Trial Outcomes & Findings for A Multinational, Open-Label, Non-Controlled Trial on Safety, Efficacy and Pharmacokinetics of NNC 0129-0000-1003 in Previously Treated Paediatric Patients With Severe Haemophilia A (NCT NCT01731600)

Last Updated: 2020-11-23

Results Overview

The number of participants with inhibitory antibodies against coagulation factor VIII (FVIII) ≥0.6 Bethesda units was presented.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

68 participants

Primary outcome timeframe

During the main phase of the trial (from 0-26 weeks of treatment)

Results posted on

2020-11-23

Participant Flow

The trial was conducted at 36 sites in 15 countries as follows: Canada (1), France (2), Germany (1), Greece (2 sites screened/1 site randomised subjects), Israel (1), Italy (1), Japan (2), Lithuania (1), Malaysia (1), Portugal (1), Switzerland (3), Turkey (3), Ukraine (2), United Kingdom (3), and United States (12).

Participant milestones

Participant milestones
Measure	Younger Children (0 - 5 Years) Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). Prophylaxis: N8-GP as a single bolus iv injection 60 IU/kg twice weekly. Treatment of bleeding episodes: N8-GP ranging from 20-75 IU/kg, according to severity and location of bleeding episode. The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.	Older Children (6 - 11 Years) Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). Prophylaxis: N8-GP as a single bolus iv injection 60 IU/kg twice weekly. Treatment of bleeding episodes: N8-GP ranging from 20-75 IU/kg, according to severity and location of bleeding episode. The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.
Overall Study STARTED	34	34
Overall Study COMPLETED	28	34
Overall Study NOT COMPLETED	6	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Younger Children (0 - 5 Years) Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). Prophylaxis: N8-GP as a single bolus iv injection 60 IU/kg twice weekly. Treatment of bleeding episodes: N8-GP ranging from 20-75 IU/kg, according to severity and location of bleeding episode. The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.	Older Children (6 - 11 Years) Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). Prophylaxis: N8-GP as a single bolus iv injection 60 IU/kg twice weekly. Treatment of bleeding episodes: N8-GP ranging from 20-75 IU/kg, according to severity and location of bleeding episode. The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.
Overall Study Adverse Event	2	0
Overall Study Withdrawal criteria	1	0
Overall Study Other reasons	3	0

Baseline Characteristics

A Multinational, Open-Label, Non-Controlled Trial on Safety, Efficacy and Pharmacokinetics of NNC 0129-0000-1003 in Previously Treated Paediatric Patients With Severe Haemophilia A

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Younger Children (0 - 5 Years) n=34 Participants Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). Prophylaxis: N8-GP as a single bolus iv injection 60 IU/kg twice weekly. Treatment of bleeding episodes: N8-GP ranging from 20-75 IU/kg, according to severity and location of bleeding episode. The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.	Older Children (6 - 11 Years) n=34 Participants Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). Prophylaxis: N8-GP as a single bolus iv injection 60 IU/kg twice weekly. Treatment of bleeding episodes: N8-GP ranging from 20-75 IU/kg, according to severity and location of bleeding episode. The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.	Total n=68 Participants Total of all reporting groups
Age, Continuous	3.0 years STANDARD_DEVIATION 1.3 • n=5 Participants	8.9 years STANDARD_DEVIATION 1.7 • n=7 Participants	6.0 years STANDARD_DEVIATION 3.3 • n=5 Participants
Age, Customized Infants and toddlers (28 days-23 months)	6 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants
Age, Customized Children (2-11 years)	28 Participants n=5 Participants	34 Participants n=7 Participants	62 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	34 Participants n=5 Participants	34 Participants n=7 Participants	68 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	34 Participants n=5 Participants	30 Participants n=7 Participants	64 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White	30 Participants n=5 Participants	25 Participants n=7 Participants	55 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Not applicable	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: During the main phase of the trial (from 0-26 weeks of treatment)

Population: Results were based on safety analysis set (SAS). The SAS consists of all patients exposed to at least one dose of turoctocog alfa pegol. Number analysed = participants with minimum of 50 exposure days and developed inhibitory antibodies

The number of participants with inhibitory antibodies against coagulation factor VIII (FVIII) ≥0.6 Bethesda units was presented.

Outcome measures

Outcome measures
Measure	Younger Children (0 - 5 Years) [Main Trial] n=34 Participants Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Older Children (6 - 11 Years) [Main Trial] n=34 Participants Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Younger Children (0 - 5 Years) [Full Trial] Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.	Older Children (6 - 11 Years) [Full Trial] Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.
Number of Participants With Inhibitory Antibodies Against Coagulation Factor VIII (FVIII) ≥0.6 Bethesda Units	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)

Population: Results were based on SAS.

The frequency of adverse events including serious adverse events reported during the main and extension phase of the trial. The data presented is the rate of AE i.e. number of AEs per patient years of exposue.

Outcome measures

Outcome measures
Measure	Younger Children (0 - 5 Years) [Main Trial] n=34 Participants Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Older Children (6 - 11 Years) [Main Trial] n=34 Participants Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Younger Children (0 - 5 Years) [Full Trial] n=34 Participants Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.	Older Children (6 - 11 Years) [Full Trial] n=34 Participants Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.
Frequency of Adverse Events Including Serious Adverse Events Reported During the Trial Period	4.87 Events per patient years of exposure	4.74 Events per patient years of exposure	3.09 Events per patient years of exposure	2.45 Events per patient years of exposure

SECONDARY outcome

Timeframe: Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)

Population: Results were based on full analysis set (FAS). All trial patients allocated to treatment, for which at least one of the pharmacokinetic or efficacy endpoints was assessed, were included in the FAS.

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 patient and/or parent(s)/caregiver 8 hours after first injection as follows: Excellent: Abrupt pain relief and/or clear improvement in objective signs of bleeding within approximately 8 hours after a single injection; Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hours 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.

Outcome measures

Outcome measures
Measure	Younger Children (0 - 5 Years) [Main Trial] n=30 Bleeding episodes Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Older Children (6 - 11 Years) [Main Trial] n=40 Bleeding episodes Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Younger Children (0 - 5 Years) [Full Trial] n=108 Bleeding episodes Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.	Older Children (6 - 11 Years) [Full Trial] n=222 Bleeding episodes Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.
Haemostatic Effect of N8-GP When Used for Treatment of Bleeding Episodes and Assessed as: Excellent, Good, Moderate, or None Excellent	11 Bleeding episodes	12 Bleeding episodes	47 Bleeding episodes	96 Bleeding episodes
Haemostatic Effect of N8-GP When Used for Treatment of Bleeding Episodes and Assessed as: Excellent, Good, Moderate, or None Good	13 Bleeding episodes	19 Bleeding episodes	48 Bleeding episodes	74 Bleeding episodes
Haemostatic Effect of N8-GP When Used for Treatment of Bleeding Episodes and Assessed as: Excellent, Good, Moderate, or None Moderate	4 Bleeding episodes	7 Bleeding episodes	9 Bleeding episodes	44 Bleeding episodes
Haemostatic Effect of N8-GP When Used for Treatment of Bleeding Episodes and Assessed as: Excellent, Good, Moderate, or None None	1 Bleeding episodes	0 Bleeding episodes	2 Bleeding episodes	2 Bleeding episodes
Haemostatic Effect of N8-GP When Used for Treatment of Bleeding Episodes and Assessed as: Excellent, Good, Moderate, or None Missing	1 Bleeding episodes	2 Bleeding episodes	2 Bleeding episodes	6 Bleeding episodes

SECONDARY outcome

Timeframe: Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)

Population: Results were based on FAS.

The number of bleeding episodes per year reported during the prophylactic treatment with N8-GP.

Outcome measures

Outcome measures
Measure	Younger Children (0 - 5 Years) [Main Trial] n=34 Participants Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Older Children (6 - 11 Years) [Main Trial] n=34 Participants Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Younger Children (0 - 5 Years) [Full Trial] n=34 Participants Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.	Older Children (6 - 11 Years) [Full Trial] n=34 Participants Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.
Number of Bleeding Episodes During Prophylactic Treatment With N8-GP (Annualised Bleeding Rate)	1.94 bleeds/patient/year Interval 0.0 to 2.08	1.97 bleeds/patient/year Interval 0.0 to 3.91	0.61 bleeds/patient/year Interval 0.2 to 1.19	0.93 bleeds/patient/year Interval 0.2 to 2.11

SECONDARY outcome

Timeframe: Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)

Population: Results were based on FAS.

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

Outcome measures

Outcome measures
Measure	Younger Children (0 - 5 Years) [Main Trial] n=30 Bleeding episodes Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Older Children (6 - 11 Years) [Main Trial] n=40 Bleeding episodes Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Younger Children (0 - 5 Years) [Full Trial] n=108 Bleeding episodes Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.	Older Children (6 - 11 Years) [Full Trial] n=222 Bleeding episodes Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.
Consumption of N8-GP Per Bleeding Episode (Number of Injections)	1.9 Number of injections Standard Deviation 1.5	1.6 Number of injections Standard Deviation 0.9	1.6 Number of injections Standard Deviation 1.3	1.5 Number of injections Standard Deviation 1.1

SECONDARY outcome

Timeframe: Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)

Population: Results were based on FAS.

The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed.

Outcome measures

Outcome measures
Measure	Younger Children (0 - 5 Years) [Main Trial] n=34 Participants Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Older Children (6 - 11 Years) [Main Trial] n=40 Bleeding episodes Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Younger Children (0 - 5 Years) [Full Trial] n=108 Bleeding episodes Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.	Older Children (6 - 11 Years) [Full Trial] n=222 Bleeding episodes Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.
Consumption of N8-GP Per Bleeding Episode (U/kg)	123 IU/kg/bleed Standard Deviation 104.9	99 IU/kg/bleed Standard Deviation 54.4	102.8 IU/kg/bleed Standard Deviation 81	91 IU/kg/bleed Standard Deviation 58.3

SECONDARY outcome

Timeframe: Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)

Population: Results were based on FAS.

The mean number of injections of N8-GP used for treatment of a bleed from start to stop of a bleed during prophylaxis.

Outcome measures

Outcome measures
Measure	Younger Children (0 - 5 Years) [Main Trial] n=1592 Injections Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Older Children (6 - 11 Years) [Main Trial] n=1799 Injections Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Younger Children (0 - 5 Years) [Full Trial] n=14442 Injections Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.	Older Children (6 - 11 Years) [Full Trial] n=17243 Injections Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.
Consumption of N8-GP During Prophylaxis (Number of Injections)	65.3 Number of injections Standard Deviation 6.5	62.3 Number of injections Standard Deviation 7.4	65.4 Number of injections Standard Deviation 7.5	64.1 Number of injections Standard Deviation 5.3

SECONDARY outcome

Timeframe: Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)

Population: Results were based on FAS.

The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed during prophylaxis (per month per subject). Consumption used for treatment includes all doses given (prophylaxis, treatment of bleed, minor surgery and pharmacokinetics \[PK\])

Outcome measures

Outcome measures
Measure	Younger Children (0 - 5 Years) [Main Trial] n=34 Participants Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Older Children (6 - 11 Years) [Main Trial] n=34 Participants Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Younger Children (0 - 5 Years) [Full Trial] n=34 Participants Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.	Older Children (6 - 11 Years) [Full Trial] n=34 Participants Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.
Consumption of N8-GP During Prophylaxis (U/kg Per Month)	572.5 U/kg/month Standard Deviation 97.4	555.8 U/kg/month Standard Deviation 44.6	564.9 U/kg/month Standard Deviation 86.6	563.4 U/kg/month Standard Deviation 15.1

SECONDARY outcome

Timeframe: Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)

Population: Results were based on FAS.

The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed during prophylaxis (per year per subject). Consumption used for treatment includes all doses given (prophylaxis, treatment of bleed, minor surgery and pharmacokinetics)

Outcome measures

Outcome measures
Measure	Younger Children (0 - 5 Years) [Main Trial] n=34 Participants Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Older Children (6 - 11 Years) [Main Trial] n=34 Participants Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Younger Children (0 - 5 Years) [Full Trial] n=34 Participants Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.	Older Children (6 - 11 Years) [Full Trial] n=34 Participants Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.
Consumption of N8-GP During Prophylaxis (U/kg Per Year)	6870.3 U/kg/year Standard Deviation 1169	6669.6 U/kg/year Standard Deviation 535.8	6778.6 U/kg/year Standard Deviation 1039	6760.4 U/kg/year Standard Deviation 181.8

SECONDARY outcome

Timeframe: 2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product

Population: Results were based on FAS.

The incremental recovery was defined as the increase in plasma FVIII activity per IU/kg of factor administered recorded 60 minutes after end of injection. It was calculated as (Factor VIII procoagulant \[FVIII:C\] activity measured in plasma 60 min after dosing - FVIII:C activity measured in plasma immediately before dosing) / (dose injected at time 0 min), where the dose was expressed as U FVIII product per kg body weight. A chromogenic assay with normal human plasma (NHP) as calibrator was used.

Outcome measures

Outcome measures
Measure	Younger Children (0 - 5 Years) [Main Trial] n=34 Participants Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Older Children (6 - 11 Years) [Main Trial] n=34 Participants Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Younger Children (0 - 5 Years) [Full Trial] Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.	Older Children (6 - 11 Years) [Full Trial] Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.
Incremental Recovery (Defined as the Peak Level Recorded 60 Min After End of Injection) Evaluated for Previous FVIII Product	0.017 (IU/mL)/(U/kg) Interval 0.014 to 0.021	0.022 (IU/mL)/(U/kg) Interval 0.018 to 0.027	—	—

SECONDARY outcome

Timeframe: From 1 hour prior to and up to 96 hours after initial administration of N8-GP

Population: Results were based on FAS.

The incremental recovery was defined as the peak level recorded 60 min after end of injection and dose-normalised. It was calculated as (FVIII:C activity measured in plasma 60 min after dosing - FVIII:C activity measured in plasma immediately before dosing) / (dose injected at time 0 min), where the dose was expressed as U FVIII product per kg body weight. A chromogenic assay with product specific calibrator (PSS) as calibrator was used.

Outcome measures

Outcome measures
Measure	Younger Children (0 - 5 Years) [Main Trial] n=34 Participants Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Older Children (6 - 11 Years) [Main Trial] n=34 Participants Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Younger Children (0 - 5 Years) [Full Trial] Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.	Older Children (6 - 11 Years) [Full Trial] Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.
Incremental Recovery (Defined as the Peak Level Recorded 60 Min After End of Injection) Evaluated for N8-GP	0.018 (IU/mL)/(U/kg) Interval 0.015 to 0.022	0.020 (IU/mL)/(U/kg) Interval 0.016 to 0.024	—	—

SECONDARY outcome

Timeframe: 2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product

Population: Results were based on FAS

Area under the curve (AUC) versus time from zero to infinity. This is calculated as AUC = AUClast + (C(t) / λz), where C(t) is the last measurable concentration. A chromogenic assay with NHP as calibrator was used.

Outcome measures

Outcome measures
Measure	Younger Children (0 - 5 Years) [Main Trial] n=34 Participants Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Older Children (6 - 11 Years) [Main Trial] n=34 Participants Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Younger Children (0 - 5 Years) [Full Trial] Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.	Older Children (6 - 11 Years) [Full Trial] Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.
Area Under the Curve Evaluated for Previous FVIII Product	11.628 IU×h/mL Interval 9.17 to 14.744	12.203 IU×h/mL Interval 9.336 to 15.951	—	—

SECONDARY outcome

Timeframe: From 1 hour prior to and up to 96 hours after initial administration of N8-GP

Population: Results were based on FAS.

Area under the curve versus time from zero to infinity. This is calculated as AUC = AUClast + (C(t) / λz), where C(t) is the last measurable concentration. A chromogenic assay with product specific standard (PSS) as calibrator was used.

Outcome measures

Outcome measures
Measure	Younger Children (0 - 5 Years) [Main Trial] n=34 Participants Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Older Children (6 - 11 Years) [Main Trial] n=34 Participants Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Younger Children (0 - 5 Years) [Full Trial] Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.	Older Children (6 - 11 Years) [Full Trial] Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.
Area Under the Curve Evaluated for N8-GP	21.489 IU*h/mL Interval 16.785 to 27.511	25.026 IU*h/mL Interval 19.145 to 32.713	—	—

SECONDARY outcome

Timeframe: 2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product

Population: Results were based on FAS.

t½ = ln(2) / λz, where t½ is terminal half-life and λz is the terminal elimination rate. The terminal elimination rate was planned estimated using linear regression on the terminal part of the time versus log(concentration) curve. A population-based method simultaneously estimating individual t½ values for all patients was applied, including patients with few values above the lower limit of quantification (LLOQ). This was estimated using time points from 1h to 30h. A chromogenic assay with PSS as calibrator was used.

Outcome measures

Outcome measures
Measure	Younger Children (0 - 5 Years) [Main Trial] n=34 Participants Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Older Children (6 - 11 Years) [Main Trial] n=34 Participants Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Younger Children (0 - 5 Years) [Full Trial] Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.	Older Children (6 - 11 Years) [Full Trial] Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.
Terminal Half-life Evaluated for Previous FVIII Product	7.2 hours Geometric Coefficient of Variation 20.1	7.5 hours Geometric Coefficient of Variation 19.1	—	—

SECONDARY outcome

Timeframe: From 1 hour prior to and up to 96 hours after initial administration of N8-GP

Population: Results were based on FAS.

t½ = ln(2) / λz, where λz is the terminal elimination rate. The terminal elimination rate was planned estimated using linear regression on the terminal part of the time versus log(concentration) curve. A population-based method simultaneously estimating individual t½ values for all patients was applied, including patients with few values above the LLOQ. This was estimated using time points from 6h to 96h. A chromogenic assay with PSS as calibrator was used.

Outcome measures

Outcome measures
Measure	Younger Children (0 - 5 Years) [Main Trial] n=34 Participants Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Older Children (6 - 11 Years) [Main Trial] n=34 Participants Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Younger Children (0 - 5 Years) [Full Trial] Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.	Older Children (6 - 11 Years) [Full Trial] Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.
Terminal Half-life Evaluated for N8-GP	13.6 hours Geometric Coefficient of Variation 20.4	14.1 hours Geometric Coefficient of Variation 25.0	—	—

SECONDARY outcome

Timeframe: 2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product

Population: Results were based on FAS.

Total plasma clearance of drug after intravenous administration measured as actual dose/AUC. A chromogenic assay with NHP as calibrator was used.

Outcome measures

Outcome measures
Measure	Younger Children (0 - 5 Years) [Main Trial] n=34 Participants Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Older Children (6 - 11 Years) [Main Trial] n=34 Participants Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Younger Children (0 - 5 Years) [Full Trial] Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.	Older Children (6 - 11 Years) [Full Trial] Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.
Clearance Evaluated for Previous FVIII Product	4.322 mL/h/kg Interval 3.404 to 5.486	3.867 mL/h/kg Interval 2.955 to 5.061	—	—

SECONDARY outcome

Timeframe: From 1 hour prior to and up to 96 hours after initial administration of N8-GP.

Population: Results were based on FAS.

Total plasma clearance of drug after intravenous administration measured as actual dose/AUC. A chromogenic assay with PSS as calibrator was used.

Outcome measures

Outcome measures
Measure	Younger Children (0 - 5 Years) [Main Trial] n=34 Participants Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Older Children (6 - 11 Years) [Main Trial] n=34 Participants Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).	Younger Children (0 - 5 Years) [Full Trial] Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.	Older Children (6 - 11 Years) [Full Trial] Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.
Clearance Evaluated for N8-GP	2.601 mL/h/kg Interval 2.03 to 3.333	2.386 mL/h/kg Interval 1.823 to 3.123	—	—

Adverse Events

Younger Children£(0-5 Years)

Serious events: 11 serious events

Other events: 33 other events

Deaths: 0 deaths

Older Children£(6-11 Years)

Serious events: 5 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Reporting Anchor and Disclosure (1452)

Novo Nordisk A/S

Phone: (+1) 866-867-7178

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property
Publication restrictions are in place

Restriction type: OTHER

Measure	Younger Children£(0-5 Years) n=34 participants at risk	Older Children£(6-11 Years) n=34 participants at risk
Gastrointestinal disorders Abdominal hernia	0.00% 0/34 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.	2.9% 1/34 • Number of events 1 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.
Reproductive system and breast disorders Acquired phimosis	2.9% 1/34 • Number of events 1 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.	0.00% 0/34 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.
Respiratory, thoracic and mediastinal disorders Adenoidal hypertrophy	0.00% 0/34 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.	2.9% 1/34 • Number of events 1 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.
Respiratory, thoracic and mediastinal disorders Asthma	2.9% 1/34 • Number of events 1 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.	0.00% 0/34 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.
Infections and infestations Cellulitis	2.9% 1/34 • Number of events 1 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.	0.00% 0/34 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.
Infections and infestations Device related infection	2.9% 1/34 • Number of events 2 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.	0.00% 0/34 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.
Infections and infestations Encephalitis	2.9% 1/34 • Number of events 1 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.	0.00% 0/34 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.
Injury, poisoning and procedural complications Fall	2.9% 1/34 • Number of events 1 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.	0.00% 0/34 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.
Gastrointestinal disorders Gastritis	0.00% 0/34 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.	2.9% 1/34 • Number of events 1 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.
Vascular disorders Haemorrhage	2.9% 1/34 • Number of events 1 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.	0.00% 0/34 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.
Injury, poisoning and procedural complications Hand fracture	2.9% 1/34 • Number of events 1 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.	0.00% 0/34 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.
Injury, poisoning and procedural complications Head injury	0.00% 0/34 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.	2.9% 1/34 • Number of events 1 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.
Immune system disorders Hypersensitivity	2.9% 1/34 • Number of events 1 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.	0.00% 0/34 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.
Musculoskeletal and connective tissue disorders Muscle haemorrhage	2.9% 1/34 • Number of events 1 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.	0.00% 0/34 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.
General disorders Pyrexia	2.9% 1/34 • Number of events 1 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.	0.00% 0/34 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.
Infections and infestations Sepsis syndrome	2.9% 1/34 • Number of events 1 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.	0.00% 0/34 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.
Infections and infestations Tonsillitis	0.00% 0/34 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.	2.9% 1/34 • Number of events 1 • From first exposure to N8-GP (visit 2) of main phase to end of extension phase (>=4 days after last dose of N8-GP, up to 4.5 years). The safety analysis set consists of all patients exposed to at least one dose of N8-GP.