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

Phase 2

Completed

Conditions: FSGS
MCD
Focal Segmental Glomerulosclerosis
Minimal Change Disease

Interventions: Drug: adalimumab

Registration Number: NCT04009668

Lead Sponsor: University of Michigan

Brief Summary: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 7

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
adalimumab	adalimumab	Adalimumab dose every other week (study weeks 0, 2, 4, 6, and 8), subcutaneously

Primary Outcome Measures

Name	Time	Method
Change in Urine MCP1/Cr Levels	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	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.

Secondary Outcome Measures

Name	Time	Method
Incidence of Adverse Events (AEs)	14 weeks	AEs for this outcome measure were classified using the following definitions: * Mild: no or mild symptoms, and not requiring intervention * Moderate: with minimal or local intervention, and limiting age-appropriate activities * Severe: intervention necessary and limiting age-appropriate activities but not immediately life-threatening, and requiring hospitalization or prolongation of hospitalization * Serious AE: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, pregnancy or congenital anomaly/birth defect. Some participants experienced multiple types of AE during the course of the trial.
Change in Estimated Glomerular Filtration Rate (eGFR)	10 Weeks	eGFR is a measure of kidney functioning based on a blood sample and clinical information to calculate it. Normal kidney function is greater than 90 ml/min/1.73 m2. Result data is the percent change in eGFR following the intervention. The lower the number shows the greater decline in kidney function.
Change in Urine Protein Creatinine Ratio (UPCR)	10 Weeks	UPCR is a measure of protein spillage from the kidney based on a urine specimen. Normal reference range is less than 0.03 mg/mg. Result is the percent change in UPCR following the intervention, with lower number showing less protein spilling from the kidney, reflecting better disease control.
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	UPCR is a measure of protein spillage from the kidney based on a urine specimen. Normal reference range is less than 0.03 mg/mg. Result is the count of participants who simultaneously met the criteria of having both a raw UPCR value of less than 1.5 g/g and at least a 40% reduction from baseline.

Trial Locations

Locations (4): The University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
Levine Children's Hospital/Atrium Health
🇺🇸
Charlotte, North Carolina, United States
New York University
🇺🇸
New York, New York, United States
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States