The goal of this clinical trial to investigate the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary efficacy of BCD-256 alone and in combination with anti-CD20 therapy (divozilimab) as second- or later-line therapy in subjects with skin lesions due to mild to moderate systemic lupus erythematosus. The study consists of the first stage (cohorts 1-5) and the second stage (cohorts A - D).
Signed informed consent to participate in the study and the subject's ability to comply with the requirements of the clinical study protocol.
Age from 18 to 70 years at the time of signing the informed consent form.
Body weight from 45 kg, BMI of 18 to 30 kg/m2.
Diagnosed with SLE in accordance with at least 4 classification criteria of SLICC (2012), including 1 clinical sign or 1 immunological manifestation.
Presence of active lupus nephritis or chronic kidney disease (urine protein to creatinine ratio >2.0 or estimated glomerular filtration rate < 30 mL/min/1.73m2).
A history of CNS associated with SLE, involvement including, but not limited to, the following symptoms: seizures, impaired consciousness, psychosis, delirium or confusion, aseptic meningitis, ascending or transverse myelitis, chorea, cerebellar ataxia, multiple mononeuritis, or demyelinating syndromes.
The presence of uncontrolled neuropsychiatric disorders, severe depression and/or suicide attempts at the time of signing the ICF or within 1 year prior to signing the informed consent form, as well as the risk of suicide and/or any mental illness as assessed by the investigator.
A history of antiphospholipid syndrome.
Sequential
BCD-256
DrugAnti-BDCA2 human monoclonal antibody, concentrate for solution for infusion intravenously
BCD-256
DrugAnti-BDCA2 human monoclonal antibody, concentrate for solution for infusion intravenously
BCD-256
DrugAnti-BDCA2 human monoclonal antibody, concentrate for solution for infusion intravenously
Divozilimab
DrugAnt-CD0 human monoclonal antibody, Concentrate for solution for infusion intravenously
BCD-256
DrugAnti-BDCA2 human monoclonal antibody, concentrate for solution for infusion intravenously
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Treatment groupsSee each treatment group below.
Proportion of subjects with adverse events
Proportion of subjects with serious adverse events
Proportion of subjects with treatment-related adverse events
Proportion of subjects with CTCAE 5.0 grade ≥ 3 adverse events
Time to Reach Maximum Observed Concentration (Tmax) in the first cycle of therapy
Terminal Elimination Half-Life (t1/2) in the first cycle of therapy
Area Under the Concentration-Time Curve from Time 0 to ending at the last measured concentration at time t (AUC0-t) in the first cycle of therapy
Area Under the Concentration-Time Curve from Time 0 Extrapolated to Infinity (AUC0-∞) in the first cycle of therapy
Area Under the plasma-concentration versus time curve (AUC) over one dosing interval (τ) when steady-state (ss) conditions have been reached, representing the average drug exposure during that interval n the third cycle of therapy
Maximum Observed Concentration (Cmax) in the first cycle of therapy
