Evaluation of Safety, Tolerability, and Efficacy of INZ-701 in Adults With ABCC6 Deficiency Causing PXE

NCT05030831 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: INZ701-201
• Study Type: interventional
• Target: 10
• Locations: 2 countries
• Sites: 2

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) 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.

Conditions

ATP-Binding Cassette Subfamily C Member 6 Deficiency; Pseudoxanthoma Elasticum; Generalized Arterial Calcification of Infancy

Keywords

ATP-Binding Cassette Subfamily C Member 6 Deficiency; ABCC6; Pseudoxanthoma elasticum; PXE; Generalized Arterial Calcification of Infancy; GACI; hypopyrophosphatemia

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• Incidence of Anti-Drug Antibodies (ADAs)

  32 days (Dose Evaluation Period)

• Incidence of Anti-Drug Antibodies (ADAs)

  52 weeks (Day 1 through Safety Follow-up Visit)

• Area under the Plasma Concentration versus Time Curve (AUC) of INZ-701

  32 days (Dose Evaluation Period)

• Maximum Plasma Concentration (Cmax) of INZ-701

  32 days (Dose Evaluation Period)

• Systemic Clearance of INZ-701

  32 days (Dose Evaluation Period)

Study Arms (1)

INZ-701

EXPERIMENTAL

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

Interventions

INZ-701 DRUG

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).

Also known as: rhENPP1-Fc

INZ-701

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Clinical diagnosis of PXE supported by prior genetic identification of biallelic ABCC6 mutations (ie, homozygous or compound heterozygous)
• Male or female, 18 to \<70 years of age at Screening
• Plasma 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) as defined in Clinical Trials Facilitation and Coordination Group (CTFG 2020) 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 the Dose Evaluation Period
• Agree to provide access to relevant medical records

You may not qualify if:

• 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 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
• Known active fungal, bacterial, and/or viral infection including human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or COVID-19 infection.
• 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 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.
• 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

Sponsors & Collaborators

• Inozyme Pharma: lead
• IQVIA Biotech: collaborator

Study Sites (2)

Clinilabs

Eatontown, New Jersey, 07724, United States

Location

Richmond Pharmacology Ltd (RPL)

London, SE1 1YR, United Kingdom

Location

MeSH Terms

Conditions

Pseudoxanthoma Elasticum; Arterial calcification of infancy

Condition Hierarchy (Ancestors)

Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Kurt Gunter, MD

  Inozyme Pharma, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Study INZ701-201 is a Phase 1/2, multicenter, open-label, multiple ascending dose (MAD) study followed by a long-term open-label extension period conducted in adults with ABCC6 Deficiency manifesting as PXE. The study design during the Dose Evaluation Period is a MAD 3+3 with 3 dose cohorts.

Study Record Dates

• First Submitted: August 26, 2021
• First Posted: September 1, 2021
• Study Start: April 11, 2022
• Primary Completion: July 9, 2024
• Study Completion: July 9, 2024
• Last Updated: February 5, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); GB (1)