Tumor Necrosis Factor Inhibition in Focal Segmental Glomerulosclerosis and Treatment Resistant Minimal Change Disease

Study Overview
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Brief Summary
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The researchers are testing adalimumab, a treatment which blocks tumor necrosis factor (TNF), to see if it changes levels of urine biomarker levels (TIMP1 and MCP1). The outcomes may help develop individualized treatment options for future patients with TNF driven Focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD).

Official Title
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Precision Medicine Proof of Concept for Tumor Necrosis Factor Inhibition in Focal Segmental Glomerulosclerosis and Treatment Resistant Minimal Change Disease

Conditions
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MCD, FSGS, Focal Segmental Glomerulosclerosis, Minimal Change Disease

Intervention / Treatment
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* Drug: adalimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: adalimumab<br>Adalimumab dose every other week (study weeks 0, 2, 4, 6, and 8), subcutaneously | Drug: adalimumab<br>* Adalimumab will be dosed based on weight<br>* Other names: Humira;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in urine MCP1/Cr levels | Change measured by for enzyme-linked immunosorbent assay (ELISA) testing | Baseline, Week 10 | 
| Change in urine TIMP1/Cr levels | Change measured by for enzyme-linked immunosorbent assay (ELISA) testing | Baseline, Week 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence adverse events (AEs) | Adverse events (AEs) include abnormal clinical laboratory tests and severe AEs. | Through study week 14 | 
| Percent change of estimated glomerular filtration rate (eGFR) | Measured by a blood sample. Summarized descriptively, including baseline, follow-up and changes from baseline. | Baseline, Week 10 | 
| Percent change in Urine Protein Creatinine Ratio (UPC) | Measured by a blood sample. Summarized descriptively, including baseline, follow-up and changes from baseline. | Baseline, Week 10 | 
| Proportion of participants achieving a nadir Urine Protein Creatinine Ratio (UPC) less than 1.5 g/g and at least a 40% reduction from baseline | Urine specimen | Week 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney Disease, Minimal Change Disease, Nephrotic Syndrome, Focal Segmental Glomerulosclerosis, FSGS