Refractory Active Systemic Lupus Erythematosus
Conditions
Brief summary
This study aimed to observe the safety and tolerability of SYS6020 in adult participants with refractory active systemic lupus erythematosus, determine the recommended dose (RD) that may be explored for subsequent studies, and preliminly evaluate the clinical efficacy of this product,and explore the pharmacokinetics and immunogenicity of SYS6020 injection in those participants.
Interventions
DRUGSYS6020
BCMA Chimeric Antigen Receptor T Cell（SYS6020）Injection Intravenous infusion
Sponsors
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single Group
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Age ≥18 years old, ≤70 years old; * 2\. SLE is diagnosed according to SLICC 2012 or EULAR/ACR 2019 revised criteria. * 3\. Patients are required to have received glucocorticoid combined with immunosuppressive agents and/or biological agents for more than 3 months, with a stable dose for more than 2 weeks, and the disease is still in an active state. * 4\. Antinuclear antibody, anti-ds-DNA antibody and/or anti-Smith antibody are positive. * 5\. SLEDAI-2K score≥7. * 6\. BILAG2004 meets one of the following two criteria:a）BILAG grade A is defined as ≥1 organ system；b）BILAG grade B is defined as ≥2 organ systems * 7\. PGA \> 1.0;
Exclusion criteria
* 1\. Severe lupus nephritis within 8 weeks before screening; * 2\. SLE or non-SLE-related central nervous system disease or lesion within 8 weeks before screening; * 3\. uncontrolled lupus crisis within 8 weeks before screening; * 4\. clinically significant central nervous system diseases or pathological changes other than lupus before screening; * 5\. vasculitis or inflammatory arthritis or skin disease other than SLE or at screening; * 6\. complicated with other autoimmune diseases; * 7\. A B-cell-targeting agent have been used or is planned to be used within 8 weeks before screening， * 8\. received Renal Replacement Therapy（RRT）within 3 months before the screening period or anticipates the need for RRT during the study period; * 9\. participants who will undergo major surgery or invasive intervention within 4 weeks prior to apheresis or plan for systemic or local tumor resection during the study period; * 10\. participants with a known allergy, hypersensitivity, intolerance, or contraindications to SYS6020 or any component of the drugs that may be used in the study, * 11\. active bacterial, fungal, or viral infection within 2 weeks before apheresis;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The frequency and nature of DLT and the incidence of all adverse events and serious adverse events | 28 days after infusion | Assess safety and tolerability of SYS6020 in patients with systemic lupus erythematosus |
| recommended dose (RD) | 6 Months | recommended dose (RD) |
| Proportion of participants who achieved systemic lupus erythematosus remission (DORIS). | 6 Months | Proportion of participants who achieved systemic lupus erythematosus remission (DORIS) at 6 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants achieving low disease activity status (LLDAS) | 12weeks、6 Months | Proportion of participants achieving low disease activity status (LLDAS) |
| Absolute and percentage changes from baseline in SLEDA1-2K, BILAG-2004 and PGA scores | 6 Months | Absolute and percentage changes from baseline in SLEDA1-2K, BILAG-2004 and PGA scores |
| Changes from baseline in antinuclear antibody, anti-ds-DNA antibody, anti-Smith antibody, C3, C4, and 24-hour urinary protein | 6 Months | Changes from baseline in antinuclear antibody, anti-ds-DNA antibody, anti-Smith |
| Changes of immunoglobulin (IgG, IgM, IgA, IgE) from baseline | 6 Months | Changes of immunoglobulin (IgG, IgM, IgA, IgE) from baseline |
| Proportion of participants who achieved systemic lupus erythematosus remission (DORIS) | 12 weeks | Proportion of participants who achieved systemic lupus erythematosus remission (DORIS) |
| BCMA CAR+ gene copy numberCAR gene copies | 6 Months | BCMA CAR+ gene copy numberCAR gene copies |
| Number of CAR+ cells | 6 Months | Number of CAR+ cells |
| Incidence of all adverse events and serious adverse events | 6 Months | Incidence of all adverse events and serious adverse events |
| Change from baseline in SF-36 | 6 Months | Change from baseline in SF-36 |
| Proportion of participants with complete reduction of hormone dose | 6 Months | Proportion of participants with complete reduction of hormone dose |
| Proportion of participants taking ≤5mg/ day of hormone | 6 Months | Proportion of participants taking ≤5mg/ day of hormone |
Outcome results
None listed