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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
11
Recombinant fusion protein that contains the extracellular domains of human ENPP1 coupled with an Fc fragment from an immunoglobulin gamma-1 (IgG1) antibody.
South Florida Nephrology Research
Coral Springs, Florida, United States
Elixia Health
Hollywood, Florida, United States
Change From Baseline in Plasma Inorganic Pyrophosphate (PPi) Concentrations
Change from baseline in pre-hemodialysis plasma inorganic pyrophosphate concentrations throughout the study.
Time frame: Baseline through Follow-up Period (up to 12 months)
Serum INZ-701 Concentrations
Observed serum concentration-time profile of INZ-701.
Time frame: Day 1 to Day 26
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 26 days (Treatment Period)
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