Congenital Bleeding Disorder, Haemophilia A
Conditions
Brief summary
This trial is conducted in Asia, Europe and North America. The purpose of the trial is to evaluate the safety and efficacy of turoctocog alfa in prevention and treatment of bleeds in previously untreated children with haemophilia A.
Interventions
DRUGturoctocog alfa
Patients will be scheduled to receive treatment with turoctocog alfa for at least 100 exposure days. In most cases, treatment will be given at home with intravenous (i.v., into the vein) self-injection by the parent/caregiver/support person.
Sponsors
Novo Nordisk A/S
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
0 Years to 6 Years
Healthy volunteers
No
Inclusion criteria
* Age below 6 years * Informed consent obtained before any trial-related activities (trial-related activities are any procedure that would not have been performed during normal management of the patient) * Male patients diagnosed with congenital severe haemophilia A (FVIII level equal to or below 1%) * No prior use of purified clotting factor products (previous exposure, equal to or less than 5 ED to blood components, e.g. cryoprecipitate, fresh frozen plasma, is accepted) including commercially available NovoEight® /Novoeight®
Exclusion criteria
* Known or suspected allergy to hamster protein or intolerance to trial product(s) or related products * Previous participation in this trial defined as withdrawal after administration of trial product * Congenital or acquired coagulation disorders other than haemophilia A * Any history of Factor VIII inhibitor * Ongoing treatment or planned treatment during the trial with immunomodulatory agents (e.g. intravenous immunoglobulin (IVIG), routine systemic corticosteroids)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rate of Factor VIII Inhibitors (Above or Equal to 0.6 BU (Bethesda Units)/mL) for the Main Phase of the Trial | From Visit 2 (21 days after screening) to Visit 5 (50-55 exposure day) | The incidence rate (percentage of participants with inhibitors) of inhibitors defined as inhibitor titres ≥0.6 BU for main phase of the trial. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases 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 (ABR) | From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial | 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. |
| Number of Turoctocog Alfa (N8) Injections Required Per Bleed | From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial | 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. |
| Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Month | From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial | 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. |
| Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Year | From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial | 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. |
| Consumption of Turoctocog Alfa (N8) (IU/kg/Bleed) Per Bleed | From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial | 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. |
| Consumption of Turoctocog Alfa (N8) (IU/kg/Months) for Bleed Prevention | From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial | 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. |
| Incidence Rate of Clinically Relevant Inhibitors Defined as an Inhibitor Titre (≥ 0.6 BU/mL) Combined With a Decreased Recovery (<66% of Expected Level) | From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial | 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 of High-titre Inhibitors Defined as Inhibitor Titre ≥ 5 BU (Bethesda Units)/mL) | From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the 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). |
| Change in Total Scores for Parent Reported Treatment Satisfaction | Visit 3 (10th-15th ED); Visit 5 (50th-55th ED); End of trial (within 8 weeks of their last scheduled visit in the extension phase) | 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. |
| Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Month Per Patient) | From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial | 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. |
| Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Year Per Patient) | From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial | 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. |
| Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) Reported During the Trial Period | From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial | 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. |
Countries
Algeria, Austria, Brazil, China, Denmark, Greece, Hong Kong, Hungary, Japan, Lithuania, Poland, Portugal, Puerto Rico, Russia, Serbia, Spain, Turkey (Türkiye), United States
Participant flow
Recruitment details
Participants were enrolled at 40 sites in 15 countries: Algeria (1 site), Austria (2 sites), China (6 sites), Denmark (1 site), Greece (2 sites), Hong Kong (1 site), Hungary (1 site), Japan (2 sites), Lithuania (1 site), Poland (2 sites), Russian Federation (2 sites), Serbia (1 site), Spain (3 sites), Turkey (3 sites), United States (12).
Pre-assignment details
Sixty (60) participants were enrolled in the trial and received at least one dose of turoctocog alfa.The trial consisted of two phases: the main phase including the screening visit (visit 1) and 4 subsequent visits, and an extension phase with a rolling visit schedule consisting of 6 planned visits including 4 dispensing visits) per year.
Participants by arm
| Arm | Count |
|---|---|
| Turoctocog Alfa (N8) (Preventive+On-demand) Participants received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. Participants who enrolled into the trial initiated the preventive treatment no later than their second birthday or after a maximum of 2 bleeding episodes requiring treatment, whichever came first. The trial consisted of two phases. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. After that the participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). The estimated total duration of the trial was approximately 7 years. | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 8 |
Baseline characteristics
| Characteristic | Turoctocog Alfa (N8) (Preventive+On-demand) |
|---|---|
| Age, Continuous | 10.2 Months STANDARD_DEVIATION 7.88 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 44 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 60 |
| other Total, other adverse events | 55 / 60 |
| serious Total, serious adverse events | 36 / 60 |
Outcome results
Primary
Incidence Rate of Factor VIII Inhibitors (Above or Equal to 0.6 BU (Bethesda Units)/mL) for the Main Phase of the Trial
The incidence rate (percentage of participants with inhibitors) of inhibitors defined as inhibitor titres ≥0.6 BU for main phase of the trial.
Time frame: From Visit 2 (21 days after screening) to Visit 5 (50-55 exposure day)
Population: Analysis was based on participants who completed the main phase of the trial.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Incidence Rate of Factor VIII Inhibitors (Above or Equal to 0.6 BU (Bethesda Units)/mL) for the Main Phase of the Trial | 43.1 Percentage of participants |
Secondary
Annualised Bleeding Rate (ABR)
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.
Time frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial
Population: The full analysis (FAS) set included all dosed participants with data after dosing. Participants in FAS with only one exposure day were excluded from preventive treatment in main when calculating the Poisson estimates of ABR as the small amount of information introduces uncertainty to the estimated ABR.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Annualised Bleeding Rate (ABR) | 4.27 bleeds/patient/year |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Annualised Bleeding Rate (ABR) | 5.63 bleeds/patient/year |
| Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Annualised Bleeding Rate (ABR) | 3.81 bleeds/patient/year |
| Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Annualised Bleeding Rate (ABR) | 4.26 bleeds/patient/year |
| Turoctocog Alfa (N8): Inhibitor Cohort | Annualised Bleeding Rate (ABR) | 6.09 bleeds/patient/year |
Secondary
Change in Total Scores for Parent Reported Treatment Satisfaction
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.
Time frame: Visit 3 (10th-15th ED); Visit 5 (50th-55th ED); End of trial (within 8 weeks of their last scheduled visit in the extension phase)
Population: The full analysis set included all dosed participants with data after dosing. Number of participants analysed=number of participants who answered the questionnaire
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Change in Total Scores for Parent Reported Treatment Satisfaction | Ease/convenience visit 3 Range: 0 - 100 | 27.1 Score on a scale | Standard Deviation 14.6 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Change in Total Scores for Parent Reported Treatment Satisfaction | Efficacy - visit 3 Score range: 0-100 | 10.2 Score on a scale | Standard Deviation 12.8 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Change in Total Scores for Parent Reported Treatment Satisfaction | Ease and convenience - visit 5 Score range: 0-100 | 21.4 Score on a scale | Standard Deviation 14.9 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Change in Total Scores for Parent Reported Treatment Satisfaction | Ease and convenience - EoT Score range:0-100 | 21.9 Score on a scale | Standard Deviation 13.4 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Change in Total Scores for Parent Reported Treatment Satisfaction | Efficacy - visit 5 Score range: 0-100 | 9.8 Score on a scale | Standard Deviation 10.5 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Change in Total Scores for Parent Reported Treatment Satisfaction | Efficacy - end of trial Score range: 0-100 | 11.7 Score on a scale | Standard Deviation 17.4 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Change in Total Scores for Parent Reported Treatment Satisfaction | Burden - visit 3 Score range: 0-100 | 20.5 Score on a scale | Standard Deviation 21 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Change in Total Scores for Parent Reported Treatment Satisfaction | Burden - visit 5 Score range: 0-100 | 15.4 Score on a scale | Standard Deviation 17.4 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Change in Total Scores for Parent Reported Treatment Satisfaction | Burden - end of trial Score range: 0-100 | 16.9 Score on a scale | Standard Deviation 16.6 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Change in Total Scores for Parent Reported Treatment Satisfaction | Specialist/Nurses- visit 3 Score range: 0-100 | 4.1 Score on a scale | Standard Deviation 8.4 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Change in Total Scores for Parent Reported Treatment Satisfaction | Specialist/Nurses- visit 5 Score range: 0-100 | 4.0 Score on a scale | Standard Deviation 6.6 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Change in Total Scores for Parent Reported Treatment Satisfaction | Specialist/Nurses- end of trial Score range: 0-100 | 4.9 Score on a scale | Standard Deviation 8.2 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Change in Total Scores for Parent Reported Treatment Satisfaction | Centre/Hospital - visit 3 Score range: 0-100 | 2.8 Score on a scale | Standard Deviation 5.7 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Change in Total Scores for Parent Reported Treatment Satisfaction | Centre/Hospital - visit 5 Score range: 0-100 | 3.1 Score on a scale | Standard Deviation 5.7 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Change in Total Scores for Parent Reported Treatment Satisfaction | Centre/Hospital - end of trial Score range: 0-100 | 5.0 Score on a scale | Standard Deviation 8.9 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Change in Total Scores for Parent Reported Treatment Satisfaction | General satisfaction - visit 3 Score range: 0-100 | 5.7 Score on a scale | Standard Deviation 10.7 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Change in Total Scores for Parent Reported Treatment Satisfaction | General satisfaction - visit 5 Score range: 0-100 | 3.8 Score on a scale | Standard Deviation 8.5 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Change in Total Scores for Parent Reported Treatment Satisfaction | General satisfaction - end of trial Range: 0-100 | 6.4 Score on a scale | Standard Deviation 15.3 |
Secondary
Consumption of Turoctocog Alfa (N8) (IU/kg/Bleed) Per Bleed
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.
Time frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial
Population: The full analysis set included all dosed participants with data after dosing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Consumption of Turoctocog Alfa (N8) (IU/kg/Bleed) Per Bleed | 86.1 IU/kg/bleed | Standard Deviation 116.8 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Consumption of Turoctocog Alfa (N8) (IU/kg/Bleed) Per Bleed | 80.8 IU/kg/bleed | Standard Deviation 126.4 |
| Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Consumption of Turoctocog Alfa (N8) (IU/kg/Bleed) Per Bleed | 107.9 IU/kg/bleed | Standard Deviation 137.7 |
| Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Consumption of Turoctocog Alfa (N8) (IU/kg/Bleed) Per Bleed | 98.9 IU/kg/bleed | Standard Deviation 134.5 |
| Turoctocog Alfa (N8): Inhibitor Cohort | Consumption of Turoctocog Alfa (N8) (IU/kg/Bleed) Per Bleed | 279.1 IU/kg/bleed | Standard Deviation 821.7 |
Secondary
Consumption of Turoctocog Alfa (N8) (IU/kg/Months) for Bleed Prevention
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.
Time frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial
Population: The full analysis set included all dosed participants with data after dosing. Participants in on-demand treatment did not receive treatment for bleed prevention and therefore are not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Consumption of Turoctocog Alfa (N8) (IU/kg/Months) for Bleed Prevention | 293.5 IU/kg/month/patient | Standard Deviation 281.1 |
| Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Consumption of Turoctocog Alfa (N8) (IU/kg/Months) for Bleed Prevention | 446.3 IU/kg/month/patient | Standard Deviation 206.2 |
| Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Consumption of Turoctocog Alfa (N8) (IU/kg/Months) for Bleed Prevention | 399.0 IU/kg/month/patient | Standard Deviation 234.7 |
| Turoctocog Alfa (N8): Inhibitor Cohort | Consumption of Turoctocog Alfa (N8) (IU/kg/Months) for Bleed Prevention | 1692.6 IU/kg/month/patient | Standard Deviation 1553.9 |
Secondary
Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) Reported During the Trial Period
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.
Time frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial
Population: The safety analysis set included all dosed participants with data after dosing. The arm group - 'main phase' includes subjects who were treated both on-demand and preventively in the main phase. 'On-Demand' and 'Preventive' were not described as separate arms/groups in the protocol. These were not analysed separately for this endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) Reported During the Trial Period | All adverse events | 5.85 events per patient years of exposure |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) Reported During the Trial Period | Serious adverse events | 1.02 events per patient years of exposure |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) Reported During the Trial Period | Serious adverse events | 0.24 events per patient years of exposure |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) Reported During the Trial Period | All adverse events | 3.76 events per patient years of exposure |
| Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) Reported During the Trial Period | All adverse events | 5.12 events per patient years of exposure |
| Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) Reported During the Trial Period | Serious adverse events | 0.73 events per patient years of exposure |
| Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) Reported During the Trial Period | All adverse events | 7.41 events per patient years of exposure |
| Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) Reported During the Trial Period | Serious adverse events | 1.52 events per patient years of exposure |
Secondary
Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None
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.
Time frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial
Population: The full analysis set included all dosed participants with data after dosing.
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | Moderate | 5 bleeds |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | Missing | 4 bleeds |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | Good | 36 bleeds |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | Excellent | 53 bleeds |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | None | 0 bleeds |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | Excellent | 83 bleeds |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | None | 1 bleeds |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | Missing | 8 bleeds |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | Good | 29 bleeds |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | Moderate | 12 bleeds |
| Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | None | 1 bleeds |
| Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | Missing | 3 bleeds |
| Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | Moderate | 31 bleeds |
| Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | Good | 73 bleeds |
| Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | Excellent | 161 bleeds |
| Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | None | 2 bleeds |
| Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | Missing | 11 bleeds |
| Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | Good | 102 bleeds |
| Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | Moderate | 43 bleeds |
| Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | Excellent | 244 bleeds |
| Turoctocog Alfa (N8): Inhibitor Cohort | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | Excellent | 9 bleeds |
| Turoctocog Alfa (N8): Inhibitor Cohort | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | Missing | 137 bleeds |
| Turoctocog Alfa (N8): Inhibitor Cohort | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | None | 4 bleeds |
| Turoctocog Alfa (N8): Inhibitor Cohort | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | Moderate | 10 bleeds |
| Turoctocog Alfa (N8): Inhibitor Cohort | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None | Good | 19 bleeds |
Secondary
Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Month Per Patient)
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.
Time frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial
Population: The full analysis set included all dosed participants with data after dosing. Number of participants analysed=number of participants with data available
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Month Per Patient) | Patient's use of mobility aids | 0.0 days/month/patient | Standard Deviation 0 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Month Per Patient) | Caregiver/parent's absence from work | 0.011 days/month/patient | Standard Deviation 0.05 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Month Per Patient) | Patient's use of mobility aids | 0.0 days/month/patient | Standard Deviation 0 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Month Per Patient) | Caregiver/parent's absence from work | 0.533 days/month/patient | Standard Deviation 1.645 |
| Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Month Per Patient) | Caregiver/parent's absence from work | 0.007 days/month/patient | Standard Deviation 0.027 |
| Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Month Per Patient) | Patient's use of mobility aids | 0.0 days/month/patient | Standard Deviation 0 |
| Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Month Per Patient) | Patient's use of mobility aids | 0.0 days/month/patient | Standard Deviation 0 |
| Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Month Per Patient) | Caregiver/parent's absence from work | 0.232 days/month/patient | Standard Deviation 1.117 |
| Turoctocog Alfa (N8): Inhibitor Cohort | Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Month Per Patient) | Patient's use of mobility aids | 0.025 days/month/patient | Standard Deviation 0.084 |
| Turoctocog Alfa (N8): Inhibitor Cohort | Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Month Per Patient) | Caregiver/parent's absence from work | 0.271 days/month/patient | Standard Deviation 0.641 |
Secondary
Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Year Per Patient)
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.
Time frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial
Population: The full analysis set included all dosed participants with data after dosing. Number of participants analysed=number of participants with data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Year Per Patient) | Patient's use of mobility aids | 0.0 days/year/patient | Standard Deviation 0 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Year Per Patient) | Caregiver/parent's absence from work | 0.127 days/year/patient | Standard Deviation 0.601 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Year Per Patient) | Caregiver/parent's absence from work | 6.396 days/year/patient | Standard Deviation 19.736 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Year Per Patient) | Patient's use of mobility aids | 0.0 days/year/patient | Standard Deviation 0 |
| Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Year Per Patient) | Caregiver/parent's absence from work | 0.082 days/year/patient | Standard Deviation 0.319 |
| Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Year Per Patient) | Patient's use of mobility aids | 0.0 days/year/patient | Standard Deviation 0 |
| Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Year Per Patient) | Patient's use of mobility aids | 0.0 days/year/patient | Standard Deviation 0 |
| Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Year Per Patient) | Caregiver/parent's absence from work | 2.779 days/year/patient | Standard Deviation 13.406 |
| Turoctocog Alfa (N8): Inhibitor Cohort | Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Year Per Patient) | Caregiver/parent's absence from work | 3.252 days/year/patient | Standard Deviation 7.691 |
| Turoctocog Alfa (N8): Inhibitor Cohort | Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Year Per Patient) | Patient's use of mobility aids | 0.296 days/year/patient | Standard Deviation 1.006 |
Secondary
Incidence Rate of Clinically Relevant Inhibitors Defined as an Inhibitor Titre (≥ 0.6 BU/mL) Combined With a Decreased Recovery (<66% of Expected Level)
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).
Time frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial
Population: The full analysis set included all dosed participants with data after dosing. The arm group - 'main phase' includes subjects who were treated both on-demand and preventively in the main phase. 'On-Demand' and 'Preventive' were not described as separate arms/groups in the protocol. These were not analysed separately for this endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Incidence Rate of Clinically Relevant Inhibitors Defined as an Inhibitor Titre (≥ 0.6 BU/mL) Combined With a Decreased Recovery (<66% of Expected Level) | One-stage FVIII clotting activity assay | 36.2 Percentage of participants |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Incidence Rate of Clinically Relevant Inhibitors Defined as an Inhibitor Titre (≥ 0.6 BU/mL) Combined With a Decreased Recovery (<66% of Expected Level) | Two-stage chromogenic assay | 36.2 Percentage of participants |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Incidence Rate of Clinically Relevant Inhibitors Defined as an Inhibitor Titre (≥ 0.6 BU/mL) Combined With a Decreased Recovery (<66% of Expected Level) | Two-stage chromogenic assay | 3.0 Percentage of participants |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Incidence Rate of Clinically Relevant Inhibitors Defined as an Inhibitor Titre (≥ 0.6 BU/mL) Combined With a Decreased Recovery (<66% of Expected Level) | One-stage FVIII clotting activity assay | 3.0 Percentage of participants |
| Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Incidence Rate of Clinically Relevant Inhibitors Defined as an Inhibitor Titre (≥ 0.6 BU/mL) Combined With a Decreased Recovery (<66% of Expected Level) | One-stage FVIII clotting activity assay | 37.9 Percentage of participants |
| Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Incidence Rate of Clinically Relevant Inhibitors Defined as an Inhibitor Titre (≥ 0.6 BU/mL) Combined With a Decreased Recovery (<66% of Expected Level) | Two-stage chromogenic assay | 37.9 Percentage of participants |
Secondary
Incidence Rate of High-titre Inhibitors Defined as Inhibitor Titre ≥ 5 BU (Bethesda Units)/mL)
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).
Time frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial
Population: The full analysis set included all dosed participants with data after dosing. The arm group - 'main phase' includes subjects who were treated both on-demand and preventively in the main phase. 'On-Demand' and 'Preventive' were not described as separate arms/groups in the protocol. These were not analysed separately for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Incidence Rate of High-titre Inhibitors Defined as Inhibitor Titre ≥ 5 BU (Bethesda Units)/mL) | 27.6 Percentage of participants |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Incidence Rate of High-titre Inhibitors Defined as Inhibitor Titre ≥ 5 BU (Bethesda Units)/mL) | 0.0 Percentage of participants |
| Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Incidence Rate of High-titre Inhibitors Defined as Inhibitor Titre ≥ 5 BU (Bethesda Units)/mL) | 27.6 Percentage of participants |
Secondary
Number of Turoctocog Alfa (N8) Injections Required Per Bleed
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.
Time frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial
Population: Full Analysis Set included all dosed participants with data after dosing. Number of participants analysed=number of participants with bleeding episodes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Number of Turoctocog Alfa (N8) Injections Required Per Bleed | 2.1 injections/bleed | Standard Deviation 2.18 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Number of Turoctocog Alfa (N8) Injections Required Per Bleed | 1.8 injections/bleed | Standard Deviation 2.98 |
| Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Number of Turoctocog Alfa (N8) Injections Required Per Bleed | 2.4 injections/bleed | Standard Deviation 3.04 |
| Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Number of Turoctocog Alfa (N8) Injections Required Per Bleed | 2.2 injections/bleed | Standard Deviation 3.03 |
| Turoctocog Alfa (N8): Inhibitor Cohort | Number of Turoctocog Alfa (N8) Injections Required Per Bleed | 2.8 injections/bleed | Standard Deviation 6.24 |
Secondary
Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Month
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.
Time frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial
Population: Full Analysis Set included all dosed participants with data after dosing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Month | 117.6 IU/kg/month/patient | Standard Deviation 190.7 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Month | 359.8 IU/kg/month/patient | Standard Deviation 323.2 |
| Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Month | 476.9 IU/kg/month/patient | Standard Deviation 209.3 |
| Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Month | 437.2 IU/kg/month/patient | Standard Deviation 244.4 |
| Turoctocog Alfa (N8): Inhibitor Cohort | Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Month | 1815.2 IU/kg/month/patient | Standard Deviation 1653.8 |
Secondary
Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Year
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.
Time frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial
Population: Full Analysis Set included all dosed participants with data after dosing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Year | 1410.8 IU/kg/year/patient | Standard Deviation 2288.4 |
| Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Year | 4317.2 IU/kg/year/patient | Standard Deviation 3878.9 |
| Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Year | 5722.5 IU/kg/year/patient | Standard Deviation 2512 |
| Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Year | 5245.9 IU/kg/year/patient | Standard Deviation 2933.1 |
| Turoctocog Alfa (N8): Inhibitor Cohort | Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Year | 21782.8 IU/kg/year/patient | Standard Deviation 19845.6 |