Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Autoimmune Diseases, Primary Sjögren Syndrome, Rheumatoid Arthritis, Systemic Lupus Erythematosus, Systemic Sclerosis
Conditions
Brief summary
A single arm, open-label pilot study is designed to determine the safety and effectiveness of anti-CD19/BCMA U CAR T cells in patients with autoimmune diseases. 60 patients are planned to be enrolled in the dose-escalation trial.
Interventions
BIOLOGICALanti-CD19/BCMA U CAR T cells
Patients will receive Fludarabine and Cyclophosphamide on day-5, -4, and -3. Dose escalation will be performed for the single dose injection of anti-CD19/BCMA CAR T cells (KN3601)
Sponsors
Changhai Hospital
Rui Therapeutics Co., Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Common inclusion criteria: 1. Age: ≥ 18 years old and ≤ 70 years old, male or female; 2. The functions of critical organs meet the following requirements: a )Neutrophil count ≥ 1 x 10\^9/L, Hemoglobin ≥60g/L; b) Liver function: ALT ≤ 3 x ULN,AST≤3 x ULN, TBIL≤1.5 x ULN; c) Coagulation function: International standardized ratio (INR) ≤1.5x ULN, prothrombin time (PT) ≤1.5 x ULN; d) Cardiac function: good hemodynamic stability, left ventricular ejection fraction (LVEF) ≥50%; 3. Female subjects of childbearing potential and male subjects whose partner is a female of childbearing potential are required to use medically approved contraception or abstain from sex for at least 6 months during and at least 6 months after the end of the study treatment period; female subjects of childbearing potential have had a negativeserum HCG test within 7 days prior to study enrollment and are not lactating; 4. Voluntarily participate in this clinical study, sign an informed consent form, have good compliance, and cooperate with follow-up. Specific inclusion criteria: Relapsed/Refractory Systemic lupus erythematosus 1. Subject have previous diagnosis of systemic lupus erythematosus (SLE) (according to the 1997 American College of Rheumatology revised SLE classification criteria, the 2012 Systemic Lupus International Collaborating Clinics classification criteria, or the 2019 European League Against Rheumatism/American College of Rheumatology joint classification criteria); 2. Subjects had a modified SLEDAI-2K score of ≥8 at screening; 3. Subject has ≥ 1 organ system with BILAG-2004 Class A mobility score or ≥ 2 organ systems with BILAG-2004 Class B mobility score at screening; 4. Based on the results of the central laboratory tests at screening, the subject meets one of the following: a. ANA by immunofluorescence ≥ 1:80 b. Anti-dsDNA antibodies above the normal level c. Anti-Smith antibodies above the normal level. Relapsed/Refractory Systemic Sclerosis 1. Meets 2013 ACR classification criteria for systemic sclerosis; 2. If combined with interstitial pneumonia, interstitial changes suggestive of ground-glass exudates on chest HRCT and FVC or DLCO \<70% predictive value on pulmonary function tests; 3. Ineffective conventional treatment or relapse of disease activity after remission. Definition of routine treatment: Use of glucocorticoids (above 1mg/Kg/d) and cyclophosphamide, as well as any of the following immunomodulatory drugs for more than 6 months: antimalarials, 4. methotrexate, leflunomide, cyclophosphamide, azathioprine, mertiomate, tacrolimus, cyclosporine, and biologics, including rituximab, belimumab and tetracycline; 5. Definition of progressiveness; 1) Definition of cutaneous progression: increase in mRSS \>10%; 2) Definition of lung disease progression: 10% decrease in FVC or 5% decrease in FVC with 15% decrease in DLCO (OMERACT progression). Relapsed/Refractory Primary Sjögren's Syndrome 1. Meets 2002 AECG criteria or 2016 ACR/EULAR classification criteria for primary dry syndrome (pSS); 2. Definition of disease activity: investigator-assessed disease ESSDAI score of 5 or higher; 3. Ineffective conventional treatment or relapse of disease activity after remission. Definition of routine treatment: Use of glucocorticoids (above 1mg/Kg/d) and cyclophosphamide, as well as any of the following immunomodulatory drugs for more than 6 months: antimalarials, methotrexate, leflunomide, cyclophosphamide, azathioprine, mertiomate, tacrolimus, cyclosporine, and biologics, including rituximab, belimumab and tetracycline. Relapsed/Refractory rheumatoid arthritis 1. Meets the diagnostic criteria of the 2010 ACR/EULAR classification. Diagnosis of moderately or severely active rheumatoid arthritis with a previous diagnosis of rheumatoid arthritis ≥ 6 months; 2. A swollen joint count of ≥ 6 (based on 66 joint counts) and a tender joint count of ≥ 6 (based on 68 joint counts) during the Screening Period; 3. C-reactive protein (CRP) ≥ 10 mg/L or erythrocyte sedimentation rate (ESR) ≥ 28 mm/h during the Screening Period; 4. EULAR definition of refractory rheumatoid arthritis: 1） Failure of treatment according to EULAR recommended guidelines and failure of treatment with ≥2 b/tsDMARDs despite failure of treatment with csDMARDs. (i) unless treatment with bDMARDs/tsDMARDs is limited due to socioeconomic factors; and (ii) if treatment with csDMARDs is contraindicated, then failure of treatment with ≥2 b/tsDMARDs of different mechanisms also fulfills the condition); 2） Symptom management of RA is considered problematic by both the patient and the physician; 3） Signs suggestive of active or progressive disease if at least 1 of the following 5 items is met (Meeting all three of the below criteria can be diagnosed as rheumatoid arthritis): i. At least moderate disease activity (DAS28-ESR \>3.2 or CDAI\>10); ii. Signs and/or symptoms suggestive of active disease; iii. Inability to reduce glucocorticoids to less than 7.5 mg/dayprednisone or equivalent; iv. Rapid imaging progression (1-year increase of ≥5 points in vander Heijde modified Sharp score); v. Decreased quality of life due to RA, although RA is well controlled. Relapsed/refractory anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis 1. Meets 2022 ACR/EULAR diagnostic criteria for ANCA vasculitis, including microscopic polyangiitis, granulomatous polyangiitis, eosinophilic granulomatous polyangiitis; 2. Positive ANCA related antibodies (MPO-ANCA or PR3-ANCA positive); 3. The Birmingham Vasculitis Activity Scale (BVAS) is ≥ 15 points (a total score of 63 points), indicating the activity of the vasculitis condition; 4. Glomerular filtration rate (eGFR, CKD-EPI formula) ≥15 ml/min/1.73 m2 during the screening period.
Exclusion criteria
Subjects who meet any of the following common
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-Limiting Toxicity (DLT) | up to 52 weeks after infusion | To characterize the safety of anti-CD19/BCMA U CAR T Cells (KN3601) for patients with Relapsed/Refractory autoimmune diseases |
| Incidence of Treatment Emergent Adverse Events (TEAEs) | up to 52 weeks after infusion | To characterize the safety of anti-CD19/BCMA U CAR T Cells (KN3601) for patients with Relapsed/Refractory autoimmune diseases |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The overall response rate (ORR) | up to 52 weeks after infusion | To characterize the efficacy of anti-CD19/BCMA U CAR T Cells (KN3601) for patients with Relapsed/Refractory autoimmune diseases |
| Disease control rate (DCR) | up to 52 weeks after infusion | To characterize the efficacy of anti-CD19/BCMA U CAR T Cells (KN3601) for patients with Relapsed/Refractory autoimmune diseases |
| B cell depletion rate | up to 52 weeks after infusion | To characterize the efficacy of anti-CD19/BCMA U CAR T Cells (KN3601) for patients with Relapsed/Refractory autoimmune diseases |
| B cell reconstitution | up to 52 weeks after infusion | B cell subsets in peripheral blood measured by flow cytometry |
Countries
China
Contacts
CONTACTDongbao Zhao
Outcome results
None listed