Myasthenia Gravis
Conditions
Brief summary
The purpose of this study is to determine whether eculizumab is safe and effective in the treatment of patients with generalized myasthenia gravis despite treatment with various immunosuppressants, such as prednisone, methotrexate, Cellcept, cyclosporine, and cyclophosphamide, that are currently available.
Interventions
DRUGeculizumab
eculizumab 600 mg IV weekly for 4 doses followed by eculizumab 900 mg IV every two weeks for 7 doses
DRUGPlacebo
Placebo IV weekly for 4 doses then every two weeks for 7 doses
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Generalized MG * MGFA Clinical Classification Class II, III or IVa. * QMG total score ≥12 * Minimum score of two (2) in four (4) or more test items in the QMG * Able to give informed consent. * Have failed at least two immunosuppressants after one year of treatment * A positive serologic test for binding anti-acetylcholine receptor Abs at Screening and one of the following a) history of abnormal neuromuscular transmission test demonstrated by single-fiber electromyography or repetitive nerve stimulation, or b) history of positive anticholinesterase test, eg, edrophonium chloride test, or c) patient has demonstrated improvement in MG signs on acetylcholinesterase inhibitors as assessed by treating physician.
Exclusion criteria
* History of thymoma or other neoplasms of the thymus. * History of thymectomy within 12 months prior to screening. * Pregnancy or lactation * Current or chronic use of plasmapheresis/plasma exchange * IVIG treatment within 8 weeks prior to screening. * Use of etanercept within 2 months prior to screening. * Use of rituximab (RITUXAN®) within 6 months prior to screening. * MGFA Class I, IVb, and V * Crisis or impending crisis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quantitative Myasthenia Gravis (QMG): The Primary Efficacy Endpoint in This Study Was the Percentage of Patients With a 3-point Reduction From Baseline in the QMG Total Score for Disease Severity. | 16 weeks | The QMG scoring system is considered to be an objective evaluation of muscle strength based on quantitative testing of sentinel muscle groups. The MGFA task force has recommended that the QMG score be used in prospective studies of therapy for MG. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the MGFA Post-Intervention Status (PIS) | 16 weeks | The MGFA PIS is designed to assess the clinical state of MG patients at any time after treatment of MG is initiated. Change in status categories of Improved, Unchanged, Worse, Exacerbation, and Died of MG was to be assessed and recorded at every visit from Visits 3 to 24 (Weeks 1 to 16). Minimal manifestations were to be assessed at these visits. |
| Change From Baseline in the MG-Activity of Daily Living Profile (MG-ADL) | 16 weeks | The MG-ADL is an 8-point questionnaire that focuses on relevant symptoms and functional performance of activities of daily living (ADL) in MG patients. The 8 items of the MG-ADL were derived from symptom-based components of the original 13-item QMG to assess disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. In this functional status instrument, each response is graded 0 (normal) to 3 (most severe). The range of total MG-ADL score is 0 - 24. MG-ADL was to be performed at every study visit. The recall period for MG-ADL was since the preceding study visit (1 or 2 weeks). |
| Change From Baseline in the QoL Instrument, SF-36. | 16 weeks | The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (physical functioning, role-physical, bodily pain, general health, mental health, role-emotional, social functioning and vitality) as well as psychometrically-based physical and mental health summary measures. It is a generic measure, as opposed to one that targets a specific age, disease or treatment group. The lower the score the more disability; the higher the score the less disability. Norm-based scoring involving a linear T-score transformation method was used so that scores for each of the health domain scales and component summary measures have a mean of 50 and a standard deviation of 10 based on the 1998 US general population. Thus, scores above and below 50 are above and below the average, respectively, in the 1998 US general. |
| Mean Change From Baseline in QMG Total Score | 16 weeks | The QMG scoring system is considered to be an objective evaluation of muscle strength based on quantitative testing of sentinel muscle groups. The Myasthenia Gravis Foundation of America task force has recommended that the QMG score be used in prospective studies of therapy for MG. The QMG scoring system consists of 13 items. Each item is graded 0 to 3, with 3 being the most severe. The range of total QMG score is 0-39. |
| Change From Baseline to the End of Treatment (16 Weeks) in the Two Most Affected QMG Items for Disease Severity (Individual Test Item: Double Vision) | 16 weeks | The QMG scoring system is considered to be an objective evaluation of muscle strength based on quantitative testing of sentinel muscle groups. The MGFA task force has recommended that the QMG score be used in prospective studies of therapy for MG. All individual QMG items are scored 0 to 3, with 3 being the most severe. Negative values imply an improvement in QMG Item Score. |
| Change From Baseline to the End of Treatment (16 Weeks) in the Two Most Affected QMG Items for Disease Severity (Individual Test Item: Ptosis) | 16 weeks | The QMG scoring system is considered to be an objective evaluation of muscle strength based on quantitative testing of sentinel muscle groups. The MGFA task force has recommended that the QMG score be used in prospective studies of therapy for MG. All individual QMG items are scored 0 to 3, with 3 being the most severe. Negative values imply an improvement in QMG Item Score. |
| Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles. | 16 weeks | Change from Baseline in Forced Vital Capacity |
Countries
Canada, United Kingdom, United States
Participant flow
Recruitment details
There were 26 IRB/IEC-approved study sites. Patients were screened at 13 Institutional Review Board/Independent Ethics Committee approved study sites; and 14 patients were randomized at 8 sites.
Pre-assignment details
Patients received standard of care during the Screening Period. Patients were randomized to a treatment sequence to receive eculizumab in Period 1 followed by placebo in Period 2 or placebo in Period 1 followed by eculizumab in Period 2. Patients were permitted to continue on background immunosuppressive therapy throughout the study.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Eculizumab:
Eculizumab \[600 mg IV weekly (4 doses) followed by 900 mg IV every other week (7 doses)\].
Period 1: patients received eculizumab for 16 weeks; Period 2: wash-out period for 5 weeks (the cross-over treatment period). Patients then received placebo for 16 weeks.
Placebo:
Matching placebo \[IV weekly (4 doses) followed by IV every other week (7 doses)\] Period 1: patients received placebo for 16 weeks; Period 2: wash-out period for 5 weeks (the cross-over treatment period). Patients then received eculizumab for 16 weeks. | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Screening Period | History of thymoma | 0 | 0 | 1 |
| Screening Period | Lacked AChR antibodies | 0 | 0 | 5 |
| Screening Period | Low QMG scores | 0 | 0 | 6 |
| Screening Period | Not stable on concomitant MG therapy | 0 | 0 | 2 |
| Screening Period | Severe infections | 0 | 0 | 2 |
| Treatment Period 2 | Lack of Efficacy | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 49 years STANDARD_DEVIATION 14 |
| Cholinesterase inhibitor use at Screening No | 2 participants |
| Cholinesterase inhibitor use at Screening Yes | 12 participants |
| Immunosuppression therapy other than prednisone at Screening No | 7 participants |
| Immunosuppression therapy other than prednisone at Screening Yes | 7 participants |
| Myasthenia Gravis-Activity of Daily Living (MG-ADL) | 8.2 units on a scale |
| Myasthenia Gravis Foundation of America (MGFA) classification at Screening IIa | 2 participants |
| Myasthenia Gravis Foundation of America (MGFA) classification at Screening IIb | 2 participants |
| Myasthenia Gravis Foundation of America (MGFA) classification at Screening IIIa | 8 participants |
| Myasthenia Gravis Foundation of America (MGFA) classification at Screening IVa | 2 participants |
| Number of MG crisis/exacerbation prior to Screening | 5 Events STANDARD_DEVIATION 6 |
| Prednisone use at Screening No prednisone use | 7 participants |
| Prednisone use at Screening Prednisone use | 7 participants |
| Quantitative Myasthenia Gravis (QMG) at Screening | 19 QMG score STANDARD_DEVIATION 6 |
| Race/Ethnicity, Customized Black | 1 participants |
| Race/Ethnicity, Customized Caucasian | 11 participants |
| Race/Ethnicity, Customized Hispanic | 2 participants |
| Region of Enrollment United Kingdom | 1 participants |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 13 | 13 / 13 |
| serious Total, serious adverse events | 1 / 13 | 1 / 13 |
Outcome results
Primary
Quantitative Myasthenia Gravis (QMG): The Primary Efficacy Endpoint in This Study Was the Percentage of Patients With a 3-point Reduction From Baseline in the QMG Total Score for Disease Severity.
The QMG scoring system is considered to be an objective evaluation of muscle strength based on quantitative testing of sentinel muscle groups. The MGFA task force has recommended that the QMG score be used in prospective studies of therapy for MG.
Time frame: 16 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eculizumab Period 1 | Quantitative Myasthenia Gravis (QMG): The Primary Efficacy Endpoint in This Study Was the Percentage of Patients With a 3-point Reduction From Baseline in the QMG Total Score for Disease Severity. | 86 percentage of patients |
| Placebo Period 1 | Quantitative Myasthenia Gravis (QMG): The Primary Efficacy Endpoint in This Study Was the Percentage of Patients With a 3-point Reduction From Baseline in the QMG Total Score for Disease Severity. | 57 percentage of patients |
Secondary
Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles.
Change from Baseline in Forced Vital Capacity
Time frame: 16 weeks
Population: Comparison of FVC at the Last Visit Between Eculizumab and Placebo Cohorts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eculizumab Period 1 | Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles. | 76.43 percentage of predicted | Standard Deviation 15.328 |
| Placebo Period 1 | Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles. | 87.00 percentage of predicted | Standard Deviation 23.544 |
| Eculizumab Both Periods | Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles. | 80.00 percentage of predicted | Standard Deviation 14.894 |
| Placebo Both Periods | Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles. | 76.75 percentage of predicted | Standard Deviation 23.152 |
Comparison: Forced Vital Capacityp-value: 0.337795% CI: [-3.94, 10.44]paired t-test
Comparison: Forced Vital Capacityp-value: 0.339195% CI: [-33.71, 12.56]t-test, 2 sided
Comparison: Negative Inspiratory Forcep-value: 195% CI: [-4.35, 4.35]paired t test
Comparison: Negative Inspiratory Forcep-value: 0.229295% CI: [-17.87, 4.73]t-test, 2 sided
Secondary
Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles.
Change from Baseline in Negative Inspiratory Force. NIF is a measurement of respiratory muscle strength and ventilator reserve. NIF is represented by centimeters of water pressure (cmH2O). A normal NIF measurement is negative 60 cmH2O, or as 100% predicted value.
Time frame: 16 weeks
Population: Comparison of NIF at the Last Visit Between Eculizumab and Placebo Cohorts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eculizumab Period 1 | Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles. | 92.43 percentage of predicted | Standard Deviation 13.464 |
| Placebo Period 1 | Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles. | 99.00 percentage of predicted | Standard Deviation 2.646 |
| Eculizumab Both Periods | Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles. | 93.50 percentage of predicted | Standard Deviation 12.087 |
| Placebo Both Periods | Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles. | 93.50 percentage of predicted | Standard Deviation 12.042 |
Secondary
Change From Baseline in the MG-Activity of Daily Living Profile (MG-ADL)
The MG-ADL is an 8-point questionnaire that focuses on relevant symptoms and functional performance of activities of daily living (ADL) in MG patients. The 8 items of the MG-ADL were derived from symptom-based components of the original 13-item QMG to assess disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. In this functional status instrument, each response is graded 0 (normal) to 3 (most severe). The range of total MG-ADL score is 0 - 24. MG-ADL was to be performed at every study visit. The recall period for MG-ADL was since the preceding study visit (1 or 2 weeks).
Time frame: 16 weeks
Population: Comparison of MG Activities of Daily Living (Total score) at the Last Visit Between Eculizumab and Placebo Cohorts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eculizumab Period 1 | Change From Baseline in the MG-Activity of Daily Living Profile (MG-ADL) | 4.29 units on a scale | Standard Deviation 1.799 |
| Placebo Period 1 | Change From Baseline in the MG-Activity of Daily Living Profile (MG-ADL) | 7.86 units on a scale | Standard Deviation 3.716 |
| Eculizumab Both Periods | Change From Baseline in the MG-Activity of Daily Living Profile (MG-ADL) | 5.42 units on a scale | Standard Deviation 3.315 |
| Placebo Both Periods | Change From Baseline in the MG-Activity of Daily Living Profile (MG-ADL) | 7.00 units on a scale | Standard Deviation 3.464 |
p-value: 0.187395% CI: [-4.08, 0.91]paired t-test
p-value: 0.04195% CI: [-6.97, -0.17]t-test, 2 sided
Secondary
Change From Baseline in the MGFA Post-Intervention Status (PIS)
The MGFA PIS is designed to assess the clinical state of MG patients at any time after treatment of MG is initiated. Change in status categories of Improved, Unchanged, Worse, Exacerbation, and Died of MG was to be assessed and recorded at every visit from Visits 3 to 24 (Weeks 1 to 16). Minimal manifestations were to be assessed at these visits.
Time frame: 16 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eculizumab Period 1 | Change From Baseline in the MGFA Post-Intervention Status (PIS) | Exacerbation | 0 participants |
| Eculizumab Period 1 | Change From Baseline in the MGFA Post-Intervention Status (PIS) | Unchanged | 2 participants |
| Eculizumab Period 1 | Change From Baseline in the MGFA Post-Intervention Status (PIS) | Died of MG | 0 participants |
| Eculizumab Period 1 | Change From Baseline in the MGFA Post-Intervention Status (PIS) | Worse | 0 participants |
| Eculizumab Period 1 | Change From Baseline in the MGFA Post-Intervention Status (PIS) | Improved | 5 participants |
| Placebo Period 1 | Change From Baseline in the MGFA Post-Intervention Status (PIS) | Exacerbation | 0 participants |
| Placebo Period 1 | Change From Baseline in the MGFA Post-Intervention Status (PIS) | Worse | 0 participants |
| Placebo Period 1 | Change From Baseline in the MGFA Post-Intervention Status (PIS) | Died of MG | 0 participants |
| Placebo Period 1 | Change From Baseline in the MGFA Post-Intervention Status (PIS) | Unchanged | 1 participants |
| Placebo Period 1 | Change From Baseline in the MGFA Post-Intervention Status (PIS) | Improved | 6 participants |
| Eculizumab Both Periods | Change From Baseline in the MGFA Post-Intervention Status (PIS) | Improved | 6 participants |
| Eculizumab Both Periods | Change From Baseline in the MGFA Post-Intervention Status (PIS) | Unchanged | 0 participants |
| Eculizumab Both Periods | Change From Baseline in the MGFA Post-Intervention Status (PIS) | Worse | 0 participants |
| Eculizumab Both Periods | Change From Baseline in the MGFA Post-Intervention Status (PIS) | Exacerbation | 0 participants |
| Eculizumab Both Periods | Change From Baseline in the MGFA Post-Intervention Status (PIS) | Died of MG | 0 participants |
| Placebo Both Periods | Change From Baseline in the MGFA Post-Intervention Status (PIS) | Improved | 2 participants |
| Placebo Both Periods | Change From Baseline in the MGFA Post-Intervention Status (PIS) | Died of MG | 0 participants |
| Placebo Both Periods | Change From Baseline in the MGFA Post-Intervention Status (PIS) | Worse | 0 participants |
| Placebo Both Periods | Change From Baseline in the MGFA Post-Intervention Status (PIS) | Unchanged | 4 participants |
| Placebo Both Periods | Change From Baseline in the MGFA Post-Intervention Status (PIS) | Exacerbation | 0 participants |
p-value: 1Chi-squared
p-value: 0.0606Chi-squared
Secondary
Change From Baseline in the QoL Instrument, SF-36.
The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (physical functioning, role-physical, bodily pain, general health, mental health, role-emotional, social functioning and vitality) as well as psychometrically-based physical and mental health summary measures. It is a generic measure, as opposed to one that targets a specific age, disease or treatment group. The lower the score the more disability; the higher the score the less disability. Norm-based scoring involving a linear T-score transformation method was used so that scores for each of the health domain scales and component summary measures have a mean of 50 and a standard deviation of 10 based on the 1998 US general population. Thus, scores above and below 50 are above and below the average, respectively, in the 1998 US general.
Time frame: 16 weeks
Population: Comparison of SF-36 at the Last Visit Between Eculizumab and Placebo Cohorts.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eculizumab Period 1 | Change From Baseline in the QoL Instrument, SF-36. | Mental Component Score (Last Visit) | 49.50 units on a scale | Standard Deviation 12.066 |
| Eculizumab Period 1 | Change From Baseline in the QoL Instrument, SF-36. | Social Functioning (Last Visit) | 66.07 units on a scale | Standard Deviation 25.733 |
| Eculizumab Period 1 | Change From Baseline in the QoL Instrument, SF-36. | Vitality (Last Visit) | 50.00 units on a scale | Standard Deviation 23.936 |
| Eculizumab Period 1 | Change From Baseline in the QoL Instrument, SF-36. | Role Physical (Last Visit) | 61.61 units on a scale | Standard Deviation 38.6 |
| Eculizumab Period 1 | Change From Baseline in the QoL Instrument, SF-36. | Role Emotional (Last Visit) | 77.38 units on a scale | Standard Deviation 36.233 |
| Eculizumab Period 1 | Change From Baseline in the QoL Instrument, SF-36. | Physical Component Score (Last Visit) | 38.73 units on a scale | Standard Deviation 10.235 |
| Eculizumab Period 1 | Change From Baseline in the QoL Instrument, SF-36. | Mental Health (Last Visit) | 76.43 units on a scale | Standard Deviation 17.728 |
| Eculizumab Period 1 | Change From Baseline in the QoL Instrument, SF-36. | Bodily Pain (Last Visit) | 60.00 units on a scale | Standard Deviation 24.235 |
| Eculizumab Period 1 | Change From Baseline in the QoL Instrument, SF-36. | Physical Functioning (Last Visit) | 56.43 units on a scale | Standard Deviation 29.255 |
| Eculizumab Period 1 | Change From Baseline in the QoL Instrument, SF-36. | General Health (Last Visit) | 47.86 units on a scale | Standard Deviation 16.994 |
| Placebo Period 1 | Change From Baseline in the QoL Instrument, SF-36. | Role Emotional (Last Visit) | 71.43 units on a scale | Standard Deviation 29.603 |
| Placebo Period 1 | Change From Baseline in the QoL Instrument, SF-36. | Role Physical (Last Visit) | 68.75 units on a scale | Standard Deviation 25.769 |
| Placebo Period 1 | Change From Baseline in the QoL Instrument, SF-36. | General Health (Last Visit) | 40.43 units on a scale | Standard Deviation 23.201 |
| Placebo Period 1 | Change From Baseline in the QoL Instrument, SF-36. | Vitality (Last Visit) | 52.68 units on a scale | Standard Deviation 15.67 |
| Placebo Period 1 | Change From Baseline in the QoL Instrument, SF-36. | Social Functioning (Last Visit) | 82.14 units on a scale | Standard Deviation 17.466 |
| Placebo Period 1 | Change From Baseline in the QoL Instrument, SF-36. | Mental Health (Last Visit) | 58.57 units on a scale | Standard Deviation 25.284 |
| Placebo Period 1 | Change From Baseline in the QoL Instrument, SF-36. | Physical Component Score (Last Visit) | 44.97 units on a scale | Standard Deviation 7.721 |
| Placebo Period 1 | Change From Baseline in the QoL Instrument, SF-36. | Physical Functioning (Last Visit) | 64.29 units on a scale | Standard Deviation 24.054 |
| Placebo Period 1 | Change From Baseline in the QoL Instrument, SF-36. | Bodily Pain (Last Visit) | 74.86 units on a scale | Standard Deviation 20.651 |
| Placebo Period 1 | Change From Baseline in the QoL Instrument, SF-36. | Mental Component Score (Last Visit) | 43.95 units on a scale | Standard Deviation 12.53 |
| Eculizumab Both Periods | Change From Baseline in the QoL Instrument, SF-36. | Role Physical (Last Visit) | 64.06 units on a scale | Standard Deviation 31.771 |
| Eculizumab Both Periods | Change From Baseline in the QoL Instrument, SF-36. | Mental Component Score (Last Visit) | 46.11 units on a scale | Standard Deviation 12.596 |
| Eculizumab Both Periods | Change From Baseline in the QoL Instrument, SF-36. | Mental Health (Last Visit) | 69.17 units on a scale | Standard Deviation 20.542 |
| Eculizumab Both Periods | Change From Baseline in the QoL Instrument, SF-36. | Physical Component Score (Last Visit) | 41.40 units on a scale | Standard Deviation 8.591 |
| Eculizumab Both Periods | Change From Baseline in the QoL Instrument, SF-36. | Vitality (Last Visit) | 53.13 units on a scale | Standard Deviation 19.31 |
| Eculizumab Both Periods | Change From Baseline in the QoL Instrument, SF-36. | Role Emotional (Last Visit) | 70.83 units on a scale | Standard Deviation 34.542 |
| Eculizumab Both Periods | Change From Baseline in the QoL Instrument, SF-36. | General Health (Last Visit) | 44.67 units on a scale | Standard Deviation 16.267 |
| Eculizumab Both Periods | Change From Baseline in the QoL Instrument, SF-36. | Physical Functioning (Last Visit) | 57.92 units on a scale | Standard Deviation 26.921 |
| Eculizumab Both Periods | Change From Baseline in the QoL Instrument, SF-36. | Social Functioning (Last Visit) | 66.67 units on a scale | Standard Deviation 24.034 |
| Eculizumab Both Periods | Change From Baseline in the QoL Instrument, SF-36. | Bodily Pain (Last Visit) | 66.75 units on a scale | Standard Deviation 22.511 |
| Placebo Both Periods | Change From Baseline in the QoL Instrument, SF-36. | Social Functioning (Last Visit) | 78.13 units on a scale | Standard Deviation 17.778 |
| Placebo Both Periods | Change From Baseline in the QoL Instrument, SF-36. | Role Emotional (Last Visit) | 82.64 units on a scale | Standard Deviation 25.981 |
| Placebo Both Periods | Change From Baseline in the QoL Instrument, SF-36. | Role Physical (Last Visit) | 60.94 units on a scale | Standard Deviation 27.324 |
| Placebo Both Periods | Change From Baseline in the QoL Instrument, SF-36. | Mental Health (Last Visit) | 68.75 units on a scale | Standard Deviation 23.27 |
| Placebo Both Periods | Change From Baseline in the QoL Instrument, SF-36. | Physical Component Score (Last Visit) | 40.32 units on a scale | Standard Deviation 10.025 |
| Placebo Both Periods | Change From Baseline in the QoL Instrument, SF-36. | Physical Functioning (Last Visit) | 57.08 units on a scale | Standard Deviation 27.507 |
| Placebo Both Periods | Change From Baseline in the QoL Instrument, SF-36. | Mental Component Score (Last Visit) | 49.03 units on a scale | Standard Deviation 11.476 |
| Placebo Both Periods | Change From Baseline in the QoL Instrument, SF-36. | Bodily Pain (Last Visit) | 76.17 units on a scale | Standard Deviation 15.689 |
| Placebo Both Periods | Change From Baseline in the QoL Instrument, SF-36. | General Health (Last Visit) | 37.50 units on a scale | Standard Deviation 19.365 |
| Placebo Both Periods | Change From Baseline in the QoL Instrument, SF-36. | Vitality (Last Visit) | 48.96 units on a scale | Standard Deviation 18.238 |
Comparison: Physical Functioningp-value: 0.91995% CI: [-16.94, 18.6]paired t-test
Comparison: Physical Functioningp-value: 0.593195% CI: [-39.05, 23.33]t-test, 2 sided
Comparison: Role Physicalp-value: 0.731995% CI: [-16.64, 22.89]Paired t-test
Comparison: Role Physicalp-value: 0.69195% CI: [-45.36, 31.08]t-test, 2 sided
Comparison: Bodily Painp-value: 0.131195% CI: [-22.18, 3.34]Paired t-test
Comparison: Bodily Painp-value: 0.240695% CI: [-41.08, 11.36]t-test, 2 sided
Comparison: General Healthp-value: 0.057895% CI: [-0.29, 14.62]Paired t-test
Comparison: General Healthp-value: 0.507395% CI: [-16.26, 31.11]t-test, 2 sided
Comparison: Vitalityp-value: 0.247495% CI: [-3.39, 11.72]Paired t-test
Comparison: Vitalityp-value: 0.808595% CI: [-26.24, 20.88]t-test, 2 sided
Comparison: Social Functioningp-value: 0.071695% CI: [-24.13, 1.21]Paired t-test
Comparison: Social Functioningp-value: 0.196695% CI: [-41.68, 9.54]t-test, 2 sided
Comparison: Role Emotionalp-value: 0.170195% CI: [-29.6, 5.99]paired t-test
Comparison: Role Emotionalp-value: 0.742295% CI: [-32.58, 44.48]t-test, 2 sided
Comparison: Mental Healthp-value: 0.900795% CI: [-6.83, 7.67]Paired t-test
Comparison: Mental Healthp-value: 0.151995% CI: [-7.57, 43.29]t-test, 2 sided
Comparison: Physical Component Scorep-value: 0.680795% CI: [-4.57, 6.72]Paired t-test
Comparison: Physical Component Scorep-value: 0.222695% CI: [-16.79, 4.32]t-test, 2 sided
Comparison: Mental Component Scorep-value: 0.150595% CI: [-7.1, 1.26]Paired t-test
Comparison: Mental Component Scorep-value: 0.415195% CI: [-8.77, 19.87]t-test, 2 sided
Secondary
Change From Baseline to the End of Treatment (16 Weeks) in the Two Most Affected QMG Items for Disease Severity (Individual Test Item: Double Vision)
The QMG scoring system is considered to be an objective evaluation of muscle strength based on quantitative testing of sentinel muscle groups. The MGFA task force has recommended that the QMG score be used in prospective studies of therapy for MG. All individual QMG items are scored 0 to 3, with 3 being the most severe. Negative values imply an improvement in QMG Item Score.
Time frame: 16 weeks
Population: The Investigators selected the 2 most affected items (double vision, ptosis) out of the 13 items in the QMG scoring system for each of their patients based on their clinical evaluation at Baseline. The count is provided when the item was selected as the most affected by the Investigator, for participants who were treated in the respective sequence.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eculizumab Period 1 | Change From Baseline to the End of Treatment (16 Weeks) in the Two Most Affected QMG Items for Disease Severity (Individual Test Item: Double Vision) | -0.71 units on a scale | Standard Deviation 1.113 |
| Placebo Period 1 | Change From Baseline to the End of Treatment (16 Weeks) in the Two Most Affected QMG Items for Disease Severity (Individual Test Item: Double Vision) | -0.29 units on a scale | Standard Deviation 0.488 |
Secondary
Change From Baseline to the End of Treatment (16 Weeks) in the Two Most Affected QMG Items for Disease Severity (Individual Test Item: Ptosis)
The QMG scoring system is considered to be an objective evaluation of muscle strength based on quantitative testing of sentinel muscle groups. The MGFA task force has recommended that the QMG score be used in prospective studies of therapy for MG. All individual QMG items are scored 0 to 3, with 3 being the most severe. Negative values imply an improvement in QMG Item Score.
Time frame: 16 weeks
Population: The Investigators selected the 2 most affected items (double vision, ptosis) out of the 13 items in the QMG scoring system for each of their patients based on their clinical evaluation at Baseline. The count is provided when the item was selected as the most affected by the Investigator, for participants who were treated in the respective sequence.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eculizumab Period 1 | Change From Baseline to the End of Treatment (16 Weeks) in the Two Most Affected QMG Items for Disease Severity (Individual Test Item: Ptosis) | -1.00 units on a scale | Standard Deviation 1.155 |
| Placebo Period 1 | Change From Baseline to the End of Treatment (16 Weeks) in the Two Most Affected QMG Items for Disease Severity (Individual Test Item: Ptosis) | -0.5 units on a scale | Standard Deviation 1 |
Secondary
Mean Change From Baseline in QMG Total Score
The QMG scoring system is considered to be an objective evaluation of muscle strength based on quantitative testing of sentinel muscle groups. The Myasthenia Gravis Foundation of America task force has recommended that the QMG score be used in prospective studies of therapy for MG. The QMG scoring system consists of 13 items. Each item is graded 0 to 3, with 3 being the most severe. The range of total QMG score is 0-39.
Time frame: 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eculizumab Period 1 | Mean Change From Baseline in QMG Total Score | -7.43 units on a scale | Standard Deviation 5.563 |
| Placebo Period 1 | Mean Change From Baseline in QMG Total Score | -2.71 units on a scale | Standard Deviation 4.855 |
| Eculizumab Both Periods | Mean Change From Baseline in QMG Total Score | -7.92 units on a scale | Standard Deviation 5.054 |
| Placebo Both Periods | Mean Change From Baseline in QMG Total Score | -3.67 units on a scale | Standard Deviation 4.008 |
p-value: 0.014495% CI: [-7.45, -1.05]paired t-test
p-value: 0.11795% CI: [-10.8, 1.37]t-test, 2 sided