Avalglucosidase alfa for Pompe disease | Glycogen storage disease type II

Inclusion criteria

• {"criterion_text":"- Age ≥ 5 years and ≤ 55 years.\n- Childhood or juvenile/young adult onset.\n- Residing in the Netherlands\n- Current enzyme-replacement therapy with alglucosidase alfa ≥ 2 years (dose regimen 20 or 40 mg/kg bi-weekly).\n- Confirmed diagnosis: enzyme deficiency in any tissue source and/or 2 confirmed disease-causing variants in the GAA gene.\n- Willing and able to adhere to study procedures (incl. patient and/or parent/guardian signed informed consent).\n- Deterioration in pulmonary function and/or 6MWT and/or muscle strength despite current treatment regimen with alglucosidase alfa.\n- 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."}

Exclusion criteria

• {"criterion_text":"- Age >55 years.\n- Invasive mechanical ventilation.\n- No remaining useful functional ability (e.g. (almost) tetraplegic), as decided by the treating physician.\n- Unmanageable, severe IARs on alglucosidase alfa.\n- Deterioration due to high levels of anti-alglucosidase alfa antibodies interfering with treatment efficacy.\n- 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"}

Primary endpoints

• {"endpoint_text":"- Safety and tolerability are determined by assessing: • The number of AE’s/treatment-emergent adverse events, including infustion associated reactions • The occurrence of antibodies against avalglucosidase alfa • Clinical laboratory evaluations aimed at liver and muscle function (ASAT/ALAT/CK)","definition_or_measurement_approach":"Assessment of number and nature of AEs and treatment-emergent adverse events including infusion-associated reactions; monitoring for development/occurrence of antibodies against avalglucosidase alfa; clinical laboratory tests for liver and muscle function (ASAT/ALAT/CK)."}
• {"endpoint_text":"- Pharmacokinetics: • Single and multiple dose estimates for Cmax, AUC, CL","definition_or_measurement_approach":"Pharmacokinetic sampling to estimate single- and multiple-dose parameters including Cmax, AUC and clearance (CL)."}
• {"endpoint_text":"- Efficacy is determined by assessing: • Changes in muscle strength: Manual Muscle Testing (MMT), Hand-Held dynamometry (HHD) • Changes in muscle function: Quick Motor Function Test (QMFT), 6-Minute Walk Test(6-MWT), Timed tests • Changes in the pulmonary function o Forced vital capacity in sitting and supine positions, Maximum Inpiratory Pressure (MIP), Maximum Expiratory Pressure (MEP) • Changes in PRO-Measures: Rasch-build Pompe Activity Scale (R-PaCT), Quality of life, modified Borg scale","definition_or_measurement_approach":"Efficacy measured by changes from baseline in muscle strength (MMT, HHD), muscle function (QMFT, 6MWT, timed tests), pulmonary function (FVC sitting and supine, MIP, MEP), and patient-reported outcomes (R-PaCT, quality of life measures, modified Borg scale)."}

Netherlands

Earliest CTIS Part Ii Submission Date

03-10-2024

Latest Decision Or Authorization Date

16-10-2024

Processing Time Days

13

Number Of Sites

1

Number Of Participants

6

Primary sponsor

Full Name

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands