Systemic Lupus Erythematosus
Conditions
Interventions
Experimental group:KN5501 monotherapy
Sponsors
Peking Union Medical College Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Aged 18~70(including thresholds) when obtaining informed consent; 2. Body weight > 40.0 kg at screening; 3. Refractory SLE patients with moderate to severe activity, meeting all the following criteria. (1) Diagnosed with SLE according to the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria, with a disease duration of >=6 months; (2) At screening, at least one of the following criteria must be met: Positive antinuclear antibody (ANA) with a titer >1:80; or Anti-dsDNA antibody level above the laboratory's normal reference range (excluding borderline values); or Anti-Sm antibody level above the laboratory's normal reference range (excluding borderline values); (3) At screening, SLE with or without lupus nephritis having a SLEDAI-2000 score >=8, or severe refractory SLE-ITP (defined as platelet count = 1.5×10^9/L, Hb >= 80g/L, and PLT >= 50×10^9/L(Not applicable, if it is ITP due to active SLE disease which is judged by investigator); 5. Adequate liver, kidney, lung and heart function at screening, defined as: (1) Serum ALT and AST = 50 mL/min; (4) Oxygen saturation >= 92% on room air without supplemental oxygen; (5) Left ventricular ejection fraction >= 50%; 6. The date of last supportive therapy of hemopoietic growth factor(including EPO, G-CSF, GM-CSF and TPO, etc.)should be at least 2 weeks before screening visit, the last date of PLT infusion should be at least one week before screening visit, and the last date of RBC infusion should be at least 2 weeks before screening visit; 7. The number of CD19+ B cells in peripheral blood > 5 cells per microliter at screening; 8. Negative serum pregnancy test for WOCBPs at screening. Male or Female trial participants of child bearing potential should utilize efficient contraceptive measures from ICF signing until at least one year since the last dose, and promise not to donate ovums or sperms until at least one year since the last dose.
Exclusion criteria
Exclusion criteria: 1. Hypersensitive or allergic to any components of KN5501(e.g. DEXTRAN 40) or other trial interventions including fludarabine, cyclophosphamide, and tocilizumab, or having ever experienced severe anaphylaxis; 2. Severe lupus nephritis patients, defined as proteinuria >=3.5g/24h or a history of renal replacement therapy. Or high risk of progressive LN disease which will probably require induced intensive treatment; 3. CNS affected, including but not limited to lupus encephalopathy, seizure, strock(ischemic or hemorrhagic), dementia, cerebellar disease, organic brain syndrome, encephalitis, CNS vasculitis, or mental disease; 4. Severe lung disease, e.g. pulmonary hypertension >= grade 3(WHO), or requiring mask oxygen therapy or ventilator-assisted breathing(non-invasive or invasive) ; 5. Unstable cardiovascular system, e.g. myocardial infarction within 6 months before screening, unstable angina within 3 months before screening, uncontrolled and clinically significant ventricular arrhythmia(including ventricular tachycardia, ventricular fibrillation, or TdP), second-degree atrioventricular block of Mobitz type II or third-degree atrioventricular block, congestive heart failure with New York Heart Association class >= 3; poorly controlled hypertension (SBP > 160 mmHg and/or DBP > 100 mmHg), or accompanied by hypertensive crisis or hypertensive encephalopathy; 6. Malignancy within 5 years before screening, excluding tumors with negligible risk of metastasis or death that are curable, such as radically treated non-melanoma skin cancer, localized prostate cancer, biopsy-confirmed cervical carcinoma in situ or squamous intraepithelial lesions detected by cervical smears, and completely resected ductal carcinoma in situ of the breast; 7. Severe infections requiring intravenous anti-infection treatment within 14 days before planned lymphodepletion, however preventive therapy is permitted; 8. Active or latent tuberculosis at screening, regardless of whether adequate treatment was completed; 9. HBV or HCV infection at screening. If positve HBsAg and/or HBcAb, HBV-DNA should be tested to confirm. If positive HCV-Ab, HCV-RNA should be tested to confirm; 10. Active HIV infection history, or positive serum HIV antigen or antibody test, or positive antibody test for Treponema Pallidum at screening; 11. Received any of the following treatments within the specified time frame before lymphodepleting chemotherapy: a) Autologous or allogeneic stem cell transplantation within 3 months; b) Major surgery or administration of live vaccines within 4 weeks; c) Participation in any clinical trial involving investigational drugs within 4 weeks, or within 5 times the half-life of the investigational drug after participating in a clinical trial (whichever is longer); d) Prior treatment with T-cell engagers (TCEs), CAR-T, or CAR-NK cell infusion at any time; 12. Pregnant or lactating women; 13. Any life-threatening disease, medical condition, or organ system dysfunction, as determined by the investigator, that may affect the participant's safety or study compliance.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose limiting toxicity ;Adverse events, PE, vital signs, lab and 12-ECG; | — |
Secondary
| Measure | Time frame |
|---|---|
| PK parameters, including Tmax, Cmax, AUC and duration of retention.;PD parameters, including CD19+ B cells, cytokines, auto-antibodies, immunoglobulins, supplements, and B cell subsets. ;Remission rate of DORIS 2021;Response rate of LLDAS; | — |
Countries
China
Contacts
Public ContactLi Mengtao
Peking Union Medical College Hospital
Outcome results
None listed