Clincosm LogoSign in Get a demo

pathfinder™2: Evaluation of Safety and Efficacy, Including Pharmacokinetics, of NNC 0129-0000-1003 When Administered for Treatment and Prophylaxis of Bleeding in Subjects With Haemophilia A

Sponsor
Novo Nordisk A/S (Industry)
Overall Status
Completed
CT.gov ID
NCT01480180
Collaborator
(none)
186
Enrollment
93
Locations
2
Arms
82.3
Actual Duration (Months)
2
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This trial is conducted globally. The aim of the trial is to evaluate the safety and efficacy, including pharmacokinetics (the exposure of the trial drug in the body) of NNC 0129-0000-1003 (N8-GP) in subjects with Haemophilia A.

Condition or Disease Intervention/Treatment Phase
  • Drug: turoctocog alfa pegol
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
186 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multi-national Trial Evaluating Safety and Efficacy, Including Pharmacokinetics, of NNC 0129-0000-1003 When Administered for Treatment and Prophylaxis of Bleeding in Patients With Haemophilia A
Actual Study Start Date :
Jan 30, 2012
Actual Primary Completion Date :
Dec 10, 2018
Actual Study Completion Date :
Dec 10, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Prophylaxis

Drug: turoctocog alfa pegol
Administered i.v.
Other Names:
  • NNC 0129-0000-1003

    		•
    Experimental: On-demand

    Drug: turoctocog alfa pegol
    Administered i.v.
    Other Names:
  • NNC 0129-0000-1003

    		•

    Outcome Measures

    Primary Outcome Measures

    1. The Incidence Rate of FVIII-inhibitors ≥0.6 BU: After Approximately 19 Months [After approximately 19 months]

      All participants with neutralizing antibodies were included in the numerator and any participant with a minimum 50 exposure days plus any participant with inhibitory inhibitors was included in the denominator. A positive inhibitor test was defined as ≥0.6 bethesda unit (BU). Estimates are based on exact calculations for a binomial distribution. For the calculation of the 'inhibitor rate' the nominator included all participants with neutralising antibodies while the denominator included all participants with a minimum of 50 exposures plus any participant with less than 50 exposures but with neutralising inhibitors.

    2. Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 19 Months [After approximately 19 months]

      Annualised bleeding rate (ABR) is the number of bleeding episodes per year. This was assessed only for the prophylaxis treatment with N8-GP.

    3. The Incidence Rate of FVIII-inhibitors ≥0.6 BU: After Approximately 25 Months [After approximately 25 months]

      All participants with neutralizing antibodies were included in the numerator and any participant with a minimum 50 exposure days plus any participant with inhibitory inhibitors was included in the denominator. A positive inhibitor test was defined as ≥0.6 bethesda unit (BU). Estimates are based on exact calculations for a binomial distribution. For the calculation of the 'inhibitor rate' the nominator included all participants with neutralising antibodies while the denominator included all participants with a minimum of 50 exposures plus any participant with less than 50 exposures but with neutralising inhibitors.

    4. Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 25 Months [After approximately 25 months]

      ABR is the number of bleeding episodes per year. This was assessed only for the prophylaxis treatment with N8-GP.

    5. Incidence Rate of FVIII-inhibitors ≥0.6 BU: At Approximately 80 Months [At approximately 80 months]

      All participants with neutralizing antibodies were included in the numerator and any participant with a minimum 50 exposure days plus any participant with inhibitory inhibitors was included in the denominator. A positive inhibitor test was defined as ≥0.6 bethesda unit (BU). Estimates are based on exact calculations for a binomial distribution. For the calculation of the 'inhibitor rate' the nominator included all participants with neutralising antibodies while the denominator included all participants with a minimum of 50 exposures plus any participant with less than 50 exposures but with neutralising inhibitors.

    6. Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 80 Months [After approximately 80 months]

      Annualised bleeding rate (ABR) is the number of bleeding episodes per year reported during the prophylactic treatment with N8-GP.

    Secondary Outcome Measures

    1. Haemostatic Effect of N8-GP When Used for Treatment of Bleeds, Assessed on a Four-point Scale for Haemostatic Response (Excellent, Good, Moderate and None): After Approximately 19 Months [After approximately 19 months]

      Haemostatic effect of N8-GP for treatment of bleeding episodes was assessed by 4-point response scale: none, moderate, good or excellent. Evaluation during trial was done by participant and/or parent(s)/caregiver within approximately 8 hours after a single injection as follows: Excellent: Abrupt pain relief and/or clear improvement in objective signs of bleeding within approximately 8 hrs after a single injection; Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hrs after a single injection, but possibly requiring more than one injection for complete resolution; Moderate: Probable or slight beneficial effect within approximately 8 hours after the first injection, but usually requiring more than one injection; None: No improvement, or worsening of symptoms.

    2. Haemostatic Effect of N8-GP When Used for Treatment of Bleeds, Assessed on a Four-point Scale for Haemostatic Response (Excellent, Good, Moderate and None): After Approximately 25 Months [After approximately 25 months]

      Haemostatic effect of N8-GP for treatment of bleeding episodes was assessed by 4-point response scale: none, moderate, good or excellent. Evaluation during trial was done by participant and/or parent(s)/caregiver within approximately 8 hours after a single injection as follows: Excellent: Abrupt pain relief and/or clear improvement in objective signs of bleeding within approximately 8 hrs after a single injection; Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hrs after a single injection, but possibly requiring more than one injection for complete resolution; Moderate: Probable or slight beneficial effect within approximately 8 hours after the first injection, but usually requiring more than one injection; None: No improvement, or worsening of symptoms.

    3. Haemostatic Effect of N8-GP When Used for Treatment of Bleeds, Assessed on a Four-point Scale for Haemostatic Response (Excellent, Good, Moderate and None): After Approximately 80 Months [After approximately 80 months]

      Haemostatic effect of N8-GP for treatment of bleeding episodes was assessed by 4-point response scale: none, moderate, good or excellent. Evaluation during trial was done by participant and/or parent(s)/caregiver within approximately 8 hours after a single injection as follows: Excellent: Abrupt pain relief and/or clear improvement in objective signs of bleeding within approximately 8 hrs after a single injection; Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hrs after a single injection, but possibly requiring more than one injection for complete resolution; Moderate: Probable or slight beneficial effect within approximately 8 hours after the first injection, but usually requiring more than one injection; None: No improvement, or worsening of symptoms.

    4. Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 19 Months [After approximately 19 months]

      The mean number of infusions of N8-GP used for treatment of a bleed from start to stop of a bleed was reported.

    5. Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 25 Months [After approximately 25 months]

      The mean number of infusions of N8-GP used for treatment of a bleed from start to stop of a bleed was reported.

    6. Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 80 Months [After approximately 80 months]

      The mean number of infusions of N8-GP used for treatment of a bleed from start to stop of a bleed was reported.

    7. Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 19 Months [After approximately 19 months]

      The mean consumption of N8-GP (U/kg) used for treatment of a bleed from start to stop of a bleed was reported.

    8. Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 25 Months [After approximately 25 months]

      The mean consumption of N8-GP (U/kg) used for treatment of a bleed from start to stop of a bleed was reported.

    9. Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 80 Months [After approximately 80 months]

      The mean consumption of N8-GP (U/kg) used for treatment of a bleed from start to stop of a bleed was reported.

    10. Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 19 Months [After approximately 19 months]

      Number of infusions are presented as average dose used during propphylaxis and on-demand treatment.

    11. Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 25 Months [After approximately 25 months]

      Number of infusions are presented as average dose used during prophylaxis and on-demand treatment.

    12. Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 80 Months [After approximately 80 months]

      Number of infusions are presented as average dose used during prophylaxis and on-demand treatment.

    13. Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 19 Months [After approximately 19 months]

      The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed (per month per participant) was reported.

    14. Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 25 Months [After approximately 25 months]

      The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed (per month per participant) was reported.

    15. Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 80 Months [After approximately 80 months]

      The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed (per month per participant) was reported.

    16. Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 19 Months [After approximately 19 months]

      The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed (per year per participant) was reported.

    17. Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 25 Months [After approximately 25 months]

      The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed (per year per participant) was reported.

    18. Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 80 Months [After approximately 80 months]

      The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed (per year per participant) was reported.

    19. Haemostatic Effect as Measured by Recovery and Trough Levels FVIII:C (in All Patients Receiving Prophylaxis Treatment): After Approximately 19 Months [After approximately 19 months]

      Recovery and trough levels of FVIII:C was reported for all participants at Visit 3 (Week 4) and end of main phase (approx. 19 months). The data was reported for all participants who received prophylaxis treatment. Chromogenic assay was performed with N8-GP product specific standard (PSS) as a calibrator.

    20. Haemostatic Effect as Measured by Recovery and Trough Levels FVIII:C (in All Patients Receiving Prophylaxis Treatment): After Approximately 25 Months [After approximately 25 months]

      Recovery and trough levels of FVIII:C was reported for all participants at the end of extension phase 1 study (approx. 25 months). The data was reported for all participants who received prophylaxis treatment. Chromogenic assay was performed with N8-GP product specific standard (PSS) as a calibrator.

    21. Haemostatic Effect as Measured by Recovery and Trough Levels FVIII:C (in All Patients Receiving Prophylaxis Treatment): After Approximately 80 Months [After approximately 80 months]

      Since patients were allowed to change prophylaxis regimen at any time during the extension phase part 2, and since the visit intervals were different for the 2 prophylaxis treatment regimens (Q4D and Q7D), FVIII activity data are reported only as incremental recovery at this timepoint.

    22. Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Patients 13-16 Years Old) After Approx 19 and 25 Months [After approx 19 and 25 months]

      Reported results are change from baseline (Month 0) measured at end of main phase (approx Month 19) and change from Month 19 at end of Extension 1 (approx Month 25) of the study. The 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.

    23. Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Patients 13-16 Years Old): After Approx 80 Months [2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs]

      Reported results are change from visit 1 (Month 0) upto end of Extension phase 2 (Month 80) of the study. Time intervals are assigned based on time after first dose. It was possible that a participant could answer more than one questionnaire in a single time interval. The 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. Overall number of units analysed = Maximum no of questionnaires answered by participants for this endpoint. Overall number of participants analysed = maximum number of participants contributed to the analysis for each time point.

    24. Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Parents of Patients 13-16 Years Old): After Approx 19 and 25 Months [After approx 19 and 25 months]

      Reported results are change from baseline (Month 0) measured at end of main phase (Month 19) and change from Month 19 to end of Extension 1 (Month 25) of the study. The questionnaire was completed by parents of the patients in the 13-16 years old age bracket. The 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.

    25. Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Parents of Patients 13-16 Years Old): After Approx 80 Months [2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs]

      Reported results are change from visit 1 (Month 0) upto end of Extension phase 2 (Month 80) of the study. The questionnaire was completed by parents of the patients in the 13-16 years old age bracket. Time intervals are assigned based on time after first dose. It was possible that a participant could answer more than one questionnaire in a single time interval. The 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. Overall number of units analysed = Maximum no of questionnaires answered by participants for this endpoint. Overall number of participants analysed = maximum number of participants contributed to the analysis for each time point.

    26. Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approx 19 and 25 Months [After approx 19 and 25 months]

      Reported results are change from baseline (Month 0) measured at end of main phase (Month 19) and change from Month 19 to end of Extension 1 (Month 25) of the study. The HAEM-A-QOL (for adults (>=17 years)) assessment included questions on 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.

    27. Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approximately 80 Months [2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs]

      Reported results are change from visit 1 (Month 0) upto end of Extension phase 2 (Month 80) of the study. Time intervals are assigned based on time after first dose. It was possible that a participant could answer more than one questionnaire in a single time interval. Overall number of units analysed = Maximum no of questionnaires answered by participants for this endpoint. Overall number of participants analysed = maximum number of participants contributed to the analysis for each time point. The HAEM-A-QOL (for adults (>=17 years)) 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. Scores range for each question was 0-100, with a lower score indicating better quality of life related to haemophilia.

    28. Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months [After approx 19 and 25 months]

      Reported results are change from baseline (Month 0) measured at end of main phase (Month 19) and change from Month 19 to end of Extension 1 (Month 25) of the study. The HEMO-SAT (Hematology-satisfaction) assessment included questions on treatment aspects including Ease and convenience, efficacy, burden, specialist/nurses, centre/hospital, general satisfaction (reported by patients). 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. A decrease in the score would mean improvement.

    29. Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months [1-<2 yrs, 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs]

      Reported results are change from visit 1 (Month 0) upto end of Extension phase 2 (Month 80) of the study. Time intervals are assigned based on time after first dose. It was possible that a participant could answer more than one questionnaire in a single time interval. Overall number of units analysed = Maximum no of questionnaires answered by participants for this endpoint. Overall number of participants analysed = maximum number of participants contributed to the analysis for each time point. The HEMO-SAT assessment included questions on treatment aspects including Ease and convenience, efficacy, burden, specialist/nurses, centre/hospital, general satisfaction (reported by patients). 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. A decrease in the score would mean improvement.

    30. Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): After Approx 19 and 25 Months [After approx 19 and 25 months]

      The summary of change was based on individual changes observed at visit 13 (approximately 19 months) from visit 2a pre-dose (Month 0). The HEMO-SAT assessment included questions on treatment aspects including Ease and convenience, efficacy, burden, specialist/nurses, centre/hospital, general satisfaction (reported by parents). 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. A decrease in the score would mean improvement.

    31. Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months [2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs]

      Reported results are from Visit 1 (Month 0), and change from visit 1 upto end of Extension phase 2 (Month 80) of the study. Time intervals are assigned based on time after first dose. It was possible that a participant could answer more than one questionnaire in a single time interval. Overall number of units analysed = Max. no of questionnaires answered by participants for this endpoint. Overall number of participants analysed = max. number of participants contributed to the analysis for each time point. The HEMO-SAT assessment included questions on treatment aspects including Ease and convenience, efficacy, burden, specialist/nurses, centre/hospital, 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. A decrease in the score would mean improvement.

    32. Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approx 19 and 25 Months [After approx 19 and 25 months]

      Reported results are change from baseline (Month 0) measured at end of main phase (Month 19) and change from Month 19 to end of Extension 1 (Month 25) of the study. The European quality of life visual analogue scale (EQ5D-VAS) records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement. EQ-5D-VAS: range 0 to 100. A higher score indicates better self reported health status. A positive change indicates an improvement.

    33. Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approximately 80 Months [1-<2 yrs, 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs]

      Reported results are change from visit 1 (Month 0) upto end of Extension phase 2 (Month 80) of the study. Time intervals are assigned based on time after first dose. It was possible that a participant could answer more than one questionnaire in a single time interval. Overall number of units analysed = Maximum no of questionnaires answered by participants for this endpoint. Overall number of participants analysed = maximum number of participants contributed to the analysis for each time point. The EQ5D-VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement. EQ-5D-VAS: range 0 to 100. A higher score indicates better self reported health status. A positive change indicates an improvement.

    34. Patient Reported Outcomes - Change in European Quality of Life Utility Index: After Approx 19 and 25 Months [After approx 19 and 25 months]

      Reported results are change from baseline (Month 0) measured at end of main phase (Month 19) and change from Month 19 to end of Extension 1 (Month 25) of the study. The European quality of life utility index comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels where 1 indicates better health state (no problems) and 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; a positive change indicates an improvement.

    35. Patient Reported Outcomes - Change in European Quality of Life Utility Index Scores: After Approximately 80 Months [1-<2 yrs, 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs]

      Reported results are change from visit 1 (Month 0) upto end of Extension phase 2 (Month 80) of the study. Time intervals are assigned based on time after first dose. It is possible that a patient answers more than one questionnaire in a single time interval. Overall units analysed = Max no. of questionnaires answered by participants for this endpoint. Overall no. of participants analysed = max no. of participants analysed at each time point. This utility index has 5 dimensions: mobility, self-care, usual activities, pain/discomfort & anxiety/depression. Each dimension has 3 levels where 1 indicates better health state (no problems) and 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; a positive change indicates an improvement.

    36. Number of Hospital Admissions During the Trial [After approx 19, 25 and 80 months]

      The number of hospital admissions that took place in the study were reported.

    37. Number of Days at the Hospital During the Trial [After approx 19, 25 and 80 months]

      The mean number of days that participants spent at the hospital during the study were reported.

    38. Number of Admissions to the Emergency Room (ER) During the Trial [After approx 19, 25 and 80 months]

      The number of admissions to the ER that took place in the study were reported for each group.

    39. Number of Days Missing School or Work [Approx 19, 25 and 80 months]

      The mean number of days that participants missed to go to school or work were reported.

    40. Number of Days Using Mobility Aid [Approx 19, 25 and 80 months]

      The mean number of days that participants used any aids for mobility during the study were reported.

    41. Number of Participants Using Pain Medication [After approx 25 and 80 months]

      The number of participants using pain medication during the main plus extension phase 1 of the study (approximately 25 months) and during extension phase 2(approximately 80 months) were reported.

    42. Number of Bleeds Using Pain Medication [After approx 19 months]

      The mean number of bleeds using pain medication in the main phase of the study (approximately 19 months) were reported.

    43. Number of Adverse Events Reported During the Trial Period: After Approximately 19 Months [After approx 19 months]

      All presented adverse events (AEs) are treatment-emergent. A treatment-emergent adverse event was defined as an event with onset after first N8-GP administration.

    44. Number of Adverse Events Reported During the Trial Period: After Approximately 25 Months [After approx. 25 months]

      All presented adverse events (AEs) are treatment-emergent. A treatment-emergent adverse event was defined as an event with onset after first N8-GP administration.

    45. Number of Adverse Events Reported During the Trial Period: After Approximately 80 Months [After approximately 80 months]

      The number of adverse events observed during the study after approximately 80 months was reported.

    46. Number of Serious Adverse Events Reported During the Trial Period: After Approximately 19 Months [After approximately 19 months]

      All presented serious adverse events (SAEs) are treatment-emergent. A treatment-emergent adverse event was defined as an event with onset after first N8-GP administration.

    47. Number of Serious Adverse Events Reported During the Trial Period: After Approximately 25 Months [After approximately 25 months]

      All presented serious adverse events (SAEs) are treatment-emergent. A treatment-emergent adverse event was defined as an event with onset after first N8-GP administration.

    48. Number of Serious Adverse Events Reported During the Trial Period: After Approximately 80 Months [After approximately 80 months]

      All presented serious adverse events (SAEs) are treatment-emergent. A treatment-emergent adverse event was defined as an event with onset after first N8-GP administration.

    49. Change in Blood Pressure: After Approximately 19 Months [After approximately 19 months]

      The mean change in the systolic and diastolic blood pressure values of participants was reported. The summary of change was based on individual changes observed at visit 13 (approximately 19 months) from visit 2a pre-dose (Month 0).

    50. Change in Blood Pressure: After Approximately 25 Months [After approximately 19 and 25 months]

      The mean change in the systolic and diastolic blood pressure values of participants was reported. The summary of change was based on individual changes observed at visit 17 (approximately month 25) from visit 13 (approximately month 19).

    51. Change in Blood Pressure: After Approximately 80 Months [After approximately 80 months]

      Change in the blood pressure was not calculated in the extension phase 2 of the study since participants were allowed to change from Q4D to Q7D and vice versa.

    52. Change in Pulse: After Approximately 19 Months [After approximately 19 months]

      The mean change in the pulse values of participants was reported. The summary of change was based on individual changes observed at visit 13 (approximately 19 months) from visit 2a pre-dose (Month 0).

    53. Change in Pulse: After Approximately 25 Months [After approximately 25 months]

      The mean change in the pulse values of participants was reported. The summary of change was based on individual changes observed at visit 17 (approximately month 25) from visit 13 (approximately month 19).

    54. Change in Pulse: After Approximately 80 Months [After approximately 80 months]

      Change in pulse was not calculated in the extension phase 2 of the study since participants were allowed to change from Q4D to Q7D and vice versa.

    55. Change in Body Temperature: After Approximately 19 Months [After approximately 19 months]

      The mean change in the body temperature values of participants was reported. The summary of change was based on individual changes observed at visit 13 (approximately 19 months) from visit 2a pre-dose (Month 0).

    56. Change in Body Temperature: After Approximately 25 Months [After approximately 25 months]

      The mean change in the body temperature (C) values of participants was reported. The summary of change was based on individual changes observed at visit 17 (approximately month 25) from visit 13 (approximately month 19).

    57. Change in Body Temperature: After Approximately 80 Months [After approximately 80 months]

      Change in body temperature was not calculated in the extension phase 2 of the study since participants were allowed to change from Q4D to Q7D and vice versa.

    58. Change in Respiratory Rate: After Approximately 19 Months [After approximately 19 months]

      The mean change in the respiratory rate values of participants was reported. The summary of change was based on individual changes observed at visit 13 (approximately 19 months) from visit 2a pre-dose (Month 0).

    59. Change in Respiratory Rate: After Approximately 25 Months [After approximately 25 months]

      The mean change in the respiratory rate (breaths/min) values of participants was reported. The summary of change was based on individual changes observed at visit 17 (approximately month 25) from visit 13 (approximately month 19).

    60. Change in Respiratory Rate: After Approximately 80 Months [After approximately 80 months]

      Change in respiratory rate was not calculated in the extension phase 2 of the study since participants were allowed to change from Q4D to Q7D and vice versa.

    61. FVIII Activity 30 Min Post -Injection (C30min) [Week 0, week 28]

      FVIII plasma activity was measured after 30 mins of injection. This was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator

    62. Incremental Recovery (Single Dose and Steady State) [Week 0, week 28]

      Incremental recovery was defined as the dose-normalised activity recorded 30 min after end of injection. This was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.

    63. Trough Level (Single Dose and Steady State) [Week 0, week 28]

      Trough level was defined as the plasma FVIII activity recorded immediately before next dose is given. This was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.

    64. Area Under the Curve (AUC0-inf) [Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28]

      Area under the plasma activity versus time profile from time zero to infinity (AUC0-inf) was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. It is the measure of total plasma exposure. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.

    65. Area Under the Curve (AUC0-t) [Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28]

      Area under the plasma activity versus time profile from time zero to the last measurable activity (AUC0-t) was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.

    66. Terminal Half Life (t1/2) [Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28]

      t½ = ln(2) / λz, where λz is the terminal elimination rate constant. The terminal elimination rate constant was estimated using linear regression on the terminal part of the log(activity) versus time profile. This was measured at Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.

    67. Clearance (CL) [Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28]

      Total plasma clearance (CL) of drug after intravenous administration was reported. Clearance was calculated using the formula CL= Dose / AUC(0-inf). This was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.

    68. Mean Residence Time (MRT) [Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28]

      MRT = AUMC/AUC(0-inf), where AUMC is the area under the first moment curve, i.e. the area under the curve t∙C(t), calculated with the same method as AUC(0-inf) (linear trapezoidal method + extrapolated area). This was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.

    69. Volume of Distribution at Steady State (Vss) [Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28]

      Apparent volume of distribution at steady state is a product of the mean residence time and clearance and was calculated using the formula - Vss = CL x MRT. This was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria: - Male patients with severe congenital haemophilia A (FVIII activity below 1%, according to medical records) - Documented history of at least 150 EDs (exposure days) to other FVIII products - At least 12 years and body weight at least 35 kg (except for Croatia, France, Russia, Israel and the Netherlands where the lower age limit will be 18 years) Exclusion Criteria: - Previous participation in this trial defined as withdrawal after administration N8-GP - Any history of FVIII inhibitors - FVIII inhibitors above or equal to 0.6 BU/mL at screening - HIV (human immunodeficiency virus) positive, defined by medical records with CD4+ (T-lymphocyte subtype) count below or equal to 200/mcL or a viral load of more than 400000 copies/mL. If the data is not available in medical records within last 6 months, CD4+ will be measured at the screening visit - Congenital or acquired coagulation disorders other than haemophilia A - Previous significant thromboembolic events (e.g. myocardial infarction, cerebrovascular disease or deep venous thrombosis) as defined by available medical records - Platelet count below 50,000 platelets/mcL (laboratory value at the screening visit) - ALAT (alanine aminotransferase) above 3 times the upper limit of normal reference ranges at central laboratory - Creatinine level equal to or greater than 1.5 times above upper normal limit (according to central laboratory reference ranges) - Ongoing immune modulating or chemotherapeutic medication

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novo Nordisk Investigational Site Phoenix Arizona United States 85016
    2 Novo Nordisk Investigational Site Long Beach California United States 90806
    3 Novo Nordisk Investigational Site Sacramento California United States 95817
    4 Novo Nordisk Investigational Site Torrance California United States 90502-2004
    5 Novo Nordisk Investigational Site Washington District of Columbia United States 20007
    6 Novo Nordisk Investigational Site Washington District of Columbia United States 20010-2978
    7 Novo Nordisk Investigational Site Orlando Florida United States 32827
    8 Novo Nordisk Investigational Site Tampa Florida United States 33607
    9 Novo Nordisk Investigational Site Augusta Georgia United States 30912
    10 Novo Nordisk Investigational Site Boise Idaho United States 83712
    11 Novo Nordisk Investigational Site Iowa City Iowa United States 52242
    12 Novo Nordisk Investigational Site New Orleans Louisiana United States 70118-5720
    13 Novo Nordisk Investigational Site Baltimore Maryland United States 21205
    14 Novo Nordisk Investigational Site Boston Massachusetts United States 02115
    15 Novo Nordisk Investigational Site Detroit Michigan United States 48201
    16 Novo Nordisk Investigational Site East Lansing Michigan United States 48823
    17 Novo Nordisk Investigational Site Minneapolis Minnesota United States 55404
    18 Novo Nordisk Investigational Site Omaha Nebraska United States 68198-5456
    19 Novo Nordisk Investigational Site New Brunswick New Jersey United States 08901
    20 Novo Nordisk Investigational Site Newark New Jersey United States 07102
    21 Novo Nordisk Investigational Site Cincinnati Ohio United States 452289
    22 Novo Nordisk Investigational Site Dayton Ohio United States 45404
    23 Novo Nordisk Investigational Site Portland Oregon United States 97239
    24 Novo Nordisk Investigational Site Philadelphia Pennsylvania United States 19104
    25 Novo Nordisk Investigational Site Philadelphia Pennsylvania United States 19134
    26 Novo Nordisk Investigational Site Charleston South Carolina United States 29425
    27 Novo Nordisk Investigational Site Nashville Tennessee United States 37232-9830
    28 Novo Nordisk Investigational Site Houston Texas United States 77030
    29 Novo Nordisk Investigational Site Charlottesville Virginia United States 22908
    30 Novo Nordisk Investigational Site Norfolk Virginia United States 23507
    31 Novo Nordisk Investigational Site Spokane Washington United States 99204
    32 Novo Nordisk Investigational Site Camperdown New South Wales Australia 2050
    33 Novo Nordisk Investigational Site South Brisbane Queensland Australia 4101
    34 Novo Nordisk Investigational Site Parkville Victoria Australia 3052
    35 Novo Nordisk Investigational Site Campinas Sao Paulo Brazil 13081-970
    36 Novo Nordisk Investigational Site Sofia Bulgaria 1756
    37 Novo Nordisk Investigational Site Split Croatia 21 000
    38 Novo Nordisk Investigational Site Zagreb Croatia 10 000
    39 Novo Nordisk Investigational Site København Ø Denmark 2100
    40 Novo Nordisk Investigational Site Århus N Denmark 8200
    41 Novo Nordisk Investigational Site Bron Cedex France 69677
    42 Novo Nordisk Investigational Site Kremlin-Bicêtre France 94270
    43 Novo Nordisk Investigational Site Nantes Cedex 1 France 44093
    44 Novo Nordisk Investigational Site Paris France 75015
    45 Novo Nordisk Investigational Site Berlin Germany 10249
    46 Novo Nordisk Investigational Site Bonn Germany 53127
    47 Novo Nordisk Investigational Site Frankfurt/M. Germany 60590
    48 Novo Nordisk Investigational Site Hannover Germany 30625
    49 Novo Nordisk Investigational Site Homburg Germany 66421
    50 Novo Nordisk Investigational Site München Germany 80336
    51 Novo Nordisk Investigational Site Budapest Hungary H-1134
    52 Novo Nordisk Investigational Site Debrecen Hungary 4012
    53 Novo Nordisk Investigational Site Tel-Hashomer Israel 52621
    54 Novo Nordisk Investigational Site Firenze Italy 50134
    55 Novo Nordisk Investigational Site Milano Italy 20124
    56 Novo Nordisk Investigational Site Udine Italy 33100
    57 Novo Nordisk Investigational Site Vicenza Italy 36100
    58 Novo Nordisk Investigational Site Aichi Japan 466-8560
    59 Novo Nordisk Investigational Site Hiroshima Japan 734-8551
    60 Novo Nordisk Investigational Site Kitakyusyu, Fukuoka Japan 807 8555
    61 Novo Nordisk Investigational Site Nara Japan 634-8522
    62 Novo Nordisk Investigational Site Saitama Japan 350-0225
    63 Novo Nordisk Investigational Site Shimotsuke-shi, Tochigi Japan 329 0498
    64 Novo Nordisk Investigational Site Shizuoka Japan 420-8660
    65 Novo Nordisk Investigational Site Tokyo Japan 108-8639
    66 Novo Nordisk Investigational Site Tokyo Japan 160-0023
    67 Novo Nordisk Investigational Site Tokyo Japan 167-0035
    68 Novo Nordisk Investigational Site Yokohama-shi, Kanagawa Japan 241-0811
    69 Novo Nordisk Investigational Site Daejeon Korea, Republic of 302-799
    70 Novo Nordisk Investigational Site Kuala Lumpur Malaysia 50400
    71 Novo Nordisk Investigational Site Selangor Darul Ehsan Malaysia 68000
    72 Novo Nordisk Investigational Site Groningen Netherlands 9713 GZ
    73 Novo Nordisk Investigational Site Rotterdam Netherlands 3015 CE
    74 Novo Nordisk Investigational Site Oslo Norway 0027
    75 Novo Nordisk Investigational Site San Juan Puerto Rico 00935
    76 Novo Nordisk Investigational Site Saint-Petersburg Russian Federation 191065
    77 Novo Nordisk Investigational Site Madrid Spain 28046
    78 Novo Nordisk Investigational Site Málaga Spain 29010
    79 Novo Nordisk Investigational Site Malmö Sweden 205 02
    80 Novo Nordisk Investigational Site Genève 14 Switzerland 1211
    81 Novo Nordisk Investigational Site Lausanne Switzerland 1011
    82 Novo Nordisk Investigational Site Zürich Switzerland 8091
    83 Novo Nordisk Investigational Site Changhua Taiwan 500
    84 Novo Nordisk Investigational Site Taipei Taiwan 100
    85 Novo Nordisk Investigational Site Adana Turkey 01130
    86 Novo Nordisk Investigational Site Bornova-IZMIR Turkey 35100
    87 Novo Nordisk Investigational Site Samsun Turkey 55319
    88 Novo Nordisk Investigational Site Basingstoke United Kingdom RG24 9NA
    89 Novo Nordisk Investigational Site Cardiff United Kingdom CF14 4XW
    90 Novo Nordisk Investigational Site London United Kingdom NW3 2QG
    91 Novo Nordisk Investigational Site London United Kingdom SE1 7EH
    92 Novo Nordisk Investigational Site Oxford United Kingdom OX3 7LJ
    93 Novo Nordisk Investigational Site Sheffield United Kingdom S10 2JF

    Sponsors and Collaborators

    • Novo Nordisk A/S

    Investigators

    • Study Director: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Novo Nordisk A/S
    ClinicalTrials.gov Identifier:
    NCT01480180
    Other Study ID Numbers:
    • NN7088-3859
    • U1111-1119-7416
    • 2011-001142-15
    • JapicCTI-121749
    First Posted:
    Nov 28, 2011
    Last Update Posted:
    Nov 23, 2020
    Last Verified:
    Nov 1, 2020
    Additional relevant MeSH terms:
    Hemostatic Disorders
    Hemophilia A
    Blood Coagulation Disorders
    Hemorrhage

    Study Results

    Participant Flow

    Recruitment Details The trial was conducted at 77 sites in 22 countries as follows: Australia:3; Brazil:1; Croatia:1; Denmark:2; France:3; Germany:5; Hungary:2; Israel:1; Italy:2; Japan:8; Malaysia:2; Netherlands:2; Norway:1; Russian Federation:1; Korea, Republic of:1; Spain:2; Sweden:1; Switzerland:3; Taiwan:2; Turkey:3; United Kingdom:6; United States:25.
    Pre-assignment Detail The trial had a main phase and an extension phase 1 and phase 2.
    Arm/Group Title Prophylaxis On-demand N8-GP 50 U/kg Prophylaxis Q4D N8-GP 75 U/kg Prophylaxis Q7D N8-GP 20-75 U/kg On-demand N8-GP Prophylaxis
    Arm/Group Description Participants received one single bolus dose of 50 U/kg of body weight (BW) of turoctocog alfa pegol (N8-GP), administered intravenously (IV) every 4th day (96 hours) or twice weekly (investigator's discretion). The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. This arm is applicable only for the main phase. Participants received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5. This arm is applicable only for the main phase. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. This arm was applicable for the extension phase part-1 and part 2. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 3+ bleeding episodes during the last 6 months before entering the extension phase, were randomised to receive one single bolus dose of 75 U/kg BW of N8-GP. Participants received one single bolus dose of 75 U/kg BW of N8-GP administered IV every 7th day (Q7D). Based on the bleeding pattern, the investigator could change the dosing frequency from Q7D to Q4D, but not vice versa. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5. Participants in this arm include subjects both from the 50 U/kg Q4D and the 75 U/kg Q7D prophylaxis arms.
    Period Title: Main Phase
    STARTED 174 12 0 0 0 0
    Max. Participants After Switching 175 11 0 0 0 0
    COMPLETED 155 11 0 0 0 0
    NOT COMPLETED 19 1 0 0 0 0
    Period Title: Main Phase
    STARTED 0 0 105 38 7 0
    COMPLETED 0 0 95 28 7 0
    NOT COMPLETED 0 0 10 10 0 0
    Period Title: Main Phase
    STARTED 0 0 94 40 5 0
    COMPLETED 0 0 77 33 3 0
    NOT COMPLETED 0 0 17 7 2 0

    Baseline Characteristics

    Arm/Group Title Prophylaxis On-demand Total
    Arm/Group Description Participants received one single bolus dose of 50 U/kg of body weight (BW) of turoctocog alfa pegol (N8-GP), administered intravenously (IV) every 4th day (96 hours) or twice weekly (investigator's discretion). The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5. Total of all reporting groups
    Overall Participants 174 12 186
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    30.5
    (12.4)
    39.8
    (13.9)
    31.1
    (12.6)
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    Male
    174
    100%
    12
    100%
    186
    100%
    Race/Ethnicity, Customized (Count of Participants)
    Hispanic or Latino
    13
    7.5%
    0
    0%
    13
    7%
    Not Hispanic or Latino
    161
    92.5%
    12
    100%
    173
    93%
    Race/Ethnicity, Customized (Count of Participants)
    Asian
    31
    17.8%
    4
    33.3%
    35
    18.8%
    Black or African American
    8
    4.6%
    3
    25%
    11
    5.9%
    White
    133
    76.4%
    5
    41.7%
    138
    74.2%
    Other
    2
    1.1%
    0
    0%
    2
    1.1%

    Outcome Measures

    1. Primary Outcome
    Title The Incidence Rate of FVIII-inhibitors ≥0.6 BU: After Approximately 19 Months
    Description All participants with neutralizing antibodies were included in the numerator and any participant with a minimum 50 exposure days plus any participant with inhibitory inhibitors was included in the denominator. A positive inhibitor test was defined as ≥0.6 bethesda unit (BU). Estimates are based on exact calculations for a binomial distribution. For the calculation of the 'inhibitor rate' the nominator included all participants with neutralising antibodies while the denominator included all participants with a minimum of 50 exposures plus any participant with less than 50 exposures but with neutralising inhibitors.
    Time Frame After approximately 19 months

    Outcome Measure Data

    Analysis Population Description
    Results are based on the safety analysis set (SAS). SAS comprised all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants received one single bolus dose of 50 U/kg of body weight (BW) of N8-GP administered intravenously (IV) every 4th day (96 hours) or twice weekly (investigator's discretion). The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 12
    Number [Inhibitor rate]
    0.006
    0
    2. Primary Outcome
    Title Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 19 Months
    Description Annualised bleeding rate (ABR) is the number of bleeding episodes per year. This was assessed only for the prophylaxis treatment with N8-GP.
    Time Frame After approximately 19 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the full analysis set (FAS) which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP Prophylaxis
    Arm/Group Description Participants from both the N8-GP 50 U/kg Q4D and N8-GP 75 U/kg Q7D groups were included in this arm.
    Measure Participants 177
    Median (Inter-Quartile Range) [Bleeds per participant per year]
    1.33
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection N8-GP 50 U/kg Prophylaxis Q4D
    Comments The analysis is based on a Poisson regression model allowing for over-dispersion. For participants withdrawing prematurely, the log planned treatment duration is used as offset; for completers, the log actual treatment duration is used.
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-values are from the 1-sided test of the null hypothesis that the ABR is at least 8.5 evaluated at the 2.5% level.
    Method Poisson regression
    Comments
    Method of Estimation Estimation Parameter Poisson estimate
    Estimated Value 3.70
    Confidence Interval (2-Sided) 95%
    2.94 to 4.66
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Primary Outcome
    Title The Incidence Rate of FVIII-inhibitors ≥0.6 BU: After Approximately 25 Months
    Description All participants with neutralizing antibodies were included in the numerator and any participant with a minimum 50 exposure days plus any participant with inhibitory inhibitors was included in the denominator. A positive inhibitor test was defined as ≥0.6 bethesda unit (BU). Estimates are based on exact calculations for a binomial distribution. For the calculation of the 'inhibitor rate' the nominator included all participants with neutralising antibodies while the denominator included all participants with a minimum of 50 exposures plus any participant with less than 50 exposures but with neutralising inhibitors.
    Time Frame After approximately 25 months

    Outcome Measure Data

    Analysis Population Description
    Results are based on the SAS. SAS comprised all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 75 U/kg Prophylaxis Q7D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 3+ bleeding episodes during the last 6 months before entering the extension phase, were randomised to receive one single bolus dose of 75 U/kg BW of N8-GP. Participants received one single bolus dose of 75 U/kg BW of N8-GP administered IV every 7th day (Q7D). Based on the bleeding pattern, the investigator could change the dosing frequency from Q7D to Q4D, but not vice versa. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 61 12
    Number [Inhibitor rate]
    0.006
    0
    0
    4. Primary Outcome
    Title Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 25 Months
    Description ABR is the number of bleeding episodes per year. This was assessed only for the prophylaxis treatment with N8-GP.
    Time Frame After approximately 25 months

    Outcome Measure Data

    Analysis Population Description
    Results are based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 75 U/kg Prophylaxis Q7D
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 3+ bleeding episodes during the last 6 months before entering the extension phase, were randomised to receive one single bolus dose of 75 U/kg BW of N8-GP. Participants received one single bolus dose of 75 U/kg BW of N8-GP administered IV every 7th day (Q7D). Based on the bleeding pattern, the investigator could change the dosing frequency from Q7D to Q4D, but not vice versa. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm.
    Measure Participants 177 61
    Median (Inter-Quartile Range) [Bleeds per participant per year]
    1.36
    0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection N8-GP 50 U/kg Prophylaxis Q4D
    Comments The analysis is based on a Poisson regression model allowing for over-dispersion. For participants withdrawing prematurely, the log planned treatment duration is used as offset; for completers, the log actual treatment duration is used.
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-values are from the 1-sided test of the null hypothesis that the ABR is at least 8.5 evaluated at the 2.5% level.
    Method Poisson regression
    Comments
    Method of Estimation Estimation Parameter Poisson estimate
    Estimated Value 3.27
    Confidence Interval (2-Sided) 95%
    2.59 to 4.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Primary Outcome
    Title Incidence Rate of FVIII-inhibitors ≥0.6 BU: At Approximately 80 Months
    Description All participants with neutralizing antibodies were included in the numerator and any participant with a minimum 50 exposure days plus any participant with inhibitory inhibitors was included in the denominator. A positive inhibitor test was defined as ≥0.6 bethesda unit (BU). Estimates are based on exact calculations for a binomial distribution. For the calculation of the 'inhibitor rate' the nominator included all participants with neutralising antibodies while the denominator included all participants with a minimum of 50 exposures plus any participant with less than 50 exposures but with neutralising inhibitors.
    Time Frame At approximately 80 months

    Outcome Measure Data

    Analysis Population Description
    Results are based on the SAS. SAS comprised all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP Prophylaxis N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants from both the N8-GP 50 U/kg Q4D and N8-GP 75 U/kg Q7D groups were included in this arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 12
    Number [Inhibitor rate]
    0.006
    0
    6. Primary Outcome
    Title Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 80 Months
    Description Annualised bleeding rate (ABR) is the number of bleeding episodes per year reported during the prophylactic treatment with N8-GP.
    Time Frame After approximately 80 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 75 U/kg Prophylaxis Q7D
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 3+ bleeding episodes during the last 6 months before entering the extension phase, were randomised to receive one single bolus dose of 75 U/kg BW of N8-GP. Participants received one single bolus dose of 75 U/kg BW of N8-GP administered IV every 7th day (Q7D). Based on the bleeding pattern, the investigator could change the dosing frequency from Q7D to Q4D, but not vice versa. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm.
    Measure Participants 177 61
    Median (Inter-Quartile Range) [Bleeds per participant per year]
    0.99
    1.95
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection N8-GP 50 U/kg Prophylaxis Q4D
    Comments The analysis is based on a Poisson regression model allowing for over-dispersion. For participants withdrawing prematurely, the log planned treatment duration is used as offset; for completers, the log actual treatment duration is used.
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-values are from the 1-sided test of the null hypothesis that the ABR is at least 8.5 evaluated at the 2.5% level.
    Method Poisson regression
    Comments
    Method of Estimation Estimation Parameter Poisson estimate
    Estimated Value 2.35
    Confidence Interval (2-Sided) 95%
    1.87 to 2.95
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection N8-GP 20-75 U/kg On-demand
    Comments The analysis is based on a Poisson regression model allowing for over-dispersion. For participants withdrawing prematurely, the log planned treatment duration is used as offset; for completers, the log actual treatment duration is used.
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-values are from the 1-sided test of the null hypothesis that the ABR is at least 8.5 evaluated at the 2.5% level.
    Method Poisson regression
    Comments
    Method of Estimation Estimation Parameter Poisson estimate
    Estimated Value 4.39
    Confidence Interval (2-Sided) 95%
    3.09 to 6.24
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Haemostatic Effect of N8-GP When Used for Treatment of Bleeds, Assessed on a Four-point Scale for Haemostatic Response (Excellent, Good, Moderate and None): After Approximately 19 Months
    Description Haemostatic effect of N8-GP for treatment of bleeding episodes was assessed by 4-point response scale: none, moderate, good or excellent. Evaluation during trial was done by participant and/or parent(s)/caregiver within approximately 8 hours after a single injection as follows: Excellent: Abrupt pain relief and/or clear improvement in objective signs of bleeding within approximately 8 hrs after a single injection; Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hrs after a single injection, but possibly requiring more than one injection for complete resolution; Moderate: Probable or slight beneficial effect within approximately 8 hours after the first injection, but usually requiring more than one injection; None: No improvement, or worsening of symptoms.
    Time Frame After approximately 19 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of bleeds analysed.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 3+ bleeding episodes during the last 6 months before entering the extension phase, were randomised to receive one single bolus dose of 75 U/kg BW of N8-GP. Participants received one single bolus dose of 75 U/kg BW of N8-GP administered IV every 7th day (Q7D). Based on the bleeding pattern, the investigator could change the dosing frequency from Q7D to Q4D, but not vice versa. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm.
    Measure Participants 175 12
    Measure Bleeding episodes 436 532
    Excellent
    192
    320
    Good
    174
    170
    Moderate
    62
    41
    None
    4
    1
    Missing
    4
    0
    8. Secondary Outcome
    Title Haemostatic Effect of N8-GP When Used for Treatment of Bleeds, Assessed on a Four-point Scale for Haemostatic Response (Excellent, Good, Moderate and None): After Approximately 25 Months
    Description Haemostatic effect of N8-GP for treatment of bleeding episodes was assessed by 4-point response scale: none, moderate, good or excellent. Evaluation during trial was done by participant and/or parent(s)/caregiver within approximately 8 hours after a single injection as follows: Excellent: Abrupt pain relief and/or clear improvement in objective signs of bleeding within approximately 8 hrs after a single injection; Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hrs after a single injection, but possibly requiring more than one injection for complete resolution; Moderate: Probable or slight beneficial effect within approximately 8 hours after the first injection, but usually requiring more than one injection; None: No improvement, or worsening of symptoms.
    Time Frame After approximately 25 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of bleeds analysed.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 75 U/kg Prophylaxis Q7D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 3+ bleeding episodes during the last 6 months before entering the extension phase, were randomised to receive one single bolus dose of 75 U/kg BW of N8-GP. Participants received one single bolus dose of 75 U/kg BW of N8-GP administered IV every 7th day (Q7D). Based on the bleeding pattern, the investigator could change the dosing frequency from Q7D to Q4D, but not vice versa. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 61 12
    Measure Bleeding episodes 716 25 695
    Excellent
    330
    9
    406
    Good
    270
    11
    233
    Moderate
    98
    3
    55
    None
    4
    0
    1
    Missing
    14
    2
    0
    9. Secondary Outcome
    Title Haemostatic Effect of N8-GP When Used for Treatment of Bleeds, Assessed on a Four-point Scale for Haemostatic Response (Excellent, Good, Moderate and None): After Approximately 80 Months
    Description Haemostatic effect of N8-GP for treatment of bleeding episodes was assessed by 4-point response scale: none, moderate, good or excellent. Evaluation during trial was done by participant and/or parent(s)/caregiver within approximately 8 hours after a single injection as follows: Excellent: Abrupt pain relief and/or clear improvement in objective signs of bleeding within approximately 8 hrs after a single injection; Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hrs after a single injection, but possibly requiring more than one injection for complete resolution; Moderate: Probable or slight beneficial effect within approximately 8 hours after the first injection, but usually requiring more than one injection; None: No improvement, or worsening of symptoms.
    Time Frame After approximately 80 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of bleeds analysed.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 75 U/kg Prophylaxis Q7D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 3+ bleeding episodes during the last 6 months before entering the extension phase, were randomised to receive one single bolus dose of 75 U/kg BW of N8-GP. Participants received one single bolus dose of 75 U/kg BW of N8-GP administered IV every 7th day (Q7D). Based on the bleeding pattern, the investigator could change the dosing frequency from Q7D to Q4D, but not vice versa. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 61 12
    Measure Bleeding episodes 1312 176 1270
    Excellent
    600
    75
    859
    Good
    532
    65
    339
    Moderate
    153
    29
    71
    None
    6
    2
    1
    Missing
    21
    5
    0
    10. Secondary Outcome
    Title Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 19 Months
    Description The mean number of infusions of N8-GP used for treatment of a bleed from start to stop of a bleed was reported.
    Time Frame After approximately 19 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of infusions in respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 12
    Measure Infusions 436 532
    Mean (Standard Deviation) [Number of infusions]
    1.4
    (1.0)
    1.2
    (0.9)
    11. Secondary Outcome
    Title Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 25 Months
    Description The mean number of infusions of N8-GP used for treatment of a bleed from start to stop of a bleed was reported.
    Time Frame After approximately 25 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of infusions in respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 75 U/kg Prophylaxis Q7D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 3+ bleeding episodes during the last 6 months before entering the extension phase, were randomised to receive one single bolus dose of 75 U/kg BW of N8-GP. Participants received one single bolus dose of 75 U/kg BW of N8-GP administered IV every 7th day (Q7D). Based on the bleeding pattern, the investigator could change the dosing frequency from Q7D to Q4D, but not vice versa. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 61 12
    Measure Infusions 716 25 695
    Mean (Standard Deviation) [Number of infusions]
    1.4
    (1.3)
    1.3
    (0.6)
    1.2
    (0.8)
    12. Secondary Outcome
    Title Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 80 Months
    Description The mean number of infusions of N8-GP used for treatment of a bleed from start to stop of a bleed was reported.
    Time Frame After approximately 80 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of infusions in respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 75 U/kg Prophylaxis Q7D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 3+ bleeding episodes during the last 6 months before entering the extension phase, were randomised to receive one single bolus dose of 75 U/kg BW of N8-GP. Participants received one single bolus dose of 75 U/kg BW of N8-GP administered IV every 7th day (Q7D). Based on the bleeding pattern, the investigator could change the dosing frequency from Q7D to Q4D, but not vice versa. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 61 12
    Measure Infusions 1312 176 1270
    Mean (Standard Deviation) [Number of infusions]
    1.4
    (1.3)
    1.3
    (0.6)
    1.2
    (0.8)
    13. Secondary Outcome
    Title Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 19 Months
    Description The mean consumption of N8-GP (U/kg) used for treatment of a bleed from start to stop of a bleed was reported.
    Time Frame After approximately 19 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of bleeds analysed
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 12
    Measure Bleeding episodes 436 532
    Mean (Standard Deviation) [U/kg per bleed]
    64.6
    (48.8)
    41.0
    (35.1)
    14. Secondary Outcome
    Title Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 25 Months
    Description The mean consumption of N8-GP (U/kg) used for treatment of a bleed from start to stop of a bleed was reported.
    Time Frame After approximately 25 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of bleeds analysed.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 75 U/kg Prophylaxis Q7D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 3+ bleeding episodes during the last 6 months before entering the extension phase, were randomised to receive one single bolus dose of 75 U/kg BW of N8-GP. Participants received one single bolus dose of 75 U/kg BW of N8-GP administered IV every 7th day (Q7D). Based on the bleeding pattern, the investigator could change the dosing frequency from Q7D to Q4D, but not vice versa. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 61 12
    Measure Bleeding episodes 716 25 695
    Mean (Standard Deviation) [U/kg per bleed]
    67.8
    (72.9)
    78.2
    (37.8)
    39.3
    (32.4)
    15. Secondary Outcome
    Title Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 80 Months
    Description The mean consumption of N8-GP (U/kg) used for treatment of a bleed from start to stop of a bleed was reported.
    Time Frame After approximately 80 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of bleeds analysed.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 75 U/kg Prophylaxis Q7D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 3+ bleeding episodes during the last 6 months before entering the extension phase, were randomised to receive one single bolus dose of 75 U/kg BW of N8-GP. Participants received one single bolus dose of 75 U/kg BW of N8-GP administered IV every 7th day (Q7D). Based on the bleeding pattern, the investigator could change the dosing frequency from Q7D to Q4D, but not vice versa. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 61 12
    Measure Bleeding episodes 1310 175 1270
    Mean (Standard Deviation) [U/kg per bleed]
    68.1
    (60.0)
    88.7
    (72.4)
    37.5
    (38.0)
    16. Secondary Outcome
    Title Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 19 Months
    Description Number of infusions are presented as average dose used during propphylaxis and on-demand treatment.
    Time Frame After approximately 19 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of infusions used during prophylaxis and on-demand treatment.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 12
    Measure Infusions 436 532
    Mean (Standard Deviation) [U/kg]
    52.2
    (1.4)
    46.3
    (10.4)
    17. Secondary Outcome
    Title Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 25 Months
    Description Number of infusions are presented as average dose used during prophylaxis and on-demand treatment.
    Time Frame After approximately 25 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of infusions used during prophylaxis and on-demand treatment.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 75 U/kg Prophylaxis Q7D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 3+ bleeding episodes during the last 6 months before entering the extension phase, were randomised to receive one single bolus dose of 75 U/kg BW of N8-GP. Participants received one single bolus dose of 75 U/kg BW of N8-GP administered IV every 7th day (Q7D). Based on the bleeding pattern, the investigator could change the dosing frequency from Q7D to Q4D, but not vice versa. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 175 38 12
    Measure Infusions 22569 775 35
    Mean (Standard Deviation) [U/kg]
    52.2
    (1.9)
    77.2
    (3.2)
    44.8
    (11.4)
    18. Secondary Outcome
    Title Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 80 Months
    Description Number of infusions are presented as average dose used during prophylaxis and on-demand treatment.
    Time Frame After approximately 80 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of infusions used during prophylaxis and on-demand treatment.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 75 U/kg Prophylaxis Q7D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 3+ bleeding episodes during the last 6 months before entering the extension phase, were randomised to receive one single bolus dose of 75 U/kg BW of N8-GP. Participants received one single bolus dose of 75 U/kg BW of N8-GP administered IV every 7th day (Q7D). Based on the bleeding pattern, the investigator could change the dosing frequency from Q7D to Q4D, but not vice versa. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 61 12
    Measure Infusions 55896 6996 58
    Mean (Standard Deviation) [U/kg]
    52.2
    (1.5)
    77.1
    (3.2)
    37.5
    (13.0)
    19. Secondary Outcome
    Title Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 19 Months
    Description The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed (per month per participant) was reported.
    Time Frame After approximately 19 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 12
    Mean (Standard Deviation) [U/kg per month]
    403.8
    (53.8)
    129.2
    (71.8)
    20. Secondary Outcome
    Title Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 25 Months
    Description The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed (per month per participant) was reported.
    Time Frame After approximately 25 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 75 U/kg Prophylaxis Q7D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 3+ bleeding episodes during the last 6 months before entering the extension phase, were randomised to receive one single bolus dose of 75 U/kg BW of N8-GP. Participants received one single bolus dose of 75 U/kg BW of N8-GP administered IV every 7th day (Q7D). Based on the bleeding pattern, the investigator could change the dosing frequency from Q7D to Q4D, but not vice versa. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 61 12
    Mean (Standard Deviation) [U/kg per month]
    403.8
    (53.8)
    349.2
    (37.9)
    128.2
    (70.1)
    21. Secondary Outcome
    Title Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 80 Months
    Description The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed (per month per participant) was reported.
    Time Frame After approximately 80 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 75 U/kg Prophylaxis Q7D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 3+ bleeding episodes during the last 6 months before entering the extension phase, were randomised to receive one single bolus dose of 75 U/kg BW of N8-GP. Participants received one single bolus dose of 75 U/kg BW of N8-GP administered IV every 7th day (Q7D). Based on the bleeding pattern, the investigator could change the dosing frequency from Q7D to Q4D, but not vice versa. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 61 12
    Mean (Standard Deviation) [U/kg per month]
    402.4
    (52.4)
    353.5
    (32.9)
    130.2
    (69.2)
    22. Secondary Outcome
    Title Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 19 Months
    Description The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed (per year per participant) was reported.
    Time Frame After approximately 19 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 12
    Mean (Standard Deviation) [U/kg per year]
    4845
    (645)
    1550
    (861)
    23. Secondary Outcome
    Title Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 25 Months
    Description The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed (per year per participant) was reported.
    Time Frame After approximately 25 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 75 U/kg Prophylaxis Q7D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 3+ bleeding episodes during the last 6 months before entering the extension phase, were randomised to receive one single bolus dose of 75 U/kg BW of N8-GP. Participants received one single bolus dose of 75 U/kg BW of N8-GP administered IV every 7th day (Q7D). Based on the bleeding pattern, the investigator could change the dosing frequency from Q7D to Q4D, but not vice versa. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 61 12
    Mean (Standard Deviation) [U/kg per year]
    4846
    (645.3)
    4190
    (454.5)
    1538
    (840.6)
    24. Secondary Outcome
    Title Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 80 Months
    Description The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed (per year per participant) was reported.
    Time Frame After approximately 80 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 75 U/kg Prophylaxis Q7D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 3+ bleeding episodes during the last 6 months before entering the extension phase, were randomised to receive one single bolus dose of 75 U/kg BW of N8-GP. Participants received one single bolus dose of 75 U/kg BW of N8-GP administered IV every 7th day (Q7D). Based on the bleeding pattern, the investigator could change the dosing frequency from Q7D to Q4D, but not vice versa. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 61 12
    Mean (Standard Deviation) [U/kg per year]
    4829
    (628.8)
    4242
    (394.5)
    1562
    (830.3)
    25. Secondary Outcome
    Title Haemostatic Effect as Measured by Recovery and Trough Levels FVIII:C (in All Patients Receiving Prophylaxis Treatment): After Approximately 19 Months
    Description Recovery and trough levels of FVIII:C was reported for all participants at Visit 3 (Week 4) and end of main phase (approx. 19 months). The data was reported for all participants who received prophylaxis treatment. Chromogenic assay was performed with N8-GP product specific standard (PSS) as a calibrator.
    Time Frame After approximately 19 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm.
    Measure Participants 177
    Visit 2 Post-dose
    1.276
    (18.584)
    Visit 3 Pre-dose
    0.030
    (159.920)
    Visit 12 Post-dose
    1.359
    (18.156)
    Visit 13 Pre-dose
    0.034
    (188.891)
    26. Secondary Outcome
    Title Haemostatic Effect as Measured by Recovery and Trough Levels FVIII:C (in All Patients Receiving Prophylaxis Treatment): After Approximately 25 Months
    Description Recovery and trough levels of FVIII:C was reported for all participants at the end of extension phase 1 study (approx. 25 months). The data was reported for all participants who received prophylaxis treatment. Chromogenic assay was performed with N8-GP product specific standard (PSS) as a calibrator.
    Time Frame After approximately 25 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 75 U/kg Prophylaxis Q7D
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 3+ bleeding episodes during the last 6 months before entering the extension phase, were randomised to receive one single bolus dose of 75 U/kg BW of N8-GP. Participants received one single bolus dose of 75 U/kg BW of N8-GP administered IV every 7th day (Q7D). Based on the bleeding pattern, the investigator could change the dosing frequency from Q7D to Q4D, but not vice versa. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm.
    Measure Participants 177 61
    Visit 16 Post-dose
    1.329
    (13.357)
    1.868
    (31.919)
    Visit 17 Pre-dose
    0.028
    (205.652)
    0.015
    (272.494)
    27. Secondary Outcome
    Title Haemostatic Effect as Measured by Recovery and Trough Levels FVIII:C (in All Patients Receiving Prophylaxis Treatment): After Approximately 80 Months
    Description Since patients were allowed to change prophylaxis regimen at any time during the extension phase part 2, and since the visit intervals were different for the 2 prophylaxis treatment regimens (Q4D and Q7D), FVIII activity data are reported only as incremental recovery at this timepoint.
    Time Frame After approximately 80 months

    Outcome Measure Data

    Analysis Population Description
    Data were not collected for this endpoint.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 75 U/kg Prophylaxis Q7D
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 0 0
    28. Secondary Outcome
    Title Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Patients 13-16 Years Old) After Approx 19 and 25 Months
    Description Reported results are change from baseline (Month 0) measured at end of main phase (approx Month 19) and change from Month 19 at end of Extension 1 (approx Month 25) of the study. The 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.
    Time Frame After approx 19 and 25 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data. No participants from the 13-16 years age group received on-demand treatment. Thus on-demand treatment group is not applicable for this endpoint.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D
    Arm/Group Description Participants from the N8-GP 50 U/kg Q4D group were included in this arm.
    Measure Participants 16
    Approx month 19 (Change from baseline)
    -0.1
    (12.4)
    Approx month 25 (Change from month 19)
    0.8
    (4.5)
    29. Secondary Outcome
    Title Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Patients 13-16 Years Old): After Approx 80 Months
    Description Reported results are change from visit 1 (Month 0) upto end of Extension phase 2 (Month 80) of the study. Time intervals are assigned based on time after first dose. It was possible that a participant could answer more than one questionnaire in a single time interval. The 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. Overall number of units analysed = Maximum no of questionnaires answered by participants for this endpoint. Overall number of participants analysed = maximum number of participants contributed to the analysis for each time point.
    Time Frame 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. No participants from the 13-16 years age group received on-demand treatment. Thus on-demand treatment group is not applicable for this endpoint.
    Arm/Group Title N8-GP Prophylaxis
    Arm/Group Description Participants from both the 50 U/kg Q4D and the 75 U/kg Q7D prophylaxis arms were included in this arm.
    Measure Participants 11
    Measure Number of questionnaires 11
    2 to <3 years (Change from baseline)
    2.7
    (15.9)
    3 to <4 years (Change from baseline)
    -0.9
    (11.6)
    4 to <5 years (Change from baseline)
    2.6
    (15.8)
    5 to <6 years (Change from baseline)
    2.1
    (11.7)
    6 to <7 years (Change from baseline)
    -0.3
    (0)
    30. Secondary Outcome
    Title Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Parents of Patients 13-16 Years Old): After Approx 19 and 25 Months
    Description Reported results are change from baseline (Month 0) measured at end of main phase (Month 19) and change from Month 19 to end of Extension 1 (Month 25) of the study. The questionnaire was completed by parents of the patients in the 13-16 years old age bracket. The 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.
    Time Frame After approx 19 and 25 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data. No participants from the 13-16 years age group received on-demand treatment. Thus on-demand treatment group is not applicable for this endpoint.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D
    Arm/Group Description Participants from the N8-GP 50 U/kg Q4D group were included in this arm.
    Measure Participants 16
    After approximately 19 months
    -4.0
    (13.1)
    After approximately 25 months
    1.8
    (8.3)
    31. Secondary Outcome
    Title Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Parents of Patients 13-16 Years Old): After Approx 80 Months
    Description Reported results are change from visit 1 (Month 0) upto end of Extension phase 2 (Month 80) of the study. The questionnaire was completed by parents of the patients in the 13-16 years old age bracket. Time intervals are assigned based on time after first dose. It was possible that a participant could answer more than one questionnaire in a single time interval. The 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. Overall number of units analysed = Maximum no of questionnaires answered by participants for this endpoint. Overall number of participants analysed = maximum number of participants contributed to the analysis for each time point.
    Time Frame 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. No participants from the 13-16 years age group received on-demand treatment. Thus on-demand treatment group is not applicable for this endpoint.
    Arm/Group Title N8-GP Prophylaxis
    Arm/Group Description Participants from both the 50 U/kg Q4D and the 75 U/kg Q7D prophylaxis arms were included in this arm.
    Measure Participants 9
    Measure Number of questionnaires 8
    2 to <3 years (Change from baseline)
    1.5
    (2.1)
    3 to <4 years (Change from baseline)
    -8.1
    (7.0)
    4 to <5 years (Change from baseline)
    -7.9
    (13.8)
    5 to <6 years (Change from baseline)
    1.6
    (11.4)
    6 to <7 years (Change from baseline)
    10.7
    (0)
    32. Secondary Outcome
    Title Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approx 19 and 25 Months
    Description Reported results are change from baseline (Month 0) measured at end of main phase (Month 19) and change from Month 19 to end of Extension 1 (Month 25) of the study. The HAEM-A-QOL (for adults (>=17 years)) assessment included questions on 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.
    Time Frame After approx 19 and 25 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 157 12
    Week 76 (Change from baseline)
    -2.3
    (8.9)
    -3.1
    (10.3)
    Week 140 (Change from week 76)
    0.7
    (8.0)
    -0.6
    (4.9)
    33. Secondary Outcome
    Title Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approximately 80 Months
    Description Reported results are change from visit 1 (Month 0) upto end of Extension phase 2 (Month 80) of the study. Time intervals are assigned based on time after first dose. It was possible that a participant could answer more than one questionnaire in a single time interval. Overall number of units analysed = Maximum no of questionnaires answered by participants for this endpoint. Overall number of participants analysed = maximum number of participants contributed to the analysis for each time point. The HAEM-A-QOL (for adults (>=17 years)) 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. Scores range for each question was 0-100, with a lower score indicating better quality of life related to haemophilia.
    Time Frame 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP Prophylaxis N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants from both the 50 U/kg Q4D and the 75 U/kg Q7D prophylaxis arms were included in this arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5
    Measure Participants 122 5
    Measure Number of questionnaires 157 5
    1 to <2 years (Change from baseline)
    -6.6
    (6.7)
    2 to <3 years (Change from baseline)
    -2.6
    (10.3)
    -10.7
    (8.7)
    3 to <4 years (Change from baseline)
    -2.3
    (8.9)
    -5.8
    (12.2)
    4 to <5 years (Change from baseline)
    -3.1
    (10.4)
    -2.5
    (19.5)
    5 to <6 years (Change from baseline)
    -3.1
    (11.2)
    -1.7
    (2.8)
    6 to <7 years (Change from baseline)
    -3.5
    (9.0)
    -7.8
    (8.6)
    34. Secondary Outcome
    Title Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months
    Description Reported results are change from baseline (Month 0) measured at end of main phase (Month 19) and change from Month 19 to end of Extension 1 (Month 25) of the study. The HEMO-SAT (Hematology-satisfaction) assessment included questions on treatment aspects including Ease and convenience, efficacy, burden, specialist/nurses, centre/hospital, general satisfaction (reported by patients). 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. A decrease in the score would mean improvement.
    Time Frame After approx 19 and 25 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 157 12
    Ease & convenience (Change - Approx 19 months)
    -0.4
    (13.8)
    -4.5
    (11.5)
    Ease & convenience (Change - Approx 25 months)
    0.3
    (11.7)
    -6.3
    (6.9)
    Efficacy (Change - Approx 19 months)
    -6.3
    (15.6)
    -11.3
    (11.1)
    Efficacy (Change - Approx 25 months)
    -0.2
    (11.0)
    0.0
    (5.9)
    Burden (Change - Approx 19 months)
    -2.2
    (15.8)
    -5.0
    (18.8)
    Burden (Change - Approx 25 months)
    -0.9
    (11.3)
    0.0
    (6.3)
    Speciaist/nurses (Change - approx 19 months)
    -2.9
    (11.7)
    -4.5
    (8.3)
    Speciaist/nurses (Change - approx 25 months)
    1.8
    (9.1)
    0.0
    (8.1)
    Centre/hospital (Change - approx 19 months)
    -2.2
    (11.9)
    -3.6
    (7.8)
    Centre/hospital (Change - approx 25 months)
    1.0
    (8.1)
    4.2
    (10.7)
    Gen. satisfaction (Change - approx 19 months)
    -2.9
    (15.4)
    -3.4
    (11.3)
    Gen. satisfaction (Change - approx 25 months)
    -1.1
    (9.4)
    2.1
    (5.1)
    35. Secondary Outcome
    Title Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months
    Description Reported results are change from visit 1 (Month 0) upto end of Extension phase 2 (Month 80) of the study. Time intervals are assigned based on time after first dose. It was possible that a participant could answer more than one questionnaire in a single time interval. Overall number of units analysed = Maximum no of questionnaires answered by participants for this endpoint. Overall number of participants analysed = maximum number of participants contributed to the analysis for each time point. The HEMO-SAT assessment included questions on treatment aspects including Ease and convenience, efficacy, burden, specialist/nurses, centre/hospital, general satisfaction (reported by patients). 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. A decrease in the score would mean improvement.
    Time Frame 1-<2 yrs, 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial.
    Arm/Group Title N8-GP Prophylaxis N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants from both the 50 U/kg Q4D and the 75 U/kg Q7D prophylaxis arms were included in this arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 122 5
    Measure Number of questionnaires 151 5
    Ease & convenience 1 to <2 years
    -2.2
    (12.7)
    Ease & convenience 2 to <3 years
    -2.4
    (14.4)
    -23.8
    (12.4)
    Ease & convenience 3 to <4 years
    -3.7
    (13.6)
    -10.5
    (18.3)
    Ease & convenience 4 to <5 years
    -3.7
    (13.6)
    -4.4
    (34.4)
    Ease & convenience 5 to <6 years
    -3.3
    (13.7)
    -16.7
    (11.8)
    Ease & convenience 6 to <7 years
    -7.2
    (12.4)
    -5.6
    (8.3)
    Efficacy 1 to <2 years
    -1.9
    (9.3)
    Efficacy 2 to <3 years
    -7.1
    (14.9)
    -16.7
    (5.9)
    Efficacy 3 to <4 years
    -7.2
    (13.6)
    -17.5
    (14.3)
    Efficacy 4 to <5 years
    -9.5
    (16.4)
    2.1
    (35.8)
    Efficacy 5 to <6 years
    -7.4
    (14.4)
    -16.7
    (20.8)
    Efficacy 6 to <7 years
    -13.2
    (21.8)
    -3.1
    (13.8)
    Burden 1 to <2 years
    0.7
    (13.4)
    Burden 2 to <3 years
    -3.6
    (16.9)
    -21.9
    (4.4)
    Burden 3 to <4 years
    -5.0
    (15.1)
    -17.5
    (14.9)
    Burden 4 to <5 years
    -4.9
    (16.9)
    -3.1
    (28.2)
    Burden 5 to <6 years
    -4.9
    (13.5)
    -18.8
    (10.8)
    Burden 6 to <7 years
    -10.1
    (19.1)
    -4.7
    (9.4)
    Specialist/nurses 1 to <2 years
    -2.0
    (12.8)
    Specialist/nurses 2 to <3 years
    -2.8
    (11.4)
    0.0
    (0.0)
    Specialist/nurses 3 to <4 years
    -2.3
    (10.9)
    0.7
    (8.9)
    Specialist/nurses 4 to <5 years
    -1.4
    (11.4)
    21.4
    (47.7)
    Specialist/nurses 5 to <6 years
    -0.8
    (9.7)
    -11.9
    (8.2)
    Specialist/nurses 6 to <7 years
    -0.2
    (15.4)
    -6.3
    (7.4)
    Centre/hospital 1 to <2 years
    -5.0
    (12.0)
    Centre/hospital 2 to <3 years
    -2.9
    (11.9)
    0.0
    (0.0)
    Centre/hospital 3 to <4 years
    -1.3
    (10.5)
    3.0
    (4.5)
    Centre/hospital 4 to <5 years
    -1.1
    (12.5)
    26.3
    (43.1)
    Centre/hospital 5 to <6 years
    -1.0
    (9.7)
    1.7
    (29.3)
    Centre/hospital 6 to <7 years
    1.2
    (17.7)
    -8.8
    (6.3)
    Gen. satisfaction 1 to <2 years
    -1.4
    (11.6)
    Gen. satisfaction 2 to <3 years
    -4.1
    (15.2)
    -6.3
    (8.8)
    Gen. satisfaction 3 to <4 years
    -2.8
    (10.7)
    -17.5
    (14.3)
    Gen. satisfaction 4 to <5 years
    -5.0
    (14.4)
    0.0
    (35.4)
    Gen. satisfaction 5 to <6 years
    -2.2
    (12.2)
    -20.8
    (7.2)
    Gen. satisfaction 6 to <7 years
    -5.4
    (19.6)
    -18.8
    (16.1)
    36. Secondary Outcome
    Title Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): After Approx 19 and 25 Months
    Description The summary of change was based on individual changes observed at visit 13 (approximately 19 months) from visit 2a pre-dose (Month 0). The HEMO-SAT assessment included questions on treatment aspects including Ease and convenience, efficacy, burden, specialist/nurses, centre/hospital, general satisfaction (reported by parents). 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. A decrease in the score would mean improvement.
    Time Frame After approx 19 and 25 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm.
    Measure Participants 16
    Ease & convenience - baseline (Week 0)
    27.8
    (15.5)
    Ease & convenience (Change - Approx 19 months)
    0.4
    (3.3)
    Ease & convenience (Change - Approx 25 months)
    -6.3
    (8.1)
    Efficacy - baseline (Week 0)
    17.9
    (12.3)
    Efficacy (Change - Approx 19 months)
    -5.2
    (2.1)
    Efficacy (Change - Approx 25 months)
    2.1
    (5.7)
    Burden- baseline (Week 0)
    23.8
    (14.4)
    Burden (Change - Approx 19 months)
    -10.9
    (12.9)
    Burden (Change - Approx 25 months)
    -4.2
    (11.6)
    Specialist/nurses (Week 0)
    7.1
    (10.9)
    Speciaist/nurses (Change - approx 19 months)
    0.0
    (0.0)
    Speciaist/nurses (Change - approx 25 months)
    0.6
    (1.5)
    Centre/Hospital (Week 0)
    10.5
    (11.7)
    Centre/hospital (Change - approx 19 months)
    -3.7
    (4.8)
    Centre/hospital (Change - approx 25 months)
    -0.8
    (2.0)
    Gen. satisfaction (Week 0)
    8.8
    (11.9)
    Gen. satisfaction (Change - approx 19 months)
    0.0
    (0.0)
    Gen. satisfaction (Change - approx 25 months)
    0.0
    (0.0)
    37. Secondary Outcome
    Title Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months
    Description Reported results are from Visit 1 (Month 0), and change from visit 1 upto end of Extension phase 2 (Month 80) of the study. Time intervals are assigned based on time after first dose. It was possible that a participant could answer more than one questionnaire in a single time interval. Overall number of units analysed = Max. no of questionnaires answered by participants for this endpoint. Overall number of participants analysed = max. number of participants contributed to the analysis for each time point. The HEMO-SAT assessment included questions on treatment aspects including Ease and convenience, efficacy, burden, specialist/nurses, centre/hospital, 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. A decrease in the score would mean improvement.
    Time Frame 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial.
    Arm/Group Title N8-GP Prophylaxis
    Arm/Group Description Participants from both the 50 U/kg Q4D and the 75 U/kg Q7D prophylaxis arms were included in this arm.
    Measure Participants 11
    Measure Number of questionnaires 8
    Ease & convenience 2 to <3 years
    -0.6
    (6.8)
    Ease & convenience 3 to <4 years
    9.1
    (0)
    Ease & convenience 4 to <5 years
    -5.3
    (14.1)
    Ease & convenience 5 to <6 years
    -3.6
    (13.5)
    Ease & convenience 6 to <7 years
    0.0
    (0.0)
    Efficacy 2 to <3 years
    -6.3
    (2.4)
    Efficacy 3 to <4 years
    -8.3
    (0.0)
    Efficacy 4 to <5 years
    -6.3
    (4.4)
    Efficacy 5 to <6 years
    3.3
    (17.0)
    Efficacy 6 to <7 years
    -4.2
    (0)
    Burden 2 to <3 years
    -20.3
    (15.6)
    Burden 3 to <4 years
    -25.0
    (0)
    Burden 4 to <5 years
    -6.3
    (26.2)
    Burden 5 to <6 years
    2.5
    (15.1)
    Burden 6 to <7 years
    -31.3
    (0)
    Specialist/nurses 2 to <3 years
    -3.6
    (7.1)
    Specialist/nurses 3 to <4 years
    0.0
    (0.0)
    Specialist/nurses 4 to <5 years
    -6.5
    (11.8)
    Specialist/nurses 5 to <6 years
    3.6
    (17.5)
    Specialist/nurses 6 to <7 years
    0.0
    (0.0)
    Centre/hospital 2 to <3 years
    -3.7
    (4.8)
    Centre/hospital 3 to <4 years
    -5.0
    (0.0)
    Centre/hospital 4 to <5 years
    -8.3
    (8.8)
    Centre/hospital 5 to <6 years
    -3.0
    (14.4)
    Centre/hospital 6 to <7 years
    0.0
    (0.0)
    Gen. satisfaction 2 to <3 years
    -9.4
    (12.0)
    Gen. satisfaction 3 to <4 years
    -12.5
    (0)
    Gen. satisfaction 4 to <5 years
    -6.3
    (10.5)
    Gen. satisfaction 5 to <6 years
    5.0
    (14.3)
    Gen. satisfaction 6 to <7 years
    0.0
    (0.0)
    38. Secondary Outcome
    Title Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approx 19 and 25 Months
    Description Reported results are change from baseline (Month 0) measured at end of main phase (Month 19) and change from Month 19 to end of Extension 1 (Month 25) of the study. The European quality of life visual analogue scale (EQ5D-VAS) records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement. EQ-5D-VAS: range 0 to 100. A higher score indicates better self reported health status. A positive change indicates an improvement.
    Time Frame After approx 19 and 25 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 173 12
    Week 0 (Baseline)
    76.5
    (17.9)
    74.5
    (13.1)
    Week 76 (Change from baseline)
    2.0
    (11.1)
    4.1
    (7.2)
    Week 140 (Change from week 76)
    -0.8
    (11.8)
    2.7
    (11.0)
    39. Secondary Outcome
    Title Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approximately 80 Months
    Description Reported results are change from visit 1 (Month 0) upto end of Extension phase 2 (Month 80) of the study. Time intervals are assigned based on time after first dose. It was possible that a participant could answer more than one questionnaire in a single time interval. Overall number of units analysed = Maximum no of questionnaires answered by participants for this endpoint. Overall number of participants analysed = maximum number of participants contributed to the analysis for each time point. The EQ5D-VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement. EQ-5D-VAS: range 0 to 100. A higher score indicates better self reported health status. A positive change indicates an improvement.
    Time Frame 1-<2 yrs, 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial.
    Arm/Group Title N8-GP Prophylaxis N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants from both the 50 U/kg Q4D and the 75 U/kg Q7D prophylaxis arms were included in this arm. Participants received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 133 5
    Measure Number of questionnaires 167 5
    1 to <2 years (Change from baseline)
    4.9
    (8.2)
    2 to <3 years (Change from baseline)
    2.6
    (13.3)
    9.5
    (6.4)
    3 to <4 years (Change from baseline)
    3.0
    (13.5)
    7.3
    (7.0)
    4 to <5 years (Change from baseline)
    1.0
    (15.8)
    11.0
    (9.6)
    5 to <6 years (Change from baseline)
    2.2
    (13.2)
    15.0
    (21.2)
    6 to <7 years (Change from baseline)
    7.5
    (13.6)
    16.3
    (12.1)
    40. Secondary Outcome
    Title Patient Reported Outcomes - Change in European Quality of Life Utility Index: After Approx 19 and 25 Months
    Description Reported results are change from baseline (Month 0) measured at end of main phase (Month 19) and change from Month 19 to end of Extension 1 (Month 25) of the study. The European quality of life utility index comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels where 1 indicates better health state (no problems) and 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; a positive change indicates an improvement.
    Time Frame After approx 19 and 25 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 173 12
    Month 19 (Change from baseline)
    0.011
    (0.184)
    -0.028
    (0.047)
    Month 25 (Change from Month 19)
    -0.025
    (0.174)
    -0.028
    (0.093)
    41. Secondary Outcome
    Title Patient Reported Outcomes - Change in European Quality of Life Utility Index Scores: After Approximately 80 Months
    Description Reported results are change from visit 1 (Month 0) upto end of Extension phase 2 (Month 80) of the study. Time intervals are assigned based on time after first dose. It is possible that a patient answers more than one questionnaire in a single time interval. Overall units analysed = Max no. of questionnaires answered by participants for this endpoint. Overall no. of participants analysed = max no. of participants analysed at each time point. This utility index has 5 dimensions: mobility, self-care, usual activities, pain/discomfort & anxiety/depression. Each dimension has 3 levels where 1 indicates better health state (no problems) and 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; a positive change indicates an improvement.
    Time Frame 1-<2 yrs, 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial.
    Arm/Group Title N8-GP Prophylaxis N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants from both the 50 U/kg Q4D and the 75 U/kg Q7D prophylaxis arms were included in this arm. Participants received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 133 5
    Measure Number of questionnaires 164 5
    1 to <2 years (Change from baseline)
    0.052
    (0.252)
    2 to <3 years (Change from baseline)
    -0.008
    (0.159)
    0.000
    (0.000)
    3 to <4 years (Change from baseline)
    0.021
    (0.193)
    0.000
    (0.000)
    4 to <5 years (Change from baseline)
    0.000
    (0.165)
    -0.001
    (0.057)
    5 to <6 years (Change from baseline)
    0.011
    (0.178)
    0.000
    (0.000)
    6 to <7 years (Change from baseline)
    -0.062
    (0.163)
    0.000
    (0.000)
    42. Secondary Outcome
    Title Number of Hospital Admissions During the Trial
    Description The number of hospital admissions that took place in the study were reported.
    Time Frame After approx 19, 25 and 80 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP Prophylaxis N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants from both the N8-GP 50 U/kg Q4D and N8-GP 75 U/kg Q7D groups were included in this arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 175 12
    Measure Number of hospital admissions 110 12
    0
    49
    8
    1
    3
    0
    2
    0
    0
    0
    84
    8
    1
    4
    2
    2
    1
    0
    0
    20
    2
    1
    1
    0
    2
    0
    0
    43. Secondary Outcome
    Title Number of Days at the Hospital During the Trial
    Description The mean number of days that participants spent at the hospital during the study were reported.
    Time Frame After approx 19, 25 and 80 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP Prophylaxis N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants from both the N8-GP 50 U/kg Q4D and N8-GP 75 U/kg Q7D groups were included in this arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 12
    After approximately 19 months
    0.1
    (0.4)
    0.0
    (0.0)
    After approximately 25 months
    0.5
    (3.8)
    0.7
    (1.6)
    Month 25 to 80
    0.5
    (2.4)
    0.0
    (0.0)
    44. Secondary Outcome
    Title Number of Admissions to the Emergency Room (ER) During the Trial
    Description The number of admissions to the ER that took place in the study were reported for each group.
    Time Frame After approx 19, 25 and 80 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP Prophylaxis N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants from both the N8-GP 50 U/kg Q4D and N8-GP 75 U/kg Q7D groups were included in this arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 175 12
    Measure ER admissions 110 12
    0
    49
    8
    1
    1
    0
    2
    2
    0
    4
    0
    0
    0
    84
    8
    1
    2
    1
    2
    2
    1
    4
    1
    0
    0
    17
    2
    1
    4
    0
    2
    0
    0
    4
    0
    0
    45. Secondary Outcome
    Title Number of Days Missing School or Work
    Description The mean number of days that participants missed to go to school or work were reported.
    Time Frame Approx 19, 25 and 80 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP Prophylaxis N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants from both the N8-GP 50 U/kg Q4D and N8-GP 75 U/kg Q7D groups were included in this arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 12
    After approximately 19 months
    0.5
    (1.6)
    6.7
    (16.9)
    After approximately 25 months
    0.8
    (2.0)
    6.8
    (16.9)
    Month 25 to 80
    2.6
    (14.4)
    0.3
    (0.4)
    46. Secondary Outcome
    Title Number of Days Using Mobility Aid
    Description The mean number of days that participants used any aids for mobility during the study were reported.
    Time Frame Approx 19, 25 and 80 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP Prophylaxis N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants from both the N8-GP 50 U/kg Q4D and N8-GP 75 U/kg Q7D groups were included in this arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 12
    After approximately 24 months
    4.4
    (26.2)
    11.1
    (34.7)
    After approximately 36 months
    7.0
    (42.7)
    5.8
    (15.9)
    Month 25 to 80
    1.0
    (4.6)
    0.5
    (0.7)
    47. Secondary Outcome
    Title Number of Participants Using Pain Medication
    Description The number of participants using pain medication during the main plus extension phase 1 of the study (approximately 25 months) and during extension phase 2(approximately 80 months) were reported.
    Time Frame After approx 25 and 80 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP Prophylaxis N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants in this arm included participants from both the Q4D and the Q7D groups Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 12
    Yes
    19
    10.9%
    2
    16.7%
    No
    39
    22.4%
    5
    41.7%
    Yes
    5
    2.9%
    1
    8.3%
    No
    13
    7.5%
    0
    0%
    48. Secondary Outcome
    Title Number of Bleeds Using Pain Medication
    Description The mean number of bleeds using pain medication in the main phase of the study (approximately 19 months) were reported.
    Time Frame After approx 19 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D: N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 12
    Mean (Standard Deviation) [Number of bleeds]
    0.1
    (0.4)
    0.5
    (1.4)
    49. Secondary Outcome
    Title Number of Adverse Events Reported During the Trial Period: After Approximately 19 Months
    Description All presented adverse events (AEs) are treatment-emergent. A treatment-emergent adverse event was defined as an event with onset after first N8-GP administration.
    Time Frame After approx 19 months

    Outcome Measure Data

    Analysis Population Description
    Results are based on the SAS. SAS comprised all participants exposed to N8-GP in this trial.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 175 12
    Number [Number of adverse events]
    423
    51
    50. Secondary Outcome
    Title Number of Adverse Events Reported During the Trial Period: After Approximately 25 Months
    Description All presented adverse events (AEs) are treatment-emergent. A treatment-emergent adverse event was defined as an event with onset after first N8-GP administration.
    Time Frame After approx. 25 months

    Outcome Measure Data

    Analysis Population Description
    Results are based on the SAS. SAS comprised all participants exposed to N8-GP in this trial.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 75 U/kg Prophylaxis Q7D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 3+ bleeding episodes during the last 6 months before entering the extension phase, were randomised to receive one single bolus dose of 75 U/kg BW of N8-GP. Participants received one single bolus dose of 75 U/kg BW of N8-GP administered IV every 7th day (Q7D). Based on the bleeding pattern, the investigator could change the dosing frequency from Q7D to Q4D, but not vice versa. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 175 38 12
    Number [Number of adverse events]
    701
    71
    75
    51. Secondary Outcome
    Title Number of Adverse Events Reported During the Trial Period: After Approximately 80 Months
    Description The number of adverse events observed during the study after approximately 80 months was reported.
    Time Frame After approximately 80 months

    Outcome Measure Data

    Analysis Population Description
    Results are based on the SAS. SAS comprised all participants exposed to N8-GP in this trial.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 75 U/kg Prophylaxis Q7D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 3+ bleeding episodes during the last 6 months before entering the extension phase, were randomised to receive one single bolus dose of 75 U/kg BW of N8-GP. Participants received one single bolus dose of 75 U/kg BW of N8-GP administered IV every 7th day (Q7D). Based on the bleeding pattern, the investigator could change the dosing frequency from Q7D to Q4D, but not vice versa. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 61 12
    Number [Number of adverse events]
    1326
    369
    132
    52. Secondary Outcome
    Title Number of Serious Adverse Events Reported During the Trial Period: After Approximately 19 Months
    Description All presented serious adverse events (SAEs) are treatment-emergent. A treatment-emergent adverse event was defined as an event with onset after first N8-GP administration.
    Time Frame After approximately 19 months

    Outcome Measure Data

    Analysis Population Description
    Results are based on the SAS. SAS comprised all participants exposed to N8-GP in this trial.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 175 12
    Number [Number of serious adverse events]
    13
    4
    53. Secondary Outcome
    Title Number of Serious Adverse Events Reported During the Trial Period: After Approximately 25 Months
    Description All presented serious adverse events (SAEs) are treatment-emergent. A treatment-emergent adverse event was defined as an event with onset after first N8-GP administration.
    Time Frame After approximately 25 months

    Outcome Measure Data

    Analysis Population Description
    Results are based on the SAS. SAS comprised all participants exposed to N8-GP in this trial.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 75 U/kg Prophylaxis Q7D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 3+ bleeding episodes during the last 6 months before entering the extension phase, were randomised to receive one single bolus dose of 75 U/kg BW of N8-GP. Participants received one single bolus dose of 75 U/kg BW of N8-GP administered IV every 7th day (Q7D). Based on the bleeding pattern, the investigator could change the dosing frequency from Q7D to Q4D, but not vice versa. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 175 61 12
    Number [Number of serious adverse events]
    27
    1
    4
    54. Secondary Outcome
    Title Number of Serious Adverse Events Reported During the Trial Period: After Approximately 80 Months
    Description All presented serious adverse events (SAEs) are treatment-emergent. A treatment-emergent adverse event was defined as an event with onset after first N8-GP administration.
    Time Frame After approximately 80 months

    Outcome Measure Data

    Analysis Population Description
    Results are based on the SAS. SAS comprised all participants exposed to N8-GP in this trial.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 75 U/kg Prophylaxis Q7D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 3+ bleeding episodes during the last 6 months before entering the extension phase, were randomised to receive one single bolus dose of 75 U/kg BW of N8-GP. Participants received one single bolus dose of 75 U/kg BW of N8-GP administered IV every 7th day (Q7D). Based on the bleeding pattern, the investigator could change the dosing frequency from Q7D to Q4D, but not vice versa. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 61 12
    Number [Number of serious adverse events]
    39
    16
    8
    55. Secondary Outcome
    Title Change in Blood Pressure: After Approximately 19 Months
    Description The mean change in the systolic and diastolic blood pressure values of participants was reported. The summary of change was based on individual changes observed at visit 13 (approximately 19 months) from visit 2a pre-dose (Month 0).
    Time Frame After approximately 19 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the SAS. SAS comprised all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 12
    Systolic blood pressure
    6.8
    (9.5)
    1.3
    (20.5)
    Diastolic blood pressure
    3.3
    (8.9)
    9.0
    (5.2)
    56. Secondary Outcome
    Title Change in Blood Pressure: After Approximately 25 Months
    Description The mean change in the systolic and diastolic blood pressure values of participants was reported. The summary of change was based on individual changes observed at visit 17 (approximately month 25) from visit 13 (approximately month 19).
    Time Frame After approximately 19 and 25 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the SAS. SAS comprised all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 12
    Systolic blood pressure
    -1.337
    (13.1)
    -6.000
    (9.5)
    Diastolic blood pressure
    0.337
    (10.8)
    2.000
    (5.9)
    57. Secondary Outcome
    Title Change in Blood Pressure: After Approximately 80 Months
    Description Change in the blood pressure was not calculated in the extension phase 2 of the study since participants were allowed to change from Q4D to Q7D and vice versa.
    Time Frame After approximately 80 months

    Outcome Measure Data

    Analysis Population Description
    Data were not collected for this outcome measure.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 0 0
    58. Secondary Outcome
    Title Change in Pulse: After Approximately 19 Months
    Description The mean change in the pulse values of participants was reported. The summary of change was based on individual changes observed at visit 13 (approximately 19 months) from visit 2a pre-dose (Month 0).
    Time Frame After approximately 19 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the SAS. SAS comprised all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants in this arm received one single bolus dose of 50 U/kg BW of N8-GP administered intravenously (IV) every 4th day (96 hours) or twice weekly (investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 12
    Mean (Standard Deviation) [Beats per min]
    5.3
    (11.2)
    10.3
    (4.6)
    59. Secondary Outcome
    Title Change in Pulse: After Approximately 25 Months
    Description The mean change in the pulse values of participants was reported. The summary of change was based on individual changes observed at visit 17 (approximately month 25) from visit 13 (approximately month 19).
    Time Frame After approximately 25 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the SAS. SAS comprised all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 12
    Mean (Standard Deviation) [Beats per min]
    -0.644
    (10.7)
    3.143
    (8.2)
    60. Secondary Outcome
    Title Change in Pulse: After Approximately 80 Months
    Description Change in pulse was not calculated in the extension phase 2 of the study since participants were allowed to change from Q4D to Q7D and vice versa.
    Time Frame After approximately 80 months

    Outcome Measure Data

    Analysis Population Description
    Data were not collected for this outcome measure.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 0 0
    61. Secondary Outcome
    Title Change in Body Temperature: After Approximately 19 Months
    Description The mean change in the body temperature values of participants was reported. The summary of change was based on individual changes observed at visit 13 (approximately 19 months) from visit 2a pre-dose (Month 0).
    Time Frame After approximately 19 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the SAS. SAS comprised all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 12
    Mean (Standard Deviation) [Degree celcius]
    0.0
    (0.4)
    -0.1
    (0.2)
    62. Secondary Outcome
    Title Change in Body Temperature: After Approximately 25 Months
    Description The mean change in the body temperature (C) values of participants was reported. The summary of change was based on individual changes observed at visit 17 (approximately month 25) from visit 13 (approximately month 19).
    Time Frame After approximately 25 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the SAS. SAS comprised all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 12
    Mean (Standard Deviation) [Degree celcius]
    -0.079
    (0.3)
    -0.086
    (0.6)
    63. Secondary Outcome
    Title Change in Body Temperature: After Approximately 80 Months
    Description Change in body temperature was not calculated in the extension phase 2 of the study since participants were allowed to change from Q4D to Q7D and vice versa.
    Time Frame After approximately 80 months

    Outcome Measure Data

    Analysis Population Description
    Data were not collected for this outcome measure.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5
    Measure Participants 0 0
    64. Secondary Outcome
    Title Change in Respiratory Rate: After Approximately 19 Months
    Description The mean change in the respiratory rate values of participants was reported. The summary of change was based on individual changes observed at visit 13 (approximately 19 months) from visit 2a pre-dose (Month 0).
    Time Frame After approximately 19 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the SAS. SAS comprised all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 12
    Mean (Standard Deviation) [Breaths/min]
    -0.2
    (1.9)
    -2.3
    (2.1)
    65. Secondary Outcome
    Title Change in Respiratory Rate: After Approximately 25 Months
    Description The mean change in the respiratory rate (breaths/min) values of participants was reported. The summary of change was based on individual changes observed at visit 17 (approximately month 25) from visit 13 (approximately month 19).
    Time Frame After approximately 25 months

    Outcome Measure Data

    Analysis Population Description
    Results were based on the SAS. SAS comprised all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants in this arm received one single bolus dose of 50 U/kg BW of N8-GP administered intravenously (IV) every 4th day (96 hours) or twice weekly (investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 177 12
    Mean (Standard Deviation) [Breaths/min]
    -0.067
    (2.1)
    -0.857
    (2.5)
    66. Secondary Outcome
    Title Change in Respiratory Rate: After Approximately 80 Months
    Description Change in respiratory rate was not calculated in the extension phase 2 of the study since participants were allowed to change from Q4D to Q7D and vice versa.
    Time Frame After approximately 80 months

    Outcome Measure Data

    Analysis Population Description
    Data were not collected for this outcome measure.
    Arm/Group Title N8-GP 50 U/kg Prophylaxis Q4D N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    Measure Participants 0 0
    67. Secondary Outcome
    Title FVIII Activity 30 Min Post -Injection (C30min)
    Description FVIII plasma activity was measured after 30 mins of injection. This was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator
    Time Frame Week 0, week 28

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title Pharmacokinetics Assessment Arm
    Arm/Group Description Patients participating in the pharmacokinetic assessments received a single i.v. bolus injection of 50 U/kg BW of N8-GP at Visit 2a (Week 0) and at Visit 7 (Week 28). The PK sessions were 4 days long and with multiple site visits. After completion of the PK sessions the patients continued treatment in the prophylaxis arm with the next visit in line. Patients must not have received current FVIII product for at least 4 days prior to the PK session at Visit 2a (Week 0) and N8-GP for at least 7 days prior to the PK session at Visit 7 (Week 28).
    Measure Participants 24
    Week 0
    1.524
    (22.65)
    Week 28
    1.601
    (16.24)
    68. Secondary Outcome
    Title Incremental Recovery (Single Dose and Steady State)
    Description Incremental recovery was defined as the dose-normalised activity recorded 30 min after end of injection. This was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.
    Time Frame Week 0, week 28

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title Pharmacokinetics Assessment Arm
    Arm/Group Description Patients participating in the pharmacokinetic assessments received a single i.v. bolus injection of 50 U/kg BW of N8-GP at Visit 2a (Week 0) and at Visit 7 (Week 28). The PK sessions were 4 days long and with multiple site visits. After completion of the PK sessions the patients continued treatment in the prophylaxis arm with the next visit in line. Patients must not have received current FVIII product for at least 4 days prior to the PK session at Visit 2a (Week 0) and N8-GP for at least 7 days prior to the PK session at Visit 7 (Week 28).
    Measure Participants 24
    Week 0
    0.031
    (22.16)
    Week 28
    0.034
    (17.60)
    69. Secondary Outcome
    Title Trough Level (Single Dose and Steady State)
    Description Trough level was defined as the plasma FVIII activity recorded immediately before next dose is given. This was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.
    Time Frame Week 0, week 28

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title Pharmacokinetics Assessment Arm
    Arm/Group Description Patients participating in the pharmacokinetic assessments received a single i.v. bolus injection of 50 U/kg BW of N8-GP at Visit 2a (Week 0) and at Visit 7 (Week 28). The PK sessions were 4 days long and with multiple site visits. After completion of the PK sessions the patients continued treatment in the prophylaxis arm with the next visit in line. Patients must not have received current FVIII product for at least 4 days prior to the PK session at Visit 2a (Week 0) and N8-GP for at least 7 days prior to the PK session at Visit 7 (Week 28).
    Measure Participants 24
    Week 0
    0.032
    (138.3)
    Week 28
    0.035
    (138.4)
    70. Secondary Outcome
    Title Area Under the Curve (AUC0-inf)
    Description Area under the plasma activity versus time profile from time zero to infinity (AUC0-inf) was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. It is the measure of total plasma exposure. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.
    Time Frame Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title Pharmacokinetics Assessment Arm
    Arm/Group Description Patients participating in the pharmacokinetic assessments received a single i.v. bolus injection of 50 U/kg BW of N8-GP at Visit 2a (Week 0) and at Visit 7 (Week 28). The PK sessions were 4 days long and with multiple site visits. After completion of the PK sessions the patients continued treatment in the prophylaxis arm with the next visit in line. Patients must not have received current FVIII product for at least 4 days prior to the PK session at Visit 2a (Week 0) and N8-GP for at least 7 days prior to the PK session at Visit 7 (Week 28).
    Measure Participants 24
    Week 0
    39.77
    (34.41)
    Week 28
    41.44
    (30.09)
    71. Secondary Outcome
    Title Area Under the Curve (AUC0-t)
    Description Area under the plasma activity versus time profile from time zero to the last measurable activity (AUC0-t) was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.
    Time Frame Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title Pharmacokinetics Assessment Arm
    Arm/Group Description Patients participating in the pharmacokinetic assessments received a single i.v. bolus injection of 50 U/kg BW of N8-GP at Visit 2a (Week 0) and at Visit 7 (Week 28). The PK sessions were 4 days long and with multiple site visits. After completion of the PK sessions the patients continued treatment in the prophylaxis arm with the next visit in line. Patients must not have received current FVIII product for at least 4 days prior to the PK session at Visit 2a (Week 0) and N8-GP for at least 7 days prior to the PK session at Visit 7 (Week 28).
    Measure Participants 24
    Week 0
    38.31
    (33.22)
    Week 28
    39.87
    (28.22)
    72. Secondary Outcome
    Title Terminal Half Life (t1/2)
    Description t½ = ln(2) / λz, where λz is the terminal elimination rate constant. The terminal elimination rate constant was estimated using linear regression on the terminal part of the log(activity) versus time profile. This was measured at Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.
    Time Frame Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title Pharmacokinetics Assessment Arm
    Arm/Group Description Patients participating in the pharmacokinetic assessments received a single i.v. bolus injection of 50 U/kg BW of N8-GP at Visit 2a (Week 0) and at Visit 7 (Week 28). The PK sessions were 4 days long and with multiple site visits. After completion of the PK sessions the patients continued treatment in the prophylaxis arm with the next visit in line. Patients must not have received current FVIII product for at least 4 days prior to the PK session at Visit 2a (Week 0) and N8-GP for at least 7 days prior to the PK session at Visit 7 (Week 28).
    Measure Participants 24
    Week 0
    18.27
    (27.40)
    Week 28
    18.18
    (31.43)
    73. Secondary Outcome
    Title Clearance (CL)
    Description Total plasma clearance (CL) of drug after intravenous administration was reported. Clearance was calculated using the formula CL= Dose / AUC(0-inf). This was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.
    Time Frame Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title Pharmacokinetics Assessment Arm
    Arm/Group Description Patients participating in the pharmacokinetic assessments received a single i.v. bolus injection of 50 U/kg BW of N8-GP at Visit 2a (Week 0) and at Visit 7 (Week 28). The PK sessions were 4 days long and with multiple site visits. After completion of the PK sessions the patients continued treatment in the prophylaxis arm with the next visit in line. Patients must not have received current FVIII product for at least 4 days prior to the PK session at Visit 2a (Week 0) and N8-GP for at least 7 days prior to the PK session at Visit 7 (Week 28).
    Measure Participants 24
    Week 0
    1.210
    (33.22)
    Week 28
    1.139
    (29.24)
    74. Secondary Outcome
    Title Mean Residence Time (MRT)
    Description MRT = AUMC/AUC(0-inf), where AUMC is the area under the first moment curve, i.e. the area under the curve t∙C(t), calculated with the same method as AUC(0-inf) (linear trapezoidal method + extrapolated area). This was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.
    Time Frame Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title Pharmacokinetics Assessment Arm
    Arm/Group Description Patients participating in the pharmacokinetic assessments received a single i.v. bolus injection of 50 U/kg BW of N8-GP at Visit 2a (Week 0) and at Visit 7 (Week 28). The PK sessions were 4 days long and with multiple site visits. After completion of the PK sessions the patients continued treatment in the prophylaxis arm with the next visit in line. Patients must not have received current FVIII product for at least 4 days prior to the PK session at Visit 2a (Week 0) and N8-GP for at least 7 days prior to the PK session at Visit 7 (Week 28).
    Measure Participants 24
    Week 0
    25.12
    (27.43)
    Week 28
    24.91
    (32.25)
    75. Secondary Outcome
    Title Volume of Distribution at Steady State (Vss)
    Description Apparent volume of distribution at steady state is a product of the mean residence time and clearance and was calculated using the formula - Vss = CL x MRT. This was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.
    Time Frame Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28

    Outcome Measure Data

    Analysis Population Description
    Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of participants with available data for respective arm.
    Arm/Group Title Pharmacokinetics Assessment Arm
    Arm/Group Description Patients participating in the pharmacokinetic assessments received a single i.v. bolus injection of 50 U/kg BW of N8-GP at Visit 2a (Week 0) and at Visit 7 (Week 28). The PK sessions were 4 days long and with multiple site visits. After completion of the PK sessions the patients continued treatment in the prophylaxis arm with the next visit in line. Patients must not have received current FVIII product for at least 4 days prior to the PK session at Visit 2a (Week 0) and N8-GP for at least 7 days prior to the PK session at Visit 7 (Week 28).
    Measure Participants 24
    Week 0
    30.40
    (24.18)
    Week 28
    28.38
    (19.43)

    Adverse Events

    Time Frame From first exposure to N8-GP (week 0) to follow up visit after end of treatment in extension phase part 2. (Main phase:19 months; Extension phase 1 approximately 6 months and Extension phase 2 :approximately upto 80 months from study start).
    Adverse Event Reporting Description The results are based on the safety analysis set. All the presented AEs were treatment-emergent. A treatment-emergent AE was defined as an event with onset after first N8-GP administration.
    Arm/Group Title N8-GP 50 U/kg Q4D Prophylaxis N8-GP 75 U/kg Q7D Prophylaxis N8-GP 20-75 U/kg On-demand
    Arm/Group Description Participants who were on prophylaxis treatment with N8-GP in the main phase and had 0-2 bleeding episodes during the last 6 months before entering the extension phase, were included in this arm. Participants received one single bolus dose of 50 U/kg BW of N8-GP administered IV every 4th day (96 hours) or twice weekly (at investigator's discretion). The dose was adjusted to ensure a trough level of >1% FVIII:C activity in this arm. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants who were on prophylaxis treatment with N8-GP in the main phase and had 3+ bleeding episodes during the last 6 months before entering the extension phase, were randomised to receive one single bolus dose of 75 U/kg BW of N8-GP. Participants received one single bolus dose of 75 U/kg BW of N8-GP administered IV every 7th day (Q7D). Based on the bleeding pattern, the investigator could change the dosing frequency from Q7D to Q4D, but not vice versa. The dose was based on phase 1 data from the NN7088-3776 trial in order to ensure a trough level of >1% FVIII:C activity in the majority of participants in the prophylaxis arm. Participants in this arm received treatment with N8-GP in case of a bleeding episode. All bleeds were to be treated with doses between 20-75 U/kg BW according to the severity and location of the bleeding episode. The dosage (N8-GP units) was calculated by multiplying the participant's weight in kilograms by the desired factor level multiplied by 0.5.
    All Cause Mortality
    N8-GP 50 U/kg Q4D Prophylaxis N8-GP 75 U/kg Q7D Prophylaxis N8-GP 20-75 U/kg On-demand
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/177 (0.6%) 0/61 (0%) 0/12 (0%)
    Serious Adverse Events
    N8-GP 50 U/kg Q4D Prophylaxis N8-GP 75 U/kg Q7D Prophylaxis N8-GP 20-75 U/kg On-demand
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 24/177 (13.6%) 7/61 (11.5%) 3/12 (25%)
    Blood and lymphatic system disorders
    Factor VIII inhibition 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Cardiac disorders
    Aortic valve stenosis 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Congenital, familial and genetic disorders
    Hydrocele 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Hypertrophic cardiomyopathy 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Eye disorders
    Cataract 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    Gastrointestinal disorders
    Diarrhoea 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Duodenal ulcer 1/177 (0.6%) 1 1/61 (1.6%) 1 0/12 (0%) 0
    Gastric varices 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Gastric varices haemorrhage 0/177 (0%) 0 1/61 (1.6%) 1 0/12 (0%) 0
    Mesenteric haemorrhage 0/177 (0%) 0 1/61 (1.6%) 1 0/12 (0%) 0
    Pancreatitis acute 0/177 (0%) 0 1/61 (1.6%) 1 0/12 (0%) 0
    Rectal haemorrhage 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    General disorders
    Complication associated with device 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Hepatobiliary disorders
    Cholecystitis 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Infections and infestations
    Anal abscess 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Bacterial sepsis 0/177 (0%) 0 1/61 (1.6%) 1 0/12 (0%) 0
    Catheter site infection 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Cellulitis 1/177 (0.6%) 2 0/61 (0%) 0 0/12 (0%) 0
    Device related infection 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Diverticulitis 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Enteritis infectious 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Infective spondylitis 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Intervertebral discitis 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Localised infection 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Osteomyelitis 0/177 (0%) 0 1/61 (1.6%) 1 0/12 (0%) 0
    Pneumonia 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Skin graft infection 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Viral infection 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Injury, poisoning and procedural complications
    Ankle fracture 0/177 (0%) 0 1/61 (1.6%) 1 0/12 (0%) 0
    Chest injury 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    Clavicle fracture 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    Extradural haematoma 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    Face injury 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Fall 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    Femoral neck fracture 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Forearm fracture 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Injury 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Pelvic fracture 0/177 (0%) 0 1/61 (1.6%) 1 0/12 (0%) 0
    Rib fracture 0/177 (0%) 0 1/61 (1.6%) 2 1/12 (8.3%) 1
    Road traffic accident 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Sternal fracture 0/177 (0%) 0 1/61 (1.6%) 1 0/12 (0%) 0
    Subdural haematoma 0/177 (0%) 0 1/61 (1.6%) 1 0/12 (0%) 0
    Toxicity to various agents 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Musculoskeletal and connective tissue disorders
    Pathological fracture 0/177 (0%) 0 1/61 (1.6%) 1 0/12 (0%) 0
    Synovitis 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Hepatocellular carcinoma 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Neuroma 0/177 (0%) 0 1/61 (1.6%) 1 0/12 (0%) 0
    Pancreatic carcinoma metastatic 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Nervous system disorders
    Cerebral infarction 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Cerebral microhaemorrhage 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Seizure 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Syncope 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Product Issues
    Device dislocation 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Psychiatric disorders
    Depression 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Renal and urinary disorders
    Calculus urinary 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    IgA nephropathy 1/177 (0.6%) 1 0/61 (0%) 0 0/12 (0%) 0
    Tubulointerstitial nephritis 0/177 (0%) 0 1/61 (1.6%) 1 0/12 (0%) 0
    Ureterolithiasis 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    Vascular disorders
    Circulatory collapse 0/177 (0%) 0 1/61 (1.6%) 1 0/12 (0%) 0
    Other (Not Including Serious) Adverse Events
    N8-GP 50 U/kg Q4D Prophylaxis N8-GP 75 U/kg Q7D Prophylaxis N8-GP 20-75 U/kg On-demand
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 144/177 (81.4%) 50/61 (82%) 10/12 (83.3%)
    Blood and lymphatic system disorders
    Lymphadenopathy 2/177 (1.1%) 2 0/61 (0%) 0 1/12 (8.3%) 1
    Cardiac disorders
    Atrioventricular block first degree 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    Ear and labyrinth disorders
    Ear discomfort 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    Gastrointestinal disorders
    Abdominal pain 4/177 (2.3%) 5 1/61 (1.6%) 1 1/12 (8.3%) 1
    Abdominal pain upper 9/177 (5.1%) 12 3/61 (4.9%) 3 0/12 (0%) 0
    Dental caries 6/177 (3.4%) 11 2/61 (3.3%) 2 1/12 (8.3%) 1
    Diarrhoea 17/177 (9.6%) 22 5/61 (8.2%) 6 2/12 (16.7%) 2
    Dyspepsia 4/177 (2.3%) 4 1/61 (1.6%) 1 1/12 (8.3%) 1
    Flatulence 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 2
    Haemorrhoids 1/177 (0.6%) 1 0/61 (0%) 0 1/12 (8.3%) 1
    Irritable bowel syndrome 1/177 (0.6%) 1 0/61 (0%) 0 1/12 (8.3%) 2
    Nausea 14/177 (7.9%) 20 3/61 (4.9%) 3 1/12 (8.3%) 1
    Toothache 10/177 (5.6%) 11 3/61 (4.9%) 5 1/12 (8.3%) 1
    Vomiting 9/177 (5.1%) 11 4/61 (6.6%) 4 1/12 (8.3%) 1
    General disorders
    Chest pain 2/177 (1.1%) 2 2/61 (3.3%) 2 1/12 (8.3%) 1
    Fatigue 4/177 (2.3%) 4 1/61 (1.6%) 2 1/12 (8.3%) 1
    Pyrexia 9/177 (5.1%) 10 5/61 (8.2%) 7 2/12 (16.7%) 2
    Hepatobiliary disorders
    Hepatic function abnormal 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    Immune system disorders
    Seasonal allergy 11/177 (6.2%) 14 2/61 (3.3%) 3 0/12 (0%) 0
    Infections and infestations
    Bronchitis 9/177 (5.1%) 9 1/61 (1.6%) 1 1/12 (8.3%) 1
    Citrobacter infection 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    Conjunctivitis 5/177 (2.8%) 5 0/61 (0%) 0 1/12 (8.3%) 1
    Folliculitis 2/177 (1.1%) 2 0/61 (0%) 0 1/12 (8.3%) 2
    Gastroenteritis 6/177 (3.4%) 9 1/61 (1.6%) 1 1/12 (8.3%) 1
    Influenza 16/177 (9%) 22 6/61 (9.8%) 7 2/12 (16.7%) 2
    Nasopharyngitis 48/177 (27.1%) 78 12/61 (19.7%) 16 5/12 (41.7%) 12
    Periodontitis 1/177 (0.6%) 1 1/61 (1.6%) 1 2/12 (16.7%) 2
    Tinea infection 1/177 (0.6%) 1 1/61 (1.6%) 1 1/12 (8.3%) 1
    Tonsillitis 10/177 (5.6%) 11 4/61 (6.6%) 5 1/12 (8.3%) 2
    Upper respiratory tract infection 37/177 (20.9%) 59 9/61 (14.8%) 14 0/12 (0%) 0
    Injury, poisoning and procedural complications
    Contusion 11/177 (6.2%) 15 3/61 (4.9%) 3 2/12 (16.7%) 10
    Fall 10/177 (5.6%) 10 2/61 (3.3%) 2 0/12 (0%) 0
    Foot fracture 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    Joint injury 5/177 (2.8%) 5 0/61 (0%) 0 1/12 (8.3%) 1
    Limb injury 6/177 (3.4%) 7 5/61 (8.2%) 6 0/12 (0%) 0
    Scratch 1/177 (0.6%) 1 1/61 (1.6%) 1 1/12 (8.3%) 1
    Skin laceration 10/177 (5.6%) 12 5/61 (8.2%) 5 0/12 (0%) 0
    Spinal fracture 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    Investigations
    Alanine aminotransferase increased 12/177 (6.8%) 17 3/61 (4.9%) 3 3/12 (25%) 6
    Aspartate aminotransferase increased 10/177 (5.6%) 11 3/61 (4.9%) 5 3/12 (25%) 5
    Blood bilirubin increased 1/177 (0.6%) 1 0/61 (0%) 0 2/12 (16.7%) 2
    Blood pressure increased 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    C-reactive protein increased 5/177 (2.8%) 7 4/61 (6.6%) 4 0/12 (0%) 0
    Gamma-glutamyltransferase increased 6/177 (3.4%) 10 1/61 (1.6%) 1 3/12 (25%) 5
    Liver function test abnormal 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    Sputum abnormal 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    Metabolism and nutrition disorders
    Gout 1/177 (0.6%) 1 1/61 (1.6%) 1 1/12 (8.3%) 2
    Musculoskeletal and connective tissue disorders
    Arthralgia 27/177 (15.3%) 43 15/61 (24.6%) 21 3/12 (25%) 4
    Back pain 8/177 (4.5%) 11 6/61 (9.8%) 6 3/12 (25%) 3
    Musculoskeletal chest pain 3/177 (1.7%) 3 0/61 (0%) 0 1/12 (8.3%) 1
    Musculoskeletal pain 14/177 (7.9%) 14 4/61 (6.6%) 4 1/12 (8.3%) 1
    Osteoarthritis 3/177 (1.7%) 3 0/61 (0%) 0 1/12 (8.3%) 1
    Pain in extremity 12/177 (6.8%) 14 1/61 (1.6%) 1 0/12 (0%) 0
    Rheumatic disorder 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 2
    Synovitis 3/177 (1.7%) 5 5/61 (8.2%) 5 0/12 (0%) 0
    Tendonitis 0/177 (0%) 0 6/61 (9.8%) 6 1/12 (8.3%) 1
    Tenosynovitis 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 3
    Nervous system disorders
    Carpal tunnel syndrome 1/177 (0.6%) 1 0/61 (0%) 0 1/12 (8.3%) 1
    Dizziness 6/177 (3.4%) 7 0/61 (0%) 0 1/12 (8.3%) 1
    Headache 35/177 (19.8%) 79 13/61 (21.3%) 25 3/12 (25%) 4
    Seizure 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    Psychiatric disorders
    Depressed mood 0/177 (0%) 0 1/61 (1.6%) 1 1/12 (8.3%) 1
    Depression 9/177 (5.1%) 9 1/61 (1.6%) 1 0/12 (0%) 0
    Mental status changes 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    Renal and urinary disorders
    Haematuria 0/177 (0%) 0 1/61 (1.6%) 1 1/12 (8.3%) 1
    Urinary incontinence 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    Respiratory, thoracic and mediastinal disorders
    Cough 16/177 (9%) 20 4/61 (6.6%) 5 1/12 (8.3%) 2
    Haemothorax 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    Nasal obstruction 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    Oropharyngeal pain 16/177 (9%) 20 4/61 (6.6%) 5 1/12 (8.3%) 1
    Pneumothorax 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    Rhinorrhoea 9/177 (5.1%) 12 1/61 (1.6%) 1 0/12 (0%) 0
    Skin and subcutaneous tissue disorders
    Acne 3/177 (1.7%) 4 4/61 (6.6%) 4 0/12 (0%) 0
    Blister 1/177 (0.6%) 3 1/61 (1.6%) 1 1/12 (8.3%) 1
    Dry skin 2/177 (1.1%) 2 0/61 (0%) 0 1/12 (8.3%) 1
    Eczema 5/177 (2.8%) 8 2/61 (3.3%) 2 1/12 (8.3%) 2
    Eczema asteatotic 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    Pruritus 2/177 (1.1%) 2 0/61 (0%) 0 1/12 (8.3%) 1
    Rash 9/177 (5.1%) 10 2/61 (3.3%) 2 0/12 (0%) 0
    Urticaria 2/177 (1.1%) 2 2/61 (3.3%) 2 1/12 (8.3%) 1
    Vascular disorders
    Essential hypertension 0/177 (0%) 0 0/61 (0%) 0 1/12 (8.3%) 1
    Hypertension 17/177 (9.6%) 18 4/61 (6.6%) 5 0/12 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.

    Results Point of Contact

    Name/Title Clinical Reporting Anchor and Disclosure (1452)
    Organization Novo Nordisk A/S
    Phone (+1) 866-867-7178
    Email clinicaltrials@novonordisk.com
    Responsible Party:
    Novo Nordisk A/S
    ClinicalTrials.gov Identifier:
    NCT01480180
    Other Study ID Numbers:
    • NN7088-3859
    • U1111-1119-7416
    • 2011-001142-15
    • JapicCTI-121749
    First Posted:
    Nov 28, 2011
    Last Update Posted:
    Nov 23, 2020
    Last Verified:
    Nov 1, 2020