A Multicenter, Open-Label Study of the Safety, Tolerability and Pharmacology of Asfotase Alfa in up to 10 Severely Affected Patients With for the Treatment of Severely Affected Patients With Infantile Hypophosphatasia (HPP)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 19
- 主要终点
- Change in Rickets Severity From Baseline to Week 24, Based on Assessment of Skeletal Radiographs Using Radiologic Global Impression of Change (RGI-C)
研究概览
简要总结
This clinical trial studies the safety and efficacy of asfotase alfa in infants and young children with infantile onset HPP.
详细描述
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 no approved disease-modifying treatments for patients with this disease. There is also 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
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 36 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Legal guardian(s) must provide informed consent prior to any study procedures
- •Documented diagnosis of severe HPP as indicated by:
- •Total serum alkaline phosphatase at least 3 standard deviations (SD) below the mean for age
- •Plasma pyridoxal 5'-phosphate (PLP) at least 4 times the upper limit of normal
- •Radiographic evidence of HPP (hypophosphatasia), characterized by:
- •Flared and frayed metaphyses
- •Severe, generalized osteopenia
- •Widened growth plates
- •One or more HPP-related findings:
- •History or presence of:
- •Non-traumatic post-natal fracture
- •Delayed fracture healing
- •History of elevated serum calcium
- •Functional craniosynostosis with decreased head circumference growth
- •Nephrocalcinosis
- •Respiratory compromise
- •Rachitic chest deformity and/or vitamin B6 dependent seizures
- •Failure to thrive
- •Onset of symptoms prior to 6 months of age
- •Age ≤ 36 months
- •Otherwise medically stable (patient may be on ventilatory support)
- •Legal guardian(s) must be willing to comply with the study
排除标准
- •History of sensitivity to any of the constituents of the study drug
- •Current or prior clinically significant cardiovascular, endocrinologic, hematologic, hepatic, immunologic, metabolic, infectious, urologic, pulmonary, neurologic, dermatologic, renal condition and/or other major disease which, in the opinion of the investigator, precludes study participation
- •Treatment with an investigational drug within 1 month prior to the start of study drug administration
- •Current enrollment in any other study involving an investigational new drug, device or treatment for HPP (e.g., bone marrow transplantation)
- •Low serum calcium, phosphate or 25(OH) vitamin D
- •Current evidence of a treatable form of rickets
- •Prior treatment with bisphosphonate
结局指标
主要结局
Change in Rickets Severity From Baseline to Week 24, Based on Assessment of Skeletal Radiographs Using Radiologic Global Impression of Change (RGI-C)
时间窗: 24 weeks
A 7-point RGI-C (Radiographic Global Impression of Change) score was used to rate change in rickets severity. Scores ranged from -3 (severe worsening of rickets) to +3 (complete healing of rickets). Only those patients with a minimum score of +2 indicating substantial healing of rickets) were considered "responders". Three pediatric radiologists not affiliated with the conduct of the study performed the ratings. Average scores were derived for each patient at each assessment.
次要结局
- Area Under Serum Concentration-time Curve to Last Measurable Concentration of Asfotase Alfa (AUCt)(Study Week 1 (0 to 168 hours post-dose). Study Week 2 and Study Week 3 (0 to 48 hours post-dose).)
- Maximum Serum Concentration of Asfotase Alfa (Cmax)(Study Week 1 (0 to 168 hours post-dose). Study Week 2 and Study Week 3 (0 to 48 hours post-dose))
- Time at Maximum Serum Concentration of Asfotase Alfa (Tmax)(Study Week 1 (0 to 168 hours post-dose). Study Week 2 and Study Week 3 (0 to 48 hours post-dose).)