High Dose or High Dose Frequency Study of Alglucosidase Alfa
Condition: Pompe Disease; Glycogen Storage Disease Type II (GSD-II); Glycogenesis 2 Acid Maltase Deficiency
MeSH terms: Glycogen Storage Disease Type II; Glycogen Storage Disease
Intervention: alglucosidase alfa
Intervention description: intravenous infusion
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 6 Months
Healthy volunteers: No

Summary:

      Pompe disease (also known as glycogen storage disease Type II) is caused by a deficiency of a
      critical enzyme in the body called acid alpha-glucosidase (GAA). Normally, GAA is used by the
      body's cells to break down glycogen (a stored form of sugar) within specialized structures
      called lysosomes. In patients with Pompe disease, an excessive amount of glycogen accumulates
      and is stored in various tissues, especially heart and skeletal muscle, which prevents their
      normal function. The objective of this exploratory study is to evaluate the safety and
      efficacy of alternative dosing regimens of alglucosidase alfa in patients with Pompe disease
      who have not demonstrated an optimal response to the standard dosing regimen of 20 mg/kg
      every other week after a minimum of 6 months treatment immediately prior to study entry.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The patient or patient's legal guardian must provide signed, informed consent prior to
             performing any study-related procedures;

          -  The patient must have a clinical diagnosis of Pompe disease as defined by documented
             GAA deficiency in skin fibroblasts or blood;

          -  The patient must have been compliant with the standard dosing regimen of alglucosidase
             alfa (20 mg/kg every other week) for a minimum of 6 months immediately prior to study
             entry

          -  The patient must have clinical decline or sub-optimal improvement in at least one of
             the following parameters as compared to their condition prior to the beginning
             alglucosidase alfa treatment:

               1. Cardiac: Left Ventricular Mass (LVM) Z-score ≥6 or LVM index ≥150 g/m2 after a
                  minimum of 6 months of regular treatment with alglucosidase alfa; OR

               2. Respiratory: New development of respiratory failure requiring the use of
                  ventilatory assistance (invasive or non-invasive) after a minimum of 6 months of
                  regular treatment with alglucosidase alfa. Ventilatory assistance must have been
                  required for at least 4 weeks prior to study enrollment; OR

               3. Motor Skills:

          -  For patients ≤ 2 years of age at study entry, failure to acquire at least 2 new gross
             motor milestones after a minimum of 6 months of regular treatment with alglucosidase
             alfa; OR

          -  For patients > 2 years of age at study entry, worsening of proximal upper extremity
             muscle weakness as determined by the Investigator through loss of functional use of
             the upper extremities after a minimum of 6 months of regular treatment with
             alglucosidase alfa, OR

          -  For patients > 8 years of age at study entry, worsening of proximal upper extremity
             muscle weakness as determined by the Investigator through longitudinal assessments of
             manual muscle testing after a minimum of 6 months of regular treatment with
             alglucosidase alfa, OR

          -  For patients previously ambulatory, progression to use of an assistive device for
             ambulation due to worsening of proximal lower extremity muscle weakness after a
             minimum of 6 months of regular treatment with alglucosidase alfa.

        Exclusion Criteria:

          -  For patients < 18 years of age, negative Cross-Reactive Immunologic Material (CRIM)
             assay result (added in protocol amendment #2);

          -  Any medical condition which, in the opinion of the Investigator, could interfere with
             treatment or evaluation of safety and/or efficacy of alglucosidase alfa;

          -  The patient is not currently receiving alglucosidase alfa;

          -  The patient has major congenital abnormality;

          -  The patient has used any investigational product (other than alglucosidase alfa in
             those regions where the product is not commercially available) within 30 days prior to
             study enrollment;

          -  The patient is pregnant or lactating.