A Prospective Study to Observe & Describe Clinical Outcomes of Alglucosidase Alfa Treatment in Patients ≤6 Months of Age With Infantile-onset Pompe Disease (IOPD)

Study Overview
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Brief Summary
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Primary Objective: To describe the effect of routine practice with alglucosidase alfa in patients with IOPD ≤6 months of age, on invasive ventilation-free survival after 52 weeks of treatment. Secondary Objectives: To describe the effect of routine practice with alglucosidase alfa on invasive ventilation-free survival and survival at 12 and 18 months of age, as well as on change in left ventricular mass (LVM) Z score, Alberta Infant Motor Scale (AIMS) score, body weight, body length, and head circumference Z scores, and urinary glucose tetrasaccharide (Hex4), at Week 52 of treatment. To describe the safety, tolerability, and immunogenicity of alglucosidase alfa in the routine practice of IOPD treatment.

Detailed Description
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The planned duration of observation for each participant will be 104 weeks after enrollment, to determine secondary outcomes at 18 months (approximately 78 weeks) of age.

Official Title
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A Prospective Observational Study to Describe Clinical Outcomes of Alglucosidase Alfa Treatment in Patients ≤6 Months of Age With Infantile-onset Pompe Disease (IOPD)

Conditions
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Glycogen Storage Disease Type II

Intervention / Treatment
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* Drug: Alglucosidase alfa GZ419829


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At the time of informed consent, participants must be ≤6 months of age, corrected for gestation if necessary. Gestational age <40 weeks will be adjusted to a full-term gestational age of 40 weeks. Participants must have alglucosidase alfa enzyme replacement therapy (ERT) planned or initiated for IOPD treatment irrespective of study participation, according to the treating physician's decision regarding participants' routine disease management. Participants must have available and accessible medical records from the time of IOPD diagnosis and from subsequent follow-up. Participants must have a confirmed diagnosis of IOPD, defined as presence of 2 pathogenic acid alpha glucosidase (GAA) variants and documented GAA deficiency in blood (dried blood spot [DBS] accepted), skin, or muscle tissue, or presence of 1 pathogenic GAA variant and documented GAA deficiency in blood, skin, or muscle tissue from separate samples (either from 2 different tissues or from the same tissue but at 2 different sampling dates.) (DBS and leukocytes are acceptable as 2 different samples from blood). Participants must have established cross-reacting immunologic material (CRIM) status available prior to enrollment. CRIM status may be provided by historical CRIM testing results or prediction of CRIM status based on genotyping performed at a Clinical Laboratory Improvement Amendments (CLIA) or other appropriately certified genetic laboratory. Participants must have cardiomyopathy at the time of diagnosis (LVMI equivalent to mean age-specific LVMI): LVMI +1 standard deviation (SD) in participants diagnosed by newborn or sibling screening, LVMI +2 SD in participants diagnosed by clinical evaluation. Participants must have informed consent provided by parent(s)/legally acceptable representatives (LARs). Exclusion Criteria: Participants with respiratory insufficiency, defined as: Oxygen saturation <90% on room air as determined by pulse oximetry, Venous partial pressure of carbon dioxide (pCO2) >55 mmHg or arterial pCO2 >40 mmHg on room air, Use of invasive (with intubation or tracheostomy) or noninvasive (no intubation or tracheostomy) ventilation at enrollment, for participants not having started ERT at enrollment, Use of invasive or noninvasive ventilation at the time of ERT initiation, for participants having started ERT before enrollment. Participants with major congenital abnormality including heart defect, neural tube defect, or Down syndrome that, in the opinion of the investigator, would preclude participation in the study or potentially decrease survival. Participants with clinically significant organic disease other than signs/symptoms related to Pompe disease, including clinically significant cardiovascular, hepatic, pulmonary, neurologic, or renal disease, or other medical condition, serious intercurrent illness, or circumstance that, in the opinion of the investigator, would preclude participation or potentially decrease survival. Previous or ongoing treatment in any clinical trial of, or managed access program for, avalglucosidase alfa or any other Pompe disease-specific therapy. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 0 Days
Maximum Age: 6 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1<br> | Drug: Alglucosidase alfa GZ419829<br>* Pharmaceutical form: Lyophilized powder for solution Route of administration: intravenous<br>* Other names: Myozyme;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants alive and free of invasive ventilation at Week 52 of treatment |  | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants alive and free of invasive ventilation at 12 and 18 months of age |  | at 12 and 18 months of age | 
| Proportion of participants alive at Week 52 of treatment |  | Week 52 | 
| Proportion of participants alive at 12 months and 18 months of age |  | at 12 and 18 months of age | 
| Proportion of participants free of ventilator use and free of supplemental oxygen use at Week 52 |  | Week 52 | 
| Change from baseline to Week 52 in LVM Z score |  | from baseline to Week 52 | 
| Change from baseline to Week 52 in AIMS score |  | from baseline to Week 52 | 
| Change from baseline to Week 52 in body length Z-scores |  | from baseline to Week 52 | 
| Change from baseline to Week 52 in body weight Z-scores |  | from baseline to Week 52 | 
| Change from baseline to Week 52 in head circumference Z-scores |  | from baseline to Week 52 | 
| Change from baseline to Week 52 in body length percentiles |  | from baseline to Week 52 | 
| Change from baseline to Week 52 in body weight percentiles |  | from baseline to Week 52 | 
| Change from baseline to Week 52 in head circumference percentiles |  | from baseline to Week 52 | 
| Change from baseline to Week 52 in urinary Hex4 |  | from baseline to Week 52 | 
| Number of participants experiencing at least 1 treatment-emergent adverse events (TEAE), including infusion-associated reactions (IAR) |  | From inclusion for 104 weeks | 
| Number of participants with abnormalities in physical examinations |  | From inclusion for 104 weeks | 
| Number of participants with abnormalities in clinical laboratory results |  | From inclusion for 104 weeks | 
| Number of participants with abnormalities in vital signs measurements |  | From inclusion for 104 weeks | 
| Number of participants with abnormalities in 12-lead electrocardiogram (ECG) |  | From inclusion for 104 weeks | 
| Incidence of treatment-emergent antidrug antibodies (ADA) |  | From inclusion for 104 weeks |