high dose or high dose frequency study of alglucosidase alfa

Conditions: Pompe Disease; Glycogen Storage Disease Type II (GSD-II); Glycogenesis 2 Acid Maltase Deficiency

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.