myasthenia gravis
Conditions
Interventions
Sequential Efgartigimod and Ofatumumab Therapy:Patients in the experimental group receive Efgartigimod at a dose of 10mg/kg via intravenous infusion over 1 hour once a week for 4 consecutive weeks in
Sponsors
Peking University People's Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: Inclusion Criteria: (1) Voluntary signing of informed consent by the patient; (2) Age between 18 and 80 years, regardless of gender; (3) Diagnosis of generalized myasthenia gravis (MG), meeting the following criteria: • Weakness in specific striated muscle groups with patchy distribution, demonstrating fluctuation and fatigability; symptoms of weakness are typically worse in the morning and improve after rest; • Positive result on the neostigmine test (quantitative evaluation by Xun's method); and/or Electromyography (EMG) findings: at least one of the following - decrement of more than 10% in the low-frequency stimulation wave amplitude on repetitive nerve stimulation (RNS) examination, or two or more "jitter" findings on single-fiber electromyography (SFEMG); • Exclusion of other syndromes causing weakness, such as Guillain-Barré syndrome, Lambert-Eaton myasthenic syndrome, etc.; (4) Positive serum test for AChR-Ab; (5) Clinical classification by the Myasthenia Gravis Foundation of America (MGFA) as Class II (including IIa and IIb), Class III (including IIIa and IIIb), or Class IVa; (6) Myasthenia Gravis Activities of Daily Living (MG-ADL) score = 6, with ocular component score less than 50% of total score; (7) Quantitative Myasthenia Gravis (QMG) score = 8, with at least two items scoring = 2; (8) Maintenance of stable standard treatment regimen, defined as stable use of any of the following (alone or in combination): a. Acetylcholinesterase inhibitors: stable use for at least 2 weeks prior to the start of the clinical trial, with a maximum dose of =480mg/day; b. Corticosteroids: Prednisone dose = 15mg and = 60mg/day or equivalent dose of other corticosteroids, maintained stable for at least 1 month prior to the start of the clinical trial; c. Immunosuppressants: • Azathioprine: initiated at least 6 months prior to the start of the clinical trial, with stable dose maintained for the 3 months prior to trial initiation; • Mycophenolate mofetil: stable use for at least 3 months prior to the start of the clinical trial; • Methotrexate: stable use for at least 3 months prior to the start of the clinical trial; • Cyclosporine or tacrolimus: stable use for at least 3 months prior to the start of the clinical trial.
Exclusion criteria
Exclusion criteria: Exclusion Criteria: (1) Presence of other autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, etc., although patients with Graves' disease and Hashimoto's thyroiditis, as evaluated by the investigator, may be exempted from exclusion; (2) Significant abnormalities in laboratory indicators (e.g., markedly elevated neutrophil count); (3) Use of immunosuppressive agents other than standard treatment within 1 month prior to the commencement of the clinical trial; (4) Use of biologic agents targeting therapy, such as rituximab, complement C5 inhibitors, within 6 months prior to the commencement of the clinical trial; (5) Use of neonatal Fc receptor (FcRn) antagonists, intravenous immunoglobulin, or plasma exchange therapy within 2 months prior to the commencement of the clinical trial; (6) Significant cardiovascular diseases (including severe arrhythmias), liver, kidney, respiratory system, endocrine, or hematological disorders, or any other medical conditions that the investigator deems would hinder the subject's participation in the study or require hospitalization during the study period; (7) Presence of acute or chronic infections requiring treatment, as follows: • Receipt of any anti-infective treatment (e.g., tuberculosis, Pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria) within 4 weeks prior to baseline; • Hospitalization for anti-infective treatment within 60 days prior to baseline; • Occurrence of infections requiring intravenous antibiotic (antibacterial, antiviral, antifungal, or antiparasitic) therapy within 60 days prior to baseline; (8) Current active hepatitis or history of severe liver disease. For hepatitis B: exclusion of patients with positive HBsAg. For patients with negative HBsAg but positive HBcAb, their situation needs to be clarified through HBV-DNA testing: if HBV-DNA is positive, the patient is excluded from the study; if HBV-DNA is negative, the patient can participate in the study. For hepatitis C: exclusion of patients with positive hepatitis C antibodies; (9) HIV-positive patients; (10) Patients with positive COVID-19 infection test results within 4 weeks before screening; (11) Patients with a history of severe COVID-19 requiring hospitalization within the past 12 months before screening; (12) Poorly controlled diabetic patients: glycated hemoglobin >9.0% or fasting blood glucose =11.1mmol/L; (13) Patients currently suffering from thymoma-associated immunodeficiency syndrome (Good's syndrome), or those who have undergone thymectomy within 6 months prior to screening; (14) Receipt of any live vaccines or COVID-19 vaccines (including nasal spray) within 3 months before the start of the trial or planning to receive during the study period; (15) Patients with malignant tumors; (16) Allergy to human-derived biologics; (17) Participation in any clinical trial within 28 days before the start of the clinical trial or within 5 times the half-life of the investigational drug used in the clinical trial (whichever is longer); (18) Pregnant or lactating women and patients planning to conceive during the trial period; (19) Known alcohol or drug abuse/dependence that may affect compliance with trial requirements; (20) Patients deemed unsuitable for participation in the trial by the investigator (e.g., patients with severe mental disorders).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in MGFA-QMG score compared to baseline at Week 24.;Change in MG-ADL score compared to baseline at Week 24.;Change in MG-QOL15r score compared to baseline at Week 24.; | — |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of subjects with a decrease of =3 points in MG-ADL score compared to baseline at Week 12 and Week 24.;Proportion of subjects with a decrease of =5 points in QMG score compared to baseline at Week 12 and Week 24.;Effect of corticosteroid reduction in MG patients at Week 24.;Safety: Percentage of subjects experiencing treatment-related adverse reactions.; | — |
Countries
China
Contacts
Public ContactZhaoxu Zhang
Peking University People's Hospital
Outcome results
None listed