A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of YKST02 in Participants With Primary IgA Nephropathy
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The goal of this clinical trial is to evaluate the safety and tolerability of YKST02 and to explore its potential to treat adults with primary IgA nephropathy (IgAN). The study will also assess how the drug moves through the body and how it affects the immune system.
The main questions it aims to answer are:
- Is YKST02 safe and well tolerated?
- Does YKST02 reduce protein levels in the urine?
- How does YKST02 behave in the body (pharmacokinetics, PK)?
- How does YKST02 affect the immune system (pharmacodynamics, PD)? Participants are adults with IgAN who have persistent proteinuria despite standard treatment.
Participants will:
- Receive YKST02 by intravenous (IV) infusion
- Be monitored after each dose for safety
- Attend clinic visits for safety assessments and laboratory tests
- Provide blood and urine samples during the study and follow-up period
详细描述
This is a single-center, open-label, dose-escalation clinical trial designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary efficacy of YKST02 in adults with primary IgA nephropathy (IgAN).
Eligible participants are adults with IgAN and persistent proteinuria despite standard-of-care treatment.
The study consists of a screening period, a treatment period, and a follow-up period. During the treatment period, YKST02 will be administered by intravenous infusion. Dose levels and dosing schedules may be adjusted based on safety, tolerability, and emerging data to support dose escalation and determination of an appropriate dose level.
Safety assessments will include monitoring of adverse events, clinical laboratory evaluations, vital signs, and other relevant clinical parameters. Pharmacokinetic evaluations will characterize the concentration-time profile of YKST02. Pharmacodynamic and biomarker assessments will evaluate the biological activity of YKST02 and its effects on immune-related pathways.
Immunogenicity will be assessed by evaluating anti-drug antibodies. Preliminary efficacy will be explored using clinical measures relevant to IgAN.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Diagnosis of primary IgA nephropathy (IgAN)
- •Proteinuria above a protocol-defined threshold at screening
- •Receiving stable standard-of-care therapy for IgAN for an adequate duration prior to enrollment, unless contraindicated or not tolerated
- •Women of childbearing potential must have a negative pregnancy test prior to study drug administration and agree to use effective contraception; male participants must agree to use effective contraception
- •Able to understand the study procedures and provide written informed consent
排除标准
- •Secondary IgA nephropathy (e.g., associated with liver disease, autoimmune disorders, infections, or other systemic conditions)
- •Other clinically significant renal diseases unrelated to IgAN (e.g., diabetic nephropathy, lupus nephritis, vasculitis)
- •Nephrotic syndrome considered unsuitable for study participation
- •Rapidly progressive glomerulonephritis or rapidly declining renal function
- •Estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m²
- •Immunodeficiency or low immunoglobulin G (IgG) levels below normal
- •Clinically significant abnormal laboratory findings (e.g., hematologic, hepatic, or coagulation abnormalities)
- •Requirement for systemic corticosteroids for concomitant conditions
- •Use of immunosuppressive, targeted, or biologic therapies within a defined period prior to screening or anticipated use during the study
- •Prior treatment with B-cell-depleting or other targeted biologic therapies within a defined period
- •History of demyelinating disorders (e.g., multiple sclerosis)
- •Clinically significant cardiovascular or cerebrovascular disease within 6 months prior to screening
- •History of organ transplantation or planned transplantation during the study
- •Current dialysis or anticipated need for dialysis during the study
- •Major surgery within 4 weeks prior to screening or planned during the study
- •Active infection requiring systemic therapy, recent serious infection, or chronic/recurrent infections
- •Known active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection
- •Active or untreated latent tuberculosis
- •History of splenectomy
- •Uncontrolled comorbidities (e.g., poorly controlled hypertension or diabetes)
- •Malignancy within the past 5 years, except adequately treated non-invasive cancers
- •Known hypersensitivity to YKST02 or its components
- •Receipt of another investigational product within 4 weeks or 5 half-lives (whichever is longer) prior to screening
- •Receipt of live or attenuated vaccines within 4 weeks prior to screening or planned during the study
- •Any condition that, in the investigator's judgment, would make the participant unsuitable for the study
研究组 & 干预措施
YKST02
Participants receive YKST02 administered by intravenous infusion in this single-arm, open-label, dose-escalation study. Participants receive an initial dosing phase followed by subsequent administrations at escalating dose levels. Dose levels and dosing schedules may be adjusted based on safety, tolerability, and pharmacokinetic/pharmacodynamic (PK/PD) data. A follow-up period is included for safety and efficacy assessments.
干预措施: YKST02 (Drug)
结局指标
主要结局
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From first dose through Week 25
Safety will be assessed by the incidence and severity of adverse events (AEs) and serious adverse events (SAEs).
Change from Baseline in UPCR
时间窗: From baseline through Week 25
Efficacy will be evaluated by the change from baseline in urine protein-to-creatinine ratio (UPCR).
Change from Baseline in eGFR
时间窗: From baseline through Week 25
Efficacy will be evaluated by the change from baseline in estimated glomerular filtration rate (eGFR).
Change from Baseline in Urinary Red Blood Cells
时间窗: From baseline through Week 25
Efficacy will be evaluated by the change from baseline in urinary red blood cells.
次要结局
- Area Under the Concentration-Time Curve (AUC) of YKST02(From first dose through Week 25)
- Maximum Observed Concentration (Cmax) of YKST02(From first dose through Week 25)
- Half-life (t1/2) of YKST02(From first dose through Week 25)
- Change from Baseline in Gd-IgA1(From baseline through Week 24.)
- Change from Baseline in Serum Immunoglobulin Levels(From baseline through Week 24)
- Change from Baseline in Complement Levels(From baseline through Week 24)
- Immunogenicity of YKST02(From baseline through Week 25)
- Changes in Lymphocyte Subsets(From baseline through Week 24)
- Changes in Lymphocyte Activation Markers(From baseline through Week 24)
- Changes in Cytokine Levels(From baseline through Week 24)
研究者
Qiubai Li
Professor and Chief Physician, Head of Rheumatology Department
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology