A Clinical Study to Evaluate the Initial Efficacy and Safety of Anti-CD38 Monoclonal Antibody (SG301) Subcutaneous Injection in Children With Frequent Relapses or Steroid-Dependent Nephrotic Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 3
- 主要终点
- Incidence and rate of treatment-Emergent Adverse Events
研究概览
简要总结
This is an open - label study to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of SG301 Subcutaneous injection in children with frequently relapsing or steroid - dependent nephrotic syndrome.
详细描述
This study will recruit children aged 6 - 18 with frequently relapsing or steroid - dependent nephrotic syndrome, who have morning urine protein < 1 + or urine protein / creatinine < 0.2 g/g (<20 mg/mmol) for at least three consecutive days after steroid treatment.
The study will stratify participants into two age groups:≥6 - <12 years and≥12 - <18 years. Recruitment will start with the 12 - 18 - year - old group. After collecting sufficient safety and clinical pharmacology data to support moving to lower age groups, the 6 - 12 - year - old group will be recruited. For every 1 to 3 participants enrolled, there will be a phased data review to guide further recruitment.
The trial has three phases: screening (D - 28~D - 1), treatment (12 - week), and follow - up (40 - week). The enrolled participants will be treated with 12 mg/kg SG301 Subcutaneous injection subcutaneously. They will receive weekly injections for the first six weeks, then every two weeks for three times, totaling nine injections.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 6 - 18 years.
- •Steroid-sensitive nephrotic syndrome with frequent relapses (FRNS) or steroid dependence (SDNS).
- •Normal renal function: eGFR≥90 ml/min/1.73m².
- •After steroid treatment, morning urine protein<1 + or urine protein/creatinine<0.2 g/g (<20 mg/mmol) for ≥3 consecutive days.
- •Within 7 days before enrollment, blood tests (without growth factors or transfusions) must meet: hemoglobin>80 g/L; platelets>75×10⁹/L; neutrophils>1.5×10⁹/L.
- •Prothrombin time/INR≤1.5×ULN, unless due to anticoagulation.
- •No Tacrolimus, cyclosporine A, mycophenolate mofetil, belimumab, levamisole, azathioprine, or cyclophosphamide in prior 2 months; no rituximab or obinutuzumab in prior 6 months.
排除标准
- •Family history of nephrotic syndrome, chronic glomerulonephritis, or uremia.
- •Alanine aminotransferase >2×ULN or total bilirubin>2×ULN with a sustained increase for 2 weeks.
- •HBsAg or HBcAb positive with Hepatitis B virus DNA above the lower limit of normal; Hepatitis C virus antibody - positive with Hepatitis C virus RNA positive; HIV antibody - positive.
- •Chronic active infections (e.g., Epstein-Barr Virus, Cytomegalovirus, tuberculosis) that may worsen with steroids/ immunosuppressants.
- •Acute active infection (excluding onychomycosis) requiring systemic antibiotics/antivirals.
- •Secondary nephrotic syndrome (e.g.,immunoglobulin A - associated, lupus nephritis); steroid - resistant nephrotic syndrome (SRNS).
- •Other autoimmune diseases, primary immunodeficiency, or malignancy.
- •Prior anti - cluster of differentiation 38 (CD38) treatment.
- •Live/attenuated vaccine receipt or major surgery (non - diagnostic) within 4 weeks before first dose.
研究组 & 干预措施
SG301 Subcutaneous injection
full - dose prednisone (60 mg/m²/day, up to 80 mg) for remission induction. After 3 days of negative urine protein, start SG301 Subcutaneous injection with steroid tapering. Taper prednisolone to 60 mg/m² (max 80 mg) every other day, reducing by 1/6 every 2 weeks, and stop after 3 months.
干预措施: SG301 Subcutaneous injection (Drug)
结局指标
主要结局
Incidence and rate of treatment-Emergent Adverse Events
时间窗: From baseline through study completion, an average of 1 year
Number and percentage of adverse events which are calculated by worst CTCAE grade by CTCAE 5.0
Relapse free survival rate
时间窗: Average 1 year per subject
Relapse free survival rate at 6 and 12 months
次要结局
- Relapse frequency in times(From baseline through study completion, an average of 1 year)
- Time to Relapse(From baseline through study completion, an average of 1 year)
- SG301 anti-drug antibodies(From baseline through study completion, an average of 1 year)
- pharmacokinetics : Ctrough(From baseline through study completion, an average of 1 year)
- Serum creatinine(From baseline through study completion, an average of 1 year)
- Cumulative corticosteroid dose(From baseline through study completion, an average of 1 year)
- estimated glomerular filtration rate(From baseline through study completion, an average of 1 year)
- Neutralizing antibodies against SG301(From baseline through study completion, an average of 1 year)
研究者
Mao Jianhua
Professor
The Children's Hospital of Zhejiang University School of Medicine