A Phase 2a, Randomized, Multicenter, Open-Label, Pharmacokinetic, and Dose Response Study of Asfotase Alfa in Adult Patients With Pediatric-Onset Hypophosphatasia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 4
- 主要终点
- Change In Plasma PPi From Baseline To Pre-3rd Dose At Week 9
研究概览
简要总结
The purpose of this study was to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of asfotase alfa in adult participants with pediatric-onset 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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants or their legal representative(s) provided written informed consent prior to undergoing any study-related procedures.
- •Participants were ≥18 years of age at Screening.
- •Participant had pediatric-onset hypophosphatasia (HPP), defined as onset of first sign(s)/symptom (s) of HPP prior to 18 years of age.
- •Participants had a documented diagnosis of HPP as indicated by a documented history of HPP-related skeletal abnormalities and 1 or more of the following:
- •Documented tissue-nonspecific alkaline phosphatase (TNSALP) gene mutation(s) from a certified laboratory.
- •Serum alkaline phosphatase (ALP) level below the age-adjusted normal range AND plasma pyridoxal-5'-phosphate (PLP) above the upper limit of normal at Screening.
- •Participants had a plasma inorganic pyrophosphate (PPi) level of ≥3.9 micromolar (µM) at Screening.
- •Female participants of childbearing potential had a negative pregnancy test at the time of enrollment.
- •Sexually active male and female participants of childbearing potential agreed to use a highly effective method of birth control during the study.
- •Female participants not of child-bearing potential due to sterilization (at least 6 weeks after surgical bilateral oophorectomy with or without hysterectomy or at least 6 weeks after tubal ligation) confirmed by medical history, or menopause.
- •Participants were willing to comply with study procedures and the visit schedule.
排除标准
- •Investigational site personnel directly affiliated with this study and/or their immediate families. Immediate family was defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
- •Employees of Alexion Pharmaceuticals.
- •Currently enrolled in a clinical study involving another study drug or non-approved use of a drug or device.
- •Participated, within the last 30 days, in a clinical study involving a study drug (other than the study drug used in this study).
- •Completed or withdrawn from this study or any other study investigating asfotase alfa in the previous 3 years.
- •Women who were pregnant, planning to become pregnant, or breastfeeding.
- •Serum 25-hydroxy Vitamin D levels below 20 nanogram (ng) per milliliter (mL) at Screening.
- •Screening serum creatinine or parathyroid hormone (PTH) levels ≥1.5 times the upper limit of normal.
- •Any medical condition, serious concurrent illness and/or injury, recent orthopedic surgery, or other extenuating circumstance that, in the opinion of the Investigator, may have significantly interfered with study compliance or study endpoints.
- •Prior treatment with bisphosphonates within 2 years of study entry for any length of time or for more than 2 consecutive years at any prior timepoint.
- •Treatment with PTH, strontium, or sclerostin inhibitors within 6 months prior to the first dose of study drug.
- •Unwilling or unable to comply with the use of a data collection device on which study participants directly recorded data.
研究组 & 干预措施
Asfotase Alfa 0.5 mg/kg Dose
Participants received 0.5 milligrams (mg) per kilogram (kg) of asfotase alfa administered subcutaneously (SC) 3 times a week from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1.
干预措施: Asfotase alfa (Drug)
Asfotase Alfa 2.0 mg/kg Dose
Participants received 2.0 mg/kg of asfotase alfa administered SC 3 times a week from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1.
干预措施: Asfotase alfa (Drug)
Asfotase Alfa 3.0 mg/kg Dose
Participants received 3.0 mg/kg of asfotase alfa administered SC 3 times a week from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1.
干预措施: Asfotase alfa (Drug)
结局指标
主要结局
Change In Plasma PPi From Baseline To Pre-3rd Dose At Week 9
时间窗: Baseline to Week 9
Plasma PPi concentrations were determined using a specific enzyme-catalyzed reaction with a radiolabelled marker in a 3-step process. Baseline plasma PPi values were calculated by averaging pre-dose values from samples collected during the Run-in Period at -168, -156, -24, -12, and 0 hours before Baseline. Week 9 plasma PPi values were calculated using blood samples collected before administration of the 3rd dose. The analysis was a restricted maximum likelihood (REML)-based repeated measures mixed model with treatment, visit, sex, Baseline PPi, Baseline weight group (≥ median versus \< median), and study drug lot assignment as factors, and an unstructured covariance structure for within-participant correlation. Per inclusion criteria, participants had to have had a Screening PPi concentration of ≥3.9 micromolar (μM). Three participants (1 in each group) had Screening PPi concentrations of ≥3.9 μM, but Baseline PPi values ranged between 3.5 to 3.8 μM.
次要结局
- Change In Plasma PLP From Baseline To Pre-3rd Dose At Week 9(Baseline to Week 9)