Development and Validation of a Gd-IgA1 Guided Precision Therapy System for Targeted Therapeutic Strategies of IgA Nephropathy： An Open-label, Random Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 374
- 试验地点
- 1
- 主要终点
- Mean change in 24-hour proteinuria from baseline at the end of follow-up
研究概览
简要总结
The goal of this open-label, randomized study is to evaluate the efficacy and safety of the personalized treatment model in which Gd-IgA1 is dynamically monitored to guide medication adjustment in progressive IgAN patients treated with Nefecon or telitacicept.
Researchers will compare two groups of participants: those who have Gd-IgA1 checked regularly during treatment, and those who do not. This is to find out if regular Gd-IgA1 checks can help doctors adjust medication better and get better treatment results.
详细描述
IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and a leading cause of end-stage renal disease (ESRD) in young adults. Even with standard supportive care, many patients still experience worsening renal function and eventually develop ESRD.
The widely accepted multi-hit pathogenesis of IgAN recognizes the production of galactose-deficient IgA1 (Gd-IgA1) as the key step. Pathogenic Gd-IgA1 forms immune complexes that deposit in the kidney, triggering inflammation and renal damage, which serves as a target for new regimens.
Two novel targeted therapies have shown positive clinical effects for IgAN:
- Budesonide Enteric Capsules (Nefecon): A gut-targeted oral preparation that releases drugs in the ileocecal region, reducing Gd-IgA1 production and renal immune deposition to protect renal function.
- Telitacicept: A dual Blys/APRIL inhibitor that blocks the proliferation of B cells to reduce pathogenic Gd-IgA1 production.
However, the clinical effects of these novel therapies usually take time to appear (e.g., a significant drop in urinary protein with Nefecon is often seen 3 to 6 months after treatment). Early, sensitive indicators reflecting therapeutic effects are needed to enable timely adjustment of treatment plans.
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
- 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
- •Male or female, between 18 and 75 years age;
- •Biopsy confirmed diagnosis of primary IgA nephropathy or IgA Vasculitis-Associated Nephritis;
- •Persistent proteinuria, defined as: two separate measurements (with an interval of ≥ 4 weeks) of 24-hour urinary protein excretion (24hUTP) ≥ 0.5 g/day, or urine protein-to-creatinine ratio (UPCR) ≥ 0.44 g/g;
- •Estimated glomerular filtration rate (eGFR) (CKD-EPI) ≥ 30 ml/min per 1.73m^2;
- •Have received the angiotensin converting enzyme Inhibitors(ACEI) / angiotensin receptor blocker(ARB) standard treatment for 4 weeks prior to randomization;
- •Intending to receive or having received Nefecon or telitacicept treatment for ≤ 2 weeks at the time of screening.
排除标准
- •Secondary IgA nephropathy (excluding IgA vasculitis) caused by ankylosing spondylitis, systemic lupus erythematosus, viral hepatitis, liver cirrhosis, etc.;
- •With a known history or clinical evidence of concurrent renal diseases other than IgA nephropathy;
- •Treating with systemic corticosteroids or immunosuppressants including cyclophosphamide, azathioprine, mycophenolate mofetil, tacrolimus, cyclosporine, rituximab, etc. within 3 months prior to randomizing;
- •Have initiated or had a dose adjustment of leflunomide, tripterygium wilfordii or hydroxychloroquine within 3 months prior to randomizing;
- •Active tuberculosis or latent carrier without treatment;
- •Herpes zoster infected patients or patients with positive HIV antibody, positive HCV antibody or HBV infection (According to the HBV screening test, a) the HBsAg-positive; b) HBsAg-negative and HBcAb-positive, the HBV-DNA should be tested to determine the situation: the HBV-DNA positive subjects should be excluded, while the HBV-DNA negative subjects can participated in.)
- •Suffering from following gastrointestinal diseases: gastric ulcer bleeding within the past 6 months, active inflammatory bowel disease, a history of major gastrointestinal surgery (e.g., gastrectomy, gastroenterostomy, or bowel resection), or pancreatic injury/pancreatitis within the past 6 months;
- •A confirmed history of osteoporosis or osteonecrosis of the femoral head;
- •Type 1 or type 2 diabetes with poor glycemic control (HbA1c > 8%);
- •Body mass index (BMI) < 18.5 kg/m².;
- •Systolic blood pressure (SBP) > 180 mmHg or diastolic blood pressure (DBP) > 110 mmHg;
- •Decreased lymphocyte count (absolute value < 1.1 × 10⁹/L) or decreased immunoglobulin G (IgG < 6 g/L).
- •Hepatic dysfunction, meeting any of the following: a) Child-Pugh Class C liver dysfunction; b) ALT or AST > 2 × upper limit of normal (ULN), or total bilirubin > 2 × ULN at screening; c) history of hepatic encephalopathy, esophageal varices, or portosystemic shunt surgery;
- •Evidence of urinary tract obstruction or dysuria.
- •A history of solid organ transplantation, hematopoietic stem cell/cell/bone marrow transplantation, or kidney transplantation.
- •Pregnancy, lactation, female participants with childbearing plans during the trial or within 6 months of its completion, and male participants planning to conceive or donate sperm during the trial or within 3 months of its completion;
- •With a history of malignant tumors within the past 5 years (excluding cutaneous squamous cell carcinoma or basal cell carcinoma);
- •Allergy to human-derived biologics;
- •Nephrotoxic drugs is unavoidable during the study period;
- •Not suitable for the study judged by investigator.
研究组 & 干预措施
Participants who have Gd-IgA1 checked regularly during treatment
Based on the combined results of reductions in urinary protein, Gd-IgA1 levels and other parameters, clinicians can thus evaluate early treatment efficacy and make timely medication adjustments - either continuing the original treatment, increasing the dose, or switching to another medication.
干预措施: Gd-IgA1 monitoring (Diagnostic Test)
Participants who do not have Gd-IgA1 checked during treatment
Clinicians will make medication adjustment base on urinary protein and other laboratory test parameters if necessary.
结局指标
主要结局
Mean change in 24-hour proteinuria from baseline at the end of follow-up
时间窗: From enrollment to the end of follow-up at 12 months
次要结局
- Mean change in 24-hour proteinuria from baseline at the midpoint of follow-up(From enrollment to the middle of follow-up period at 6 months)
- Change in estimated glomerular filtration rate (eGFR)(From enrollment to the end of follow-up at 12 months)
- Complete remission of proteinuria(From enrollment to the midpoint of follow-up (6 months) and over the entire 12-month follow-up period)
- Immunosuppressant exposure measures(From enrollment to the end of follow-up at 12 months)
研究者
Hong Zhang
Chief physician and Professor
Peking University First Hospital