A Multinational, Open-Label, Non-Controlled Trial on Safe... | NCT01731600

ID	Type	Description
U1111-1129-6009	Other Identifier	WHO
2012-001711-23	EudraCT Number
JapicCTI-132214	Registry Identifier	JAPIC

Label	Type	Description	Intervention Names
N8-GP	Experimental		Drug: turoctocog alfa pegol

Name	Type	Description	Arm Group Labels	Other Names
turoctocog alfa pegol	Drug	Fixed dose of turoctocog alfa pegol for intravenous injections (i.v.) twice weekly for prophylaxis. In addition, turoctocog alfa pegol will be administered to treat bleeding episodes during the trial period. Bleeding episodes will be treated with doses of 20-75 U/kg body weight.

Measure	Description	Time Frame
Number of Participants With Inhibitory Antibodies Against Coagulation Factor VIII (FVIII) ≥0.6 Bethesda Units	The number of participants with inhibitory antibodies against coagulation factor VIII (FVIII) ≥0.6 Bethesda units was presented.	During the main phase of the trial (from 0-26 weeks of treatment)

Measure	Description	Time Frame
Frequency of Adverse Events Including Serious Adverse Events Reported During the Trial Period	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.	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)

Name	Affiliation	Role
Global Clinical Registry (GCR, 1452)	Novo Nordisk A/S	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novo Nordisk Investigational Site		Phoenix	Arizona	85016-7710	United States
Novo Nordisk Investigational Site

PubMed Identifier	Type	Citation	Retractions
32293786	Result	Tosetto A, Neff A, Lentz SR, Santagostino E, Nemes L, Sathar J, Meijer K, Chowdary P, Shen C, Landorph A, Hampton K. Turoctocog alfa pegol provides effective management for major and minor surgical procedures in patients across all age groups with severe haemophilia A: Full data set from the pathfinder 3 and 5 phase III trials. Haemophilia. 2020 May;26(3):450-458. doi: 10.1111/hae.13980. Epub 2020 Apr 15.
32940955

Label	URL
Clinical Trials at Novo Nordisk	View source

ID	Title	Description
FG000	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.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 13, 2015	Sep 19, 2019

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Inhibitory Antibodies Against Coagulation Factor VIII (FVIII) ≥0.6 Bethesda Units

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

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

Posted

Number

Participants

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

ID	Title	Description
OG000	Younger Children (0 - 5 Years) [Main 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).
OG001	Older Children (6 - 11 Years) [Main 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).

Units	Counts
Participants	OG00034 OG00134

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	A one-sided, upper 97.5% confidence limit was provided based on an exact calculation in the binomial distribution.					Incidence rate	0			1-Sided	97.5		0.067			The incidence of inhibitory antibodies was calculated as number of patients with inhibitors during the main phase of the trial divided by number of patients in the main phase of the trial.		Other

Secondary

Frequency of Adverse Events Including Serious Adverse Events Reported During the Trial Period

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.

Results were based on SAS.

Posted

Number

Events per patient years of exposure

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)

ID	Title	Description
OG000	Younger Children (0 - 5 Years) [Main 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).
OG001	Older Children (6 - 11 Years) [Main 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).
OG002	Younger Children (0 - 5 Years) [Full Trial]

Secondary

Haemostatic Effect of N8-GP When Used for Treatment of Bleeding Episodes and Assessed as: Excellent, Good, Moderate, or None

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.

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.

Posted

Count of Units

Bleeding episodes

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)

Bleeding episodes

ID	Title	Description
OG000	Younger Children (0 - 5 Years) [Main 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).

Secondary

Number of Bleeding Episodes During Prophylactic Treatment With N8-GP (Annualised Bleeding Rate)

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

Results were based on FAS.

Posted

Median

Inter-Quartile Range

bleeds/patient/year

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)

ID	Title	Description
OG000	Younger Children (0 - 5 Years) [Main 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).
OG001	Older Children (6 - 11 Years) [Main 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).
OG002	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.

Secondary

Consumption of N8-GP Per Bleeding Episode (Number of Injections)

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

Results were based on FAS.

Posted

Mean

Standard Deviation

Number of injections

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)

Bleeding episodes

ID	Title	Description
OG000	Younger Children (0 - 5 Years) [Main 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).
OG001	Older Children (6 - 11 Years) [Main 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).
OG002	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.

Secondary

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

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

Results were based on FAS.

Posted

Mean

Standard Deviation

IU/kg/bleed

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)

Bleeding episodes

ID	Title	Description
OG000	Younger Children (0 - 5 Years) [Main 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).
OG001	Older Children (6 - 11 Years) [Main 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).
OG002	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.

Secondary

Consumption of N8-GP During Prophylaxis (Number of Injections)

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

Results were based on FAS.

Posted

Mean

Standard Deviation

Number of injections

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)

Injections

ID	Title	Description
OG000	Younger Children (0 - 5 Years) [Main 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).
OG001	Older Children (6 - 11 Years) [Main 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).
OG002	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.

Secondary

Consumption of N8-GP During Prophylaxis (U/kg Per Month)

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])

Results were based on FAS.

Posted

Mean

Standard Deviation

U/kg/month

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)

ID	Title	Description
OG000	Younger Children (0 - 5 Years) [Main 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).
OG001	Older Children (6 - 11 Years) [Main 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).
OG002	Younger Children (0 - 5 Years) [Full Trial]

Secondary

Consumption of N8-GP During Prophylaxis (U/kg Per Year)

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)

Results were based on FAS.

Posted

Mean

Standard Deviation

U/kg/year

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)

ID	Title	Description
OG000	Younger Children (0 - 5 Years) [Main 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).
OG001	Older Children (6 - 11 Years) [Main 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).
OG002	Younger Children (0 - 5 Years) [Full Trial]

Secondary

Incremental Recovery (Defined as the Peak Level Recorded 60 Min After End of Injection) Evaluated for Previous FVIII Product

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.

Results were based on FAS.

Posted

Least Squares Mean

95% Confidence Interval

(IU/mL)/(U/kg)

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

ID	Title	Description
OG000	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.
OG001

Secondary

Incremental Recovery (Defined as the Peak Level Recorded 60 Min After End of Injection) Evaluated for N8-GP

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.

Results were based on FAS.

Posted

Least Squares Mean

95% Confidence Interval

(IU/mL)/(U/kg)

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

ID	Title	Description
OG000	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.
OG001	Older Children (6 - 11 Years) [Full Trial]

Secondary

Area Under the Curve Evaluated for Previous FVIII Product

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.

Results were based on FAS

Posted

Least Squares Mean

95% Confidence Interval

IU×h/mL

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

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Area Under the Curve Evaluated for N8-GP

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.

Results were based on FAS.

Posted

Least Squares Mean

95% Confidence Interval

IU*h/mL

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

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Terminal Half-life Evaluated for Previous FVIII Product

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.

Results were based on FAS.

Posted

Geometric Mean

Geometric Coefficient of Variation

hours

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

ID	Title	Description
OG000	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.
OG001	Older Children (6 - 11 Years) [Full Trial]

Secondary

Terminal Half-life Evaluated for N8-GP

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.

Results were based on FAS.

Posted

Geometric Mean

Geometric Coefficient of Variation

hours

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

ID	Title	Description
OG000	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.
OG001	Older Children (6 - 11 Years) [Full Trial]

Secondary

Clearance Evaluated for Previous FVIII Product

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

Results were based on FAS.

Posted

Least Squares Mean

95% Confidence Interval

mL/h/kg

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

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Clearance Evaluated for N8-GP

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

Results were based on FAS.

Posted

Least Squares Mean

95% Confidence Interval

mL/h/kg

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

ID	Title	Description
OG000	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.
OG001	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.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal hernia	Gastrointestinal disorders	MedDRA 21	Systematic Assessment	EG0000 events0 affected34 at risk EG0011 events1 affected34 at risk
Acquired phimosis	Reproductive system and breast disorders	MedDRA 21	Systematic Assessment	EG0001 events1 affected34 at risk EG0010 events0 affected34 at risk
Adenoidal hypertrophy	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Systematic Assessment	EG0000 events0 affected34 at risk EG0011 events1 affected34 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Systematic Assessment	EG0001 events1 affected34 at risk EG0010 events0 affected34 at risk
Cellulitis	Infections and infestations	MedDRA 21	Systematic Assessment	EG0001 events1 affected34 at risk EG0010 events0 affected34 at risk
Device related infection	Infections and infestations	MedDRA 21	Systematic Assessment	EG0002 events1 affected34 at risk EG0010 events0 affected34 at risk
Encephalitis	Infections and infestations	MedDRA 21	Systematic Assessment	EG0001 events1 affected34 at risk EG0010 events0 affected34 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 21	Systematic Assessment	EG0001 events1 affected34 at risk EG0010 events0 affected34 at risk
Gastritis	Gastrointestinal disorders	MedDRA 21	Systematic Assessment	EG0000 events0 affected34 at risk EG0011 events1 affected34 at risk
Haemorrhage	Vascular disorders	MedDRA 21	Systematic Assessment	EG0001 events1 affected34 at risk EG0010 events0 affected34 at risk
Hand fracture	Injury, poisoning and procedural complications	MedDRA 21	Systematic Assessment	EG0001 events1 affected34 at risk EG0010 events0 affected34 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA 21	Systematic Assessment	EG0000 events0 affected34 at risk EG0011 events1 affected34 at risk
Hypersensitivity	Immune system disorders	MedDRA 21	Systematic Assessment	EG0001 events1 affected34 at risk EG0010 events0 affected34 at risk
Muscle haemorrhage	Musculoskeletal and connective tissue disorders	MedDRA 21	Systematic Assessment	EG0001 events1 affected34 at risk EG0010 events0 affected34 at risk
Pyrexia	General disorders	MedDRA 21	Systematic Assessment	EG0001 events1 affected34 at risk EG0010 events0 affected34 at risk
Sepsis syndrome	Infections and infestations	MedDRA 21	Systematic Assessment	EG0001 events1 affected34 at risk EG0010 events0 affected34 at risk
Tonsillitis	Infections and infestations	MedDRA 21	Systematic Assessment	EG0000 events0 affected34 at risk EG0011 events1 affected34 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 21	Systematic Assessment	EG0007 events5 affected34 at risk EG0012 events2 affected34 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA 21	Systematic Assessment	EG0000 events0 affected34 at risk EG0015 events4 affected34 at risk
Acute sinusitis	Infections and infestations	MedDRA 21	Systematic Assessment	EG0000 events0 affected34 at risk EG0012 events2 affected34 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 21	Systematic Assessment	EG0002 events2 affected34 at risk EG0011 events1 affected34 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 21	Systematic Assessment	EG0004 events3 affected34 at risk EG0015 events4 affected34 at risk
Arthropod bite	Injury, poisoning and procedural complications	MedDRA 21	Systematic Assessment	EG0002 events1 affected34 at risk EG0012 events2 affected34 at risk
Arthropod sting	Injury, poisoning and procedural complications	MedDRA 21	Systematic Assessment	EG0003 events1 affected34 at risk EG0013 events3 affected34 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Systematic Assessment	EG0004 events2 affected34 at risk EG0011 events1 affected34 at risk
Attention deficit/hyperactivity disorder	Psychiatric disorders	MedDRA 21	Systematic Assessment	EG0003 events3 affected34 at risk EG0011 events1 affected34 at risk
Bronchitis	Infections and infestations	MedDRA 21	Systematic Assessment	EG0005 events3 affected34 at risk EG0013 events3 affected34 at risk
Cerumen impaction	Ear and labyrinth disorders	MedDRA 21	Systematic Assessment	EG0002 events2 affected34 at risk EG0010 events0 affected34 at risk
Chapped lips	Gastrointestinal disorders	MedDRA 21	Systematic Assessment	EG0000 events0 affected34 at risk EG0012 events2 affected34 at risk
Conjunctivitis	Infections and infestations	MedDRA 21	Systematic Assessment	EG0002 events2 affected34 at risk EG0012 events2 affected34 at risk
Conjunctivitis allergic	Eye disorders	MedDRA 21	Systematic Assessment	EG0000 events0 affected34 at risk EG0014 events3 affected34 at risk
Constipation	Gastrointestinal disorders	MedDRA 21	Systematic Assessment	EG0002 events2 affected34 at risk EG0015 events3 affected34 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 21	Systematic Assessment	EG0004 events4 affected34 at risk EG0014 events4 affected34 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Systematic Assessment	EG00026 events14 affected34 at risk EG0016 events6 affected34 at risk
Dental caries	Gastrointestinal disorders	MedDRA 21	Systematic Assessment	EG0005 events3 affected34 at risk EG0011 events1 affected34 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 21	Systematic Assessment	EG0000 events0 affected34 at risk EG0013 events2 affected34 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 21	Systematic Assessment	EG0001 events1 affected34 at risk EG0012 events2 affected34 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 21	Systematic Assessment	EG0007 events5 affected34 at risk EG0015 events4 affected34 at risk
Ear infection	Infections and infestations	MedDRA 21	Systematic Assessment	EG0005 events5 affected34 at risk EG0015 events3 affected34 at risk
Ear pain	Ear and labyrinth disorders	MedDRA 21	Systematic Assessment	EG0005 events4 affected34 at risk EG0012 events1 affected34 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA 21	Systematic Assessment	EG0002 events2 affected34 at risk EG0015 events5 affected34 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Systematic Assessment	EG00028 events4 affected34 at risk EG0013 events1 affected34 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 21	Systematic Assessment	EG0005 events3 affected34 at risk EG0011 events1 affected34 at risk
Face injury	Injury, poisoning and procedural complications	MedDRA 21	Systematic Assessment	EG0001 events1 affected34 at risk EG0013 events2 affected34 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 21	Systematic Assessment	EG0008 events5 affected34 at risk EG0014 events3 affected34 at risk
Food allergy	Immune system disorders	MedDRA 21	Systematic Assessment	EG0002 events1 affected34 at risk EG0014 events2 affected34 at risk
Gastroenteritis	Infections and infestations	MedDRA 21	Systematic Assessment	EG00010 events7 affected34 at risk EG00113 events9 affected34 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 21	Systematic Assessment	EG0000 events0 affected34 at risk EG0012 events2 affected34 at risk
Haematoma	Vascular disorders	MedDRA 21	Systematic Assessment	EG0002 events2 affected34 at risk EG0010 events0 affected34 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA 21	Systematic Assessment	EG0004 events3 affected34 at risk EG0015 events4 affected34 at risk
Headache	Nervous system disorders	MedDRA 21	Systematic Assessment	EG0006 events5 affected34 at risk EG00116 events9 affected34 at risk
Hyperthermia	General disorders	MedDRA 21	Systematic Assessment	EG0002 events2 affected34 at risk EG0011 events1 affected34 at risk
Influenza	Infections and infestations	MedDRA 21	Systematic Assessment	EG0009 events5 affected34 at risk EG00110 events6 affected34 at risk
Joint injury	Injury, poisoning and procedural complications	MedDRA 21	Systematic Assessment	EG0002 events2 affected34 at risk EG0014 events3 affected34 at risk
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 21	Systematic Assessment	EG0003 events3 affected34 at risk EG0010 events0 affected34 at risk
Laceration	Injury, poisoning and procedural complications	MedDRA 21	Systematic Assessment	EG0002 events2 affected34 at risk EG0014 events4 affected34 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 21	Systematic Assessment	EG0000 events0 affected34 at risk EG0016 events5 affected34 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA 21	Systematic Assessment	EG0005 events5 affected34 at risk EG00112 events4 affected34 at risk
Molluscum contagiosum	Infections and infestations	MedDRA 21	Systematic Assessment	EG0002 events2 affected34 at risk EG0011 events1 affected34 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Systematic Assessment	EG0003 events2 affected34 at risk EG0012 events2 affected34 at risk
Nasopharyngitis	Infections and infestations	MedDRA 21	Systematic Assessment	EG00021 events11 affected34 at risk EG00116 events10 affected34 at risk
Nausea	Gastrointestinal disorders	MedDRA 21	Systematic Assessment	EG0000 events0 affected34 at risk EG0012 events2 affected34 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Systematic Assessment	EG0002 events2 affected34 at risk EG00110 events8 affected34 at risk
Otitis media	Infections and infestations	MedDRA 21	Systematic Assessment	EG0004 events4 affected34 at risk EG0015 events5 affected34 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 21	Systematic Assessment	EG00011 events5 affected34 at risk EG0018 events6 affected34 at risk
Penile adhesion	Reproductive system and breast disorders	MedDRA 21	Systematic Assessment	EG0002 events2 affected34 at risk EG0010 events0 affected34 at risk
Peripheral swelling	General disorders	MedDRA 21	Systematic Assessment	EG0000 events0 affected34 at risk EG0013 events3 affected34 at risk
Pharyngitis	Infections and infestations	MedDRA 21	Systematic Assessment	EG0002 events2 affected34 at risk EG0012 events1 affected34 at risk
Pharyngitis streptococcal	Infections and infestations	MedDRA 21	Systematic Assessment	EG0002 events2 affected34 at risk EG0012 events1 affected34 at risk
Pharyngotonsillitis	Infections and infestations	MedDRA 21	Systematic Assessment	EG0000 events0 affected34 at risk EG0012 events2 affected34 at risk
Pneumonia	Infections and infestations	MedDRA 21	Systematic Assessment	EG0001 events1 affected34 at risk EG0012 events2 affected34 at risk
Pyrexia	General disorders	MedDRA 21	Systematic Assessment	EG00016 events7 affected34 at risk EG0019 events6 affected34 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 21	Systematic Assessment	EG00011 events7 affected34 at risk EG0010 events0 affected34 at risk
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA 21	Systematic Assessment	EG0000 events0 affected34 at risk EG0012 events2 affected34 at risk
Rhinitis	Infections and infestations	MedDRA 21	Systematic Assessment	EG0008 events8 affected34 at risk EG0017 events4 affected34 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Systematic Assessment	EG0003 events3 affected34 at risk EG0011 events1 affected34 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Systematic Assessment	EG0004 events4 affected34 at risk EG0014 events3 affected34 at risk
Seasonal allergy	Immune system disorders	MedDRA 21	Systematic Assessment	EG0002 events2 affected34 at risk EG0012 events2 affected34 at risk
Sinusitis	Infections and infestations	MedDRA 21	Systematic Assessment	EG0001 events1 affected34 at risk EG0012 events2 affected34 at risk
Skin abrasion	Injury, poisoning and procedural complications	MedDRA 21	Systematic Assessment	EG0002 events2 affected34 at risk EG0014 events3 affected34 at risk
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 21	Systematic Assessment	EG0001 events1 affected34 at risk EG0012 events2 affected34 at risk
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21	Systematic Assessment	EG0002 events2 affected34 at risk EG0010 events0 affected34 at risk
Tendonitis	Musculoskeletal and connective tissue disorders	MedDRA 21	Systematic Assessment	EG0000 events0 affected34 at risk EG0012 events2 affected34 at risk
Tonsillitis	Infections and infestations	MedDRA 21	Systematic Assessment	EG0002 events2 affected34 at risk EG0015 events2 affected34 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 21	Systematic Assessment	EG00020 events10 affected34 at risk EG00131 events13 affected34 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 21	Systematic Assessment	EG0001 events1 affected34 at risk EG0012 events2 affected34 at risk
Varicella	Infections and infestations	MedDRA 21	Systematic Assessment	EG0006 events6 affected34 at risk EG0011 events1 affected34 at risk
Viral infection	Infections and infestations	MedDRA 21	Systematic Assessment	EG0005 events4 affected34 at risk EG0013 events3 affected34 at risk
Viral pharyngitis	Infections and infestations	MedDRA 21	Systematic Assessment	EG0002 events2 affected34 at risk EG0010 events0 affected34 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 21	Systematic Assessment	EG0005 events4 affected34 at risk EG0015 events3 affected34 at risk
Vomiting	Gastrointestinal disorders	MedDRA 21	Systematic Assessment	EG00010 events9 affected34 at risk EG0017 events3 affected34 at risk

ID	Term
D025861	Blood Coagulation Disorders, Inherited
D001778	Blood Coagulation Disorders
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D020147	Coagulation Protein Disorders
D006474	Hemorrhagic Disorders
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities

ID	Title	Description
BG000	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.
BG001	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.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Younger Children£(0-5 Years)		0	34	11	34	33	34
EG001	Older Children£(6-11 Years)		0	34	5	34	33	34