CD19-CART(Relma-cel) for Moderate to Severe Active Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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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.

Detailed Description
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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 .

Official Title
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A Phase I Dose-escalation Study Evaluate the Safety Tolerability Pharmacokinetics(PK) and Pharmacodynamics(PD) of Relma-cel in Subjects With Moderate to Severe Active Systemic Lupus Erythematosus (SLE)

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Biological: Relma-cel


Participation Criteria
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Eligibility Criteria
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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: Prednisone (or equivalent) ≥7.5 mg/ day, and ≤30 mg/ day. There is no minimum daily dose requirement for corticosteroids when used in combination with immunosuppressants. 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: 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. 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. 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. Combined with other autoimmune diseases, systematic treatment is needed. History of major organ transplantation (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation. IgA deficiency was present during screening (serum IgA level < 10 mg/dL)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Relma-cel be administrated in four dose level<br> | Biological: Relma-cel<br>* CD19-targeted Chimeric AntigenReceptor (CAR) T Cells; Relma-cel be administrated at four dose level:25×106 CAR+ T cells、50×106 CAR+ T cells、100×106 CAR+ T cells/150×106 CAR+ T cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLT rate | The incidence of dose-limiting toxicity | 3 months | 
| determine RP2D | To determine RP2D(Phase 2 recommended dose) | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SELENA-SLEDAI （Safety of Estrogens in Systemic Lupus Erythematosus National Assessment） score； 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. | SELENA-SLEDAI score taken up to 3 months after CD19 cCAR T cells infusion | 3 months | 
| BILAG -2004（updated version of british isles lupus assessment group ） level；The BILAG 2004 index categorizes disease activity into 5 different levels from A-E.Grade A represents very active disease. | BILAG-2004 level taken up to 3 months after CD19 cCAR T cells infusion | 3 months | 
| PGA (physician global assessment) score,The PGA scale ranges from no disease activity (0) to the most severe disease activity (3).the score is between 0 to 3. | PGA score taken up to 3 months after CD19 cCAR T cells infusion | 3 months | 
| Autoantibody detection | Autoantibody detection up to 3 months after CD19 cCAR T cells infusion | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relma-cel, Systemic lupus erythematosus, CD19-CART