Generalized Myasthenia Gravis, gMG, Myasthenia Gravis, Myasthenia Gravis, Generalized
Conditions
Brief summary
The primary purpose of this study is to measure the efficacy and safety of efgartigimod IV compared to placebo in participants with Acetylcholine Receptor Binding Antibody (AChR-Ab) seronegative Generalized Myasthenia Gravis (gMG). The study consists of a Part A where participants will be randomized to receive either efgartigimod IV or placebo IV and a Part B where participants completing part A will receive open-label efgartigimod IV. Participants will be in the study for up to (approximately) 3.5 years.
Interventions
BIOLOGICALEfgartigimod IV
Intravenous infusion of efgartigimod
OTHERPlacebo IV
Intravenous infusion of placebo
Sponsors
argenx
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The participant is at least 18 years of age and the local legal age of consent for clinical studies when signing the ICF. * The participant is capable of providing signed informed consent and following with protocol requirements. * The participant agrees to use contraceptive measures consistent with local regulations and the women of child-bearing potential (WOCBP) must have a negative serum pregnancy test result at screening and a negative urine pregnancy test result at baseline before receiving the study drug. * The participant has no known weakness in infancy and later develop fatigable weakness after aged 16 years and diagnosed with acquired gMG of both of the following: 1. History of abnormal neuromuscular transmission demonstrated by single fiber electromyography or repetitive nerve stimulation (RNS) or is for anti-muscle-specific kinase antibodies (MuSK-Ab) seropositive 2. Either a history of positive edrophonium chloride test OR a demonstrated improvement in MG signs with treatments such as oral acetylcholinesterase (AChE) inhibitors, plasma exchange (PLEX), immunoabsorption, or intravenous immunoglobulin (IVIg)/ subcutaneous immunoglobulin (SCIg) treatment * The participant is receiving a stable dose of MG therapy before screening, including acetylcholinesterase (AChE) inhibitors, steroids, or nonsteroidal immunosuppressive therapies (NSISTs) in combination or alone
Exclusion criteria
* Known autoimmune disease or any medical condition that would interfere with an accurate assessment of clinical symptoms of gMG or puts the participant at undue risk * History of malignancy, cancer, unless considered cured by adequate treatment with no evidence of recurrence for ≥3 years. Adequately treated participants with the following cancers can be included at any time: Basal cell or squamous cell skin cancer, Carcinoma in situ of the cervix, Carcinoma in situ of the breast, Incidental histological findings of prostate cancer * Clinically significant active infection that is not sufficiently resolved in the investigator's opinion or positive serum test at screening for active infection with any of the following: Hepatitis B virus (HBV), Hepatitis C virus (HCV), HIV * History of or current alcohol, drug, or medication abuse as assessed by the investigator * Pregnant or lactating state or intention to become pregnant during the study * Live or live-attenuated vaccine received \<4 weeks before screening * Worsening muscle weakness secondary to concurrent infections or medications * Received a thymectomy less than 3 months before screening or thymectomy is planned during the study The complete list of
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MG-ADL Total Score Change From Baseline | Up to 29 days in part A | The Myasthenia Gravis Activities of Daily Living (MG-ADL) scale is an 8-item instrument used to assess MG symptoms and their effects on daily activities. The total score ranges from 0 (no symptoms) to 24 (most severe symptoms). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| QMG Total Score Change From Baseline | Up to 29 days in part A | The Quantitative Myasthenia Gravis (QMG) score includes 13 items that measure endurance or fatigability and accounts for fluctuations in disease state. The total score ranges from 0 (no symptoms) to 39 (highest disease severity). |
| Proportion of Participants Who Are Both MG-ADL and QMG Responders in Part A | Up to 8 weeks (part A) | A participant was an MG-ADL responder if there was a ≥2-point reduction in the MG-ADL total score compared with baseline that was maintained for at least 4 consecutive weeks (ie, at least 5 consecutive visits total), with the first reduction occurring no later than 1 week after the last administration of IMP in part A. A participant was a QMG responder if there was a ≥3-point reduction in the QMG total score compared with baseline that was maintained for at least 4 consecutive weeks (ie, at least 5 consecutive visits total), with the first reduction occurring no later than 1 week after the last administration of IMP in part A. |
| Proportion of Participants With MSE | Up to 8 weeks (part A) + 3 years (part B) | Minimal symptom expression (MSE) is defined as an MG-ADL total score of 0 or 1 |
| Proportion of Participants Who Are MG-ADL Responders in Part A | Up to 8 weeks (part A) | The Myasthenia Gravis Activities of Daily Living (MG- ADL) scale is an 8-item instrument used to assess MG symptoms and their effects on daily activities. The total score ranges from 0 (no symptoms) to 24 (most severe symptoms). A participant was an MG-ADL responder if there was a ≥2-point reduction in the MG-ADL total score compared with baseline that was maintained for at least 4 consecutive weeks (ie, at least 5 consecutive visits total), with the first reduction occurring no later than 1 week after the last administration of IMP in part A. |
| Proportion of Participants Who Are QMG Responders in Part A | Up to 8 weeks (part A) | The Quantitative myasthenia gravis (QMG) includes 13 items that measure endurance or fatigability and accounts for fluctuations in disease state. The total score ranges from 0 (no symptoms) to 39 (highest disease severity). A participant was a QMG responder if there was a ≥3-point reduction in the QMG total score compared with baseline that was maintained for at least 4 consecutive weeks (ie, at least 5 consecutive visits total), with the first reduction occurring no later than 1 week after the last administration of IMP in part A. |
| Proportion of Participants Who Are Early MG-ADL Responders in Part A | Up to 8 weeks (part A) | The Myasthenia Gravis Activities of Daily Living (MG- ADL) scale is an 8-item instrument used to assess MG symptoms and their effects on daily activities. The total score ranges from 0 (no symptoms) to 24 (most severe symptoms). An Early MG-ADL responder is an MG-ADL responder who had an onset of an MG-ADL response no later than 2 weeks after the first administration of IMP in part A. |
| MG-ADL Total Score Change From Baseline Over Time in Part A and Part A+B | Up to 8 weeks (part A) + 3 years (part B) | The Myasthenia Gravis Activities of Daily Living (MG- ADL) scale is an 8-item instrument used to assess MG symptoms and their effects on daily activities. The total score ranges from 0 (no symptoms) to 24 (most severe symptoms). |
| MG-QoL15r Change From Baseline Over Time in Part A and Part A+B | Up to 8 weeks (part A) + 3 years (part B) | The Myasthenia Gravis Quality of Life-15 revised (MG-QoL15r) is a patient-reported instrument that measures the impact of MG symptoms on quality of life. The total scores range from 0 (best outcome) to 30 (worst outcome). |
| EQ-5D-5L VAS Change From Baseline Over Time in Part A and Part A+B | Up to 8 weeks (part A) + 3 years (part B) | The EQ-5D-5L is a participant-reported measure of health status developed by the EuroQol Group. The questionnaire comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Current health status is rated on vertical visual analog score (VAS) from 0 to 100, with a score of 0 corresponding to "the worst health you can imagine" and 100 corresponding to "the best health you can imagine." |
| Total IgG Concentrations Percent Changes From Baseline Over Time in Part A and Part A+B | Up to 8 weeks (part A) + 3 years (part B) | — |
Countries
Belgium, Canada, China, Cyprus, Czechia, Denmark, Finland, France, Georgia, Germany, Greece, Hungary, Netherlands, Norway, Poland, Portugal, Romania, Saudi Arabia, Serbia, Spain, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted at 109 sites across 20 countries. A total of 245 participants were screened, of whom 119 were randomized following approval by a diagnostic adjudication committee. Participants who were historically MuSK seropositive were not adjudicated. As the study is ongoing at the time of the results reporting deadline, the submitted results are limited to primary outcome and part A safety data. Remaining results (part B) will be reported within a year of global study completion.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 51.2 Years STANDARD_DEVIATION 13.16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race/Ethnicity, Customized Asian | 16 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants |
| Race/Ethnicity, Customized Other | 5 Participants |
| Race/Ethnicity, Customized White | 94 Participants |
| Sex: Female, Male Female | 90 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 58 | 1 / 61 |
| other Total, other adverse events | 16 / 58 | 14 / 61 |
| serious Total, serious adverse events | 3 / 58 | 1 / 61 |
Outcome results
None listed