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Completed

NCT Number: NCT04009668

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

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).

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Key information

Conditions

FSGS Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Focal Segmental Glomerulosclerosis Glomerulonephritis Glomerulosclerosis, Focal Segmental Kidney Diseases MCD Macular dystrophy, corneal type 1 Male Urogenital Diseases Minimal Change Disease Nephritis Nephrosis Nephrosis, Lipoid Nephrotic Syndrome Urogenital Diseases Urologic Diseases

Age range

6 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

The University of Michigan, Ann Arbor, Michigan, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Adalimumab

Drug

Adalimumab will be dosed based on weight

Other names: Humira

Primary outcomes

  1. Change in Urine MCP1/Cr Levels

    Time frame: 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.

  2. Change in Urine TIMP1/Cr Levels

    Time frame: 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 outcomes

  1. Incidence of Adverse Events (AEs)

    Time frame: 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.

  2. Change in Estimated Glomerular Filtration Rate (eGFR)

    Time frame: 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.

  3. Change in Urine Protein Creatinine Ratio (UPCR)

    Time frame: 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.

  4. 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

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

University of Michigan

Other

Registry information

Official study title

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

Important dates

Study start
2019
Primary completion
2023
Study completion
2023
First posted
Jul 5, 2019
Registry last updated
Oct 30, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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