Last month, the U.S. Food and Drug Administration (FDA) provided guidance to Reata that a single, pivotal clinical trial utilizing a retained estimated glomerular filtration rate (eGFR) primary endpoint could serve as the basis for approval of the drug to treat the disease.
“We approached the FDA with a design for a Phase 2 study in Alport syndrome. The meeting was very collaborative, and the FDA provided us with guidance on a more efficient path to potential registration conducting a single, pivotal trial,” Reata CEO Warren Huff said in a press release.
“Bardoxolone methyl has a novel mechanism of action that has the potential to address the chronic inflammation and renal function decline that are key features of Alport syndrome,” Huff added. “Our Alport syndrome program will be similar in scope to CATALYST (NCT02657356), our ongoing Phase 3 trial in patients with connective tissue disease associated pulmonary arterial hypertension.”
Bardoxolone methyl is an experimental, oral semi-synthetic compound, based on the scaffold of the natural product oleanolic acid. The drug activates Nrf2, a transcription factor that controls the production of more than 250 antioxidant and detoxification proteins.
Activation of Nrf2 protects tissues from inflammation by increasing cellular antioxidant content and suppressing inflammatory signaling pathways. Chronic inflammation has been shown to promote type 2 diabetes and its complications, including cardiovascular events and CKD.
Results from a clinical trial that evaluated bardoxolone methyl in patients with CKD caused by type 2 diabetes showed that the drug improved the eGFR as well as other markers of renal function, supporting the drug’s effectiveness.
The new international Phase 2/3 effectiveness and safety clinical trial will evaluate whether bardoxolone methyl can slow, halt, or reverse the decline in renal function in patients with Alport syndrome, ages 12 to 60, who have eGFR values between 30 to 90 mL/min/1.73 m2. These eGFR values indicate a mild to severe reduction in normal kidney function.
The primary endpoint of the open-label Phase 2 portion of the trial is the assessment of eGFR change from baseline at 12 weeks. Patients taking part in this Phase 2 portion will be monitored for two years and will not take part in the Phase 3 portion of the trial.
The Phase 3 clinical trial will randomly assign patients to either bardoxolone methyl or a placebo. The primary effectiveness outcome is the change from baseline in eGFR in patients treated with bardoxolone methyl versus treatment with a placebo after 12 months.
According to the FDA guidance, upon successful completion for the trial, the results may help to accelerate approval of bardoxolone methyl.
Enrollment of patients for the Phase 2 portion of this trial is scheduled to begin early in 2017.