Clinical trial NCT02177786: Efficacy, Safety, and Tolerability of Selonsertib (GS-4997) in Participants With Diabetic Kidney Disease
Official title: A Phase 2, Double-Blind, Placebo-Controlled, Dose-Ranging Study Evaluating the Efficacy, Safety, and Tolerability of GS-4997 in Subjects With Diabetic Kidney Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Kidney Disease
Keywords: Diabetic Kidney Disease
Gilead
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2014-06-30
Enrollment: 334
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to determine the effect of selonsertib (formerly GS-4997) on estimated glomerular filtration rate (eGFR) decline in participants with diabetic kidney disease (DKD). Participants will be randomized with a 1:1:1:1 allocation to receive 1 of 3 doses of selonsertib (2 mg, 6 mg, or 18 mg) or matching placebo.


Eligibility criteria: Key Inclusion Criteria:

* Adult male or females with prior diagnosis of Diabetic Kidney Disease
* Type 2 diabetes mellitus diagnosis for at least 6 months
* eGFR (MDRD) at screening ≥ 15 mL/min/1.73m\^2 to \< 60 mL/min/1.73m\^2
* Urine albumin to creatinine ratio (UACR) as follows:

  * Stage/Stratum 3a: eGFR range 45 to \< 60 mL/min; UACR ≥ 600 mg/g
  * Stage/Stratum 3b: eGFR range 30 to \< 45 mL/min; UACR ≥ 300 mg/g
  * Stage/Stratum 4: eGFR range 15 to \< 30 mL/min; UACR ≥ 150 mg/g
* Receiving angiotensin-converting-enzyme inhibitor (ACEi) or angiotensin receptor blockers (ARB) at a minimum dose deemed appropriate for the individual by the investigator and be at a stable dose for the last three months

  * Individuals not on ACEi/ARB may be screened if there is documented intolerance to ACE inhibitor and/or ARB

Key Exclusion Criteria:

* Type 1 diabetes mellitus
* HbA1c \> 9.5%
* Non-diabetic kidney disease
* UACR \> 5000 mg/g on any measurement during screening
* End stage renal disease (ESRD; receiving peritoneal dialysis, hemodialysis, or status post renal transplantation) or anticipated to occur within the treatment period
* Unstable cardiovascular disease
* Pregnant or lactating females

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Change in eGFR From Baseline at Week 48
timeFrame: Baseline; Week 48
Secondary outcomes:
measure: Percentage of Participants Achieving at Least a 30% Reduction From Baseline in Albuminuria (As Measured by Urine Albumin to Creatinine Ratio) at Week 48
timeFrame: Baseline; Week 48
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham (UAB)
state: Alabama
city: Huntsville
country: United States
facility: Chase Medcare
state: Alabama
city: Toney
country: United States
facility: Choice Medicine
state: Alabama
city: Peoria
country: United States
facility: Akdhc Medical Research Services, Llc
state: Arizona
city: Phoenix
country: United States
facility: Akdhc Medical Research Services, Llc
state: Arizona
city: Phoenix
country: United States
facility: Akdhc Medical Research Services, Llc
state: Arizona
city: Prescott
country: United States
facility: Akdhc Medical Research Services, Llc
state: Arizona
city: Tempe
country: United States
facility: Robert J. Bloomberg, MD
state: Arizona
city: Tucson
country: United States
facility: AKDHC East Office
state: Arizona
city: Harrisburg
country: United States
facility: Clinical Research Connections, LLC
state: Arkansas
city: Azusa
country: United States
facility: North America Research Institute
state: California
city: Chula Vista
country: United States
facility: California Institute of Renal Research
state: California
city: El Centro
country: United States
facility: California Institute of Renal Research Inc.
state: California
city: Granada Hills
country: United States
facility: Renal Consultants Medical Group Granada Hills
state: California
city: Lomita
country: United States
facility: Torrance Clinical Research
state: California
city: Los Angeles
country: United States
facility: IMD Medical Group
state: California
city: Los Angeles
country: United States
facility: Academic Medical Research Institute
state: California
city: Lynwood
country: United States
facility: Kidney Research Center
state: California
city: Riverside
country: United States
facility: Apex Research of Riverside
state: California
city: San Francisco
country: United States
facility: San Francisco General Hospital
state: California
city: Santa Clarita
country: United States
facility: Clearview Medical Research, LLC
state: California
city: Whittier
country: United States
facility: American Institute of Research
state: California
city: DeBary
country: United States
facility: Omega Research Consultants
state: Florida
city: DeLand
country: United States
facility: Creekside Medical Research
state: Florida
city: Edgewater
country: United States
facility: Riverside Clinical Research
state: Florida
city: Jupiter
country: United States
facility: ASA Clinical Research
state: Florida
city: Kissimmee
country: United States
facility: FPA Clinical Research
state: Florida
city: Kissimmee
country: United States
facility: The Chappel Group LLC
state: Florida
city: Lauderdale Lakes
country: United States
facility: South Florida Research Institute
state: Florida
city: Miami
country: United States
facility: Prestige Clinical Research Center Inc
state: Florida
city: Miami
country: United States
facility: International Physicians Research / Nephrology Associates of South Miami
state: Florida
city: Miami
country: United States
facility: Tellus Clinical Research, Inc
state: Florida
city: Miami
country: United States
facility: Coral Research Clinic Corp
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Research, Inc.
state: Florida
city: Ocala
country: United States
facility: Discovery Medical Research Group
state: Florida
city: Orlando
country: United States
facility: Central Florida Internists
state: Florida
city: Palm Harbor
country: United States
facility: Sunset Point Medical Associates DBA
state: Florida
city: Pembroke Pines
country: United States
facility: Pines Clinical Research Inc.
state: Florida
city: Saint Cloud
country: United States
facility: Central Florida Internists
state: Florida
city: Winter Park
country: United States
facility: Florida Pulmonary Research Institute
state: Florida
city: Conyers
country: United States
facility: Rockdale Medical Research Associates
state: Georgia
city: Chicago
country: United States
facility: John H. Stroger Jr. Hospital Of Cook County
state: Illinois
city: Crystal Lake
country: United States
facility: Midwest Endocrinology
state: Illinois
city: Mishawaka
country: United States
facility: Beacon Medical Group Kidney and Hypertension Center
state: Indiana
city: Council Bluffs
country: United States
facility: West Broadway Clinic
state: Iowa
city: Hutchinson
country: United States
facility: Hutchinson Clinic, P.A
state: Kansas
city: Wichita
country: United States
facility: Kansas Nephrology Research Institute, LLC
state: Kansas
city: Louisville
country: United States
facility: L-MARC Research Center
state: Kentucky
city: Paducah
country: United States
facility: Four Rivers Clinical Research
state: Kentucky
city: Lafayette
country: United States
facility: Research Nurse Specialists, LLc
state: Louisiana
city: Metairie
country: United States
facility: Crescent City Clinical Research Center
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: New Orleans
country: United States
facility: Internal Medicine Specialists
state: Louisiana
city: Ruston
country: United States
facility: Green Clinic LLC
state: Louisiana
city: Shreveport
country: United States
facility: Northwest Louisiana Nephrology
state: Louisiana
city: Zachary
country: United States
facility: Southern Clinical Research
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Hospital/University
state: Maryland
city: Bethesda
country: United States
facility: A. Kaldun Nossuli MD Research
state: Maryland
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Flint
country: United States
facility: Apex Medical Research.Com
state: Michigan
city: Flint
country: United States
facility: Elite Clinical Research
state: Michigan
city: Troy
country: United States
facility: Troy Internal Medicine, PC
state: Michigan
city: Kansas City
country: United States
facility: VA Medical Center
state: Missouri
city: Butte
country: United States
facility: Mercury Street Medical Group, PLLC, Big Sky Clinical Research, LLC
state: Montana
city: Omaha
country: United States
facility: Alegent Creighton Health
state: Nebraska
city: Omaha
country: United States
facility: Creighton Diabetes Center
state: Nebraska
city: Voorhees
country: United States
facility: Nephrology and Hypertension Associates of New Jersey
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials
state: New Mexico
city: Flushing
country: United States
facility: Nephrology Associates, PC
state: New York
city: Asheville
country: United States
facility: Mountain Kidney and Hypertension Associates
state: North Carolina
city: Rocky Mount
country: United States
facility: Boice-Willis Clinic
state: North Carolina
city: Shelby
country: United States
facility: Carolina Research Center
state: North Carolina
city: Cincinnati
country: United States
facility: Hightop Medical Research Center
state: Ohio
city: Marion
country: United States
facility: Craig S Thompson MD LLC
state: Ohio
city: Mentor
country: United States
facility: Your Diabetes Endocrine Nutrition Group Inc
state: Ohio
city: Oklahoma City
country: United States
facility: Chris Sholer, MD, PC
state: Oklahoma
city: Bend
country: United States
facility: Bend Memorial Clinic
state: Oregon
city: Chattanooga
country: United States
facility: Southeast Renal Research Institute
state: Tennessee
city: Knoxville
country: United States
facility: Knoxville Kidney Center
state: Tennessee
city: Arlington
country: United States
facility: Arlington Nephrology
state: Texas
city: Beaumont
country: United States
facility: MW Clinical Research Center
state: Texas
city: Corpus Christi
country: United States
facility: Padre Coast Clinical Research
state: Texas
city: Corsicana
country: United States
facility: Corsicana Medical Research, PLLC
state: Texas
city: El Paso
country: United States
facility: Texas Tech Univ. Health Sciences Center
state: Texas
city: Gonzales
country: United States
facility: TVC Clinical Research
state: Texas
city: Houston
country: United States
facility: Diagnostic Clinic of Houston
state: Texas
city: Houston
country: United States
facility: Mercury Clinical Research
state: Texas
city: Houston
country: United States
facility: Lakewood Family Practice
state: Texas
city: Houston
country: United States
facility: Southwest Clinical Trials
state: Texas
city: Houston
country: United States
facility: Southwest Houston Research, Ltd.
state: Texas
city: Pearland
country: United States
facility: HMRI CCAT Pearland
state: Texas
city: San Antonio
country: United States
facility: Clinical Advancement Center, PLLC
state: Texas
city: San Antonio
country: United States
facility: Briggs Clinical Research, LLC
state: Texas
city: San Antonio
country: United States
facility: San Antonio Kidney Disease Center Physicians Group, P.L.L.C.
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Bountiful
country: United States
facility: Val R. Hansen, M.D.
state: Utah
city: Burlington
country: United States
facility: Fletcher Allen Health Care
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Zablocki VAMC
state: Wisconsin
city: Vancouver
country: Canada
facility: BC Diabetes
state: British Columbia
city: Courtice
country: Canada
facility: Co-Medica Research Network
state: Ontario
city: Kitchener
country: Canada
facility: Clinical Research Solutions, Inc.
state: Ontario
city: Scarborough
country: Canada
facility: OTT Healthcare Inc.
state: Ontario
city: Toronto
country: Canada
facility: Toronto East General Medical Centre
state: Ontario
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Chertow GM, Pergola PE, Chen F, Kirby BJ, Sundy JS, Patel UD; GS-US-223-1015 Investigators. Effects of Selonsertib in Patients with Diabetic Kidney Disease. J Am Soc Nephrol. 2019 Oct;30(10):1980-1990. doi: 10.1681/ASN.2018121231. Epub 2019 Sep 10.
citation: Tesch GH, Ma FY, Han Y, Liles JT, Breckenridge DG, Nikolic-Paterson DJ. ASK1 Inhibitor Halts Progression of Diabetic Nephropathy in Nos3-Deficient Mice. Diabetes. 2015 Nov;64(11):3903-13. doi: 10.2337/db15-0384. Epub 2015 Jul 15.