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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05030831
Recruitment Status : Recruiting
First Posted : September 1, 2021
Last Update Posted : January 13, 2022
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, an ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) recombinant fusion protein, for the treatment of ABCC6 Deficiency (including Generalized Arterial Calcification of Infancy Type 2 [GACI-2] and Pseudoxanthoma elasticum [PXE]).

Condition or disease Intervention/treatment Phase
ATP-Binding Cassette Subfamily C Member 6 Deficiency Pseudoxanthoma Elasticum Generalized Arterial Calcification of Infancy Drug: INZ-701 Phase 1 Phase 2

Detailed Description:

INZ-701 is an ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) recombinant fusion protein in development for the treatment of ABCC6 Deficiency (including Generalized Arterial Calcification of Infancy Type 2 [GACI-2] and Pseudoxanthoma elasticum [PXE]).

This study is a Phase 1/2, multi-center, open-label, first-in-human (FIH), first-in-patient (FIP), and multiple ascending dose (MAD) study followed by a long-term open-label extension period conducted in adults with ABCC6 Deficiency manifesting as pseudoxanthoma elasticum (PXE). It 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 safe, tolerable dose that restores inorganic pyrophosphate (PPi) to therapeutically effective levels in ABCC6 Deficiency to be used in further clinical development. Exploratory endpoints for the Extension Period of the study will include evaluations of cardiac, vascular, ophthalmologic, skeletal, and physical function as well as patient reported outcomes.

Subject participation consists of a Screening Period, a 32-day Dose Evaluation Period, and a 48-week Extension Period following completion of the Dose Evaluation Period.

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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 INZ701-201 is a Phase 1/2, multi-center, open-label, first-in-human (FIH), first-in-patient (FIP), and 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.
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 Followed by an Open-Label Long-Term Extension Period in Adults With ABCC6 Deficiency Manifesting as Pseudoxanthoma Elasticum (PXE)
Actual Study Start Date : September 22, 2021
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : May 2023


Arm Intervention/treatment
Experimental: INZ-701
The study design 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.
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)
Other Name: rhENPP1-Fc




Primary Outcome Measures :
  1. Number of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 32 days (Dose Evaluation Period) ]
    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.

  2. Number of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 52 weeks (Day 1 through Safety Follow-up Visit) ]
    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.


Secondary Outcome Measures :
  1. Incidence of Anti-Drug Antibodies (ADAs) [ Time Frame: 32 days (Dose Evaluation Period) ]
    The presence of ADAs will be assessed and, if present, further evaluation will determine specificity and subtypes.

  2. Incidence of Anti-Drug Antibodies (ADAs) [ Time Frame: 52 weeks (Day 1 through Safety Follow-up Visit) ]
    The presence of ADAs will be assessed and, if present, further evaluation will determine specificity and subtypes.

  3. Area under the Plasma Concentration versus Time Curve (AUC) of INZ-701 [ Time Frame: 32 days (Dose Evaluation Period) ]
    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.

  4. Maximum Plasma Concentration (Cmax) of INZ-701 [ Time Frame: 32 days (Dose Evaluation Period) ]
    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.

  5. Systemic Clearance of INZ-701 [ Time Frame: 32 days (Dose Evaluation Period) ]
    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.

  6. Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) Levels [ Time Frame: 32 days (Dose Evaluation Period) ]
    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.

  7. Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) Levels [ Time Frame: 52 weeks (Baseline through Safety Follow-up Visit) ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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, per International Conference on Harmonisation (ICH) Good Clinical Practice (GCP)
  2. Clinical diagnosis of PXE supported by prior genetic identification of biallelic Abcc6 mutations
  3. Male or female, 18 to <65 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 be on stable doses for 3 years prior to enrollment and be planning to maintain stable doses through end of study unless the investigator deems, in consultation with the sponsor, that the change will not confound interpretation of the study data
  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 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

Exclusion Criteria:

  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 disease or unrelated connective tissue, bone, mineral, ophthalmologic, or muscle disease
  2. At high risk for sudden blindness (eg, blood in the macula, and/or retinal bleeding, and/or uncontrolled choroidal neovascularization [CNV], and/or visual acuity of less than 20/70 at Screening. Blindness is not an exclusion.)
  3. Clinically significant abnormal laboratory result at Screening in the opinion of the Investigator including but not limited to screening laboratory results demonstrating

    1. eGFR <60 mL/min/1.73m2 (CKD-EPI equation),
    2. 25 hydroxyvitamin D (25[OH]D) levels <20 ng/mL,
    3. parathyroid hormone (PTH) >40% above the upper limit of normal, or
    4. calcium outside of the laboratory reference range; however, minor deviations from the normal range may not be exclusionary if considered to be not clinically significant by the Investigator.
  4. Known active fungal, bacterial, and/or viral infection including including human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or COVID-19 infection. A negative COVID-19 test result is required within 5 days prior to first dose of INZ-701.
  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 or unwilling to discontinue the use of any prohibited medication.

    Examples:

    • Calcimimetics (no use within 3 months prior to initiation of the study)
    • Systemic corticosteroids ≥5 mg prednisone equivalent per day (no use for more than 14 days within 3 months prior to initiation of study)
    • Systemic oral or transdermal estrogen (use for contraception is allowed), selective estrogen receptor modulators (SERMs), hormone ablation therapy, tibolone (no more than 1 month of cumulative use within 6 months prior to initiation of the study)
    • Biologic bone modulators (no use within 18 months prior to initiation of study)
    • Oral bisphosphonates (no use within the past 2 years prior to initiation of study)
    • Intravenous (IV) bisphosphonates: Zoledronic acid (no use within 3 years prior to initiation of study, no more than 1 dose received within 3 to 5 years prior to initiation of study); Ibandronate or pamidronate (no use within 12 months prior to initiation of study, no more than 1 month of cumulative use within 3 years prior to initiation of the study, no more than 3 years of cumulative use, unless last dose received ≥5 years prior to initiation of study)
    • Calcium supplements - including antacids containing calcium (no use within 36 hours of the first dose of study drug)
    • Pyrophosphate containing medications (no use within 14 days prior to initiation of study)
  8. Concurrent participation in another non-Inozyme 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. Last symptoms from a COVID-19 vaccination within 14 days prior to the first dose of INZ-701 or as described in Inozyme COVID-19 Vaccine Guidance Document
  10. Subjects who are pregnant, trying to become pregnant, or breastfeeding
  11. Subjects who are trying to father a child

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): NCT05030831


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

Locations
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United States, New Jersey
Clinilabs Recruiting
Eatontown, New Jersey, United States, 07724
Contact: Imani Beard    212-994-4567    ARHR2-PXEstudies@clinilabs.com   
United Kingdom
Richmond Pharmacology Ltd (RPL) Recruiting
London, United Kingdom, SE1 1YR
Contact: Omari-Jordan Daniel    +44 (0)20 7042 5800    o.daniel@richmondpharmacology.com   
Sponsors and Collaborators
Inozyme Pharma
IQVIA Biotech
Investigators
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Study Director: Deborah Wenkert, MD Inozyme Pharma, Inc.
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Responsible Party: Inozyme Pharma
ClinicalTrials.gov Identifier: NCT05030831    
Other Study ID Numbers: INZ701-201
First Posted: September 1, 2021    Key Record Dates
Last Update Posted: January 13, 2022
Last Verified: September 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:
ATP-Binding Cassette Subfamily C Member 6 Deficiency
ABCC6
Pseudoxanthoma elasticum
PXE
Generalized Arterial Calcification of Infancy
GACI
hypopyrophosphatemia
Additional relevant MeSH terms:
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Pseudoxanthoma Elasticum
Calcinosis
Vascular Calcification
Calcium Metabolism Disorders
Metabolic Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Hemorrhagic Disorders
Hematologic Diseases
Skin Abnormalities
Congenital Abnormalities
Skin Diseases, Genetic
Genetic Diseases, Inborn
Connective Tissue Diseases
Skin Diseases