Treatment Frequency Reduction in Pompe Disease

NCT06575829 | Not Yet Recruiting Phase 4

• 2 other identifiers: NL99999.999.992024-514255-15-00
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Pompe Disease (Late-onset); GAA Deficiency; Glycogen Storage Disease Type II; Acid Maltase Deficiency

Outcome Measures

Primary Outcomes (12)

• 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.

  At baseline and every 3 months for a duration of 21 months.

• 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.

  At baseline and every 3 months for a duration of 21 months.

• 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.

  At baseline and every 3 months for a duration of 21 months.

• 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.

  Every 3 months for a duration of 21 months.

• Changes in pulmonary function by testing forced vital capacity (FVC) in sitting and supine positions

  Pulmonary function testing will be performed at the time points specified. Forced vital capacity will be measured during sitting and supine positions as a measure of lung volume (and indirect measure of the strength of the diaphragm and abdominal muscles). The pulmonary testing protocol is standardized in accordance with ATS/ERS Guidelines36. Three repeated reproducible flow volume curves will be made. The best effort will be used for further analyses. Values will be expressed as a percentage of the predicted normal values or as z-score, based on age, gender, race, and height. Global Lung Initiative (GLI) 2012 reference equations will be used.

  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)

  In addition to the vital capacity, inspiratory (MIP) and expiratory (MEP) mouth pressures will be measured in upright seated position to determine the maximum force that can be exerted by the respiratory muscles. MIP will be measured at residual volume after maximal expiration, while MEP is registered at total lung capacity after maximal inspiration. Pressures must be maintained at least 1 second. Maneuvers will be repeated until three reproducible methods are obtained. The highest value will be taken for analyses.

  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

  The Rasch-built Pompe-specific activity (R-PAct) scale is a self-reported, 18-items questionnaire designed specifically for use in patients with Pompe disease, based upon experiences from patients about their most important and limiting aspects in daily life. All items have three response options: \[0\] unable to perform; \[1\] able to perform, but with difficulty or \[2\] able to perform without difficulty. If all items are answered, an appropriate centile metric score (range 0-100) will be calculated.

  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

  The SF-36 is a health-related quality of life questionnaire, consisting of 36 items. The items are assigned to the domains of physical functioning, role functioning-physical, role functioning-emotional, social functioning, body pain, mental health, vitality, general health perception and change in health.

  At baseline, after 9 months and at the end of the study (21 months).

• Body weight

  Body weight will be measured in kilograms (kg).

  At baseline and every 3 months for a duration of 21 months.

• Heart rate

  Heart rate will be measured in beats per minute (bpm).

  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.

• Systolic and diastolic blood pressure

  Systolic and diastolic blood pressure will be measured in millimeter of mercury (mmHg).

  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.

• Respiratory rate

  Respiratory rate will be measured in breaths per minute.

  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 (8)

• Changes in lean body mass assessed by DEXA-scans

  At baseline, after 9 months and at the end of the study (21 months).

• Changes in lean body mass assessed by DEXA-scans

  At baseline, after 9 months and at the end of the study (21 months).

• Bone density assessed by DEXA-scans

  At baseline, after 9 months and at the end of the study (21 months).

• Need for walking devices and artificial ventilation (yes/no)

  At baseline and every 3 months for a duration of 21 months.

• Changes in alglucosidase alfa activity in plasma

  At 3 months and 9 months.

Study Arms (1)

Algucosidase alfa 20 mg/kg once every 4 weeks instead of once every 2 weeks

EXPERIMENTAL

Alglucosidase alfa will be administered by intravenous infusion at a dose of 20 mg/kg once every 4 weeks instead of once every 2 weeks for a duration of 9 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). 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, leading to a total study duration of 21 months.

Drug: Algucosidase alfa 20 mg/kg once every 4 weeks instead of once every 2 weeks

Interventions

Algucosidase alfa 20 mg/kg once every 4 weeks instead of once every 2 weeks DRUG

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.

Algucosidase alfa 20 mg/kg once every 4 weeks instead of once every 2 weeks

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Erasmus Medical Center: lead

MeSH Terms

Conditions

Glycogen Storage Disease Type II

Condition Hierarchy (Ancestors)

Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Glycogen Storage Disease; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Pieter A. van Doorn, Prof. dr.

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

• Nadine A.M.E. van der Beek, Dr.

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

• Tim Preijers, Dr.

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ina Barzel, MSc

CONTACT

+31(0)107031182 |; i.barzel@erasmusmc.nl

Lianne H. Potters, MSc

CONTACT

+31(0)0633342010; l.potters@erasmusmc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Coordinating investigator

Model Details: This study is a self-controlled cohort study.

Study Record Dates

• First Submitted: August 22, 2024
• First Posted: August 28, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 28, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: These data will become available 3 months after the start of the trial.
• Access Criteria: Upon a reasonable request