Calciphylaxis
Conditions
Keywords
calcific uremic arteriolopathy, calcinosis cutis, calcification, calcium metabolism disorders, mineral bone disorder (MBD), fusion protein, vascular calcification, end stage renal disease (ESKD), chronic kidney disease (CKD), calcinosis
Brief summary
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.
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.
Interventions
DRUGINZ-701
Recombinant fusion protein that contains the extracellular domains of human ENPP1 coupled with an Fc fragment from an immunoglobulin gamma-1 (IgG1) antibody.
Sponsors
Inozyme Pharma
BioMarin Pharmaceutical
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single-group assignment. All enrolled participants received INZ-701 1.8 mg/kg administered subcutaneously once weekly for 4 weeks. The study was designed to evaluate the safety, pharmacokinetics, and pharmacodynamics of INZ-701 in adults with hemodialysis-dependent end-stage kidney disease and low plasma inorganic pyrophosphate (PPi) levels. No placebo or active comparator group was included.
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plasma Inorganic Pyrophosphate (PPi) Concentrations | Baseline through Follow-up Period (up to 12 months) | Change from baseline in pre-hemodialysis plasma inorganic pyrophosphate concentrations throughout the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum INZ-701 Concentrations | Day 1 to Day 26 | Observed serum concentration-time profile of INZ-701. |
| Assess the Maximum Serum Concentration (Cmax) of INZ-701 | 26 days (Treatment Period) | 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. |
| Assess the Area under the concentration-time curve over the dosing interval (AUCtau) | 26 days (Treatment Period) | 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. |
| Assess the Clearance after extravascular administration of drug (CL/F) | 26 days (Treatment Period) | 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. |
| Assess ENPP1 Activity | 26 days (Treatment Period) | For each participant, ENPP1 activity is a measurement of INZ-701 activity in human serum using a chromogenic based method. |
Countries
United States
Outcome results
None listed