A Multicenter, Randomised, Double-Blinded, Placebo-Controlled Study to Evaluate the Safety and Efficacy of STL303 In Patients With Primary Immunoglobulin A (IgA) Nephropathy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 15
- 试验地点
- 8
- 主要终点
- Treatment emergent adverse events (TEAEs), adverse events (AEs) and serious adverse events (SAEs)
研究概览
简要总结
This is a multicenter, randomized, double-blind, placebo controlled Phase IIb study to explore the efficacy and safety of STL303 capsules in IgAN patients. About 15 patients dignosed with primary IgAN will be enrolled and randomized to three cohorts and take different dosage of STL303 or placebo capsules orally according to protocol.
详细描述
This is a multicenter, randomized, double-blind, placebo-controlled study in approximately 15 patients with primary IgA nephropathy (IgAN).
Participants receiving background therapy will be randomized in a 1:1:1 ratio to receive STL303 capsules dose 1, dose 2, or placebo, administered orally once daily.
The study aims to evaluate the efficacy and safety of STL303 in patients with primary IgAN and to identify the optimal clinical dose.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients aged 18 years and older, with primary IgAN confirmed by renal biopsy:
- •eGFR (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula) greater than or equal to 30 mL/min/1.73 m2 at screening and after completion of run-in.
- •UPCR greater than or equal to 0.75 g/g at screening and after completion of run-in.
- •Vaccinated against Neisseria meningitidis and Streptococcus pneumoniae before the first dose.
- •Have received stable treatment with RASis (ACEi or ARB) at the maximum recommended dose or MTD for at least 90 days prior to the first dose.
- •If the patient has been treated with SGLT2i, diuretics, other antihypertensive treatments, ERA, and/or hydroxychloroquine for IgAN prior to the first dose, the drug should also be used stably for at least 90 days.
排除标准
- •Secondary IgAN or unclear exclusion of secondary causes.
- •Rapidly progressive IgAN (eGFR decline greater than or equal to 50% in 3 months, or less than 50% but at high risk).
- •Other systemic diseases causing proteinuria/CKD or severe urinary obstruction.
- •Known or suspected immunodeficiency or hereditary complement deficiency.
- •Any organ transplant recipients except corneal.
- •Poorly controlled blood pressure (SBP greater than 150 or DBP great than 90).
- •Use of immunosuppressive drugs within 90 days or 5 half-lives.
- •Prior oral budesonide (Nefecon/Tarpeyo/Kinpeygo) within 6 months.
- •Prior complement inhibitors within 30 days, 5 half-lives, or residual effect period.
- •Major systemic diseases preventing participation (e.g., NYHA IV, severe pulmonary disease).
- •Significantly abnormal liver function (greater than 3× ULN enzymes or greater than 2× ULN bilirubin).
- •QTcF greater than 500 ms.
- •History of malignancy within 5 years (exceptions apply).
- •History of meningococcal, pneumococcal, or Hib infection.
- •Chronic/recurrent infections in past year (e.g., liver abscess, pyelonephritis).
- •Active systemic infections within 2 weeks or fever greater than 38°C within 7 days.
研究组 & 干预措施
Placebo
Participants will receive placebo
干预措施: Placebo capsule (Drug)
STL303 Dose Level 2
Participants will receive STL303 dose level 2
干预措施: STL303 (Drug)
STL303 dose level 1
Participants will receive STL303 dose level 1
干预措施: STL303 (Drug)
结局指标
主要结局
Treatment emergent adverse events (TEAEs), adverse events (AEs) and serious adverse events (SAEs)
时间窗: Adverse events will be closely monitored, and participants will report to the clinic on Days 7, 14, 30, 45, 60, 90, 135 and at end of treatment on Day 180. On Day 210 an End of study safety follow up will also be conducted.
All participants will be observed for any AE during the clinical study, including abnormalities in clinical symptoms and vital signs, physical examination, laboratory tests, and 12-lead ECG. Incidence, severity, and relationship of TEAEs and serious adverse events (SAEs) to STL303. Possible adverse events include: palpitations, nausea, vomiting, dizziness, sore throat, upper respiratory infection, loss of appetite, high temperature, chest discomfort, weakness, rash, headache, lethargy (feeling tired and low on energy) and urinary tract infection.
次要结局
- Change from baseline urine protein-to-creatinine ratio (UPCR)(24-hour urine collection pre-dose on Days 1 (baseline), 30, 60, 90 and 180)
- Change in UPCR(24-hour urine collection pre-dose on Days 1 (baseline), 30, 60 and 90)
- Change in urine albumin-to-creatinine ratio (UACR)(24-hour urine collection pre-dose on Days 1 (baseline), 30, 60, 90 and 180)
- Change in blood creatinine level(Blood sampling pre-dose on Days 1 (baseline), 14, 30, 45, 60, 90 and 180)
- Change in eGFR slope(Blood sampling pre-dose on Days 1 (baseline), 14, 30, 45, 60, 90 and 180)
- Maximum Concentration at steady-state (Tmax, ss) of STL303(Pre-dose on Days 1, 7, 14, 60, 90, 135, and 180. On Day 30 pre-dose and at 1 hour (± 5 minutes), 2 hours (± 5 minutes), 4 hours (± 10 minutes), 6 hours (± 10 minutes), 8 hours (± 10 minutes), 12 hours (± 10 minutes), and 24 hours (± 1 hour) after dosing)
- Maximum plasma concentration at steady-state (Cmax, ss) of STL303(Pre-dose on Days 1, 7, 14, 60, 90, 135, and 180. On Day 30 pre-dose and at 1 hour (± 5 minutes), 2 hours (± 5 minutes), 4 hours (± 10 minutes), 6 hours (± 10 minutes), 8 hours (± 10 minutes), 12 hours (± 10 minutes), and 24 hours (± 1 hour) after dosing)
- Trough plasma concentration at steady-state of STL303(Pre-dose on Days 1, 7, 14, 60, 90, 135, and 180. On Day 30 pre-dose and at 1 hour (± 5 minutes), 2 hours (± 5 minutes), 4 hours (± 10 minutes), 6 hours (± 10 minutes), 8 hours (± 10 minutes), 12 hours (± 10 minutes), and 24 hours (± 1 hour) after dosing)
- Area under plasma concentration-time curve for STL303(Pre-dose on Days 1, 7, 14, 60, 90, 135, and 180. On Day 30 pre-dose and at 1 hour (± 5 minutes), 2 hours (± 5 minutes), 4 hours (± 10 minutes), 6 hours (± 10 minutes), 8 hours (± 10 minutes), 12 hours (± 10 minutes), and 24 hours (± 1 hour) after dosing)
- Change urine protein excretion (UPE),(24-hour urine collection pre-dose Days 1 (baseline), 30, 60, 90 and 180)
- Alternative Pathway Activity (Wieslab Assay)(Pre-dose and post-dose on Day 1 and Day 14; pre-dose on Days 7, 60, 90, 135, and 180; intensive time points (pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours post-dose) on Day 30)
- Urinary Complement Biomarker C3a(Day 1, Day 7 (FMV only), Day 14 (FMV only), Day 30, Day 60, Day 90, Day 135 (FMV only), and Day 180 (all pre-dose))
- Plasma Soluble Terminal Complement Complex (sC5b-9)(Day 1 through Day 180 (pre-dose at scheduled visits))
- Complement Factor B Cleavage Fragment (Bb)(Day 1 through Day 180 (pre-dose at scheduled visits))