Phase 3
Completed N=100
Study to Compare the Efficacy and Safety of Enzyme Replacement Therapies Avalglucosidase Alfa and Alglucosidase Alfa Administered Every Other Week in Patients With Late-onset Pompe Disease Who Have Not Been Previously Treated for Pompe Disease
Glycogen Storage Disease Type II;Pompe's Disease
Source: ClinicalTrials.gov NCT02782741 ↗
Enrolled (actual)
100
Serious AEs
24.5%
Results posted
Apr 2021
Primary outcomePrimary: PAP: Change From Baseline in Percent Predicted FVC in Upright Position at Week 49 — 2.89; 0.46 percent predicted FVC — p=0.0074
◆ Published Evidence
Highly cited
184citations · ~37 / year
Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial.
Summary
Primary Objective:
To determine the effect of avalglucosidase alfa treatment on respiratory muscle strength measured by percent (%) predicted forced vital capacity (FVC) in the upright position, as compared to alglucosidase alfa.
Secondary Objective:
To determine the safety and effect of avalglucosidase alfa treatment on functional endurance (6-minute walk test, inspiratory muscle strength (maximum inspiratory pressure), expiratory muscle strength (maximum expiratory pressure), lower extremity muscle strength (hand-held dynamometry), motor function (Quick Motor Function Test), and health-related quality of life (Short Form-12).
Linked Publications (4)
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Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial.
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Efficacy and Safety of Avalglucosidase Alfa in Patients With Late-Onset Pompe Disease After 97 Weeks: A Phase 3 Randomized Clinical Trial.
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Efficacy and safety of avalglucosidase alfa in patients with late-onset Pompe disease after 145 weeks of treatment during the COMET trial.
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Measurement Properties of 2 Novel PROs, the Pompe Disease Symptom Scale and Pompe Disease Impact Scale, in the COMET Study.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY PAP: Change From Baseline in Percent Predicted FVC in Upright Position at Week 49 |
2.89; 0.46 | 0.0074 sig |
| SECONDARY PAP: Change From Baseline in Total Distance Walked During Six-minute Walk Test (6MWT) at Week 49 |
32.21; 2.19 | 0.0405 sig |
| SECONDARY PAP: Change From Baseline in Percent Predicted Maximal Inspiratory Pressure (MIP) in Upright Position at Week 49 |
0.17; -2.96 | 0.5522 |
| SECONDARY PAP: Change From Baseline in Percent Predicted Maximal Expiratory Pressure (MEP) in Upright Position at Week 49 |
3.02; 4.95 | 0.7321 |
| SECONDARY PAP: Change From Baseline in Lower Extremity Muscle Strength at Week 49 as Assessed by Hand-Held Dynamometry (HHD) |
260.69; 153.72 | 0.1150 |
| SECONDARY PAP: Change From Baseline in Quick Motor Function Test (QMFT) Total Scores at Week 49 |
3.98; 1.89 | 0.0288 sig |
| SECONDARY PAP: Change From Baseline in 12-Item Short-Form Health Survey (SF-12): Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Week 49 |
2.37; 1.60; 2.88; 0.76 | 0.5996 |
| SECONDARY PAP: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Infusion-Associated Reactions (IARs) |
44; 45; 13; 16; 15; 20 | — |
| SECONDARY Open-label Period: Number of Participants With TEAEs and IARs |
51; 43; 1; 12; 22; 0 | — |
| SECONDARY PAP: Percentage of Participants With Treatment-Emergent Antidrug Antibodies (ADA) Response |
95.9; 95.7; 100; 100; 96.1; 95.8 | — |
Eligibility Criteria
Inclusion criteria
- The participant has confirmed acid alpha-glucosidase (GAA) enzyme deficiency from any tissue source and/or 2 confirmed GAA gene mutations.
- The participant must provide signed, informed consent prior to performing any study related procedures. Consent of a legally authorized guardian(s) is (are) required for legally minor participant as defined by local regulation. If the participant is legally minor, signed written consent shall be obtained from parent(s)/legal guardian and assent obtained from participants, if applicable.
Exclusion criteria
- The participant is <3 years of age.
- The participant has known Pompe specific cardiac hypertrophy.
- The participant is wheelchair dependent.
- The participant is not able to ambulate 40 meters (approximately 130 feet) without stopping and without an assistive device.
- The participant requires invasive-ventilation (non-invasive ventilation is allowed).
- The participant is not able to successfully perform repeated forced vital capacity (FVC) measurements in upright position of greater than or equal to 30% predicted and less than or equal to 85% predicted.
- The participant (and participant's legal guardian if participant is legally minor as defined by local regulation) is (are) not able to comply with the clinical protocol.
- The participant has had previous treatment with alglucosidase alfa or any investigational therapy for Pompe disease.
- The participant has prior or current use of immune tolerance induction therapy.
- The participant, if female and of childbearing potential, has a positive pregnancy test (beta-human chorionic gonadotropin) at baseline.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Data sourced from ClinicalTrials.gov (NCT02782741) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.