An Exploratory, Open-Label Study of the Safety and Efficacy of High Dose or High Dosing Frequency Alglucosidase Alfa Treatment in Patients With Pompe Disease Who Do Not Have an Optimal Response to the Standard Dose Regimen
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 13
- 试验地点
- 11
- 主要终点
- Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Respiratory Decline on Standard Treatment
研究概览
简要总结
Pompe disease (also known as glycogen storage disease Type II) is caused by a deficiency of a critical enzyme in the body called acid alpha-glucosidase (GAA). Normally, GAA is used by the body's cells to break down glycogen (a stored form of sugar) within specialized structures called lysosomes. In patients with Pompe disease, an excessive amount of glycogen accumulates and is stored in various tissues, especially heart and skeletal muscle, which prevents their normal function. The objective of this exploratory study is to evaluate the safety and efficacy of alternative dosing regimens of alglucosidase alfa in patients with Pompe disease who have not demonstrated an optimal response to the standard dosing regimen of 20 mg/kg every other week after a minimum of 6 months treatment immediately prior to study entry.
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
- 6 Months 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient or patient's legal guardian must provide signed, informed consent prior to performing any study-related procedures;
- •The patient must have a clinical diagnosis of Pompe disease as defined by documented GAA deficiency in skin fibroblasts or blood;
- •The patient must have been compliant with the standard dosing regimen of alglucosidase alfa (20 mg/kg every other week) for a minimum of 6 months immediately prior to study entry
- •The patient must have clinical decline or sub-optimal improvement in at least one of the following parameters as compared to their condition prior to the beginning alglucosidase alfa treatment:
- •Cardiac: Left Ventricular Mass (LVM) Z-score ≥6 or LVM index ≥150 g/m2 after a minimum of 6 months of regular treatment with alglucosidase alfa; OR
- •Respiratory: New development of respiratory failure requiring the use of ventilatory assistance (invasive or non-invasive) after a minimum of 6 months of regular treatment with alglucosidase alfa. Ventilatory assistance must have been required for at least 4 weeks prior to study enrollment; OR
- •Motor Skills:
- •For patients ≤ 2 years of age at study entry, failure to acquire at least 2 new gross motor milestones after a minimum of 6 months of regular treatment with alglucosidase alfa; OR
- •For patients > 2 years of age at study entry, worsening of proximal upper extremity muscle weakness as determined by the Investigator through loss of functional use of the upper extremities after a minimum of 6 months of regular treatment with alglucosidase alfa, OR
- •For patients > 8 years of age at study entry, worsening of proximal upper extremity muscle weakness as determined by the Investigator through longitudinal assessments of manual muscle testing after a minimum of 6 months of regular treatment with alglucosidase alfa, OR
- •For patients previously ambulatory, progression to use of an assistive device for ambulation due to worsening of proximal lower extremity muscle weakness after a minimum of 6 months of regular treatment with alglucosidase alfa.
排除标准
- •For patients < 18 years of age, negative Cross-Reactive Immunologic Material (CRIM) assay result (added in protocol amendment #2);
- •Any medical condition which, in the opinion of the Investigator, could interfere with treatment or evaluation of safety and/or efficacy of alglucosidase alfa;
- •The patient is not currently receiving alglucosidase alfa;
- •The patient has major congenital abnormality;
- •The patient has used any investigational product (other than alglucosidase alfa in those regions where the product is not commercially available) within 30 days prior to study enrollment;
- •The patient is pregnant or lactating.
结局指标
主要结局
Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Respiratory Decline on Standard Treatment
时间窗: Baseline, Week 52
Participants were enrolled based on clinical decline or sub-optimal clinical response in cardiac, respiratory and/or motor function parameters pre-study while on standard treatment. Each participant was evaluated at Week 52 for change from baseline in the criteria that declined; respiratory decline as measured by change in ventilator use is summarized in this outcome. Ventilator use might have improved (less use of ventilator support), had no change, or worsened (more use of ventilator support). Each participant served as his or her own control.
Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Motor Function Decline on Standard Treatment
时间窗: Baseline, Week 52
Participants were enrolled based on clinical decline or sub-optimal clinical response in cardiac, respiratory and/or motor function parameters pre-study while on standard treatment. Each participant was evaluated at Week 52 for change from baseline in the criteria that declined; motor function decline primarily based on Gross Motor Function Measure 66 and Pompe Pediatric Evaluation of Disability Inventory results is summarized. Participants could gain motor function (improve), had no change (declined stopped), or continued loss (worsened). Each participant served as his or her own control.
Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period
时间窗: Day 1 up to Week 52
Overall safety summary of participants experiencing Adverse Events (AEs), Serious Adverse Events (SAEs), treatment-related AEs, and Infusion Associated Reactions (IARs). Summary is based on Treatment-emergent AEs (TEAEs), defined as AEs that occurred following the initiation of study treatment.
次要结局
- Change From Baseline in Body Strength Measured by the Manual Muscle Testing (MMT) Total Score at Week 52(Baseline, Week 52)
- Baseline Values for Left Ventricular Mass (LVM) Z-Scores(Day 0)
- Baseline Values for Left Ventricular Mass Index (LVMI)(Day 0)
- Change From Baseline in Left Ventricular Mass (LVM) Z-Score at Week 52(Baseline, Week 52)
- Change From Baseline in Left Ventricular Mass Index (LVMI) at Week 52(Baseline, Week 52)
- Change From Baseline in Ventilator Use at Last Assessment (Approximately Week 52)(Baseline, approximately Week 52)
- Baseline Values of Raw Scores for Gross Motor Function Measure 66 (GMFM-66) Results(Day 0)
- Change From Baseline in Raw Scores for Gross Motor Function Measure 66 (GMFM-66) Results at Week 52(Baseline, Week 52)
- Baseline Values in Mobility as Measured by the Pompe Pediatric Evaluation of Disability Inventory (Pompe PEDI)(Day 0)
- Change From Baseline in Mobility as Measured by the Pompe Pediatric Evaluation of Disability Inventory (Pompe PEDI) at Week 52(Baseline, Week 52)
- Baseline Values for Normative Physical Component Summary of Medical Outcomes Study Short Form Health Survey (SF-36)(Day 0)
- Change From Baseline in Normative Physical Component Summary of Medical Outcomes Study Short Form Health Survey (SF-36) at Week 52(Baseline, Week 52)