Systemic Lupus Erythematosus
Conditions
Keywords
CD19-CART
Brief summary
To assess the safety tolerability pharmacokinetics and pharmacodynamics of Relma-cel in moderate or severe active systemic lupus erythematosus (SLE) subjects in China.
Detailed description
For phase I to evaluate the safety and tolerability of Relma-cel in moderate to severe active systemic lupus erythematosus (SLE) and determine the Phase II Recommended Dose (RP2D). For phase II to evaluation of the efficacy of Relma-cel (treatment group) in moderate to severe active SLE using the Low Disease Activity State of Lupus (LLDAS) under Phase II Recommended Dose (RP2D) compared to conventional therapy combined with or without biologics (control group).
Interventions
DRUGRelma-cel
CD19-targeted Chimeric AntigenReceptor (CAR) T Cells
Sponsors
Shanghai Ming Ju Biotechnology 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. Voluntarily signed an informed consent form (ICF). 2. Applicants must be between 18 and 70 years old (inclusive) at the time of signing the ICF, male or female. 3. Diagnosed with SLE according to the 2012 SLICC or 2019 EULAR/ACR version of the revised criteria. 4. Disease remaining active after receiving corticosteroids combined immunosuppressive therapy and/or biological agents, with a stable treatment plan for at least 2 months and a stable dose for at least 2 weeks before screening. Oral corticosteroids must meet the following requirements: 1. Prednisone (or equivalent) ≥7.5 mg/day and ≤60 mg/day. 2. When used in combination with immunosuppressants, there is no minimum daily dose requirement for corticosteroids. 5\. Positive antinuclear antibody, and/or anti-dsDNA antibody, and/or anti-Smith antibody at screening. 6\. SELENA-2k score ≥7 points during the screening period. 7. Active organ involvement during screening period. 8. No active infection (e.g., pneumonia, tuberculosis) within 2 weeks prior to screening period. 9\. Vascular access is sufficient for leukapheresis. 10. Adequate organ function: 1. Renal function: defined as creatinine clearance (Cockcroft-Gault) ≥40 mL/min calculated without hydration assistance. 2. Bone marrow function: defined as absolute neutrophil count (ANC) ≥1000 /μL, absolute lymphocyte count (ALC) ≥100 /μL, hemoglobin (Hb) ≥60 g/L, platelet count (PLT) ≥20,000 /μL. Blood transfusions and CSF must not be used to meet these requirements during the 7 days prior to eligibility screening. 3. Liver function: defined as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN, total bilirubin \< 2.0 mg/dL (total bilirubin \< 3.0 mg/dL in subjects with Gilbert syndrome, except for caused by SLE). 4. Coagulation function: defined as international ratio (INR) or activated partial thromboplastin time (APTT) ≤1.5×ULN. 5. Lung function: defined as ≤CTCAE grade 1 dyspnea and blood oxygen saturation (SpO2) ≥92% in indoor air (measured by pulse oximeter). 6. Cardiac function: defined as left ventricular ejection fraction (LVEF) ≥40% as assessed by echocardiography (ECHO) or cardiac radionuclide angiography (MUGA) within 8 weeks prior to screening. 11\. Fertile women (defined as all women biologically capable of becoming pregnant) must consent to the use of a highly effective contraceptive method for contraception from at least 28 days before the start of lymphodepleting and 2 years after infusion of Relma-cel (including the duration of the dose-interrupted study treatment). Men whose partners are fertile must agree to use an effective barrier method of contraception from the start of lymphodepleting until 2 year after Relma-cel infusion and should not donate semen or sperm throughout the study period. 12\. Fertile women must test negative for serum beta human chorionic gonadotropin (β-hCG) at the time of screening and within 48 hours before the first day of lymphodepleting treatment.
Exclusion criteria
Subjects who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DLT rate | 6months | The incidence of dose-limiting toxicity |
| determine RP2D | 6months | To determine RP2D(Phase 2 recommended dose) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SELENA-SLEDAI | 3 months after CD19 cCAR T cells infusion | 0 to 4 is basically no disease activity;5 to 9 is light activity;10 to 14 is moderate activity;≥15 is considered heavy activity. |
| BILAG -2004 | 3 months after CD19 cCAR T cells infusion | The BILAG 2004 index categorizes disease activity into 5 different levels from A-E.Grade A represents very active disease. |
| PGA (physician global assessment) score | 3 months after CD19 cCAR T cells infusion | The PGA scale ranges from no disease activity (0) to the most severe disease activity (3).the score is between 0 to 3. |
Contacts
Primary ContactJW Medical
Backup ContactYue Dong
Outcome results
None listed