An Exploratory Clinical Study of GC012F Injection for the Treatment of Refractory Generalized Myasthenia Gravis
Overview
- Phase
- Early Phase 1
- Intervention
- GC012F injection
- Conditions
- Refractory Generalized Myasthenia Gravis
- Sponsor
- Zhejiang University
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- MTD
- Status
- Withdrawn
- Last Updated
- 10 months ago
Overview
Brief Summary
This study is a single-arm, open-label early exploratory clinical trial designed to evaluate the safety, tolerability, and preliminary efficacy of GC012F injection in subjects with refractory GMG. Additionally, the study aims to assess the pharmacokinetic (PK), pharmacodynamic (PD) characteristics, and immunogenicity of GC012F injection in subjects.
Detailed Description
This study is a single-arm, open-label early exploratory clinical trial designed to evaluate the safety, tolerability, and preliminary efficacy of GC012F injection in subjects with refractory GMG. Additionally, the study aims to assess the pharmacokinetic (PK), pharmacodynamic (PD) characteristics, and immunogenicity of GC012F injection in subjects. The trial consists of several phases: screening period, apheresis day, baseline period, lymphodepletion period, pre-infusion assessment period, GC012F infusion period, safety and efficacy follow-up period, long-term follow-up period, and study discontinuation visit (if applicable). Qualified subjects will undergo apheresis and receive the infusion after the production of CAR-T products. Subjects will undergo lymphodepletion before CAR-T cell infusion and assessment before infusion. Subjects meeting the cell infusion criteria will receive CAR-T cell infusion according to the dose specified in the protocol. Dose adjustments may occur based on safety and clinical efficacy for subjects in the same group or subsequent trial groups.
Investigators
He Huang
Director
Zhejiang University
Eligibility Criteria
Inclusion Criteria
- •Subjects or his/her legal proxy/guardian voluntary signing the ICF, and willing and able to follow the procedure in this study.
- •Aged ≥18 years old, no gender limitation;
- •Patients with confirmed refractory GMG, and the clinical classification is IIa-IVb (including IIa, IIb, IIIa, IIIb, IVa and IVb) in screening;
- •Patients whose MG-ADL score is 5 or more, and the proportion of ocular symptoms is less than 50% in the total score;
- •Patients with poor efficacy of conventional treatment and/or no effective treatment means relapse or exacerbation despite conventional hormone, immunosuppressant (e.g., azathioprine, mycophenolate mofetil, tacrolimus, cyclosporin A, cyclophosphamide, etc.), or rituximab treatment;
- •Patients who are on corticosteroids, the dose of prednisone should not exceed 20 mg/d (or no more than an equivalent dose of another corticosteroid) during the 3 weeks prior to apheresis, and the dose isn't escalated during 3weeksk prior to apheresis, the dose isn't changed within 4 weeks prior to infusion;
- •Patients with positive MG-specific autoantibodies in the screening period: acetylcholine receptor autoantibody (anti-AChR) titer or muscle-specific tyrosine kinase autoantibody (anti-MuSK) or low-density lipoprotein receptor-associated protein 4 autoantibody (anti-LRP4) or anti-acetylcholine receptor cluster antibody must be higher than the upper limit of the laboratory reference normal value;
- •Life expectancy ≥3 months;
- •The results of laboratory test during screening period shall meet all following criteria:
- •Neu ≥1.0 × 109/L; Hb ≥8.0 g/dL; PLT ≥50 × 109/L;
Exclusion Criteria
- Not provided
Arms & Interventions
Refractory gMG subjects
Refractory Generalized Myasthenia Gravis
Intervention: GC012F injection
Outcomes
Primary Outcomes
MTD
Time Frame: 2 years after GC012F injection infusion
maximum tolerated dose
RP1D
Time Frame: 2 years after GC012F injection infusion
Recommended phase I dose
Incidence of DLT
Time Frame: Within 28 days after GC012F injection infusion
DLT
Frequency and severity of abnormal findings of adverse events.
Time Frame: Within 96 weeks after GC012F injection infusion
Any untoward medical event that occurs after a subject has administered an investigational product, which may be manifested as a symptom, sign, disease or laboratory abnormality but does not necessarily have a causal relationship with the investigational product.
Frequency and severity of abnormal findings in vital signs
Time Frame: Within 96 weeks after GC012F injection infusion
Vital signs shall be measured after 5 minutes of rest, and assessments included as follows: Temperature, oxygen saturation, heart rate, respiratory rate, resting systolic and diastolic blood pressure.
Frequency and severity of abnormal findings in physical examinations
Time Frame: Within 96 weeks after GC012F injection infusion
The full physical examination at least includes assessments of skin, mucosa, lymph nodes, head, neck, chest, abdomen, spine/limbs, and nervous system. A full physical examination needs to be completed only during the screening period, and the physical examination can be performed in subsequent visit as per changes in signs and symptoms.
Frequency and severity of abnormal findings in electrocardiograms
Time Frame: Within 96 weeks after GC012F injection infusion
The electrocardiography shall be measured after 5 minutes of rest, and assessments included as follows: Heart rate, RR interval, PR interval, QT interval, QRS wave, QT interval and other indexes.
Frequency and severity of abnormal findings in laboratory tests
Time Frame: Within 96 weeks after GC012F injection infusion
Laboratory tests include blood test，Coagulation function ，Infectious disease detection and tests recommended by the Investigator
Secondary Outcomes
- Disease activity indices:MG-ADL(Within 96 weeks after GC012F injection infusion)
- Disease activity indices:QMG(Within 96 weeks after GC012F injection infusion)
- Disease activity indices: post-intervention status according to the Myasthenia Gravis Foundation of America (MGFA) classification(Within 96 weeks after GC012F injection infusion)
- Disease activity indices: MG-QoL 15r(Within 96 weeks after GC012F injection infusion)
- PK parameters of CAR-T cells in peripheral blood after GC012F infusion (Cmax);(Within 96 weeks after GC012F injection infusion)
- PK parameters of CAR-T cells in peripheral blood after GC012F infusion ( AUC);(Within 96 weeks after GC012F injection infusion)
- Levels of cytokines [IL-6、IL-10、IFN-γ、TNF-α、MCP-1(as applicable)], lymphocyte subsets, and soluble BCMA in peripheral blood after GC012F infusion;(Within 28 days after GC012F injection infusion)
- Disease activity indices:MGC(Within 96 weeks after GC012F injection infusion)
- PK parameters of CAR-T cells in peripheral blood after GC012F infusion (Tmax);(Within 96 weeks after GC012F injection infusion)