A Trial of Bardoxolone Methyl in Patients With CKD at Risk of Rapid Progression (MERLIN) (MERLIN)

Inclusion Criteria:

• Diagnosis of CKD with screening eGFR (average of Screen A and Screen B eGFR values) ≥ 20 to < 60 mL/min/1.73 m2

• Patient must meet at least one of the following criteria:

  1. UACR ≥ 300 mg/g; OR
  2. eGFR decline at a rate of ≥ 4 mL/min/1.73 m2 in prior year; OR
  3. Hematuria defined as > 5-10 red blood cells (RBCs) per high power field (HPF, manual method), or documented history of positive urinary dipstick for blood in prior year, or macroscopic hematuria in prior 3 years;
• Systolic blood pressure ≤ 150 mmHg and diastolic blood pressure ≤ 90 mmHg at Screen A visit after a period of rest (≥ 5 minutes);
• Treatment with an angiotensin-converting enzyme inhibitor (ACEi) and/or an angiotensin II receptor blocker (ARB) at the maximally tolerated labeled daily dose for at least 6 weeks prior to the Screen A visit and with no anticipated changes to dose(s) during study participation.
• Able to swallow capsules -

Exclusion Criteria:

• Prior exposure to bardoxolone methyl;

• CKD secondary to or associated with any of the following:

  1. History of rapidly progressive glomerulonephritis (RPGN)
  2. Glomerulonephritis requiring immunosuppression in the last 6 months prior to Screen A;
• Concomitant use of tolvaptan.
• Systemic immunosuppression for more than 2 weeks, cumulatively, within the 12 weeks prior to Day 1 or anticipated need for immunosuppression during the study;
• Patients currently taking a sodium/glucose cotransporter-2 inhibitor (SGLT2i), requiring dose adjustments within 12 weeks prior to Day 1 or if dose is anticipated to change during study participation;
• B-type natriuretic peptide (BNP) level > 200 pg/mL at Screen A visit;
• Uncontrolled diabetes (HbA1c > 11.0%) at Screen A visit;
• Serum albumin < 3 g/dL at Screen A visit;
• Kidney or any other solid organ transplant recipient or a planned transplant during the study;
• Acute dialysis or acute kidney injury within 12 weeks prior to Screen A visit or during Screening;
• History of clinically significant cardiac disease;
• Systolic blood pressure < 90 mmHg at Screen A visit after a period of rest;
• Body mass index < 18.5 kg/m2 at the Screen A visit;
• History of malignancy within 5 years prior to Screen A visit, with the exception of localized skin or cervical carcinomas;
• Coronavirus disease 2019 (COVID-19) diagnosis within 3 months prior to Screen A or have ever required COVID-19 related hospitalization;
• Participation in other interventional clinical studies within 3 months (or if relevant 5 half-lives of that study medication, whichever is the longer) prior to Screen B;
• Unwilling to practice acceptable methods of birth control;
• Women who are pregnant or breastfeeding.