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
1 other identifier
interventional
7
1 country
4
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Oct 2019
Typical duration for phase_2
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 2, 2019
CompletedFirst Posted
Study publicly available on registry
July 5, 2019
CompletedStudy Start
First participant enrolled
October 2, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 5, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
October 3, 2023
CompletedResults Posted
Study results publicly available
October 30, 2024
CompletedOctober 30, 2024
October 1, 2024
3.9 years
July 2, 2019
October 3, 2024
October 3, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Change in Urine MCP1/Cr Levels
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.
10 Weeks
Change in Urine TIMP1/Cr Levels
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.
10 Weeks
Secondary Outcomes (4)
Incidence of Adverse Events (AEs)
14 weeks
Change in Estimated Glomerular Filtration Rate (eGFR)
10 Weeks
Change in Urine Protein Creatinine Ratio (UPCR)
10 Weeks
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
Study Arms (1)
adalimumab
EXPERIMENTALAdalimumab dose every other week (study weeks 0, 2, 4, 6, and 8), subcutaneously
Interventions
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (4)
The University of Michigan
Ann Arbor, Michigan, 48109, United States
New York University
New York, New York, 10016, United States
Levine Children's Hospital/Atrium Health
Charlotte, North Carolina, 28207, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Related Publications (1)
Trachtman H, Modi ZJ, Ju W, Lee E, Chinnakotla S, Massengill S, Sedor J, Mariani L, Zhai Y, Hao W, Desmond H, Eddy S, Ramani K, Spino C, Kretzler M. Precision Medicine Proof-of-Concept Study of a TNF Inhibitor in FSGS and Treatment-Resistant Minimal Change Disease. Kidney360. 2025 Feb 1;6(2):284-295. doi: 10.34067/KID.0000000635. Epub 2024 Nov 18.
PMID: 39808779DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Recruitment was launched in Dec. 2019 and was significantly impacted by the COVID-19 pandemic with most participants enrolling in 2022. One participant was unable to attend the week 10 visit because of COVID-19 infection, and the week 8 biomarker results were used to determine the primary outcome.
Results Point of Contact
- Title
- Dr. Zubin Modi
- Organization
- University of Michigan
Study Officials
- STUDY DIRECTOR
Zubin Modi, MD
University of Michigan
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Assistant Professor of Pediatrics, Division of Nephrology
Study Record Dates
First Submitted
July 2, 2019
First Posted
July 5, 2019
Study Start
October 2, 2019
Primary Completion
September 5, 2023
Study Completion
October 3, 2023
Last Updated
October 30, 2024
Results First Posted
October 30, 2024
Record last verified: 2024-10
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- 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.
- 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.
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.