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.
This study is a single-arm, open-label, early-stage exploratory clinical study designed to evaluate safety, tolerability and preliminary efficacy of GC012F injection in the treatment of subjects with refractory GMG,the PK, PD characteristics and immunogenicity of GC012F injection in subjects were evaluated. This trial is divided into:screening period, apheresis day, baseline period, lymphodepletion pretreatment period, infusion day, safety and efficacy follow-up period, long-term follow-up period and withdrawal visits.Eligible subjects will undergo apheresis collection and then receive the CAR-T infusion after the manufacturing of the products. Subjects in the lymphodepletion cohort will receive the conditioning regimen and then receive CAR-T cell infusion (per the schedule of assessment). Subjects who meet the cell infusion criteria will receive CAR-T cell infusion at the doses levels which were specified in the protocol, and the dose levels could be adjusted according to safety and clinical efficacy. 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. In the completion dose group of all subjects ,after the DLT observation period, DLTs will be observed for this dose group , all clinical study data collected during the period, especially safety data, were evaluated by the investigator discuss with the collaborator whether to add new subjects to the dose group or explore higher doses group. After CAR-T cell infusion, subjects will be followed up for safety, cell proliferation, survival, and efficacy until the subject progresses on the disease, or withdraws from the study and refuses to accept follow-up , or dies, or withdraws informed consent, or is lost to follow-up (whichever occurs first).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
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.
Tongji Hospital of Tongji Medical Colledge, Huazhong University of Science and Technology
Wuhan, Hubei, China
RECRUITINGThe frequency and severity of adverse events.
Time frame: 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- Cmax(based on data availability).
Time frame: 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).
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: Since signing the ICF until 24-week post-infusion or withdrawal from the study, whichever comes first.
Proportion of patients with improvement in MG-Activities of Daily Living (MG-ADL) score and quantitative muscle weakness (QMG) score and MG-ADL and QMG score with different improvement scores from baseline to 24 weeks after GC012F infusion.
Time frame: Since signing the ICF until 24-week post-infusion or withdrawal from the study, whichever comes first.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Proportion of patients with MG composite score (MGC) improvement and MGC score improvement scores from baseline to 24 weeks after infusion and reinfusion of GC012F.
Time frame: Since signing the ICF until 24-week post-infusion or withdrawal from the study, whichever comes first.
Mean change in patient-reported outcome scores such as MG-QoL15r score from baseline to 24 weeks after infusion and return infusion of GC012F.
Time frame: Since signing the ICF until 24-week post-infusion or withdrawal from the study, whichever comes first.
Change in the patient's status after MGFA intervention 24 weeks after the infusion of GC012F.
Time frame: Since signing the ICF until 24-week post-infusion or withdrawal from the study, whichever comes first.
Reduction in pathogenic antibody levels and proportion of patients in a cohort of MG-specific autoantibody-positive patients from baseline to 24 weeks after GC012F infusion and reinfusion.
Time frame: Since signing the ICF until 24-week post-infusion or withdrawal from the study, whichever comes first.