Results of a multicenter, prospective, open, uncontrolled study of the efficacy and safety of the drug Innonafactor in patients aged 12 years and older with severe and moderate hemophilia B

The multicentre prospective open uncontrolled study investigated efficiency and safety of national recombinant factor IX (rFIX, nonacog alfa, Innonafactor®, JSC “Generium” for preventive  treatment of 15 patients at the age of 12 years and older with  severe (n = 10, FIX activity < 1 %) and moderate (n = 5, FIX  activity 1–2 %) hemophilia B. Patients included to the study were 8  adolescents from 12 to 18 years and 7 adults at the age of 18 years  and older. Innonafactor was administered at a dose of 40–50 IU/kg  (in patients at the age of 12–18 years) and at a dose of 40–46 IU/kg (in patients at the age of 18 and older) twice a week with an interval of 72–96 h. The duration of preventive therapy was 26 ± 1 week  (not less than 50 days of administration of drug study). The average value of increasing the FIX activity (K-value) in 30 min after administration of Innonafactor was 1.38 ± 0.34 IU/dl of IU/kg in the  whole group of the patients, 1.26 ± 0.11 IU/dl of IU/kg in  adolescents, 1.53 ± 0.46 IU/dl of IU/kg in patients at the age of 18  years and older (p = 0.165). The average value of the recovery  degree of the FIX activity was 60.38 ± 13.44 % in all 15 patients,  62.91 ± 18.71 % – in adults, 58.17 ± of 7.03 % – in adolescents (p  = 0.563). During preventive treatment with the Innonafactor drug  18 hemorrhagic episodes were registered in 7 (46.7 %) patients.  Hemorrhagic episodes were registered mainly among adolescents, 17 (94.4 %) of the cases. The average number of bleeding episodes in 15 patients for the whole observation period was 1.2 ± 1.7, in  adolescents – 2.1 ± 1.9. 13 (72.2 %) episodes among 18  hemorrhagic episodes were post-traumatic, 5 (27.8 %) –  spontaneous (all have been observed in adolescents). The average  number of spontaneous bleeding episodes that occurred within 72 h  after administration of the Innonafactor, during the entire period of  the study (the main criterion of efficiency) in all 15 patients was 0.3 ± 0.8, and in adolescents – 0.6 ± 1.1. All registered hemorrhagic episodes were mild (8, or 44.4 %) or moderate (10, or 55.6 %). Among spontaneous bleeding 2 (40 %) episodes were mild and 3  (60 %) – moderate (additional criterion of efficiency). 6 (33.3 %)  hemorrhagic episodes (2 mild and 4 moderate) required additional  drug administration for the relief, 10 (55.6 %) of hemorrhagic  episodes (6 mild and 4 moderate) were stopped after 1 injection of the Innonafactor, 2 (11.1 %) episodes of moderate severity took 3 drug administration. 3 (60 %) spontaneous hemorrhagic episodes (1 mild and 2 moderate) did not require additional administration of the drug for relief, the remaining 2 (40 %) episodes (1 mild and 1  moderate) were treated with a single injection of the Innonafactor.  The average amount of drug Innonafactor injected in all patients  during the period of preventive treatment, was 134.3 ± 33.1  thousand IU, in adolescents – 122.4 ± 36.0 thousand IU, in adult  patients – 147.9 ± 25.4 thousand IU. The total amount of drug  Innonafactor injected in all 15 patients (additional criterion of efficiency), was 2014 thousand IU, in adolescents – 979 thousand IU, in adult patients – 1035 thousand IU. During the 2nd and 4th  visits in all 10 (100 %) patients with severe hemophilia B residual  FIX activity in 72–96 h after administration of the Innonafactor was  1 % or more (additional criterion of efficiency), during the 3rd visit  there were 9 (90 %) such patients. Among patients with moderate  hemophilia B the number of patients with residual FIX activity of 2 % or more in 72–96 h after administration of the Innonafactor (additional criterion of efficiency) during the 2nd, 3rd and 4th visits was 80 % (4 of 5). During the study 5 adverse events (AES) were registered, 2 (40 %) events were laboratory and 3 (60  %) events – clinical. All AES were mild severу and, according to  clinical investigator, were not related to the study drug.  Thromboembolic complications and immunogenic reactions were not  registered. Thus, the obtained data demonstrate the efficiency and  safety of the drug Innonafactor both to prevent and stop bleeding in  patients at the age of 12 years and older with severe and moderate hemophilia B.

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