A Noninferiority Study of Alglucosidase Alfa Manufactured at the 160 L and 4000 L Scales in Treatment Naïve Patients With Infantile-Onset Pompe Disease

Study Overview
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Brief Summary
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A study to demonstrate comparable safety, efficacy, and pharmacokinetics (PK) of alglucosidase alfa manufactured at the 160 litre (L) and 4000 L scales in participants who had been diagnosed with infantile-onset Pompe disease. Participants were treated with alglucosidase alfa 160 L scale product in the United States (US) and 4000 L scale product in the regions outside the US.

Official Title
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A Phase 3/4, Prospective, Multinational, Open-label, Noninferiority Study of Alglucosidase Alfa Manufactured at the 160 L and 4000 L Scales in Treatment Naïve Patients With Infantile-Onset Pompe Disease

Conditions
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Pompe Disease (Infantile-Onset), Glycogen Storage Disease Type II (GSD II), Glycogenosis 2, Acid Maltase Deficiency

Intervention / Treatment
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* Biological: alglucosidase alfa
* Biological: alglucosidase alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant's parent/legal guardian was willing and able to provide signed informed consent. The participant might be less than or equal to 12 months of age. The participant might have documented GAA enzyme deficiency from blood, skin, or muscle tissue. The participant might be naïve to treatment with alglucosidase alfa. Exclusion Criteria: The participant was cross-reactive immunologic material negative. The participant required invasive ventilator support at the time of enrollment. The participant had decompensated clinical heart failure. The participant had a major congenital abnormality, excluding cardiac hypertrophy. The participant had a clinically significant organ disease (excluding the signs and symptoms of Pompe disease). The participant was currently receiving any investigational product. The participant was participating in another clinical study. The participant and/or the patient's parent/legal guardian was unable to adhere to the requirements of the study.

Ages Eligible for Study
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Maximum Age: 12 Months

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alglucosidase Alfa 4000 L material (Non-US participants)<br>Alglucosidase alfa 4000 L material for 52 weeks. | Biological: alglucosidase alfa<br>* Intravenous (IV) infusion of alglucosidase alfa (4000 L material) 20 mg/kg every other week (QOW)<br>* Other names: Lumizyme;|
| Active Comparator: Alglucosidase Alfa 160 L material (US participants)<br>Alglucosidase alfa 160 L material for 52 weeks. | Biological: alglucosidase alfa<br>* IV infusion of alglucosidase alfa (160 L material) 20 mg/kg QOW.<br>* Other names: Myozyme;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Cardiac Function at Week 52 | Cardiac function was measured by the left ventricular mass Z-score (LVM-Z). Z-Scores indicate the number of standard deviations (SD) from the mean in a normal distribution. A negative change from baseline indicates a decrease and positive 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Motor Development Status at Week 52 | Motor development status was assessed by the Gross Motor Function Measure - 88 Scale (GMFM-88) total percent scores. GMFM-88 is an 88-item measure to detect gross motor function. It consists of 5 categories: lying and rolling; sitting; crawling and kneeling; standing; walking, running and jumping. Each item was scored on a 4-point Likert scale (0 = cannot do; 1 = initiates [<10% of the task]; 2 = partially completes [10% to <100% of the task]; 3 = task completion). 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 | 
| Percentage of Participants With Estimated Probability of Survival |  | Up to Week 52 | 
| Number of Participants With Invasive Ventilator-Free Survival | Invasive ventilator-free survival was defined as the time during which the participant is alive and not invasively ventilated. Number of Participants with invasive ventilator-free survival were reported. | Up to Week 52 |