Clinical trial NCT04026165: Study to Evaluate the Efficacy and Safety of Selonsertib in Participants With Moderate to Advanced Diabetic Kidney Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Kidney Disease
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2019-07-19
Enrollment: 384
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Participants received Run-in and Randomized treatments sequentially and in the Randomized Phase, the treatments were assigned in parallel.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Treatment-specific Baseline Estimated Glomerular Filtration Rate Based on Creatinine (eGFRcr)
timeFrame: 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)
measure: eGFRcr Slope
timeFrame: Treatment-specific Baselines through Week 84
Secondary outcomes:
measure: Percentage of Participants With Kidney Clinical Events at Week 48
timeFrame: Week 48
measure: Time From Randomization to First Occurrence of a Kidney Clinical Event: Event Rate Per 100 Participant-years for First Occurrence of Kidney Clinical Event
timeFrame: From randomization up to Week 101
measure: Pre-run-in Baseline Estimated Glomerular Filtration Rate Based on Cystatin C (eGFRcys)
timeFrame: Pre-run-in Baseline (Pre-run in Baseline = Average of visit A (Enrollment) and Visit B (7-14 days after Visit A) eGFRcys values)
measure: eGFRcys Slope
timeFrame: Pre-run-in Baseline through Week 84
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Arizona Kidney Disease and Hypertension Centers
state: Arizona
city: Tucson
country: United States
facility: AKDHC Medical Research Services, LLC
state: Arizona
city: Canyon Country
country: United States
facility: Clearview Medical Research, LLC
state: California
city: Glendale
country: United States
facility: Kidney Disease Medical Group, Inc.
state: California
city: Granada Hills
country: United States
facility: Renal Consultants Medical Group
state: California
city: Greenbrae
country: United States
facility: Marin Endocrine Care & Research, Inc.
state: California
city: La Mesa
country: United States
facility: California Institute of Renal Research
state: California
city: Los Angeles
country: United States
facility: Academic Medical Research Institute
state: California
city: Newport Beach
country: United States
facility: Rose Salter Medical Research Foundation
state: California
city: Northridge
country: United States
facility: Valley Renal Medical Group Research
state: California
city: San Diego
country: United States
facility: California Institute of Renal Research
state: California
city: San Dimas
country: United States
facility: California Kidney Specialist
state: California
city: Denver
country: United States
facility: Creekside Endocrine Associates, PC
state: Colorado
city: Golden
country: United States
facility: New West Physicians, Inc
state: Colorado
city: Westminster
country: United States
facility: Western Nephrology and Metabolic Bone Disease, PC
state: Colorado
city: DeBary
country: United States
facility: Omega Research Maitland, LLC
state: Florida
city: Lauderdale Lakes
country: United States
facility: South Florida Research Institute
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, Inc
state: Florida
city: Port Charlotte
country: United States
facility: Coastal Nephrology Associates Research Center, LLC. D/B/A Volunteer Medical Research
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Clinical Research
state: Georgia
city: Lawrenceville
country: United States
facility: Georgia Nephrology Research Institute
state: Georgia
city: Honolulu
country: United States
facility: East-West Medical Research Institute
state: Hawaii
city: Meridian
country: United States
facility: Boise Kidney & Hypertension, PLLC
state: Idaho
city: Chicago
country: United States
facility: Research By Design, LLC
state: Illinois
city: Valparaiso
country: United States
facility: Buynak Clinical Research, P.C.
state: Indiana
city: Council Bluffs
country: United States
facility: West Broadway Clinic
state: Iowa
city: Wichita
country: United States
facility: Kansas Nephrology Research Institute, LLC
state: Kansas
city: Paducah
country: United States
facility: Four Rivers Clinical Research
state: Kentucky
city: New Orleans
country: United States
facility: Internal Medicine Specialists, Inc
state: Louisiana
city: Shreveport
country: United States
facility: Northwest Louisiana Nephrology L.L.C
state: Louisiana
city: Flint
country: United States
facility: Aa Mrc, Llc
state: Michigan
city: Flint
country: United States
facility: Elite Research Center
state: Michigan
city: Troy
country: United States
facility: Arcturus Healthcare, PLC, Troy Internal Medicine Research Division
state: Michigan
city: Kansas City
country: United States
facility: Clinical Research Consultants, LLC
state: Missouri
city: Las Vegas
country: United States
facility: Pelican Point Dialysis - DaVita Clinical Research
state: Nevada
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Bronx
country: United States
facility: CHEAR Center LLC
state: New York
city: Great Neck
country: United States
facility: North Shore University Hospital: Division of Nephrology
state: New York
city: Smithtown
country: United States
facility: Endocrine Associates of Long Island, PC
state: New York
city: Asheville
country: United States
facility: Mountain Kidney and Hypertension Associates
state: North Carolina
city: Asheville
country: United States
facility: Mountain Diabetes & Endocrine Center
state: North Carolina
city: Morehead City
country: United States
facility: Carteret Medical Group
state: North Carolina
city: Morehead City
country: United States
facility: Diabetes And Endocrinology Consultants, P.C.
state: North Carolina
city: Rocky Mount
country: United States
facility: PMG Research of Rocky Mount, LLC
state: North Carolina
city: Statesville
country: United States
facility: PMG Research Inc., d/b/a PMG Research of Piedmont Healthcare
state: North Carolina
city: Wilmington
country: United States
facility: Wilmington Health, PLLC
state: North Carolina
city: Winston-Salem
country: United States
facility: PMG Research of Winston-Salem, LLC
state: North Carolina
city: Marion
country: United States
facility: SV Research LLC
state: Ohio
city: Midwest City
country: United States
facility: Midwest Nephrology Group, PLLC
state: Oklahoma
city: Beaver
country: United States
facility: Heritage Valley Medical Group, Inc.
state: Pennsylvania
city: Bethlehem
country: United States
facility: Northeast Clinical Research Center, LLC
state: Pennsylvania
city: East Providence
country: United States
facility: Lifespan Clinical Research Center
state: Rhode Island
city: Mount Pleasant
country: United States
facility: PMG Research Of Charleston, LLC
state: South Carolina
city: Chattanooga
country: United States
facility: Southeast Renal Research Institute
state: Tennessee
city: Chattanooga
country: United States
facility: University Diabetes and Endocrine Consultants
state: Tennessee
city: Knoxville
country: United States
facility: PMG Research, Inc d/b/a/ PMG Research of Knoxville
state: Tennessee
city: Knoxville
country: United States
facility: Knoxville Kidney Center, PLLC
state: Tennessee
city: Knoxville
country: United States
facility: PMG Research, Inc. d/b/a PMG Research of Knoxville
state: Tennessee
city: Memphis
country: United States
facility: Memphis Veteran Affairs Medical Center
state: Tennessee
city: Arlington
country: United States
facility: Arlington Nephrology
state: Texas
city: Corsicana
country: United States
facility: Corsicana Medical Research, LLC
state: Texas
city: Dallas
country: United States
facility: North Texas Endocrine Center
state: Texas
city: Fort Worth
country: United States
facility: The Medical Group of Texas
state: Texas
city: Houston
country: United States
facility: Primecare Medical Group
state: Texas
city: Houston
country: United States
facility: DaVita Clinical Research
state: Texas
city: Houston
country: United States
facility: Mercury Clinical Research
state: Texas
city: Lewisville
country: United States
facility: DaVita Clinical Research
state: Texas
city: Pearland
country: United States
facility: Houston Methodist Research Institute - CCAT Pearland
state: Texas
city: San Antonio
country: United States
facility: Northeast Clinical Research of San Antonio
state: Texas
city: San Antonio
country: United States
facility: Clinical Advancement Center, PLLC
state: Texas
city: Heidelberg
country: Australia
facility: Austin Health and University of Melbourne
state: Victoria
city: Fitzroy
country: Australia
facility: St. Vincent Hospital, Melbourne
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
city: Barrie
country: Canada
facility: LMC Clinical Research Inc. (Barrie)
city: Brampton
country: Canada
facility: LMC Clinical Research Inc. (Brampton)
city: Concord
country: Canada
facility: LMC Clinical research Inc. (Thornhill)
city: Etobicoke
country: Canada
facility: LMC Clinical Research Inc. (Etobicoke)
city: Kitchener
country: Canada
facility: Clinical Research Solution Inc.
city: Laval
country: Canada
facility: Centre de Recherche Clinique de Lava
city: Vancouver
country: Canada
facility: Dr TGElliott Inc dba BC Diabetes
city: Winnipeg
country: Canada
facility: Winnipeg Clinic
city: Asahikawa
country: Japan
facility: Asahikawa Medical University Hospital
city: Chiba
country: Japan
facility: National Hospital Organization Chiba-East-Hospital
city: Kagoshima
country: Japan
facility: Kagoshima University Hospital
city: Kitakyushu-shi
country: Japan
facility: Kokura Memorial Hospital
city: Kofu
country: Japan
facility: Yamanashi Prefectural Central Hospital
city: Kurobe-shi
country: Japan
facility: Kurobe City Hospital
city: Kurume-shi
country: Japan
facility: Kurume University Hospital
city: Mito-shi
country: Japan
facility: Nakamoto Medical Clinic
city: Mito-shi
country: Japan
facility: Kozawa Eye Hospital and Diabetes Center
city: Musashino
country: Japan
facility: Japanese Red Cross Musashino Hospital
city: Nagasaki
country: Japan
facility: Nagasaki University Hospital
city: Nagoya-shi
country: Japan
facility: Japan Organization of Occupational Health and Safety Chubu Rosai Hospital
city: Nagoya-shi
country: Japan
facility: Daido Clinic
city: Naka-shi
country: Japan
facility: Nakakinen Clinic
city: Niigata
country: Japan
facility: Niigata University Medical & Dental Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: Osaka General Medical Center
city: Saitama-shi
country: Japan
facility: Hoshina Clinic
city: Sanuki-shi
country: Japan
facility: Sanuki Municipal Hospital
city: Tachikawa-shi
country: Japan
facility: Tachikawa Hospital
city: Tokyo
country: Japan
facility: Mishuku Hospital
city: Tokyo
country: Japan
facility: Nihon University Itabashi Hospital
city: Toyota-shi
country: Japan
facility: TOYOTA Memorial Hospital
city: Yokohama-shi
country: Japan
facility: Yokohama City University Hospital
city: Auckland
country: New Zealand
facility: Auckland City Hospital (Auckland District Health Board)
city: Auckland
country: New Zealand
facility: Middlemore Clinical Trials Trust trading as Middlemore Clinical Trials
city: Christchurch
country: New Zealand
facility: Lipid and Diabetes Research Group
city: North Shore
country: New Zealand
facility: Waitemata District Health Board- North Shore Hospital
city: Wellington
country: New Zealand
facility: Endocrine, Diabetes & Research Centre (Capital and Coast District Health Board)
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: