Evaluation of Safety, Tolerability, and Efficacy of INZ-701 in Adults With ENPP1 Deficiency

NCT04686175 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: INZ701-1012020-003716-27
• Study Type: interventional
• Target: 9
• Locations: 5 countries
• Sites: 7

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.

Conditions

Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency; Autosomal Recessive Hypophosphatemic Rickets; Generalized Arterial Calcification of Infancy

Keywords

ectonucleotide pyrophosphatase/phosphodiesterase1 deficiency; hypopyrophosphatemia; ENPP1; Generalized Arterial Calcification of Infancy; GACI; Autosomal Recessive Hypophosphatemic Rickets Type 2; ARHR2

Outcome Measures

Primary Outcomes (9)

• 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.

  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)

Study Arms (1)

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.

Drug: INZ-701

Interventions

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.

Also known as: rhENPP1-Fc

INZ-701

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

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 ENPP1 Deficiency supported by prior identification of biallelic ENPP1 mutations (ie, homozygous or compound heterozygous)
• Male or female, 18 to \<65 years of age at Screening
• PPi \<1300 nM at 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 1 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 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
• estimated glomerular filtration rate (eGFR) (Chronic Kidney Disease-Epidemiology Collaboration \[CKD-EPI\] equation) \< 60 mL/min/1.73m\^2,
• hydroxyvitamin D (25\[OH\]D) levels \<12 ng/mL, or
• Intact parathyroid hormone (PTH) \>40% above the upper limit of normal
• 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

Sponsors & Collaborators

• Inozyme Pharma: lead

Study Sites (7)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Clinilabs Drug Development Corporation

Eatontown, New Jersey, 07724, United States

Location

University of Saskatchewan

Saskatoon, Saskatchewan, S7N 0W8, Canada

Location

Necker University Hospital-Sick Children

Paris, 75015, France

Location

Parexel International GmbH

Berlin, 14050, Germany

Location

University of Hamburg (Universitatklinikum Hamburg-Eppendorf)

Hamburg, 22529, Germany

Location

Richmond Pharmacology (RPL)

London, London Bridge, SE1 1YR, United Kingdom

Location

MeSH Terms

Conditions

Hypophosphatemic Rickets, Autosomal Recessive, 1; Arterial calcification of infancy

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 INZ701-101 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.

Study Record Dates

• First Submitted: December 22, 2020
• First Posted: December 28, 2020
• Study Start: November 21, 2021
• Primary Completion: October 29, 2024
• Study Completion: December 13, 2024
• Last Updated: February 5, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); FR (1); US (2); CA (1); DE (2)