IgG4-related Disease
Conditions
Brief summary
This is an investigator initiated trial to assess the safety and efficacy of BCT301 cell Injection (CAR-iT cells derived from chemically induced pluripotent stem cells) in patients with refractory/recurrent IgG4-related disease.
Detailed description
This is a single-arm, open-label, single-center clinical study in which all patients receive a unified treatment regimen. The primary objective is to evaluate the safety and tolerability of BCT301 Cell Injection in patients with refractory/recurrent IgG4-RD. Secondary objective is to evaluate the improvement in disease activity in patients with refractory/recurrent IgG4-RD treated with BCT301 Cell Injection. Six subjects with refractory/recurrent IgG4-RD meeting the inclusion/exclusion criteria are planned to be enrolled and will receive a single infusion of 1.8 × 10\^8 BCT301 Cell Injection to evaluate the safety, efficacy, and PK/PD characteristics following BCT301 Cell Injection infusion. The study flow consists of a screening period, a lymphodepletion pretreatment period, a treatment period, and a follow-up period. Patients without relapse or deterioration after BCT301 Cell Injection infusion and not requiring protocol-prohibited treatment will undergo a primary follow-up of up to 360 days.
Interventions
OTHERBCT301 Cell Injection
BCT301 Cell Injection are CAR-iT cells derived from chemically induced pluripotent stem cells. Six subjects with refractory/recurrent IgG4-RD meeting the inclusion/exclusion criteria are planned to be enrolled and will receive a single infusion of 1.8 × 10\^8 BCT301 Cell Injection to evaluate the safety, efficacy, and PK/PD characteristics following BCT301 Cell Injection infusion.
Sponsors
Peking University Third Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Voluntarily participate in this trial and sign the informed consent form; * Male or female patients aged 18 to 75 years (inclusive), with body weight ≥ 40 kg; * Women of childbearing potential must have a negative serum pregnancy test before the start of the trial and agree to use effective contraception during the trial and until the last follow-up; male subjects whose partners are of childbearing potential agree to use effective contraception during the trial and until the last follow-up; * Confirmed diagnosis of IgG4-related disease meeting the classification criteria for IgG4-RD (the 2020 updated version of the comprehensive diagnostic criteria for IgG4-RD established in Japan) or the 2019 ACR/EULAR classification criteria for IgG4-RD; and with at least one of the following organ involvements: pancreas, bile ducts, kidneys, lungs, heart or pericardium, aorta and great vessels, retroperitoneal fibrosis, sclerosing mediastinitis, dura mater, or pituitary gland; * Clinically meets the criteria for refractory/recurrent IgG4-RD: disease remains active, or relapses after remission, or progresses despite systemic treatment with standard-of-care regimens-glucocorticoids, immunosuppressants (cyclophosphamide, mycophenolate mofetil, methotrexate, azathioprine, etc.)-or biologic agents; * Currently receiving one or more of the following stable-dose standard therapies: * If the patient is receiving glucocorticoid therapy, the following conditions must be met: at screening and during the screening period, the maximum glucocorticoid dose is 30 mg/day of prednisone (or equivalent). The glucocorticoid dose must remain stable for ≥ 7 days prior to screening; during the screening period, glucocorticoid dose adjustments must not exceed 5 mg/day of prednisone (or equivalent); * If the patient is receiving immunomodulators/immunosuppressants: initiation of drug therapy must be ≥ 12 weeks prior to screening. A stable drug dose must be maintained for ≥ 4 weeks prior to screening and during the screening period; * If biologic agents (e.g., belimumab or telitacicept) were used before the screening period, they must be discontinued for at least 5 half-lives before screening; if anti-CD20 monoclonal antibody therapy was used before the screening period, an interval of 6 months is required before screening; * IgG4-RD Responder Index (RI) ≥ 2, with disease in an active state; * Peripheral blood B cells show positive CD19 expression by flow cytometry; * Major organ function must meet the following requirements (conditions caused by the immune disease itself are exempt): * Bone marrow hematopoietic function must meet: a. White blood cell count ≥ 3 × 10\^9/L; b. Neutrophil count ≥ 1 × 10\^9/L (no colony-stimulating factor treatment within 2 weeks prior to the examination); c. Hemoglobin ≥ 70 g/L; * Hepatic function: Alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN), aspartate aminotransferase (AST) ≤ 3 × ULN, total bilirubin (TBIL) ≤ 2 × ULN (excluding Gilbert syndrome, for which total bilirubin ≤ 3.0 × ULN); * Renal function: Creatinine clearance ≥ 40 mL/min (Cockcroft-Gault formula); * Coagulation function: International normalized ratio (INR) \< 1.5 × ULN, prothrombin time (PT) \< 1.5 × ULN; * Cardiac function: Good hemodynamic stability.
Exclusion criteria
* The patient must not participate in this study if any of the following criteria are met: * 1\) Diseases that, after evaluation by the investigator, are considered inappropriate for participation in this study, for example life-threatening conditions; * 2\) Reduced organ functional reserve not caused by the primary disease: * Neutrophil count \< 1 × 10\^9/L; lymphocyte count \< 0.3 × 10\^9/L; hemoglobin \< 70 g/L; platelet count \< 50 × 10\^9/L; * ALT \> 3 × ULN; AST \> 3 × ULN; total bilirubin \> 2 × ULN; * Creatinine clearance \< 40 mL/min, estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m², or serum creatinine \> 2.5 mg/dL; * Left ventricular ejection fraction ≤ 45% as diagnosed by echocardiography; * Blood oxygen saturation ≤ 92%; * 3\) History of alcohol abuse or drug abuse within the past 24 weeks; * 4\) History of malignancy other than B-cell lymphoma within the past 5 years (excluding non-melanoma skin cancer, surgically cured cervical cancer, etc.); * 5\) Presence of infection with human immunodeficiency virus (HIV), agammaglobulinemia, T-cell deficiency virus, syphilis, chronic hepatitis B or C, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), etc.; * 6\) Known active tuberculosis (TB) infection or bacterial infection; * 7\) History of myocardial infarction, coronary angioplasty or stent placement, unstable angina, active arrhythmia, or other clinically significant cardiac disease requiring clinical intervention within 6 months before the start of screening; * 8\) History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months before the start of screening; * 9\) Known severe allergic reactions to cell-therapy-related components or their excipients, or to other immunotherapeutic agents; * 10\) Prior organ transplantation requiring long-term immunosuppressive medication; * 11\) Known simultaneous participation in other clinical trials affecting the disease or treatment; * 12\) Prior treatment with CD19- and/or BCMA-targeted therapy or any CAR-T cell product targeting any antigen; unless, as assessed by the investigator, the prior treatment has clearly failed (including failure to achieve remission after treatment, remission duration below the required standard, or disease progression), the current disease state is suitable for treatment in this study, and there is no clear evidence that toxicity related to prior treatment may affect the safety of this study; * 13\) Severe psychiatric illness and severe cognitive impairment; * 14\) Pregnant or lactating women, or women planning pregnancy; * 15\) Any condition considered by the investigator to be inappropriate for enrollment in this clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The safety and tolerability of BCT301 Cell Injection in patients with refractory/recurrent IgG4-RD. | 28 days after BCT301 Cell Injection infusion | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The change in IgG4-RD RI from baseline at 180 days after BCT301 Cell Injection infusion. | 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. | 90, 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. | 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. | 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. |
| Changes in IgG4 levels at 90, 180, and 360 days after BCT301 Cell Injection infusion. | 90, 180, and 360 days after BCT301 Cell Injection infusion. | This endpoint assesses the absolute change from baseline in serum IgG4 concentration (measured in g/L) at Day 90, Day 180, and Day 360 post-infusion. |
| Physician Global Assessment (PhGA) and Patient Global Assessment (PtGA) compared with baseline. | 90, 180, and 360 days after BCT301 Cell Injection infusion. | This endpoint evaluates the change from baseline in both the Physician Global Assessment (PhGA) and the Patient Global Assessment (PtGA), each measured using a single-item visual analogue scale (VAS) ranging from 0 to 100 mm, where 0 indicates no disease activity and 100 indicates the worst possible disease activity/symptoms. Higher scores indicate a worse outcome. Changes are assessed at predefined time points (consistent with other endpoints, e.g., 90, 180, and 360 days) to capture the treatment effect from both clinician and patient perspectives. |
Contacts
CONTACTJinxia Zhao, MD
Outcome results
None listed