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FSGSPhase 2NCT04009668

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

A Phase 2 study testing adalimumab in people with FSGS and MCD, run by University of Michigan at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 6 to 80 years
Conditions the study is for
FSGS, MCD, Focal Segmental Glomerulosclerosis
What is being tested?
adalimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
4 sitesUnited States
Study dates
2 Oct 2019to 3 Oct 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 to 80 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • The University of Michigan

    Ann Arbor, Michigan, 48109

  • Levine Children's Hospital/Atrium Health

    Charlotte, North Carolina, 28207

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • New York University

    New York, New York, 10016

Other trials in United States

About this study

Official title: Precision Medicine Proof of Concept for 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).

Being tested
adalimumab
Keywords
Kidney Disease, Minimal Change Disease, Nephrotic Syndrome, Focal Segmental Glomerulosclerosis, FSGS
Medical subject headings
Macular dystrophy, corneal type 1, Glomerulosclerosis, Focal Segmental, Nephrosis, Lipoid, Kidney Diseases, Nephrotic Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • adalimumabDrug

    Also called Humira

    Adalimumab will be dosed based on weight

Study groups in NCT04009668
Study groupRoleWhat they receive
adalimumabExperimentalAdalimumab dose every other week (study weeks 0, 2, 4, 6, and 8), subcutaneously
Receives: Drug: adalimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 10 Weeks

  2. 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.

    Measured: 10 Weeks

Secondary outcomes (4)

  1. Incidence of Adverse Events (AEs)

    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.

    Measured: 14 weeks

  2. Change in Estimated Glomerular Filtration Rate (eGFR)

    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.

    Measured: 10 Weeks

  3. Change in Urine Protein Creatinine Ratio (UPCR)

    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.

    Measured: 10 Weeks

  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

    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.

    Measured: 10 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jul 2019
  2. Study start2 Oct 2019
  3. Primary completion5 Sep 2023
  4. Study completion3 Oct 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04009668
Sponsor's protocol ID
HUM00147018
Status last verified
Oct 2024
First submitted
2 Jul 2019
Last updated
30 Oct 2024
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 39808779

  • Meliambro K, He JC, Campbell KN. Podocyte-targeted therapies - progress and future directions. Nat Rev Nephrol. 2024 Oct;20(10):643-658. doi: 10.1038/s41581-024-00843-z. Epub 2024 May 9.

    PubMed 38724717

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing adalimumab in people with FSGS and MCD, run by University of Michigan at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Urine MCP1/Cr Levels (time frame: 10 Weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04009668, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2024.

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