This study consists of the following periods: screening period, apheresis day, baseline period, lymphodepleting preconditioning period, GC012F infusion, safety and efficacy follow-up period, and long-term follow-up period.
Eligible subjects will undergo apheresis and will receive the infusion following the manufacture of the chimeric antigen receptor T cell (CAR-T) product. Prior to CAR-T cell infusion, subjects will receive lymphodepleting preconditioning and will be assessed before infusion. Subjects who meet the criteria for cell infusion will receive CAR-T cell infusion, and the infusion dose for the same group or subsequent study groups may be adjusted based on safety and clinical efficacy. In this study, the CAR-T cell infusion dose is set as follows: one target dose group (Dose Group 1): 3.0×10\^5 CAR-T cells/kg, and one alternative dose group (Dose Group -1): 2.0×10\^5 CAR-T cells/kg or 1.0×10\^5 CAR-T cells/kg, with a total of 15 evaluable subjects to be enrolled. Among them, 6 subjects will be enrolled during the dose-limiting toxicity (DLT) observation stage, and 9 subjects will be enrolled during the expansion stage. This study does not establish separate cohorts for different indications (systemic sclerosis \[SSc\] or idiopathic inflammatory myopathies \[IIM\]). Eligible subjects will receive a single infusion of GC012F Injection. After all 6 subjects in the DLT observation stage have completed DLT observation, all clinical study data collected during the DLT observation stage (primarily safety data) will be assessed. If no more than 1 out of the 6 subjects experiences a DLT, 9 additional subjects will be enrolled in the dose expansion stage. If 2 subjects experience a DLT, the investigators and partner will discuss and decide whether to explore a lower dose group (Dose Group -1).
After CAR-T cell infusion, subjects will be followed up for safety, cellular expansion and persistence, and efficacy until 672 days (96 weeks) after infusion, or until the subject withdraws from the study and declines further follow-up, death, withdrawal of informed consent, or loss to follow-up, whichever occurs first.
Leukapheresis: Only subjects who have completed screening and fully meet the eligibility criteria may be enrolled. Mononuclear cells will be collected from the enrolled subjects and transported to a Good Manufacturing Practice (GMP)-compliant manufacturing workshop for cell preparation.
Lymphodepleting preconditioning: After confirming that the cells have passed quality control and met the release criteria, the investigator will determine whether to initiate lymphodepleting preconditioning based on the subject's condition on Day -5 prior to GC012F Injection infusion. The preconditioning will last for a total of 3 days (Days -5, -4, and -3 or Days -4, -3, and -2). The recommended preconditioning regimen is as follows:
1. Fludarabine 30 mg/m\^2/day, via intravenous infusion for 3 days;
2. Cyclophosphamide 300 mg/m\^2/day, via intravenous infusion for 3 days. GC012F Injection infusion: Subjects who meet the CAR-T cell infusion criteria will receive GC012F Injection infusion within 48-72 hours after completion of lymphodepleting preconditioning.
Safety and efficacy follow-up: Subjects who receive GC012F Injection infusion should continue with all subsequent post-infusion assessments.
The inpatient observation period should start from the infusion (Day 0) and continue for 14 days; hospitalization from Day 15 to Day 28 should follow local diagnosis and treatment guidelines. The window for the Day 4, Day 7 (Week 1), Day 10, and Day 14 (Week 2) visits is ±1 day; for the Day 28 (Week 4) visit, the window is +3 days. Within 12 weeks after GC012F Injection infusion, follow-up visits will be conducted every 28 days (4 weeks) ±7 days (1 week). From Weeks 12 to 48, follow-up visits will be conducted every 84 days (12 weeks) ±7 days (1 week). After Week 48, follow-up visits will be conducted every 6 months (24 weeks) ±14 days (2 weeks), until 672 days (96 weeks) after infusion, withdrawal of informed consent, withdrawal from the study with refusal to undergo subsequent follow-up, death, or loss to follow-up, whichever occurs first. Subjects who do not withdraw from the study prematurely within 672 days (96 weeks) will proceed to the long-term follow-up period. The end of this study is defined as 672 days (96 weeks) after the last GC012F Injection infusion to the last subject.
Long-term follow-up: Subjects who do not withdraw from the study prematurely within 672 days (96 weeks) after infusion will proceed to the long-term follow-up period, which will continue until withdrawal of informed consent, withdrawal from the study with refusal to undergo subsequent follow-up, death, loss to follow-up, or 15 years after cell infusion, whichever occurs first. During this period, the primary focus will be on the collection of serious adverse events related to GC012F Injection. From Years 3 to 5 post-infusion, subjects will undergo follow-up every six months for replication competent lentivirus (RCL) and lentiviral integration site testing, and disease assessment-related examinations. From Years 6 to 15 post-infusion, subjects are required to undergo annual follow-up for RCL testing, lentiviral vector integration site testing, and disease assessment-related examinations.
Withdrawal visit: Subjects who withdraw from the study will undergo a withdrawal visit as specified. If a subject has initiated a new treatment prior to the withdrawal visit, details regarding the diagnostic basis for disease activity and the treatment process should be documented in chronological order unless the subject withdraws consent. There is no need to repeat the efficacy assessment at the withdrawal visit if it occurs within 4 weeks after the last two consecutive efficacy assessments. Other assessments do not need to be repeated if they are conducted within 2 weeks after the last assessment.
