Efficacy, Safety, and Tolerability of Selonsertib (GS-4997) in Participants With Diabetic Kidney Disease

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetic Kidney Disease
• Intervention / Treatment: Drug: Selonsertib; Drug: Placebo to match selonsertib

• Study Type: Interventional
• Enrollment (Actual): 334
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z1M9
      • BC Diabetes
  • Ontario
    • Courtice, Ontario, Canada, L1E 3C3
      • Co-Medica Research Network
    • Kitchener, Ontario, Canada, N2H 5Z8
      • Clinical Research Solutions, Inc.
    • Scarborough, Ontario, Canada, M1H 3G4
      • OTT Healthcare Inc.
    • Toronto, Ontario, Canada
      • Toronto East General Medical Centre
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • The University of Alabama at Birmingham (UAB)
    • Huntsville, Alabama, United States, 35811
      • Chase Medcare
    • Toney, Alabama, United States, 35773
      • Choice Medicine
  • Arizona
    • Peoria, Arizona, United States, 85381
      • AKDHC Medical Research Services, LLC
    • Phoenix, Arizona, United States, 85012
      • AKDHC Medical Research Services, LLC
    • Phoenix, Arizona, United States, 85027
      • AKDHC Medical Research Services, LLC
    • Prescott, Arizona, United States, 86301
      • AKDHC Medical Research Services, LLC
    • Tempe, Arizona, United States, 85283
      • Robert J. Bloomberg, MD
    • Tucson, Arizona, United States, 85712
      • AKDHC East Office
  • Arkansas
    • Harrisburg, Arkansas, United States, 72432
      • Clinical Research Connections, LLC
  • California
    • Azusa, California, United States, 91702
      • North America Research Institute
    • Chula Vista, California, United States, 91910
      • California Institute of Renal Research
    • El Centro, California, United States, 92243
      • California Institute of Renal Research Inc.
    • Granada Hills, California, United States, 91344
      • Renal Consultants Medical Group Granada Hills
    • Lomita, California, United States, 90717
      • Torrance Clinical Research
    • Los Angeles, California, United States, 90022
      • Academic Medical Research Institute
    • Los Angeles, California, United States, 90020
      • IMD Medical Group
    • Lynwood, California, United States, 90262
      • Kidney Research Center
    • Riverside, California, United States, 92505
      • Apex Research of Riverside
    • San Francisco, California, United States, 94110
      • San Francisco General Hospital
    • Santa Clarita, California, United States, 91350
      • Clearview Medical Research, LLC
    • Whittier, California, United States, 90603
      • American Institute of Research
  • Florida
    • DeBary, Florida, United States, 32713
      • Omega Research Consultants
    • DeLand, Florida, United States, 32720
      • Creekside Medical Research
    • Edgewater, Florida, United States, 32132
      • Riverside Clinical Research
    • Jupiter, Florida, United States, 33458
      • ASA Clinical Research
    • Kissimmee, Florida, United States, 34741
      • FPA Clinical Research
    • Kissimmee, Florida, United States, 34741
      • The Chappel Group LLC
    • Lauderdale Lakes, Florida, United States, 33313
      • South Florida Research Institute
    • Miami, Florida, United States, 33133
      • Prestige Clinical Research Center Inc
    • Miami, Florida, United States, 33173
      • International Physicians Research / Nephrology Associates of South Miami
    • Miami, Florida, United States, 33173
      • Tellus Clinical Research, Inc
    • Miami, Florida, United States, 33175
      • Coral Research Clinic Corp
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research, Inc.
    • Ocala, Florida, United States, 34471
      • Discovery Medical Research Group
    • Orlando, Florida, United States, 32811
      • Central Florida Internists
    • Palm Harbor, Florida, United States, 34684
      • Sunset Point Medical Associates DBA
    • Pembroke Pines, Florida, United States, 33028
      • Pines Clinical Research Inc.
    • Saint Cloud, Florida, United States, 34769
      • Central Florida Internists
    • Winter Park, Florida, United States, 32789
      • Florida Pulmonary Research Institute
  • Georgia
    • Conyers, Georgia, United States, 30094
      • Rockdale Medical Research Associates
  • Illinois
    • Chicago, Illinois, United States, 60612
      • John H. Stroger Jr. Hospital of Cook County
    • Crystal Lake, Illinois, United States, 60012
      • Midwest Endocrinology
  • Indiana
    • Mishawaka, Indiana, United States, 46544
      • Beacon Medical Group Kidney and Hypertension Center
  • Iowa
    • Council Bluffs, Iowa, United States, 51501
      • West Broadway Clinic
  • Kansas
    • Hutchinson, Kansas, United States, 67502
      • Hutchinson Clinic, P.A
    • Wichita, Kansas, United States, 67214
      • Kansas Nephrology Research Institute, LLC
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • L-MARC Research Center
    • Paducah, Kentucky, United States, 42003
      • Four Rivers Clinical Research
  • Louisiana
    • Lafayette, Louisiana, United States, 70503
      • Research Nurse Specialists, LLc
    • Metairie, Louisiana, United States, 70006
      • Crescent City Clinical Research Center
    • New Orleans, Louisiana, United States, 70112
      • Tulane University
    • New Orleans, Louisiana, United States, 70115
      • Internal Medicine Specialists
    • Ruston, Louisiana, United States, 71270
      • Green Clinic LLC
    • Shreveport, Louisiana, United States, 71101
      • Northwest Louisiana Nephrology
    • Zachary, Louisiana, United States, 70791
      • Southern Clinical Research
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins Hospital/University
    • Bethesda, Maryland, United States, 20814
      • A. Kaldun Nossuli MD Research
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University
    • Flint, Michigan, United States, 48504
      • Apex Medical Research.Com
    • Flint, Michigan, United States, 48532
      • Elite Clinical Research
    • Troy, Michigan, United States, 48098
      • Troy Internal Medicine, PC
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • VA Medical Center
  • Montana
    • Butte, Montana, United States, 59701
      • Mercury Street Medical Group, PLLC, Big Sky Clinical Research, LLC
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Creighton Diabetes Center
    • Omaha, Nebraska, United States, 68131
      • Alegent Creighton Health
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
      • Nephrology and Hypertension Associates of New Jersey
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials
  • New York
    • Flushing, New York, United States, 11355
      • Nephrology Associates, PC
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mountain Kidney and Hypertension Associates
    • Rocky Mount, North Carolina, United States, 27804
      • Boice-Willis Clinic
    • Shelby, North Carolina, United States, 28150
      • Carolina Research Center
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • Hightop Medical Research Center
    • Marion, Ohio, United States, 43302
      • Craig S Thompson MD LLC
    • Mentor, Ohio, United States, 44060
      • Your Diabetes Endocrine Nutrition Group Inc
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73116
      • Chris Sholer, MD, PC
  • Oregon
    • Bend, Oregon, United States, 97701
      • Bend Memorial Clinic
  • Tennessee
    • Chattanooga, Tennessee, United States, 37408
      • Southeast Renal Research Institute
    • Knoxville, Tennessee, United States, 37923
      • Knoxville Kidney Center
  • Texas
    • Arlington, Texas, United States, 76015
      • Arlington Nephrology
    • Beaumont, Texas, United States, 77701
      • MW Clinical Research Center
    • Corpus Christi, Texas, United States, 78404
      • Padre Coast Clinical Research
    • Corsicana, Texas, United States, 75110
      • Corsicana Medical Research, PLLC
    • El Paso, Texas, United States, 79905
      • Texas Tech Univ. Health Sciences Center
    • Gonzales, Texas, United States, 78629
      • TVC Clinical Research
    • Houston, Texas, United States, 77004
      • Diagnostic Clinic of Houston
    • Houston, Texas, United States, 77074
      • Southwest Clinical Trials
    • Houston, Texas, United States, 77099
      • Southwest Houston Research, Ltd.
    • Houston, Texas, United States, 77036
      • Mercury Clinical Research
    • Houston, Texas, United States, 77070
      • Lakewood Family Practice
    • Pearland, Texas, United States, 77584
      • HMRI CCAT Pearland
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78215
      • Clinical Advancement Center, PLLC
    • San Antonio, Texas, United States, 78229
      • San Antonio Kidney Disease Center Physicians Group, P.L.L.C.
    • San Antonio, Texas, United States, 78224
      • Briggs Clinical Research, LLC
  • Utah
    • Bountiful, Utah, United States, 84010
      • Val R. Hansen, M.D.
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Fletcher Allen Health Care
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
  • Wisconsin
    • Madison, Wisconsin, United States, 53713
      • University of Wisconsin
    • Milwaukee, Wisconsin, United States, 53295
      • Zablocki VAMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Selonsertib 2 mg; Participants will receive selonsertib 2 mg for 48 weeks.	Drug: Selonsertib; Tablets administered orally once daily; Other Names: GS-4997
Experimental: Selonsertib 6 mg; Participants will receive selonsertib 6 mg for 48 weeks.	Drug: Selonsertib; Tablets administered orally once daily; Other Names: GS-4997
Experimental: Selonsertib 18 mg; Participants will receive selonsertib 18 mg for 48 weeks.	Drug: Selonsertib; Tablets administered orally once daily; Other Names: GS-4997
Placebo Comparator: Placebo to match selonsertib; Participants will receive placebo to match selonsertib for 48 weeks.	Drug: Placebo to match selonsertib; Tablets administered orally once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in eGFR From Baseline at Week 48	The values of eGFR were calculated using the MDRD equation: eGFR = 175 x Serum Creatinine^-1.154 × age^-0.203 × 1.212 (if participant is black) × 0.742 (if female).	Baseline; Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving at Least a 30% Reduction From Baseline in Albuminuria (As Measured by Urine Albumin to Creatinine Ratio) at Week 48	Baseline was the average of the last 2 values prior to randomization and the last value on or after the randomization date, but prior to or on the first dose date. Urine Albumin to Creatinine Ratio= urine albumin/urine creatinine.	Baseline; Week 48

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: June 26, 2014
• First Submitted That Met QC Criteria: June 26, 2014
• First Posted (Estimate): June 30, 2014

Study Record Updates

• Last Update Posted (Actual): November 5, 2019
• Last Update Submitted That Met QC Criteria: October 23, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Diabetic Kidney Disease; Gilead
• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Kidney Diseases; Diabetic Nephropathies; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Selonsertib
• Other Study ID Numbers: GS-US-223-1015

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No