Study to Evaluate the Efficacy and Safety of Selonsertib in Participants With Moderate to Advanced Diabetic Kidney Disease
Condition: Diabetic Kidney Disease
MeSH terms: Kidney Diseases; Diabetic Nephropathies
Intervention: SEL; Placebo
Intervention description: Tablet administered orally once daily; Tablet administered orally once daily
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
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)
Enrollment: 384.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

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).
    

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.