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 pharmacokinetics of INZ-701 and PPi levels will be evaluated.
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, pharmacokinetics (PK), and pharmacodynamics (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- or 60- days after the last dose of INZ-701, , and a Follow-Up Period lasting up to 365 days after the last dose During the Follow-Up Period, safety, PPi, ENPP1 activity, anti-drug antibodies (ADA) assessments, and genetic testing will be conducted. Participants may be followed for \> 1 year if they have increasing ADA titers or have serious adverse events (SAEs) related to ADAs as determined by the Sponsor
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
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.
Time frame: 26 days (Treatment Period)
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.
Time frame: 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.
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.
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Time frame: 26 days (Treatment Period)