Phase 2
N=7
Tumor Necrosis Factor Inhibition in Focal Segmental Glomerulosclerosis and Treatment Resistant Minimal Change Disease
FSGS · MCD · Focal Segmental Glomerulosclerosis · Minimal Change Disease
Bottom Line
View on ClinicalTrials.gov: NCT04009668 ↗Enrolled (actual)
7
Serious AEs
14.3%
Results posted
Oct 2024
Primary outcome: Primary: Change in Urine MCP1/Cr Levels — 5.57; 2.89 ng/mg
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- adalimumab (Drug)
- Age
- Pediatric, Adult, Older Adult · 6+ yrs
- Sex
- All
- Sponsor
- University of Michigan
- Primary completion
- Sep 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Urine MCP1/Cr Levels |
5.57; 2.89 | — |
| PRIMARY Change in Urine TIMP1/Cr Levels |
41.34; 31.36 | — |
| SECONDARY Incidence of Adverse Events (AEs) |
7; 4; 1; 10 | — |
| SECONDARY Change in Estimated Glomerular Filtration Rate (eGFR) |
-28.90 | — |
| SECONDARY Change in Urine Protein Creatinine Ratio (UPCR) |
-11.60 | — |
| SECONDARY 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 |
2 | — |
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).
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
Data sourced from ClinicalTrials.gov (NCT04009668). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.