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

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: NCT04686175
Recruitment Status : Recruiting
First Posted : December 28, 2020
Last Update Posted : January 5, 2022
Sponsor:
Information provided by (Responsible Party):
Inozyme Pharma

Brief Summary:
The purpose of this study is to assess the safety and tolerability of INZ-701, an ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) enzyme replacement therapy, for the treatment of ENPP1 Deficiency (including Generalized Arterial Calcification of Infancy Type 1 [GACI] and Autosomal Recessive Hypophosphatemic Rickets Type 2 [ARHR2]).

Condition or disease Intervention/treatment Phase
Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency Autosomal Recessive Hypophosphatemic Rickets Generalized Arterial Calcification of Infancy Drug: INZ-701 Phase 1 Phase 2

Detailed Description:

INZ-701 is an ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) enzyme replacement therapy in development for the treatment of ENPP1 Deficiency (including Generalized Arterial Calcification of Infancy Type 1 [GACI] and Autosomal Recessive Hypophosphatemic Rickets Type 2 [ARHR2]).

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 ENPP1 Deficiency. 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 ENPP1 Deficiency to be used in further clinical development. Exploratory endpoints for the Extension Period of the study will include evaluations of skeletal, vascular, 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 INZ701-101 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 ENPP1 Deficiency. 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 ENPP1 Deficiency
Actual Study Start Date : June 18, 2021
Estimated Primary Completion Date : February 2023
Estimated Study Completion Date : March 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)




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.

  3. 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.

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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

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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 ICH GCP
  2. Clinical diagnosis of ENPP1 Deficiency supported by prior genetic identification of biallelic ENPP1 mutations
  3. Male or female, 18 to <65 years of age at Screening
  4. Plasma PPi < 1300nM 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 through end of study unless previously cleared with the Sponsor
  6. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test at Screening
  7. WOCBP and partners of fertile males who are WOCBP must agree to use 1 highly effective form of contraception 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 ENPP1 Deficiency) that precludes study participation or may confound interpretation of study results, including known uncontrolled thyroid disease or unrelated connective tissue, bone, mineral, or muscle disease
  2. Clinically significant abnormal laboratory result at Screening in the opinion of the Investigator, including but not limited to screening laboratory results demonstrating

    1. eGFR (CKD-EPI equation) less than 60 mL/min/1.73m2,
    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
  3. Known active fungal, bacterial, and/or viral infection 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.
  4. Malignancy within the last 5 years, except non-melanoma skin cancers or cervical carcinoma in situ
  5. Known intolerance to INZ-701 or any of its excipients
  6. Unable or unwilling to discontinue the use of any prohibited medication (examples: calcimimetics or parathyroid hormone suppressors and modulators, systemic corticosteroids, include 1,25[OH]2D, anti-fibroblast growth factor 23 (FGF23) [eg, burosumab], phosphate or calcium supplements, antacids, oral/intravenous bisphosphonates) as provided in the protocol. Discontinuation should be undertaken only if considered not detrimental and indicated by the subject's treating physician.
  7. 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 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
  8. Last symptoms from a COVID-19 vaccination within 14 days prior to the first dose of INZ-701 or as described in the Inozyme COVID-19 Vaccine Guidance Document
  9. Subjects who are pregnant, trying to become pregnant, or breastfeeding
  10. 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): NCT04686175


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

Locations
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United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Gang Liu    507-255-8112    Liu.Gang@mayo.edu   
Contact: Vishakantha (Vishu) Murthy    507-255-8112    Murthy.Vishakantha@mayo.edu   
United States, New Jersey
Clinilabs Drug Development Corporation Recruiting
Eatontown, New Jersey, United States, 07724
Contact: Imani Beard    212-994-4567    ARHR2-PXEstudies@clinilabs.com   
United Kingdom
Richmond Pharmacology (RPL) Recruiting
London, London Bridge, United Kingdom, SE1 1YR
Contact: Omari-Jordan Daniel    +44 (0)20 7042 5800    volunteer@richmondpharmacology.com   
Sponsors and Collaborators
Inozyme Pharma
Investigators
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Study Director: Deborah Wenkert, MD Inozyme Pharma, Inc.
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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, 2022
Last Verified: December 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/phosphodiesterase1 deficiency
hypopyrophosphatemia
ENPP1
Generalized Arterial Calcification of Infancy
GACI
Autosomal Recessive Hypophosphatemic Rickets Type 2
ARHR2
Additional relevant MeSH terms:
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Rickets
Rickets, Hypophosphatemic
Familial Hypophosphatemic Rickets
Calcinosis
Vascular Calcification
Calcium Metabolism Disorders
Metabolic Diseases
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Vitamin D Deficiency
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Hypophosphatemia
Phosphorus Metabolism Disorders
Hypophosphatemia, Familial
Renal Tubular Transport, Inborn Errors
Kidney Diseases
Urologic Diseases
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn