A Phase 1, Open-label, Dose-escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ALXN1850 in Adults With Hypophosphatasia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
研究概览
简要总结
This is an open-label, dose-escalating study to assess safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and immunogenicity of ALXN1850 when given intravenous (IV) and subcutaneous (SC) to adults with HPP.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed clinical diagnosis of HPP
- •Not anticipated to require further treatment with enzyme replacement therapy to treat participant's HPP after study completion
- •Willing and able to follow protocol-specified contraception requirements
- •Willing and able to give informed consent
排除标准
- •Primary or secondary hyperparathyroidism or hypoparathyroidism
- •Fracture within 12 weeks of screening
- •Current or relevant history of unstable physical or psychiatric illness
- •Significant allergies
- •Asfotase alfa use within 6 months and/or positive for asfotase alfa antidrug antibody/neutralizing antibodies
研究组 & 干预措施
ALXN1850
Three experimental cohorts will be administered 3 dosages (low, medium, high) of ALXN1850, respectively, via IV infusion and/or SC over multiple administration intervals.
干预措施: ALXN1850 (Biological)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
时间窗: Day 1 up to Day 85
TEAEs were defined as any adverse events (AEs) that began or worsened on or after the first dose of treatment until the final follow-up visit. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction. TESAEs were defined as any serious AEs that began or worsened on or after the first dose of treatment until the final follow-up visit. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
次要结局
- Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Values of the First SC Versus IV Administration of ALXN1850(Predose, 2, 6 and 12 hour postdose on Days 1, 15, 22 and 29)
- Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity Following IV Dose of ALXN1850(Predose, 2, 6 and 12 hours postdose on Days 1, 15, 22 and 29)
- Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Following SC Dose 1, SC Dose 2 and SC Dose 3(Predose, 2, 6 and 12 hour postdose on Days 1, 15, 22 and 29)
- Maximum Observed Plasma Concentration (Cmax) of ALXN1850 Following Intravenous (IV) Dose, Subcutaneous (SC) Dose 1, SC Dose 2 and SC Dose 3(Predose, 2, 6 and 12 hours postdose on Days 1, 15, 22 and 29)
- Absolute Change From Baseline in Plasma Concentration of Pyridoxal-5' Phosphate (PLP) at Week 1(Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3)
- Absolute Change From Baseline in Plasma Concentration of Inorganic Pyrophosphate (PPi) at Week 1(Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3)
- Absolute Change From Baseline in Plasma Concentration of Pyridoxal Phosphate/ Pyridoxal (PLP/PL) Ratio at Week 1(Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3)
- Percent Change From Baseline in Plasma Concentration of PLP at Week 1(Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3)
- Percent Change From Baseline in Plasma Concentration of PPi at Week 1(Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3)
- Percent Change From Baseline in Plasma Concentration of PLP/PL Ratio Over Time at Week 1(Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3)
- Number of Participants With Anti-drug Antibody (ADA) Positive and Neutralizing Antibody (NAb) Positive Status(Baseline up to Day 85)