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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Diabetic Kidney Disease

Intervention / Treatment
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* Drug: Selonsertib
* Drug: Placebo to match selonsertib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic Kidney Disease, Gilead