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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 4
- 主要终点
- Determine if INZ-701 increases PPi levels
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Individuals meeting the following inclusion criteria may participate:
- •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)
- •Have ESKD and are receiving HD treatment
- •Are compliant with receiving 3 treatments of HD per week with a functioning arteriovenous (AV) fistula, AV graft, or central venous catheter
- •PPi level <700 nmol/L at Screening
- •Must be willing and able to comply with the diet prescribed by their treating physician and/or the Investigator
- •Male or female aged >18 years to <70 years
- •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
- •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.
- •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.
- •In the opinion of the Investigator, study participants are able and willing to complete all study procedures per protocol.
排除标准
- •Individuals meeting any of the following exclusion criteria may not participate:
- •Study participants receiving other types of dialysis than HD (eg, peritoneal dialysis, hemodiafiltration)
- •Study participants who are hospitalized
- •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
- •Malignancy within the last year, except non-melanoma skin cancers or cervical carcinoma in situ
- •Advanced liver disease manifesting as liver cirrhosis
- •Myocardial infarction, stroke, or congestive heart failure requiring hospitalization within the last 6 months
- •Known intolerance to INZ-701 or any of its excipients
- •Weight >125 kg
- •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
研究组 & 干预措施
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.
干预措施: INZ-701 (Drug)
结局指标
主要结局
Determine if INZ-701 increases PPi levels
时间窗: 26 days (Treatment Period)
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.
Change From Baseline in Plasma Inorganic Pyrophosphate (PPi) Concentrations
时间窗: Baseline through Follow-up Period (up to 12 months)
Change from baseline in pre-hemodialysis plasma inorganic pyrophosphate concentrations throughout the study.
次要结局
- Assess the Area under the concentration-time curve over the dosing interval (AUCtau)(26 days (Treatment Period))
- Assess the Time to Maximum Serum Concentration (Tmax)(26 days (Treatment Period))
- Assess the Clearance after extravascular administration of drug (CL/F)(26 days (Treatment Period))
- Assess the Maximum Serum Concentration (Cmax) of INZ-701(26 days (Treatment Period))
- Assess ENPP1 Activity(26 days (Treatment Period))
- Serum INZ-701 Concentrations(Day 1 to Day 26)