A Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity, and Preliminary Efficacy of YKST02 as Monotherapy or in Combination With YK012 in Patients With Active or Refractory Systemic Lupus Erythematosus
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Incidence of Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
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
详细描述
This is a single-center, open-label clinical trial evaluating YKST02 administered alone or in combination with YK012 in participants with active or refractory systemic lupus erythematosus (SLE). The study is designed to assess safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary efficacy.
The study consists of two cohorts:
Cohort 1 (YKST02 Monotherapy):
Participants will receive YKST02 as a single agent to evaluate its safety, tolerability, and preliminary efficacy.
Cohort 2 (Combination Therapy):
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
- •Able and willing to provide written informed consent and comply with study procedures.
排除标准
- •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.
- •Presence of other active autoimmune diseases or inflammatory conditions (except secondary Sjögren's syndrome) that may interfere with assessment of SLE disease activity.
- •History of major organ transplantation.
- •History of malignancy within the past 5 years (except adequately treated low-risk cancers).
- •Clinically significant or uncontrolled cardiovascular, cerebrovascular, neurological, hepatic, renal, hematologic, or metabolic diseases.
- •Active or uncontrolled infections, including tuberculosis (active or untreated latent), hepatitis B or C, human immunodeficiency virus (HIV), or other clinically significant infections.
- •Active or severe neuropsychiatric conditions that may interfere with study participation.
- •Uncontrolled hypertension or clinically significant electrocardiogram abnormalities (including prolonged QT interval).
- •Clinically significant abnormal laboratory findings at screening (e.g., severe cytopenias, impaired liver or renal function, or coagulation abnormalities).
- •Recent major surgery or planned surgery during the study period.
- •Recent use of investigational agents or participation in another clinical study within 4 weeks prior to enrollment.
- •Pregnant or breastfeeding women, or women of childbearing potential unwilling to use effective contraception during the study and for an appropriate period after the last dose.
- •Any other condition that, in the opinion of the investigator, would make the participant unsuitable for the study.
研究组 & 干预措施
YKST02 + YK012 Combination Therapy
Participants receive YKST02 in combination with YK012 via intravenous (IV) infusion. Treatment includes induction dosing followed by continued administration at protocol-defined dose levels.
干预措施: YK012 (Drug)
YKST02 + YK012 Combination Therapy
Participants receive YKST02 in combination with YK012 via intravenous (IV) infusion. Treatment includes induction dosing followed by continued administration at protocol-defined dose levels.
干预措施: YKST02 (Drug)
YKST02 Monotherapy
Participants receive YKST02 as monotherapy via intravenous (IV) infusion. Treatment includes induction doses followed by target dose administration.
干预措施: YKST02 (Drug)
结局指标
主要结局
Incidence of Dose-Limiting Toxicities (DLTs)
时间窗: From first dose through Day 35
Number and proportion of participants experiencing dose-limiting toxicities (DLTs) as defined in the protocol.
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From first dose up to Week 49
Number and proportion of participants experiencing adverse events (AEs) and serious adverse events (SAEs), graded according to CTCAE criteria.
次要结局
- Changes in Peripheral B Cell and T Cell Populations(From baseline up to Week 49)
- Pharmacokinetic (PK) Parameters(From first dose up to Week 49)
- Change from Baseline in Urinary Protein(From baseline up to Week 49)
- Change from Baseline in Anti-dsDNA Antibodies(From baseline up to Week 49)
- Change from Baseline in Complement Levels (C3 and C4)(From baseline up to Week 49)
- Change from Baseline in Immunoglobulin Levels (IgG, IgM, IgA)(From baseline up to Week 49)
- Incidence of Anti-Drug Antibodies (ADA)(From first dose up to Week 49)
- Systemic Lupus Erythematosus Responder Index-4 (SRI-4) Response Rate(Weeks 12, 24, and 48)
- British Isles Lupus Assessment Group-Based Composite Lupus Assessment (BICLA) Response Rate(Weeks 12, 24, and 48)
- Definitions Of Remission In Systemic Lupus Erythematosus (DORIS) Remission Rate(Weeks 12, 24, and 48)
- Lupus Low Disease Activity State (LLDAS) Achievement Rate(Weeks 12, 24, and 48)
- Cutaneous Lupus Erythematosus Disease Area and Severity Index 50 (CLASI-50) Response Rate(Up to Week 49)
- Joint Response Rate(From baseline up to Week 49)
- Glucocorticoid Dose Reduction(Weeks 12, 24, and 48)
- Time to Disease Flare After Achieving LLDAS(Up to Week 49)
- Change from Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)(From baseline up to Week 49)
- Change from Baseline in British Isles Lupus Assessment Group 2004 Index (BILAG-2004)(From baseline up to Week 49)
- Change from Baseline in Physician's Global Assessment (PGA)(From baseline up to Week 49)
- Change from Baseline in Patient-Reported Outcomes (Quality of Life and Fatigue)(From baseline up to Week 49)
研究者
Qiubai Li
Professor and Chief Physician, Head of Rheumatology Department
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology