Clinical trial NCT06958939: The Safety and Efficacy of S103 in the Treatment of Refractory Generalized Myasthenia Gravis
Official title: A Single-center, Single-arm, Dose-exploration Study Evaluating the Safety and Efficacy of SENL103 Autologous T-cell Injection (S103) in the Treatment of Refractory Generalized Myasthenia Gravis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Myasthenia Gravis, Generalized
Lead sponsor: Tang-Du Hospital
Sponsor class: OTHER
Collaborators: name: Hebei Senlang Biotechnology Co., LTD
First posted: 2025-05-06
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Dose 1 1.0 × 10e6/kg S103 CAR-T cells

Dose 2 2.0 × 10e6/kg S103 CAR-T cells

Dose 3 4.0 × 10e6/kg S103 CAR-T cells

Dose 4 8.0 × 10e6/kg S103 CAR-T cells
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years, ≤80 years;
2. MGFA classification type IIa-IVa;
3. Voluntary participation in the study: understanding and awareness of the study and voluntary signing of the informed consent form;
4. Meeting the diagnosis of myasthenia gravis;
5. Assessed by the investigator as meeting the diagnostic criteria for refractory MG: fulfilling one of the following 4 conditions:

   1. After adequate dose and duration of at least 2 conventional immunotherapies (including steroid and non-steroid immunosuppressants), the post-intervention status (PIS) is unchanged or worsened.
   2. After adequate dose and duration of at least 2 conventional immunotherapies, the PIS is improved, but the MG-ADL score remains

      * 6 for at least 6 months.
   3. After adequate dose and duration of at least 2 conventional immunotherapies, the PIS is remission or improvement, but during regular tapering of immunotherapy, there are still ≥2 exacerbations per year (MG-ADL score ≥6).
   4. The investigator considers that, despite current conventional immunotherapy, MG still imposes a significant functional burden on the patient.
6. MG-ADL score ≥6 or QMG score ≥11 at screening and baseline, with ocular muscle score less than 50% of the total score.

Exclusion Criteria:

1. Any medical or psychiatric condition that the investigator deems may endanger the study participant or affect their ability to participate in the study; or any condition the investigator considers associated with poor compliance;
2. Females who are breastfeeding or pregnant, or plan to become pregnant at any time during the 12-month period after receiving CAR-T therapy, or have a history of spontaneous or induced abortion within 4 weeks prior to screening;
3. Study participants with clinically relevant active infections (e.g., sepsis, pneumonia, or abscess) or severe infections (requiring hospitalization or antibiotic treatment) within 4 weeks prior to screening;
4. Thymectomy within 6 months prior to baseline or planned thymectomy during the study period, or thymoma requiring chemotherapy and/or radiotherapy at any time;
5. Study participants who received live attenuated vaccines within 8 weeks prior to screening; or plan to receive live vaccines within 8 weeks after treatment;
6. Study participants who received prior rituximab treatment within 6 months before screening;
7. Treatment with tocilizumab, eculizumab, or efgartigimod within 3 months prior to screening;
8. Intravenous immunoglobulin, plasma exchange, or immunotherapy within 4 weeks prior to screening;
9. Known severe underlying diseases, such as liver or kidney dysfunction, hematologic disorders, prior severe cardiovascular diseases, severe hypertension, diabetes, or poorly controlled blood pressure or blood glucose;
10. Unresected thymoma;
11. Rapid symptom deterioration during the lead-in period, progressing to crisis or pre-crisis state (MGFA IVb-V);
12. Other conditions deemed by the investigator as unsuitable for study participation.

Primary outcomes:
measure: Dose-limiting toxicity
timeFrame: Day 28
Secondary outcomes:
measure: Proportion of subjects who reach MSE (ADL≤1 score, for 4 weeks) at 3 months and 6 months after infusion
timeFrame: 3 month, 6 month
measure: Changes in ADL score relative to baseline at 28 days, 3 months, 6 months after infusion
timeFrame: 28 days, 3 months, 6 months
measure: Changes in QMG score relative to baseline at 28 days, 3 months, 6 months after infusion
timeFrame: 28 days, 3 months, 6 months
measure: Changes in MGC score relative to baseline at 28 days, 3 months, 6 months after infusion
timeFrame: 28 days, 3 months, 6 months
measure: Changes in QOL15 score relative to baseline at 28 days, 3 months, 6 months after infusion
timeFrame: 28 days, 3 months, 6 months
measure: Median time to re-infusion to achieve MSE status
timeFrame: 6 months
measure: Changes of blood pressure
timeFrame: 28 days, 3 months, 6 months
measure: Changes of pulse rate
timeFrame: 28 days, 3 months, 6 months
measure: Changes of weight
timeFrame: 28 days, 3 months, 6 months
measure: Changes in myasthenia gravis-specific autoantibody titers relative to baseline at 28 days, 3 months, 6 months after infusion
timeFrame: 28 days, 3 months, 6 months
measure: Changes in immunoglobulins relative to baseline at 28 days, 3 months, 6 months after infusion
timeFrame: 28 days, 3 months, 6 months
measure: Incidence and grading of severe adverse events (SAE) from 28 days to 2 years after re-infusion
timeFrame: 2 years
Other outcomes:
Locations:
city: Xi'an
country: China
facility: The Second Affiliated Hospital of Air Force Medical University
state: Shaanxi
Study officials:
affiliation: The Second Affiliated Hospital of Air Force Medical University
name: Ting Chang
role: STUDY_CHAIR
References: