SEAPORT 1: Study of INZ-701 in Adults With Hemodialysis-Dependent End-Stage Kidney Disease (SEAPORT 1)

The SEAPORT 1 Study: An Open-label Exploratory Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of INZ-701 in Study Participants With End-Stage Kidney Disease Undergoing Hemodialysis

This Phase 1, open-label, multicenter study evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of INZ-701 in adults with hemodialysis-dependent end-stage kidney disease (ESKD) and low plasma inorganic pyrophosphate (PPi) levels. Participants received INZ-701 1.8 mg/kg subcutaneously once weekly for 4 weeks. The study assessed changes in plasma PPi levels, PK characteristics, ENPP1-Fc activity, safety, tolerability, and immunogenicity.

Study Overview

• Status: Completed
• Conditions: Calciphylaxis
• Intervention / Treatment: Drug: INZ-701

Detailed Description

SEAPORT 1 was a Phase 1 open-label study conducted at two sites in the United States. Participants with ESKD receiving maintenance hemodialysis and with plasma PPi levels <700 nmol/L received INZ-701 1.8 mg/kg by subcutaneous injection on Days 3, 10, 17, and 24. The primary objective was to evaluate changes from baseline in plasma PPi concentrations. Secondary objectives evaluated PK and ENPP1-Fc activity. Safety assessments included adverse events, laboratory parameters, vital signs, ECGs, physical examinations, and anti-drug antibodies. Participants were followed for up to 12 months after last dose.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Coral Springs, Florida, United States, 33071
      • South Florida Nephrology Research
    • Hollywood, Florida, United States, 33024
      • Elixia Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Individuals meeting the following inclusion criteria may participate:

1. Study participants must provide written or electronic consent after the nature of the study has been explained, and prior to any research-related procedures, per International Council for Harmonisation (ICH) Good Clinical Practice (GCP)
2. Have ESKD and are receiving HD treatment
3. Are compliant with receiving 3 treatments of HD per week with a functioning arteriovenous (AV) fistula, AV graft, or central venous catheter
4. PPi level <700 nmol/L at Screening
5. Must be willing and able to comply with the diet prescribed by their treating physician and/or the Investigator
6. Male or female aged >18 years to <70 years
7. Women of child-bearing potential (WOCBP) as defined in Clinical Trials Coordination Group (CTFG 2020) and provided in Appendix B, must have a negative serum pregnancy test at Screening and within 3 days of INZ-701 administration
8. 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 to 30 days after the last dose (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 time of the first INZ-701 dose to 30 days after the last dose.
9. Males who are sexually active must agree to use condoms from the time of the first INZ-701 dose to 30 days after the last dose. Males must also agree to not donate sperm from the time of the first INZ-701 dose to 30 days after the last dose.
10. In the opinion of the Investigator, study participants are able and willing to complete all study procedures per protocol.

Exclusion Criteria:

Individuals meeting any of the following exclusion criteria may not participate:

1. Study participants receiving other types of dialysis than HD (eg, peritoneal dialysis, hemodiafiltration)
2. Study participants who are hospitalized
3. In the opinion of the Investigator, presence of any clinically significant disease or laboratory abnormality that may impact study participation and/or confound interpretation of the study results
4. Malignancy within the last year, except non-melanoma skin cancers or cervical carcinoma in situ
5. Advanced liver disease manifesting as liver cirrhosis
6. Myocardial infarction, stroke, or congestive heart failure requiring hospitalization within the last 6 months
7. Known intolerance to INZ-701 or any of its excipients
8. Weight >125 kg
9. Concurrent participation in another 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: INZ-701; Participants received INZ-701 1.8 mg/kg administered subcutaneously once weekly on Days 3, 10, 17, and 24.	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.; Other Names: (rhENPP1-Fc).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Plasma Inorganic Pyrophosphate (PPi) Concentrations	Change from baseline in pre-hemodialysis plasma inorganic pyrophosphate concentrations throughout the study.	Baseline through Follow-up Period (up to 12 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the Maximum Serum Concentration (Cmax) of INZ-701	For each participant, the maximum concentration of INZ-701 in the serum will be measured via a series of blood samples obtained throughout the study, comparing the participant's baseline value over time.	26 days (Treatment Period)
Assess the Area under the concentration-time curve over the dosing interval (AUCtau)	For each participant, variation of concentration of INZ-701 in the serum will be measured via a series of blood samples obtained throughout the study, comparing the participant's baseline value over time.	26 days (Treatment Period)
Assess the Clearance after extravascular administration of drug (CL/F)	For each participant, clearance of INZ-701 from the body will be measured via a series of blood samples obtained throughout the study, comparing the participant's baseline value over time.	26 days (Treatment Period)
Assess ENPP1 Activity	For each participant, ENPP1 activity is a measurement of INZ-701 activity in human serum using a chromogenic based method.	26 days (Treatment Period)
Serum INZ-701 Concentrations	Observed serum concentration-time profile of INZ-701.	Day 1 to Day 26

Collaborators and Investigators

• Sponsor: Inozyme Pharma
• Collaborators: BioMarin Pharmaceutical
• Investigators: Study Director: Kurt Gunter, MD, Inozyme Pharma

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2024
• Primary Completion (Actual): July 27, 2024
• Study Completion (Actual): December 13, 2024

Study Registration Dates

• First Submitted: February 21, 2024
• First Submitted That Met QC Criteria: February 21, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): August 24, 2026
• Last Update Submitted That Met QC Criteria: August 20, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: calcification; vascular calcification; calcinosis; calcium metabolism disorders; chronic kidney disease (CKD); calcific uremic arteriolopathy; fusion protein; calcinosis cutis; mineral bone disorder (MBD); end stage renal disease (ESKD)
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Metabolic Diseases; Skin Diseases; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Calcinosis Cutis; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Calcinosis; Vascular Calcification; Calciphylaxis; Calcium Metabolism Disorders
• Other Study ID Numbers: INZ701-401

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The sponsor does not plan to share any data as this product is still in development

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No