The SEAPORT 1 Study: Evaluation of the Safety and Tolerability of INZ-701 in Adults With End-Stage Kidney Disease Undergoing Hemodialysis

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

The purpose of this study is to determine if multiple doses of INZ-701, given once per week over 4 weeks are safe and increase pyrophosphate (PPi) levels in hemodialysis-dependent (HD) end stage kidney disease (ESKD) study participants who have low PPi levels. In addition, the effect of hemodialysis on the PK of INZ-701 and PPi levels will be evaluated.

Study Overview

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

Detailed Description

INZ-701 is an ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) recombinant fusion protein in development for the treatment of calciphylaxis. The SEAPORT 1 (INZ701-401) Study is a Phase 1, open-label study to evaluate the safety, PK, and PD of multiple doses of INZ-701 in study participants aged >18 to < 70 years with HD-dependent ESKD. Anticipated enrollment in the study is up to 10 study participants. The purpose of this study is to determine if INZ-701 increases PPi levels, as well as assess the PK/ PD characteristics of INZ-701 in patients with clinically low PPi levels.

The study will consist of a Screening Period lasting up to 30 days, a Treatment and Assessment Period lasting 26 days, an end of study (EOS) Visit 30 days after the last dose of INZ-701, and if necessary, a safety visit 60 days after the last dose of INZ-701.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Inozyme Clinical Trial Information; Phone Number: +1 857 330 4340; Email: clinicaltrials@inozyme.com

Study Locations

• United States
  • Florida
    • Coral Springs, Florida, United States, 33071
      • Recruiting
      • South Florida Nephrology Research
      • Contact: Ashgar Chaudhry, MD; Phone Number: 954-510-7620; Email: info@flkidney.com
    • Hollywood, Florida, United States, 33024
      • Recruiting
      • Elixia Health
      • Contact: Steven Zeig; Phone Number: 954-900-1101; Email: info@elixiacrc.com

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 Conference on 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 Facilitation and 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; The study consists of a 26-day treatment period where the dose of INZ-701 will be 1.8 mg/kg once weekly. INZ-701 will be administered as a subcutaneous injection once weekly for 4 weeks on Days 3, 10, 17, and 24. The study participant's post-hemodialysis body weight on Day 1 will be used to calculate the dose to be administered.	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
Determine if INZ-701 increases PPi levels	For each participant, plasma PPi will be measured via a series of blood samples obtained throughout the study, comparing the participant's baseline value over time to determine if there's been a change.	26 days (Treatment Period)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the Time to Maximum Serum Concentration (Tmax)	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 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)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2024
• Primary Completion (Estimated): July 19, 2024
• Study Completion (Estimated): August 19, 2024

Study Registration Dates

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

Study Record Updates

• Last Update Posted (Estimated): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

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

Drug and device information, study documents

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