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.
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
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
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).
- Conditions
- FSGS, MCD, Focal Segmental Glomerulosclerosis, Minimal Change Disease
- 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 group | Role | What they receive |
|---|---|---|
| adalimumab | Experimental | Adalimumab 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.
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
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)
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
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
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
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.
- First posted5 Jul 2019
- Study start2 Oct 2019
- Primary completion5 Sep 2023
- Study completion3 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for FSGSStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zubin Juzer Modi, University of Michigan
- Investigators
- Zubin Modi, MD, Study director, University of Michigan
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
- Results posted
- Yes, on ClinicalTrials.gov
- 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 39808779Meliambro 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