Reata Pharmaceuticals has begun screening patients for the new Phase 2/3 trial evaluating bardoxolone methyl as a treatment for patients of Alport syndrome-associated chronic kidney disease (CKD).
The aim of the Phase 2/3 CARDINAL study (NCT03019185) is to assess the safety and effectiveness of bardoxolone methyl in patients with Alport syndrome (Phase 2 portion) and to evaluate if these patients report an improved kidney function (Phase 3).
The Phase 2 part of the study will include up to 30 patients between the ages of 12 and 60 years who have estimated glomerular filtration rates (eGFR) between 30 to 90 mL/min/1.73 m2. The primary endpoint of this part of the study is change in eGFR at week 12 in compared to levels measured at baseline.
The Phase 3 part of the study will support regulatory approval of bardoxolone methyl and enroll about 180 patients on a 1:1 ratio to bardoxolone methyl and placebo. Primary effectiveness endpoint is the change from baseline in eGFR in patients treated with bardoxolone methyl against placebo after 48 weeks. This portion will study the dose escalation of the candidate from 5 mg to 20 mg or 30 mg daily, based on baseline proteinuria (the excessive presence of proteins through urination) at randomization.
If the trial shows positive results, it could support accelerated approval from the U.S. Food and Drug Administration (FDA). Reata expects data from this trial to be available by the end of this year.
Bardoxolone methyl is an investigational, oral, once-daily activator of Nrf2, a transcription factor that restores mitochondrial function (mitochondria are organelles essential to cellular energy production), reduces oxidative stress (imbalance that results in cell damage), and resolves inflammation.
Bardoxolone methyl helps Alport syndrome patients because this rare condition is caused by mutations in the genes, whose abnormal function causes oxidative stress, chronic inflammation and fibrosis in the kidneys.
“As there are currently no FDA approved treatments for those with Alport Syndrome, the Alport Syndrome Foundation encourages the development of therapies that will delay or prevent the need for dialysis and transplantation,” Gina Parziale, executive director of the Alport Syndrome Foundation, said in a press release.
“Based on our extensive clinical experience with bardoxolone methyl in patients with diabetic CKD, as well as in our ongoing Phase 2 and Phase 3 trials for bardoxolone in other orphan diseases, we hope to demonstrate that bardoxolone methyl can serve as a meaningful new treatment option for patients with Alport syndrome,” said Warren Huff, Reata’s president and CEO.