A Phase 3 Randomized, Multicenter, Multinational, Double-blinded Study Comparing the Efficacy and Safety of Repeated Biweekly Infusions of Avalglucosidase Alfa (neoGAA, GZ402666) and Alglucosidase Alfa in Treatment naïve Patients With Late-onset Pompe Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 101
- 试验地点
- 69
- 主要终点
- PAP: Change From Baseline in Percent Predicted FVC in Upright Position at Week 49
研究概览
简要总结
Primary Objective:
To determine the effect of avalglucosidase alfa treatment on respiratory muscle strength measured by percent (%) predicted forced vital capacity (FVC) in the upright position, as compared to alglucosidase alfa.
Secondary Objective:
To determine the safety and effect of avalglucosidase alfa treatment on functional endurance (6-minute walk test, inspiratory muscle strength (maximum inspiratory pressure), expiratory muscle strength (maximum expiratory pressure), lower extremity muscle strength (hand-held dynamometry), motor function (Quick Motor Function Test), and health-related quality of life (Short Form-12).
详细描述
The duration of the study per participant will be up to approximately 6 years that will consist of a 14-day screening period (may be extended up to 8 weeks in pre-specified situations), a 49-week blinded treatment period (except for the subgroup of pediatric patients aged 3 to less than (<) 18 years enrolling directly in the open-label long-term follow-up phase), a 240-week open-label treatment period, and a 4-week post-treatment observation period.
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
- 3 Years 至 —（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
avalglucosidase alfa (GZ402666)
Administered intravenously every 2 weeks
干预措施: Avalglucosidase alfa (GZ402666) (Drug)
alglucosidase alfa (GZ419829)
Administered intravenously every 2 weeks
干预措施: Alglucosidase alfa (GZ419829) (Drug)
结局指标
主要结局
PAP: Change From Baseline in Percent Predicted FVC in Upright Position at Week 49
时间窗: Baseline, Week 49
FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC is the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position. Least square (LS) mean and standard error (SE) were derived from mixed model for repeated measure (MMRM) model with baseline FVC \[percent (%) predicted, as continuous\], sex, age (in years at baseline), treatment group, visit, interaction term between treatment group and visit as fixed effects. Percent of predicted FVC = (actual FVC measurement)/(predicted value of FVC) \* 100. After non-inferiority (NI) testing, a test for superiority of avalglucosidase alfa versus alglucosidase alfa was performed with an overall 2-sided 5% level of significance.
次要结局
- PAP: Change From Baseline in Total Distance Walked During Six-minute Walk Test (6MWT) at Week 49(Baseline, Week 49)
- PAP: Change From Baseline in Percent Predicted Maximal Expiratory Pressure (MEP) in Upright Position at Week 49(Baseline, Week 49)
- PAP: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Infusion-Associated Reactions (IARs)(From Baseline up to Week 49)
- PAP: Change From Baseline in Percent Predicted Maximal Inspiratory Pressure (MIP) in Upright Position at Week 49(Baseline, Week 49)
- PAP: Change From Baseline in Lower Extremity Muscle Strength at Week 49 as Assessed by Hand-Held Dynamometry (HHD)(Baseline, Week 49)
- PAP: Change From Baseline in Quick Motor Function Test (QMFT) Total Scores at Week 49(Baseline, Week 49)
- PAP: Change From Baseline in 12-Item Short-Form Health Survey (SF-12): Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Week 49(Baseline, Week 49)
- Open-label Period: Number of Participants With TEAEs and IARs(Week 50 to 289 in open-label long-term period)
- PAP: Percentage of Participants With Treatment-Emergent Antidrug Antibodies (ADA) Response(From Baseline up to Week 49)