Study of YK012 in Moderate to Severe Systemic Lupus Erythematosus

A Phase Ib/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of YK012 in the Treatment of Moderate to Severe Systemic Lupus Erythematosus

The goal of this clinical trial is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of YK012 in participants with Moderate to Severe Systemic Lupus Erythematosus (SLE).

This clinical trial consists of Phase Ib and Phase II. Phase Ib consists of dose escalation stage and dose expansion stage. The main goal of dose escalation stage is to evaluate the safety and tolerability of YK012 in participants with Moderate to Severe Systemic Lupus Erythematosus (SLE), and the main goal of dose expansion stage is to evaluate the safety, tolerability and effectiveness in reducing disease activity of YK012 in participants with SLE. The main goal of phase II is to assess the efficacy of YK012 in participants with Moderate to Severe SLE. Pharmacokinetics, pharmacodynamics and immunogenicity of YK012 in participants are evaluated as secondary objectives in both phases.

Inclusion Criteria:

• Aged 18 to 75 years (inclusive) at screening, regardless of sex
• Meet the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE, with a confirmed SLE diagnosis for at least 24 weeks at screening
• Positive for anti-dsDNA antibody and/or antinuclear antibody (ANA) and/or anti-Smith antibody at screening, as determined using the local laboratory's reference ranges at the study site
• Medium to high disease activity at screening, defined as: Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≥7
• Receiving stable background therapy at screening
• Capable of understanding and voluntarily participating in this clinical trial, having provided written informed consent, and able to comply with scheduled visits, treatments, examinations, and other study procedures.

Exclusion Criteria:

• Known allergy to monoclonal antibodies or exogenous human immunoglobulins, or hypersensitivity to the investigational drug or any of its components
• Received any anti-CD19/CD20 therapy or any B-cell depleting agents within 6 months prior to enrollment, or B-cell stimulatory factor inhibitors within 3 months or 5 half-lives prior to enrollment
• Received TNF inhibitors, interleukin receptor blockers, other small molecules or biologics within 3 months or 5 half-lives prior to enrollment
• Received intravenous immunoglobulins or plasmapheresis within 3 months prior to enrollment
• Used traditional Chinese medicines/herbal preparations for SLE treatment containing within 2 weeks prior to enrollment
• Received live or attenuated vaccines within 1 month prior to enrollment
• Has other autoimmune diseases, inflammatory joint diseases, or skin disorders (other than SLE) that may interfere with disease activity assessment
• History of malignancy within 5 years before screening, except for cured cases with no recurrence for at least 5 years, such as basal cell or squamous cell skin cancer, cervical carcinoma in situ, ductal carcinoma in situ of breast, or papillary thyroid cancer
• Clinically significant cardiovascular/cerebrovascular diseases within 6 months prior to screening
• Presence of QTcF interval prolongation on electrocardiogram (ECG)
• Presence of poorly controlled hypertension at screening
• History of non-SLE conditions requiring oral/intravenous/intramuscular/subcutaneous corticosteroid therapy (>2 weeks) within 6 months prior to enrollment
• Active tuberculosis at screening or untreated latent tuberculosis
• History of solid organ or bone marrow transplantation
• Presence of active infections
• Lupus nephritis requiring protocol-prohibited medications as assessed by the investigator
• Uncontrolled lupus crisis within 8 weeks prior to screening
• History of central nervous system (CNS) disorders
• Presence of clinically unstable or uncontrolled medical conditions at screening
• Presence of clinically significant abnormal laboratory test results
• Presence of active viral infections (e.g., hepatitis B, hepatitis C, HIV, or active syphilis)
• Had major surgery within 4 weeks prior to enrollment or planned during study;
• Participation in other interventional clinical trials within 4 weeks prior to enrollment
• Pregnant or lactating women, or individuals with pregnancy plans during the study and within a specified period after treatment who are unwilling to use effective contraception
• Other conditions deemed by investigators to preclude study participation.