Study to Evaluate the Efficacy and Safety of Selonsertib in Participants With Moderate to Advanced Diabetic Kidney Disease
- Conditions
- Diabetic Kidney Disease
- Interventions
- Drug: SELDrug: Placebo
- Registration Number
- NCT04026165
- Lead Sponsor
- Gilead Sciences
- Brief Summary
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).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 384
-
Diagnosis of type 2 diabetes mellitus (T2DM) as per local guidelines.
-
Estimated glomerular filtration rate (eGFR) value calculated by central laboratory utilizing samples collected during screening and prior to enrollment of ≥ 20 mL/min/1.73 m^2 to < 60 mL/min/1.73 m^2 with albuminuria
-
eGFR and urine albumin to creatinine ratio (UACR) must meet criteria a, b, or c
- a: eGFR (mL/min/1.73 m^2): ≥ 45 to < 60; UACR (mg/g): ≥ 600 to 5000
- b: eGFR (mL/min/1.73 m^2): ≥ 30 to < 45; UACR (mg/g): ≥ 300 to 5000
- c: eGFR (mL/min/1.73 m^2): ≥ 20 to < 30; UACR (mg/g): ≥ 150 to 5000
-
-
Treatment with either an angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB)
- Individuals not receiving an ACEi or ARB may be enrolled if there is documented intolerance to ACEi and ARB
- Individuals receiving less-than-maximal dose of an ACEi or ARB may be enrolled if there is a documented reason that the maximum labeled dose of ACEi and ARB could not be reached
-
Individuals already receiving sodium-glucose co-transporter-2 (SGLT-2) inhibitors must be on a stable dose for at least 2 weeks prior to enrollment
-
Mean systolic blood pressure (SBP) must be <160 mmHg and mean diastolic blood pressure (DBP) must be <100 mmHg
-
Required baseline laboratory data, analyzed by central laboratory, within 30 days prior to enrollment
Key
-
Hemoglobin A1c (HbA1c) > 12.0% within 30 days prior to enrollment
-
Individuals with diagnosis of type 1 diabetes mellitus (T1DM) or maturity onset diabetes of the young (MODY)
-
Body mass index (BMI) > 50 kg/m^2
-
UACR > 5000 mg/g on any measurement during screening
-
End stage kidney disease (ESKD) (i.e., chronic hemodialysis, chronic peritoneal dialysis, or history of kidney transplantation)
-
Anticipated progression to ESKD (need for chronic hemodialysis, chronic peritoneal dialysis or receipt of kidney transplant) within 3 months after enrollment
-
Unstable cardiovascular disease
-
Pregnant or lactating females or planning to become pregnant or breastfeed during the study
-
Concurrent use of either
- ACEi and ARB or
- Mineralocorticoid receptor antagonist (MRA) or direct renin inhibitor (DRI) in combination with an ACEi or ARB for at least 2 weeks prior to Enrollment
-
Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, ECG finding, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the individual or impair the assessment of study results
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Selonsertib SEL Run-in Period (5 Weeks): Participants will receive placebo-to-match SEL for at least one week and then SEL 18 mg for at least 4 weeks. Randomized Period: Participants will be randomized to receive SEL 18 mg for at least 48 weeks. Selonsertib Placebo Run-in Period (5 Weeks): Participants will receive placebo-to-match SEL for at least one week and then SEL 18 mg for at least 4 weeks. Randomized Period: Participants will be randomized to receive SEL 18 mg for at least 48 weeks. Placebo SEL Run-in Period (5 Weeks): Participants will receive placebo-to-match SEL for at least one week and then SEL 18 mg for at least 4 weeks. Randomized Period: Participants will be randomized to receive placebo-to-match SEL for at least 48 weeks. Placebo Placebo Run-in Period (5 Weeks): Participants will receive placebo-to-match SEL for at least one week and then SEL 18 mg for at least 4 weeks. Randomized Period: Participants will be randomized to receive placebo-to-match SEL for at least 48 weeks.
- Primary Outcome Measures
Name Time Method Treatment-specific Baseline Estimated Glomerular Filtration Rate Based on Creatinine (eGFRcr) 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) 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.eGFRcr Slope Treatment-specific Baselines through Week 84 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.
- Secondary Outcome Measures
Name Time Method Time From Randomization to First Occurrence of a Kidney Clinical Event: Event Rate Per 100 Participant-years for First Occurrence of Kidney Clinical Event From randomization up to Week 101 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.
Pre-run-in Baseline Estimated Glomerular Filtration Rate Based on Cystatin C (eGFRcys) 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 = 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.
eGFRcys Slope Pre-run-in Baseline through Week 84 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.
Percentage of Participants With Kidney Clinical Events at Week 48 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.
Trial Locations
- Locations (109)
North Shore University Hospital: Division of Nephrology
🇺🇸Great Neck, New York, United States
Knoxville Kidney Center, PLLC
🇺🇸Knoxville, Tennessee, United States
Research By Design, LLC
🇺🇸Chicago, Illinois, United States
California Institute of Renal Research
🇺🇸San Diego, California, United States
Pelican Point Dialysis - DaVita Clinical Research
🇺🇸Las Vegas, Nevada, United States
Mercury Clinical Research
🇺🇸Houston, Texas, United States
California Kidney Specialist
🇺🇸San Dimas, California, United States
Suncoast Clinical Research, Inc.
🇺🇸New Port Richey, Florida, United States
Discovery Medical Research Group, Inc
🇺🇸Ocala, Florida, United States
Western Nephrology and Metabolic Bone Disease, PC
🇺🇸Westminster, Colorado, United States
Kansas Nephrology Research Institute, LLC
🇺🇸Wichita, Kansas, United States
South Florida Research Institute
🇺🇸Lauderdale Lakes, Florida, United States
Buynak Clinical Research, P.C.
🇺🇸Valparaiso, Indiana, United States
Aa Mrc, Llc
🇺🇸Flint, Michigan, United States
SV Research LLC
🇺🇸Marion, Ohio, United States
Four Rivers Clinical Research
🇺🇸Paducah, Kentucky, United States
Wilmington Health, PLLC
🇺🇸Wilmington, North Carolina, United States
New West Physicians, Inc
🇺🇸Golden, Colorado, United States
Omega Research Maitland, LLC
🇺🇸DeBary, Florida, United States
Elite Research Center
🇺🇸Flint, Michigan, United States
University Diabetes and Endocrine Consultants
🇺🇸Chattanooga, Tennessee, United States
Northeast Clinical Research Center, LLC
🇺🇸Bethlehem, Pennsylvania, United States
The Medical Group of Texas
🇺🇸Fort Worth, Texas, United States
Austin Health and University of Melbourne
🇦🇺Heidelberg, Victoria, Australia
Waitemata District Health Board- North Shore Hospital
🇳🇿North Shore, New Zealand
LMC Clinical research Inc. (Thornhill)
🇨🇦Concord, Canada
Primecare Medical Group
🇺🇸Houston, Texas, United States
Yamanashi Prefectural Central Hospital
🇯🇵Kofu, Japan
Kurobe City Hospital
🇯🇵Kurobe-shi, Japan
Nakakinen Clinic
🇯🇵Naka-shi, Japan
Yokohama City University Hospital
🇯🇵Yokohama-shi, Japan
St. Vincent Hospital, Melbourne
🇦🇺Fitzroy, Australia
Asahikawa Medical University Hospital
🇯🇵Asahikawa, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
North Texas Endocrine Center
🇺🇸Dallas, Texas, United States
Kokura Memorial Hospital
🇯🇵Kitakyushu-shi, Japan
Houston Methodist Research Institute - CCAT Pearland
🇺🇸Pearland, Texas, United States
National Hospital Organization Chiba-East-Hospital
🇯🇵Chiba, Japan
Middlemore Clinical Trials Trust trading as Middlemore Clinical Trials
🇳🇿Auckland, New Zealand
Centre de Recherche Clinique de Lava
🇨🇦Laval, Canada
Arlington Nephrology
🇺🇸Arlington, Texas, United States
Mishuku Hospital
🇯🇵Tokyo, Japan
LMC Clinical Research Inc. (Barrie)
🇨🇦Barrie, Canada
Winnipeg Clinic
🇨🇦Winnipeg, Canada
Kurume University Hospital
🇯🇵Kurume-shi, Japan
Auckland City Hospital (Auckland District Health Board)
🇳🇿Auckland, New Zealand
Lipid and Diabetes Research Group
🇳🇿Christchurch, New Zealand
Clinical Advancement Center, PLLC
🇺🇸San Antonio, Texas, United States
Northeast Clinical Research of San Antonio
🇺🇸San Antonio, Texas, United States
Nakamoto Medical Clinic
🇯🇵Mito-shi, Japan
Kozawa Eye Hospital and Diabetes Center
🇯🇵Mito-shi, Japan
Nagasaki University Hospital
🇯🇵Nagasaki, Japan
Daido Clinic
🇯🇵Nagoya-shi, Japan
Niigata University Medical & Dental Hospital
🇯🇵Niigata, Japan
Osaka General Medical Center
🇯🇵Osaka, Japan
Nihon University Itabashi Hospital
🇯🇵Tokyo, Japan
Sanuki Municipal Hospital
🇯🇵Sanuki-shi, Japan
Tachikawa Hospital
🇯🇵Tachikawa-shi, Japan
TOYOTA Memorial Hospital
🇯🇵Toyota-shi, Japan
Dr TGElliott Inc dba BC Diabetes
🇨🇦Vancouver, Canada
PMG Research, Inc. d/b/a PMG Research of Knoxville
🇺🇸Knoxville, Tennessee, United States
Memphis Veteran Affairs Medical Center
🇺🇸Memphis, Tennessee, United States
Endocrine Associates of Long Island, PC
🇺🇸Smithtown, New York, United States
Arcturus Healthcare, PLC, Troy Internal Medicine Research Division
🇺🇸Troy, Michigan, United States
Midwest Nephrology Group, PLLC
🇺🇸Midwest City, Oklahoma, United States
PMG Research Inc., d/b/a PMG Research of Piedmont Healthcare
🇺🇸Statesville, North Carolina, United States
Atlanta Center for Clinical Research
🇺🇸Atlanta, Georgia, United States
Georgia Nephrology Research Institute
🇺🇸Lawrenceville, Georgia, United States
Kagoshima University Hospital
🇯🇵Kagoshima, Japan
AKDHC Medical Research Services, LLC
🇺🇸Tucson, Arizona, United States
Arizona Kidney Disease and Hypertension Centers
🇺🇸Glendale, Arizona, United States
Clearview Medical Research, LLC
🇺🇸Canyon Country, California, United States
Renal Consultants Medical Group
🇺🇸Granada Hills, California, United States
Kidney Disease Medical Group, Inc.
🇺🇸Glendale, California, United States
Academic Medical Research Institute
🇺🇸Los Angeles, California, United States
Marin Endocrine Care & Research, Inc.
🇺🇸Greenbrae, California, United States
Rose Salter Medical Research Foundation
🇺🇸Newport Beach, California, United States
Valley Renal Medical Group Research
🇺🇸Northridge, California, United States
East-West Medical Research Institute
🇺🇸Honolulu, Hawaii, United States
Boise Kidney & Hypertension, PLLC
🇺🇸Meridian, Idaho, United States
Coastal Nephrology Associates Research Center, LLC. D/B/A Volunteer Medical Research
🇺🇸Port Charlotte, Florida, United States
Internal Medicine Specialists, Inc
🇺🇸New Orleans, Louisiana, United States
West Broadway Clinic
🇺🇸Council Bluffs, Iowa, United States
CHEAR Center LLC
🇺🇸Bronx, New York, United States
Northwest Louisiana Nephrology L.L.C
🇺🇸Shreveport, Louisiana, United States
Albany Medical College
🇺🇸Albany, New York, United States
Mountain Diabetes & Endocrine Center
🇺🇸Asheville, North Carolina, United States
Carteret Medical Group
🇺🇸Morehead City, North Carolina, United States
Mountain Kidney and Hypertension Associates
🇺🇸Asheville, North Carolina, United States
PMG Research of Rocky Mount, LLC
🇺🇸Rocky Mount, North Carolina, United States
Diabetes And Endocrinology Consultants, P.C.
🇺🇸Morehead City, North Carolina, United States
Lifespan Clinical Research Center
🇺🇸East Providence, Rhode Island, United States
Southeast Renal Research Institute
🇺🇸Chattanooga, Tennessee, United States
Heritage Valley Medical Group, Inc.
🇺🇸Beaver, Pennsylvania, United States
PMG Research, Inc d/b/a/ PMG Research of Knoxville
🇺🇸Knoxville, Tennessee, United States
PMG Research Of Charleston, LLC
🇺🇸Mount Pleasant, South Carolina, United States
Corsicana Medical Research, LLC
🇺🇸Corsicana, Texas, United States
DaVita Clinical Research
🇺🇸Lewisville, Texas, United States
Royal Melbourne Hospital
🇦🇺Parkville, Australia
LMC Clinical Research Inc. (Etobicoke)
🇨🇦Etobicoke, Canada
LMC Clinical Research Inc. (Brampton)
🇨🇦Brampton, Canada
Clinical Research Solution Inc.
🇨🇦Kitchener, Canada
Japan Organization of Occupational Health and Safety Chubu Rosai Hospital
🇯🇵Nagoya-shi, Japan
Japanese Red Cross Musashino Hospital
🇯🇵Musashino, Japan
Hoshina Clinic
🇯🇵Saitama-shi, Japan
Endocrine, Diabetes & Research Centre (Capital and Coast District Health Board)
🇳🇿Wellington, New Zealand
Creekside Endocrine Associates, PC
🇺🇸Denver, Colorado, United States
Clinical Research Consultants, LLC
🇺🇸Kansas City, Missouri, United States
PMG Research of Winston-Salem, LLC
🇺🇸Winston-Salem, North Carolina, United States