Treatment Frequency Reduction in Pompe Disease
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Algucosidase alfa 20 mg/kg once every 4 weeks instead of once every 2 weeks.
- Who it may be relevant to
- Registry conditions: Pompe Disease (Late-onset), GAA Deficiency, Glycogen Storage Disease Type II, Acid Maltase Deficiency. Basic parameters: from 50 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Center list to be confirmed — check the primary protocol.
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Open Label, Single-center Pilot Study to Investigate Alglucosidase Alfa (20 mg/kg) Frequency Reduction From 2 to 4 Weeks in a Subgroup of Elderly Patients With Late-onset Pompe Disease (TRIPOD-Study)
Overview
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.
Detailed description
All eligible patients with late-onset Pompe disease will be treated with alglucosidase alfa 20 mg/kg once every 4 weeks for 9 months. During the study, patients will be monitored once every 3 months.
After 9 months of treatment with the extended interval, it will be determined for each patient whether it is considered safe to discontinue enzyme replacement therapy (ERT). The investigators consider it safe: 1\] if the patient is stable compared to the year prior to reducing the ERT frequency, or, 2\] if the patient previously deteriorated (slightly) despite standard ERT and this deterioration is not exaggerated by the alternative dosing regimen. If after 9 months there is no valid medical reason to switch back to standard dosing (once every 2 weeks) and the patient does not wish to discontinue treatment, the 4-week dosing regimen will be continued. If at any moment a patient shows an unexpectedly rapid decline in clinical outcome parameters (significantly higher than their own course at regular treatment dosage), treatment will be switched back to or be restarted with the standard dosing regimen of 20 mg/kg every 2 weeks.
Both, patients who stop ERT after 9 months and those who continue with either the new or the previous dosing schedule, will be closely followed for an additional 12 months to be able to take action (e.g., switch to a standard dosing regimen or restart ERT) if a more rapid clinical deterioration occurs than expected, or to investigate if muscle and pulmonary function regain when standard dosage has been re-instituted after signs of clinical deterioration during the 4-week treatment interval. After the end of the study (21 months), patients will be carefully followed according to the standard frequency (once every 6 months). If a patient shows an unexpectedly rapid decline in clinical outcome parameters henceforth, treatment will be switched back to or be restarted with the standard dosing regimen of 20 mg/kg eow.
Interventions
- Drug Algucosidase alfa 20 mg/kg once every 4 weeks instead of once every 2 weeks
The 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.
Primary outcome measures
- Changes in muscle strength and function by manual muscle testing with Medical Research Council (MRC) grading scale [Time frame: At baseline and every 3 months for a duration of 21 months.]
- Changes in muscle strength and function by testing hand-held dynamometry (HHD) [Time frame: At baseline and every 3 months for a duration of 21 months.]
- Changes in muscle strength and function by quick motor function test (QMFT) [Time frame: At baseline and every 3 months for a duration of 21 months.]
- Changes in muscle strength and function by 6-minute walk test (6MWT) [Time frame: Every 3 months for a duration of 21 months.]
- Changes in pulmonary function by testing forced vital capacity (FVC) in sitting and supine positions [Time frame: At baseline and every 3 months for a duration of 21 months.]
- Changes in pulmonary function by testing maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) [Time frame: At baseline and every 3 months for a duration of 21 months.]
- Changes in patient reported outcome measures by filling in the Rasch-built Pompe-specific activity (R-PAct) scale [Time frame: At baseline and every 3 months for a duration of 21 months.]
- Changes in patient reported outcome measures by filling in the SF-36 questionnaire [Time frame: At baseline, after 9 months and at the end of the study (21 months).]
- Body weight [Time frame: At baseline and every 3 months for a duration of 21 months.]
- Heart rate [Time frame: At baseline and every 4 weeks at the start and at the end of the aglucosidase alfa infusion for a duration of 9 months. If alglucosidase alfa treatment is not stopped after 9 months, the measurement will take place for a total duration of 21 months.]
Secondary outcome measures (8)
- Changes in lean body mass assessed by DEXA-scans [Time frame: At baseline, after 9 months and at the end of the study (21 months).]
- Changes in lean body mass assessed by DEXA-scans [Time frame: At baseline, after 9 months and at the end of the study (21 months).]
- Bone density assessed by DEXA-scans [Time frame: At baseline, after 9 months and at the end of the study (21 months).]
- Need for walking devices and artificial ventilation (yes/no) [Time frame: At baseline and every 3 months for a duration of 21 months.]
- Changes in alglucosidase alfa activity in plasma [Time frame: At 3 months and 9 months.]
- Serological testing of serum creatine kinase (CK) and antibodies against alglucosidase alfa [Time frame: At baseline and every 3 months for a duration of 21 months.]
- Urine tetraglucoside [Time frame: At baseline and every 3 months for a duration of 21 months.]
- Assessment of treatment-emergent adverse events (TEAEs), including infusion associated reactions (IARs) [Time frame: At baseline and every 3 months for a duration of 21 months.]
Eligibility criteria
Inclusion criteria
- 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
- Able to walk ≥150 m within 6 minutes (6MWT)
- (Forced) vital capacity (FVC) in sitting position: >55% of expected value and in supine position: >45% of expected value
- Willing and able to adhere to the study procedures
Exclusion criteria
- 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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Center list to be confirmed — check the primary protocol.
Identifiers
NCT: NCT06575829 · NL99999.999.99 · 2024-514255-15-00