A Phase 1/2 Open-label Study in Patients With Arginase I Deficiency to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of Intravenous AEB1102
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 9
- 主要终点
- Number of subjects with adverse events
研究概览
简要总结
A Phase 1/2 Open-label Study in Patients with Arginase I Deficiency to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of Intravenous AEB1102. This study is designed to evaluate the safety and tolerability of IV administration of AEB1102 for the treatment of pediatric and adult patients with Arginase I deficiency and hyperargininemia. This study will be conducted in 2 parts: Part 1 (Single Ascending Dose Escalation) and Part 2 (Repeated Dosing). Each part will be preceded by a baseline assessment of arginine levels. All patients who participate in Part 1 may continue AEB1102 dosing in Part 2 if they qualify for continued dosing. A data safety monitoring board (DSMB) will provide independent review of study safety data and recommend whether the sponsor should continue the study as planned, modify the study protocol, or discontinue 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
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented diagnosis of Arginase I deficiency
- •Adequate organ function: Hgb ≥ 10 g/dL, ANC ≥ 1.5 x 109/L, plt count ≥ 100,000/µL; liver transaminase levels ≤ 2.5x ULN, total bilirubin ≤ 2.0 mg/dL; serum creatinine <1.5 x ULN
- •If female and of child-bearing potential, has a negative serum pregnancy test within 7 days before enrollment
- •If a sexually active (male or female), must be surgically sterile, post-menopausal (female), or must agree to use a physician-approved method of birth control during the study and for a minimum of 30 days after the last study drug administration
- •Patient or legal guardian is able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures and continuation of prescribed diet without modification) prior to any screening procedures
排除标准
- •Transfusion of ≥ 2 u RBC within 60 days
- •Active infection requiring systemic treatment
- •Known infection with HIV, Hep B or Hep C
- •Severe hyperammonemia requiring hospitalization within 14 days. Had more than one episode of hyperammonemia requiring hospitalization within the 30 days prior to enrollment.
- •Current uncontrolled hyperammonemia
- •Has a history of hypersensitivity to PEG or any other component of the AEB1102 (Co-ArgI-PEG) formulation
- •If female, is lactating or breast feeding
- •PART 2 INCLUSION CRITERION:
- •Did not experience any safety or tolerability event in Part 1 which would preclude continued participation and dosing of AEB1102
研究组 & 干预措施
AEB1102
AEB1102, modified human Arginase I administered IV Part 1 Each patient may receive up to 7 doses given up to every other week over a maximum of 14 weeks.
Part 2 Each patient will receive up to 8 weeks of repeat-dose therapy.
干预措施: AEB1102 (Drug)
结局指标
主要结局
Number of subjects with adverse events
时间窗: weekly throughout the study, up to 14 weeks
Includes significant changes in hematology, chemistry and coagulation laboratory studies as well as in physical exam and vital signs
次要结局
- Number of subjects with a decrease from baseline in plasma guanidino compound levels(Baseline to 2, 4, 6, 8 weeks)
- Number of subjects with a decrease from baseline in plasma arginine level(Baseline to 2, 4, 6, 8 weeks)
- Pharmacokinetic profile including Cmax, AUC, Tmax, T1/2 for each subject(At 15 min, 1, 2, 4, 8, 12, 24, 48, 72, and 120 hours following dose escalation)