A FIH, single arm, open-label, Investigator Initiated Trial (IIT) study to evaluate the safety and tolerability of EVM18001 in the treatment of active refractory autoimmune diseases (SLE, MG, and SSc), and determine the recommended dose for subsequent treatment. At the same time, the PK/PD characteristics of EVM18001 will be evaluated, preliminary efficacy will be observed, and related biomarkers and immunogenicity will be explored.
The main questions it aims to answer are: * If EVM18001 is safe and tolerate in patients with active refractory autoimmune diseases (SLE, MG, and SSc)? * What the recommended dose for subsequent treatment? * What the PK/PD profiles of EVM18001 in patients with active refractory autoimmune diseases (SLE, MG, and SSc)? * What the efficacy of EVM18001 in patients with active refractory autoimmune diseases (SLE, MG, and SSc)# * What the biomarkers and immunogenicity of EVM18001 in treating of patients with active refractory autoimmune diseases (SLE, MG, and SSc)? Participants will: * Inform the investigator in a timely manner when unable to attend a visit. * Report any changes in their health condition to the study doctor, including discomfort or other health issues during the screening period. * Inform the study doctor of any other medications taken before and during the study; inform the study doctor before starting any new medications. * Be informed of any medications which may be affected by the study drug that should not be used during the study. * Agree to use effective contraception during the study and for 12 months after the last infusion of EVM18001EVM injection.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
All enrolled participants will receive multiple doses of EVM18001 according to the assigned dosage group.
Union hospital Tongji medical college Huazhong university of science and technology
Wuhan, Hubei, China
RECRUITINGEvaluate the safety/tolerability of EVM18001 in patients with SLE/MG/SSc by rates and severity of AE/SAE.
Subsequent recommended dose will be determined by the results of the clinical study.
Time frame: Day 1 ~ Month 24
Determine the subsequent recommended dose of EVM18001 in patients with SLE/MG/SSc.
Subsequent recommended dose will be determined by the results of the clinical study.
Time frame: Day 1~ Month 24
Evaluate the efficacy of EVM18001 in patients with SLE/MG/SSc by proportion of patients get relief during the whole study.
Evaluated by PI
Time frame: Day 1 ~ Month 24
Evaluate the efficacy of EVM18001 in patients with SLE/MG/SSc by Duration of Response (DOR).
Evaluated by PI
Time frame: Day 1 ~ Month 24
Cmax of EVM18001 and CAR-T cells.
Samples will be sent to the central laboratory for testing and analysis. The content of peripheral blood mRNA EVM18001 will be detected by quantitative polymerase chain reaction (qPCR), the concentration of ionizable lipid L84 will be measured by liquid chromatography-mass spectrometry (LCMS), and the pharmacokinetic characteristics after EVM18001 administration will be monitored by detecting peripheral blood CAR-T cells using flow cytometry.
Time frame: Day1~ Day29
AUC0-t of EVM18001 and CAR-T cells.
Samples will be sent to the central laboratory for testing and analysis. The content of peripheral blood mRNA EVM18001 will be detected by quantitative polymerase chain reaction (qPCR), the concentration of ionizable lipid L84 will be measured by liquid chromatography-mass spectrometry (LCMS), and the pharmacokinetic characteristics after EVM18001 administration will be monitored by detecting peripheral blood CAR-T cells using flow cytometry.
Time frame: Day1~ Day29
Detection of CAR expression on the surface of immune cells in peripheral blood.
PD indicator
Time frame: Day1~ Day29
Evaluate the efficacy of EVM18001 in patients with SLE/MG/SSc by proportion of patients relieve after 6 months.
Evaluated by PI
Time frame: Day 1 ~ Month 24
Evaluate the efficacy of EVM18001 in patients with SLE/MG/SSc by proportion of patients get relapse during the whole study.
Evaluated by PI
Time frame: Day 1 ~ Month 24
Evaluate the efficacy of EVM18001 in patients with SLE/MG/SSc by proportion of patients achieving no hormone/immunosuppressant use or low-dose hormone use during the whole study.
Evaluated by PI
Time frame: Day 1 ~ Month 24
PK detection of EVM18001 in peripheral blood.
Samples will be sent to the central laboratory for testing and analysis. The content of peripheral blood mRNA EVM18001 will be detected by quantitative polymerase chain reaction (qPCR), the concentration of ionizable lipid L84 will be measured by liquid chromatography-mass spectrometry (LCMS), and the pharmacokinetic characteristics after EVM18001 administration will be monitored by detecting peripheral blood CAR-T cells using flow cytometry.
Time frame: Day1~ Day29
Tmax of EVM18001 and CAR-T cells.
Samples will be sent to the central laboratory for testing and analysis. The content of peripheral blood mRNA EVM18001 will be detected by quantitative polymerase chain reaction (qPCR), the concentration of ionizable lipid L84 will be measured by liquid chromatography-mass spectrometry (LCMS), and the pharmacokinetic characteristics after EVM18001 administration will be monitored by detecting peripheral blood CAR-T cells using flow cytometry.
Time frame: Day1~ Day29
AUC0-30d of EVM18001 and CAR-T cells.
Samples will be sent to the central laboratory for testing and analysis. The content of peripheral blood mRNA EVM18001 will be detected by quantitative polymerase chain reaction (qPCR), the concentration of ionizable lipid L84 will be measured by liquid chromatography-mass spectrometry (LCMS), and the pharmacokinetic characteristics after EVM18001 administration will be monitored by detecting peripheral blood CAR-T cells using flow cytometry.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Day1~ Day29
Number of decreased B cells in peripheral blood.
PD indicator
Time frame: Day1~ Day29