A Phase 1/2, Open-Label, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INZ-701 Followed by an Open-Label Long-Term Extension Period in Adults With ABCC6 Deficiency Manifesting as Pseudoxanthoma Elasticum (PXE)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Number of Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics PD) of multiple ascending doses of INZ-701, an ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) recombinant fusion protein, for the treatment of ABCC6 Deficiency. The goal of the study is to identify a dose regimen for further clinical development in the treatment of ABCC6 Deficiency.
详细描述
INZ-701 is an ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) recombinant fusion protein in development for the treatment of ABCC6 Deficiency, a rare genetic disorder.
Study INZ701-201 is a Phase 1/2, multicenter, open-label, multiple ascending dose (MAD), dose-finding study followed by a long-term open-label Extension Period conducted in adults with ABCC6 Deficiency manifesting as Pseudoxanthoma elasticum (PXE). This study is designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of multiple ascending doses of INZ-701. The goal of the study is to identify a dose and dose schedule (number of doses per week) for further clinical development in ABCC6 Deficiency. No placebo will be used in this study.
Exploratory endpoints for the Extension Period of the study include evaluations of arterial and organ calcification, ophthalmologic, cardiac and renal parameters, and physical function as well as patient reported outcomes.
Subject participation consists of a Screening Period of up to 60 days, a 32-day Dose Evaluation Period, and an Extension Period during which subjects may continue to receive INZ-701 (with options for self-, caregiver-, or healthcare provider administration) until INZ-701 is approved and available in the country where the subject resides or until an alternative study for subjects to continue receiving study drug is available. During the Extension Period, follow-up visits will be conducted every 4 weeks until Week 48 of the Extension Period and then every 12 weeks (remote or in-clinic) until the subject leaves the study.
Subjects will complete a follow up visit 30 days after their last dose of INZ-701.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
INZ-701
The study design of the Dose Evaluation Period is a MAD 3 + 3 with 3 dose cohorts.
Based on nonclinical findings and nonclinical pharmacology modeling, the initial planned doses will be 0.2 mg/kg, 0.6 mg/kg, and 1.8 mg/kg, with a twice weekly dose regimen.
During the Extension Period, INZ-701 administration will initially be at the dose and dose schedule assigned in the Dose Evaluation Period; however, the Sponsor may modify the assigned dose and/or dosing regimen in the Extension Period post-Week 48 based on cumulative review of safety and PK/PD data, including population PK.
Study visits will be in-clinic every 4 weeks until Week 48 of the Extension Period and then every 12 weeks (remote or in-clinic) until the subject leaves the study. Subjects will complete an End of Study (EOS) Visit (Safety Follow-up Visit) 30 days after their last dose of INZ-701.
干预措施: INZ-701 (Drug)
结局指标
主要结局
Number of Treatment Emergent Adverse Events (TEAEs)
时间窗: 52 weeks (Day 1 through Safety Follow-up Visit)
Treatment-emergent AEs are defined as any AE occurring from the first dose of INZ-701 through 30 days after the last dose of INZ-701.
次要结局
- Incidence of Anti-Drug Antibodies (ADAs)(52 weeks (Day 1 through Safety Follow-up Visit))
- Maximum Plasma Concentration (Cmax) of INZ-701(32 days (Dose Evaluation Period))
- Area under the Plasma Concentration versus Time Curve (AUC) of INZ-701(32 days (Dose Evaluation Period))
- Systemic Clearance of INZ-701(32 days (Dose Evaluation Period))
- Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) Levels(52 weeks (Baseline through Safety Follow-up Visit))