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

NCT04702997 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 402-C-2002
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 12

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

Keywords

Advanced CKD; Chronic Kidney Disease; Bardoxolone methyl; RTA 402; eGFR; Advanced Chronic Kidney Disease

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12

  To assess the change in eGFR from baseline to week 12. eGFR is a measure of kidney function assessed through blood/serum. Higher eGFRs represent better/improved kidney function. Lower eGFRs represent poorer/decreased kidney function.

  Baseline through 12 weeks after participant receives the first dose

Study Arms (2)

Bardoxolone methyl

EXPERIMENTAL

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.

Drug: Bardoxolone methyl oral capsule

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo oral capsule

Interventions

Bardoxolone methyl oral capsule DRUG

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

Also known as: RTA 402

Bardoxolone methyl

Placebo oral capsule DRUG

Capsule containing an inert placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• UACR ≥ 300 mg/g; OR
• eGFR decline at a rate of ≥ 4 mL/min/1.73 m2 in prior year; OR
• 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 -

You may not qualify if:

• Prior exposure to bardoxolone methyl;
• CKD secondary to or associated with any of the following:
• History of rapidly progressive glomerulonephritis (RPGN)
• 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;

Sponsors & Collaborators

• Biogen: lead

Study Sites (12)

California Institute of Renal Research

La Mesa, California, 91942, United States

Location

Western Nephrology

Arvada, Colorado, 80002, United States

Location

Colorado Kidney Care

Denver, Colorado, 80230, United States

Location

Boise Kidney & Hypertension, PLLC

Nampa, Idaho, 83687, United States

Location

Renal Associates of Baton Rouge

Baton Rouge, Louisiana, 70808, United States

Location

Nephrology Center, PC

Kalamazoo, Michigan, 49007, United States

Location

DaVita Clinical Research

Las Vegas, Nevada, 89128, United States

Location

Columbia Nephrology Associates, PA

Columbia, South Carolina, 29203, United States

Location

Renal Disease Research Intitute

Dallas, Texas, 75235, United States

Location

DaVita Clinical Research

Houston, Texas, 77004, United States

Location

Gamma Medical Research Inc

McAllen, Texas, 78503, United States

Location

Clinical Advancement Center, PLLC

San Antonio, Texas, 78212, United States

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

bardoxolone methyl

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: US Biogen Clinical Trial Center
• Organization: Biogen

clinicaltrials@biogen.com

866-633-4636

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2021
• First Posted: January 11, 2021
• Study Start: February 9, 2021
• Primary Completion: October 20, 2021
• Study Completion: November 23, 2021
• Last Updated: June 3, 2025
• Results First Posted: December 1, 2022

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (12)