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

NCT04026165 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: GS-US-223-1017JapicCTI-1949112018-003951-39
• Study Type: interventional
• Target: 384
• Locations: 5 countries
• Sites: 111

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).

Conditions

Diabetic Kidney Disease

Outcome Measures

Primary Outcomes (2)

• 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)

• 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 Outcomes (4)

• Percentage of Participants With Kidney Clinical Events at Week 48

  Week 48

• 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

• 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 Slope

  Pre-run-in Baseline through Week 84

Study Arms (2)

Selonsertib

EXPERIMENTAL

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.

Drug: SEL; Drug: Placebo

Placebo

PLACEBO COMPARATOR

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.

Drug: SEL; Drug: Placebo

Interventions

SEL DRUG

Tablet administered orally once daily

Placebo; Selonsertib

Placebo DRUG

Tablet administered orally once daily

Placebo; Selonsertib

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (111)

Arizona Kidney Disease and Hypertension Centers

Glendale, Arizona, 85306, United States

Location

AKDHC Medical Research Services, LLC

Tucson, Arizona, 85712, United States

Location

Clearview Medical Research, LLC

Canyon Country, California, 91350, United States

Location

Kidney Disease Medical Group, Inc.

Glendale, California, 91206, United States

Location

Renal Consultants Medical Group

Granada Hills, California, 91344, United States

Location

Marin Endocrine Care & Research, Inc.

Greenbrae, California, 94904, United States

Location

California Institute of Renal Research

La Mesa, California, 91942-3059, United States

Location

Academic Medical Research Institute

Los Angeles, California, 90022, United States

Location

Rose Salter Medical Research Foundation

Newport Beach, California, 92663, United States

Location

Valley Renal Medical Group Research

Northridge, California, 91324, United States

Location

California Institute of Renal Research

San Diego, California, 92123, United States

Location

California Kidney Specialist

San Dimas, California, 91773, United States

Location

Creekside Endocrine Associates, PC

Denver, Colorado, 80246, United States

Location

New West Physicians, Inc

Golden, Colorado, 80401, United States

Location

Western Nephrology and Metabolic Bone Disease, PC

Westminster, Colorado, 80031, United States

Location

Omega Research Maitland, LLC

DeBary, Florida, 32713, United States

Location

South Florida Research Institute

Lauderdale Lakes, Florida, 33313, United States

Location

Suncoast Clinical Research, Inc.

New Port Richey, Florida, 34652, United States

Location

Discovery Medical Research Group, Inc

Ocala, Florida, 34471, United States

Location

Coastal Nephrology Associates Research Center, LLC. D/B/A Volunteer Medical Research

Port Charlotte, Florida, 33952, United States

Location

Atlanta Center for Clinical Research

Atlanta, Georgia, 30342, United States

Location

Georgia Nephrology Research Institute

Lawrenceville, Georgia, 30046, United States

Location

East-West Medical Research Institute

Honolulu, Hawaii, 96814, United States

Location

Boise Kidney & Hypertension, PLLC

Meridian, Idaho, 83642, United States

Location

Research By Design, LLC

Chicago, Illinois, 60643, United States

Location

Buynak Clinical Research, P.C.

Valparaiso, Indiana, 46383, United States

Location

West Broadway Clinic

Council Bluffs, Iowa, 51501, United States

Location

Kansas Nephrology Research Institute, LLC

Wichita, Kansas, 67214, United States

Location

Four Rivers Clinical Research

Paducah, Kentucky, 42003, United States

Location

Internal Medicine Specialists, Inc

New Orleans, Louisiana, 70115, United States

Location

Northwest Louisiana Nephrology L.L.C

Shreveport, Louisiana, 71101, United States

Location

Aa Mrc, Llc

Flint, Michigan, 48504, United States

Location

Elite Research Center

Flint, Michigan, 48532, United States

Location

Arcturus Healthcare, PLC, Troy Internal Medicine Research Division

Troy, Michigan, 48098, United States

Location

Clinical Research Consultants, LLC

Kansas City, Missouri, 64111, United States

Location

Pelican Point Dialysis - DaVita Clinical Research

Las Vegas, Nevada, 89129, United States

Location

Albany Medical College

Albany, New York, 12206, United States

Location

North Shore University Hospital: Division of Nephrology

Great Neck, New York, 11021, United States

Location

Endocrine Associates of Long Island, PC

Smithtown, New York, 11787, United States

Location

CHEAR Center LLC

The Bronx, New York, 10455, United States

Location

Mountain Kidney and Hypertension Associates

Asheville, North Carolina, 28801, United States

Location

Mountain Diabetes & Endocrine Center

Asheville, North Carolina, 28803, United States

Location

Carteret Medical Group

Morehead City, North Carolina, 28557, United States

Location

Diabetes And Endocrinology Consultants, P.C.

Morehead City, North Carolina, 28557, United States

Location

PMG Research of Rocky Mount, LLC

Rocky Mount, North Carolina, 27804, United States

Location

PMG Research Inc., d/b/a PMG Research of Piedmont Healthcare

Statesville, North Carolina, 28625, United States

Location

Wilmington Health, PLLC

Wilmington, North Carolina, 28401, United States

Location

PMG Research of Winston-Salem, LLC

Winston-Salem, North Carolina, 27103, United States

Location

SV Research LLC

Marion, Ohio, 43302, United States

Location

Midwest Nephrology Group, PLLC

Midwest City, Oklahoma, 73130, United States

Location

Heritage Valley Medical Group, Inc.

Beaver, Pennsylvania, 15009, United States

Location

Northeast Clinical Research Center, LLC

Bethlehem, Pennsylvania, 18017, United States

Location

Lifespan Clinical Research Center

East Providence, Rhode Island, 02915, United States

Location

PMG Research Of Charleston, LLC

Mt. Pleasant, South Carolina, 29464, United States

Location

Southeast Renal Research Institute

Chattanooga, Tennessee, 37408, United States

Location

University Diabetes and Endocrine Consultants

Chattanooga, Tennessee, 37411, United States

Location

PMG Research, Inc d/b/a/ PMG Research of Knoxville

Knoxville, Tennessee, 37912, United States

Location

Knoxville Kidney Center, PLLC

Knoxville, Tennessee, 37923, United States

Location

PMG Research, Inc. d/b/a PMG Research of Knoxville

Knoxville, Tennessee, 37938, United States

Location

Memphis Veteran Affairs Medical Center

Memphis, Tennessee, 38104, United States

Location

Arlington Nephrology

Arlington, Texas, 76015, United States

Location

Corsicana Medical Research, LLC

Corsicana, Texas, 75110, United States

Location

North Texas Endocrine Center

Dallas, Texas, 75231, United States

Location

The Medical Group of Texas

Fort Worth, Texas, 76116, United States

Location

Primecare Medical Group

Houston, Texas, 77024, United States

Location

DaVita Clinical Research

Houston, Texas, 77030, United States

Location

Mercury Clinical Research

Houston, Texas, 77036, United States

Location

DaVita Clinical Research

Lewisville, Texas, 75057, United States

Location

Houston Methodist Research Institute - CCAT Pearland

Pearland, Texas, 77584, United States

Location

Northeast Clinical Research of San Antonio

San Antonio, Texas, 78154, United States

Location

Clinical Advancement Center, PLLC

San Antonio, Texas, 78215, United States

Location

Austin Health and University of Melbourne

Heidelberg, Victoria, 3081, Australia

Location

St. Vincent Hospital, Melbourne

Fitzroy, 3065, Australia

Location

Royal Melbourne Hospital

Parkville, 3052, Australia

Location

LMC Clinical Research Inc. (Barrie)

Barrie, L4M 7G1, Canada

Location

LMC Clinical Research Inc. (Brampton)

Brampton, L6S 0C6, Canada

Location

LMC Clinical research Inc. (Thornhill)

Concord, L4K 4M2, Canada

Location

LMC Clinical Research Inc. (Etobicoke)

Etobicoke, M9R 4E1, Canada

Location

Clinical Research Solution Inc.

Kitchener, N2H 5Z8, Canada

Location

Centre de Recherche Clinique de Lava

Laval, H7T 2P5, Canada

Location

Dr TGElliott Inc dba BC Diabetes

Vancouver, V5Y 3W2, Canada

Location

Winnipeg Clinic

Winnipeg, R3C 0N2, Canada

Location

Asahikawa Medical University Hospital

Asahikawa, 078-8510, Japan

Location

National Hospital Organization Chiba-East-Hospital

Chiba, 260-0801, Japan

Location

Kagoshima University Hospital

Kagoshima, 890-8520, Japan

Location

Kokura Memorial Hospital

Kitakyushu-shi, 802-8555, Japan

Location

Yamanashi Prefectural Central Hospital

Kofu, 400-0027, Japan

Location

Kurobe City Hospital

Kurobe-shi, 938-8502, Japan

Location

Kurume University Hospital

Kurume-shi, 830-0011, Japan

Location

Nakamoto Medical Clinic

Mito, 310-0826, Japan

Location

Kozawa Eye Hospital and Diabetes Center

Mito, 310-0845, Japan

Location

Japanese Red Cross Musashino Hospital

Musashino, 180-8610, Japan

Location

Nagasaki University Hospital

Nagasaki, 852-8501, Japan

Location

Japan Organization of Occupational Health and Safety Chubu Rosai Hospital

Nagoya, 455-8530, Japan

Location

Daido Clinic

Nagoya, 457-8511, Japan

Location

Nakakinen Clinic

Naka, 311-0113, Japan

Location

Niigata University Medical & Dental Hospital

Niigata, 9518520, Japan

Location

Okayama University Hospital

Okayama, 700-8558, Japan

Location

Osaka General Medical Center

Osaka, 558-8558, Japan

Location

Hoshina Clinic

Saitama-shi, 338-0837, Japan

Location

Sanuki Municipal Hospital

Sanuki-shi, 769-2393, Japan

Location

Tachikawa Hospital

Tachikawa-shi, 190-8531, Japan

Location

Mishuku Hospital

Tokyo, 153-0051, Japan

Location

Nihon University Itabashi Hospital

Tokyo, 173-8610, Japan

Location

TOYOTA Memorial Hospital

Toyota-shi, 471-8513, Japan

Location

Yokohama City University Hospital

Yokohama, 236-0004, Japan

Location

Auckland City Hospital (Auckland District Health Board)

Auckland, 1023, New Zealand

Location

Middlemore Clinical Trials Trust trading as Middlemore Clinical Trials

Auckland, New Zealand

Location

Lipid and Diabetes Research Group

Christchurch, 8011, New Zealand

Location

Waitemata District Health Board- North Shore Hospital

North Shore, 622, New Zealand

Location

Endocrine, Diabetes & Research Centre (Capital and Coast District Health Board)

Wellington, 6021, New Zealand

Location

Related Publications (1)

• Heerspink HJL, Perkovic V, Tuttle KR, Pergola PE, Mahaffey KW, Patel UD, Ishida JH, Kuo A, Chen F, Kustra R, Petrovic V, Rossing P, Kashihara N, Chertow GM. Selonsertib in Patients with Diabetic Kidney Disease: A Phase 2b Randomized Active Run-In Clinical Trial. J Am Soc Nephrol. 2024 Dec 1;35(12):1726-1736. doi: 10.1681/ASN.0000000000000444. Epub 2024 Jul 17.

  PMID: 39018154 DERIVED

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Diabetic Nephropathies

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants received Run-in and Randomized treatments sequentially and in the Randomized Phase, the treatments were assigned in parallel.

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: July 19, 2019
• Study Start: July 24, 2019
• Primary Completion: September 3, 2021
• Study Completion: September 3, 2021
• Last Updated: December 21, 2022
• Results First Posted: December 21, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3); JP (24); NZ (5); US (71); CA (8)