Refractory Generalized Myasthenia Gravis
Conditions
Keywords
Myasthenia Gravis, Eculizumab, safety, efficacy
Brief summary
The purpose of this study is to determine if eculizumab is safe and effective for the treatment of refractory generalized Myasthenia Gravis.
Interventions
BIOLOGICALEculizumab
Induction Phase: 900 mg IV weekly X 4 Maintenance Phase: 1200 mg IV every 2 weeks during Weeks 4-26
DRUGPlacebo
Placebo
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Male or female patients ≥18 years old * Diagnosis of MG made by the following tests: 1. Positive serologic test for anti-AChR Abs as confirmed at screening, and 2. One of the following: 1. History of abnormal neuromuscular transmission test demonstrated by single-fiber electromyography (SFEMG) or repetitive nerve stimulation, or 2. History of positive anticholinesterase test, e.g. edrophonium chloride test, or 3. Subject has demonstrated improvement in MG signs on oral cholinesterase inhibitors, as assessed by the treating physician. * MGFA Clinical Classification Class II to IV at screening. * MG-ADL total score must be ≥6 at screening and Randomization (Day 1). * Subjects who have: 1. Failed treatment with at least two immunosuppressive agents. Or, 2. Failed treatment with at least one immunosuppressive agent and require chronic plasma exchange or IVIg Key
Exclusion criteria
* History of thymoma or other neoplasms of the thymus * History of thymectomy within 12 months prior to screening * MGFA Class I or MG crisis at screening (MGFA Class V) * Use of rituximab within 6 months prior to screening * Use of IVIg or PE within 4 weeks prior to Randomization (Day 1)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Myasthenia Gravis Activities of Daily Living Profile (MG-ADL): Change From Baseline in MG-ADL Total Score at Week 26 by Worst-Rank Analysis of Covariance (ANCOVA) | End of study (Week 26) | In the Worst-Rank analysis, the 125 total patients were ranked from best outcome (rank/score of 1) to worst outcome (rank/score of 125). |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Czechia, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Japan, Netherlands, South Korea, Spain, Sweden, Turkey (Türkiye), United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Eculizumab Induction phase: 3 vials of study drug (equivalent to 900 mg of eculizumab) weekly for 4 doses (every 7 days ± 2 days) followed by 4 vials of study drug (equivalent to 1200 mg of eculizumab) 1 week later for the fifth dose (Week 4).
Maintenance phase: 4 vials of study drug (equivalent to 1200 mg of eculizumab) every 2 weeks (14 days ± 2 days) from the fifth dose onwards (Week 6 through Week 26). | 62 |
| Placebo Induction phase: 3 vials of study drug (placebo) weekly for 4 doses (every 7 days ± 2 days) followed by 4 vials of study drug (placebo) 1 week later for the fifth dose (Week 4).
Maintenance phase: 4 vials of study drug (placebo) every 2 weeks (14 days ± 2 days) from the fifth dose onwards (Week 6 through Week 26). | 63 |
| Total | 125 |
Baseline characteristics
| Characteristic | Eculizumab | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 47.5 years STANDARD_DEVIATION 15.66 | 46.9 years STANDARD_DEVIATION 17.98 | 47.2 years STANDARD_DEVIATION 16.8 |
| Sex: Female, Male Female | 41 Participants | 41 Participants | 82 Participants |
| Sex: Female, Male Male | 21 Participants | 22 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 62 | 0 / 63 |
| other Total, other adverse events | 52 / 62 | 53 / 63 |
| serious Total, serious adverse events | 9 / 62 | 18 / 63 |
Outcome results
Primary
Myasthenia Gravis Activities of Daily Living Profile (MG-ADL): Change From Baseline in MG-ADL Total Score at Week 26 by Worst-Rank Analysis of Covariance (ANCOVA)
In the Worst-Rank analysis, the 125 total patients were ranked from best outcome (rank/score of 1) to worst outcome (rank/score of 125).
Time frame: End of study (Week 26)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Eculizumab | Myasthenia Gravis Activities of Daily Living Profile (MG-ADL): Change From Baseline in MG-ADL Total Score at Week 26 by Worst-Rank Analysis of Covariance (ANCOVA) | 56.6 scores on a scale | Standard Error 4.53 |
| Placebo | Myasthenia Gravis Activities of Daily Living Profile (MG-ADL): Change From Baseline in MG-ADL Total Score at Week 26 by Worst-Rank Analysis of Covariance (ANCOVA) | 68.3 scores on a scale | Standard Error 4.49 |
p-value: 0.069895% CI: [-24.33, 0.96]ANCOVA