The inno(2)vate phase 3 program of vadadustat for treatment of anemia in dialysis-dependent ckd: Rationale and study design.
Winkelmayer W, Block G, Chertow G, Fishbane S, Komatsu Y, McCullough P, Pergola P, Rosenberger C, Williamson D, Yee J, Collins A, Khawaja Z, Sharma A, Zuraw Q, and Maroni B. The inno(2)vate phase 3 program of vadadustat for treatment of anemia in dialysis-dependent ckd: Rationale and study design. Am J Kidney Dis 2017; 69(4):A102-A102.
Am J Kidney Dis
Vadadustat is an investigational, oral, hypoxia-inducible factor prolylhydroxylase domain (HIF-PHD) inhibitor for the treatment of renal anemia. HIF-PHD inhibitors transiently stabilize HIF and stimulate erythropoiesis and iron mobilization. Vadadustat use has been studied in healthy adults and in patients with CKD stages 3–5D. The INNO2VATE program will evaluate the efficacy and safety of vadadustat vs. darbepoetin alfa in correcting anemia and maintaining hemoglobin (Hb) levels over ≥52 weeks in patients with dialysis-dependent (DD)-CKD. INNO2VATE comprises 2 global, randomized, open-label, activecontrolled, non-inferiority studies. INNO2VATE-CORRECTION (NCT02865850) is enrolling ~400 adults with DD-CKD and anemia (Hb <10 g/dL) not receiving an erythropoiesis-stimulating agent (ESA). The INNO2VATE-CONVERSION (NCT02892149) is enrolling ~2200 adults with DD-CKD and anemia (US: Hb ≥8–≤11 g/dL; Ex-US: ≥9– ≤12 g/dL) currently receiving ESA therapy. Patients will be randomized 1:1 to vadadustat or darbepoetin alfa, and study drugs titrated to achieve target Hb levels as per regional guidelines. The primary efficacy endpoint is the mean change in Hb from baseline to average during weeks 24–36. Key secondary endpoints include the mean change in Hb from baseline to weeks 40–52 and proportion of patients with mean Hb in target range during weeks 24–36. The primary safety endpoint— accrued over the 2 studies—is the time to the first occurrence of a major adverse cardiovascular event (MACE), defined as all-cause mortality, non-fatal myocardial infarction, or non-fatal stroke. INNO2VATE is a global Phase 3 program evaluating the efficacy and safety of vadadustat in patients with anemia secondary to DD-CKD.