Efgartigimod, Intravenous Immunoglobulin, Myasthenia Gravis Associated With Thymoma
Conditions
Brief summary
This study is a prospective, multi-center, randomized controlled study to evaluate the efficacy and safety of efgartigimod (EFG) and intravenous immunoglobulin (IVIG) in the perioperative application for acetylcholine receptor (AChR) antibody-positive thymoma patients with myasthenia gravis in order to provide reliable evidence for clinical decision-making.
Interventions
COMBINATION_PRODUCTEfgartigimod + Thymectomy
Patients receive weight-based EFG infusions (10 mg/kg; fixed 1200 mg for ≥120 kg) administered over 1 hour once weekly for 4 total doses. If a scheduled infusion is missed, EFG may be administered within 48 hours of the planned time, followed by resumption of the original schedule to complete all 4 infusions. Thymectomy is performed on the day following the second EFG infusion with a permitted ±3-day surgical window.
COMBINATION_PRODUCTIntravenous immunglobulin + Thymectomy
Patients receive weight-based IVIG infusions (400 mg/kg) administered daily for 5 consecutive days. Thymectomy is performed approximately 7 days after completing the final IVIG infusion, with a permitted ±3-day surgical window.
Sponsors
The Affiliated Hospital of Xuzhou Medical University
First Affiliated Hospital of Wenzhou Medical University
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Tang-Du Hospital
West China Hospital
Second Affiliated Hospital of Soochow University
Huashan Hospital
The Affiliated Brain Hospital of Nanjing Medical University
The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine
Wuhan TongJi Hospital
Shanghai Zhongshan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patients aged \>18 years and ≤75 years, with an expected survival time \>12 months; 2. Patients with generalized myasthenia gravis; 3. MG-ADL ≥6; 4. Positive for AChR antibody; 5. Diagnosed with thymoma by enhanced chest CT or MRI; 6. Patients with thymoma combined with myasthenia gravis who are diagnosed by MDT and need to undergo thymectomy; 7. Patients with American Society of Anesthesiologists (ASA) grade 1-2; 8. Able to understand the study situation and sign the Informed Consent.
Exclusion criteria
1. MGFA type V; 2. Patients who have undergone median sternotomy; 3. Confirmed history of congestive heart failure; poorly controlled angina pectoris with drug treatment; electrocardiogram (ECG) confirmed transmural myocardial infarction; poorly controlled hypertension; clinically significant valvular heart disease; or high-risk uncontrolled arrhythmia; 4. Patients with weight loss of more than 5kg in the past month; severe uncontrolled systemic disease, such as active infection or poorly controlled diabetes; patients with hemorrhagic diseases and bleeding tendencies; coagulation dysfunction, bleeding tendency or receiving thrombolytic or anticoagulant therapy; patients with grade II-IV bone marrow suppression; 5. Females with positive serum pregnancy test or in lactation period, and males and females of childbearing age who are unwilling to use adequate contraceptive measures during treatment; 6. History of organ transplantation (including autologous bone marrow transplantation and peripheral stem cell transplantation); 7. Patients with peripheral nervous system disorders or significant mental disorders and a history of central nervous system disorders; 8. Patients participating in other clinical studies simultaneously; 9. Patients who cannot tolerate single-lung ventilation during surgery; severe cardiac complications, cardiovascular decompensation, patients with implanted cardiac pacemakers; 10. Patients in the acute inflammatory period due to bacterial, viral or other microbial infections; known active infections of human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV), or known HIV seropositivity; 11. Patients who have undergone thoracic surgery due to tuberculous pleurisy, mesothelioma, lung disease, or diaphragmatic disease, with ipsilateral lung atelectasis involving one lobe or more than one lobe; 12. Serum IgG level \<4.5 g/L; 13. Received biological agents such as rituximab or ibritumomab tiuxetan within 6 months; underwent plasma exchange within 1 month; 14. Thrombosis, renal impairment or renal failure; 15. Allergic to human immunoglobulin or have other severe allergic history; 16. Selective IgA deficiency with anti-IgA antibodies; 17. Subjects with impaired function of major organs, abnormal blood routine, lung, liver, kidney and cardiac function, and the following laboratory test results: Blood: white blood cells \<4.0×10\^9/L, absolute neutrophil count (ANC) \<2.0×10\^9/L, platelet count \<100×10\^9/L, hemoglobin \<90g/L; Liver function: serum bilirubin \>1.5 times the upper normal limit; ALT and AST \>1.5 times the upper normal limit; Renal function: serum creatinine (SCr) \>120 μmol/L, creatinine clearance rate (CCr) \<60 ml/min;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quantitative Myasthenia Gravis (QMG) reduction | From baseline to 2 weeks postoperatively | The total QMG score ranges from 0 to 39, with higher scores indicating more severe condition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Myasthenia Gravis Composite (MGC) reduction | From baseline to 2 weeks postoperatively | The total MGC score ranges from 0 to 50, with higher scores indicating more severe condition. |
| QMG change (1 day preoperatively) | From baseline to 1 day preoperatively | The change in the QMG score from baseline to 1 day preoperatively |
| QMG change (1 week postoperatively) | From baseline to 1 week postoperatively | The change in the QMG score from baseline to 1 week postoperatively |
| QMG change (1 month postoperatively) | From baseline to 1 month postoperatively | The change in the QMG score from baseline to 1 month postoperatively |
| QMG change (2 months postoperatively) | From baseline to 2 months postoperatively | The change in the QMG score from baseline to 2 months postoperatively |
| MG-ADL change (1 day preoperatively) | From baseline to 1 day preoperatively | The change in the MG-ADL score from baseline to 1 day preoperatively |
| MG-ADL change (1 week postoperatively) | From baseline to 1 week postoperatively | The change in the MG-ADL score from baseline to 1 week postoperatively |
| MG-ADL change (1 month postoperatively) | From baseline to 1 month postoperatively | The change in the MG-ADL score from baseline to 1 month postoperatively |
| MG-ADL change (2 months postoperatively) | From baseline to 2 months postoperatively | The change in the MG-ADL score from baseline to 2 months postoperatively |
| MGC change (1 day preoperatively) | From baseline to 1 day preoperatively | The change in the MGC score from baseline to 1 day preoperatively |
| MGC change (1 week postoperatively) | From baseline to 1 week postoperatively | The change in the MGC score from baseline to 1 week postoperatively |
| MGC change (1 month postoperatively) | From baseline to 1 month postoperatively | The change in the MGC score from baseline to 1 month postoperatively |
| Myasthenia Gravis Activities of Daily Living (MG-ADL) reduction | From baseline to 2 weeks postoperatively | The total MG-ADL score ranges from 0 to 24, with higher scores indicating more severe condition |
| IgG reduction (1 day preoperatively) | From baseline to 1 day preoperatively | The reduction in the IgG level from baseline to 1 day preoperatively |
| IgG reduction (1 week postoperatively) | From baseline to 1 week postoperatively | The reduction in the IgG level from baseline to 1 week postoperatively |
| IgG reduction (2 weeks postoperatively) | From baseline to 2 weeks postoperatively | The reduction in the IgG level from baseline to 2 weeks postoperatively |
| IgG reduction (1 month postoperatively) | From baseline to 1 month postoperatively | The reduction in the IgG level from baseline to 1 month postoperatively |
| IgG reduction (2 months postoperatively) | From baseline to 2 months postoperatively | The reduction in the IgG level from baseline to 2 months postoperatively |
| AChR-Ab reduction (1 day preoperatively) | From baseline to 1 day preoperatively | The reduction in the AChR-Ab level from baseline to 1 day preoperatively |
| AChR-Ab reduction (2 weeks postoperatively) | From baseline to 2 weeks postoperatively | The reduction in the AChR-Ab level from baseline to 2 weeks postoperatively |
| AChR-Ab reduction (1 month postoperatively) | From baseline to 1 month postoperatively | The reduction in the AChR-Ab level from baseline to 1 month postoperatively |
| Proportion of steroid dose reduction | From baseline to 2 months postoperatively | The rate of reduction in steroid dose from baseline to 2 months postoperatively |
| Incidence of myasthenic crisis | Perioperative period | The incidence of postoperative myasthenia gravis crisis, from the start of the trial to the end of the follow-up period |
| Incidence of total perioperative complications (≥3) | Perioperative period | The incidence of total perioperative complications assessed by Clavien-Dindo classification |
| Incidence of perioperative infection-related complications | Perioperative period | The incidence of perioperative infection-related complications assessed by Clavien-Dindo classification. |
| MGC change (2 months postoperatively) | From baseline to 2 months postoperatively | The change in the MGC score from baseline to 2 months postoperatively |
Countries
China
Contacts
Primary ContactJianyong Ding
Outcome results
None listed