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

University of Michigan

Status and phase

Completed

Phase 2

Conditions

Minimal Change Disease

FSGS

MCD

Focal Segmental Glomerulosclerosis

Treatments

Drug: adalimumab

Study type

Interventional

Funder types

Other

Identifiers

NCT04009668

HUM00147018

Details and patient eligibility

About

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).

Enrollment

7 patients

Sex

All

Ages

6 to 80 years old

Volunteers

No Healthy Volunteers

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