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

Primary Purpose

FSGS, MCD, Focal Segmental Glomerulosclerosis

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
adalimumab
Sponsored by
University of Michigan
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for FSGS focused on measuring Kidney Disease, Minimal Change Disease, Nephrotic Syndrome, Focal Segmental Glomerulosclerosis, FSGS

Eligibility Criteria

6 Years - 80 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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
  • Qualifying archived biopsy tissue is available for testing of gene expression profiling
  • Increased urinary excretion of biomarkers of Tumor Necrosis Factor (TNF) activation (MCP1/Cr and/ or TIMP1/Cr) at study screening
  • eGFR>45 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

Sites / Locations

  • The University of Michigan
  • New York University
  • Levine Children's Hospital/Atrium Health
  • Cleveland Clinic Foundation

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

adalimumab

Arm Description

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

Outcomes

Primary Outcome Measures

Change in urine MCP1/Cr levels
Change measured by for enzyme-linked immunosorbent assay (ELISA) testing
Change in urine TIMP1/Cr levels
Change measured by for enzyme-linked immunosorbent assay (ELISA) testing

Secondary Outcome Measures

Incidence adverse events (AEs)
Adverse events (AEs) include abnormal clinical laboratory tests and severe AEs.
Percent change of estimated glomerular filtration rate (eGFR)
Measured by a blood sample. Summarized descriptively, including baseline, follow-up and changes from baseline.
Percent change in Urine Protein Creatinine Ratio (UPC)
Measured by a blood sample. Summarized descriptively, including baseline, follow-up and changes from baseline.
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

Full Information

First Posted
July 2, 2019
Last Updated
July 18, 2023
Sponsor
University of Michigan
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1. Study Identification

Unique Protocol Identification Number
NCT04009668
Brief Title
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

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 2, 2019 (Actual)
Primary Completion Date
October 31, 2023 (Anticipated)
Study Completion Date
October 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Michigan

4. Oversight

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

5. Study Description

Brief 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
FSGS, MCD, Focal Segmental Glomerulosclerosis, Minimal Change Disease
Keywords
Kidney Disease, Minimal Change Disease, Nephrotic Syndrome, Focal Segmental Glomerulosclerosis, FSGS

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
adalimumab
Arm Type
Experimental
Arm Description
Adalimumab dose every other week (study weeks 0, 2, 4, 6, and 8), subcutaneously
Intervention Type
Drug
Intervention Name(s)
adalimumab
Other Intervention Name(s)
Humira
Intervention Description
Adalimumab will be dosed based on weight
Primary Outcome Measure Information:
Title
Change in urine MCP1/Cr levels
Description
Change measured by for enzyme-linked immunosorbent assay (ELISA) testing
Time Frame
Baseline, Week 10
Title
Change in urine TIMP1/Cr levels
Description
Change measured by for enzyme-linked immunosorbent assay (ELISA) testing
Time Frame
Baseline, Week 10
Secondary Outcome Measure Information:
Title
Incidence adverse events (AEs)
Description
Adverse events (AEs) include abnormal clinical laboratory tests and severe AEs.
Time Frame
Through study week 14
Title
Percent change of estimated glomerular filtration rate (eGFR)
Description
Measured by a blood sample. Summarized descriptively, including baseline, follow-up and changes from baseline.
Time Frame
Baseline, Week 10
Title
Percent change in Urine Protein Creatinine Ratio (UPC)
Description
Measured by a blood sample. Summarized descriptively, including baseline, follow-up and changes from baseline.
Time Frame
Baseline, Week 10
Title
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
Description
Urine specimen
Time Frame
Week 10

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zubin Modi, MD
Organizational Affiliation
University of Michigan
Official's Role
Study Director
Facility Information:
Facility Name
The University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
New York University
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Levine Children's Hospital/Atrium Health
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28207
Country
United States
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
http://neptune-study.org/

Learn more about this trial

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

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