The aim of this study is to assess if dosing frequency reduction of alglucosidase alfa 20 mg/kg once every 2 weeks to once every 4 weeks is safe and does not lead to increased progression of disease in a selected group of patients with late-onset Pompe disease.
LOPD (confirmed diagnosis: enzyme deficiency in any tissue source and/or 2 confirmed disease-causing variants in the GAA gene)
Age ≥50 years
Current treatment with alglucosidase alfa at a standard dose of 20 mg/kg once every 2 weeks for ≥4 years
Relatively stable clinical condition over the past year
Rapidly progressive muscle weakness
Severely limited muscle strength almost requiring/requiring daily wheelchair use
Requiring respiratory support (non-invasive/invasive ventilation) or being at high risk to require respiratory support (ventilation) due to further deterioration of current pulmonary function. Using continuous positive airway pressure (CPAP) support only for obstructive sleep apnea syndrome (OSAS) is permitted.
Comorbidities which are expected to influence the primary outcome measures within the next 2 years
Single group
Algucosidase alfa 20 mg/kg once every 4 weeks instead of once every 2 weeks
DrugThe interval of ERT with alglucosidase alfa will be extended from once every 2 weeks to once every 4 weeks. The dose of 20 mg/kg per infusion remains the same.
Changes in muscle strength and function by manual muscle testing with Medical Research Council (MRC) grading scale
Muscle strength will be determined by manual muscle testing using the Medical Research Council (MRC) grading scale. Muscle strength is graded from 0-5 by physical examination, in which grade 5 represents normal muscle strength and grade 0 means paralysis of the muscle group tested. Muscle groups tests will include neck flexors/extensors, shoulder abductors, elbow extensors/flexors, wrist extensors/flexors, hip extension, hip flexors, hip adductors/abductors, knee extensors/flexors, and foot extensors/flexors.
Changes in muscle strength and function by testing hand-held dynamometry (HHD)
Muscle strength will be measured with the CITEC hand-held dynamometer (HHD). Thirteen muscle groups will be tested: neck extension, neck flexion, and bilateral shoulder abduction, elbow flexion, elbow extension, wrist extension, squeezing, hip flexion, hip extension, hip abduction, knee flexion, knee extension, ankle dorsiflexion, and ankle plantar flexion. A mean value in Newton (N) is calculated from three consecutive measurements per muscle group.
Changes in muscle strength and function by quick motor function test (QMFT)
The QMFT will be administered at the time points specified. This 16-item functional test has been developed to evaluate the function of the muscle groups that are specifically affected in patients with Pompe disease. The patient is asked to perform multiple activities in supine, sitting and standing position. The performance of the patient is scored on a 5-point ordinal scale (range 0-4). This standardized test can be performed within 5-10 minutes and can be performed in children and adults with varying disease severity.
Changes in muscle strength and function by 6-minute walk test (6MWT)
The 6MWT is a timed test that measures functional endurance. The primary measurement is the distance walked in 6 minutes, measured in meters. The percent of predicted distance and the amount of time walked (to quantify endurance, as not all patients may complete the full 6-minute walk) will also be recorded. The patient is instructed to walk the length of a pre-measured hallway for six minutes. It is widely regarded as an objective measure, which is easy to perform and reflects the performance in ADL of the patient.
Changes in lean body mass assessed by DEXA-scans
Body composition will be measured conform DEXA technology (currently at Erasmus MC: GE Healthcare Lunar iDXA equipment: densitometer and encore software). This is a low-cost technology and simultaneously accurate, easy to perform and involves very low radiation dose (8 µSv per scan) to the patient which brings no harm. This imaging technique is the gold standard technique for the assessment of body composition. Body composition will be presented as mineral bone, fat and fatty free body mass in kilograms.
Changes in lean body mass assessed by DEXA-scans
Percentages of total body fat mass, android and gynoid fat will be measured. Percentages of fat mass will also be measured at regional level (arms, trunk and legs).
Bone density assessed by DEXA-scans
Bone mineral density is measured at total body in g/cm2.
Need for walking devices and artificial ventilation (yes/no)
For the purpose of stabilization and if deemed necessary by the investigator, the patient may use a walking device during the assessment, such as cane or walker. If such a device is used during the assessment, this must be recorded in the CRF/HiX. It will also be determined whether patients may need non-invasive or invasive ventilation during the study, including the hours of ventilation per day.
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