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

NCT06958939 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: CART-20250321
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Myasthenia Gravis, Generalized

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 28

Secondary Outcomes (12)

• Proportion of subjects who reach MSE (ADL≤1 score, for 4 weeks) at 3 months and 6 months after infusion

  3 month, 6 month

• Changes in ADL score relative to baseline at 28 days, 3 months, 6 months after infusion

  28 days, 3 months, 6 months

• Changes in QMG score relative to baseline at 28 days, 3 months, 6 months after infusion

  28 days, 3 months, 6 months

• Changes in MGC score relative to baseline at 28 days, 3 months, 6 months after infusion

  28 days, 3 months, 6 months

• Changes in QOL15 score relative to baseline at 28 days, 3 months, 6 months after infusion

  28 days, 3 months, 6 months

Study Arms (1)

S103 CAR-T

EXPERIMENTAL

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; Drug: Dose level 2 group; Drug: Dose level 3 group; Drug: Dose level 4 group

Interventions

Dose level 1 group DRUG

1.0 × 10e6/kg S103 CAR-T cells

S103 CAR-T

Dose level 2 group DRUG

2.0 × 10e6/kg S103 CAR-T cells

S103 CAR-T

Dose level 3 group DRUG

4.0 × 10e6/kg S103 CAR-T cells

S103 CAR-T

Dose level 4 group DRUG

8.0 × 10e6/kg S103 CAR-T cells

S103 CAR-T

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years, ≤80 years;
• MGFA classification type IIa-IVa;
• Voluntary participation in the study: understanding and awareness of the study and voluntary signing of the informed consent form;
• Meeting the diagnosis of myasthenia gravis;
• Assessed by the investigator as meeting the diagnostic criteria for refractory MG: fulfilling one of the following 4 conditions:
• 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.
• After adequate dose and duration of at least 2 conventional immunotherapies, the PIS is improved, but the MG-ADL score remains
• for at least 6 months.
• 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).
• The investigator considers that, despite current conventional immunotherapy, MG still imposes a significant functional burden on the patient.
• MG-ADL score ≥6 or QMG score ≥11 at screening and baseline, with ocular muscle score less than 50% of the total score.

You may not qualify if:

• 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;
• 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;
• 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;
• Thymectomy within 6 months prior to baseline or planned thymectomy during the study period, or thymoma requiring chemotherapy and/or radiotherapy at any time;
• Study participants who received live attenuated vaccines within 8 weeks prior to screening; or plan to receive live vaccines within 8 weeks after treatment;
• Study participants who received prior rituximab treatment within 6 months before screening;
• Treatment with tocilizumab, eculizumab, or efgartigimod within 3 months prior to screening;
• Intravenous immunoglobulin, plasma exchange, or immunotherapy within 4 weeks prior to screening;
• 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;
• Unresected thymoma;
• Rapid symptom deterioration during the lead-in period, progressing to crisis or pre-crisis state (MGFA IVb-V);
• Other conditions deemed by the investigator as unsuitable for study participation.

Sponsors & Collaborators

• Ting Chang, MD: lead
• Hebei Senlang Biotechnology Co., LTD: collaborator

Study Sites (1)

The Second Affiliated Hospital of Air Force Medical University

Xi'an, Shaanxi, 710038, China

Location

MeSH Terms

Conditions

Myasthenia Gravis

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Ting Chang

  The Second Affiliated Hospital of Air Force Medical University

  STUDY CHAIR

Central Study Contacts

Zhe Ruan

CONTACT

86 29 84777741; ruanzhe1988@fmmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Model Details: 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

Study Record Dates

• First Submitted: April 13, 2025
• First Posted: May 6, 2025
• Study Start: May 1, 2025
• Primary Completion: March 31, 2026
• Study Completion (Estimated): August 30, 2026
• Last Updated: May 6, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF, CSR

Locations

CN (1)