Kidney Week

Abstract: SA-PO919

Results of Phase 2 MERLIN: An Evaluation of Safety, Tolerability, and Efficacy of Bardoxolone Methyl in Patients With Rapidly Progressing CKD

Session Information

• CKD: Clinical Trials and Pharmacoepidemiology
  November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2202 CKD (Non-Dialysis): Clinical‚ Outcomes‚ and Trials

Authors

• Pergola, Pablo E., Renal Associates PA, San Antonio, Texas, United States

Pablo E. Pergola,

• Kooienga, Laura, Colorado Kidney Care, Denver, Colorado, United States

Laura Kooienga,

• Goldsberry, Angie, Reata Pharmaceuticals Inc, Irving, Texas, United States

Angie Goldsberry,

• Meyer, Colin John, Reata Pharmaceuticals Inc, Irving, Texas, United States

Colin John Meyer,

• Silva, Arnold L., Boise Kidney and Hypertension Institute, Meridian, Idaho, United States

Arnold L. Silva,

• Khan, Samina, Reata Pharmaceuticals Inc, Irving, Texas, United States

Samina Khan,

Background

Bardoxolone methyl (Bard) is an investigational drug that activates Nrf2. Improvements in eGFR, creatinine clearance, and inulin clearance have been observed with Bard treatment in multiple clinical trials in patients with CKD of various etiologies like Alport syndrome, ADPKD, IgA nephropathy and DKD.

Methods

MERLIN (NCT04702997) was a multi-center, randomized, double-blind, placebo-controlled, phase 2 trial that enrolled patients with CKD of multiple etiologies at risk of rapid kidney disease progression (rate of eGFR decline ≥4 mL/min/1.73 m² in prior year or urine albumin-to-creatinine ratio ≥300 mg/g or persistent hematuria). Patients 18-75 years of age with eGFR ≥20 to <60 mL/min/1.73m² were randomized 1:1 to receive Bard or placebo. Patients with BNP >200 pg/mL at screening visit were excluded. The primary efficacy endpoint was the change from baseline (CFB) in eGFR at Week 12. To assess the exploratory objective of characterizing change in eGFR during the off-treatment (OT) period, serial eGFR was assessed at 3, 7, 14, 21, 28, and 35 days after last dose of Bard. Safety endpoints included lab results, vital signs, ECG, weight, and AEs.

Results

Eighty-one patients were treated with Bard (n=39) or placebo (n=42). Baseline eGFR was 35.7±9.9 mL/min/1.73m² (mean±SD), with 68 patients (84%) having eGFR <45 mL/min/1.73 m². The CFB in eGFR after 12 weeks of treatment was 6.79±0.93 (mean±SE) in patients treated with Bard as compared to -0.92±0.87 (mean±SE) mL/min/1.73m² in patients treated with placebo (p<0.0001). Mean eGFR CFB for patients on Bard declined once it was discontinued and stabilized at 1.58±0.83 (mean±SE) mL/min/1.73m² by Day 21 OT, with no further decline after that. Most TEAEs were mild to moderate in severity. Those reported in >5% of patients in either treatment group were muscle spasms, nausea and decrease in weight.

Conclusion

Consistent with previous studies of patients treated with Bard, the 12-week treatment in the MERLIN study resulted in significant increases in eGFR in patients taking Bard when compared with placebo. The acute eGFR increase associated with Bard was resolved by Day 21 OT. Bard was found to be safe and well tolerated. Overall, no new safety signals emerged during the study.

Funding

• Commercial Support