The ENERGY Study: An Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INZ-701 in Infants With Ectonucleotide Pyrophosphatase/ Phosphodiesterase 1 (ENPP1) Deficiency or ATP-binding Cassette Sub-family C Member 6 (ABCC6) Deficiency
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 16
- 试验地点
- 6
- 主要终点
- Number of Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
The primary purpose of Study INZ701-104 (the ENERGY study) is to assess the safety and tolerability of INZ-701 in infants with ENPP1 Deficiency or with ABCC6 Deficiency.
详细描述
INZ-701 is an ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) enzyme replacement therapy in development for the treatment of the ultra-rare genetic disorder, ENPP1 Deficiency or with ABCC6 Deficiency.
Study INZ701-104 (the ENERGY study) is a Phase 1b, open-label study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of INZ-701 in infant study participants with ENPP1 Deficiency or ABCC6 Deficiency.
The study will consist of up to a 60-day Screening Period, a 52-week Treatment Period during which study participants will receive INZ-701, an Extension Period during which participants may continue to receive INZ-701 until it is commercially available in the country where the participant resides, or until an alternative study of INZ-701 is available, and an End of Treatment (EOT) visit 30 days after the last dose of INZ-701. Upon treatment discontinuation, participants will continue to be followed for their ongoing disposition for survival outcome at least quarterly through the end of the study.
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
- — 至 1 Year（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Infant aged ≤ 1 year at the time of enrollment
- •Study participant must have a confirmed post-natal molecular genetic diagnosis of ENPP1 Deficiency or ABCC6 Deficiency
- •Study participants must have clinical manifestations of generalized arterial calcification of infancy (GACI) or GACI-2, which must include at least one of the following: ectopic calcification, heart failure, respiratory distress, edema, cyanosis, hypertension, and cardiomegaly.
- •Study participant must weigh ≥0.5 kg at the time of the first dose of INZ-701 in this study
- •Written informed consent provided by a parent or legal guardian
排除标准
- •In the opinion of the Investigator, presence of any clinically significant disease or laboratory abnormality that precludes study participation or may confound interpretation of study result
- •Receiving end of life or hospice care
- •Known malignancy
- •Concurrent participation in another non-Inozyme interventional study
- •Treatment with any non-Inozyme product or investigational device during study participation
研究组 & 干预措施
INZ-701
The first 2 study participants will receive 1 dose of 0.2 mg/kg on Day 1 and start at Dose Level A (0.2 mg/kg twice weekly) on Day 8.
The Data Review Committee (DRC) comprised of representatives of the Sponsor, the study Investigators, and a physician who is a subject matter expert not affiliated with the study or Sponsor, will review the safety data of the first study participant through Day 8. Contingent upon this review, the Sponsor will decide if additional study participants can begin receiving INZ-701.
After the second study participant completes Day 32, the DRC will perform a cumulative review of safety and PK/PD data and will make dosing recommendations, for example, modifying the dose of the ongoing study participants and/or changing the starting dose for future participants.
Dose Level A: 0.2 mg/kg twice weekly
Dose Level B: 0.6 mg/kg twice weekly
Dose Level C: 0.2 mg/kg once weekly
Dose Level D: 0.6 mg/kg once weekly
Dose Level E: 1.8 mg/kg once weekly
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 (Treatment Period)
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.
Incidence of Anti-Drug Antibodies (ADA)
时间窗: 52 weeks (Treatment Period)
For each participant, the presence of ADAs will be assessed and, if present, further evaluation will determine specificity and subtypes.
Left Ventricular Ejection Fraction
时间窗: 52 weeks (Treatment Period)
For each participant, an echocardiogram will be collected, and used to assess heart function. (Including measurement of left ventricular ejection fraction), and to identify any other abnormalities, for example, calcification of heart valves.
次要结局
- Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) Levels(52 weeks (Treatment Period))
- ENPP1 Activity(52 weeks (Treatment Period))
- Area under the Plasma Concentration versus Time Curve (AUC) of INZ-701(52 weeks (Treatment Period))
- Maximum Plasma Concentration (Cmax) of INZ-701(52 weeks (Treatment Period))