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

Focal Segmental Glomerulosclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04009668
• Other study ID #: HUM00147018
• Status: Completed
• Phase: Phase 2
• Start date: October 2, 2019
• Est. completion date: October 3, 2023

Study information

• Verified date: November 2023
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: October 3, 2023
• Est. primary completion date: October 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Focal Segmental Glomerulosclerosis
• FSGS
• Glomerulosclerosis, Focal Segmental
• MCD
• Minimal Change Disease
• Necrosis
• Nephrosis, Lipoid

Intervention

Drug:
• adalimumab
Adalimumab will be dosed based on weight

Locations

Country	Name	City	State
United States	The University of Michigan	Ann Arbor	Michigan
United States	Levine Children's Hospital/Atrium Health	Charlotte	North Carolina
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	New York University	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
University of Michigan

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in urine MCP1/Cr levels	Change measured by for enzyme-linked immunosorbent assay (ELISA) testing	Baseline, Week 10
Primary	Change in urine TIMP1/Cr levels	Change measured by for enzyme-linked immunosorbent assay (ELISA) testing	Baseline, Week 10
Secondary	Incidence adverse events (AEs)	Adverse events (AEs) include abnormal clinical laboratory tests and severe AEs.	Through study week 14
Secondary	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
Secondary	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
Secondary	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