Overview
This is a phase I, open-label, single-arm, multicenter study to asess the safety tolerability pharmacokinetics and pharmacodynamics of Relma-cel in moderate or severe active systemic lupus erythematosus (SLE) subjects in China.
Description
This is a phase I, open-label, single-arm, multicenter study to asess the safety tolerability pharmacokinetics(PK) and pharmacodynamics(PD) of Relma-cel in moderate or severe active systemic lupus erythematosus (SLE) subjects in China.
There will be 4 dose level (15x106 CAR+ T cells as the back up dose ,25x106 CAR+ T cells as the starting dose 、50x106 CAR+ T cells and 100x106(or 150 x106CAR+ T cells）Dose escalation, to evaluate the safety、 tolerability of Relma-cel in adult subjects of SLE and determine RP2D .
Eligibility
Inclusion Criteria:
- Sign an informed consent form (ICF) voluntarily.
- At the time of signing the ICF, you must be between 18 and 70 years old (inclusive), male or female.
- A diagnosis of SLE according to the 1997 revised criteria of the American College of Rheumatology (ACR).
- The history of SLE prior to screening was at least 6 months, and the disease remained active at least 2 months after the use of a stable standard SLE regimen prior to screening.
Standard treatment regimen refers to the steady use of any of the following (alone or in
combination) : corticosteroids, antimalarials, non-steroidal anti-inflammatory drugs
(NSAIDs), and other immunosuppressants or immunomodulators including azathioprine,
Mycophenolate Mofetil, cyclophosphamide, methotrexate, leflunomide, tacrolimus, and
cyclosporine.
Oral corticosteroids must meet the following requirements:
1. Prednisone (or equivalent) ≥7.5 mg/ day, and ≤30 mg/ day.
2. There is no minimum daily dose requirement for corticosteroids when used in
combination with immunosuppressants.
3. At least 8 weeks of treatment prior to screening, and the dose must be kept stable for
> 2 weeks.
5. Screening is positive for antinuclear antibodies, and/or anti-DS-DNA antibodies, and/or
anti-Smith antibodies.
6. SELENA-SLEDAI score ≥8 during the screening period. Score ≥6 for SELENA-SLEDAI clinical
symptoms (except for low complement and/or anti-DS-DNA antibodies) if low complement and/or
anti-DS-DNA antibody score is present.
Exclusion Criteria:
1. Severe lupus nephritis (defined as proteinuria > 6 g/24h or serum creatinine > 2.5
mg/dL or 221 μmol/L), treatment with active nephritis with Prohibited drugs,
hemodialysis, or prednisone ≥100 within 8 weeks prior to screening mg/d or equivalent
glucocorticoid therapy ≥14 days.
2. Prior to screening, other lupus crises, such as active central nervous system lupus,
severe hemolytic anemia, severe thrombocytopenic purpura, severe agranulocytosis,
severe myocardial damage, severe lupus pneumonia or pulmonary hemorrhage, severe lupus
hepatitis, and severe vasculitis.
3. Clinically significant central nervous system diseases or pathological changes not
caused by lupus prior to screening, including but not limited to: cerebrovascular
accident, aneurysm, epilepsy, convulsions/convulsions, aphasia, stroke, severe brain
injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or
psychosis.
4. Combined with other autoimmune diseases, systematic treatment is needed.
5. History of major organ transplantation (e.g., heart, lung, kidney, liver) or
hematopoietic stem cell/bone marrow transplantation.
6. IgA deficiency was present during screening (serum IgA level < 10 mg/dL)