BCT301 in Treating Refractory/Recurrent IgG4-related Disease

The safety and tolerability of BCT301 Cell Injection in patients with refractory/recurrent IgG4-RD.

The occurrence of cell-infusion-related adverse events within 28 days after BCT301 Cell Injection infusion, with special emphasis on cell-therapy-specific adverse reactions such as CRS and ICANS.

The change in IgG4-RD RI from baseline at 180 days after BCT301 Cell Injection infusion.

This endpoint evaluates the absolute change in the IgG4-Related Disease Responder Index (IgG4-RD RI) score from baseline to Day 180 post-infusion. The IgG4-RD RI is a validated, disease-specific composite scoring system that quantifies organ involvement and disease activity across multiple domains (e.g., head/neck, chest, retroperitoneum, etc.). The change is calculated as the Day 180 score minus the baseline score; a negative value indicates improvement (reduction in disease activity), while a positive value indicates worsening. This continuous variable complements the binary response rate endpoint by providing a more granular assessment of the degree of clinical improvement or deterioration over time, and will be analyzed using descriptive statistics (mean, median, standard deviation) as well as inferential tests (e.g., paired t-test or Wilcoxon signed-rank test) for within-subject change.

IgG4-RD RI response rate (decrease ≥ 2 points from baseline) at 90 and 180 days after BCT301 Cell Injection infusion.

This endpoint measures the proportion of subjects achieving at least a 2-point reduction from baseline in the IgG4-Related Disease Responder Index (IgG4-RD RI) at Day 90 and Day 180 post-infusion. The IgG4-RD RI is a validated disease activity scoring system; a decrease of ≥2 points is considered clinically meaningful and indicates a partial response to treatment.

IgG4-RD complete remission rate at 180 and 360 days after BCT301 Cell Injection infusion.

This endpoint evaluates the proportion of subjects who achieve stringent complete remission at Day 180 and Day 360. Complete remission requires all three criteria to be met simultaneously: (1) IgG4-RD RI score of 0 (no active disease manifestations); (2) prednisone dose of 0 mg/day after Week 4 (excluding any short-term glucocorticoid pulse used specifically to manage cytokine release syndrome \[CRS\] or allogeneic immune reactions, which are not counted as maintenance therapy); and (3) no documented recurrence or flare of disease activity from baseline through the assessment time point.

Proportion of patients with relapse after remission at 90, 180, and 360 days after BCT301 Cell Injection infusion.

This endpoint measures the cumulative proportion of subjects who, having achieved any remission (partial or complete) after infusion, subsequently experience disease relapse at Day 90, Day 180, or Day 360. Relapse is specifically defined as an increase in IgG4-RD RI score during the follow-up period that necessitates additional therapeutic intervention not specified in the study protocol, thereby indicating loss of disease control.

CAR gene copy number in peripheral blood after BCT301 Cell Injection infusion and the duration of persistence after infusion.

This endpoint quantifies the level of CAR transgene in peripheral blood using a validated quantitative polymerase chain reaction (qPCR) assay specific to the CAR construct. CAR gene copy number is measured at baseline and at multiple post-infusion time points: Days 1, 3, 7, 10, 14, 28, 90. Results are expressed as copies per microgram of genomic DNA or copies per milliliter of blood. The persistence duration is defined as the last time point at which the CAR copy number remains above the lower limit of quantification for each subject.

Time to maximum concentration (Tmax) of CAR gene copies after BCT301 Cell Injection infusion.

This PK parameter is derived from the CAR gene copy number-time profile. Tmax is defined as the time (in days) from the end of BCT301 infusion to the first occurrence of the peak CAR copy number (Cmax) in peripheral blood. It is estimated using non-compartmental analysis based on serial measurements collected during the early post-infusion period (Days 1, 3, 7, 10, 14, and 28). Tmax reflects the kinetics of CAR-T cell expansion and trafficking to the peripheral circulation.

Maximum concentration (Cmax) of CAR gene copies after BCT301 Cell Injection infusion.

This PK parameter represents the peak observed CAR gene copy number in peripheral blood after infusion. Cmax is determined directly from the concentration-time data as the highest measured value ( copies/mL) during sampling period. It quantifies the maximal expansion level of the infused CAR-T cells and is a key exposure metric for correlating with efficacy and toxicity.

Area under the concentration-time curve from 0 to 28 days (AUC28) of CAR gene copies after BCT301 Cell Injection infusion.

AUC28 is the integral of the CAR gene copy number-time curve from the time of infusion (Day 0) to Day 28, calculated using the linear trapezoidal rule (or log-linear for descending part). It quantifies the total early systemic exposure to CAR-T cells over the first 28 days, capturing the initial expansion and contraction phase. Missing intermediate values are handled by standard PK imputation methods. AUC28 is expressed as copies·day/mL.