Refractory Generalized Myasthenia Gravis
Conditions
Keywords
gMG, Myasthenia Gravis, safety, efficacy
Brief summary
To evaluate the safety and efficacy of eculizumab in the treatment of refractory generalized myasthenia gravis (gMG) as an extension study for the participants who previously completed Study ECU-MG-301(NCT01997229).
Detailed description
ECU-MG-302 was an extension study designed to provide the participants who completed Study ECU-MG-301 an opportunity to receive eculizumab and collect clinical data to provide long-term safety and efficacy information on eculizumab in participants with refractory gMG. After receiving blinded study treatment (eculizumab or placebo) in Study ECU-MG-301 for 26 weeks, participants were eligible to enroll in the ECU-MG-302 extension study. Participants were to enter Study ECU-MG-302 within 2 weeks after completing their Week 26 visit in Study ECU-MG-301. Study ECU-MG-302 consisted of a 4-week Blind Induction Phase to preserve the blinded nature of Study ECU-MG-301, an Open-Label Maintenance Phase (up to 4 years), and a Safety Follow-up visit 8 weeks after the last dose for participants who withdrew from the study or discontinued eculizumab treatment at any time and for any reason after receiving any amount of eculizumab.
Interventions
BIOLOGICALEculizumab
Intravenous administration of eculizumab.
DRUGPlacebo
Intravenous administration of matching placebo. Participants received placebo only during the Blind Induction Phase.
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
The study consisted of a 4-week Blind Induction Phase to preserve the blinded nature of Study ECU-MG-301, followed by an Open-Label Maintenance Phase.
Intervention model description
Following the Blind Induction Phase, all participants received open-label eculizumab.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participant has completed Study ECU-MG-301. 2. Participant has given written informed consent. 3. Participant was willing and able to comply with the protocol requirements for the duration of the study. 4. Female participant of childbearing potential must have had a negative pregnancy test (serum human chorionic gonadotropin). All participants were required to practice an effective, reliable, and medically approved contraceptive regimen during the study and for up to 5 months following discontinuation of treatment.
Exclusion criteria
1. Participants who withdrew from Study ECU-MG-301 as a result of an adverse event related to study drug. 2. Female participants who were pregnant, breastfeeding, or intended to conceive during the course of the study. 3. Unresolved meningococcal infection 4. Hypersensitivity to murine proteins or to one of the excipients of eculizumab 5. Any medical condition or circumstances that, in the opinion of the investigator, might have interfered with the participant's participation in the study, posed any added risk for the participant, or confounded the assessment of the participants.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Count Of Participants With Treatment-Emergent Adverse Events | Day 1 (after dosing) through End of Study (Week 208) | Treatment-emergent adverse events (TEAEs) are adverse events with onset on or after the first study drug dose in Study ECU-MG-302. Likewise, treatment-emergent serious adverse events (TESAEs) are serious adverse events that onset on or after the first study drug dose in Study ECU-MG-302. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline In Myasthenia Gravis Activities Of Daily Living Profile (MG-ADL) Total Score At Week 4 And Week 130 | Baseline, Week 4 and Week 130 | The MG-ADL scale is a validated 8-item patient-reported outcome measure. Participants assessed their functional disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb impairment (2 items). These 8 items were not weighted and were individually graded from 0 (normal) to 3 (most severe), providing a total MG-ADL score ranging from 0 to 24 points. A reduction in score indicates improvement in condition. Baseline was defined as the last available assessment prior to treatment (first study drug infusion) with eculizumab in Study ECU-MG-302. Change from Baseline in MG-ADL total score at Week 4 (blind induction phase) and at Week 130 (open-label eculizumab phase) are presented. |
Countries
Argentina, Belgium, Brazil, Canada, Czechia, Denmark, Finland, Hungary, Italy, Japan, Netherlands, South Korea, Spain, Sweden, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Participants who completed Study ECU-MG-301 (NCT01997229) were eligible to participate in Study ECU-MG-302.
Participants by arm
| Arm | Count |
|---|---|
| Eculizumab/Eculizumab Blind Induction Phase: Participants who had received blinded treatment with eculizumab in Study ECU-MG-301 were administered eculizumab (4 vials/1200 mg) on Day 1 and Week 2 and placebo (4 vials/0 mg) at Weeks 1 and 3.
Open-Label Maintenance Phase: Participants received open-label eculizumab (4 vials/1200 mg) every 2 weeks starting at Week 4 and continued throughout the study.
Eculizumab 1200 mg was administered for up to 4 years in this extension study. | 56 |
| Placebo/Eculizumab Blind Induction Phase: Participants who had received blinded treatment with placebo in Study ECU-MG-301 were administered eculizumab/placebo (3 vials/900 mg, plus 1 vial/0 mg, respectively) on Day 1 and Weeks 1 through 3.
Open-Label Maintenance Phase: Participants received open-label eculizumab (4 vials/1200 mg) every 2 weeks starting at Week 4 and continued throughout the study.
Eculizumab 1200 mg was administered for up to 4 years in this extension study. | 61 |
| Total | 117 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Blind Induction Phase | Withdrawal by Subject | 1 | 0 |
| Open-label Maintenance Phase | Adverse Event | 2 | 5 |
| Open-label Maintenance Phase | Death | 2 | 1 |
| Open-label Maintenance Phase | Participant felt no change in condition | 1 | 0 |
| Open-label Maintenance Phase | Physician Decision | 3 | 3 |
| Open-label Maintenance Phase | Withdrawal by Subject | 4 | 8 |
Baseline characteristics
| Characteristic | Placebo/Eculizumab | Total | Eculizumab/Eculizumab |
|---|---|---|---|
| Age, Continuous | 47.5 years STANDARD_DEVIATION 17.85 | 47.4 years STANDARD_DEVIATION 16.7 | 47.2 years STANDARD_DEVIATION 15.52 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 18 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants | 93 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 6 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 16 Participants | 19 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 6 Participants | 4 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 41 Participants | 88 Participants | 47 Participants |
| Sex: Female, Male Female | 41 Participants | 79 Participants | 38 Participants |
| Sex: Female, Male Male | 20 Participants | 38 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 56 | 1 / 61 | 3 / 117 |
| other Total, other adverse events | 54 / 56 | 59 / 61 | 113 / 117 |
| serious Total, serious adverse events | 30 / 56 | 30 / 61 | 60 / 117 |
Outcome results
Primary
Count Of Participants With Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are adverse events with onset on or after the first study drug dose in Study ECU-MG-302. Likewise, treatment-emergent serious adverse events (TESAEs) are serious adverse events that onset on or after the first study drug dose in Study ECU-MG-302. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
Time frame: Day 1 (after dosing) through End of Study (Week 208)
Population: All participants who received at least 1 dose of eculizumab in this extension study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Eculizumab/Eculizumab | Count Of Participants With Treatment-Emergent Adverse Events | TEAEs | 55 Participants |
| Eculizumab/Eculizumab | Count Of Participants With Treatment-Emergent Adverse Events | TESAEs leading to withdrawal | 3 Participants |
| Eculizumab/Eculizumab | Count Of Participants With Treatment-Emergent Adverse Events | TESAEs | 30 Participants |
| Eculizumab/Eculizumab | Count Of Participants With Treatment-Emergent Adverse Events | Deaths | 2 Participants |
| Eculizumab/Eculizumab | Count Of Participants With Treatment-Emergent Adverse Events | TEAEs leading to withdrawal | 3 Participants |
| Placebo/Eculizumab | Count Of Participants With Treatment-Emergent Adverse Events | Deaths | 1 Participants |
| Placebo/Eculizumab | Count Of Participants With Treatment-Emergent Adverse Events | TEAEs | 59 Participants |
| Placebo/Eculizumab | Count Of Participants With Treatment-Emergent Adverse Events | TEAEs leading to withdrawal | 5 Participants |
| Placebo/Eculizumab | Count Of Participants With Treatment-Emergent Adverse Events | TESAEs | 30 Participants |
| Placebo/Eculizumab | Count Of Participants With Treatment-Emergent Adverse Events | TESAEs leading to withdrawal | 4 Participants |
Secondary
Change From Baseline In Myasthenia Gravis Activities Of Daily Living Profile (MG-ADL) Total Score At Week 4 And Week 130
The MG-ADL scale is a validated 8-item patient-reported outcome measure. Participants assessed their functional disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb impairment (2 items). These 8 items were not weighted and were individually graded from 0 (normal) to 3 (most severe), providing a total MG-ADL score ranging from 0 to 24 points. A reduction in score indicates improvement in condition. Baseline was defined as the last available assessment prior to treatment (first study drug infusion) with eculizumab in Study ECU-MG-302. Change from Baseline in MG-ADL total score at Week 4 (blind induction phase) and at Week 130 (open-label eculizumab phase) are presented.
Time frame: Baseline, Week 4 and Week 130
Population: All participants who received at least 1 dose of eculizumab in this extension study and had an MG-ADL efficacy assessment after study drug infusion at the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eculizumab/Eculizumab | Change From Baseline In Myasthenia Gravis Activities Of Daily Living Profile (MG-ADL) Total Score At Week 4 And Week 130 | Change from Baseline At Week 4 (Blind Induction) | -0.2 units on a scale | Standard Deviation 1.77 |
| Eculizumab/Eculizumab | Change From Baseline In Myasthenia Gravis Activities Of Daily Living Profile (MG-ADL) Total Score At Week 4 And Week 130 | Change from Baseline at Week 130 (Open-label) | -0.7 units on a scale | Standard Deviation 4.19 |
| Placebo/Eculizumab | Change From Baseline In Myasthenia Gravis Activities Of Daily Living Profile (MG-ADL) Total Score At Week 4 And Week 130 | Change from Baseline At Week 4 (Blind Induction) | -2.4 units on a scale | Standard Deviation 3.04 |
| Placebo/Eculizumab | Change From Baseline In Myasthenia Gravis Activities Of Daily Living Profile (MG-ADL) Total Score At Week 4 And Week 130 | Change from Baseline at Week 130 (Open-label) | -3.9 units on a scale | Standard Deviation 3.68 |