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Trial record 1 of 1 for:    GS-US-223-1017
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Study to Evaluate the Efficacy and Safety of Selonsertib in Participants With Moderate to Advanced Diabetic Kidney Disease (MOSAIC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04026165
Recruitment Status : Completed
First Posted : July 19, 2019
Results First Posted : December 21, 2022
Last Update Posted : December 21, 2022
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Description
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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).

Condition or disease Intervention/treatment Phase
Diabetic Kidney Disease Drug: SEL Drug: Placebo Phase 2

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 384 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Participants received Run-in and Randomized treatments sequentially and in the Randomized Phase, the treatments were assigned in parallel.
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : July 24, 2019
Actual Primary Completion Date : September 3, 2021
Actual Study Completion Date : September 3, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Selonsertib

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
Tablet administered orally once daily

Drug: Placebo
Tablet administered orally once daily
Placebo Comparator: Placebo

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
Tablet administered orally once daily

Drug: Placebo
Tablet administered orally once daily


Outcome Measures
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Primary Outcome Measures :
  1. Treatment-specific Baseline Estimated Glomerular Filtration Rate Based on Creatinine (eGFRcr) [ Time Frame: 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) ]

    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.


  2. eGFRcr Slope [ Time Frame: Treatment-specific Baselines through Week 84 ]
    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.


Secondary Outcome Measures :
  1. Percentage of Participants With Kidney Clinical Events at Week 48 [ Time Frame: 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.

  2. Time From Randomization to First Occurrence of a Kidney Clinical Event: Event Rate Per 100 Participant-years for First Occurrence of Kidney Clinical Event [ Time Frame: From randomization up to Week 101 ]
    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.

  3. Pre-run-in Baseline Estimated Glomerular Filtration Rate Based on Cystatin C (eGFRcys) [ Time Frame: 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 = 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.

  4. eGFRcys Slope [ Time Frame: Pre-run-in Baseline through Week 84 ]
    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.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04026165


Locations
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Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
  Study Documents (Full-Text)

Documents provided by Gilead Sciences:
Study Protocol  [PDF] April 13, 2020
Statistical Analysis Plan  [PDF] December 3, 2021

More Information
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Additional Information:

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT04026165    
Other Study ID Numbers: GS-US-223-1017
JapicCTI-194911 ( Registry Identifier: Japan Pharmaceutical Information Center )
2018-003951-39 ( EudraCT Number )
First Posted: July 19, 2019    Key Record Dates
Results First Posted: December 21, 2022
Last Update Posted: December 21, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Kidney Diseases
Diabetic Nephropathies
Urologic Diseases
 Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases