Clinical trial NCT06575829: Treatment Frequency Reduction in Pompe Disease
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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Pompe Disease (Late-onset)
GAA Deficiency
Glycogen Storage Disease Type II
Acid Maltase Deficiency
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
First posted: 2024-08-28
Enrollment: 10
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This study is a self-controlled cohort study.
Primary purpose: TREATMENT

Brief summary: 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.

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

Primary outcomes:
measure: Changes in muscle strength and function by manual muscle testing with Medical Research Council (MRC) grading scale
timeFrame: At baseline and every 3 months for a duration of 21 months.
measure: Changes in muscle strength and function by testing hand-held dynamometry (HHD)
timeFrame: At baseline and every 3 months for a duration of 21 months.
measure: Changes in muscle strength and function by quick motor function test (QMFT)
timeFrame: At baseline and every 3 months for a duration of 21 months.
measure: Changes in muscle strength and function by 6-minute walk test (6MWT)
timeFrame: Every 3 months for a duration of 21 months.
measure: Changes in pulmonary function by testing forced vital capacity (FVC) in sitting and supine positions
timeFrame: At baseline and every 3 months for a duration of 21 months.
measure: Changes in pulmonary function by testing maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP)
timeFrame: At baseline and every 3 months for a duration of 21 months.
measure: Changes in patient reported outcome measures by filling in the Rasch-built Pompe-specific activity (R-PAct) scale
timeFrame: At baseline and every 3 months for a duration of 21 months.
measure: Changes in patient reported outcome measures by filling in the SF-36 questionnaire
timeFrame: At baseline, after 9 months and at the end of the study (21 months).
measure: Body weight
timeFrame: At baseline and every 3 months for a duration of 21 months.
measure: Heart rate
timeFrame: 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.
measure: Systolic and diastolic blood pressure
timeFrame: 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.
measure: Respiratory rate
timeFrame: At baseline and every 4 weeks at the start 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 outcomes:
measure: Changes in lean body mass assessed by DEXA-scans
timeFrame: At baseline, after 9 months and at the end of the study (21 months).
measure: Changes in lean body mass assessed by DEXA-scans
timeFrame: At baseline, after 9 months and at the end of the study (21 months).
measure: Bone density assessed by DEXA-scans
timeFrame: At baseline, after 9 months and at the end of the study (21 months).
measure: Need for walking devices and artificial ventilation (yes/no)
timeFrame: At baseline and every 3 months for a duration of 21 months.
measure: Changes in alglucosidase alfa activity in plasma
timeFrame: At 3 months and 9 months.
measure: Serological testing of serum creatine kinase (CK) and antibodies against alglucosidase alfa
timeFrame: At baseline and every 3 months for a duration of 21 months.
measure: Urine tetraglucoside
timeFrame: At baseline and every 3 months for a duration of 21 months.
measure: Assessment of treatment-emergent adverse events (TEAEs), including infusion associated reactions (IARs)
timeFrame: At baseline and every 3 months for a duration of 21 months.
Other outcomes:
Locations:
Study officials:
affiliation: Erasmus Medical Center
name: Pieter A. van Doorn, Prof. dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Erasmus Medical Center
name: Nadine A.M.E. van der Beek, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Erasmus Medical Center
name: Tim Preijers, Dr.
role: PRINCIPAL_INVESTIGATOR
References: