NCT06759948

An Early Exploratory Clinical Study of GC012F Injection in the Treatment of Refractory Generalized Myasthenia Gravis

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Sponsor: Chongbo Zhao · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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 includes periods of screening, apheresis, baseline, lymphodepletion pretreatment, assessment before infusion, infusion of CAR-T cells, and Safety and efficacy follow-ups, long-term follow-ups, and withdrawal of study visits (if any). Eligible subjects will receive the apheresis and then infusion after the production of CAR-T product. Subjects will receive lymphodepletion pretreatment, and assessments prior to CAR-T cell infusion. Subjects who meet the cell infusion criteria will receive CAR-T cell infusion with the doses specified in the protocol, and the doses in the same group or subsequent group can be adjusted based on the safety and clinical efficacy. There're 3 dose groups in this study for CAR-T cell infusion: 1×10\^5/kg, 2×10\^5/kg, 3×10\^5/kg. Dose will be escalated based on "3+3" rule. 3\~6 subjects will be enrolled into each dose group, approximately 9\~18 subjects in total will be enrolled. Subjects of each dose group will be observed for DLT within 28 days (Dose-limiting toxicities (DLT) observation period) after GC012F injection infusion. After all proposed subjects in each dose group complete the 28-day DLT observation period, the Safety Monitoring Committee (SMC) will evaluate the clinical safety and pharmacokinetic data (if available). Only after obtaining the approval of SMC and collaborator may new subjects be enrolled in the next dose group. Additionally, in order to ensure the safety of CAR-T therapy, the SMC may recommend increasing the frequency of safety committee evaluations according to the safety situation and study progress (e.g., conducting an SMC assessment for each newly enrolled subject). The dose escalation rules are as follows: Each dose level will enroll 3 to 6 subjects, and only after all subjects in a dose group complete the DLT assessment, meet escalation criteria, and have undergone evaluation by the SMC (considering clinical safety and pharmacokinetic data, if available) and received collaborator approval will they proceed to the next dose level. The criteria for dose escalation are: if none of the first 3 patients in a group experience DLT during the observation period, the study may proceed to the next dose group. If one patient among the first three experiences DLT during the observation period, three additional patients will be enrolled to the same dose group. If DLT cases are ≤1 out of the total 6 enrolled patients during the DLT observation period, the study can proceed to the next dose group. If the number of DLT cases exceeds 1, dose escalation will be halted (see the table below for details) Number of DLT cases Measures 0/3 Escalation to the next dose group 1/3 Enrolled 3 additional subjects 1/6 Escalation to the next dose group ≥2/3 or ≥2/6 1. Dose escalation will be halted 2. Dose de-escalation to a lower dose level: 1. If only 3 subjects were enrolled at the dose level, 3 additional subjects will be enrolled at that dose level; 2. If there have been 6 subjects at the dose level, DLT cases are ≤1, the dose is MTD. After all subjects in a dose group have completed the DLT observation period, all clinical study data collected during that period, particularly safety data, will be assessed. Following evaluation and approval by the SMC, which will consider the clinical safety and pharmacokinetic data (if available), the collaborator will decide whether to enroll new subjects in that dose group, halt or continue dose escalation, or introduce an intermediate dose group. If more than one DLT is observed in the 1×10\^5/kg dose group, following approval by the SMC, the researchers and collaborators will discuss whether to explore a lower dose group. If no DLT is observed after escalating to 3×10\^5/kg, the decision to explore a higher dose group will be based on a comprehensive review of safety data, CAR-T cell expansion persistence parameters, and efficacy data, after SMC evaluation and approval, followed by discussions between researchers and collaborators. Given that the activity of cell-based therapies (which are long-lasting) does not show a clear dose dependency, exposure of subjects to excessively low doses may not yield clinical benefit. Therefore, this study will determine or adjust the infusion dose for patients based on the safety of the GC012F injection, parameters for CAR-T cell expansion persistence, and clinical efficacy, following assessment and agreement by the SMC along with further discussions with the researchers and collaborators. DLT assessments will be performed for evaluable subjects within 28 days post-GC012F injection. Subjects will be replaced if any of the following situations occur during the DLT assessment period: (1) subjects withdraw from the study for reasons not related to DLT, (2) prohibited medications were used prior to DLT occurrence, or (3) safety evaluations required for DLT assessment are not completed. Following CAR-T cell infusion, subjects will be monitored for safety, cell proliferation persistence, and efficacy, until disease progression, withdrawal from the study with refusal of further follow-up, death, withdrawal of informed consent, loss to follow-up, or 24 weeks post-infusion(whichever occurs first).

Conditions

• Generalized Myasthenia Gravis (gMG)

Interventions

Type	Name	Description
DRUG	GC012F injection	Subjects will be infused with GC012F Injection within 48-72 hours after lymphodepletion pretreatment, the infusion dose (CAR-T cells) and groups are as follows: 1. Dose group 1: 1 × 10\^5/kg; 2. Dose group 2: 2 × 10\^5/kg; 3. Dose group 3: 3 × 10\^5/kg; Note: For subjects weighing ≤70 kg: number of infused CAR-T cells = (1, 2 or 3) (±20%) × 10\^5 × body weight(kg); for subjects weighing \>70 kg: number of infused CAR-T cells (fixed doses of GC012F Injection) = (1, 2 or 3) (±20%) × 10\^5 × 70 kg.

Timeline

• Start date: 2025-02-15
• Primary completion: 2027-02-13
• Completion: 2027-09-10
• First posted: 2025-01-06
• Last updated: 2025-01-06

Locations

1 site across 1 country: China