ation of Hemophilia (WFH)
guidelines was targeted. All subjects returned to the adolescent/adult trial after the surgery trial assessments were
completed.
On-demand Treatment and Control of Bleeding Episodes
There were 1506 bleeds reported in 171 of 254 subjects across the completed clinical trials, and the most common bleed
types were joint (65.2%), muscle (14.5%), and subcutaneous (8.9%). Table 6 summarizes the efficacy in control of bleeding
episodes by age.
Doses used for treatment of bleeding episodes depended on age, treatment regimen and the severity of the bleed.
Of the 1407 mild and moderate bleeding episodes in all subjects in the adolescent/adult study, the median dose used was
42 IU/kg. For subjects who were on the on-demand arm the median initial dose was 28 IU/kg and 88.4% of the bleeds were
treated successfully with a single dose. In subjects receiving routine prophylaxis, the median initial dose was 52 IU/kg, and
76.4% of the bleeds were successfully treated with a single dose. Of the 15 severe bleeds, 12 (80%) required more than one
dose with a total median dose of 111 IU/kg.
In the pediatric study, 70 mild/moderate bleeds in children < 12 years old receiving routine prophylaxis were treated with a
median initial dose of 64 IU/kg per injection, with 63% treated with a single injection. When needed, additional median doses
of 62 IU/kg were used at approximately 24 hour intervals. The median total dose was 70 IU/kg per bleed.
Table 6: Summary of efficacy in control of bleeding episodes by age
Age range
# of subjects
<6 years
N=34
6 - <12 years
N=34
12 - <18years
N=25
≥ 18 years
N=161
Total
N= 254
# of bleeds 30 40 112 1324 1506
# of injections
1–2 76.7% 82.5% 88.4% 95.5% 94.3%
> 2 23.3% 17.5% 11.6% 4.5% 5.7%
Response to
first treatment
Excellent/
Good 80.0% 77.5% 75.0% 88.7% 87.3%
Moderate 13.3% 17.5% 17.9% 10.3% 11.1 %
Definition of Hemostatic Response:
Excellent: Abrupt pain relief and/or unequivocal improvement in objective signs of bleeding within approximately 8 hours after a single injection.
Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hours after one injection, but possibly requiring more than one
injection for complete resolution.
Moderate: Probable or slight beneficial effect within approximately 8 hours after the first injection; usually requiring more than one injection.
Perioperative Management
The efficacy analysis of ESPEROCT in perioperative management included 45 major surgical procedures performed in 33adolescent and adult subjects. The procedures included 15 joint replacements, 9 arthroscopic orthopedic interventions, 17other orthopedic interventions, and 4 non-orthopedic surgeries.
The clinical eva luation of hemostatic response during major surgery was assessed using a 4-point scale of excellent, good,moderate, or none. The hemostatic effect of ESPEROCT was rated as “excellent” or “good” in 43 of 45 surgeries (95.6%),while the effect was rated as “moderate” in 2 surgeries (4.4%). No surgery had an outcome rated as “none” or “missing.”
The median pre-operative dose for adults and adolescents undergoing major surgeries was 52 IU/kg, and the median totaldose was 702 IU/kg. During post-operative days 1-6, the median dose was 32 IU/kg at approximately 24 hour intervals.
During post-operative days 7-14, the media |
