A phase 2 study of the safety, tolerability and pharmacodynamics of FBS0701, a novel oral iron chelator, in transfusional iron overload

This was a 24-week, multicenter Phase-2 study designed to assess safety, tolerability, and pharmacodynamics of FBS0701, a novel oral chelator, in adults with transfusional iron overload. Fifty-one patients, stratified by transfusional iron intake, were randomized to FBS0701 at either 14.5 or 29 mg/kg/d (16 and 32 mg/kg/d salt form). FBS0701 was generally well tolerated at both doses. Forty-nine patients (96\%) completed the study. There were no drug-related serious adverse events. No adverse events (AEs) showed dose-dependency in frequency or severity. Treatment-related nausea, vomiting, abdominal pain, and diarrhea were each noted in <5\% of patients. The most common treatment-related AE was increased transaminases (16\%, N=8). Three of the eight acquired HCV on-study from a single blood bank; the five others had abnormal baseline ALT. Mean serum creatinine did not change significantly from Baseline or between dose groups. The two FBS0701 doses demonstrated a difference in change in 24-week liver iron concentration (ΔLIC). Mean ΔLIC at 14.5 mg/kg/d was +3.1 mg/g (dw); 29\% achieved a decrease in LIC. Mean ΔLIC at 29 mg/kg/d was -0.3 mg/g (dw); 44\% achieved a decrease in LIC (P<0.03 for ΔLIC between doses). The safety and tolerability profile at therapeutic doses compares favorably to other oral chelators. This paper is registered at www.clinicaltrials.gov as NCT01186419.