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

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

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).

Study Overview

• Status: Completed
• Conditions: Focal Segmental Glomerulosclerosis; Minimal Change Disease; FSGS; MCD
• Intervention / Treatment: Drug: adalimumab

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Catherine Kilda; Phone Number: 734-232-4830; Email: umkidneystudies@umich.edu
• Study Contact Backup: Name: Hailey Desmond; Phone Number: 734-232-4830; Email: umkidneystudies@umich.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • The University of Michigan
  • New York
    • New York, New York, United States, 10016
      • New York University
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Levine Children's Hospital/Atrium Health
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: adalimumab; Adalimumab dose every other week (study weeks 0, 2, 4, 6, and 8), subcutaneously	Drug: adalimumab; Adalimumab will be dosed based on weight; Other Names: Humira

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in urine MCP1/Cr levels	Change measured by for enzyme-linked immunosorbent assay (ELISA) testing	Baseline, Week 10
Change in urine TIMP1/Cr levels	Change measured by for enzyme-linked immunosorbent assay (ELISA) testing	Baseline, Week 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence adverse events (AEs)	Adverse events (AEs) include abnormal clinical laboratory tests and severe AEs.	Through study week 14
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
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
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

Collaborators and Investigators

• Sponsor: University of Michigan
• Investigators: Study Director: Zubin Modi, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2019
• Primary Completion (Actual): October 3, 2023
• Study Completion (Actual): October 3, 2023

Study Registration Dates

• First Submitted: July 2, 2019
• First Submitted That Met QC Criteria: July 2, 2019
• First Posted (Actual): July 5, 2019

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 3, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Kidney Disease; Nephrotic Syndrome; FSGS; Focal Segmental Glomerulosclerosis; Minimal Change Disease
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Nephrosis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Necrosis; Glomerulosclerosis, Focal Segmental; Nephrosis, Lipoid; Anti-Inflammatory Agents; Antirheumatic Agents; Tumor Necrosis Factor Inhibitors; Adalimumab
• Other Study ID Numbers: HUM00147018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

This trial will follow the publication and data sharing policies of the NEPTUNE study, www.NEPTUNE-study.org

Request for ancillary studies should be submitted through the project contact and will be reviewed by the project steering committee.

After the study is completed, data will be submitted to the Nephrotic Syndrome Study Network (NEPTUNE), an NIH funded consortium. Proposals to access the data will then be submitted via the NEPTUNE Ancillary Studies program (NEPTUNE-study.org). Following closure of NEPTUNE, the trial data will convey with the NEPTUNE date to the NIH/NIDDK repository and can be accessed through this mechanism following approval.

• IPD Sharing Time Frame: At the latest, data will be shared with the NEPTUNE Data Analysis and Coordinating Center at the time of publication of final results or 24 months after transfer of samples or raw data sets.

IPD Sharing Access Criteria

While this study is open data requests from this study will need to seek approval from the trial steering committee.

Once the data is transferred to the NEPTUNE study, all study data will become part of the aggregate NEPTUNE data and available to NEPTUNE participant sites and other requesting third parties upon request. Subsequent access to these data will be governed by the NIH Office of Rare Diseases (ORD) data sharing policies.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No