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)

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) recombinant fusion protein, for the treatment of ABCC6 Deficiency. The goal of the study is to identify a dose regimen for further clinical development in the treatment of ABCC6 Deficiency.

Study Overview

• Status: Completed
• Conditions: Pseudoxanthoma Elasticum; Generalized Arterial Calcification of Infancy; ATP-Binding Cassette Subfamily C Member 6 Deficiency
• Intervention / Treatment: Drug: INZ-701

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 in ABCC6 Deficiency. No placebo will be used in this study.

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 of the Extension Period and then every 12 weeks (remote or in-clinic) until the subject leaves the study.

Subjects will complete a follow up visit 30 days after their last dose of INZ-701.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 1YR
    • Richmond Pharmacology Ltd (RPL)
• United States
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Clinilabs

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

Individuals eligible to participate must meet all of the following 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, per International Conference on Harmonisation (ICH) Good Clinical Practice (GCP)
2. Clinical diagnosis of PXE supported by prior genetic identification of biallelic ABCC6 mutations (ie, homozygous or compound heterozygous)
3. Male or female, 18 to <70 years of age at Screening
4. Plasma PPi <1300 nM at Screening
5. 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
6. Women of child-bearing potential (WOCBP) as defined in Clinical Trials Facilitation and Coordination Group (CTFG 2020) must have a negative serum pregnancy test at Screening
7. 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.
8. 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.
9. In the opinion of the Investigator, must be willing and able to complete the Dose Evaluation Period
10. Agree to provide access to relevant medical records

Individuals who meet any of the following exclusion criteria will not be eligible to participate:

1. 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
2. Active retinal bleeding in both eyes during Screening
3. Clinically significant abnormal laboratory result at Screening in the opinion of the Investigator, including but not limited to, estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 (Chronic Kidney Disease-Epidemiology Collaboration equation) or 25-hydroxyvitamin D levels <12 ng/mL
4. Known active fungal, bacterial, and/or viral infection including human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or COVID-19 infection.
5. Malignancy within the last 5 years, except non-melanoma skin cancers or cervical carcinoma in situ
6. Known intolerance to INZ-701 or any of its excipients
7. Unable to or unwilling to discontinue the use of any prohibited medication as provided in the protocol. Discontinuation should be undertaken only if considered not detrimental and indicated by the subject's treating physician.
8. 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
9. Subjects who are pregnant, trying to become pregnant, or breastfeeding
10. 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)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: INZ-701; The study design of the Dose Evaluation Period is a MAD 3 + 3 with 3 dose cohorts. 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, with a twice weekly dose regimen. During the Extension Period, INZ-701 administration will initially be at the dose and dose schedule assigned in the Dose Evaluation Period; however, the Sponsor may modify the assigned dose and/or dosing regimen in the Extension Period post-Week 48 based on cumulative review of safety and PK/PD data, including population PK. Study visits will be in-clinic every 4 weeks until Week 48 of the Extension Period and then every 12 weeks (remote or in-clinic) 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.

Drug: INZ-701; 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 (rhENPP1-Fc).; Other Names: rhENPP1-Fc

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Anti-Drug Antibodies (ADAs)	The presence of ADAs will be assessed and, if present, further evaluation will determine specificity and subtypes.	32 days (Dose Evaluation Period)
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.	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)
Incidence of Anti-Drug Antibodies (ADAs)	The presence of ADAs will be assessed and, if present, further evaluation will determine specificity and subtypes.	52 weeks (Day 1 through Safety Follow-up Visit)

Collaborators and Investigators

• Sponsor: Inozyme Pharma
• Collaborators: IQVIA Biotech
• Investigators: Study Director: Kurt Gunter, MD, Inozyme Pharma, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2022
• Primary Completion (Actual): July 9, 2024
• Study Completion (Actual): July 9, 2024

Study Registration Dates

• First Submitted: August 26, 2021
• First Submitted That Met QC Criteria: August 26, 2021
• First Posted (Actual): September 1, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 4, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Generalized Arterial Calcification of Infancy; PXE; ABCC6; GACI; hypopyrophosphatemia; ATP-Binding Cassette Subfamily C Member 6 Deficiency; Pseudoxanthoma elasticum
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Metabolic Diseases; Connective Tissue Diseases; Hematologic Diseases; Skin Diseases; Congenital Abnormalities; Hemostatic Disorders; Hemorrhagic Disorders; Skin Diseases, Genetic; Skin Abnormalities; Calcium Metabolism Disorders; Calcinosis; Vascular Calcification; Pseudoxanthoma Elasticum
• Other Study ID Numbers: INZ701-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No