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

• Status: Recruiting
• Trial end date: 2023-03-01
• Target enrollment: 0
• Participant gender: All

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]).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Inozyme Pharma
• Collaborator: IQVIA Biotech

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