Congenital Bleeding Disorder, Haemophilia A
Conditions
Brief summary
This trial is conducted in China. The aim of this trial is to evaluate the clinical efficacy of turoctocog alfa in treatment of bleeding episodes in Chinese patients with severe haemophilia A (FVIII≤1%).
Interventions
DRUGturoctocog alfa
The preventative treatment is administered intravenously (i.v.) at specific intervals either every second day or three times a week. Bleeding treatment will be administered if a bleed should occur.
Sponsors
Novo Nordisk A/S
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Healthy volunteers
No
Inclusion criteria
* Male patients * Age from 0 years * With the diagnosis of severe congenital haemophilia A (FVIII≤1%) * History of exposure days (ED) to any FVIII products fulfilling the criteria of previously treated patients: * Patients of 12 years or above: 100 exposures days (ED) or more * Patients below 12 years: 50 exposure days (ED) or more
Exclusion criteria
* Inhibitors to factor VIII (≥0.6 BU) at screening as assessed by central laboratory * Known history of FVIII inhibitors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months | Month 0-6 | The haemostatic effect of turoctocog alfa when used for treatment of bleeding episodes in both prophylaxis and on-demand regimen was evaluated during month 0-6. The effect was assessed on a four-point scale for haemostatic response, excellent, good, moderate and none. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rate of Inhibitory Antibodies Against FVIII (≥0.6 BU): 6 Months | Month 0-6 | This endpoint presented 'percentage of participants with inhibitory antibodies against FVIII (≥0.6 BU)' in both prophylaxis and on-demand regimen, evaluated during month 0-6. |
| Incidence Rate of Inhibitory Antibodies Against FVIII (≥0.6 BU): 24 Months | Month 0-24 | This endpoint presented 'percentage of participants with inhibitory antibodies against FVIII (≥0.6 BU)' in both prophylaxis and on-demand regimen, evaluated during month 0-24. |
| Number of Bleeds (Total Bleeds Assessed as Annual Bleeding Rate) Per Participant: 6 Months | Month 0-6 | Number of bleeds (total bleeds assessed as annual bleeding rate) per participant in the prophylaxis regimen was evaluated during month 0-6. The annualised bleeding rate was analysed by a negative binomial model. |
| Number of Bleeds (Total Bleeds Assessed as Annual Bleeding Rate) Per Participant: 24 Months | Month 0-24 | Number of bleeds (total bleeds assessed as annual bleeding rate) per participant in the prophylaxis regimen was evaluated during month 0-24. The annualised bleeding rate was analysed by a negative binomial model. |
| Consumption of Turoctocog Alfa for Bleeding Treatment: Average Dose to Treat a Bleed (6 Months) | Month 0-6 | Average dose of turoctocog alfa used to treat a bleed in both prophylaxis and on-demand regimen was evaluated during month 0-6. |
| Consumption of Turoctocog Alfa for Bleeding Treatment: Average Dose to Treat a Bleed (24 Months) | Month 0-24 | Average dose of turoctocog alfa used to treat a bleed in both prophylaxis and on-demand regimen was evaluated during month 0-24. |
| Consumption of Turoctocog Alfa for Bleeding Treatment: Number of Injections Per Bleed (6 Months) | Month 0-6 | Number of turoctocog alfa injections consumed to treat a bleeding episode in both prophylaxis and on-demand regimen was evaluated during month 0-6. |
| Consumption of Turoctocog Alfa for Bleeding Treatment: Number of Injections Per Bleed (24 Months) | Month 0-24 | Number of turoctocog alfa injections consumed to treat a bleeding episode in both prophylaxis and on-demand regimen was evaluated during month 0-24. |
| Consumption of Turoctocog Alfa for Bleeding Treatment: IU/kg Per Bleed (6 Months) | Month 0-6 | Consumption of turoctocog alfa IU/kg BW per bleed in both prophylaxis and on-demand regimen was evaluated during month 0-6. |
| Consumption of Turoctocog Alfa for Bleeding Treatment: IU/kg Per Bleed (24 Months) | Month 0-24 | Consumption of turoctocog alfa IU/kg BW per bleed in both prophylaxis and on-demand regimen was evaluated during month 0-24. |
| Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: Average Preventive Dose (6 Months) | Month 0-6 | Average preventive dose of turoctocog alfa consumed per participant in the prophylaxis regimen was evaluated during month 0-6. |
| Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: Average Preventive Dose (24 Months) | Month 0-24 | Average preventive dose of turoctocog alfa consumed per participant in the prophylaxis regimen was evaluated during month 0-24. |
| Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Month (6 Months) | Month 0-6 | Preventive dose of turoctocog alfa (IU/kg body weight (BW) per month) per participant in the prophylaxis regimen was evaluated during month 0-6. |
| Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Month (24 Months) | Month 0-24 | Preventive dose of turoctocog alfa (IU/kg body weight (BW) per month) per participant in the prophylaxis regimen was evaluated during month 0-24. |
| Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Year (6 Months) | Month 0-6 | Preventive dose of turoctocog alfa (IU/kg body weight per year) per participant in the prophylaxis regimen was evaluated during month 0-6. |
| Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Year (24 Months) | Month 0-24 | Preventive dose of turoctocog alfa (IU/kg body weight (BW) per year) per participant in the prophylaxis regimen was evaluated during month 0-24. |
| Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Month (6 Months) | Month 0-6 | Total consumption of turoctocog alfa (IU/kg body weight per month) per participant in both prophylaxis and on-demand regimen was evaluated during month 0-6. |
| Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Month (24 Months) | Month 0-24 | Total consumption of turoctocog alfa (IU/kg body weight per month) per participant in both prophylaxis and on-demand regimen was evaluated during month 0-24. |
| Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Year (6 Months) | Month 0-6 | Total consumption of turoctocog alfa (IU/kg body weight per year) per participant in both prophylaxis and on-demand regimen was evaluated during month 0-6. |
| Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Year (24 Months) | Month 0-24 | Total consumption of turoctocog alfa (IU/kg body weight per year) per participant in both prophylaxis and on-demand regimen was evaluated during month 0-24. |
| Frequency of Adverse Events (6 Months) | Month 0-6 | Frequency of adverse events (AEs) are presented as rate of events, which was calculated as the number of AEs per patient years. All presented AEs are treatment emergent (TEAEs), which were defined as the events reported after trial product administration until the end of the post-treatment follow-up period. |
| Frequency of Adverse Events (24 Months) | Month 0-24 | Frequency of adverse events (AEs) are presented as rate of events, which was calculated as the number of AEs per patient years. All presented AEs are treatment emergent (TEAEs), which were defined as the events reported after trial product administration until the end of the post-treatment follow-up period. |
| Frequency of Serious Adverse Events (6 Months) | Month 0-6 | Frequency of serious adverse events (SAEs) are presented as rate of events, which was calculated as the number of SAEs per patient years. All presented SAEs are treatment emergent, which were defined as the events reported after trial product administration until the end of the post-treatment follow-up period. |
| Frequency of Serious Adverse Events (24 Months) | Month 0-24 | Frequency of serious adverse events (SAEs) are presented as rate of events, which was calculated as the number of SAEs per patient years. All presented SAEs are treatment emergent, which were defined as the events reported after trial product administration until the end of the post-treatment follow-up period. |
| Haemostatic Effect of Turoctocog Alfa (Surgery): 6 Months | Month 0-6 | The haemostatic effect of turoctocog alfa when used for surgery was evaluated during month 0-6. The effect was assessed on a four-point scale for haemostatic response (excellent, good, moderate and none) and assessed by the investigator/surgeon on the day of surgery (day 1) and on the last day in the post-operative period the participant was at the trial/surgery site. |
| Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months | Month 0-24 | The haemostatic effect of turoctocog alfa when used for surgery was evaluated during month 0-24. The effect was assessed on a four-point scale for haemostatic response (excellent, good, moderate and none) and assessed by the investigator/surgeon on the day of surgery (day 1) and on the last day in the post-operative period the participant was at the trial/surgery site. Haemostatic response of 'not applicable' indicated that turoctocog alfa was not used. |
| Loss of Blood (Surgery): 6 Months | Month 0-6 | Loss of blood was evaluated during month 0-6: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant was at the trial/surgery site whatever comes first. |
| Loss of Blood (Surgery): 24 Months | Month 0-24 | Loss of blood was evaluated during month 0-24: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant was at the trial/surgery site whatever comes first. |
| Requirements for Transfusion (Surgery): 6 Months | Month 0-6 | Surgeries required transfusion was evaluated during month 0-6: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant was at the trial/surgery site whatever comes first. |
| Requirements for Transfusion (Surgery): 24 Months | Month 0-24 | Surgeries required transfusion was evaluated during month 0-24: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant was at the trial/surgery site whatever comes first. |
| Adverse Events (Surgery): 6 Months | Month 0-6 | TEAEs during surgery were recorded during month 0-6: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant was at the trial/surgery site whatever comes first. TEAEs were defined as the events reported after trial product administration until the end of the post-treatment follow-up period. |
| Adverse Events (Surgery): 24 Months | Month 0-24 | TEAEs during surgery were recorded during month 0-24: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant was at the trial/surgery site whatever comes first. TEAEs were defined as the events reported after trial product administration until the end of the post-treatment follow-up period. |
| Serious Adverse Events (Surgery): 6 Months | Month 0-6 | Treatment emergent serious adverse events occurred during surgery were recorded from month 0 to month 6: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant is at the trial/surgery site whatever comes first. Treatment emergent events were defined as the events reported after trial product administration until the end of the post-treatment follow-up period. |
| Serious Adverse Events (Surgery): 24 Months | Month 0-24 | Treatment emergent serious adverse events occurred during surgery were recorded from month 0 to month 24: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant is at the trial/surgery site whatever comes first. Treatment emergent events were defined as the events reported after trial product administration until the end of the post-treatment follow-up period. |
| Change in Total Scores for Reported Health-related Quality of Life (for Participants): Month 6 | Month 0, Month 6 | Reported results are baseline (month 0) and change from baseline (at month 6) of end of disease and age specific HRQOL. HRQOL was collected through use of the patient reported outcome (PRO) instruments, HAEMO-QOL (for children (8-12 years)/adolescents (13-16 years)) and HAEM-A-QOL (for adults (\>=17 years)). HAEMO-QOL assessment included questions on physical health, feeling, view of yourself, family, friends, perceived support, other persons, sports and school, dealing with haemophilia, treatment, future, and relationships. HAEM-A-QOL assessment included questions on physical health, feeling, view of yourself, sports and leisure, work and school, dealing with haemophilia, treatment, future, family planning, and partnership and sexuality. Scores range for each question was 0-100, with a lower score indicating better quality of life related to haemophilia. Observed mean of the means of all the questions for HAEMO-QOL and HAEM-A-QOL, respectively are presented. |
| Change in Total Scores for Reported Health-related Quality of Life (for Participants): Month 24 | Month 0, Month 24 | Reported results are baseline (month 0) and change from baseline (at month 24) of end of disease and age specific HRQOL. HRQOL was collected through use of the patient reported outcome (PRO) instruments, HAEM-A-QOL (for adults (\>=17 years)) and HAEMO-QOL (for children (8-12 years)/adolescents (13-16 years)). HAEM-A-QOL assessment included questions on physical health, feeling, view of yourself, sports and leisure, work and school, dealing with haemophilia, treatment, future, family planning, and partnership and sexuality. HAEMO-QOL assessment included questions on physical health, feeling, view of yourself, family, friends, perceived support, other persons, sports and school, dealing with haemophilia, treatment, future, and relationships. Scores range for each question was 0-100, with a lower score indicating better quality of life related to haemophilia. Observed mean of the means of all the questions for HAEM-A-QOL and HAEMO-QOL, respectively are presented. |
| Change in Total Scores for Reported Health-related Quality of Life (for Parents): Month 6 | Month 0, Month 6 | Reported results are baseline (month 0) and change from baseline (at month 6) of end of disease and age specific health related quality of life (HRQOL). HRQOL was collected through use of the PRO instrument, HAEMO-QOL (for parents of the children (4-7 years and 8-12 years)/adolescents (13-16 years)). HAEMO-QOL assessment included questions on physical health, feeling, view of himself, family, friends, perceived support, other persons, nursery School or Kindergarten, sports and school, dealing with haemophilia, treatment, future, and relationships. Scores range for each question was 0-100, with a lower score indicating better quality of life related to haemophilia. Observed mean of the means of all the questions for HAEMO-QOL are presented. |
| Change in Total Scores for Reported Health-related Quality of Life (for Parents): Month 24 | Month 0, Month 24 | Reported results are baseline (month 0) and change from baseline (at month 24) of end of disease and age specific health related quality of life (HRQOL). HRQOL was collected through use of the PRO instrument, HAEMO-QOL (for parents of the children (4-7 years and 8-12 years)/adolescents (13-16 years)). HAEMO-QOL assessment included questions on physical health, feeling, view of himself, family, friends, perceived support, other persons, nursery School or Kindergarten, sports and school, dealing with haemophilia, treatment, future, and relationships. Scores range for each question was 0-100, with a lower score indicating better quality of life related to haemophilia. Observed mean of the means of all the questions for HAEMO-QOL are presented. |
| Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months | Month 0-24 | The haemostatic effect of turoctocog alfa when used for treatment of bleeding episodes in both prophylaxis and on-demand regimen was evaluated during month 0-24. The effect was assessed on a four-point scale for haemostatic response, excellent, good, moderate and none. |
| Area Under the Curve (AUC0-inf) | Days 1-2 | Blood samples for the evaluation of AUC0-inf were taken during a period of 48 hours post-dosing for participants 12 years and older and 24 hours post-dosing for participants below the age of 12 years. AUC0-inf was defined as the area under the concentration versus time from time curve zero to infinity. The results are based on the chromogenic assay. |
| Half-life (t½) | Days 1-2 | Blood samples for the evaluation of t½ were taken during a period of 48 hours post-dosing for participants 12 years and older and 24 hours post-dosing for participants below the age of 12 years. The results are based on the chromogenic assay. |
| Clearance (CL) | Days 1-2 | Blood samples for the evaluation of CL were taken during a period of 48 hours post-dosing for participants 12 years and older and 24 hours post-dosing for participants below the age of 12 years. The results are based on the chromogenic assay. |
| Highest Measured FVIII Activity in the Profile (Cmax) | Days 1-2 | Blood samples for the evaluation of Cmax were taken during a period of 48 hours post-dosing for participants 12 years and older and 24 hours post-dosing for participants below the age of 12 years. The results are based on the chromogenic assay. |
| Incremental Recovery of FVIII | Days 1-2 | Blood samples for the evaluation of incremental recovery of FVIII were taken during a period of 48 hours post-dosing for participants 12 years and older and 24 hours post-dosing for participants below the age of 12 years. The incremental recovery was calculated as (FVIII: coagulant (C) activity measured in plasma 30 minutes after dosing - FVIII:C activity measured in plasma immediately before dosing)/(dose injected at time 0 minute), where the dose was expressed as IU FVIII product per kg body weight. The results are based on the chromogenic assay. |
Countries
China
Participant flow
Recruitment details
The trial was conducted at 10 sites in mainland China.
Pre-assignment details
Study design: This was an open-label and non-randomised trial. Participants with severe haemophilia A were administered a prophylaxis (preventive) or on-demand regimen of turoctocog alfa (trial product) at the investigator's discretion.
Participants by arm
| Arm | Count |
|---|---|
| Small Children (0 to <6 Years) Participants were to receive turoctocog alfa intravenous (i.v.) injections for at least 6 months (main phase) as either prophylaxis or on-demand treatment at investigator's discretion. The recommended prophylaxis starting dose was 30 IU/kg. Prophylaxis doses ranged from 25-50 IU/kg (once every-second-day), or 25-60 IU/kg (3-times-weekly). Bleeds were treated with one or more turoctocog alfa i.v. bolus injections as determined by the investigator and based on the World Federation of Haemophilia (WFH) guidance. Participants who underwent surgery were treated with turoctocog alfa according to WFH guidance and their coagulation factor VIII (FVIII) activity levels were to be maintained as per the following guidance: Minor surgery: 30-60 IU/dL. Major surgery: 80-100 IU/dL pre- and postoperatively. | 9 |
| Older Children (6 to <12 Years) Participants were to receive turoctocog alfa i.v. injections for at least 6 months (main phase) as either prophylaxis or on-demand treatment at investigator's discretion. The recommended prophylaxis starting dose was 30 IU/kg. Prophylaxis doses ranged from 25-50 IU/kg (once every-second-day), or 25-60 IU/kg (3-times-weekly). Bleeds were treated with one or more turoctocog alfa i.v. bolus injections as determined by investigator and based on the WFH guidance. Participants who underwent surgery were treated with turoctocog alfa according to WFH guidance, and their FVIII activity levels were to be maintained as per the following guidance: Minor surgery: 30-60 IU/dL. Major surgery: 80-100 IU/dL pre- and postoperatively. | 33 |
| Adolescents (12 to <18 Years) Participants were to receive turoctocog alfa i.v. injections for at least 6 months (main phase) as either prophylaxis or on-demand treatment at investigator's discretion. The recommended prophylaxis starting dose was 25 IU/kg. Prophylaxis doses ranged from 20-40 IU/kg (once every-second-day), or 20-50 IU/kg (3-times-weekly). Bleeds were treated with one or more turoctocog alfa i.v. bolus injections as determined by the investigator and based on the WFH guidance. Participants who underwent surgery were treated with turoctocog alfa according to WFH guidance and their FVIII activity levels were to be maintained as per the following guidance: Minor surgery: 30-60 IU/dL. Major surgery: 80-100 IU/dL pre- and postoperatively. | 11 |
| Adults (>=18 Years) Participants were to receive turoctocog alfa i.v. injections for at least 6 months (main phase) as either prophylaxis or on-demand treatment at investigator's discretion. Participants who completed 6 months of treatment (prophylaxis or on-demand) in the main phase, were to continue the same treatment for up to approximately 18 months (extension phase). Participants were allowed to switch between treatments in the 'extension phase'. The recommended prophylaxis starting dose was 25 IU/kg. Prophylaxis doses ranged from 20-40 IU/kg (once every-second-day), or 20-50 IU/kg (3-times-weekly). Bleeds were treated with one or more turoctocog alfa i.v. bolus injections as determined by the investigator and based on the WFH guidance. Participants who underwent surgery were treated with turoctocog alfa according to WFH guidance and their FVIII activity levels were to be maintained as per the following guidance: Minor surgery: 30-60 IU/dL. Major surgery: 80-100 IU/dL pre- and postoperatively. | 15 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by parent or guardian | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 5 |
Baseline characteristics
| Characteristic | Small Children (0 to <6 Years) | Older Children (6 to <12 Years) | Adolescents (12 to <18 Years) | Adults (>=18 Years) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 4.00 Years STANDARD_DEVIATION 1.12 | 8.70 Years STANDARD_DEVIATION 1.91 | 14.55 Years STANDARD_DEVIATION 1.92 | 31.00 Years STANDARD_DEVIATION 11.2 | 13.94 Years STANDARD_DEVIATION 10.99 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 33 Participants | 11 Participants | 15 Participants | 68 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 33 Participants | 11 Participants | 15 Participants | 68 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 9 Participants | 33 Participants | 11 Participants | 15 Participants | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 33 | 0 / 11 | 0 / 15 |
| other Total, other adverse events | 8 / 9 | 18 / 33 | 7 / 11 | 10 / 15 |
| serious Total, serious adverse events | 1 / 9 | 0 / 33 | 2 / 11 | 0 / 15 |
Outcome results
Primary
Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months
The haemostatic effect of turoctocog alfa when used for treatment of bleeding episodes in both prophylaxis and on-demand regimen was evaluated during month 0-6. The effect was assessed on a four-point scale for haemostatic response, excellent, good, moderate and none.
Time frame: Month 0-6
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants with bleeding episodes, from both prophylaxis and on-demand regimen.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months | None | 0 Bleeding episodes |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months | Good | 12 Bleeding episodes |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months | Missing | 0 Bleeding episodes |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months | Moderate | 1 Bleeding episodes |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months | Excellent | 35 Bleeding episodes |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months | Moderate | 15 Bleeding episodes |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months | None | 0 Bleeding episodes |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months | Missing | 1 Bleeding episodes |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months | Good | 73 Bleeding episodes |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months | Excellent | 156 Bleeding episodes |
| Adolescents (12 to <18 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months | Moderate | 0 Bleeding episodes |
| Adolescents (12 to <18 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months | Excellent | 20 Bleeding episodes |
| Adolescents (12 to <18 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months | Good | 8 Bleeding episodes |
| Adolescents (12 to <18 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months | None | 0 Bleeding episodes |
| Adolescents (12 to <18 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months | Missing | 0 Bleeding episodes |
| Adults (>=18 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months | None | 0 Bleeding episodes |
| Adults (>=18 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months | Good | 87 Bleeding episodes |
| Adults (>=18 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months | Excellent | 190 Bleeding episodes |
| Adults (>=18 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months | Moderate | 13 Bleeding episodes |
| Adults (>=18 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months | Missing | 0 Bleeding episodes |
Secondary
Adverse Events (Surgery): 24 Months
TEAEs during surgery were recorded during month 0-24: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant was at the trial/surgery site whatever comes first. TEAEs were defined as the events reported after trial product administration until the end of the post-treatment follow-up period.
Time frame: Month 0-24
Population: The safety analysis set included participants who received at least one dose of the trial product. Overall Number of Participants Analyzed = number of participants who underwent surgeries, from both prophylaxis and on-demand regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Small Children (0 to <6 Years) | Adverse Events (Surgery): 24 Months | 4 Events |
| Older Children (6 to <12 Years) | Adverse Events (Surgery): 24 Months | 1 Events |
Secondary
Adverse Events (Surgery): 6 Months
TEAEs during surgery were recorded during month 0-6: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant was at the trial/surgery site whatever comes first. TEAEs were defined as the events reported after trial product administration until the end of the post-treatment follow-up period.
Time frame: Month 0-6
Population: The safety analysis set included participants who received at least one dose of the trial product. Overall Number of Participants Analyzed = number of participants who underwent surgeries, from both prophylaxis and on-demand regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Small Children (0 to <6 Years) | Adverse Events (Surgery): 6 Months | 1 Events |
| Older Children (6 to <12 Years) | Adverse Events (Surgery): 6 Months | 1 Events |
Secondary
Area Under the Curve (AUC0-inf)
Blood samples for the evaluation of AUC0-inf were taken during a period of 48 hours post-dosing for participants 12 years and older and 24 hours post-dosing for participants below the age of 12 years. AUC0-inf was defined as the area under the concentration versus time from time curve zero to infinity. The results are based on the chromogenic assay.
Time frame: Days 1-2
Population: Full analysis set excluding outliers. The full analysis set included all dosed participants with data after dosing. Exceptional outlier PK profiles and/or individual plasma concentrations were excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Small Children (0 to <6 Years) | Area Under the Curve (AUC0-inf) | 16.4 IU*h/mL | Standard Deviation 3.5 |
| Older Children (6 to <12 Years) | Area Under the Curve (AUC0-inf) | 17.7 IU*h/mL | Standard Deviation 7.3 |
| Adolescents (12 to <18 Years) | Area Under the Curve (AUC0-inf) | 11.2 IU*h/mL | Standard Deviation 4.7 |
| Adults (>=18 Years) | Area Under the Curve (AUC0-inf) | 16.9 IU*h/mL | Standard Deviation 1.5 |
Secondary
Change in Total Scores for Reported Health-related Quality of Life (for Parents): Month 24
Reported results are baseline (month 0) and change from baseline (at month 24) of end of disease and age specific health related quality of life (HRQOL). HRQOL was collected through use of the PRO instrument, HAEMO-QOL (for parents of the children (4-7 years and 8-12 years)/adolescents (13-16 years)). HAEMO-QOL assessment included questions on physical health, feeling, view of himself, family, friends, perceived support, other persons, nursery School or Kindergarten, sports and school, dealing with haemophilia, treatment, future, and relationships. Scores range for each question was 0-100, with a lower score indicating better quality of life related to haemophilia. Observed mean of the means of all the questions for HAEMO-QOL are presented.
Time frame: Month 0, Month 24
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants from both prophylaxis and on-demand regimen. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Small Children (0 to <6 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Parents): Month 24 | Baseline | 45.7 Scores | Standard Deviation 15.2 |
| Small Children (0 to <6 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Parents): Month 24 | Change from baseline | -6.7 Scores | Standard Deviation 11.5 |
| Older Children (6 to <12 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Parents): Month 24 | Baseline | 48.3 Scores | Standard Deviation 14.1 |
| Older Children (6 to <12 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Parents): Month 24 | Change from baseline | -11.3 Scores | Standard Deviation 10.7 |
| Adolescents (12 to <18 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Parents): Month 24 | Baseline | 40.8 Scores | Standard Deviation 11.7 |
| Adolescents (12 to <18 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Parents): Month 24 | Change from baseline | -3.1 Scores | Standard Deviation 3.9 |
Secondary
Change in Total Scores for Reported Health-related Quality of Life (for Parents): Month 6
Reported results are baseline (month 0) and change from baseline (at month 6) of end of disease and age specific health related quality of life (HRQOL). HRQOL was collected through use of the PRO instrument, HAEMO-QOL (for parents of the children (4-7 years and 8-12 years)/adolescents (13-16 years)). HAEMO-QOL assessment included questions on physical health, feeling, view of himself, family, friends, perceived support, other persons, nursery School or Kindergarten, sports and school, dealing with haemophilia, treatment, future, and relationships. Scores range for each question was 0-100, with a lower score indicating better quality of life related to haemophilia. Observed mean of the means of all the questions for HAEMO-QOL are presented.
Time frame: Month 0, Month 6
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants from both prophylaxis and on-demand regimen. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Small Children (0 to <6 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Parents): Month 6 | Baseline | 45.7 Scores | Standard Deviation 15.2 |
| Small Children (0 to <6 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Parents): Month 6 | Change from baseline | -6.2 Scores | Standard Deviation 7.7 |
| Older Children (6 to <12 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Parents): Month 6 | Baseline | 48.3 Scores | Standard Deviation 14.1 |
| Older Children (6 to <12 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Parents): Month 6 | Change from baseline | -9.9 Scores | Standard Deviation 8.7 |
| Adolescents (12 to <18 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Parents): Month 6 | Baseline | 40.8 Scores | Standard Deviation 11.7 |
| Adolescents (12 to <18 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Parents): Month 6 | Change from baseline | -1.5 Scores | Standard Deviation 7.2 |
Secondary
Change in Total Scores for Reported Health-related Quality of Life (for Participants): Month 24
Reported results are baseline (month 0) and change from baseline (at month 24) of end of disease and age specific HRQOL. HRQOL was collected through use of the patient reported outcome (PRO) instruments, HAEM-A-QOL (for adults (\>=17 years)) and HAEMO-QOL (for children (8-12 years)/adolescents (13-16 years)). HAEM-A-QOL assessment included questions on physical health, feeling, view of yourself, sports and leisure, work and school, dealing with haemophilia, treatment, future, family planning, and partnership and sexuality. HAEMO-QOL assessment included questions on physical health, feeling, view of yourself, family, friends, perceived support, other persons, sports and school, dealing with haemophilia, treatment, future, and relationships. Scores range for each question was 0-100, with a lower score indicating better quality of life related to haemophilia. Observed mean of the means of all the questions for HAEM-A-QOL and HAEMO-QOL, respectively are presented.
Time frame: Month 0, Month 24
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants from both prophylaxis and on-demand regimen. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Small Children (0 to <6 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Participants): Month 24 | Baseline | 41.3 Scores | Standard Deviation 16.4 |
| Small Children (0 to <6 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Participants): Month 24 | Change from baseline | -10.1 Scores | Standard Deviation 15 |
| Older Children (6 to <12 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Participants): Month 24 | Baseline | 42.2 Scores | Standard Deviation 12.8 |
| Older Children (6 to <12 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Participants): Month 24 | Change from baseline | -4.9 Scores | Standard Deviation 8.8 |
| Adolescents (12 to <18 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Participants): Month 24 | Baseline | 47.2 Scores | Standard Deviation 13.8 |
| Adolescents (12 to <18 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Participants): Month 24 | Change from baseline | -6.3 Scores | Standard Deviation 9.7 |
Secondary
Change in Total Scores for Reported Health-related Quality of Life (for Participants): Month 6
Reported results are baseline (month 0) and change from baseline (at month 6) of end of disease and age specific HRQOL. HRQOL was collected through use of the patient reported outcome (PRO) instruments, HAEMO-QOL (for children (8-12 years)/adolescents (13-16 years)) and HAEM-A-QOL (for adults (\>=17 years)). HAEMO-QOL assessment included questions on physical health, feeling, view of yourself, family, friends, perceived support, other persons, sports and school, dealing with haemophilia, treatment, future, and relationships. HAEM-A-QOL assessment included questions on physical health, feeling, view of yourself, sports and leisure, work and school, dealing with haemophilia, treatment, future, family planning, and partnership and sexuality. Scores range for each question was 0-100, with a lower score indicating better quality of life related to haemophilia. Observed mean of the means of all the questions for HAEMO-QOL and HAEM-A-QOL, respectively are presented.
Time frame: Month 0, Month 6
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants from both prophylaxis and on-demand regimen. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Small Children (0 to <6 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Participants): Month 6 | Baseline | 41.3 Scores | Standard Deviation 16.4 |
| Small Children (0 to <6 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Participants): Month 6 | Change from baseline | -6.8 Scores | Standard Deviation 14.5 |
| Older Children (6 to <12 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Participants): Month 6 | Baseline | 42.2 Scores | Standard Deviation 12.8 |
| Older Children (6 to <12 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Participants): Month 6 | Change from baseline | -3.5 Scores | Standard Deviation 3.6 |
| Adolescents (12 to <18 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Participants): Month 6 | Baseline | 47.2 Scores | Standard Deviation 13.8 |
| Adolescents (12 to <18 Years) | Change in Total Scores for Reported Health-related Quality of Life (for Participants): Month 6 | Change from baseline | -3.4 Scores | Standard Deviation 12.8 |
Secondary
Clearance (CL)
Blood samples for the evaluation of CL were taken during a period of 48 hours post-dosing for participants 12 years and older and 24 hours post-dosing for participants below the age of 12 years. The results are based on the chromogenic assay.
Time frame: Days 1-2
Population: Full analysis set excluding outliers. The full analysis set included all dosed participants with data after dosing. Exceptional outlier PK profiles and/or individual plasma concentrations were excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Small Children (0 to <6 Years) | Clearance (CL) | 3.7 mL/h/kg | Standard Deviation 0.9 |
| Older Children (6 to <12 Years) | Clearance (CL) | 3.5 mL/h/kg | Standard Deviation 1.2 |
| Adolescents (12 to <18 Years) | Clearance (CL) | 5.5 mL/h/kg | Standard Deviation 2.2 |
| Adults (>=18 Years) | Clearance (CL) | 3.5 mL/h/kg | Standard Deviation 0.3 |
Secondary
Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: Average Preventive Dose (24 Months)
Average preventive dose of turoctocog alfa consumed per participant in the prophylaxis regimen was evaluated during month 0-24.
Time frame: Month 0-24
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants from the prophylaxis regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Small Children (0 to <6 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: Average Preventive Dose (24 Months) | 47.97 IU/kg BW | Standard Deviation 8 |
| Older Children (6 to <12 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: Average Preventive Dose (24 Months) | 40.33 IU/kg BW | Standard Deviation 7.05 |
| Adolescents (12 to <18 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: Average Preventive Dose (24 Months) | 36.20 IU/kg BW | Standard Deviation 7.15 |
| Adults (>=18 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: Average Preventive Dose (24 Months) | 38.13 IU/kg BW | Standard Deviation 7.51 |
Secondary
Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: Average Preventive Dose (6 Months)
Average preventive dose of turoctocog alfa consumed per participant in the prophylaxis regimen was evaluated during month 0-6.
Time frame: Month 0-6
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants from the prophylaxis regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Small Children (0 to <6 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: Average Preventive Dose (6 Months) | 47.05 IU/kg BW | Standard Deviation 9.21 |
| Older Children (6 to <12 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: Average Preventive Dose (6 Months) | 39.46 IU/kg BW | Standard Deviation 7.12 |
| Adolescents (12 to <18 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: Average Preventive Dose (6 Months) | 35.40 IU/kg BW | Standard Deviation 7.41 |
| Adults (>=18 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: Average Preventive Dose (6 Months) | 37.28 IU/kg BW | Standard Deviation 5.22 |
Secondary
Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Month (24 Months)
Preventive dose of turoctocog alfa (IU/kg body weight (BW) per month) per participant in the prophylaxis regimen was evaluated during month 0-24.
Time frame: Month 0-24
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants from the prophylaxis regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Small Children (0 to <6 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Month (24 Months) | 606.3 IU/kg BW/month/participant | Standard Deviation 118.5 |
| Older Children (6 to <12 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Month (24 Months) | 533.0 IU/kg BW/month/participant | Standard Deviation 82.9 |
| Adolescents (12 to <18 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Month (24 Months) | 467.6 IU/kg BW/month/participant | Standard Deviation 91.4 |
| Adults (>=18 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Month (24 Months) | 490.8 IU/kg BW/month/participant | Standard Deviation 115.7 |
Secondary
Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Month (6 Months)
Preventive dose of turoctocog alfa (IU/kg body weight (BW) per month) per participant in the prophylaxis regimen was evaluated during month 0-6.
Time frame: Month 0-6
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants from the prophylaxis regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Small Children (0 to <6 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Month (6 Months) | 600.3 IU/kg BW/month/participant | Standard Deviation 112.6 |
| Older Children (6 to <12 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Month (6 Months) | 522.5 IU/kg BW/month/participant | Standard Deviation 87.59 |
| Adolescents (12 to <18 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Month (6 Months) | 454.5 IU/kg BW/month/participant | Standard Deviation 92.79 |
| Adults (>=18 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Month (6 Months) | 500.7 IU/kg BW/month/participant | Standard Deviation 84.39 |
Secondary
Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Year (24 Months)
Preventive dose of turoctocog alfa (IU/kg body weight (BW) per year) per participant in the prophylaxis regimen was evaluated during month 0-24.
Time frame: Month 0-24
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants from the prophylaxis regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Small Children (0 to <6 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Year (24 Months) | 7276 IU/kg BW/year/participant | Standard Deviation 1422 |
| Older Children (6 to <12 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Year (24 Months) | 6396 IU/kg BW/year/participant | Standard Deviation 994.7 |
| Adolescents (12 to <18 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Year (24 Months) | 5611 IU/kg BW/year/participant | Standard Deviation 1097 |
| Adults (>=18 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Year (24 Months) | 5890 IU/kg BW/year/participant | Standard Deviation 1388 |
Secondary
Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Year (6 Months)
Preventive dose of turoctocog alfa (IU/kg body weight per year) per participant in the prophylaxis regimen was evaluated during month 0-6.
Time frame: Month 0-6
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants from the prophylaxis regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Small Children (0 to <6 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Year (6 Months) | 7204 IU/kg BW/year/participant | Standard Deviation 1351 |
| Older Children (6 to <12 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Year (6 Months) | 6270 IU/kg BW/year/participant | Standard Deviation 1051 |
| Adolescents (12 to <18 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Year (6 Months) | 5454 IU/kg BW/year/participant | Standard Deviation 1113 |
| Adults (>=18 Years) | Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Year (6 Months) | 6009 IU/kg BW/year/participant | Standard Deviation 1013 |
Secondary
Consumption of Turoctocog Alfa for Bleeding Treatment: Average Dose to Treat a Bleed (24 Months)
Average dose of turoctocog alfa used to treat a bleed in both prophylaxis and on-demand regimen was evaluated during month 0-24.
Time frame: Month 0-24
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants with bleeding episodes, from both prophylaxis and on-demand regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Small Children (0 to <6 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: Average Dose to Treat a Bleed (24 Months) | 43.99 IU/kg BW | Standard Deviation 6.95 |
| Older Children (6 to <12 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: Average Dose to Treat a Bleed (24 Months) | 36.00 IU/kg BW | Standard Deviation 12.32 |
| Adolescents (12 to <18 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: Average Dose to Treat a Bleed (24 Months) | 43.58 IU/kg BW | Standard Deviation 6.93 |
| Adults (>=18 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: Average Dose to Treat a Bleed (24 Months) | 21.07 IU/kg BW | Standard Deviation 7.49 |
Secondary
Consumption of Turoctocog Alfa for Bleeding Treatment: Average Dose to Treat a Bleed (6 Months)
Average dose of turoctocog alfa used to treat a bleed in both prophylaxis and on-demand regimen was evaluated during month 0-6.
Time frame: Month 0-6
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants with bleeding episodes, from both prophylaxis and on-demand regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Small Children (0 to <6 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: Average Dose to Treat a Bleed (6 Months) | 42.96 IU/kg BW | Standard Deviation 5.35 |
| Older Children (6 to <12 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: Average Dose to Treat a Bleed (6 Months) | 36.69 IU/kg BW | Standard Deviation 14.04 |
| Adolescents (12 to <18 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: Average Dose to Treat a Bleed (6 Months) | 46.79 IU/kg BW | Standard Deviation 5.31 |
| Adults (>=18 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: Average Dose to Treat a Bleed (6 Months) | 20.29 IU/kg BW | Standard Deviation 6.48 |
Secondary
Consumption of Turoctocog Alfa for Bleeding Treatment: IU/kg Per Bleed (24 Months)
Consumption of turoctocog alfa IU/kg BW per bleed in both prophylaxis and on-demand regimen was evaluated during month 0-24.
Time frame: Month 0-24
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants with bleeding episodes, from both prophylaxis and on-demand regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Small Children (0 to <6 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: IU/kg Per Bleed (24 Months) | 59.01 IU/kg BW | Standard Deviation 28.61 |
| Older Children (6 to <12 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: IU/kg Per Bleed (24 Months) | 44.75 IU/kg BW | Standard Deviation 34.15 |
| Adolescents (12 to <18 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: IU/kg Per Bleed (24 Months) | 45.07 IU/kg BW | Standard Deviation 15.33 |
| Adults (>=18 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: IU/kg Per Bleed (24 Months) | 27.44 IU/kg BW | Standard Deviation 22.52 |
Secondary
Consumption of Turoctocog Alfa for Bleeding Treatment: IU/kg Per Bleed (6 Months)
Consumption of turoctocog alfa IU/kg BW per bleed in both prophylaxis and on-demand regimen was evaluated during month 0-6.
Time frame: Month 0-6
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants with bleeding episodes, from both prophylaxis and on-demand regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Small Children (0 to <6 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: IU/kg Per Bleed (6 Months) | 56.60 IU/kg BW | Standard Deviation 25.32 |
| Older Children (6 to <12 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: IU/kg Per Bleed (6 Months) | 42.37 IU/kg BW | Standard Deviation 26.54 |
| Adolescents (12 to <18 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: IU/kg Per Bleed (6 Months) | 48.82 IU/kg BW | Standard Deviation 15.05 |
| Adults (>=18 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: IU/kg Per Bleed (6 Months) | 26.20 IU/kg BW | Standard Deviation 17.55 |
Secondary
Consumption of Turoctocog Alfa for Bleeding Treatment: Number of Injections Per Bleed (24 Months)
Number of turoctocog alfa injections consumed to treat a bleeding episode in both prophylaxis and on-demand regimen was evaluated during month 0-24.
Time frame: Month 0-24
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants with bleeding episodes, from both prophylaxis and on-demand regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Small Children (0 to <6 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: Number of Injections Per Bleed (24 Months) | 1.34 Injections | Standard Deviation 0.62 |
| Older Children (6 to <12 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: Number of Injections Per Bleed (24 Months) | 1.30 Injections | Standard Deviation 0.88 |
| Adolescents (12 to <18 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: Number of Injections Per Bleed (24 Months) | 1.09 Injections | Standard Deviation 0.3 |
| Adults (>=18 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: Number of Injections Per Bleed (24 Months) | 1.33 Injections | Standard Deviation 1.21 |
Secondary
Consumption of Turoctocog Alfa for Bleeding Treatment: Number of Injections Per Bleed (6 Months)
Number of turoctocog alfa injections consumed to treat a bleeding episode in both prophylaxis and on-demand regimen was evaluated during month 0-6.
Time frame: Month 0-6
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants with bleeding episodes, from both prophylaxis and on-demand regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Small Children (0 to <6 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: Number of Injections Per Bleed (6 Months) | 1.31 Injections | Standard Deviation 0.59 |
| Older Children (6 to <12 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: Number of Injections Per Bleed (6 Months) | 1.22 Injections | Standard Deviation 0.61 |
| Adolescents (12 to <18 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: Number of Injections Per Bleed (6 Months) | 1.07 Injections | Standard Deviation 0.26 |
| Adults (>=18 Years) | Consumption of Turoctocog Alfa for Bleeding Treatment: Number of Injections Per Bleed (6 Months) | 1.29 Injections | Standard Deviation 0.89 |
Secondary
Frequency of Adverse Events (24 Months)
Frequency of adverse events (AEs) are presented as rate of events, which was calculated as the number of AEs per patient years. All presented AEs are treatment emergent (TEAEs), which were defined as the events reported after trial product administration until the end of the post-treatment follow-up period.
Time frame: Month 0-24
Population: The safety analysis set included participants who received at least one dose of the trial product. Overall Number of Participants Analyzed = number of participants from both prophylaxis and on-demand regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Small Children (0 to <6 Years) | Frequency of Adverse Events (24 Months) | 2.941 Events per person-year |
| Older Children (6 to <12 Years) | Frequency of Adverse Events (24 Months) | 1.210 Events per person-year |
| Adolescents (12 to <18 Years) | Frequency of Adverse Events (24 Months) | 1.074 Events per person-year |
| Adults (>=18 Years) | Frequency of Adverse Events (24 Months) | 1.123 Events per person-year |
Secondary
Frequency of Adverse Events (6 Months)
Frequency of adverse events (AEs) are presented as rate of events, which was calculated as the number of AEs per patient years. All presented AEs are treatment emergent (TEAEs), which were defined as the events reported after trial product administration until the end of the post-treatment follow-up period.
Time frame: Month 0-6
Population: The safety analysis set included participants who received at least one dose of the trial product. Overall Number of Participants Analyzed = number of participants from both prophylaxis and on-demand regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Small Children (0 to <6 Years) | Frequency of Adverse Events (6 Months) | 4.908 Events per person-year |
| Older Children (6 to <12 Years) | Frequency of Adverse Events (6 Months) | 2.093 Events per person-year |
| Adolescents (12 to <18 Years) | Frequency of Adverse Events (6 Months) | 2.325 Events per person-year |
| Adults (>=18 Years) | Frequency of Adverse Events (6 Months) | 1.922 Events per person-year |
Secondary
Frequency of Serious Adverse Events (24 Months)
Frequency of serious adverse events (SAEs) are presented as rate of events, which was calculated as the number of SAEs per patient years. All presented SAEs are treatment emergent, which were defined as the events reported after trial product administration until the end of the post-treatment follow-up period.
Time frame: Month 0-24
Population: The safety analysis set included participants who received at least one dose of the trial product. Overall Number of Participants Analyzed = number of participants from both prophylaxis and on-demand regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Small Children (0 to <6 Years) | Frequency of Serious Adverse Events (24 Months) | 0.065 Events per person-year |
| Older Children (6 to <12 Years) | Frequency of Serious Adverse Events (24 Months) | 0 Events per person-year |
| Adolescents (12 to <18 Years) | Frequency of Serious Adverse Events (24 Months) | 0.161 Events per person-year |
| Adults (>=18 Years) | Frequency of Serious Adverse Events (24 Months) | 0 Events per person-year |
Secondary
Frequency of Serious Adverse Events (6 Months)
Frequency of serious adverse events (SAEs) are presented as rate of events, which was calculated as the number of SAEs per patient years. All presented SAEs are treatment emergent, which were defined as the events reported after trial product administration until the end of the post-treatment follow-up period.
Time frame: Month 0-6
Population: The safety analysis set included participants who received at least one dose of the trial product. Overall Number of Participants Analyzed = number of participants from both prophylaxis and on-demand regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Small Children (0 to <6 Years) | Frequency of Serious Adverse Events (6 Months) | 0 Events per person-year |
| Older Children (6 to <12 Years) | Frequency of Serious Adverse Events (6 Months) | 0 Events per person-year |
| Adolescents (12 to <18 Years) | Frequency of Serious Adverse Events (6 Months) | 0.634 Events per person-year |
| Adults (>=18 Years) | Frequency of Serious Adverse Events (6 Months) | 0 Events per person-year |
Secondary
Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months
The haemostatic effect of turoctocog alfa when used for surgery was evaluated during month 0-24. The effect was assessed on a four-point scale for haemostatic response (excellent, good, moderate and none) and assessed by the investigator/surgeon on the day of surgery (day 1) and on the last day in the post-operative period the participant was at the trial/surgery site. Haemostatic response of 'not applicable' indicated that turoctocog alfa was not used.
Time frame: Month 0-24
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants who underwent surgeries, from both prophylaxis and on-demand regimen.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months | During surgery: Excellent | 3 Surgeries |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months | During surgery: Good | 1 Surgeries |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months | During surgery: Moderate | 0 Surgeries |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months | During surgery: None | 0 Surgeries |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months | During surgery: Not applicable | 2 Surgeries |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months | After surgery: Excellent | 5 Surgeries |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months | After surgery: Good | 0 Surgeries |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months | After surgery: Moderate | 0 Surgeries |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months | After surgery: None | 0 Surgeries |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months | After surgery: Not applicable | 1 Surgeries |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months | After surgery: Moderate | 0 Surgeries |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months | During surgery: Excellent | 1 Surgeries |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months | After surgery: Excellent | 2 Surgeries |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months | During surgery: Good | 3 Surgeries |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months | After surgery: Not applicable | 0 Surgeries |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months | During surgery: Moderate | 0 Surgeries |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months | After surgery: Good | 2 Surgeries |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months | During surgery: None | 0 Surgeries |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months | After surgery: None | 0 Surgeries |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months | During surgery: Not applicable | 0 Surgeries |
Secondary
Haemostatic Effect of Turoctocog Alfa (Surgery): 6 Months
The haemostatic effect of turoctocog alfa when used for surgery was evaluated during month 0-6. The effect was assessed on a four-point scale for haemostatic response (excellent, good, moderate and none) and assessed by the investigator/surgeon on the day of surgery (day 1) and on the last day in the post-operative period the participant was at the trial/surgery site.
Time frame: Month 0-6
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants who underwent surgeries, from both prophylaxis and on-demand regimen.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 6 Months | During surgery: Excellent | 2 Surgeries |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 6 Months | During surgery: Good | 1 Surgeries |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 6 Months | During surgery: Moderate | 0 Surgeries |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 6 Months | During surgery: None | 0 Surgeries |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 6 Months | After surgery: Excellent | 3 Surgeries |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 6 Months | After surgery: Good | 0 Surgeries |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 6 Months | After surgery: Moderate | 0 Surgeries |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 6 Months | After surgery: None | 0 Surgeries |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 6 Months | After surgery: None | 0 Surgeries |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 6 Months | During surgery: Excellent | 1 Surgeries |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 6 Months | After surgery: Excellent | 2 Surgeries |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 6 Months | During surgery: Good | 2 Surgeries |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 6 Months | After surgery: Moderate | 0 Surgeries |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 6 Months | During surgery: Moderate | 0 Surgeries |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 6 Months | After surgery: Good | 1 Surgeries |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Surgery): 6 Months | During surgery: None | 0 Surgeries |
Secondary
Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months
The haemostatic effect of turoctocog alfa when used for treatment of bleeding episodes in both prophylaxis and on-demand regimen was evaluated during month 0-24. The effect was assessed on a four-point scale for haemostatic response, excellent, good, moderate and none.
Time frame: Month 0-24
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants with bleeding episodes, from both prophylaxis and on-demand regimen.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months | Moderate | 2 Bleeding episodes |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months | Excellent | 45 Bleeding episodes |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months | None | 0 Bleeding episodes |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months | Good | 18 Bleeding episodes |
| Small Children (0 to <6 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months | Missing | 0 Bleeding episodes |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months | Moderate | 26 Bleeding episodes |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months | Good | 103 Bleeding episodes |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months | None | 0 Bleeding episodes |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months | Excellent | 275 Bleeding episodes |
| Older Children (6 to <12 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months | Missing | 1 Bleeding episodes |
| Adolescents (12 to <18 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months | None | 0 Bleeding episodes |
| Adolescents (12 to <18 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months | Excellent | 42 Bleeding episodes |
| Adolescents (12 to <18 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months | Good | 11 Bleeding episodes |
| Adolescents (12 to <18 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months | Moderate | 0 Bleeding episodes |
| Adolescents (12 to <18 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months | Missing | 0 Bleeding episodes |
| Adults (>=18 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months | None | 0 Bleeding episodes |
| Adults (>=18 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months | Good | 116 Bleeding episodes |
| Adults (>=18 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months | Excellent | 272 Bleeding episodes |
| Adults (>=18 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months | Missing | 0 Bleeding episodes |
| Adults (>=18 Years) | Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months | Moderate | 14 Bleeding episodes |
Secondary
Half-life (t½)
Blood samples for the evaluation of t½ were taken during a period of 48 hours post-dosing for participants 12 years and older and 24 hours post-dosing for participants below the age of 12 years. The results are based on the chromogenic assay.
Time frame: Days 1-2
Population: Full analysis set excluding outliers. The full analysis set included all dosed participants with data after dosing. Exceptional outlier PK profiles and/or individual plasma concentrations were excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Small Children (0 to <6 Years) | Half-life (t½) | 8.5 Hour (h) | Standard Deviation 1.4 |
| Older Children (6 to <12 Years) | Half-life (t½) | 8.3 Hour (h) | Standard Deviation 3.1 |
| Adolescents (12 to <18 Years) | Half-life (t½) | 11.6 Hour (h) | Standard Deviation 0.6 |
| Adults (>=18 Years) | Half-life (t½) | 8.4 Hour (h) | Standard Deviation 1.9 |
Secondary
Highest Measured FVIII Activity in the Profile (Cmax)
Blood samples for the evaluation of Cmax were taken during a period of 48 hours post-dosing for participants 12 years and older and 24 hours post-dosing for participants below the age of 12 years. The results are based on the chromogenic assay.
Time frame: Days 1-2
Population: Full analysis set excluding outliers. The full analysis set included all dosed participants with data after dosing. Exceptional outlier PK profiles and/or individual plasma concentrations were excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Small Children (0 to <6 Years) | Highest Measured FVIII Activity in the Profile (Cmax) | 1.2 IU/mL | Standard Deviation 0.2 |
| Older Children (6 to <12 Years) | Highest Measured FVIII Activity in the Profile (Cmax) | 1.4 IU/mL | Standard Deviation 0.3 |
| Adolescents (12 to <18 Years) | Highest Measured FVIII Activity in the Profile (Cmax) | 0.9 IU/mL | Standard Deviation 0.5 |
| Adults (>=18 Years) | Highest Measured FVIII Activity in the Profile (Cmax) | 1.6 IU/mL | Standard Deviation 0.2 |
Secondary
Incidence Rate of Inhibitory Antibodies Against FVIII (≥0.6 BU): 24 Months
This endpoint presented 'percentage of participants with inhibitory antibodies against FVIII (≥0.6 BU)' in both prophylaxis and on-demand regimen, evaluated during month 0-24.
Time frame: Month 0-24
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants, from both prophylaxis and on-demand regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Small Children (0 to <6 Years) | Incidence Rate of Inhibitory Antibodies Against FVIII (≥0.6 BU): 24 Months | 0 Percentage of participants |
| Older Children (6 to <12 Years) | Incidence Rate of Inhibitory Antibodies Against FVIII (≥0.6 BU): 24 Months | 0 Percentage of participants |
| Adolescents (12 to <18 Years) | Incidence Rate of Inhibitory Antibodies Against FVIII (≥0.6 BU): 24 Months | 0 Percentage of participants |
| Adults (>=18 Years) | Incidence Rate of Inhibitory Antibodies Against FVIII (≥0.6 BU): 24 Months | 0 Percentage of participants |
Secondary
Incidence Rate of Inhibitory Antibodies Against FVIII (≥0.6 BU): 6 Months
This endpoint presented 'percentage of participants with inhibitory antibodies against FVIII (≥0.6 BU)' in both prophylaxis and on-demand regimen, evaluated during month 0-6.
Time frame: Month 0-6
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants, from both prophylaxis and on-demand regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Small Children (0 to <6 Years) | Incidence Rate of Inhibitory Antibodies Against FVIII (≥0.6 BU): 6 Months | 0 Percentage of participants |
| Older Children (6 to <12 Years) | Incidence Rate of Inhibitory Antibodies Against FVIII (≥0.6 BU): 6 Months | 0 Percentage of participants |
| Adolescents (12 to <18 Years) | Incidence Rate of Inhibitory Antibodies Against FVIII (≥0.6 BU): 6 Months | 0 Percentage of participants |
| Adults (>=18 Years) | Incidence Rate of Inhibitory Antibodies Against FVIII (≥0.6 BU): 6 Months | 0 Percentage of participants |
Secondary
Incremental Recovery of FVIII
Blood samples for the evaluation of incremental recovery of FVIII were taken during a period of 48 hours post-dosing for participants 12 years and older and 24 hours post-dosing for participants below the age of 12 years. The incremental recovery was calculated as (FVIII: coagulant (C) activity measured in plasma 30 minutes after dosing - FVIII:C activity measured in plasma immediately before dosing)/(dose injected at time 0 minute), where the dose was expressed as IU FVIII product per kg body weight. The results are based on the chromogenic assay.
Time frame: Days 1-2
Population: Full analysis set excluding outliers. The full analysis set included all dosed participants with data after dosing. Exceptional outlier pharmacokinetic (PK) profiles and/or individual plasma concentrations were excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Small Children (0 to <6 Years) | Incremental Recovery of FVIII | 0.022 (IU/mL)/(IU/kg BW) | Standard Deviation 0.003 |
| Older Children (6 to <12 Years) | Incremental Recovery of FVIII | 0.026 (IU/mL)/(IU/kg BW) | Standard Deviation 0.005 |
| Adolescents (12 to <18 Years) | Incremental Recovery of FVIII | 0.014 (IU/mL)/(IU/kg BW) | Standard Deviation 0.007 |
| Adults (>=18 Years) | Incremental Recovery of FVIII | 0.026 (IU/mL)/(IU/kg BW) | Standard Deviation 0.004 |
Secondary
Loss of Blood (Surgery): 24 Months
Loss of blood was evaluated during month 0-24: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant was at the trial/surgery site whatever comes first.
Time frame: Month 0-24
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants who underwent surgeries, from both prophylaxis and on-demand regimen. Overall Number of Units Analyzed = number of surgeries where blood loss happened.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Small Children (0 to <6 Years) | Loss of Blood (Surgery): 24 Months | 2.0 mL | Standard Deviation 1.4 |
| Older Children (6 to <12 Years) | Loss of Blood (Surgery): 24 Months | 81.3 mL | Standard Deviation 89.5 |
Secondary
Loss of Blood (Surgery): 6 Months
Loss of blood was evaluated during month 0-6: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant was at the trial/surgery site whatever comes first.
Time frame: Month 0-6
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants who underwent surgeries, from both prophylaxis and on-demand regimen. Overall Number of Units Analyzed = number of surgeries where blood loss happened.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Small Children (0 to <6 Years) | Loss of Blood (Surgery): 6 Months | 2.0 mL | Standard Deviation 1.4 |
| Older Children (6 to <12 Years) | Loss of Blood (Surgery): 6 Months | 106.7 mL | Standard Deviation 90.2 |
Secondary
Number of Bleeds (Total Bleeds Assessed as Annual Bleeding Rate) Per Participant: 24 Months
Number of bleeds (total bleeds assessed as annual bleeding rate) per participant in the prophylaxis regimen was evaluated during month 0-24. The annualised bleeding rate was analysed by a negative binomial model.
Time frame: Month 0-24
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants from the prophylaxis regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Small Children (0 to <6 Years) | Number of Bleeds (Total Bleeds Assessed as Annual Bleeding Rate) Per Participant: 24 Months | 2.28 Bleeding episodes/year |
| Older Children (6 to <12 Years) | Number of Bleeds (Total Bleeds Assessed as Annual Bleeding Rate) Per Participant: 24 Months | 2.63 Bleeding episodes/year |
| Adolescents (12 to <18 Years) | Number of Bleeds (Total Bleeds Assessed as Annual Bleeding Rate) Per Participant: 24 Months | 1.97 Bleeding episodes/year |
| Adults (>=18 Years) | Number of Bleeds (Total Bleeds Assessed as Annual Bleeding Rate) Per Participant: 24 Months | 4.97 Bleeding episodes/year |
Secondary
Number of Bleeds (Total Bleeds Assessed as Annual Bleeding Rate) Per Participant: 6 Months
Number of bleeds (total bleeds assessed as annual bleeding rate) per participant in the prophylaxis regimen was evaluated during month 0-6. The annualised bleeding rate was analysed by a negative binomial model.
Time frame: Month 0-6
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants from the prophylaxis regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Small Children (0 to <6 Years) | Number of Bleeds (Total Bleeds Assessed as Annual Bleeding Rate) Per Participant: 6 Months | 4.36 Bleeding episodes/year |
| Older Children (6 to <12 Years) | Number of Bleeds (Total Bleeds Assessed as Annual Bleeding Rate) Per Participant: 6 Months | 4.11 Bleeding episodes/year |
| Adolescents (12 to <18 Years) | Number of Bleeds (Total Bleeds Assessed as Annual Bleeding Rate) Per Participant: 6 Months | 2.34 Bleeding episodes/year |
| Adults (>=18 Years) | Number of Bleeds (Total Bleeds Assessed as Annual Bleeding Rate) Per Participant: 6 Months | 10.67 Bleeding episodes/year |
Secondary
Requirements for Transfusion (Surgery): 24 Months
Surgeries required transfusion was evaluated during month 0-24: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant was at the trial/surgery site whatever comes first.
Time frame: Month 0-24
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants who underwent surgeries, from both prophylaxis and on-demand regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Small Children (0 to <6 Years) | Requirements for Transfusion (Surgery): 24 Months | 0 Surgeries |
| Older Children (6 to <12 Years) | Requirements for Transfusion (Surgery): 24 Months | 0 Surgeries |
Secondary
Requirements for Transfusion (Surgery): 6 Months
Surgeries required transfusion was evaluated during month 0-6: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant was at the trial/surgery site whatever comes first.
Time frame: Month 0-6
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants who underwent surgeries, from both prophylaxis and on-demand regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Small Children (0 to <6 Years) | Requirements for Transfusion (Surgery): 6 Months | 0 Surgeries |
| Older Children (6 to <12 Years) | Requirements for Transfusion (Surgery): 6 Months | 0 Surgeries |
Secondary
Serious Adverse Events (Surgery): 24 Months
Treatment emergent serious adverse events occurred during surgery were recorded from month 0 to month 24: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant is at the trial/surgery site whatever comes first. Treatment emergent events were defined as the events reported after trial product administration until the end of the post-treatment follow-up period.
Time frame: Month 0-24
Population: The safety analysis set included participants who received at least one dose of the trial product. Overall Number of Participants Analyzed = number of participants who underwent surgeries, from both prophylaxis and on-demand regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Small Children (0 to <6 Years) | Serious Adverse Events (Surgery): 24 Months | 0 Events |
| Older Children (6 to <12 Years) | Serious Adverse Events (Surgery): 24 Months | 0 Events |
Secondary
Serious Adverse Events (Surgery): 6 Months
Treatment emergent serious adverse events occurred during surgery were recorded from month 0 to month 6: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant is at the trial/surgery site whatever comes first. Treatment emergent events were defined as the events reported after trial product administration until the end of the post-treatment follow-up period.
Time frame: Month 0-6
Population: The safety analysis set included participants who received at least one dose of the trial product. Overall Number of Participants Analyzed = number of participants who underwent surgeries, from both prophylaxis and on-demand regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Small Children (0 to <6 Years) | Serious Adverse Events (Surgery): 6 Months | 0 Events |
| Older Children (6 to <12 Years) | Serious Adverse Events (Surgery): 6 Months | 0 Events |
Secondary
Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Month (24 Months)
Total consumption of turoctocog alfa (IU/kg body weight per month) per participant in both prophylaxis and on-demand regimen was evaluated during month 0-24.
Time frame: Month 0-24
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants from both prophylaxis and on-demand regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Small Children (0 to <6 Years) | Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Month (24 Months) | 615.3 IU/kg BW/month/participant | Standard Deviation 123.8 |
| Older Children (6 to <12 Years) | Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Month (24 Months) | 516.7 IU/kg BW/month/participant | Standard Deviation 121.1 |
| Adolescents (12 to <18 Years) | Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Month (24 Months) | 477.0 IU/kg BW/month/participant | Standard Deviation 94.37 |
| Adults (>=18 Years) | Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Month (24 Months) | 429.1 IU/kg BW/month/participant | Standard Deviation 192.7 |
Secondary
Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Month (6 Months)
Total consumption of turoctocog alfa (IU/kg body weight per month) per participant in both prophylaxis and on-demand regimen was evaluated during month 0-6.
Time frame: Month 0-6
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants from both prophylaxis and on-demand regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Small Children (0 to <6 Years) | Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Month (6 Months) | 603.5 IU/kg BW/month/participant | Standard Deviation 141.2 |
| Older Children (6 to <12 Years) | Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Month (6 Months) | 496.0 IU/kg BW/month/participant | Standard Deviation 146.7 |
| Adolescents (12 to <18 Years) | Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Month (6 Months) | 479.6 IU/kg BW/month/participant | Standard Deviation 103.9 |
| Adults (>=18 Years) | Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Month (6 Months) | 377.2 IU/kg BW/month/participant | Standard Deviation 218.9 |
Secondary
Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Year (24 Months)
Total consumption of turoctocog alfa (IU/kg body weight per year) per participant in both prophylaxis and on-demand regimen was evaluated during month 0-24.
Time frame: Month 0-24
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants from both prophylaxis and on-demand regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Small Children (0 to <6 Years) | Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Year (24 Months) | 7384 IU/kg BW/year/participant | Standard Deviation 1486 |
| Older Children (6 to <12 Years) | Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Year (24 Months) | 6201 IU/kg BW/year/participant | Standard Deviation 1453 |
| Adolescents (12 to <18 Years) | Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Year (24 Months) | 5724 IU/kg BW/year/participant | Standard Deviation 1132 |
| Adults (>=18 Years) | Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Year (24 Months) | 5149 IU/kg BW/year/participant | Standard Deviation 2312 |
Secondary
Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Year (6 Months)
Total consumption of turoctocog alfa (IU/kg body weight per year) per participant in both prophylaxis and on-demand regimen was evaluated during month 0-6.
Time frame: Month 0-6
Population: The full analysis set included all dosed participants with data after dosing. Overall Number of Participants Analyzed = number of participants from both prophylaxis and on-demand regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Small Children (0 to <6 Years) | Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Year (6 Months) | 7242 IU/kg BW/year/participant | Standard Deviation 1695 |
| Older Children (6 to <12 Years) | Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Year (6 Months) | 5951 IU/kg BW/year/participant | Standard Deviation 1760 |
| Adolescents (12 to <18 Years) | Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Year (6 Months) | 5756 IU/kg BW/year/participant | Standard Deviation 1247 |
| Adults (>=18 Years) | Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Year (6 Months) | 4527 IU/kg BW/year/participant | Standard Deviation 2627 |