GC012F Injection in the Treatment of Refractory Generalized Myasthenia Gravis(24103)

NCT07058298 | Recruiting Early Phase 1 DMC

• 1 other identifier: GC012FinGMG
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, open-label and early exploratory clinical study, with the purpose to study the safety, tolerability and initial clinical efficacy of GC012F Injection in the treatment of refractory GMG and to evaluate the PK, PD characteristics and immunogenicity in subjects with refractory GMG infused with GC012F Injection.

Conditions

Generalized Myasthenia Gravis (gMG)

Outcome Measures

Primary Outcomes (1)

• The frequency and severity of adverse events.

  Since signing the ICF until 24-week post-infusion or withdrawal from the study, whichever comes first.

Secondary Outcomes (10)

• Analysis of cell dynamics (CK) parameters of the copy number of the GC012F CAR gene in peripheral blood- Cmax(based on data availability).

  Since signing the ICF until 24-week post-infusion or withdrawal from the study, whichever comes first.

• Analysis of cell dynamics (CK) parameters of the copy number of the GC012F CAR gene in peripheral blood- Tmax(based on data availability).

  Since signing the ICF until 24-week post-infusion or withdrawal from the study, whichever comes first.

• Analysis of cell dynamics (CK) parameters of the copy number of the GC012F CAR gene in peripheral blood- AUC(based on data availability).

  Since signing the ICF until 24-week post-infusion or withdrawal from the study, whichever comes first.

• T/B lymphocyte subsets in peripheral blood after GC012F infusion.

  Since signing the ICF until 24-week post-infusion or withdrawal from the study, whichever comes first.

• Levels of cytokines in peripheral blood after GC012F infusion.

  Since signing the ICF until 24-week post-infusion or withdrawal from the study, whichever comes first.

Other Outcomes (3)

• To evaluate the immunogenicity of GC012F injection

  Since signing the ICF until 24-week post-infusion or withdrawal from the study, whichever comes first.

• To evaluate immune reconstitution after infusion of GC012F injection

  Since signing the ICF until 24-week post-infusion or premature withdrawal from the study, whichever comes first.

• To determine the presence of replication competent lentivirus (RCL) and lentiviral integration site in subjects after infusion of GC012F lnjection.

  Since signing the ICF until 24-week post-infusion or withdrawal from the study, whichever comes first.

Study Arms (1)

3×10^5/kg

EXPERIMENTAL

In this study, the infusion dose of CAR-T cells was set up in one dose group: 3×10\^5/kg. About 6 participants are planned to be included. The subjects will be monitored for DLT for 28 days after the infusion of GC012F injection. For the first 3 patients to receive GC012F infusion, if ≤1/3 of the patients develop a DLT at a given dose level, the additional 3 patients will be enrolled in this cohort. If 2/3 or more DLTs occur at this dose level, subsequent subjects may be given a backup dose group of 2.0×10\^5/kg or 1.0×10\^5/kg after discussion between the investigator and the collaborator.

Drug: GC012F injection

Interventions

GC012F injection DRUG

Subjects will be infused with GC012F Injection within 48-72 hours after lymphodepletion pretreatment,the infusion doses will be (CAR-T cell count) 3 × 10\^5/kg. Note: for subjects weighing ≤70 kg: number of infused CAR-T cells = 3 (±20%) × 10\^5 × body weight(kg); for subjects weighing \>70 kg: number of infused CART cells (fixed doses of GC012F Injection) = 3 (±20%) × 10\^5 × 70 kg.

3×10^5/kg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be enrolled, subjects must meet all of the following criteria:
• Subjects or their legal representatives voluntarily sign a written informed consent and are willing and able to comply with the procedures of the study;
• Subjects aged 18-75 years old (both inclusive), male or female;
• Subjects with confirmed refractory gMG of classes IIa - IVb by MGFA clinical classification (including classes IIa, IIb, IIIa, IIIb, IVa and IVb) at screening;
• Subjects with the Myasthenia Gravis - Activities of Daily Living (MG-ADL) score of ≥6, the proportion of ocular symptoms of \<50% of the total score, and the Quantitative Myasthenia Gravis (QMG) score of ≥11;
• Subjects with poor response and/or who do not respond to the conventional therapies, that means subjects who are still at risk of relapse or exacerbation after conventional therapies with hormones, immunosuppressants (e.g., azathioprine, mycophenolate mofetil, tacrolimus, cyclosporin A, cyclophosphamide, methotrexate, etc.), or biological agents (e.g., rituximab);
• For patients who are taking corticosteroids, the dose of prednisone should not exceed 30 mg/day (or an equivalent dose of other corticosteroids), and the dose must be stable for at least 4 weeks before infusion;
• The laboratory test results during the screening period meet the following criteria:
• Neutrophil count ≥ 1.0×10\^9/L; Hemoglobin ≥ 8.0 g/dL; Platelet count≥50×10\^9/L;
• Alanine aminotransferase ≤ 3× upper limit of normal (ULN); Aspartate aminotransferase ≤ 3×ULN; total bilirubin (TBIL) \< 2× ULN (for subjects with Gilbert's syndrome), direct bilirubin (DBIL)) ≤ 1.5×ULN
• Creatinine clearance (19.3 Appendix 3) ≥ 30 mL/min;
• Activated partial thromboplastin time (APTT) ≤ 1.5×ULN, prothrombin time (PT)≤ 1.5×ULN;
• Subject's left ventricular ejection fraction (LVEF) is ≥ 50% by echocardiography, with no evidence of pericardial effusion as determined;
• Female subjects of child-bearing age must:
• At screening, a negative serum β human chorionic gonadotropin β-hCG pregnancy test result confirmed by the investigator;

You may not qualify if:

• Participants who meet any of the following criteria are not included in the study:
• Have a history of severe hypersensitivity or allergy;
• Contraindications or hypersensitivity to fludarabine, cyclophosphamide and any component of the test drug;
• Subjects who have received intravenous immunoglobulin or plasma exchange therapy or immunoadsorption therapy within 4 weeks prior to infusion;
• Received CD20-targeted drugs within 6 months prior to apheresis;
• Received Tacrolimus, Cyclosporine, Azathioprine, Mycophenol Mofetil within 1 week before apheresis;
• Treatment with neonatal Fc receptor (FcRn) antagonists within 1 week prior to apheresis;
• Patients who have received complement inhibitors (e.g., eculizumab, etc.) within 1 weeks before apheresis ;
• Subjects with any of the following heart diseases:
• Class III or Class IV congestive heart failure based on New York Heart Association (NYHA) Functional Classification;
• Unstable angina, myocardial infarction or coronary artery bypass grafting (CABG) within 6 months prior to screening;
• Clinically significant ventricular arrhythmia or a history of unexplained syncope not due to vasovagal reaction or dehydration; or a QTc interval \>480 ms at screening;
• Has a history of severe non-ischemic cardiomyopathy;
• Severe cardiovascular abnormalities (such as brain natriuretic peptide (BNP)/troponin and other indices) and the investigator judges that such subjects are not eligible for enrollment.
• Subjects with other uncontrolled malignancies. The following conditions will be excluded: early-stage tumors that have been treated by radical surgery (carcinoma in situ or grade 1 tumors, or non-ulcerative primary melanoma with a depth of \<1 mm and with no involvement of lymph nodes), basal cell carcinoma, cutaneous squamous cell carcinoma, cervical carcinoma in situ, or breast cancer in situ that has been treated by potential radical treatment;

Sponsors & Collaborators

• Daishi Tian: lead
• Gracell Biotechnologies (Shanghai) Co., Ltd.: collaborator

Study Sites (1)

Tongji Hospital of Tongji Medical Colledge, Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

RECRUITING

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

Central Study Contacts

Chuan Qin Sub-I

CONTACT

13886052650; chuanqin@tjh.tjmu.edu.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician of Neurology

Model Details: None (Open Label)

Study Record Dates

• First Submitted: June 7, 2025
• First Posted: July 10, 2025
• Study Start: July 15, 2025
• Primary Completion (Estimated): February 13, 2027
• Study Completion (Estimated): September 10, 2027
• Last Updated: September 8, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)