The Safety and Efficacy of S103 in the Treatment of Refractory Generalized Myasthenia Gravis

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

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 Overview

• Status: Active, not recruiting
• Conditions: Myasthenia Gravis, Generalized
• Intervention / Treatment: Drug: Dose level 1 group; Drug: Dose level 2 group; Drug: Dose level 3 group; Drug: Dose level 4 group

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710038
      • The Second Affiliated Hospital of Air Force Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: S103 CAR-T; This study adopted a single-arm design, with all patients receiving sequential administration of different doses of S103 CAR-T	Drug: Dose level 1 group; 1.0 × 10e6/kg S103 CAR-T cells; Drug: Dose level 2 group; 2.0 × 10e6/kg S103 CAR-T cells; Drug: Dose level 3 group; 4.0 × 10e6/kg S103 CAR-T cells; Drug: Dose level 4 group; 5.0 × 10e6/kg S103 CAR-T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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: All treatments with grade 4 or 5 cytokine release syndrome (CRS);; Grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS) possibly related to CAR-T therapy in all treatments;; Grade 3 hematologic toxicity lasting more than 7 days, not caused by the underlying disease (excluding lymphocyte count decrease due to lymphodepletion);; 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;; Treatment-related death;; Other toxicities determined to be DLT after discussion by the SRC.	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	28 days, 3 months, 6 months
Changes in QMG score relative to baseline at 28 days, 3 months, 6 months after infusion	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.	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.	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.	28 days, 3 months, 6 months
Median time to re-infusion to achieve MSE status		6 months
Changes of blood pressure		28 days, 3 months, 6 months
Changes of pulse rate		28 days, 3 months, 6 months
Changes of weight		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		28 days, 3 months, 6 months
Changes in immunoglobulins relative to baseline at 28 days, 3 months, 6 months after infusion		28 days, 3 months, 6 months
Incidence and grading of severe adverse events (SAE) from 28 days to 2 years after re-infusion		2 years

Collaborators and Investigators

• Sponsor: Ting Chang, MD
• Collaborators: Hebei Senlang Biotechnology Co., LTD
• Investigators: Study Chair: Ting Chang, The Second Affiliated Hospital of Air Force Military Medical University

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2025
• Primary Completion (Actual): April 30, 2026
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: April 13, 2025
• First Submitted That Met QC Criteria: April 27, 2025
• First Posted (Actual): May 6, 2025

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Neurodegenerative Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Myasthenia Gravis
• Other Study ID Numbers: CART-20250321

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Experimental data may be shared with the consent of the principal investigator
• IPD Sharing Supporting Information Type: ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No