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

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.

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.

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