Study to Evaluate the Efficacy and Safety of Selonsertib in Participants With Moderate to Advanced Diabetic Kidney Disease

Diabetic Kidney Disease Clinical Trial

— MOSAIC  

Official title:

MOSAIC - A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter Study Evaluating the Efficacy and Safety of Selonsertib in Subjects With Moderate to Advanced Diabetic Kidney Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04026165
• Other study ID #: GS-US-223-1017
• Secondary ID: JapicCTI-1949112
• Status: Completed
• Phase: Phase 2
• Start date: July 24, 2019
• Est. completion date: September 3, 2021

Study information

• Verified date: November 2022
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 384
• Est. completion date: September 3, 2021
• Est. primary completion date: September 3, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Key Inclusion Criteria:

• 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 Exclusion Criteria:

• 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

1. ACEi and ARB or

2. 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.

Related Conditions & MeSH terms

• Diabetic Kidney Disease
• Diabetic Nephropathies
• Kidney Diseases

Intervention

Drug:
• SEL
Tablet administered orally once daily
• Placebo
Tablet administered orally once daily

Locations

Country	Name	City	State
Australia	St. Vincent Hospital, Melbourne	Fitzroy
Australia	Austin Health and University of Melbourne	Heidelberg	Victoria
Australia	Royal Melbourne Hospital	Parkville
Canada	LMC Clinical Research Inc. (Barrie)	Barrie
Canada	LMC Clinical Research Inc. (Brampton)	Brampton
Canada	LMC Clinical research Inc. (Thornhill)	Concord
Canada	LMC Clinical Research Inc. (Etobicoke)	Etobicoke
Canada	Clinical Research Solution Inc.	Kitchener
Canada	Centre de Recherche Clinique de Lava	Laval
Canada	Dr TGElliott Inc dba BC Diabetes	Vancouver
Canada	Winnipeg Clinic	Winnipeg
Japan	Asahikawa Medical University Hospital	Asahikawa
Japan	National Hospital Organization Chiba-East-Hospital	Chiba
Japan	Kagoshima University Hospital	Kagoshima
Japan	Kokura Memorial Hospital	Kitakyushu-shi
Japan	Yamanashi Prefectural Central Hospital	Kofu
Japan	Kurobe City Hospital	Kurobe-shi
Japan	Kurume University Hospital	Kurume-shi
Japan	Kozawa Eye Hospital and Diabetes Center	Mito-shi
Japan	Nakamoto Medical Clinic	Mito-shi
Japan	Japanese Red Cross Musashino Hospital	Musashino
Japan	Nagasaki University Hospital	Nagasaki
Japan	Daido Clinic	Nagoya-shi
Japan	Japan Organization of Occupational Health and Safety Chubu Rosai Hospital	Nagoya-shi
Japan	Nakakinen Clinic	Naka-shi
Japan	Niigata University Medical & Dental Hospital	Niigata
Japan	Okayama University Hospital	Okayama
Japan	Osaka General Medical Center	Osaka
Japan	Hoshina Clinic	Saitama-shi
Japan	Sanuki Municipal Hospital	Sanuki-shi
Japan	Tachikawa Hospital	Tachikawa-shi
Japan	Mishuku Hospital	Tokyo
Japan	Nihon University Itabashi Hospital	Tokyo
Japan	TOYOTA Memorial Hospital	Toyota-shi
Japan	Yokohama City University Hospital	Yokohama-shi
New Zealand	Auckland City Hospital (Auckland District Health Board)	Auckland
New Zealand	Middlemore Clinical Trials Trust trading as Middlemore Clinical Trials	Auckland
New Zealand	Lipid and Diabetes Research Group	Christchurch
New Zealand	Waitemata District Health Board- North Shore Hospital	North Shore
New Zealand	Endocrine, Diabetes & Research Centre (Capital and Coast District Health Board)	Wellington
United States	Albany Medical College	Albany	New York
United States	Arlington Nephrology	Arlington	Texas
United States	Mountain Diabetes & Endocrine Center	Asheville	North Carolina
United States	Mountain Kidney and Hypertension Associates	Asheville	North Carolina
United States	Atlanta Center for Clinical Research	Atlanta	Georgia
United States	Heritage Valley Medical Group, Inc.	Beaver	Pennsylvania
United States	Northeast Clinical Research Center, LLC	Bethlehem	Pennsylvania
United States	CHEAR Center LLC	Bronx	New York
United States	Clearview Medical Research, LLC	Canyon Country	California
United States	Southeast Renal Research Institute	Chattanooga	Tennessee
United States	University Diabetes and Endocrine Consultants	Chattanooga	Tennessee
United States	Research By Design, LLC	Chicago	Illinois
United States	Corsicana Medical Research, LLC	Corsicana	Texas
United States	West Broadway Clinic	Council Bluffs	Iowa
United States	North Texas Endocrine Center	Dallas	Texas
United States	Omega Research Maitland, LLC	DeBary	Florida
United States	Creekside Endocrine Associates, PC	Denver	Colorado
United States	Lifespan Clinical Research Center	East Providence	Rhode Island
United States	Aa Mrc, Llc	Flint	Michigan
United States	Elite Research Center	Flint	Michigan
United States	The Medical Group of Texas	Fort Worth	Texas
United States	Arizona Kidney Disease and Hypertension Centers	Glendale	Arizona
United States	Kidney Disease Medical Group, Inc.	Glendale	California
United States	New West Physicians, Inc	Golden	Colorado
United States	Renal Consultants Medical Group	Granada Hills	California
United States	North Shore University Hospital: Division of Nephrology	Great Neck	New York
United States	Marin Endocrine Care & Research, Inc.	Greenbrae	California
United States	East-West Medical Research Institute	Honolulu	Hawaii
United States	DaVita Clinical Research	Houston	Texas
United States	Mercury Clinical Research	Houston	Texas
United States	Primecare Medical Group	Houston	Texas
United States	Clinical Research Consultants, LLC	Kansas City	Missouri
United States	Knoxville Kidney Center, PLLC	Knoxville	Tennessee
United States	PMG Research, Inc d/b/a/ PMG Research of Knoxville	Knoxville	Tennessee
United States	PMG Research, Inc. d/b/a PMG Research of Knoxville	Knoxville	Tennessee
United States	California Institute of Renal Research	La Mesa	California
United States	Pelican Point Dialysis - DaVita Clinical Research	Las Vegas	Nevada
United States	South Florida Research Institute	Lauderdale Lakes	Florida
United States	Georgia Nephrology Research Institute	Lawrenceville	Georgia
United States	DaVita Clinical Research	Lewisville	Texas
United States	Academic Medical Research Institute	Los Angeles	California
United States	SV Research LLC	Marion	Ohio
United States	Memphis Veteran Affairs Medical Center	Memphis	Tennessee
United States	Boise Kidney & Hypertension, PLLC	Meridian	Idaho
United States	Midwest Nephrology Group, PLLC	Midwest City	Oklahoma
United States	Carteret Medical Group	Morehead City	North Carolina
United States	Diabetes And Endocrinology Consultants, P.C.	Morehead City	North Carolina
United States	PMG Research Of Charleston, LLC	Mount Pleasant	South Carolina
United States	Internal Medicine Specialists, Inc	New Orleans	Louisiana
United States	Suncoast Clinical Research, Inc.	New Port Richey	Florida
United States	Rose Salter Medical Research Foundation	Newport Beach	California
United States	Valley Renal Medical Group Research	Northridge	California
United States	Discovery Medical Research Group, Inc	Ocala	Florida
United States	Four Rivers Clinical Research	Paducah	Kentucky
United States	Houston Methodist Research Institute - CCAT Pearland	Pearland	Texas
United States	Coastal Nephrology Associates Research Center, LLC. D/B/A Volunteer Medical Research	Port Charlotte	Florida
United States	PMG Research of Rocky Mount, LLC	Rocky Mount	North Carolina
United States	Clinical Advancement Center, PLLC	San Antonio	Texas
United States	Northeast Clinical Research of San Antonio	San Antonio	Texas
United States	California Institute of Renal Research	San Diego	California
United States	California Kidney Specialist	San Dimas	California
United States	Northwest Louisiana Nephrology L.L.C	Shreveport	Louisiana
United States	Endocrine Associates of Long Island, PC	Smithtown	New York
United States	PMG Research Inc., d/b/a PMG Research of Piedmont Healthcare	Statesville	North Carolina
United States	Arcturus Healthcare, PLC, Troy Internal Medicine Research Division	Troy	Michigan
United States	AKDHC Medical Research Services, LLC	Tucson	Arizona
United States	Buynak Clinical Research, P.C.	Valparaiso	Indiana
United States	Western Nephrology and Metabolic Bone Disease, PC	Westminster	Colorado
United States	Kansas Nephrology Research Institute, LLC	Wichita	Kansas
United States	Wilmington Health, PLLC	Wilmington	North Carolina
United States	PMG Research of Winston-Salem, LLC	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Japan,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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)
Primary	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.	Treatment-specific Baselines through Week 84
Secondary	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.	Week 48
Secondary	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.	From randomization up to Week 101
Secondary	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.	Pre-run-in Baseline (Pre-run in Baseline = Average of visit A (Enrollment) and Visit B (7-14 days after Visit A) eGFRcys values)
Secondary	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.	Pre-run-in Baseline through Week 84

External Links

•   Gilead Clinical Trials Website