A Phase 2 Trial to Evaluate Safety, Tolerability, and Efficacy of Bardoxolone Methyl in Patients With Chronic Kidney Disease at Risk of Rapid Progression
Overview
- Phase
- Phase 2
- Intervention
- Bardoxolone methyl oral capsule
- Conditions
- Chronic Kidney Diseases
- Sponsor
- Biogen
- Enrollment
- 81
- Locations
- 11
- Primary Endpoint
- Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12
- Status
- Completed
- Last Updated
- 11 months ago
Overview
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.
Detailed Description
Study Sponsor, originally Reata Pharmaceuticals, Inc., is now Reata Pharmaceuticals, Inc., a wholly owned subsidiary of Biogen.
Investigators
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;
Arms & Interventions
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.
Intervention: Bardoxolone methyl oral capsule
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.
Intervention: Placebo oral capsule
Outcomes
Primary Outcomes
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12
Time Frame: Baseline through 12 weeks after participant receives the first dose
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.