Clinical Study for Treatment-naïve IOPD Babies to Evaluate Efficacy and Safety of ERT With Avalglucosidase Alfa

Study Overview
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Brief Summary
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This is a single group, treatment, Phase 3, open-label study to assess efficacy, safety, pharmacokinetic (PK), pharmacodynamics (PD) of avalglucosidase alfa in treatment-naïve male and female participants with IOPD. Study details include: Study duration: Screening - up to 4 weeks; Primary Analysis Period (PAP) - 52 weeks; Extended Treatment Period (ETP) - 52 weeks; Extended Long term Treatment Period (ELTP) - 104 weeks; 4-week follow-up period for a total study duration - up to 4.08 years. Treatment duration: Up to 4 years Visit frequency: every other week and potentially every week

Detailed Description
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Study duration may be variable by country, but until avalglucosidase alfa is approved in the patient's country or up to 4.08 years, whichever comes first.

Official Title
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An Open-label, Multinational, Multicenter, Intravenous Infusion Study of the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Avalglucosidase Alfa in Treatment naïve Pediatric Participants With Infantile-Onset Pompe Disease (IOPD)

Conditions
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Glycogen Storage Disease Type II

Intervention / Treatment
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* Drug: avalglucosidase alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have confirmed diagnosis of infantile-onset Pompe disease defined as: the presence of 2 lysosomal acid α-glucosidase (GAA) pathogenic variants and a documented GAA deficiency from blood, skin, or muscle tissue; or the presence of 1 GAA pathogenic variant and a documented GAA deficiency from blood, skin and muscle tissue in 2 separate samples (from either 2 different tissues or from the same tissue but at 2 different sampling dates). Participants must have established cross-reactive immunological material (CRIM) status available prior to enrollment. Participants must have cardiomyopathy at the time of diagnosis: ie, left ventricular mass index (LVMI) equivalent to mean age specific LVMI +1 standard deviation for participants diagnosed by newborn screening or sibling screening; +2 standard deviation for participants diagnosed by clinical evaluation. Parents or legally authorized representative(s) must be capable of giving signed informed consent. Exclusion Criteria: Participants with symptoms of respiratory insufficiency, including any ventilation use (invasive or noninvasive) at the time of enrollment. Participants with major congenital abnormality. Participants with clinically significant organic disease (with the exception of symptoms relating to Pompe disease). Participant received any Pompe disease specific treatment, eg enzyme-replacement gene therapy (ERT). Participant who has previously been treated in any clinical trial of avalglucosidase alfa. Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures. 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: 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Avalglucosidase alfa<br>Administered intravenously every 2 weeks | Drug: avalglucosidase alfa<br>* Sterile lyophilized powder intravenous (IV) infusion<br>* Other names: GZ402666;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who are alive and free of invasive ventilation at 12 and 18 months of age |  | at 12 and 18 months of age | 
| Proportion of participants who are alive at Week 52 |  | Week 52 | 
| Proportion of participants who are alive at 12 and 18 months of age |  | at 12 and 18 months of age | 
| Proportion of participants who are free of ventilator use (invasive and non-invasive separate and combined) at Week 52 |  | Week 52 | 
| Proportion of participants who are free of supplemental oxygen use at Week 52 |  | Week 52 | 
| Change from baseline to Week 52 in left ventricular mass (LVM)-Z score |  | Week 52 | 
| Change from baseline to Week 52 in Alberta Infant Motor Scale (AIMS) score |  | Week 52 | 
| Change from baseline to Week 52 in body length Z-scores |  | Week 52 | 
| Change from baseline to Week 52 in body weight Z-scores |  | Week 52 | 
| Change from baseline to Week 52 in head circumference Z-scores |  | Week 52 | 
| Change from baseline to Week 52 in body length percentiles |  | Week 52 | 
| Change from baseline to Week 52 in body weight percentiles |  | Week 52 | 
| Change from baseline to Week 52 in head circumference percentiles |  | Week 52 | 
| Change from baseline to Week 52 in urinary Hex4 |  | Week 52 | 
| Number of participants experiencing at least 1 treatment-emergent adverse events (TEAE), including infusion associated reactions (IAR) |  | Week 52, Week 212 | 
| Number of participants with abnormalities in physical examinations |  | Week 52, Week 208 | 
| Number of participants with potentially clinically significant abnormality (PCSA) in clinical laboratory results |  | Week 52, Week 208 | 
| Number of participants with PCSA in vital signs measurements |  | Week 52, Week 208 | 
| Number of participants with PCSA in 12-lead electrocardiogram (ECG) |  | Week 52, Week 208 | 
| Incidence of treatment-emergent anti-drug antibodies (ADA) |  | Week 52, Week 208 | 
| Plasma concentration of avalglucosidase alfa |  | at Day 1, Week 12, and Week 52 |