Title: The Efficacy, Safety, and PK/PD of Efgartigimod Followed by Telitacicept in Generalized Myasthenia Gravis: Protocol of a Randomized Controlled Trial Objective: This study aims to evaluate the efficacy, safety, and pharmacokinetics/pharmacodynamics (PK/PD) of efgartigimod followed by telitacicept in patients with generalized myasthenia gravis (gMG). Specifically, the trial seeks to determine the optimal treatment strategy for gMG by assessing the effect of sequential biologic therapy on disease management.
Study Design: This is a multi-center, open-label, randomized controlled trial involving 60 acetylcholine receptor antibody-positive gMG patients.
The patient voluntarily signs the informed consent form.
Age ≥18 and ≤80 years, regardless of gender.
Meets the diagnostic criteria for Myasthenia Gravis (MG) as per the 2020 China MG Diagnosis and Treatment Guidelines, with serological evidence of positive AChR-Ab.
MG Clinical Classification according to the Myasthenia Gravis Foundation of America (MGFA) Staging System: Grade II-IV.
Coexisting active autoimmune diseases, such as Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis, Sjögren's Syndrome, etc.
Patients with active infections, such as Herpes Zoster, HIV, active Tuberculosis, active Hepatitis.
Patients with thymoma who have undergone surgery within the past 6 months.
Patients with malignancies other than thymoma.
Parallel
Efgartigimod + Telitacicept (1-week interval) group
DrugDrug 1: Efgartigimod Generic Name: Efgartigimod Formulation: Injection (Intravenous) Dose: 10 mg/kg Frequency: Once a week Route of Administration: Intravenous infusion Duration: 4 weeks (Week 0 to Week 4) Drug 2: Telitacicept Generic Name: Telitacicept Formulation: Injection (Subcutaneous) Dose: 240 mg Frequency: Once a week Route of Administration: Subcutaneous injection Duration: 25 weeks (Week 5 to Week 29)
Efgartigimod + Telitacicept (2-week interval) group
DrugDrug 1: Efgartigimod Generic Name: Efgartigimod Formulation: Injection (Intravenous) Dose: 10 mg/kg Frequency: Once a week Route of Administration: Intravenous infusion Duration: 4 weeks (Week 0 to Week 4) Drug 2: Telitacicept Generic Name: Telitacicept Formulation: Injection (Subcutaneous) Dose: 240 mg Frequency: Once a week Route of Administration: Subcutaneous injection Duration: 24 weeks (Week 6 to Week 29)
Telitacicept-only group
DrugDrug: Telitacicept Generic Name: Telitacicept Formulation: Injection (Subcutaneous) Dose: 240 mg Frequency: Once a week Route of Administration: Subcutaneous injection Duration: 30 weeks (Week 0 to Week 29)
Change from baseline in QMG score
Change in QMG score from baseline to Weeks 30. Total QMG scores range from 0 (none) to 39 (severe).
Change from baseline in MG-ADL score
Change in Myasthenia Gravis Activities of Daily Living (MG-ADL) score from baseline at weeks 4, 8, 12, 18, 24, and 30. Total MG -ADL scores range from 0 (normal) to 24 (severe).
Proportion of subjects with minimal manifestation status (MMS)
Proportion of patients achieving minimal status (MMS) at weeks 4, 8, 12, 18, 24, and 30 (MMS is defined as the absence of any functional limitations due to myasthenia, although mild myasthenia may be detected upon examination by a specialized neuromuscular physician).
Proportion of subjects with a ≥2-point reduction in MG-ADL score from baseline
Proportion of subjects in each group with a decrease of ≥2 points in MG-ADL .score from baseline at weeks 4, 8, 12, 18, 24, and 30.
Proportion of subjects with a ≥3-point reduction in QMG score from baseline
Proportion of subjects in each group with a decrease of ≥3 points in QMG score from baseline at weeks 4, 8, 12, 18, 24, and 30.
Plasma concentration of telitacicept in the two sequential treatment groups
The study will measure the plasma concentration of telitacicept in patients receiving the sequential treatment regimen. Blood samples will be collected at the following time points: 30 minutes before the first dose, 6 hours ± 15 minutes post-dose, 24 hours ± 1 hour (1 day), 48 hours ± 2 hours (2 days), 72 hours ± 3 hours (3 days), pre-dose at Week 1 ± 12 hours, pre-dose at Week 4 ± 3 days, and pre-dose at Week 8 ± 3 days. Subsequently, blood samples will be collected every 3 months before each telitacicept dose at the following time points: pre-dose at Week 12 ± 3 days and pre-dose at Week 24 ± 3 days.
Serum immunoglobulins
Serum immunoglobulin levels, as a pharmacodynamic marker for both efgartigimod and telitacicept, will be measured at baseline, after 1 cycle (4 weeks) of efgartigimod treatment, before the first dose of telitacicept, and at Weeks 1, 4, and every subsequent 4-week interval after telitacicept administration.
B-cell subpopulation count and BLyS/APRIL measurement
B-cell subpopulation count and BLyS/APRIL measurement will be performed before the first dose of telitacicept and before dosing at Week 4, Week 12, and Week 24.
Clearance(CI) of telitacicept in the two sequential treatment groups
The study will measure the clearance(CI) of telitacicept in patients receiving the sequential treatment regimen. Blood samples will be collected at the following time points: 30 minutes before the first dose, 6 hours ± 15 minutes post-dose, 24 hours ± 1 hour (1 day), 48 hours ± 2 hours (2 days), 72 hours ± 3 hours (3 days), pre-dose at Week 1 ± 12 hours, pre-dose at Week 4 ± 3 days, and pre-dose at Week 8 ± 3 days. Subsequently, blood samples will be collected every 3 months before each telitacicept dose at the following time points: pre-dose at Week 12 ± 3 days and pre-dose at Week 24 ± 3 days.
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First Affiliated Hospital of Wenzhou Medical University
Lead sponsor
Zhejiang Provincial People's Hospital
Collaborator
Sir Run Run Shaw Hospital
Collaborator
Second Affiliated Hospital, School of Medicine, Zhejiang University
Collaborator
Ningbo Medical Center Lihuili Hospital
Collaborator
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