ANCA Associated Vasculitis, Idiopathic Inflammatory Myopathies, Sjögren Syndrome, SLE - Systemic Lupus Erythematosus, Systemic Sclerosis
Conditions
Keywords
CD19/BCMA CAR-T
Brief summary
This is a single-arm, open-label, investigator-initiated trial (IIT) designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of RD06-05 in patients with autoantibody-mediated autoimmune diseases. The enrolled population consists of patients with active autoimmune diseases, including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), ANCA-associated vasculitis (AAV), idiopathic inflammatory myopathies (IIM), Sjögren's syndrome (SS), among others. The CAR-T cell dose used in this study is 6×10⁶ CAR⁺ T cells/kg. Six subjects will be enrolled for each indication, with a total of 30 subjects to be enrolled.
Interventions
DRUGRD06-05 CAR-T Cell Injection
CAR T-cell therapy administered intravenously after a lymphodepleting therapy regimen consisting of fludarabine and cyclophosphamide.
Sponsors
Nanjing Bioheng Biotech 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
1. General Inclusion Criteria (All Patients) 1. Voluntarily provides written informed consent. 2. Age ≥18 and ≤70 years, any gender. 3. Adequate organ function: * ALT and AST ≤3×ULN; total bilirubin ≤2×ULN (excluding Gilbert syndrome). * Creatinine ≤1.5×ULN or creatinine clearance ≥40 mL/min. * Neutrophils ≥1×10⁹/L; hemoglobin ≥60 g/L; platelets ≥20×10⁹/L; lymphocytes \>0.3×10⁹/L. * INR ≤1.5×ULN or PT ≤1.5×ULN. * Resting room-air SpO₂ ≥92%. * LVEF ≥50% on echocardiogram. 4. Negative serum or urine pregnancy test for females of childbearing potential at screening. 5. Highly effective contraception required from 28 days before lymphodepletion until 12 months after RD06-05 infusion for females; effective barrier contraception required from lymphodepletion until 12 months after RD06-05 infusion for males, with no sperm donation during the study. 2. For SLE Patients 1. Diagnosis of SLE per 2019 EULAR/ACR or 2012 SLICC criteria. 2. Active disease despite ≥2 months of stable (≥2 weeks) treatment with glucocorticoids plus immunosuppressants and/or biologics; prednisone ≥7.5 mg/day or equivalent. 3. Positive ANA, anti-dsDNA antibody, and/or anti-Smith antibody at screening. 4. SLEDAI-2K \>6 and clinical SLEDAI-2K ≥4 at screening. Patients with lupus nephritis (proteinuria \>0.5 g/24h, UPCR \>500 mg/g, or active urinary sediment) are exempt from clinical SLEDAI-2K requirement. 5. Physician Global Assessment (PGA) ≥1.0 (0-3 VAS) at screening. 3. For SSc Patients 1. Diagnosis of SSc per 2013 ACR/EULAR criteria. 2. Diffuse cutaneous SSc at screening. 3. Active disease defined by at least one of: new SSc within 2 years; new/worsening skin or thoracic/abdominal involvement within 6 months; worsening skin thickening (mRSS ≥2); tendon friction rubs within 3 months; worsening respiratory symptoms with FVC decline ≥5% predicted or DLCO decline ≥10% predicted; or ILD progression on HRCT compared to 12 months prior. 4. Refractory or relapsing disease after \>6 months of conventional therapy including glucocorticoids, cyclophosphamide, immunosuppressants, and/or biologics. 4. For AAV Patients 1. Diagnosis of ANCA-associated vasculitis (MPA, GPA, EGPA) per 2022 ACR/EULAR criteria. 2. Positive MPO-ANCA or PR3-ANCA. 3. BVAS with at least 1 major item, 3 minor items, or 2 renal items. 4. Failure of standard of care: no remission after ≥4 months of glucocorticoids plus cyclophosphamide/rituximab; relapse after prior remission; or persistent active disease despite ≥6 months of SOC. 5. For IIM Patients 1. Diagnosis of IIM (DM, ASS, IMNM) per 2017 ACR/EULAR criteria (probability ≥55%). 2. Active disease defined by ≥2 abnormal core measures, or active myositis on muscle MRI, or active inflammation on muscle biopsy within 16 weeks. 3. Positive myositis-specific autoantibodies. 4. Refractory or relapsing disease after ≥6 months of conventional therapy including glucocorticoids, immunosuppressants, and/or biologics. 6. For pSS Patients 1. Diagnosis of primary Sjögren's syndrome per 2016 ACR/EULAR criteria. 2. Positive anti-SSA/Ro antibody. 3. ESSDAI ≥6 at screening. 4. Refractory or relapsing disease after ≥6 months of conventional therapy including glucocorticoids, immunosuppressants, and/or biologics.
Exclusion criteria
1. General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SLE (systemic lupus erythematosus) | 2 years | Proportion of patients achieving lupus low disease activity state (LLDAS) and DORIS(Definition Of Remission In SLE) remission, as well as the proportion of patients achieving drug-free remission |
| AAV (ANCA-associated vasculitis) | 2 years | Change in Birmingham Vasculitis Activity Score (BVAS) from baseline. The Birmingham Vasculitis Activity Score (BVAS) ranges from a minimum of 0 to a maximum of 63, with higher scores indicating worse disease activity and clinical outcomes. |
| IIM (idiopathic inflammatory myopathies) | 2 years | Major clinical remission assessed according to the 2016 ACR/EULAR myopathy remission criteria |
| SSc (systemic sclerosis) | 2 years | Changes in modified Rodnan Skin Score (mRSS) from baseline |
| SS (Sjögren's syndrome ) | 2 years | Change in ESSDAI(EULAR Sjögren's Syndrome Disease Activity Index) score from baseline. ESSDAI has a score range from 0 to 105, with higher scores indicating greater disease activity and poorer clinical outcomes. |
Countries
China
Contacts
CONTACTMing Gao, Master
PRINCIPAL_INVESTIGATORQiong Fu, Doctor
RenJi Hospital
Outcome results
None listed