A Randomized, Double-blind, Placebo-controlled Phase II Clinical Study to Evaluate the Efficacy and Safety of SLN12140 in Adult Patients With Primary IgA Nephropathy
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Mean change from baseline in urine protein-to-creatinine ratio (UPCR)at Week 36
研究概览
简要总结
This study is a randomized, parallel, double-blind, placebo-controlled, subcutaneous administration Phase II dose-exploration clinical trial aimed at evaluating the efficacy, safety, PK, PD, and immunogenicity characteristics of SLN12140 at different doses in IgA nephropathy subjects who have previously received standard treatment (the standard treatment drugs allowed in this study include: angiotensin-converting enzyme inhibitors [ACEi], angiotensin II receptor blockers [ARB], and sodium-glucose co-transporter 2 inhibitors [SGLT2i]) but have poor control.
The study is divided into four stages, including a screening period of up to 8 weeks, an introduction period of up to 12 weeks, a 40-week double-blind period (including a 36-week treatment period and a 4-week safety follow-up period; all subjects in the three dose groups who are willing to continue treatment and are judged by the investigator to potentially benefit from subsequent treatment will enter the open-label extension period for continued treatment after completing the double-blind period), and a 56-week open-label extension period (all subjects in the three dose groups who are willing to continue treatment and are judged by the investigator to potentially benefit from subsequent treatment will continue SLN12140 at the same dose group [the optimal dose], including a 52-week open treatment period and a 4-week safety follow-up period).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subject has fully understood the purpose, nature, methods and potential adverse reactions of this trial, volunteers to participate as a subject, is able to communicate effectively with the investigators, understands and complies with all requirements of this study, and voluntarily signs the Informed Consent Form (ICF) prior to initiation of any study procedures.
- •Male and female subjects aged 18 to 80 years (inclusive) at the time of signing the ICF, with body weight ≥ 50 kg for males and ≥ 45 kg for females; body mass index (BMI) 18.0-35.0 kg/m² (inclusive).
- •Patients with IgA nephropathy confirmed by biopsy within the past 3 years before screening, with renal tubulointerstitial fibrosis < 50%.
- •Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m² during the screening period, calculated using the 2021 creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
- •During the screening period, 24-hour urine protein-to-creatinine ratio (24h UPCR) ≥ 1.0 g/g; after completion of the run-in period, UPCR ≥ 0.75 g/g or urine protein excretion (UPE) ≥ 0.75 g/day.
- •Must have received standard of care therapy for at least 12 weeks (and at a stable dose for at least 4 weeks) prior to the first dose of study medication, and agree to maintain stable dosing throughout the study period. (Note: Permitted standard of care medications in this study include ACEi/ARB and SGLT2i.)
- •Males and women of childbearing potential (WOCBP; as defined by the Clinical Trials Facilitation and Coordination Group [CTFG] 2020) must agree to follow the contraception guidelines specified in the protocol from the screening period until 6 months after the last dose of study medication.
- •The subject is willing to receive quadrivalent meningococcal vaccine and pneumococcal vaccine at least 14 days before dosing (for subjects vaccinated within 14 days before dosing, antibiotic prophylaxis for at least 14 days is required after the first vaccination). Re-vaccination is not required for those who have received quadrivalent meningococcal vaccine within 3 years before the first dose, or pneumococcal vaccine within 5 years before the first dose.
排除标准
- •A known history of hypersensitivity, allergy, or anaphylactic reaction to any component of the investigational product, including hypersensitivity to human, humanized, or murine monoclonal antibodies, or known hypersensitivity to any ingredient of the product.
- •Secondary IgA nephropathy as determined by the investigator, such as that caused by Henoch-Schönlein purpura, systemic lupus erythematosus, hepatitis, ankylosing spondylitis, infection, or other etiologies.
- •Diagnosis of IgA vasculitis.
- •Current presence or history of nephrotic syndrome.
- •Clinical suspicion of IgA nephropathy with rapidly progressive glomerulonephritis in accordance with the Kidney Disease: Improving Global Outcomes (KDIGO) 2025 guidelines (≥50% decline in eGFR within 3 months prior to ICF signature, or a <50% decline but at risk of rapid renal function deterioration as assessed by the investigator).
- •Clinical suspicion or biopsy-confirmed chronic kidney disease caused by any disease other than IgA nephropathy, including other glomerulopathies or podocytopathies.
- •Other protocol-defined exclusion criteria may apply.
研究组 & 干预措施
SLN12140
SLN12140 by subcutaneous (sc) injection:100mg QW; SLN12140 by subcutaneous (sc) injection:200mg QW; SLN12140 by subcutaneous (sc) injection:600mg Q4W;
干预措施: SLN12140 (Drug)
Placebo
Placebo (0.9% sodium chloride solution) will be provided as an injectable solution without active ingredient for 36 weeks.
干预措施: Placebo (Other)
结局指标
主要结局
Mean change from baseline in urine protein-to-creatinine ratio (UPCR)at Week 36
时间窗: Week 36
Change from baseline in Urine protein-to-creatinine ratio (UPCR) by visit.
次要结局
- Mean changes from baseline in quantitative FMV-UACR at weeks 2, 4, 8, 12, 24, and 36.(Weeks 2, 4, 8, 12, 24, and 36.)
- Mean changes from baseline in quantitative first morning void (FMV) UPCR at weeks 2, 4, 8, 12, 24, and 36.(Weeks 2, 4, 8, 12, 24, and 36.)
- Mean change from baseline in urine protein-to-creatinine ratio (UPCR)at Week 24(Week 24)
- Mean change from baseline in urine albumin-to-creatinine ratio (UACR) at Weeks 24, 36;(Weeks 24, 36)
- Mean change from baseline in estimated glomerular filtration rate (eGFR) at Weeks 12, 24, 36(Weeks 12, 24, 36)
- Mean changes from baseline in 24-hour urinary protein excretion (24h-UPE) at weeks 24 and 36.(Weeks 24 and 36)
- Mean changes from baseline in 24-hour urinary albumin excretion (24h-UAE) at weeks 24 and 36.(Weeks 24 and 36)
- Number and severity of treatment-emergent adverse events(106 weeks)
- Incidence of treatment-induced anti-drug antibodies(Weeks 4、8、12、24、36 and 40)
- Pharmacokinetics (PK)parameters of SLN12140: Area Under The Plasma Concentration-time Curve(Baseline through week 92 (predose and postdose))
- PK: Maximum Plasma Concentration (Cmax)(Baseline through week 92( predose and postdose))
- PK: Time To Maximum Concentration (Tmax)(Baseline through week 92( predose and postdose))
- Complement Alternative Pathway (AP) Functional Activity(Baseline through week 92( predose and post dose))
- Complement FP(Baseline through week 92(predose and postdose))