Multicentre, randomized, open‐label study of on‐demand treatment with two prophylaxis regimens of recombinant coagulation factor IX in haemophilia B subjects

Summary Few randomized studies have reported on the use of factor IX ( FIX ) for secondary prophylaxis in haemophilia B patients. This study aimed to evaluate the efficacy and safety of two secondary prophylaxis regimens of recombinant coagulation FIX , nonacog alfa, compared with on‐demand therapy. Male subjects aged 6–65 years with severe or moderately severe haemophilia B ( FIX :C ≤ 2, n  = 50) and ≥12 bleeding episodes (including ≥6 haemarthroses episodes) within 12 months of study participation were enrolled in this multicentre, randomized, open‐label, four‐period crossover trial. The primary measure was the annualized bleeding rate ( ABR ) of two prophylactic regimens vs. on‐demand therapy. In the intent‐to‐treat group, mean ABR values were 35.1, 2.6 and 4.6 for the first on‐demand period, the 50  IU  kg −1 twice‐weekly period, and the 100  IU  kg −1 once‐weekly period respectively. Differences in ABR between the first on‐demand period and both prophylaxis regimens were significant ( P  <   0.0001); no significant differences were observed between prophylaxis regimens ( P  =   0.22). Seven serious adverse events occurred in five subjects, none related to study drug. Results demonstrated that secondary prophylaxis therapy with nonacog alfa 50  IU  kg −1 twice weekly or 100  IU  kg −1 once weekly reduced ABR by 89.4% relative to on‐demand treatment. Both prophylaxis regimens demonstrated favourable safety profiles in subjects with haemophilia B.