Safety and Efficacy of Turoctocog Alfa in Prevention and Treatment of Bleeds in Previously Untreated Children With Haemophilia A

The incidence rate (percentage of participants with inhibitors) of inhibitors defined as inhibitor titres ≥0.6 BU for main phase of the trial.

The haemostatic effect of turoctocog alfa was summarised by frequency tables containing count of all bleeds and assessed on a predefined four point scale: Excellent, Good, Moderate and None. The analysis was based on the total number of bleeds and their response to treatment. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.

Annualised bleeding rate defined as number of bleeds in total per patient per year following treatment were estimated by a Poisson model allowing for over-dispersion. The Poisson estimate is presented with a 95% confidence interval (CI). The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.

The number of injections of turoctocog alfa (N8) required per bleed was calculated as the number of injections of turoctocog alfa used in the time period from start of the bleed to stop of the bleed. The mean number of turoctocog alfa injections required to stop the bleed is presented. The analysis was based on the total number of bleeds. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.

Mean total consumption of turoctocog alfa (N8) used for treatment (includes all injections given: prevention, treatment of bleeds and during surgery) per patient per month. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.

Mean total consumption of turoctocog alfa (N8) used for treatment (includes all injections given: prevention, treatment of bleeds and during surgery) per patient per year. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.

Mean consumption of turoctocog alfa (N8) used for treatment of bleed from start to stop of bleed. The analysis was based on number of bleeds. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.

Mean consumption of turoctocog alfa (N8) used for preventive treatment per month per patient. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.

Number of adverse events and serious adverse events per patient years of exposure. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial (exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.

The incidence rates (number of patients with new inhibitor in the period/number of participants at risk, expressed in percentage) of clinically relevant inhibitors were defined as an inhibitor titre (≥ 0.6 BU) combined with a decreased recovery (<66% of expected level). Incidence rate of clinically relevant inhibitors according to the type of assay used is presented. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation) and the combined main and extension phase (from Visit 2 to end of trial).

Incidence rate (number of patients with new inhibitor in the period/number of participants at risk, expressed in percentage) of high-titre inhibitors defined as inhibitor titre ≥ 5 BU (Bethesda Units)/mL). The inhibitors were evaluated for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation) and the combined main and extension phase (from Visit 2 to end of trial).

The caregivers/parent reported treatment satisfaction is assessed by the parents using the haemophilia satisfaction questionnaire (HEMO-SAT). The questionnaire contained questions related to treatment that covered 6 domains (ease and convenience, efficacy, burden, specialist, centre and general satisfaction). Adults completing the questionnaire could achieve a score from 0 to 100, with lower scores reflecting greater treatment satisfaction. The scale range for each of the 6 domains was 0-100 with lower scores reflecting greater treatment satisfaction.

The scores of the domains at visit 3 (10th-15th ED), visit 5 (50th-55th ED) and end of trial (EoT) are presented.

Resource utilisation and caregiver burden are analysed in terms of average number of days absent from work and use of mobility aids (e.g. wheelchair or crutches) as a consequence of bleeds. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.

Resource utilisation and caregiver burden are analysed in terms of average number of days of absence from work and use of mobility aids (e.g. wheelchair or crutches) as a consequence of bleeds. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.