A Randomised, Placebo Controlled, Double-Blind, Single-Ascending Dose And Multiple-Ascending Dose First-In-Human Study To Investigate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Orally Administered ALE1 With Or Without Food In Healthy Adult Subjects And Adult Patients With Hypophosphatasia
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 3
- 主要终点
- Evaluate safety of ALE1 by assessing changes in heart rhythms via electrocardiogram
研究概览
简要总结
This is a phase 1/2a randomised, placebo controlled, double-blind study investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of ALE1 on healthy adult subjects and adult patients with Hypophosphatasia (HPP).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants are overtly healthy as determined by a medical evaluation
- •No concurrent medical conditions or significant medical history, in the opinion of the investigator.
- •Key Inclusion Criteria Part 2:
- •1. Documented ALPL gene variant
排除标准
- •1. History of conditions affecting bone or mineral metabolism
- •Key Exclusion Criteria Part 2:
- •Previous treatment with an enzyme replacement therapy (ERT) or any advanced therapeutic agent (e.g., gene therapy) for the treatment of hypophosphatasia (HPP) or any treatment for osteoporotic diseases
- •Previous exposure to any medication or investigational agent potentially affecting bone structure, muscle volume, muscle strength, or muscle or nerve function
- •Diagnosis of hyperparathyroidism
- •Diagnosis of hypoparathyroidism, unless secondary to HPP
- •New fracture within 12 weeks before first dosing
研究组 & 干预措施
Part 2 Cohort A
干预措施: ALE1 (Drug)
Part 1 Cohort A
干预措施: Placebo (Drug)
Part 1 Cohort B
干预措施: ALE1 (Drug)
Part 2 Cohort B
干预措施: ALE1 (Drug)
Part 1 Cohort C
干预措施: ALE1 (Drug)
Part 1 Cohort B
干预措施: Placebo (Drug)
Part 2 Cohort A
干预措施: Placebo (Drug)
Part 2 Cohort B
干预措施: Placebo (Drug)
Part 1 Cohort C
干预措施: Placebo (Drug)
Part 1 Cohort A
干预措施: ALE1 (Drug)
结局指标
主要结局
Evaluate safety of ALE1 by assessing changes in heart rhythms via electrocardiogram
时间窗: From baseline up to day 16
Evaluate the safety of ALE1 by assessing the number of treatment emergent adverse events (TEAEs)
时间窗: From baseline up to day 16
Evaluate safety of ALE1 by assessing the presence of clinically significant changes in participants haematology parameters post-dose
时间窗: From baseline up to day 16
Evaluate safety of ALE1 by assessing the presence of clinically significant changes in participants biochemistry parameters post-dose
时间窗: From baseline up to day 16
Evaluate safety of ALE 1 by assessing the presence of clinically significiant changes in participants vital signs
时间窗: From baseline up to day 16
次要结局
- Pharmacokinetic parameter: volume of distribution (Vd/F)(From baseline up to day 16)
- Pharmacokinetic parameter: area under the plasma concentration versus time curve (AUC (D0 - INF))(From baseline up to day 16)
- Pharmacokinetic parameter: time at which maximum plasma concentration occurs (Tmax)(From baseline up to day 16)
- Pharmacokinetic parameter: terminal elimination phase half-life (t(1/2))(From baseline up to day 16)
- Pharmacokinetic parameter: total clearance (CL/F)(From baseline up to day 16)
- Change in pharmacodynamic biomarker levels in blood samples of ALE1(From baseline up to day 16)
- Dose proportionality of maximum observed plasma concentration (Cmax) Time at which maximum plasma concentration occurs (Tmax)(From baseline up to day 16)
- Effect of food on area under the plasma concentration versus time curve (AUC (D0 - INF))(From baseline up to 16 days post dose)
- Effect of food on maximum observed plasma concentration (Cmax)(From baseline up to day 16)
- Dose proportionality of area under the plasma concentration versus time curve (AUC (D0 - INF))(From baseline up to day 16)