Trial Outcomes & Findings for Tumor Necrosis Factor Inhibition in Focal Segmental Glomerulosclerosis and Treatment Resistant Minimal Change Disease (NCT NCT04009668)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

7 participants

Primary outcome timeframe

10 Weeks

Results posted on

2024-10-30

Participant Flow

Recruitment Period: 2019-2023 Recruitment Sites: University of Michigan, Ann Arbor, MI; New York University Langone Health, New York, NY; Cleveland Clinic, Cleveland, OH; Levine Children's Hospital at Atrium Health, Charlotte, NC.

Following consent, participants provided a urine sample to measure urinary monocyte chemoattractant protein-1 (uMCP-1) and urinary tissue inhibitor of metalloprotease-1 (uTIMP-1), two indicators of intra-renal tumor necrosis factor (TNF) pathway activation. Participants with present TNF activation were advanced to screening. Upon confirmation of eligibility, participants proceeded to the treatment phase.

Participant milestones

Participant milestones
Measure	Adalimumab Adalimumab dose every other week (study weeks 0, 2, 4, 6, and 8), subcutaneously. Adalimumab will be dosed based on weight (20 mg for subjects weighing 15kg to \<30kg, or 40 mg for subjects \>30kg).
Overall Study STARTED	7
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Adalimumab n=7 Participants Adalimumab dose every other week (study weeks 0, 2, 4, 6, and 8), subcutaneously. Adalimumab will be dosed based on weight (20 mg for subjects weighing 15kg to \<30kg, or 40 mg for subjects \>30kg).
Age, Continuous	15.9 years n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	5 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	3 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	4 Participants n=5 Participants
Region of Enrollment United States	7 participants n=5 Participants

PRIMARY outcome

Timeframe: 10 Weeks

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.

Outcome measures

Outcome measures
Measure	Adalimumab n=7 Participants Adalimumab dose every other week (study weeks 0, 2, 4, 6, and 8), subcutaneously. Adalimumab will be dosed based on weight (20 mg for subjects weighing 15kg to \<30kg, or 40 mg for subjects \>30kg).
Change in Urine MCP1/Cr Levels Baseline	5.57 ng/mg Interval 0.79 to 6.61
Change in Urine MCP1/Cr Levels Week 10	2.89 ng/mg Interval 1.36 to 7.14

PRIMARY outcome

Timeframe: 10 Weeks

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.

Outcome measures

Outcome measures
Measure	Adalimumab n=7 Participants Adalimumab dose every other week (study weeks 0, 2, 4, 6, and 8), subcutaneously. Adalimumab will be dosed based on weight (20 mg for subjects weighing 15kg to \<30kg, or 40 mg for subjects \>30kg).
Change in Urine TIMP1/Cr Levels Baseline	41.34 ng/mg Interval 3.64 to 75.38
Change in Urine TIMP1/Cr Levels Week 10	31.36 ng/mg Interval 4.39 to 146.86

SECONDARY outcome

Timeframe: 14 weeks

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.

Outcome measures

Outcome measures
Measure	Adalimumab n=7 Participants Adalimumab dose every other week (study weeks 0, 2, 4, 6, and 8), subcutaneously. Adalimumab will be dosed based on weight (20 mg for subjects weighing 15kg to \<30kg, or 40 mg for subjects \>30kg).
Incidence of Adverse Events (AEs) Moderate AEs	4 Adverse Event
Incidence of Adverse Events (AEs) Severe AEs	1 Adverse Event
Incidence of Adverse Events (AEs) Serious AEs	10 Adverse Event
Incidence of Adverse Events (AEs) Mild AEs	7 Adverse Event

SECONDARY outcome

Timeframe: 10 Weeks

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.

Outcome measures

Outcome measures
Measure	Adalimumab n=7 Participants Adalimumab dose every other week (study weeks 0, 2, 4, 6, and 8), subcutaneously. Adalimumab will be dosed based on weight (20 mg for subjects weighing 15kg to \<30kg, or 40 mg for subjects \>30kg).
Change in Estimated Glomerular Filtration Rate (eGFR)	-28.90 Percent Change Interval -30.5 to -12.18

SECONDARY outcome

Timeframe: 10 Weeks

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.

Outcome measures

Outcome measures
Measure	Adalimumab n=7 Participants Adalimumab dose every other week (study weeks 0, 2, 4, 6, and 8), subcutaneously. Adalimumab will be dosed based on weight (20 mg for subjects weighing 15kg to \<30kg, or 40 mg for subjects \>30kg).
Change in Urine Protein Creatinine Ratio (UPCR)	-11.60 Percent Change Interval -23.45 to -9.28

SECONDARY outcome

Timeframe: 10 Weeks

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.

Outcome measures

Outcome measures
Measure	Adalimumab n=7 Participants Adalimumab dose every other week (study weeks 0, 2, 4, 6, and 8), subcutaneously. Adalimumab will be dosed based on weight (20 mg for subjects weighing 15kg to \<30kg, or 40 mg for subjects \>30kg).
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 Participants

Adverse Events

Adalimumab

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Adalimumab n=7 participants at risk Adalimumab dose every other week (study weeks 0, 2, 4, 6, and 8), subcutaneously. Adalimumab will be dosed based on weight (20 mg for subjects weighing 15kg to \<30kg, or 40 mg for subjects \>30kg).
Infections and infestations Influenza	14.3% 1/7 • Number of events 1 • 14 Weeks
Renal and urinary disorders Edema	14.3% 1/7 • Number of events 5 • 14 Weeks
Renal and urinary disorders Anasarca and AKI	14.3% 1/7 • Number of events 4 • 14 Weeks

Other adverse events

Other adverse events
Measure	Adalimumab n=7 participants at risk Adalimumab dose every other week (study weeks 0, 2, 4, 6, and 8), subcutaneously. Adalimumab will be dosed based on weight (20 mg for subjects weighing 15kg to \<30kg, or 40 mg for subjects \>30kg).
Blood and lymphatic system disorders Anemia	14.3% 1/7 • Number of events 1 • 14 Weeks
Gastrointestinal disorders Diarrhea	14.3% 1/7 • Number of events 1 • 14 Weeks
General disorders Volume depletion	14.3% 1/7 • Number of events 1 • 14 Weeks
Infections and infestations COVID-19	28.6% 2/7 • Number of events 2 • 14 Weeks
Infections and infestations Rhinovirus	14.3% 1/7 • Number of events 1 • 14 Weeks
Renal and urinary disorders Increased edema	14.3% 1/7 • Number of events 1 • 14 Weeks
Renal and urinary disorders eGFR decline (greater than 25% since baseline)	57.1% 4/7 • Number of events 4 • 14 Weeks
Skin and subcutaneous tissue disorders Rash	14.3% 1/7 • Number of events 1 • 14 Weeks

Additional Information

Dr. Zubin Modi

University of Michigan

Phone: (734) 232-6798

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place