Avalglucosidase Alfa Extension Study

Study Overview
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Brief Summary
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Primary Objective: Long-term safety and pharmacokinetics (PK) of avalglucosidase alfa Secondary Objective: Long-term effect of avalglucosidase alfa on pharmacodynamic and exploratory efficacy variables

Detailed Description
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The duration of the study will be 6 years from the date the first patient enters the study. Each patient will continue with the study until the patient withdraws, the Investigator withdraws the patient, or the Sponsor terminates the study. An additional follow-up phase will begin after the patient's last planned visit in the 6-year study and last until avalglucosidase alfa is approved in the patient's country for all patients.

Official Title
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An Open-Label, Multicenter, Multinational Extension Study Of The Long-Term Safety And Pharmacokinetics Of Repeated Biweekly Infusions Of Avalglucosidase Alfa In Patients With Pompe Disease

Conditions
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Glycogen Storage Disease Type II Pompe Disease

Intervention / Treatment
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* Drug: GZ402666


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients with Pompe disease who previously completed a an avalglucosidase study. The patient and/or their parent/legal guardian is willing and able to provide signed informed consent, and the patient, if <18 years of age, is willing to provide assent if deemed able to do so. The patient (and patient's legal guardian if patient is <18 years of age) must have the ability to comply with the clinical protocol. The patient, if female and of childbearing potential, must have a negative pregnancy test [urine beta-human chorionic gonadotropin] at baseline. Exclusion criteria: The patient is concurrently participating in another clinical study using investigational treatment. The patient, in the opinion of the Investigator, is unable to adhere to the requirements of the study. The patient has clinically significant organic disease (with the exception of symptoms relating to Pompe disease), including clinically significant cardiovascular, hepatic, pulmonary, neurologic, or renal disease, or other medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, precludes participation in the study or potentially decreases survival. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
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: GZ402666<br>* Pharmaceutical form: lyophilized powder reconstituted for infusion Route of administration: intravenous<br>* Other names: avalglucosidase alfa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of adverse events (AEs) and treatment-emergent adverse events (TEAEs), including infusion-associated reactions (IARs) and deaths |  | screening/baseline until approximately Year 8 | 
| Laboratory assessments including hematology, biochemistry and urinalysis |  | Monthly, from baseline until Year 3 then quarterly until approximately Year 8 | 
| Vital signs |  | screening/baseline until approximately Year 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Electrocardiogram |  | every 6 months, from baseline until approximately Year 8 | 
| Anti-avalglucosidase alfa antibodies, and neutralizing antibody formation in anti-avalglucosidase alfa positive patients; anti-alglucosidase alfa IgG antibodies |  | monthly, from baseline up to 6 months, then every 3 months until approximately Year 8; every 6 months from baseline until approximately Year 8 | 
| Cmax (maximal concentration of the compound in the blood) |  | at 6 months, then yearly until approximately Year 8 | 
| AUC (area under the curve, relates to the quantity of compound that produces an effect) |  | at 6 months, then yearly until approximately Year 8 | 
| t1/2 (half-life, which is the time needed to eliminate half of the compound) |  | at 6 months, then yearly until approximately Year 8 | 
| Skeletal muscle glycogen content |  | every 2 years, from baseline until approximately Year 8 | 
| Skeletal muscle magnetic resonance images for qualitative and quantitative muscle degenerative assessments |  | every 2 years, from baseline until approximately Year 8 | 
| Urinary Hex4 |  | at 6 months, then yearly until approximately Year 8 | 
| Plasma analyses of circulating RNA |  | at 6 months, then yearly until approximately Year 8 | 
| Serum analyses of skeletal muscle RNA expression |  | at 6 months, then yearly until approximately Year 8 |