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

Primary Purpose

Chronic Kidney Diseases

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bardoxolone methyl oral capsule
Placebo oral capsule
Sponsored by
Reata Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Kidney Diseases focused on measuring Advanced CKD, Chronic Kidney Disease, Bardoxolone methyl, RTA 402, eGFR, Advanced Chronic Kidney Disease

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • California Institute of Renal Research
  • Western Nephrology
  • Colorado Kidney Care
  • Boise Kidney & Hypertension, PLLC
  • Renal Associates of Baton Rouge
  • Nephrology Center, PC
  • DaVita Clinical Research
  • Columbia Nephrology Associates, PA
  • Renal Disease Research Intitute
  • DaVita Clinical Research
  • Gamma Medical Research Inc
  • Clinical Advancement Center, PLLC

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Bardoxolone methyl

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
January 7, 2021
Last Updated
November 4, 2022
Sponsor
Reata Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04702997
Brief Title
A Trial of Bardoxolone Methyl in Patients With CKD at Risk of Rapid Progression (MERLIN)
Acronym
MERLIN
Official Title
A Phase 2 Trial to Evaluate Safety, Tolerability, and Efficacy of Bardoxolone Methyl in Patients With Chronic Kidney Disease at Risk of Rapid Progression
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
February 9, 2021 (Actual)
Primary Completion Date
October 20, 2021 (Actual)
Study Completion Date
November 23, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Reata Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Kidney Diseases
Keywords
Advanced CKD, Chronic Kidney Disease, Bardoxolone methyl, RTA 402, eGFR, Advanced Chronic Kidney Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
81 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bardoxolone methyl
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bardoxolone methyl oral capsule
Other Intervention Name(s)
RTA 402
Intervention Description
Bardoxolone methyl capsules dose escalated from 5 mg to a maximum of 20 or 30 mg, depending on baseline proteinuria status
Intervention Type
Drug
Intervention Name(s)
Placebo oral capsule
Intervention Description
Capsule containing an inert placebo
Primary Outcome Measure Information:
Title
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12
Description
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.
Time Frame
Baseline through 12 weeks after participant receives the first dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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: 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 - Exclusion Criteria: 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; 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.
Facility Information:
Facility Name
California Institute of Renal Research
City
La Mesa
State/Province
California
ZIP/Postal Code
91942
Country
United States
Facility Name
Western Nephrology
City
Arvada
State/Province
Colorado
ZIP/Postal Code
80002
Country
United States
Facility Name
Colorado Kidney Care
City
Denver
State/Province
Colorado
ZIP/Postal Code
80230
Country
United States
Facility Name
Boise Kidney & Hypertension, PLLC
City
Nampa
State/Province
Idaho
ZIP/Postal Code
83687
Country
United States
Facility Name
Renal Associates of Baton Rouge
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70808
Country
United States
Facility Name
Nephrology Center, PC
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49007
Country
United States
Facility Name
DaVita Clinical Research
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89128
Country
United States
Facility Name
Columbia Nephrology Associates, PA
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29203
Country
United States
Facility Name
Renal Disease Research Intitute
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
DaVita Clinical Research
City
Houston
State/Province
Texas
ZIP/Postal Code
77004
Country
United States
Facility Name
Gamma Medical Research Inc
City
McAllen
State/Province
Texas
ZIP/Postal Code
78503
Country
United States
Facility Name
Clinical Advancement Center, PLLC
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78212
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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