The purpose of this clinical trial is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary efficacy of YKST02 administered alone or in combination with YK012 in participants with active or refractory systemic lupus erythematosus (SLE).
The main questions this study aims to address are:
* Whether YKST02 alone or in combination with YK012 is safe and well tolerated in participants with active or refractory SLE * Whether YKST02 alone or in combination with YK012 demonstrates preliminary efficacy in treating SLE * What the PK and PD characteristics of YKST02 are when administered alone or in combination with YK012 * Whether treatment with YKST02 induces anti-drug antibody responses
Participants will:
* Receive intravenous infusions of YKST02 alone or in combination with YK012 according to the assigned cohort * Undergo safety assessments, including monitoring for adverse events * Provide blood samples for PK, PD, and immunogenicity analyses * Be followed for approximately 49 weeks to assess safety and efficacy
Diagnosed with systemic lupus erythematosus (SLE) according to the 2019 EULAR/ACR classification criteria, with active disease defined as SLEDAI-2K ≥6 at screening, and considered to have inadequate response, intolerance, or ineligibility to standard therapy.
Have received standard therapy for SLE for at least 12 weeks prior to screening (including corticosteroids and at least one immunosuppressant and/or biologic agent), or are intolerant to or unsuitable for such therapies.
Receiving stable background therapy prior to enrollment, including stable doses of corticosteroids (within 2 weeks prior to enrollment), and/or antimalarial agents or one immunosuppressant (within 4 weeks prior to enrollment).
Positive for at least one lupus-related autoantibody at screening (e.g., anti-dsDNA, antinuclear antibody, or anti-Smith antibody).
Known hypersensitivity to monoclonal antibodies, immunoglobulins, or any component of the study drug.
Prior treatment with B cell-depleting therapies, B cell-targeting biologics, or other biologic or targeted therapies within protocol-defined washout periods.
Receipt of intravenous immunoglobulin or plasma exchange within protocol-defined washout periods.
Receipt of live or attenuated vaccines within 4 weeks prior to enrollment.