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Abstract: FR-OR54

Global Phase 3 Clinical Trials of Vadadustat vs. Darbepoetin Alfa for Treatment of Anemia in Patients with Non-Dialysis-Dependent CKD

Session Information

Category: Anemia and Iron Metabolism

  • 200 Anemia and Iron Metabolism

Author

  • Chertow, Glenn Matthew, Stanford University School of Medicine, Stanford, California, United States

Group or Team Name

  • PRO2TECT Author Group
Background

Vadadustat (VADA) is an investigational, oral, hypoxia-inducible factor prolyl hydroxylase inhibitor which has completed patient enrollment in its phase 3 development for treatment of anemia of chronic kidney disease (CKD). In phase 2 trials, VADA safely raised and maintained hemoglobin (Hb) concentrations.

Methods

We conducted two randomized, phase 3, global, open-label, sponsor-blind, parallel-group, active-controlled noninferiority trials comparing oral daily VADA to parenteral darbepoetin alfa (DA) in patients with anemia of non-dialysis dependent (NDD)-CKD (PRO2TECT program). The PRO2TECT program included (1) Correction trial of patients previously not on erythropoiesis-stimulating agents (ESA) (ESA-untreated NDD-CKD trial, NCT02648347) and (2) Conversion trial of patients previously on an ESA (ESA-treated NDD-CKD trial, NCT02680574). The primary safety endpoint of PRO2TECT program was time to first major adverse cardiovascular event (all-cause mortality, nonfatal myocardial infarction, nonfatal stroke), prespecified as a pooled event-driven analysis of both trials. Primary and key secondary efficacy endpoints, prespecified as separate analyses for each trial, were difference in mean change in Hb between baseline and weeks 24-36 and weeks 40-52, respectively, comparing VADA vs DA.

Results

In total, 4708 patients were screened for the ESA-untreated NDD-CKD trial, and 1751 were randomized. Most (N=1061) were from the United States; the remainder were from Europe or elsewhere. A total of 2961 patients were screened for the ESA-treated NDD-CKD trial, 1725 of whom were randomized. Most (N=1060) were from Europe or non-United States/non-European countries; the remainder were from the United States. The database was locked on July 31, 2020. Topline data and results of these global trials will be available in September 2020.

Conclusion

The trials will test if oral daily VADA is noninferior to parenteral DA, a common ESA, in patients with anemia of NDD-CKD, with respect to cardiovascular safety and hematologic efficacy.

Funding

  • Commercial Support