Safety and Efficacy of Avalglucosidase Alfa in Patients With Non-classic Pompe Disease Aged ≥ 5 Years

NCT07652814 | Active Not Recruiting Phase 4

• 3 other identifiers: NL70885.078.212024-518215-18-002019-002251-42
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to study the efficacy and safety of treatment with avalglucosidase alfa in patients with late onset Pompe disease that previously deteriorated on alglucosidase alfa. The main question it aims to answer is:

• Is switching to avalglucosidase alfa in late-onset Pompe patients deteriorating on alglucosidase alfa safe?
• Is switching to avalglucosidase alfa in late-onset Pompe patients deteriorating on alglucosidase alfa potentially more effective? Participants will switch to biweekly avalglucosidase alfa infusions (instead of alglucosidase alfa infusions) and perform assessment for:
• Efficacy: muscle strength and function, pulmonary function, patient-reported outcomes.
• Safety: Adverse events assessment, physical examination, clinical laboratory evaluations, vital signs, ECGs and immunogenicity assessments.
• Pharmacokinetic assessments during 2 avalglucosidase alfa infusions.

Conditions

Glycogen Storage Disease Type II Late Onset; Pompe Disease Late-Onset; Pompe's Disease Juvenile Onset; Pompe Disease

Outcome Measures

Primary Outcomes (15)

• Incidence/occurrence of adverse events

  Assessment of the occurrence/number of adverse events / treatment-emergent adverse events, including infusion associated reactions (IARs). Adverse events are scored using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

  From enrollment to the end of study duration at 5 years

• The occurence of antibodies against avalglucosidase alfa

  The titer of antibodies against avalglucosidase alfa, scored as either no to low antibodies (\< 1:1,250), intermediate (1:1,250 to \< 1:31,250), or high (≥ 1:31,250).

  From enrollment to the end of study duration at 5 years

• Clinical laboratory evaluations aimed at liver and muscle function.

  Values of ASAT, ALAT and CK (measured in U/L) as markers for muscle and liver function.

  From enrollment to the end of study duration at 5 years

• Changes in muscle strength using manual muscle testing (MMT)

  Manual muscle testing (MMT) is performed 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.

  From enrollment to the end of study duration at 5 years

• Changes in muscle strength using hand-held dynamometry (HHD)

  Muscle strength will also be measured with the Cytec handheld dynamometer (HHD). A mean value in Newton is calculated from three consecutive measurements per muscle group.

  From enrollment to the end of study duration at 5 years

• Changes in muscle function using Quick Motor Function Test (QMFT)

  For the quick motor function test, the patient is asked to perform several activities in supine, sitting and standing position, the performance of the patient is scored on a 5-point ordinal scale (range 0-4). A sumscore is calculated based on the maximum total score.

  From enrollment to the end of study duration at 5 years

• Changes in muscle function using the 6-Minute Walk Test (6-MWT)

  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. Eventual score is reported as a distance in meters (m) and a percent of the predicted score using the 1000 norms reference values.

  From enrollment to the end of study duration at 5 years

• Changes in muscle function using timed tests

  Four timed tests will be performed to evaluate the impact of muscle weakness on the ability to perform functional activities of daily living. These timed tests include walking 10 meters, climbing four stairs, getting up from a supine position on the floor, and standing up from a chair. The number of seconds required to perform each activity will be noted.

  From enrollment to the end of study duration at 5 years

• Changes in pulmonary function using forced vital capacity (FVC)

  Forced vital capacity in sitting and supine position will be measured and reported as percentage of predicted values, using the GLI 2012 reference values.

  From enrollment to the end of study duration at 5 years

• Changes in pulmonary function using Maximum Inspiratory Pressure (MIP) and Maximum Expiratory Pressure (MEP)

  Both MIP and MEP are measured in kPa and then converted to a percentage of predicted values based on reference values.

  From enrollment to the end of study duration at 5 years

• Changes in patient reported outcome (PRO) measures using the Rasch-built Pompe-specific Activity scale (R-PAct)

  The Rasch-Built Pompe-specific activity scale (R-PAct) will be performed in all patients who are ≥16 years at baseline. The 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.

  From enrollment to the end of study duration at 5 years

• Changes in patient reported outcome (PRO) measures using the 36-Item Short Form Health Survey (SF-36)

  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. The questionnaire will be used only for patients aged 16 years and older. A sumscore will be calculated based on the score on each item, and converted to a percentage of predicted score based on Dutch norm-based values.

  From enrollment to the end of study duration at 5 years

• Changes in patient reported outcome (PRO) measures using the TNO-AZL Child Quality of Life Questionnaire)

  The TACQOL (TNO-AZL Child Quality of Life Questionnaire) is a generic instrument that measures quality of life in children aged 6-15 years. The questionnaire includes items representing the following concepts: physical complaints, motor functioning, autonomous functioning, social functioning, cognitive functioning, positive moods, and negative moods. For each of these scales, a scale score is calculated, where a higher score corresponds with a better quality of life.

  From enrollment to the end of study duration at 5 years

• Changes in patient reported outcome (PRO) measures using the modified Borg scale

  The modified Borg scale is a patient-reported scale, derived from the original Borg scale, which is used to assess the subjective sensation of dyspnea of a patient. It is quantified from 0 to 10, in which 0 represents no symptoms (i.e. no dyspnea/shortness of breath) and 10 represents maximum symptoms.

  From enrollment to the end of study duration at 5 years

• Pharmacokinetics of avalglucocidase alfa

  Single and multiple dose estimates for Cmax (in µg/mL), AUC (in μg∙hr/ml) and CL (in L/h), measured at two separate avalglucosidase alfa infusions (at baseline and 52 weeks).

  From enrollment up to 1 year of study duration.

Secondary Outcomes (5)

• Changes in vital signs using heart rate

  From enrollment to the end of study duration at 5 years

• Changes in vital signs using blood pressure

  From enrollment to the end of study duration at 5 years

• Changes in vital signs using respiratory rate

  From enrollment to the end of study duration at 5 years

• Changes or abnormalities of cardiac function measured by electrocardiogram (ECG)

  From enrollment to the end of study duration at 5 years

• Assessment of use of ventilator

  From enrollment to the end of study duration at 5 years

Study Arms (1)

avalglucosidase alfa treatment

OTHER

Treatment with avalglucosidase alfa, 20 mg/kg/every other week for a period of 5 years.

Drug: Avalglucosidase Alfa

Interventions

Avalglucosidase Alfa DRUG

Enzyme replacement therapy

avalglucosidase alfa treatment

Eligibility Criteria

• Age: 5 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age\> 5 years and \< 55 years
• Childhood or juvenile/adult onset
• Residing in the Netherlands
• Current ERT with alglucosidase alfa\> 2 years (dose regimen 20 or 40 mg/kg bi-weekly).
• Confirmed diagnosis: enzyme deficiency in any tissue source and/or 2 confirmed disease-causing variants in the GAA gene.
• Willing and able to adhere to study procedures
• Deterioration in pulmonary function and/or 6MWT and/or muscle strength despite current treatment regimen with alglucosidase alfa.
• Disease status: measurable pulmonary (dys)function: (F)VC ≤ 80% predicted (mechanic ventilation during the day or night allowed); Measurable muscle weakness in proximal and/or distal muscle groups (non- ambulant/wheelchair bound patients allowed); measurable functional ability

You may not qualify if:

• Age\>55 years
• Invasive mechanical ventilation
• No remaining useful functional ability, as decided by the treating physician
• Unmanageable, sever IAR's on alglucosidase alfa
• Deterioration due to high levels of anti-alglucosidase alfa antibodies interfering with treatment efficacy
• Female patient of childbearing potential not protected by highly effective contraceptive method of birth control and/or who is unwilling or unable to be tested for pregnancy

Sponsors & Collaborators

• Iris Plug: lead
• Sanofi: collaborator

Study Sites (1)

Erasmus MC

Rotterdam, 3015 GD, Netherlands

Location

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

• Nadine van der Beek, MD PHD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sub-investigator, epidemiologist

Model Details: 6 patients with late onset Pompe disease will be treated

Study Record Dates

• First Submitted: November 1, 2022
• First Posted: June 17, 2026
• Study Start: October 13, 2022
• Primary Completion (Estimated): March 9, 2028
• Study Completion (Estimated): March 9, 2028
• Last Updated: June 17, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)