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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01480180

Acronym

pathfinder™2

Enrollment

186

Registered

2011-11-28

Start date

2012-01-30

Completion date

2018-12-10

Last updated

2020-11-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Congenital Bleeding Disorder, Haemophilia A

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.

Interventions

DRUGturoctocog alfa pegol

Administered i.v.

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

12 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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.
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.
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.
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.
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.
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

Measure	Time frame	Description
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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).
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.
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).
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).
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.
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).
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.
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).
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).
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Countries

Australia, Brazil, Bulgaria, Croatia, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Malaysia, Netherlands, Norway, Puerto Rico, Russia, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States

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 details

The trial had a main phase and an extension phase 1 and phase 2.

Participants by arm

Arm	Count
Prophylaxis 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.	174
On-demand 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.	12
Total	186

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Extension Phase, Part 1	Adverse Event	0	0	4	1	0
Extension Phase, Part 1	Change of treatment	0	0	0	9	0
Extension Phase, Part 1	Unclassified	0	0	1	0	0
Extension Phase, Part 1	Withdrawal criteria	0	0	5	0	0
Extension Phase, Part 2	Lack of Efficacy	0	0	4	0	0
Extension Phase, Part 2	Unclassified	0	0	3	1	1
Extension Phase, Part 2	Withdrawal criteria	0	0	10	6	1
Main Phase	Lack of Efficacy	1	0	0	0	0
Main Phase	Non-compliance	3	0	0	0	0
Main Phase	Unclassified	3	0	0	0	0
Main Phase	Withdrawal criteria	12	1	0	0	0

Baseline characteristics

Characteristic	Total	On-demand	Prophylaxis
Age, Continuous	31.1 years STANDARD_DEVIATION 12.6	39.8 years STANDARD_DEVIATION 13.9	30.5 years STANDARD_DEVIATION 12.4
Race/Ethnicity, Customized Asian	35 Participants	4 Participants	31 Participants
Race/Ethnicity, Customized Black or African American	11 Participants	3 Participants	8 Participants
Race/Ethnicity, Customized Hispanic or Latino	13 Participants	0 Participants	13 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	173 Participants	12 Participants	161 Participants
Race/Ethnicity, Customized Other	2 Participants	0 Participants	2 Participants
Race/Ethnicity, Customized White	138 Participants	5 Participants	133 Participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	186 Participants	12 Participants	174 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	1 / 177	0 / 61	0 / 12
other Total, other adverse events	144 / 177	50 / 61	10 / 12
serious Total, serious adverse events	24 / 177	7 / 61	3 / 12

Outcome results

Primary

Annualised Bleeding Rate in the Prophylaxis Arm: 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.

Time frame: After approximately 19 months

Population: 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	Measure	Value (MEDIAN)
N8-GP 50 U/kg Prophylaxis Q4D	Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 19 Months	1.33 Bleeds per participant per year

Comparison: 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.p-value: <0.00195% CI: [2.94, 4.66]Poisson regression

Primary

Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 25 Months

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

Population: 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	Measure	Value (MEDIAN)
N8-GP 50 U/kg Prophylaxis Q4D	Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 25 Months	1.36 Bleeds per participant per year
N8-GP 20-75 U/kg On-demand	Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 25 Months	0 Bleeds per participant per year

Primary

Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 80 Months

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

Population: 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	Measure	Value (MEDIAN)
N8-GP 50 U/kg Prophylaxis Q4D	Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 80 Months	0.99 Bleeds per participant per year
N8-GP 20-75 U/kg On-demand	Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 80 Months	1.95 Bleeds per participant per year

Primary

Incidence Rate of FVIII-inhibitors ≥0.6 BU: 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.

Time frame: At approximately 80 months

Population: 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	Measure	Value (NUMBER)
N8-GP 50 U/kg Prophylaxis Q4D	Incidence Rate of FVIII-inhibitors ≥0.6 BU: At Approximately 80 Months	0.006 Inhibitor rate
N8-GP 20-75 U/kg On-demand	Incidence Rate of FVIII-inhibitors ≥0.6 BU: At Approximately 80 Months	0 Inhibitor rate

Primary

The Incidence Rate of FVIII-inhibitors ≥0.6 BU: After Approximately 19 Months

Time frame: After approximately 19 months

Population: 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	Measure	Value (NUMBER)
N8-GP 50 U/kg Prophylaxis Q4D	The Incidence Rate of FVIII-inhibitors ≥0.6 BU: After Approximately 19 Months	0.006 Inhibitor rate
N8-GP 20-75 U/kg On-demand	The Incidence Rate of FVIII-inhibitors ≥0.6 BU: After Approximately 19 Months	0 Inhibitor rate

Primary

The Incidence Rate of FVIII-inhibitors ≥0.6 BU: After Approximately 25 Months

Time frame: After approximately 25 months

Population: 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	Measure	Value (NUMBER)
N8-GP 50 U/kg Prophylaxis Q4D	The Incidence Rate of FVIII-inhibitors ≥0.6 BU: After Approximately 25 Months	0.006 Inhibitor rate
N8-GP 20-75 U/kg On-demand	The Incidence Rate of FVIII-inhibitors ≥0.6 BU: After Approximately 25 Months	0 Inhibitor rate
N8-GP 20-75 U/kg On-demand	The Incidence Rate of FVIII-inhibitors ≥0.6 BU: After Approximately 25 Months	0 Inhibitor rate

Secondary

Area Under the Curve (AUC0-inf)

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

Population: 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	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Area Under the Curve (AUC0-inf)	Week 0	39.77 IU*h/mL	Geometric Coefficient of Variation 34.41
N8-GP 50 U/kg Prophylaxis Q4D	Area Under the Curve (AUC0-inf)	Week 28	41.44 IU*h/mL	Geometric Coefficient of Variation 30.09

Secondary

Area Under the Curve (AUC0-t)

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

Population: 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	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Area Under the Curve (AUC0-t)	Week 0	38.31 IU*h/mL	Geometric Coefficient of Variation 33.22
N8-GP 50 U/kg Prophylaxis Q4D	Area Under the Curve (AUC0-t)	Week 28	39.87 IU*h/mL	Geometric Coefficient of Variation 28.22

Secondary

Change in Blood Pressure: 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).

Time frame: After approximately 19 months

Population: 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	Measure	Group	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Change in Blood Pressure: After Approximately 19 Months	Systolic blood pressure	6.8 mmHg	Standard Deviation 9.5
N8-GP 50 U/kg Prophylaxis Q4D	Change in Blood Pressure: After Approximately 19 Months	Diastolic blood pressure	3.3 mmHg	Standard Deviation 8.9
N8-GP 20-75 U/kg On-demand	Change in Blood Pressure: After Approximately 19 Months	Systolic blood pressure	1.3 mmHg	Standard Deviation 20.5
N8-GP 20-75 U/kg On-demand	Change in Blood Pressure: After Approximately 19 Months	Diastolic blood pressure	9.0 mmHg	Standard Deviation 5.2

Secondary

Change in Blood Pressure: After Approximately 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).

Time frame: After approximately 19 and 25 months

Population: 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	Measure	Group	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Change in Blood Pressure: After Approximately 25 Months	Systolic blood pressure	-1.337 mmHg	Standard Deviation 13.1
N8-GP 50 U/kg Prophylaxis Q4D	Change in Blood Pressure: After Approximately 25 Months	Diastolic blood pressure	0.337 mmHg	Standard Deviation 10.8
N8-GP 20-75 U/kg On-demand	Change in Blood Pressure: After Approximately 25 Months	Systolic blood pressure	-6.000 mmHg	Standard Deviation 9.5
N8-GP 20-75 U/kg On-demand	Change in Blood Pressure: After Approximately 25 Months	Diastolic blood pressure	2.000 mmHg	Standard Deviation 5.9

Secondary

Change in Blood Pressure: 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.

Time frame: After approximately 80 months

Population: Data were not collected for this outcome measure.

Arm	Measure	Group	Value
Unknown	Change in Blood Pressure: After Approximately 80 Months	Systolic blood pressure	—
Unknown	Change in Blood Pressure: After Approximately 80 Months	Diastolic blood pressure	—

Secondary

Change in Body Temperature: 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).

Time frame: After approximately 19 months

Population: 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	Measure	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Change in Body Temperature: After Approximately 19 Months	0.0 Degree celcius	Standard Deviation 0.4
N8-GP 20-75 U/kg On-demand	Change in Body Temperature: After Approximately 19 Months	-0.1 Degree celcius	Standard Deviation 0.2

Secondary

Change in Body Temperature: 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).

Time frame: After approximately 25 months

Population: 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	Measure	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Change in Body Temperature: After Approximately 25 Months	-0.079 Degree celcius	Standard Deviation 0.3
N8-GP 20-75 U/kg On-demand	Change in Body Temperature: After Approximately 25 Months	-0.086 Degree celcius	Standard Deviation 0.6

Secondary

Change in Body Temperature: 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.

Time frame: After approximately 80 months

Population: Data were not collected for this outcome measure.

Arm	Measure	Group	Value
Unknown	Change in Body Temperature: After Approximately 80 Months	Systolic blood pressure	—
Unknown	Change in Body Temperature: After Approximately 80 Months	Diastolic blood pressure	—

Secondary

Change in Pulse: 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).

Time frame: After approximately 19 months

Population: 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	Measure	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Change in Pulse: After Approximately 19 Months	5.3 Beats per min	Standard Deviation 11.2
N8-GP 20-75 U/kg On-demand	Change in Pulse: After Approximately 19 Months	10.3 Beats per min	Standard Deviation 4.6

Secondary

Change in Pulse: 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).

Time frame: After approximately 25 months

Population: 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	Measure	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Change in Pulse: After Approximately 25 Months	-0.644 Beats per min	Standard Deviation 10.7
N8-GP 20-75 U/kg On-demand	Change in Pulse: After Approximately 25 Months	3.143 Beats per min	Standard Deviation 8.2

Secondary

Change in Pulse: 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.

Time frame: After approximately 80 months

Population: Data were not collected for this outcome measure.

Arm	Measure	Group	Value
Unknown	Change in Pulse: After Approximately 80 Months	Systolic blood pressure	—
Unknown	Change in Pulse: After Approximately 80 Months	Diastolic blood pressure	—

Secondary

Change in Respiratory Rate: 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).

Time frame: After approximately 19 months

Population: 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	Measure	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Change in Respiratory Rate: After Approximately 19 Months	-0.2 Breaths/min	Standard Deviation 1.9
N8-GP 20-75 U/kg On-demand	Change in Respiratory Rate: After Approximately 19 Months	-2.3 Breaths/min	Standard Deviation 2.1

Secondary

Change in Respiratory Rate: 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).

Time frame: After approximately 25 months

Population: 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	Measure	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Change in Respiratory Rate: After Approximately 25 Months	-0.067 Breaths/min	Standard Deviation 2.1
N8-GP 20-75 U/kg On-demand	Change in Respiratory Rate: After Approximately 25 Months	-0.857 Breaths/min	Standard Deviation 2.5

Secondary

Change in Respiratory Rate: 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.

Time frame: After approximately 80 months

Population: Data were not collected for this outcome measure.

Arm	Measure	Group	Value
Unknown	Change in Respiratory Rate: After Approximately 80 Months	Systolic blood pressure	—
Unknown	Change in Respiratory Rate: After Approximately 80 Months	Diastolic blood pressure	—

Secondary

Clearance (CL)

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

Population: 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	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Clearance (CL)	Week 0	1.210 mL/h/kg	Geometric Coefficient of Variation 33.22
N8-GP 50 U/kg Prophylaxis Q4D	Clearance (CL)	Week 28	1.139 mL/h/kg	Geometric Coefficient of Variation 29.24

Secondary

Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 19 Months

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

Time frame: After approximately 19 months

Population: 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	Measure	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 19 Months	52.2 U/kg	Standard Deviation 1.4
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 19 Months	46.3 U/kg	Standard Deviation 10.4

Secondary

Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 25 Months

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

Time frame: After approximately 25 months

Population: 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	Measure	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 25 Months	52.2 U/kg	Standard Deviation 1.9
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 25 Months	77.2 U/kg	Standard Deviation 3.2
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 25 Months	44.8 U/kg	Standard Deviation 11.4

Secondary

Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 80 Months

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

Time frame: After approximately 80 months

Population: 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	Measure	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 80 Months	52.2 U/kg	Standard Deviation 1.5
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 80 Months	77.1 U/kg	Standard Deviation 3.2
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 80 Months	37.5 U/kg	Standard Deviation 13

Secondary

Consumption of N8-GP Per Bleeding Episode (Number of Infusions): 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.

Time frame: After approximately 19 months

Population: 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	Measure	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 19 Months	1.4 Number of infusions	Standard Deviation 1
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 19 Months	1.2 Number of infusions	Standard Deviation 0.9

Secondary

Consumption of N8-GP Per Bleeding Episode (Number of Infusions): 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.

Time frame: After approximately 25 months

Population: 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	Measure	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 25 Months	1.4 Number of infusions	Standard Deviation 1.3
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 25 Months	1.3 Number of infusions	Standard Deviation 0.6
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 25 Months	1.2 Number of infusions	Standard Deviation 0.8

Secondary

Consumption of N8-GP Per Bleeding Episode (Number of Infusions): 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.

Time frame: After approximately 80 months

Population: 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	Measure	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 80 Months	1.4 Number of infusions	Standard Deviation 1.3
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 80 Months	1.3 Number of infusions	Standard Deviation 0.6
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 80 Months	1.2 Number of infusions	Standard Deviation 0.8

Secondary

Consumption of N8-GP Per Bleeding Episode (U/kg): 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.

Time frame: After approximately 19 months

Population: Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of bleeds analysed

Arm	Measure	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 19 Months	64.6 U/kg per bleed	Standard Deviation 48.8
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 19 Months	41.0 U/kg per bleed	Standard Deviation 35.1

Secondary

Consumption of N8-GP Per Bleeding Episode (U/kg): 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.

Time frame: After approximately 25 months

Population: Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of bleeds analysed.

Arm	Measure	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 25 Months	67.8 U/kg per bleed	Standard Deviation 72.9
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 25 Months	78.2 U/kg per bleed	Standard Deviation 37.8
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 25 Months	39.3 U/kg per bleed	Standard Deviation 32.4

Secondary

Consumption of N8-GP Per Bleeding Episode (U/kg): 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.

Time frame: After approximately 80 months

Population: Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of bleeds analysed.

Arm	Measure	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 80 Months	68.1 U/kg per bleed	Standard Deviation 60
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 80 Months	88.7 U/kg per bleed	Standard Deviation 72.4
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 80 Months	37.5 U/kg per bleed	Standard Deviation 38

Secondary

Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: 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.

Time frame: After approximately 19 months

Population: 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	Measure	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 19 Months	403.8 U/kg per month	Standard Deviation 53.8
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 19 Months	129.2 U/kg per month	Standard Deviation 71.8

Secondary

Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: 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.

Time frame: After approximately 25 months

Population: 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	Measure	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 25 Months	403.8 U/kg per month	Standard Deviation 53.8
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 25 Months	349.2 U/kg per month	Standard Deviation 37.9
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 25 Months	128.2 U/kg per month	Standard Deviation 70.1

Secondary

Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: 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.

Time frame: After approximately 80 months

Population: 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	Measure	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 80 Months	402.4 U/kg per month	Standard Deviation 52.4
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 80 Months	353.5 U/kg per month	Standard Deviation 32.9
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 80 Months	130.2 U/kg per month	Standard Deviation 69.2

Secondary

Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: 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.

Time frame: After approximately 19 months

Population: 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	Measure	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 19 Months	4845 U/kg per year	Standard Deviation 645
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 19 Months	1550 U/kg per year	Standard Deviation 861

Secondary

Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: 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.

Time frame: After approximately 25 months

Population: 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	Measure	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 25 Months	4846 U/kg per year	Standard Deviation 645.3
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 25 Months	4190 U/kg per year	Standard Deviation 454.5
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 25 Months	1538 U/kg per year	Standard Deviation 840.6

Secondary

Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: 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.

Time frame: After approximately 80 months

Population: 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	Measure	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 80 Months	4829 U/kg per year	Standard Deviation 628.8
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 80 Months	4242 U/kg per year	Standard Deviation 394.5
N8-GP 20-75 U/kg On-demand	Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 80 Months	1562 U/kg per year	Standard Deviation 830.3

Secondary

FVIII Activity 30 Min Post -Injection (C30min)

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

Population: 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	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	FVIII Activity 30 Min Post -Injection (C30min)	Week 0	1.524 IU/mL	Geometric Coefficient of Variation 22.65
N8-GP 50 U/kg Prophylaxis Q4D	FVIII Activity 30 Min Post -Injection (C30min)	Week 28	1.601 IU/mL	Geometric Coefficient of Variation 16.24

Secondary

Haemostatic Effect as Measured by Recovery and Trough Levels FVIII:C (in All Patients Receiving Prophylaxis Treatment): 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.

Time frame: After approximately 19 months

Population: 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	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Haemostatic Effect as Measured by Recovery and Trough Levels FVIII:C (in All Patients Receiving Prophylaxis Treatment): After Approximately 19 Months	Visit 2 Post-dose	1.276 U/mL	Geometric Coefficient of Variation 18.584
N8-GP 50 U/kg Prophylaxis Q4D	Haemostatic Effect as Measured by Recovery and Trough Levels FVIII:C (in All Patients Receiving Prophylaxis Treatment): After Approximately 19 Months	Visit 3 Pre-dose	0.030 U/mL	Geometric Coefficient of Variation 159.92
N8-GP 50 U/kg Prophylaxis Q4D	Haemostatic Effect as Measured by Recovery and Trough Levels FVIII:C (in All Patients Receiving Prophylaxis Treatment): After Approximately 19 Months	Visit 12 Post-dose	1.359 U/mL	Geometric Coefficient of Variation 18.156
N8-GP 50 U/kg Prophylaxis Q4D	Haemostatic Effect as Measured by Recovery and Trough Levels FVIII:C (in All Patients Receiving Prophylaxis Treatment): After Approximately 19 Months	Visit 13 Pre-dose	0.034 U/mL	Geometric Coefficient of Variation 188.891

Secondary

Haemostatic Effect as Measured by Recovery and Trough Levels FVIII:C (in All Patients Receiving Prophylaxis Treatment): 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.

Time frame: After approximately 25 months

Population: 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	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Haemostatic Effect as Measured by Recovery and Trough Levels FVIII:C (in All Patients Receiving Prophylaxis Treatment): After Approximately 25 Months	Visit 16 Post-dose	1.329 U/mL	Geometric Coefficient of Variation 13.357
N8-GP 50 U/kg Prophylaxis Q4D	Haemostatic Effect as Measured by Recovery and Trough Levels FVIII:C (in All Patients Receiving Prophylaxis Treatment): After Approximately 25 Months	Visit 17 Pre-dose	0.028 U/mL	Geometric Coefficient of Variation 205.652
N8-GP 20-75 U/kg On-demand	Haemostatic Effect as Measured by Recovery and Trough Levels FVIII:C (in All Patients Receiving Prophylaxis Treatment): After Approximately 25 Months	Visit 16 Post-dose	1.868 U/mL	Geometric Coefficient of Variation 31.919
N8-GP 20-75 U/kg On-demand	Haemostatic Effect as Measured by Recovery and Trough Levels FVIII:C (in All Patients Receiving Prophylaxis Treatment): After Approximately 25 Months	Visit 17 Pre-dose	0.015 U/mL	Geometric Coefficient of Variation 272.494

Secondary

Haemostatic Effect as Measured by Recovery and Trough Levels FVIII:C (in All Patients Receiving Prophylaxis Treatment): 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.

Time frame: After approximately 80 months

Population: Data were not collected for this endpoint.

Secondary

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

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

Population: Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of bleeds analysed.

Arm	Measure	Category	Value (COUNT_OF_UNITS)
N8-GP 50 U/kg Prophylaxis Q4D	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	Good	174 Bleeding episodes
N8-GP 50 U/kg Prophylaxis Q4D	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	None	4 Bleeding episodes
N8-GP 50 U/kg Prophylaxis Q4D	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	Moderate	62 Bleeding episodes
N8-GP 50 U/kg Prophylaxis Q4D	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	Missing	4 Bleeding episodes
N8-GP 50 U/kg Prophylaxis Q4D	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	Excellent	192 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	Missing	0 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	Excellent	320 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	Good	170 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	Moderate	41 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	None	1 Bleeding episodes

Secondary

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

Time frame: After approximately 25 months

Population: Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of bleeds analysed.

Arm	Measure	Category	Value (COUNT_OF_UNITS)
N8-GP 50 U/kg Prophylaxis Q4D	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	None	4 Bleeding episodes
N8-GP 50 U/kg Prophylaxis Q4D	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	Moderate	98 Bleeding episodes
N8-GP 50 U/kg Prophylaxis Q4D	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	Excellent	330 Bleeding episodes
N8-GP 50 U/kg Prophylaxis Q4D	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	Good	270 Bleeding episodes
N8-GP 50 U/kg Prophylaxis Q4D	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	Missing	14 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	Moderate	3 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	Excellent	9 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	Good	11 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	None	0 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	Missing	2 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	Missing	0 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	None	1 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	Excellent	406 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	Moderate	55 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	Good	233 Bleeding episodes

Secondary

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

Time frame: After approximately 80 months

Population: Results were based on the FAS which included all participants exposed to N8-GP in this trial. Number analysed = Number of bleeds analysed.

Arm	Measure	Category	Value (COUNT_OF_UNITS)
N8-GP 50 U/kg Prophylaxis Q4D	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	None	6 Bleeding episodes
N8-GP 50 U/kg Prophylaxis Q4D	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	Moderate	153 Bleeding episodes
N8-GP 50 U/kg Prophylaxis Q4D	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	Excellent	600 Bleeding episodes
N8-GP 50 U/kg Prophylaxis Q4D	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	Good	532 Bleeding episodes
N8-GP 50 U/kg Prophylaxis Q4D	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	Missing	21 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	Moderate	29 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	Excellent	75 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	Good	65 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	None	2 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	Missing	5 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	Missing	0 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	None	1 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	Excellent	859 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	Moderate	71 Bleeding episodes
N8-GP 20-75 U/kg On-demand	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	Good	339 Bleeding episodes

Secondary

Incremental Recovery (Single Dose and Steady State)

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

Population: 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	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Incremental Recovery (Single Dose and Steady State)	Week 0	0.031 [(U/mL)/(IU/kg)]	Geometric Coefficient of Variation 22.16
N8-GP 50 U/kg Prophylaxis Q4D	Incremental Recovery (Single Dose and Steady State)	Week 28	0.034 [(U/mL)/(IU/kg)]	Geometric Coefficient of Variation 17.6

Secondary

Mean Residence Time (MRT)

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

Population: 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	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Mean Residence Time (MRT)	Week 0	25.12 Hour (h)	Geometric Coefficient of Variation 27.43
N8-GP 50 U/kg Prophylaxis Q4D	Mean Residence Time (MRT)	Week 28	24.91 Hour (h)	Geometric Coefficient of Variation 32.25

Secondary

Number of Admissions to the Emergency Room (ER) During the Trial

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

Population: 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	Measure	Group	Category	Value (COUNT_OF_UNITS)
N8-GP 50 U/kg Prophylaxis Q4D	Number of Admissions to the Emergency Room (ER) During the Trial	After approximately 19 months	4	0 ER admissions
N8-GP 50 U/kg Prophylaxis Q4D	Number of Admissions to the Emergency Room (ER) During the Trial	After approximately 19 months	0	49 ER admissions
N8-GP 50 U/kg Prophylaxis Q4D	Number of Admissions to the Emergency Room (ER) During the Trial	After approximately 19 months	1	1 ER admissions
N8-GP 50 U/kg Prophylaxis Q4D	Number of Admissions to the Emergency Room (ER) During the Trial	After approximately 19 months	2	2 ER admissions
N8-GP 50 U/kg Prophylaxis Q4D	Number of Admissions to the Emergency Room (ER) During the Trial	After approximately 25 months	0	84 ER admissions
N8-GP 50 U/kg Prophylaxis Q4D	Number of Admissions to the Emergency Room (ER) During the Trial	After approximately 25 months	1	2 ER admissions
N8-GP 50 U/kg Prophylaxis Q4D	Number of Admissions to the Emergency Room (ER) During the Trial	After approximately 25 months	2	2 ER admissions
N8-GP 50 U/kg Prophylaxis Q4D	Number of Admissions to the Emergency Room (ER) During the Trial	After approximately 25 months	4	1 ER admissions
N8-GP 50 U/kg Prophylaxis Q4D	Number of Admissions to the Emergency Room (ER) During the Trial	Month 25 to 80	0	17 ER admissions
N8-GP 50 U/kg Prophylaxis Q4D	Number of Admissions to the Emergency Room (ER) During the Trial	Month 25 to 80	1	4 ER admissions
N8-GP 50 U/kg Prophylaxis Q4D	Number of Admissions to the Emergency Room (ER) During the Trial	Month 25 to 80	2	0 ER admissions
N8-GP 50 U/kg Prophylaxis Q4D	Number of Admissions to the Emergency Room (ER) During the Trial	Month 25 to 80	4	0 ER admissions
N8-GP 20-75 U/kg On-demand	Number of Admissions to the Emergency Room (ER) During the Trial	Month 25 to 80	2	0 ER admissions
N8-GP 20-75 U/kg On-demand	Number of Admissions to the Emergency Room (ER) During the Trial	After approximately 25 months	2	1 ER admissions
N8-GP 20-75 U/kg On-demand	Number of Admissions to the Emergency Room (ER) During the Trial	After approximately 19 months	0	8 ER admissions
N8-GP 20-75 U/kg On-demand	Number of Admissions to the Emergency Room (ER) During the Trial	Month 25 to 80	1	0 ER admissions
N8-GP 20-75 U/kg On-demand	Number of Admissions to the Emergency Room (ER) During the Trial	After approximately 19 months	1	0 ER admissions
N8-GP 20-75 U/kg On-demand	Number of Admissions to the Emergency Room (ER) During the Trial	After approximately 25 months	4	0 ER admissions
N8-GP 20-75 U/kg On-demand	Number of Admissions to the Emergency Room (ER) During the Trial	After approximately 19 months	2	0 ER admissions
N8-GP 20-75 U/kg On-demand	Number of Admissions to the Emergency Room (ER) During the Trial	After approximately 19 months	4	0 ER admissions
N8-GP 20-75 U/kg On-demand	Number of Admissions to the Emergency Room (ER) During the Trial	Month 25 to 80	4	0 ER admissions
N8-GP 20-75 U/kg On-demand	Number of Admissions to the Emergency Room (ER) During the Trial	After approximately 25 months	0	8 ER admissions
N8-GP 20-75 U/kg On-demand	Number of Admissions to the Emergency Room (ER) During the Trial	Month 25 to 80	0	2 ER admissions
N8-GP 20-75 U/kg On-demand	Number of Admissions to the Emergency Room (ER) During the Trial	After approximately 25 months	1	1 ER admissions

Secondary

Number of Adverse Events Reported During the Trial Period: After Approximately 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.

Time frame: After approx 19 months

Population: Results are based on the SAS. SAS comprised all participants exposed to N8-GP in this trial.

Arm	Measure	Value (NUMBER)
N8-GP 50 U/kg Prophylaxis Q4D	Number of Adverse Events Reported During the Trial Period: After Approximately 19 Months	423 Number of adverse events
N8-GP 20-75 U/kg On-demand	Number of Adverse Events Reported During the Trial Period: After Approximately 19 Months	51 Number of adverse events

Secondary

Number of Adverse Events Reported During the Trial Period: After Approximately 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.

Time frame: After approx. 25 months

Population: Results are based on the SAS. SAS comprised all participants exposed to N8-GP in this trial.

Arm	Measure	Value (NUMBER)
N8-GP 50 U/kg Prophylaxis Q4D	Number of Adverse Events Reported During the Trial Period: After Approximately 25 Months	701 Number of adverse events
N8-GP 20-75 U/kg On-demand	Number of Adverse Events Reported During the Trial Period: After Approximately 25 Months	71 Number of adverse events
N8-GP 20-75 U/kg On-demand	Number of Adverse Events Reported During the Trial Period: After Approximately 25 Months	75 Number of adverse events

Secondary

Number of Adverse Events Reported During the Trial Period: After Approximately 80 Months

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

Time frame: After approximately 80 months

Population: Results are based on the SAS. SAS comprised all participants exposed to N8-GP in this trial.

Arm	Measure	Value (NUMBER)
N8-GP 50 U/kg Prophylaxis Q4D	Number of Adverse Events Reported During the Trial Period: After Approximately 80 Months	1326 Number of adverse events
N8-GP 20-75 U/kg On-demand	Number of Adverse Events Reported During the Trial Period: After Approximately 80 Months	369 Number of adverse events
N8-GP 20-75 U/kg On-demand	Number of Adverse Events Reported During the Trial Period: After Approximately 80 Months	132 Number of adverse events

Secondary

Number of Bleeds Using Pain Medication

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

Population: 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	Measure	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Number of Bleeds Using Pain Medication	0.1 Number of bleeds	Standard Deviation 0.4
N8-GP 20-75 U/kg On-demand	Number of Bleeds Using Pain Medication	0.5 Number of bleeds	Standard Deviation 1.4

Secondary

Number of Days at the Hospital During the Trial

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

Population: 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	Measure	Group	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Number of Days at the Hospital During the Trial	After approximately 19 months	0.1 Days	Standard Deviation 0.4
N8-GP 50 U/kg Prophylaxis Q4D	Number of Days at the Hospital During the Trial	After approximately 25 months	0.5 Days	Standard Deviation 3.8
N8-GP 50 U/kg Prophylaxis Q4D	Number of Days at the Hospital During the Trial	Month 25 to 80	0.5 Days	Standard Deviation 2.4
N8-GP 20-75 U/kg On-demand	Number of Days at the Hospital During the Trial	After approximately 19 months	0.0 Days	Standard Deviation 0
N8-GP 20-75 U/kg On-demand	Number of Days at the Hospital During the Trial	After approximately 25 months	0.7 Days	Standard Deviation 1.6
N8-GP 20-75 U/kg On-demand	Number of Days at the Hospital During the Trial	Month 25 to 80	0.0 Days	Standard Deviation 0

Secondary

Number of Days Missing School or Work

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

Time frame: Approx 19, 25 and 80 months

Population: 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	Measure	Group	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Number of Days Missing School or Work	After approximately 19 months	0.5 Days	Standard Deviation 1.6
N8-GP 50 U/kg Prophylaxis Q4D	Number of Days Missing School or Work	After approximately 25 months	0.8 Days	Standard Deviation 2
N8-GP 50 U/kg Prophylaxis Q4D	Number of Days Missing School or Work	Month 25 to 80	2.6 Days	Standard Deviation 14.4
N8-GP 20-75 U/kg On-demand	Number of Days Missing School or Work	After approximately 19 months	6.7 Days	Standard Deviation 16.9
N8-GP 20-75 U/kg On-demand	Number of Days Missing School or Work	After approximately 25 months	6.8 Days	Standard Deviation 16.9
N8-GP 20-75 U/kg On-demand	Number of Days Missing School or Work	Month 25 to 80	0.3 Days	Standard Deviation 0.4

Secondary

Number of Days Using Mobility Aid

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

Population: 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	Measure	Group	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Number of Days Using Mobility Aid	After approximately 24 months	4.4 Days	Standard Deviation 26.2
N8-GP 50 U/kg Prophylaxis Q4D	Number of Days Using Mobility Aid	After approximately 36 months	7.0 Days	Standard Deviation 42.7
N8-GP 50 U/kg Prophylaxis Q4D	Number of Days Using Mobility Aid	Month 25 to 80	1.0 Days	Standard Deviation 4.6
N8-GP 20-75 U/kg On-demand	Number of Days Using Mobility Aid	After approximately 24 months	11.1 Days	Standard Deviation 34.7
N8-GP 20-75 U/kg On-demand	Number of Days Using Mobility Aid	After approximately 36 months	5.8 Days	Standard Deviation 15.9
N8-GP 20-75 U/kg On-demand	Number of Days Using Mobility Aid	Month 25 to 80	0.5 Days	Standard Deviation 0.7

Secondary

Number of Hospital Admissions During the Trial

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

Time frame: After approx 19, 25 and 80 months

Population: 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	Measure	Group	Category	Value (COUNT_OF_UNITS)
N8-GP 50 U/kg Prophylaxis Q4D	Number of Hospital Admissions During the Trial	After approximately 19 months	1	3 Number of hospital admissions
N8-GP 50 U/kg Prophylaxis Q4D	Number of Hospital Admissions During the Trial	After approximately 25 months	2	1 Number of hospital admissions
N8-GP 50 U/kg Prophylaxis Q4D	Number of Hospital Admissions During the Trial	After approximately 25 months	0	84 Number of hospital admissions
N8-GP 50 U/kg Prophylaxis Q4D	Number of Hospital Admissions During the Trial	Month 25 to Month 80	0	20 Number of hospital admissions
N8-GP 50 U/kg Prophylaxis Q4D	Number of Hospital Admissions During the Trial	After approximately 19 months	2	0 Number of hospital admissions
N8-GP 50 U/kg Prophylaxis Q4D	Number of Hospital Admissions During the Trial	Month 25 to Month 80	1	1 Number of hospital admissions
N8-GP 50 U/kg Prophylaxis Q4D	Number of Hospital Admissions During the Trial	After approximately 25 months	1	4 Number of hospital admissions
N8-GP 50 U/kg Prophylaxis Q4D	Number of Hospital Admissions During the Trial	Month 25 to Month 80	2	0 Number of hospital admissions
N8-GP 50 U/kg Prophylaxis Q4D	Number of Hospital Admissions During the Trial	After approximately 19 months	0	49 Number of hospital admissions
N8-GP 20-75 U/kg On-demand	Number of Hospital Admissions During the Trial	Month 25 to Month 80	2	0 Number of hospital admissions
N8-GP 20-75 U/kg On-demand	Number of Hospital Admissions During the Trial	After approximately 19 months	0	8 Number of hospital admissions
N8-GP 20-75 U/kg On-demand	Number of Hospital Admissions During the Trial	After approximately 19 months	1	0 Number of hospital admissions
N8-GP 20-75 U/kg On-demand	Number of Hospital Admissions During the Trial	After approximately 19 months	2	0 Number of hospital admissions
N8-GP 20-75 U/kg On-demand	Number of Hospital Admissions During the Trial	After approximately 25 months	0	8 Number of hospital admissions
N8-GP 20-75 U/kg On-demand	Number of Hospital Admissions During the Trial	After approximately 25 months	1	2 Number of hospital admissions
N8-GP 20-75 U/kg On-demand	Number of Hospital Admissions During the Trial	After approximately 25 months	2	0 Number of hospital admissions
N8-GP 20-75 U/kg On-demand	Number of Hospital Admissions During the Trial	Month 25 to Month 80	0	2 Number of hospital admissions
N8-GP 20-75 U/kg On-demand	Number of Hospital Admissions During the Trial	Month 25 to Month 80	1	0 Number of hospital admissions

Secondary

Number of Participants Using Pain Medication

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

Population: 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	Measure	Group	Category	Value (COUNT_OF_PARTICIPANTS)
N8-GP 50 U/kg Prophylaxis Q4D	Number of Participants Using Pain Medication	After approximately 25 months	Yes	19 Participants
N8-GP 50 U/kg Prophylaxis Q4D	Number of Participants Using Pain Medication	After approximately 25 months	No	39 Participants
N8-GP 50 U/kg Prophylaxis Q4D	Number of Participants Using Pain Medication	Month 25 to 80	Yes	5 Participants
N8-GP 50 U/kg Prophylaxis Q4D	Number of Participants Using Pain Medication	Month 25 to 80	No	13 Participants
N8-GP 20-75 U/kg On-demand	Number of Participants Using Pain Medication	Month 25 to 80	No	0 Participants
N8-GP 20-75 U/kg On-demand	Number of Participants Using Pain Medication	After approximately 25 months	Yes	2 Participants
N8-GP 20-75 U/kg On-demand	Number of Participants Using Pain Medication	Month 25 to 80	Yes	1 Participants
N8-GP 20-75 U/kg On-demand	Number of Participants Using Pain Medication	After approximately 25 months	No	5 Participants

Secondary

Number of Serious Adverse Events Reported During the Trial Period: 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.

Time frame: After approximately 19 months

Population: Results are based on the SAS. SAS comprised all participants exposed to N8-GP in this trial.

Arm	Measure	Value (NUMBER)
N8-GP 50 U/kg Prophylaxis Q4D	Number of Serious Adverse Events Reported During the Trial Period: After Approximately 19 Months	13 Number of serious adverse events
N8-GP 20-75 U/kg On-demand	Number of Serious Adverse Events Reported During the Trial Period: After Approximately 19 Months	4 Number of serious adverse events

Secondary

Number of Serious Adverse Events Reported During the Trial Period: 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.

Time frame: After approximately 25 months

Population: Results are based on the SAS. SAS comprised all participants exposed to N8-GP in this trial.

Arm	Measure	Value (NUMBER)
N8-GP 50 U/kg Prophylaxis Q4D	Number of Serious Adverse Events Reported During the Trial Period: After Approximately 25 Months	27 Number of serious adverse events
N8-GP 20-75 U/kg On-demand	Number of Serious Adverse Events Reported During the Trial Period: After Approximately 25 Months	1 Number of serious adverse events
N8-GP 20-75 U/kg On-demand	Number of Serious Adverse Events Reported During the Trial Period: After Approximately 25 Months	4 Number of serious adverse events

Secondary

Number of Serious Adverse Events Reported During the Trial Period: 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.

Time frame: After approximately 80 months

Population: Results are based on the SAS. SAS comprised all participants exposed to N8-GP in this trial.

Arm	Measure	Value (NUMBER)
N8-GP 50 U/kg Prophylaxis Q4D	Number of Serious Adverse Events Reported During the Trial Period: After Approximately 80 Months	39 Number of serious adverse events
N8-GP 20-75 U/kg On-demand	Number of Serious Adverse Events Reported During the Trial Period: After Approximately 80 Months	16 Number of serious adverse events
N8-GP 20-75 U/kg On-demand	Number of Serious Adverse Events Reported During the Trial Period: After Approximately 80 Months	8 Number of serious adverse events

Secondary

Patient Reported Outcomes - Change in EQ-5D-VAS Scores: 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.

Time frame: After approx 19 and 25 months

Population: 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	Measure	Group	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approx 19 and 25 Months	Week 0 (Baseline)	76.5 Scores on a scale	Standard Deviation 17.9
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approx 19 and 25 Months	Week 76 (Change from baseline)	2.0 Scores on a scale	Standard Deviation 11.1
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approx 19 and 25 Months	Week 140 (Change from week 76)	-0.8 Scores on a scale	Standard Deviation 11.8
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approx 19 and 25 Months	Week 0 (Baseline)	74.5 Scores on a scale	Standard Deviation 13.1
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approx 19 and 25 Months	Week 76 (Change from baseline)	4.1 Scores on a scale	Standard Deviation 7.2
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approx 19 and 25 Months	Week 140 (Change from week 76)	2.7 Scores on a scale	Standard Deviation 11

Secondary

Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approximately 80 Months

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

Population: Results were based on the FAS which included all participants exposed to N8-GP in this trial.

Arm	Measure	Group	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approximately 80 Months	1 to <2 years (Change from baseline)	4.9 Scores on a scale	Standard Deviation 8.2
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approximately 80 Months	2 to <3 years (Change from baseline)	2.6 Scores on a scale	Standard Deviation 13.3
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approximately 80 Months	3 to <4 years (Change from baseline)	3.0 Scores on a scale	Standard Deviation 13.5
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approximately 80 Months	4 to <5 years (Change from baseline)	1.0 Scores on a scale	Standard Deviation 15.8
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approximately 80 Months	5 to <6 years (Change from baseline)	2.2 Scores on a scale	Standard Deviation 13.2
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approximately 80 Months	6 to <7 years (Change from baseline)	7.5 Scores on a scale	Standard Deviation 13.6
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approximately 80 Months	4 to <5 years (Change from baseline)	11.0 Scores on a scale	Standard Deviation 9.6
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approximately 80 Months	2 to <3 years (Change from baseline)	9.5 Scores on a scale	Standard Deviation 6.4
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approximately 80 Months	6 to <7 years (Change from baseline)	16.3 Scores on a scale	Standard Deviation 12.1
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approximately 80 Months	3 to <4 years (Change from baseline)	7.3 Scores on a scale	Standard Deviation 7
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approximately 80 Months	5 to <6 years (Change from baseline)	15.0 Scores on a scale	Standard Deviation 21.2

Secondary

Patient Reported Outcomes - Change in European Quality of Life Utility Index: 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.

Time frame: After approx 19 and 25 months

Population: 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	Measure	Group	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in European Quality of Life Utility Index: After Approx 19 and 25 Months	Month 19 (Change from baseline)	0.011 Scores on a scale	Standard Deviation 0.184
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in European Quality of Life Utility Index: After Approx 19 and 25 Months	Month 25 (Change from Month 19)	-0.025 Scores on a scale	Standard Deviation 0.174
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in European Quality of Life Utility Index: After Approx 19 and 25 Months	Month 19 (Change from baseline)	-0.028 Scores on a scale	Standard Deviation 0.047
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in European Quality of Life Utility Index: After Approx 19 and 25 Months	Month 25 (Change from Month 19)	-0.028 Scores on a scale	Standard Deviation 0.093

Secondary

Patient Reported Outcomes - Change in European Quality of Life Utility Index Scores: After Approximately 80 Months

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

Population: Results were based on the FAS which included all participants exposed to N8-GP in this trial.

Arm	Measure	Group	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in European Quality of Life Utility Index Scores: After Approximately 80 Months	1 to <2 years (Change from baseline)	0.052 Scores on a scale	Standard Deviation 0.252
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in European Quality of Life Utility Index Scores: After Approximately 80 Months	2 to <3 years (Change from baseline)	-0.008 Scores on a scale	Standard Deviation 0.159
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in European Quality of Life Utility Index Scores: After Approximately 80 Months	3 to <4 years (Change from baseline)	0.021 Scores on a scale	Standard Deviation 0.193
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in European Quality of Life Utility Index Scores: After Approximately 80 Months	4 to <5 years (Change from baseline)	0.000 Scores on a scale	Standard Deviation 0.165
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in European Quality of Life Utility Index Scores: After Approximately 80 Months	5 to <6 years (Change from baseline)	0.011 Scores on a scale	Standard Deviation 0.178
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in European Quality of Life Utility Index Scores: After Approximately 80 Months	6 to <7 years (Change from baseline)	-0.062 Scores on a scale	Standard Deviation 0.163
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in European Quality of Life Utility Index Scores: After Approximately 80 Months	4 to <5 years (Change from baseline)	-0.001 Scores on a scale	Standard Deviation 0.057
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in European Quality of Life Utility Index Scores: After Approximately 80 Months	2 to <3 years (Change from baseline)	0.000 Scores on a scale	Standard Deviation 0
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in European Quality of Life Utility Index Scores: After Approximately 80 Months	6 to <7 years (Change from baseline)	0.000 Scores on a scale	Standard Deviation 0
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in European Quality of Life Utility Index Scores: After Approximately 80 Months	3 to <4 years (Change from baseline)	0.000 Scores on a scale	Standard Deviation 0
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in European Quality of Life Utility Index Scores: After Approximately 80 Months	5 to <6 years (Change from baseline)	0.000 Scores on a scale	Standard Deviation 0

Secondary

Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: 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.

Time frame: After approx 19 and 25 months

Population: 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	Measure	Group	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approx 19 and 25 Months	Week 76 (Change from baseline)	-2.3 Scores on a scale	Standard Deviation 8.9
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approx 19 and 25 Months	Week 140 (Change from week 76)	0.7 Scores on a scale	Standard Deviation 8
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approx 19 and 25 Months	Week 76 (Change from baseline)	-3.1 Scores on a scale	Standard Deviation 10.3
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approx 19 and 25 Months	Week 140 (Change from week 76)	-0.6 Scores on a scale	Standard Deviation 4.9

Secondary

Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approximately 80 Months

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

Population: 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	Measure	Group	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approximately 80 Months	1 to <2 years (Change from baseline)	-6.6 Scores on a scale	Standard Deviation 6.7
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approximately 80 Months	2 to <3 years (Change from baseline)	-2.6 Scores on a scale	Standard Deviation 10.3
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approximately 80 Months	3 to <4 years (Change from baseline)	-2.3 Scores on a scale	Standard Deviation 8.9
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approximately 80 Months	4 to <5 years (Change from baseline)	-3.1 Scores on a scale	Standard Deviation 10.4
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approximately 80 Months	5 to <6 years (Change from baseline)	-3.1 Scores on a scale	Standard Deviation 11.2
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approximately 80 Months	6 to <7 years (Change from baseline)	-3.5 Scores on a scale	Standard Deviation 9
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approximately 80 Months	4 to <5 years (Change from baseline)	-2.5 Scores on a scale	Standard Deviation 19.5
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approximately 80 Months	2 to <3 years (Change from baseline)	-10.7 Scores on a scale	Standard Deviation 8.7
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approximately 80 Months	6 to <7 years (Change from baseline)	-7.8 Scores on a scale	Standard Deviation 8.6
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approximately 80 Months	3 to <4 years (Change from baseline)	-5.8 Scores on a scale	Standard Deviation 12.2
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approximately 80 Months	5 to <6 years (Change from baseline)	-1.7 Scores on a scale	Standard Deviation 2.8

Secondary

Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Parents of Patients 13-16 Years Old): 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.

Time frame: After approx 19 and 25 months

Population: 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	Measure	Group	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Parents of Patients 13-16 Years Old): After Approx 19 and 25 Months	After approximately 19 months	-4.0 Scores on a scale	Standard Deviation 13.1
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Parents of Patients 13-16 Years Old): After Approx 19 and 25 Months	After approximately 25 months	1.8 Scores on a scale	Standard Deviation 8.3

Secondary

Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Parents of Patients 13-16 Years Old): After Approx 80 Months

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

Population: 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	Measure	Group	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Parents of Patients 13-16 Years Old): After Approx 80 Months	2 to <3 years (Change from baseline)	1.5 Scores on a scale	Standard Deviation 2.1
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Parents of Patients 13-16 Years Old): After Approx 80 Months	3 to <4 years (Change from baseline)	-8.1 Scores on a scale	Standard Deviation 7
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Parents of Patients 13-16 Years Old): After Approx 80 Months	4 to <5 years (Change from baseline)	-7.9 Scores on a scale	Standard Deviation 13.8
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Parents of Patients 13-16 Years Old): After Approx 80 Months	5 to <6 years (Change from baseline)	1.6 Scores on a scale	Standard Deviation 11.4
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Parents of Patients 13-16 Years Old): After Approx 80 Months	6 to <7 years (Change from baseline)	10.7 Scores on a scale	Standard Deviation 0

Secondary

Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Patients 13-16 Years Old) 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.

Time frame: After approx 19 and 25 months

Arm	Measure	Group	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Patients 13-16 Years Old) After Approx 19 and 25 Months	Approx month 19 (Change from baseline)	-0.1 Scores on a scale	Standard Deviation 12.4
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Patients 13-16 Years Old) After Approx 19 and 25 Months	Approx month 25 (Change from month 19)	0.8 Scores on a scale	Standard Deviation 4.5

Secondary

Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Patients 13-16 Years Old): After Approx 80 Months

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

Arm	Measure	Group	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Patients 13-16 Years Old): After Approx 80 Months	2 to <3 years (Change from baseline)	2.7 Scores on a scale	Standard Deviation 15.9
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Patients 13-16 Years Old): After Approx 80 Months	3 to <4 years (Change from baseline)	-0.9 Scores on a scale	Standard Deviation 11.6
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Patients 13-16 Years Old): After Approx 80 Months	4 to <5 years (Change from baseline)	2.6 Scores on a scale	Standard Deviation 15.8
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Patients 13-16 Years Old): After Approx 80 Months	5 to <6 years (Change from baseline)	2.1 Scores on a scale	Standard Deviation 11.7
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Patients 13-16 Years Old): After Approx 80 Months	6 to <7 years (Change from baseline)	-0.3 Scores on a scale	Standard Deviation 0

Secondary

Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months

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

Population: Results were based on the FAS which included all participants exposed to N8-GP in this trial.

Arm	Measure	Group	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Ease & convenience 2 to <3 years	-0.6 Scores on a scale	Standard Deviation 6.8
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Ease & convenience 3 to <4 years	9.1 Scores on a scale	Standard Deviation 0
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Ease & convenience 4 to <5 years	-5.3 Scores on a scale	Standard Deviation 14.1
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Ease & convenience 5 to <6 years	-3.6 Scores on a scale	Standard Deviation 13.5
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Ease & convenience 6 to <7 years	0.0 Scores on a scale	Standard Deviation 0
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Efficacy 2 to <3 years	-6.3 Scores on a scale	Standard Deviation 2.4
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Efficacy 3 to <4 years	-8.3 Scores on a scale	Standard Deviation 0
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Efficacy 4 to <5 years	-6.3 Scores on a scale	Standard Deviation 4.4
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Efficacy 5 to <6 years	3.3 Scores on a scale	Standard Deviation 17
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Efficacy 6 to <7 years	-4.2 Scores on a scale	Standard Deviation 0
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Burden 2 to <3 years	-20.3 Scores on a scale	Standard Deviation 15.6
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Burden 3 to <4 years	-25.0 Scores on a scale	Standard Deviation 0
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Burden 4 to <5 years	-6.3 Scores on a scale	Standard Deviation 26.2
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Burden 5 to <6 years	2.5 Scores on a scale	Standard Deviation 15.1
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Burden 6 to <7 years	-31.3 Scores on a scale	Standard Deviation 0
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Specialist/nurses 2 to <3 years	-3.6 Scores on a scale	Standard Deviation 7.1
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Specialist/nurses 3 to <4 years	0.0 Scores on a scale	Standard Deviation 0
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Specialist/nurses 4 to <5 years	-6.5 Scores on a scale	Standard Deviation 11.8
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Specialist/nurses 5 to <6 years	3.6 Scores on a scale	Standard Deviation 17.5
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Specialist/nurses 6 to <7 years	0.0 Scores on a scale	Standard Deviation 0
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Centre/hospital 2 to <3 years	-3.7 Scores on a scale	Standard Deviation 4.8
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Centre/hospital 3 to <4 years	-5.0 Scores on a scale	Standard Deviation 0
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Centre/hospital 4 to <5 years	-8.3 Scores on a scale	Standard Deviation 8.8
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Centre/hospital 5 to <6 years	-3.0 Scores on a scale	Standard Deviation 14.4
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Centre/hospital 6 to <7 years	0.0 Scores on a scale	Standard Deviation 0
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Gen. satisfaction 2 to <3 years	-9.4 Scores on a scale	Standard Deviation 12
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Gen. satisfaction 3 to <4 years	-12.5 Scores on a scale	Standard Deviation 0
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Gen. satisfaction 4 to <5 years	-6.3 Scores on a scale	Standard Deviation 10.5
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Gen. satisfaction 5 to <6 years	5.0 Scores on a scale	Standard Deviation 14.3
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months	Gen. satisfaction 6 to <7 years	0.0 Scores on a scale	Standard Deviation 0

Secondary

Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: 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.

Time frame: After approx 19 and 25 months

Population: 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	Measure	Group	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Ease & convenience (Change - Approx 19 months)	-0.4 Scores on a scale	Standard Deviation 13.8
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Ease & convenience (Change - Approx 25 months)	0.3 Scores on a scale	Standard Deviation 11.7
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Efficacy (Change - Approx 19 months)	-6.3 Scores on a scale	Standard Deviation 15.6
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Efficacy (Change - Approx 25 months)	-0.2 Scores on a scale	Standard Deviation 11
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Burden (Change - Approx 19 months)	-2.2 Scores on a scale	Standard Deviation 15.8
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Burden (Change - Approx 25 months)	-0.9 Scores on a scale	Standard Deviation 11.3
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Speciaist/nurses (Change - approx 19 months)	-2.9 Scores on a scale	Standard Deviation 11.7
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Speciaist/nurses (Change - approx 25 months)	1.8 Scores on a scale	Standard Deviation 9.1
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Centre/hospital (Change - approx 19 months)	-2.2 Scores on a scale	Standard Deviation 11.9
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Centre/hospital (Change - approx 25 months)	1.0 Scores on a scale	Standard Deviation 8.1
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Gen. satisfaction (Change - approx 19 months)	-2.9 Scores on a scale	Standard Deviation 15.4
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Gen. satisfaction (Change - approx 25 months)	-1.1 Scores on a scale	Standard Deviation 9.4
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Gen. satisfaction (Change - approx 19 months)	-3.4 Scores on a scale	Standard Deviation 11.3
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Ease & convenience (Change - Approx 19 months)	-4.5 Scores on a scale	Standard Deviation 11.5
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Speciaist/nurses (Change - approx 19 months)	-4.5 Scores on a scale	Standard Deviation 8.3
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Ease & convenience (Change - Approx 25 months)	-6.3 Scores on a scale	Standard Deviation 6.9
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Centre/hospital (Change - approx 25 months)	4.2 Scores on a scale	Standard Deviation 10.7
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Efficacy (Change - Approx 19 months)	-11.3 Scores on a scale	Standard Deviation 11.1
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Speciaist/nurses (Change - approx 25 months)	0.0 Scores on a scale	Standard Deviation 8.1
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Efficacy (Change - Approx 25 months)	0.0 Scores on a scale	Standard Deviation 5.9
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Gen. satisfaction (Change - approx 25 months)	2.1 Scores on a scale	Standard Deviation 5.1
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Burden (Change - Approx 19 months)	-5.0 Scores on a scale	Standard Deviation 18.8
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Centre/hospital (Change - approx 19 months)	-3.6 Scores on a scale	Standard Deviation 7.8
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months	Burden (Change - Approx 25 months)	0.0 Scores on a scale	Standard Deviation 6.3

Secondary

Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months

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

Population: Results were based on the FAS which included all participants exposed to N8-GP in this trial.

Arm	Measure	Group	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Ease & convenience 1 to <2 years	-2.2 Scores on a scale	Standard Deviation 12.7
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Ease & convenience 2 to <3 years	-2.4 Scores on a scale	Standard Deviation 14.4
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Efficacy 1 to <2 years	-1.9 Scores on a scale	Standard Deviation 9.3
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Efficacy 2 to <3 years	-7.1 Scores on a scale	Standard Deviation 14.9
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Efficacy 3 to <4 years	-7.2 Scores on a scale	Standard Deviation 13.6
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Efficacy 4 to <5 years	-9.5 Scores on a scale	Standard Deviation 16.4
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Efficacy 5 to <6 years	-7.4 Scores on a scale	Standard Deviation 14.4
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Efficacy 6 to <7 years	-13.2 Scores on a scale	Standard Deviation 21.8
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Burden 1 to <2 years	0.7 Scores on a scale	Standard Deviation 13.4
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Burden 2 to <3 years	-3.6 Scores on a scale	Standard Deviation 16.9
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Burden 3 to <4 years	-5.0 Scores on a scale	Standard Deviation 15.1
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Burden 4 to <5 years	-4.9 Scores on a scale	Standard Deviation 16.9
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Burden 5 to <6 years	-4.9 Scores on a scale	Standard Deviation 13.5
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Burden 6 to <7 years	-10.1 Scores on a scale	Standard Deviation 19.1
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Specialist/nurses 1 to <2 years	-2.0 Scores on a scale	Standard Deviation 12.8
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Specialist/nurses 2 to <3 years	-2.8 Scores on a scale	Standard Deviation 11.4
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Specialist/nurses 3 to <4 years	-2.3 Scores on a scale	Standard Deviation 10.9
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Specialist/nurses 4 to <5 years	-1.4 Scores on a scale	Standard Deviation 11.4
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Specialist/nurses 5 to <6 years	-0.8 Scores on a scale	Standard Deviation 9.7
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Specialist/nurses 6 to <7 years	-0.2 Scores on a scale	Standard Deviation 15.4
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Centre/hospital 1 to <2 years	-5.0 Scores on a scale	Standard Deviation 12
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Centre/hospital 2 to <3 years	-2.9 Scores on a scale	Standard Deviation 11.9
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Centre/hospital 3 to <4 years	-1.3 Scores on a scale	Standard Deviation 10.5
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Centre/hospital 4 to <5 years	-1.1 Scores on a scale	Standard Deviation 12.5
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Centre/hospital 5 to <6 years	-1.0 Scores on a scale	Standard Deviation 9.7
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Centre/hospital 6 to <7 years	1.2 Scores on a scale	Standard Deviation 17.7
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Gen. satisfaction 1 to <2 years	-1.4 Scores on a scale	Standard Deviation 11.6
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Gen. satisfaction 2 to <3 years	-4.1 Scores on a scale	Standard Deviation 15.2
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Gen. satisfaction 3 to <4 years	-2.8 Scores on a scale	Standard Deviation 10.7
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Gen. satisfaction 4 to <5 years	-5.0 Scores on a scale	Standard Deviation 14.4
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Gen. satisfaction 5 to <6 years	-2.2 Scores on a scale	Standard Deviation 12.2
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Gen. satisfaction 6 to <7 years	-5.4 Scores on a scale	Standard Deviation 19.6
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Ease & convenience 3 to <4 years	-3.7 Scores on a scale	Standard Deviation 13.6
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Ease & convenience 4 to <5 years	-3.7 Scores on a scale	Standard Deviation 13.6
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Ease & convenience 5 to <6 years	-3.3 Scores on a scale	Standard Deviation 13.7
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Ease & convenience 6 to <7 years	-7.2 Scores on a scale	Standard Deviation 12.4
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Ease & convenience 2 to <3 years	-23.8 Scores on a scale	Standard Deviation 12.4
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Burden 6 to <7 years	-4.7 Scores on a scale	Standard Deviation 9.4
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Ease & convenience 3 to <4 years	-10.5 Scores on a scale	Standard Deviation 18.3
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Centre/hospital 3 to <4 years	3.0 Scores on a scale	Standard Deviation 4.5
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Ease & convenience 4 to <5 years	-4.4 Scores on a scale	Standard Deviation 34.4
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Gen. satisfaction 2 to <3 years	-6.3 Scores on a scale	Standard Deviation 8.8
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Ease & convenience 5 to <6 years	-16.7 Scores on a scale	Standard Deviation 11.8
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Specialist/nurses 2 to <3 years	0.0 Scores on a scale	Standard Deviation 0
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Ease & convenience 6 to <7 years	-5.6 Scores on a scale	Standard Deviation 8.3
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Centre/hospital 4 to <5 years	26.3 Scores on a scale	Standard Deviation 43.1
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Specialist/nurses 3 to <4 years	0.7 Scores on a scale	Standard Deviation 8.9
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Efficacy 2 to <3 years	-16.7 Scores on a scale	Standard Deviation 5.9
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Gen. satisfaction 6 to <7 years	-18.8 Scores on a scale	Standard Deviation 16.1
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Efficacy 3 to <4 years	-17.5 Scores on a scale	Standard Deviation 14.3
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Specialist/nurses 4 to <5 years	21.4 Scores on a scale	Standard Deviation 47.7
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Efficacy 4 to <5 years	2.1 Scores on a scale	Standard Deviation 35.8
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Centre/hospital 5 to <6 years	1.7 Scores on a scale	Standard Deviation 29.3
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Efficacy 5 to <6 years	-16.7 Scores on a scale	Standard Deviation 20.8
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Specialist/nurses 5 to <6 years	-11.9 Scores on a scale	Standard Deviation 8.2
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Efficacy 6 to <7 years	-3.1 Scores on a scale	Standard Deviation 13.8
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Gen. satisfaction 3 to <4 years	-17.5 Scores on a scale	Standard Deviation 14.3
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Specialist/nurses 6 to <7 years	-6.3 Scores on a scale	Standard Deviation 7.4
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Burden 2 to <3 years	-21.9 Scores on a scale	Standard Deviation 4.4
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Centre/hospital 6 to <7 years	-8.8 Scores on a scale	Standard Deviation 6.3
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Burden 3 to <4 years	-17.5 Scores on a scale	Standard Deviation 14.9
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Gen. satisfaction 5 to <6 years	-20.8 Scores on a scale	Standard Deviation 7.2
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Burden 4 to <5 years	-3.1 Scores on a scale	Standard Deviation 28.2
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Centre/hospital 2 to <3 years	0.0 Scores on a scale	Standard Deviation 0
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Burden 5 to <6 years	-18.8 Scores on a scale	Standard Deviation 10.8
N8-GP 20-75 U/kg On-demand	Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months	Gen. satisfaction 4 to <5 years	0.0 Scores on a scale	Standard Deviation 35.4

Secondary

Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): 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.

Time frame: After approx 19 and 25 months

Population: 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	Measure	Group	Value (MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): After Approx 19 and 25 Months	Ease & convenience - baseline (Week 0)	27.8 Scores on a scale	Standard Deviation 15.5
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): After Approx 19 and 25 Months	Ease & convenience (Change - Approx 19 months)	0.4 Scores on a scale	Standard Deviation 3.3
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): After Approx 19 and 25 Months	Ease & convenience (Change - Approx 25 months)	-6.3 Scores on a scale	Standard Deviation 8.1
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): After Approx 19 and 25 Months	Efficacy - baseline (Week 0)	17.9 Scores on a scale	Standard Deviation 12.3
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): After Approx 19 and 25 Months	Efficacy (Change - Approx 19 months)	-5.2 Scores on a scale	Standard Deviation 2.1
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): After Approx 19 and 25 Months	Efficacy (Change - Approx 25 months)	2.1 Scores on a scale	Standard Deviation 5.7
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): After Approx 19 and 25 Months	Burden- baseline (Week 0)	23.8 Scores on a scale	Standard Deviation 14.4
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): After Approx 19 and 25 Months	Burden (Change - Approx 19 months)	-10.9 Scores on a scale	Standard Deviation 12.9
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): After Approx 19 and 25 Months	Burden (Change - Approx 25 months)	-4.2 Scores on a scale	Standard Deviation 11.6
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): After Approx 19 and 25 Months	Specialist/nurses (Week 0)	7.1 Scores on a scale	Standard Deviation 10.9
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): After Approx 19 and 25 Months	Speciaist/nurses (Change - approx 19 months)	0.0 Scores on a scale	Standard Deviation 0
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): After Approx 19 and 25 Months	Speciaist/nurses (Change - approx 25 months)	0.6 Scores on a scale	Standard Deviation 1.5
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): After Approx 19 and 25 Months	Centre/Hospital (Week 0)	10.5 Scores on a scale	Standard Deviation 11.7
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): After Approx 19 and 25 Months	Centre/hospital (Change - approx 19 months)	-3.7 Scores on a scale	Standard Deviation 4.8
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): After Approx 19 and 25 Months	Centre/hospital (Change - approx 25 months)	-0.8 Scores on a scale	Standard Deviation 2
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): After Approx 19 and 25 Months	Gen. satisfaction (Week 0)	8.8 Scores on a scale	Standard Deviation 11.9
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): After Approx 19 and 25 Months	Gen. satisfaction (Change - approx 19 months)	0.0 Scores on a scale	Standard Deviation 0
N8-GP 50 U/kg Prophylaxis Q4D	Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): After Approx 19 and 25 Months	Gen. satisfaction (Change - approx 25 months)	0.0 Scores on a scale	Standard Deviation 0

Secondary

Terminal Half Life (t1/2)

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

Population: 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	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Terminal Half Life (t1/2)	Week 0	18.27 Hour (h)	Geometric Coefficient of Variation 27.4
N8-GP 50 U/kg Prophylaxis Q4D	Terminal Half Life (t1/2)	Week 28	18.18 Hour (h)	Geometric Coefficient of Variation 31.43

Secondary

Trough Level (Single Dose and Steady State)

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

Population: 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	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Trough Level (Single Dose and Steady State)	Week 0	0.032 IU/mL	Geometric Coefficient of Variation 138.3
N8-GP 50 U/kg Prophylaxis Q4D	Trough Level (Single Dose and Steady State)	Week 28	0.035 IU/mL	Geometric Coefficient of Variation 138.4

Secondary

Volume of Distribution at Steady State (Vss)

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

Population: 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	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
N8-GP 50 U/kg Prophylaxis Q4D	Volume of Distribution at Steady State (Vss)	Week 0	30.40 mL/kg	Geometric Coefficient of Variation 24.18
N8-GP 50 U/kg Prophylaxis Q4D	Volume of Distribution at Steady State (Vss)	Week 28	28.38 mL/kg	Geometric Coefficient of Variation 19.43

Source: ClinicalTrials.gov · Data processed: Mar 3, 2026

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

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 19 Months

Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 25 Months

Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 80 Months

Incidence Rate of FVIII-inhibitors ≥0.6 BU: At Approximately 80 Months

The Incidence Rate of FVIII-inhibitors ≥0.6 BU: After Approximately 19 Months

The Incidence Rate of FVIII-inhibitors ≥0.6 BU: After Approximately 25 Months

Area Under the Curve (AUC0-inf)

Area Under the Curve (AUC0-t)

Change in Blood Pressure: After Approximately 19 Months

Change in Blood Pressure: After Approximately 25 Months

Change in Blood Pressure: After Approximately 80 Months

Change in Body Temperature: After Approximately 19 Months

Change in Body Temperature: After Approximately 25 Months

Change in Body Temperature: After Approximately 80 Months

Change in Pulse: After Approximately 19 Months

Change in Pulse: After Approximately 25 Months

Change in Pulse: After Approximately 80 Months

Change in Respiratory Rate: After Approximately 19 Months

Change in Respiratory Rate: After Approximately 25 Months

Change in Respiratory Rate: After Approximately 80 Months

Clearance (CL)

Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 19 Months

Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 25 Months

Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 80 Months

Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 19 Months

Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 25 Months

Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 80 Months

Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 19 Months

Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 25 Months

Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 80 Months

Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 19 Months

Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 25 Months

Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 80 Months

Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 19 Months

Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 25 Months

Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 80 Months

FVIII Activity 30 Min Post -Injection (C30min)

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

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

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

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

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

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

Incremental Recovery (Single Dose and Steady State)

Mean Residence Time (MRT)

Number of Admissions to the Emergency Room (ER) During the Trial

Number of Adverse Events Reported During the Trial Period: After Approximately 19 Months

Number of Adverse Events Reported During the Trial Period: After Approximately 25 Months

Number of Adverse Events Reported During the Trial Period: After Approximately 80 Months

Number of Bleeds Using Pain Medication

Number of Days at the Hospital During the Trial

Number of Days Missing School or Work

Number of Days Using Mobility Aid

Number of Hospital Admissions During the Trial

Number of Participants Using Pain Medication

Number of Serious Adverse Events Reported During the Trial Period: After Approximately 19 Months

Number of Serious Adverse Events Reported During the Trial Period: After Approximately 25 Months

Number of Serious Adverse Events Reported During the Trial Period: After Approximately 80 Months