Precision Medicine Proof of Concept for Tumor Necrosis Factor Inhibition in Focal Segmental Glomerulosclerosis and Treatment Resistant Minimal Change Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 4
- 主要终点
- Change in Urine MCP1/Cr Levels
研究概览
简要总结
Adalimumab, a treatment which blocks tumor necrosis factor (TNF), was tested to see if it changed levels of urine biomarker levels, tissue inhibitor of metalloprotease-1 (TIMP1), and monocyte chemoattractant protein-1 (MCP1). Results may help develop individualized treatment options for future patients with TNF-driven focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Kidney biopsy confirmed Focal Segmental Glomerulosclerosis (FSGS) or Minimal Change Disease (MCD)
- •For Minimal Change Disease patients only, history of resistance to corticosteroid therapy
- •Increased urinary excretion of biomarkers of Tumor Necrosis Factor (TNF) activation (MCP1/Cr and/ or TIMP1/Cr) at study screening
- •eGFR>30 ml/min/1.73 m2 at screening
- •Urine protein:creatinine ratio ≥1.5 g/g at screening
- •Weight >15 kg
- •Stable therapy with angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and oral immunosuppression agents for at least 30 days prior to enrollment
- •Birth control use in females of child bearing potential
- •Informed consent and assent if applicable
排除标准
- •Kidney or other solid organ or bone marrow transplant recipient
- •Allergy or intolerance to investigational agent
- •Secondary Focal Segmental Glomerulosclerosis (FSGS)
- •Severe obesity
- •Live virus vaccine in the past 3 months
- •Malignancy, current or in the past 5 years
- •Active local or systemic bacterial, fungal or viral infection
- •Active or latent Hepatitis B, Hepatitis C, HIV, or tuberculosis
- •History of demyelinating disease, e.g. Multiple Sclerosis or Guillain-Barre
- •History of heart failure
- •Active liver disease
- •Systemic lupus erythematosus or ANA > 1:80
- •History of inflammatory bowel disease, e.g. ulcerative colitis or Crohns disease
- •Cyclophosphamide in past 90 days, Rituximab in the past 180 days
- •Pregnancy or nursing
- •Blood white blood cell count <4,500/mm3; Hg <9 g/dL; Platelet count <150,000/mm3 at enrollment. - Use of an erythropoiesis stimulating agent will not be an exclusion criterion.
- •Concurrent use of interleukin-1 antagonist (Anakinra), other TNF blocking agent, methotrexate or abatacept
- •Diabetes Mellitus
研究组 & 干预措施
adalimumab
Adalimumab dose every other week (study weeks 0, 2, 4, 6, and 8), subcutaneously
干预措施: adalimumab (Drug)
结局指标
主要结局
Change in Urine MCP1/Cr Levels
时间窗: 10 Weeks
MCP1 is an established marker of intra-renal TNF pathway activation. A reduction in MCP1 reflects a reduction in the activation of the TNF pathway in the kidney. Values were measured by enzyme-linked immunosorbent assay (ELISA) testing and standardized over serum creatinine.
Change in Urine TIMP1/Cr Levels
时间窗: 10 Weeks
TIMP1 is an established marker of intra-renal TNF pathway activation. A reduction in TIMP1 reflects a reduction in the activation of the TNF pathway in the kidney. Values were measured by enzyme-linked immunosorbent assay (ELISA) testing and standardized over serum creatinine.
次要结局
- Incidence of Adverse Events (AEs)(14 weeks)
- Change in Estimated Glomerular Filtration Rate (eGFR)(10 Weeks)
- Change in Urine Protein Creatinine Ratio (UPCR)(10 Weeks)
- Proportion of Participants Who Achieved Both a Nadir Urine Protein Creatinine Ratio (UPCR) of Less Than 1.5 g/g and at Least a 40% Reduction From Baseline(10 Weeks)
研究者
Zubin Juzer Modi
Assistant Professor of Pediatrics, Division of Nephrology
University of Michigan