Moroctocog alfa (AF-CC) is a B-domain deleted recombinant factor VIII product for the treatment of patients with hemophilia A. It has previously been studied in pediatric aged hemophilia patients, however direct comparisons between treatment regimens have not been evaluated. Importantly, as prophylaxis has been shown to be superior to on-demand treatment, comparisons between different prophylaxis regimens are needed. Reducing the frequency of infusions without sacrificing efficacy may reduce the burden of hemophilia management. This study was an open label, multicenter, randomized crossover study of two routine prophylaxis (RP) regimens of moroctocog alfa (AF-CC) compared to on-demand (OD) therapy in 2 cohorts of children with hemophilia A. The primary objective was to demonstrate that prophylaxis reduces ABR relative to OD therapy. A secondary objective was to compare the efficacy of two different RP regimens. Additional objectives focused on FVIII recovery and safety.
Study Design: The study was open to previously treated patients (≥20 exposure days (ED) to any FVIII replacement product) with moderately severe to severe hemophilia A (<2% FVIII) aged 6 months to <16 years. The study enrolled 2 cohorts of subjects who were treated in two segments. The first cohort started with OD treatment for 6 months (segment 1) followed by 1 year of RP of 25 international units (IU)/kg every other day (segment 2). Subjects in the second cohort were randomized to one of 2 RP regimens for 1 year (segment 1) and then crossed over to a second RP regimen for an additional year (segment 2). The RP regimens were high frequency (HF) (25 IU/kg every other day) and low frequency (LF) (45 IU/kg twice weekly). Recovery assessment after administration of 50 IU/kg of moroctocog alfa (AF-CC) was optional.
Results: A total of 51 subjects were enrolled in the study: 9 subjects (age 2.4-5.9 yr; median 4.9 yr) in the OD group, 18 subjects (age 1.1-12.7 yr; median 4.7 yr) received LF followed by HF, and 24 subjects (age 1.2 to 9.6 yr; median 4.6 yr) received HF followed by LF. The mean (standard deviation [SD]) ABR for the first cohort (n=9) during the OD segment was 47.0(32.2) and during the RP segment (HF) was 1.5(2.2). In those subjects from cohort 2 that completed both segments (n=38), the mean (standard deviation) ABR for HF was 2.2(4.1) and for LF was 3.3(5.3). Based on a prospectively defined equivalence limit of (-3, 3) bleeds per year, equivalence between these two regimens was demonstrated as the 90% CI for the difference, (0.03, 2.22) fell within this range. The mean (SD) recovery in 6 children aged 3.7 to 5.8 yrs was 1.44(0.61) IU/dL/IU/kg. Three subjects tested positive for FVIII inhibitors, however 2 were considered to be false positives for an overall rate of 2%. There were no new safety signals that emerged during this study.
Conclusion: This study met its primary objective of demonstrating that RP reduces the ABR compared to OD. Notably, LF prophylaxis with moroctocog alfa (AF-CC) is as efficacious as a HF prophylaxis regimen. This has important implications as less frequent infusions can improve adherence and the quality of life for patients with hemophilia. Additionally, recovery was as expected in this pediatric population and no new safety signals emerged. Moroctocog alfa (AF-CC) is safe and efficacious for routine prophylaxis in pediatric patients with hemophilia A and a low frequency (twice weekly) prophylaxis regimen is as efficacious as every other day prophylaxis.
Rupon:Pfizer: Employment. Korth-Bradley:Pfizer Inc.: Employment. Smith:Pfizer: Employment. Rendo:Pfizer: Employment.
Asterisk with author names denotes non-ASH members.