Long-acting recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in children. Results of a phase 3 trial

Abstract

A global phase 3 study evaluated the pharmacokinetics, efficacy and safety of a recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 27 previously treated male children (1-11 years) with severe and moderately severe haemophilia B (factor IX [FIX] activity ≤2 IU/dl). All patients received routine prophylaxis once every seven days for up to 77 weeks, and treated any bleeding episodes on-demand. The mean terminal half-life of rIX-FP was 91.4 hours (h), 4.3-fold longer than previous FIX treatment and clearance was 1.11 ml/h/kg, 6.4-fold slower than previous FIX treatment. The median (Q1, Q3) annualised spontaneous bleeding rate was 0.00 (0.00, 0.91) and was similar between the <6 years and ≥6 years age groups, with a weekly median prophylactic dose of 46 IU/kg. In addition, patients maintained a median trough level of 13.4 IU/dl FIX activity on weekly prophylaxis. Overall, 97.2 % of bleeding episodes were successfully treated with one or two injections of rIX-FP (95 % CI: 92 % to 99 %), 88.7 % with one injection, and 96 % of the treatments were rated effective (excellent or good) by the Investigator. No patient developed FIX inhibitors and no safety concerns were identified. These results indicate that rIX-FP is safe and effective for preventing and treating bleeding episodes in children with haemophilia B with weekly prophylaxis. Routine prophylaxis with rIX-FP at treatment intervals of up to 14 days are currently being investigated in children with severe and moderately severe haemophilia B. Clinicaltrials.gov (NCT01662531).

Keywords: Haemophilia B; factor IX; on-demand treatment; prophylactic regimen; rIX-FP.

Figure 1:

Patient enrolment and study flow diagram. The diagram shows the flow and disposition of patients in the study. Following screening, 27 patients were enrolled in the study. All patients participated in PK evaluation of 50 IU/kg rIX-FP. A subset of patients (n=17) also participated in a PK evaluation of their previous FIX product (pdFIX or rFIX). All patients were assigned weekly prophylaxis with a dose of 35–50 IU/kg. All patients completed the study. FIX, factor IX; pdFIX, plasma-derived FIX; PK, pharmacokinetics; rFIX, recombinant FIX; rIX-FP, recombinant fusion protein linking coagulation factor IX with albumin.

Figure 2:

FIX activity after injection of a single dose of rIX-FP or previous FIX product (PK population). Mean baseline-uncorrected FIX activity after administration of a single infusion of 50 IU/kg of rIX-FP or 50 IU/kg previous FIX product (pdFIX or rFIX). FIX activity was measured in IU/dl. Vertical bars represent standard deviation. FIX, factor IX; pdFIX, plasma-derived FIX; PK, pharmacokinetic; rFIX, recombinant FIX; rIX-FP, recombinant fusion protein linking coagulation factor IX with albumin.