A Study to Evaluate the Efficacy and Safety of Alglucosidase Alfa Produced at the 4000 L Scale for Pompe Disease

Study Overview
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Brief Summary
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The objective of this study was to evaluate the efficacy and safety of treatment with 4000 litre (L) alglucosidase alfa (Lumizyme®) in Pompe participants.

Official Title
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A Phase 4 Open Label, Prospective Study in Patients With Pompe Disease to Evaluate The Efficacy and Safety of Alglucosidase Alfa Produced at the 4000L Scale

Conditions
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Pompe Disease

Intervention / Treatment
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* Drug: Alglucosidase alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A participant might meet all of the following criteria to be eligible for this study. The participant and/or their parent/legal guardian was willing and able to provide signed informed consent. The participant might be at least 1 year of age at the time of informed consent. The participant had a diagnosis of Pompe disease and might have received treatment with 160 L alglucosidase alfa prior to screening. The participant, if female and of childbearing potential, might have a negative pregnancy test (urine beta-human chorionic gonadotropin) at baseline. Note: all female participants of childbearing potential and sexually mature males might agree to use a medically accepted method of contraception throughout the study. Exclusion Criteria: A participant who met any of the following criteria were to be excluded from this study. The participant had within the past 3 months received or was currently receiving any investigational product other than 160 L alglucosidase alfa or was currently participating in another clinical treatment study. The participant, in the opinion of the Investigator, was clinically unstable and would not be expected to survive to completion of the 52-week treatment period. The participant and/or their parent/legal guardian, in the opinion of the Investigator, was unable to adhere to the requirements of the study.

Ages Eligible for Study
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Minimum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alglucosidase alfa<br>Alglucosidase alfa (4000 L scale) intravenous (IV) infusion administered for 52 weeks as per physician's routine practice. | Drug: Alglucosidase alfa<br>* 4000 L alglucosidase alfa administered by IV infusion at the same dose and dose regimen used for the patient's routine treatment prior to the study for 52 weeks.<br>* Other names: Lumizyme®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Were Clinically Stable or Improved at Week 52 | Clinical stability was defined as absence of death due to disease progression or new dependency on invasive ventilation and; decline in cardiac status, motor function, and pulmonary function from baseline. | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival Rate at Week 52 | Percentage of participants who were alive at Week 52, were reported. Survival rate was calculated by Kaplan-Meier estimate. | Week 52 | 
| Invasive Ventilator-Free Survival Rate at Week 52 | Percentage of participants, who were invasive ventilator-free at week 52, are reported. Invasive ventilation was defined as mechanical ventilatory support applied with the use of an endotracheal tube or tracheostomy. Invasive ventilator-free survival rate was calculated by Kaplan-Meier estimate. | Week 52 | 
| Change From Baseline on Left Ventricular Mass Z-Score (LVM-Z) at Week 52 | Z-Scores indicate the number of standard deviations (SD) from the mean in a normal distribution. A negative change from baseline indicates an increase in LVM-Z score. The normal range is -2 to 2 and greater than 2 may indicate left ventricular hypertrophy. | Baseline, Week 52 | 
| Change From Baseline on Gross Motor Function Measure-88 (GMFM-88) at Week 52 | GMFM-88 (88-item measure to detect gross motor function) consists of 5 components, each measured on a 4-point Likert scale.The score for each dimension was expressed as a percentage of the maximum score for that dimension.Total score ranges from 0% to 100%, where higher scores indicate better motor functions. | Baseline, Week 52 | 
| Change From Baseline in Forced Vital Capacity (FVC) at Week 52- At Supine Position | Percent predicted FVC values are reported. FVC is the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in litres. Predicted forced vital capacity is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. Percent of predicted FVC = (observed value)/(predicted value) * 100%. | Baseline, Week 52 | 
| Change From Baseline in Forced Vital Capacity (FVC) at Week 52- At Sitting Position | Percent predicted FVC values are reported. FVC is the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in litres. Predicted forced vital capacity is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. Percent of predicted FVC = (observed value)/(predicted value) * 100%. | Baseline, Week 52 |