The primary objective of this study is to evaluate whether selonsertib (SEL) can slow the decline in kidney function in participants with moderate to advanced diabetic kidney disease (DKD).
Following the screening period, eligible participants will enroll into a Run-in period of at least 5 weeks and receive placebo to match SEL for at least 1 week and then SEL for at least 4 weeks. After completing Run-in period, eligible participants will be randomized and receive either SEL or placebo to match SEL for at least 48 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
384
Treatment-specific Baseline Estimated Glomerular Filtration Rate Based on Creatinine (eGFRcr)
The values of eGFRcr were calculated using the Chronic Kidney Disease Epidemiology (CKD-EPI) Creatinine Equation (2009). eGFRcr = 141\*min(Standardized Serum Creatinine (Scr)/kappa, 1) \^alpha\*max(Scr/ kappa, 1)\^(-1.209)\*0.993\^Age\*1.018\[if female\]\*1.159\[if Black\], where kappa=0.7(females) or 0.9(males), alpha=-0.329(females) or -0.411(males). min indicates the minimum of Scr/kappa or 1, max indicates the maximum of Scr/kappa or 1, and age is in years. Treatment-specific Baselines = the average of Visits A and B values for Placebo, and the average of Visit C and Day 1 values for SEL. Visit A= enrollment, Visit B= 7-14 days after Visit A, Visit C= 21-28 days after Visit B, and Visit 1= 7-14 days after Visit C.
Time frame: Treatment-specific Baselines (From enrollment (Visit A) up to 14 days after Visit A for placebo and from Visit C up to 14 days after Visit C for SEL)
eGFRcr Slope
The values of eGFRcr were calculated using the CKD-EPI Creatinine Equation (2009). eGFRcr = 141\*min(Scr/kappa, 1) \^alpha\*max(Scr/kappa, 1)\^(-1.209)\*0.993\^Age\*1.018\[if female\]\*1.159\[if Black\], where kappa=0.7(females) or 0.9(males), alpha=-0.329(females) or -0.411(males). min indicates the minimum of Scr/kappa or 1, max indicates the maximum of Scr/kappa or 1, and age is in years. Treatment specific baselines for eGFRcr: average of Visit A (enrollment) and Visit B (7-14 days after Visit A) values for Placebo, and average of Visit C (21-28 days after Visit B, and Visit 1 (7-14 days after Visit C) values for SEL.
Time frame: Treatment-specific Baselines through Week 84
Percentage of Participants With Kidney Clinical Events at Week 48
Kidney clinical events were defined as any of the following events: confirmed ≥ 40% decline in eGFRcr from baseline, or kidney failure (dialysis performed for at least 4 weeks, kidney transplantation, or confirmed decrease in eGFRcr to \< 15 mL/min/1.73 m\^2 for participants without dialysis or kidney transplantation), or death due to kidney disease.
Time frame: Week 48
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Arizona Kidney Disease and Hypertension Centers
Glendale, Arizona, United States
AKDHC Medical Research Services, LLC
Tucson, Arizona, United States
Clearview Medical Research, LLC
Canyon Country, California, United States
Kidney Disease Medical Group, Inc.
Glendale, California, United States
Renal Consultants Medical Group
Granada Hills, California, United States
Marin Endocrine Care & Research, Inc.
Greenbrae, California, United States
California Institute of Renal Research
La Mesa, California, United States
Academic Medical Research Institute
Los Angeles, California, United States
Rose Salter Medical Research Foundation
Newport Beach, California, United States
Valley Renal Medical Group Research
Northridge, California, United States
...and 101 more locations
Time From Randomization to First Occurrence of a Kidney Clinical Event: Event Rate Per 100 Participant-years for First Occurrence of Kidney Clinical Event
Kidney clinical events were defined as any of the following events: confirmed ≥ 40% decline in eGFRcr from baseline, or kidney failure (dialysis performed for at least 4 weeks, kidney transplantation, or confirmed decrease in eGFRcr to \< 15 mL/min/1.73 m\^2 for participants without dialysis or kidney transplantation), or death due to kidney disease. This outcome measure was analyzed using event rate per 100 participant-years for first occurrence of kidney clinical event. Participant year was calculated as total follow-up duration across all participants in a given group. Follow-up duration was defined as time from Randomization to the earliest of study completion, premature study discontinuation, death, or event of interest in each row.
Time frame: From randomization up to Week 101
Pre-run-in Baseline Estimated Glomerular Filtration Rate Based on Cystatin C (eGFRcys)
eGFRcys = Estimated Glomerular Filtration Rate calculated by CKD-EPI Cystatin C Equation (2012). eGFR = 133\*min(Standardized Serum Cystatin (Scys)/0.8, 1) \^(-0.499)\*max(Scys/0.8, 1)\^(-1.328)\*0.996\^Age\*0.932\[if female\]. min indicates the minimum of Scys/0.8 or 1, max indicates the maximum of Scr/0.8 or 1, and age is in years.
Time frame: Pre-run-in Baseline (Pre-run in Baseline = Average of visit A (Enrollment) and Visit B (7-14 days after Visit A) eGFRcys values)
eGFRcys Slope
eGFRcys = Estimated Glomerular Filtration Rate calculated by CKD-EPI Cystatin C Equation (2012). eGFR = 133\*min(Scys/0.8, 1) \^(-0.499)\*max(Scys/0.8, 1)\^(-1.328)\*0.996\^Age\*0.932\[if female\]. min indicates the minimum of Scys/0.8 or 1, max indicates the maximum of Scr/0.8 or 1, and age is in years. Pre-run in Baseline = Average of visit A (Enrollment) and Visit B (7-14 days after Visit A) eGFRcys values.
Time frame: Pre-run-in Baseline through Week 84