Lupus Erythematosis
Conditions
Keywords
Moderate-to-severe refractory systemic lupus erythematosus
Brief summary
This is a phase I clinical study to evaluate the safety , pharmacokinetic profile, and preliminary efficacy of F01 in patients with moderate-to-severe refractory systemic lupus erythematosus.
Detailed description
Approximately up to about 50 participants with moderate-to-severe refractory systemic lupus erythematosus are planned to enroll. This study is divided into two stages: dose escalation and dose extension.
Interventions
Biological: 0.5-3×10\^9 CAR+NK Cells, Treatment follows a lymphodepletion Drug: Fludarabine: 25-30 mg/m\^2 (D-5\ D-3) Drug: Cyclophosphamide: 250-300 mg/ m\^2 (D-5\ D-3)
Sponsors
Shanghai Simnova Biotechnology Co.,Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
\- Participants must meet all of the following inclusion criteria to be enrolled in the study: 1. Age ≥18 and ≤65 years old, gender unlimited. 2. Subjects with moderate-to-severe refractory SLE must meet all of the following criteria: * Diagnosis of SLE at least 24 weeks prior to screening in accordance with the European Federation of Rheumatological Societies (EULAR)/American College of Rheumatology (ACR) 2019 SLE classification criteria at screening; * Applicants must meet one of the following criteria at screening: a. positive for antinuclear antibody (ANA); b. Positive anti-dsDNA antibody;c. Positive anti-Smith antibody; * SLEDAI-2000 score ≥ 8 at screening 3. Have received adequate standard doses of glucocorticoids, antimalarials, immunosuppressants/immunomodulators, and at least one biologic agent for at least 2 months prior to screening, with a stable dose > disease remaining active after 2 weeks of treatment. Oral glucocorticoids must meet the following requirements: 1) Prednisone (or equivalent) ≥ 7.5 mg/day and ≤ 60 mg/day. 2) When used in combination with immunosuppressants and/or biologics, there is no minimum daily dose requirement for glucocorticoids. The blood routine within 7 days of clear drenching conditioning chemotherapy meets the following requirements: * Absolute neutrophil value (ANC) ≥ 1.5×109/L; * Hemoglobin (Hb) ≥ 80g/L; * Platelet count (PLT) ≥ 50×109/L. 4. Adequate hepatic, renal, lung, and cardiac function, defined as: 1. Serum ALT and AST ≤ 2.5 times the upper limit of normal; 2. Total bilirubin ≤ 1.5 times the upper limit of normal, except for patients with Gilbert's syndrome, where total bilirubin must be ≤ 3.0 times the upper limit of normal; 3. creatinine clearance (estimated by Cockcroft Gault's formula) (Appendix 1) ≥ 50 ml/min; 4. Oxygen saturation of ≥ 92% in non-oxygenated conditions under indoor ventilation; No clinically significant pleural effusion; 5. Left ventricular ejection fraction ≥ 50%; Echocardiography to confirm the absence of pericardial effusion; There were no clinically significant abnormal findings on ECG. 5. Subjects receiving hematopoietic growth factor supportive therapy, including erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage-colony-stimulating factor (GM-CSF) and platelet agonists (TPO), etc., must have a 2-week gap between the last growth factor supportive therapy and the screening period evaluation; Patients receiving blood product transfusions should have at least 1 week between the screening platelet assessment and the last platelet transfusion, and at least 2 weeks between the screening hemoglobin assessment and the last red blood cell transfusion. 6. During the screening period, female subjects of childbearing potential must have a negative serum pregnancy test result (women who have been surgically sterilized or postmenopausal for at least 2 years are considered not of childbearing potential). Female subjects of childbearing potential and male subjects must use a highly effective method of contraception throughout the clinical study period and for 1 year after the last dose of study treatment; At the same time, a commitment should be made not to donate eggs (oocytes, oocytes)/sperm for assisted reproduction within 1 year after the last study treatment. 7. Voluntarily participate in clinical trials and sign informed consent.
Exclusion criteria
* Subjects who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Outcome Measures | 12 weeks | The proportion of subjects with AEs and SAEs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Outcome Measures | 48 weeks | Efficacy of F01 cells in moderate-to-severe refractory systemic lupus erythematosus |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory | 96 weeks | Explore the correlation between the concentration of PK and PD and efficacy and safety by CTCAE v5.0 |
Countries
China
Contacts
Primary ContactDirector Clinical Trial Disclosure Simnova Director Clinical Trial Disclosure Simnova
Outcome results
None listed