This study is a single-center, open-label, single-arm, dose-exploration study to evaluate the safety and preliminary effectiveness of BCMA CAR-T(S103) in the treatment of refractory, generalized myasthenia gravis. The study is a dose escalation trial in adult, refractory, systemic MG patients. A total of 6-24 MG patients who meet the inclusion criteria are expected to be recruited.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
1.0 × 10e6/kg S103 CAR-T cells
2.0 × 10e6/kg S103 CAR-T cells
4.0 × 10e6/kg S103 CAR-T cells
The Second Affiliated Hospital of Air Force Medical University
Xi'an, Shaanxi, China
Dose-limiting toxicity
DLT is defined as the following conditions that occur during the DLT evaluation period, which are not attributed to disease progression or disease-related processes, but are related to the study drug: 1. All treatments with grade 4 or 5 cytokine release syndrome (CRS); 2. Grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS) possibly related to CAR-T therapy in all treatments; 3. Grade 3 hematologic toxicity lasting more than 7 days, not caused by the underlying disease (excluding lymphocyte count decrease due to lymphodepletion); 4. Grade ≥3 organ toxicity reactions (cardiac, skin, gastrointestinal, hepatic, pulmonary, renal/genitourinary) possibly related to CAR-T therapy in all treatments, with cardiac toxicity and renal toxicity reactions ≥ grade 2 considered as DLT; 5. Treatment-related death; 6. Other toxicities determined to be DLT after discussion by the SRC.
Time frame: Day 28
Proportion of subjects who reach MSE (ADL≤1 score, for 4 weeks) at 3 months and 6 months after infusion
Myasthenia Gravis Activities of Daily Living (MG-ADL) is a questionnaire that includes 8 items: ptosis, diplopia, speech, chewing, swallowing, breathing, and upper and lower limb functions. The scale uses a 4-level scoring system, with a total score of 0-24, and higher scores indicate more severe disability, with an improvement of 2 points or more suggesting clinical improvement.
Time frame: 3 month, 6 month
Changes in ADL score relative to baseline at 28 days, 3 months, 6 months after infusion
Myasthenia Gravis Activities of Daily Living (MG-ADL) is a questionnaire that includes 8 items: ptosis, diplopia, speech, chewing, swallowing, breathing, and upper and lower limb functions. The scale uses a 4-level scoring system, with a total score of 0-24, and higher scores indicate more severe disability, with an improvement of 2 points or more suggesting clinical improvement.
Time frame: 28 days, 3 months, 6 months
Changes in QMG score relative to baseline at 28 days, 3 months, 6 months after infusion
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8.0 × 10e6/kg S103 CAR-T cells
Quantitative Myasthenia Gravis scale(QMG), mainly measures the patient's muscle strength and endurance. The QMG assessment includes diplopia, ptosis, facial muscle strength, swallowing, articulation, arm lift on both sides, percentage of predicted forced vital capacity (FVC), head lift, grip strength on both hands, and leg lift on both sides in a supine position, with 13 items in total. Each item is scored from normal (0) to severe (3), with a total score ranging from 0 to 39, and a higher score indicates a more severe disease. A total score change of more than 3 points is considered clinically significant.
Time frame: 28 days, 3 months, 6 months
Changes in MGC score relative to baseline at 28 days, 3 months, 6 months after infusion
MG Composite (MG-C) combines physician-reported and patient-reported entries. The scale assesses 10 items, with talking, chewing, and swallowing indices self-assessed by study participants, with total scores ranging from 0 to 50. For most patients, a score change of ≥3 points is associated with clinically significant symptom change.
Time frame: 28 days, 3 months, 6 months
Changes in QOL15 score relative to baseline at 28 days, 3 months, 6 months after infusion
15-item MG-specific QOL scale, MG-QOL15, is a short survey questionnaire completed by participants, with 15 items covering three aspects: physical, psychological, and social. It aims to assess the "patient's perspective" of "quality of life" related to MG, using a 5-level scoring method (from mild to severe, 0-4 points), with a maximum score of 60 points, and higher scores indicating poorer quality of life.
Time frame: 28 days, 3 months, 6 months
Median time to re-infusion to achieve MSE status
Time frame: 6 months
Changes of blood pressure
Time frame: 28 days, 3 months, 6 months
Changes of pulse rate
Time frame: 28 days, 3 months, 6 months
Changes of weight
Time frame: 28 days, 3 months, 6 months
Changes in myasthenia gravis-specific autoantibody titers relative to baseline at 28 days, 3 months, 6 months after infusion
Time frame: 28 days, 3 months, 6 months
Changes in immunoglobulins relative to baseline at 28 days, 3 months, 6 months after infusion
Time frame: 28 days, 3 months, 6 months
Incidence and grading of severe adverse events (SAE) from 28 days to 2 years after re-infusion
Time frame: 2 years