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

NCT ID: NCT04702997

Last Updated: 2025-06-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-09
• Study Completion Date: 2021-11-23

Brief Summary

This multi-center, randomized, double-blind, placebo-controlled, Phase 2 trial will study the safety, tolerability, and efficacy of bardoxolone methyl in qualified patients with CKD due to multiple etiologies at risk of rapid disease progression. Approximately 70 patients will be enrolled and randomized 1:1 to either bardoxolone methyl or placebo. Patients with CKD secondary to varying etiologies will be enrolled from age 18-70 years with eGFR ≥ 20 to < 60 mL/min/1.73 m2, and other risk factors for rapid progression of kidney disease.

The maximum target dose will be determined by baseline proteinuria status. Patients with baseline urine albumin to creatinine ratio (UACR) ≤ 300 mg/g will be titrated to a maximum dose of 20 mg, and patients with baseline UACR > 300 mg/g will be titrated to a maximum dose of 30 mg. Qualified patients will be randomized 1:1 to receive either bardoxolone methyl or placebo once daily (preferably in the morning) throughout a 12-week dosing period.

Patients in the study will follow the same visit and assessment schedule. Patients will be assessed during treatment at Day 1, Weeks 1, 2, 4, 6, 8, and 12 and by telephone contact on Days 3, 10, 21, 31, 35, and 45. Date of last dose and the end-of-treatment assessments mark the end of the treatment period. Patients will not receive study drug during a 5-week off-treatment period between Weeks 12 and 17. The off-treatment (OT) period includes 5 visits requiring various assessments to characterize eGFR from the time of study drug discontinuation through Day 35 off-treatment.

Conditions

Chronic Kidney Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Bardoxolone methyl

Patients randomized to receive bardoxolone methyl capsules orally once daily for 12 weeks at a starting dose of 5 mg and titrated up to a maximal dose of 20 mg (participants with UACR less than or equal to 300 mg/g) or 30 mg (participants with UACR greater than 300 mg/g)

Patients will be scheduled to be assessed during treatment at Day 1, Weeks 1, 2, 4, 6, 8, and 12 and by telephone contact on Days 3, 10, 21, 31, 35, and 45. Patients will not receive any drug during a 5-week off-treatment period between Weeks 12 and 17. Patients will be assessed on Day 3 off-treatment (OT), Day 7 OT, Day 14 OT, Day 21 OT, Day 28 OT, and Day 35 OT. The OT day corresponds to days after last dose.

Patients will be assessed at and end-of-study (EOS) visit on Week 17.

Group Type: EXPERIMENTAL

Bardoxolone methyl oral capsule

Intervention Type: DRUG

Bardoxolone methyl capsules dose escalated from 5 mg to a maximum of 20 or 30 mg, depending on baseline proteinuria status

Placebo

Patients who received placebo, once-daily, orally, remained on placebo throughout the study duration of 12 weeks and followed the same titration to maintain the blind,

Patients will be scheduled to be assessed during treatment at Day 1, Weeks 1, 2, 4, 6, 8, and 12 and by telephone contact on Days 3, 10, 21, 31, 35, and 45. Patients will not receive any drug during a 5-week off-treatment period between Weeks 12 and 17. Patients will be assessed on Day 3 off-treatment (OT), Day 7 OT, Day 14 OT, Day 21 OT, Day 28 OT, and Day 35 OT. The OT day corresponds to days after last dose.

Patients will be assessed at and end-of-study (EOS) visit on Week 17.

Group Type: PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type: DRUG

Capsule containing an inert placebo

Interventions

Bardoxolone methyl oral capsule

Bardoxolone methyl capsules dose escalated from 5 mg to a maximum of 20 or 30 mg, depending on baseline proteinuria status

Intervention Type: DRUG

Placebo oral capsule

Capsule containing an inert placebo

Intervention Type: DRUG

Other Intervention Names

RTA 402

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biogen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

California Institute of Renal Research

La Mesa, California, United States

Western Nephrology

Arvada, Colorado, United States

Colorado Kidney Care

Denver, Colorado, United States

Boise Kidney & Hypertension, PLLC

Nampa, Idaho, United States

Renal Associates of Baton Rouge

Baton Rouge, Louisiana, United States

Nephrology Center, PC

Kalamazoo, Michigan, United States

DaVita Clinical Research

Las Vegas, Nevada, United States

Columbia Nephrology Associates, PA

Columbia, South Carolina, United States

Renal Disease Research Intitute

Dallas, Texas, United States

DaVita Clinical Research

Houston, Texas, United States

Gamma Medical Research Inc

McAllen, Texas, United States

Clinical Advancement Center, PLLC

San Antonio, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

402-C-2002

Identifier Type: -

Identifier Source: org_study_id