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

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ClinicalTrials.gov Identifier: NCT04686175
Recruitment Status : Not yet recruiting
First Posted : December 28, 2020
Last Update Posted : January 5, 2021
Sponsor:
Collaborator:
IQVIA Biotech
Information provided by (Responsible Party):
Inozyme Pharma

Brief Summary:
The purpose of this study is to assess safety and tolerability of INZ-701 a recombinant ENPP1 enzyme, for the treatment of ENPP1 deficiency. The study aims to establish the safety and tolerability of multiple ascending Subcutaneous (SC) doses of INZ-701.

Condition or disease Intervention/treatment Phase
Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency ENPP1 Drug: INZ-701 Phase 1 Phase 2

Detailed Description:

This study is a Phase 1/2, multi-center, assessor blind, open-label, first in human study conducted in adults with ENPP1 Deficiency 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 that restores Plasma Inorganic Pyrophosphate (PPi) to normal levels in ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) Deficiency to be used in further clinical development. No placebo/control arm or reference therapies will be used in the study, but all measurements will be assessor blinded.

The study design is a multiple ascending dose 3x3 schedule (3 dose cohorts with 3 subjects per cohort). Based on nonclinical pharmacology modeling, the planned doses will be 0.2 mg/kg, 0.6 mg/kg, and 1.8 mg/kg.

The Principal Investigator (PI) or an appropriately qualified delegate will administer INZ-701 at the prescribed dose and dosing interval for each given cohort.

The Final PK and Safety Assessment Period includes PK sample collection and safety assessments after the last dose of INZ-701 on Days 30 to 35 and the Final Safety Visit. After completion of the Final Safety Visit, where approved by regulatory agencies and ethics committees, subjects may continue dosing at their assigned dose level as part of a separate, independent long-term extension study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Study INZ701-101 is a Phase 1/2, multi-center, assessor blind, open-label, First in human (FIH), First in patient (FIP), and Multiple Ascending Dose (MAD) study conducted in adults with ENPP1 Deficiency. The study design is a MAD 3×3 (3 dose cohorts with 3 subjects per cohort).
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2, Open-Label, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INZ-701 in Adults With ENPP1 Deficiency
Estimated Study Start Date : January 2021
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : April 2022

Arm Intervention/treatment
Experimental: INZ-701
The study design is a MAD 3×3 (3 dose cohorts with 3 subjects per cohort). The planned doses will be 0.2 mg/kg, 0.6 mg/kg, and 1.8 mg/kg.
Drug: INZ-701
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)




Primary Outcome Measures :
  1. Dose Toxicity [ Time Frame: 5 weeks ]
    Occurrence of dose limiting toxicity (DLT) during first 5 weeks of therapy

  2. Determination of Immunogenicity [ Time Frame: 5 weeks ]
    The presence of anti-drug antibodies will be assayed and, if present, further evaluation will confirm positivity for antidrug antibodies and determine specificity, neutralizing ability, cell-mediated immune response and correlation with clinical responses.

  3. Measurement of Plasma Inorganic Pyrophosphate (PPi) in Plasma [ Time Frame: 5 weeks ]
    For each subject, blood plasma will be assayed for Plasma Inorganic Pyrophosphate (PPi), comparing the subjects baseline value over time

  4. Measurement of Fibroblast Growth Factor 23 (FGF23) in plasma [ Time Frame: 5 weeks ]
    For each subject, blood plasma will be assayed for FGF23, comparing the subjects baseline value over time

  5. Area under the plasma concentration versus time curve (AUC) [ Time Frame: 5 weeks ]
    For each subject, variation of concentration of INZ-701 in the plasma will be measured

  6. Peak Plasma Concentration (Cmax) [ Time Frame: 5 weeks ]
    For each subject, the maximum concentration of INZ-701 in the plasma will be measured

  7. Systemic clearance [ Time Frame: 5 weeks ]
    For each subject, clearance of INZ-701 from the body will be measured



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  2. Clinical diagnosis of Autosomal Recessive Hypophosphatemic Rickets 2 (ARHR2) supported by prior or concurrent genetic testing of the ENPP1 gene
  3. Male or female, 18 to 64 years of age
  4. Plasma PPi < lower limit of normal (LLN) at screening
  5. Willing to withhold treatment with oral phosphate and vitamin D analogs (e.g. calcitriol) beginning at least 14 days prior to first dose of INZ-701 and throughout the Treatment Period
  6. If using, discontinue use of bisphosphonates for 6 months prior to initiation of the study
  7. Women of child-bearing potential (WOCBP as defined in Clinical Trial Facilitation Group (CTFG) 2014) must have a negative urine pregnancy test at Screening and at all additional pregnancy tests during the study
  8. Fertile males with partners of child-bearing potential and WOCBP must agree to use 2 highly effective forms of contraception (per CTFG 2014) from the period following the first dose of INZ-701 through 25 days after last dose of INZ-701
  9. Males who are sexually active must agree to use condoms from the period following first dose of INZ-701 through 25 days after the last dose of INZ-701
  10. In the opinion of the Investigator, must be willing and able to complete all aspects of the study
  11. Agree to provide access to relevant medical records.

Exclusion Criteria:

  1. In the opinion of the Investigator and/or Sponsor, 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
  2. Clinically significant abnormal laboratory result at screening, including but not limited to, elevations of aspartate aminotransferase, alanine aminotransferase, bilirubin, or creatinine greater than 2 times the upper limit of normal
  3. Known active fungal, bacterial, and/or viral infection including human immunodeficiency virus, hepatitis B virus, or hepatitis C virus. If status is unknown, a local test should be completed prior to enrollment.
  4. Known intolerance to INZ-701 or any of its excipients
  5. Unable or unwilling to discontinue the use of any prohibited medication (bisphosphonates, anti-fibroblast growth factor 23 (FGF23) [e.g. burosumab], calcimimetics, antacids, systemic corticosteroids, parathyroid hormone suppressors) or procedures
  6. Receipt of any other investigational new drug or use of an investigational device within 4 weeks prior to the first dose of INZ-701.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04686175


Contacts
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Contact: Inozyme Clinical Trial Information +1 857 330 4340 clinicaltrials@inozyme.com

Sponsors and Collaborators
Inozyme Pharma
IQVIA Biotech
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Responsible Party: Inozyme Pharma
ClinicalTrials.gov Identifier: NCT04686175    
Other Study ID Numbers: INZ701-101
2020-003716-27 ( EudraCT Number )
First Posted: December 28, 2020    Key Record Dates
Last Update Posted: January 5, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Inozyme Pharma:
ectonucleotide pyrophosphatase/phosphodiesterase deficiency
hypopyrophosphatemia
ENPP1