A Randomized, Open-Label, Multicenter, Multinational, Dose-Ranging, Concurrent Control Study of the Safety, Efficacy, Pharmacokinetic of ENB-0040 (Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein) in Adolescents and Adults With Hypophosphatasia (HPP)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 3
- 主要终点
- Change From Baseline to Week 24 for Plasma Pyridoxal-5' Phosphate (PLP)
研究概览
简要总结
This clinical trial was conducted to study hypophosphatasia (HPP), a bone disorder caused by gene mutations or changes. These gene mutations cause low levels of an enzyme needed to harden bone. The purpose of this study was to test the safety and efficacy of two doses of the study drug called asfotase alfa as compared to a control group to see effects on adolescents and adults with HPP.
详细描述
Asfotase alfa was formerly referred to as ENB-0040
Hypophosphatasia (HPP) is a life-threatening, genetic, and ultra-rare metabolic disease characterized by defective bone mineralization and impaired phosphate and calcium regulation that can lead to progressive damage to multiple vital organs, including destruction and deformity of bones, profound muscle weakness, seizures, impaired renal function, and respiratory failure. There are limited data available on the natural course of this disease over time, particularly in patients with the juvenile-onset form.
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
- None
入排标准
- 年龄范围
- 13 Years 至 65 Years（Child, 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
Cohort 1
Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (2.1 mg/kg/week total)
干预措施: asfotase alfa (Drug)
Cohort 2
Cohort 2: Daily SC injections of 0.5 mg/kg asfotase alfa (3.5 mg/kg/week total)
干预措施: asfotase alfa (Drug)
结局指标
主要结局
Change From Baseline to Week 24 for Plasma Pyridoxal-5' Phosphate (PLP)
时间窗: Baseline, Week 24
Blood samples were collected to evaluate the effect of asfotase alfa on reduction in plasma pyridoxal-5' phosphate (PLP)
Safety and Tolerability of Asfotase Alfa
时间窗: Up to 288 weeks exposure to asfotase alfa
The safety and tolerability of daily subcutaneous (SC) injections of asfotase alfa was assessed by routine monitoring of patients for treatment-emergent adverse events (TEAEs) and injection-associated reactions (IARs).
Change From Baseline to Week 24 for Plasma Inorganic Pyrophosphate (PPi)
时间窗: Baseline, Week 24
Blood samples were collected to evaluate the effect of asfotase alfa on reduction in plasma inorganic pyrophosphate (PPi)
次要结局
- Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Osteoid Thickness(Baseline, Week 24 (Control group), and Week 48 (Asfotase alfa groups).)
- Change in Walking Ability as Measured by the Six-Minute Walk Test (6MWT)(Baseline, Week 24 (primary treatment period) and up to 288 weeks of asfotase alfa exposure)
- Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA)(Baseline, every 24 weeks through Week 96, then every 48 weeks until Week 288.)
- Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA)(Baseline, every 24 weeks through Week 96, then every 48 weeks until Week 288.)
- Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Osteoid Volume/Bone Volume(Baseline, Week 24 (Control group), and Week 48 (Asfotase alfa groups).)
- Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Mineralization Lag Time(Baseline, Week 24 (Control group), and Week 48 (Asfotase alfa groups).)