Clinical trial NCT04009668: Tumor Necrosis Factor Inhibition in Focal Segmental Glomerulosclerosis and Treatment Resistant Minimal Change Disease
Official title: Precision Medicine Proof of Concept for Tumor Necrosis Factor Inhibition in Focal Segmental Glomerulosclerosis and Treatment Resistant Minimal Change Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: FSGS
MCD
Focal Segmental Glomerulosclerosis
Minimal Change Disease
Keywords: Kidney Disease
Minimal Change Disease
Nephrotic Syndrome
Focal Segmental Glomerulosclerosis
FSGS
Lead sponsor: University of Michigan
Sponsor class: OTHER
First posted: 2019-07-05
Enrollment: 7
Sex: ALL
Minimum age (years): 6
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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).


Eligibility criteria: 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

Primary outcomes:
measure: Change in Urine MCP1/Cr Levels
timeFrame: 10 Weeks
measure: Change in Urine TIMP1/Cr Levels
timeFrame: 10 Weeks
Secondary outcomes:
measure: Incidence of Adverse Events (AEs)
timeFrame: 14 weeks
measure: Change in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: 10 Weeks
measure: Change in Urine Protein Creatinine Ratio (UPCR)
timeFrame: 10 Weeks
measure: 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
timeFrame: 10 Weeks
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: The University of Michigan
state: Michigan
city: New York
country: United States
facility: New York University
state: New York
city: Charlotte
country: United States
facility: Levine Children's Hospital/Atrium Health
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
Study officials:
affiliation: University of Michigan
name: Zubin Modi, MD
role: STUDY_DIRECTOR
References: