)
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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.
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52 weeks (Baseline through Safety Follow-up Visit)
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Incidence of Anti-Drug Antibodies (ADAs)
Time Frame: 52 weeks (Day 1 through Safety Follow-up Visit)
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The presence of ADAs will be assessed and, if present, further evaluation will determine specificity and subtypes.
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52 weeks (Day 1 through Safety Follow-up Visit)
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Borut Cizman, MD, Inozyme Pharma, Inc.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Metabolic Diseases
- Skin Diseases
- Congenital Abnormalities
- Hematologic Diseases
- Hemorrhagic Disorders
- Genetic Diseases, Inborn
- Connective Tissue Diseases
- Hemostatic Disorders
- Skin Diseases, Genetic
- Skin Abnormalities
- Calcium Metabolism Disorders
- Pseudoxanthoma Elasticum
- Calcinosis
- Vascular Calcification
Other Study ID Numbers
- INZ701-201
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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