Flag of the European Union

EU Clinical Trials Register

Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:

interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC

clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
Clinical Trials Information System (CTIS).

The EU Clinical Trials Register currently displays 43851 clinical trials with a EudraCT protocol, of which 7283 are clinical trials conducted with subjects less than 18 years old. The register also displays information on 18700 older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).

Examples: Cancer AND drug name. Pneumonia AND sponsor name.
How to search [pdf]

Advanced Search:

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

< Back to search results

Clinical Trial Results:
Safety and Efficacy of Turoctocog Alfa in Prevention and On-demand Treatment of Bleeding Episodes in Subjects with Haemophilia A Sub-trial: Efficacy and Safety of Turoctocog Alfa in Prevention and Treatment of Bleeding During Surgical Procedures in Subjects with Haemophilia A

Summary
EudraCT number	2008-005945-46
Trial protocol	DE ES IT GB PL LT LV
Global end of trial date	30 Jun 2016

Results information
Results version number	v1(current)
This version publication date	07 Jan 2017
First version publication date	07 Jan 2017
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

NN7008-3568

ISRCTN number

-

US NCT number

NCT00984126

WHO universal trial number (UTN)

U1111-1111-9377

Other trial identifiers

Japanese trial registration: JapicCTI-101357

Sponsor organisation name

Novo Nordisk A/S

Sponsor organisation address

Novo Allé, Bagsvaerd, Denmark, 2880

Public contact

Global Clinical Registry (GCR, 1452), Novo Nordisk A/S, clinicaltrials@novonordisk.com

Scientific contact

Global Clinical Registry (GCR, 1452), Novo Nordisk A/S, clinicaltrials@novonordisk.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-000428-PIP01-08

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

No

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

15 Dec 2016

Is this the analysis of the primary completion data?

Yes

Primary completion date

30 Jun 2016

Global end of trial reached?

Yes

Global end of trial date

30 Jun 2016

Was the trial ended prematurely?

No

Main objective of the trial

To assess the safety of turoctocog alfa for prevention (only applicable for subjects in the preventive regimen) and treatment of bleeds.

Protection of trial subjects

The trial was conducted in accordance with the Declaration of Helsinki (2008) and ICH Good Clinical Practice (1996).

Background therapy

Not applicable

Evidence for comparator

Not applicable

Actual start date of recruitment

27 Oct 2009

Long term follow-up planned

No

Independent data monitoring committee (IDMC) involvement?

No

Number of subjects enrolled per country

Country: Number of subjects enrolled

Brazil: 26

Country: Number of subjects enrolled

Croatia: 14

Country: Number of subjects enrolled

Germany: 8

Country: Number of subjects enrolled

Israel: 11

Country: Number of subjects enrolled

Italy: 9

Country: Number of subjects enrolled

Japan: 5

Country: Number of subjects enrolled

Latvia: 8

Country: Number of subjects enrolled

Lithuania: 4

Country: Number of subjects enrolled

Macedonia, the former Yugoslav Republic of: 5

Country: Number of subjects enrolled

Malaysia: 12

Country: Number of subjects enrolled

Poland: 5

Country: Number of subjects enrolled

Russian Federation: 13

Country: Number of subjects enrolled

Serbia: 24

Country: Number of subjects enrolled

Spain: 10

Country: Number of subjects enrolled

Switzerland: 5

Country: Number of subjects enrolled

Taiwan: 5

Country: Number of subjects enrolled

Turkey: 16

Country: Number of subjects enrolled

United Kingdom: 2

Country: Number of subjects enrolled

United States: 31

Worldwide total number of subjects

213

EEA total number of subjects

60

Number of subjects enrolled per age group

In utero

0

Preterm newborn - gestational age < 37 wk

0

Newborns (0-27 days)

0

Infants and toddlers (28 days-23 months)

1

Children (2-11 years)

52

Adolescents (12-17 years)

24

Adults (18-64 years)

136

From 65 to 84 years

0

85 years and over

0

Subject disposition

Top of page

Recruitment details

The subjects were enrolled at 52 sites in 19 countries:Brazil (4 sites), Croatia (2), Germany (3), Israel (1), Italy (2), Japan (5), Latvia (1), Lithuania (1), Macedonia (1), Malaysia (1), Poland (2), Russian Federation (2), Serbia (5), Spain (2), Switzerland (1), Taiwan (1), Turkey (5), the United Kingdom (1) and the United States (12).

Screening details

Subjects completing 1 of the trials NN7008-3543 (2008-003960-20),NN7008-3545 (2009-016383-36),NN7008-3600,NN7008-3893 (2010-023921-39) and NN7008-4015 (2012-001444-21) could continue treatment with turoctocog alfa in the extension trial (NN7008-3568). Both new subjects and those from the main trial (NN7008-3568) could enter the on-demand sub-trial.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Blinding implementation details

Not applicable

Are arms mutually exclusive

Yes

Small children (0 - <6 years)

Arm description

Subjects (0-<6 years) received turoctocog alfa (preventive or on-demand regimen). Subjects switched between regimens during the trial (main and on-demand sub-trial) upon investigators’ discretion. Subjects coming from main trial were allowed to switch back before completion of 6 months on-demand regimen. Preventive: Turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day,20−60 IU/kg 3 times weekly or 40−60 IU/kg once every third day or twice weekly. On-Demand: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for treatment of bleeds as they occurred and occasionally as preventive treatment. All subjects were offered participation until either turoctocog alfa was commercially available in the relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in the relevant country. The maximum treatment duration (27 Oct 2009 - 30 Jun 2016)

Arm type

Experimental

Investigational medicinal product name

Turoctocog alfa

Investigational medicinal product code

Other name

Recombinant Factor VIII

Pharmaceutical forms

Powder and solvent for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Turoctocog alfa was administered as a slow iv bolus injection at a rate of approximately 2 mL/min for all preventive doses and bleed treatments. Preventive regimen: Subjects received turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day, 20−60 IU/kg three times weekly or 40−60 IU/kg BW once every third day or twice weekly. On-Demand regimen: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for the treatment of bleeds as they occurred and occasionally as preventive treatment.

Older children (6 - <12 years)

Arm description

Subjects (6-<12 years) received turoctocog alfa (preventive or on-demand regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. Subjects coming from main trial were allowed to switch back before completion of 6 months on-demand regimen. Preventive: Turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day,20−60 IU/kg 3 times weekly or 40−60 IU/kg BW once every third day or twice weekly. On-Demand: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for treatment of bleeds as they occurred and occasionally as preventive treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. The maximum treatment duration (27 Oct 2009 - 30 Jun 2016)

Arm type

Experimental

Investigational medicinal product name

Turoctocog alfa

Investigational medicinal product code

Other name

Recombinant Factor VIII

Pharmaceutical forms

Powder and solvent for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Turoctocog alfa was administered as a slow iv bolus injection at a rate of approximately 2 mL/min for all preventive doses and bleed treatments. Preventive regimen: Subjects received turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day, 20−60 IU/kg three times weekly or 40−60 IU/kg BW once every third day or twice weekly. On-Demand regimen: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for the treatment of bleeds as they occurred and occasionally as preventive treatment.

Adolescents (12 - <18 years)

Arm description

Subjects (12-<18 years) received turoctocog alfa (preventive or on-demand regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. Subjects coming from main trial were allowed to switch back before completion of 6 months on-demand regimen.Preventive regimen: Turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day,20−60 IU/kg 3 times weekly or 40−60 IU/kg once every third day or twice weekly.On-Demand: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for treatment of bleeds as they occurred and occasionally as preventive treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. The maximum treatment duration (27 Oct 2009 - 30 Jun 2016)

Arm type

Experimental

Investigational medicinal product name

Turoctocog alfa

Investigational medicinal product code

Other name

Recombinant Factor VIII

Pharmaceutical forms

Powder and solvent for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Turoctocog alfa was administered as a slow iv bolus injection at a rate of approximately 2 mL/min for all preventive doses and bleed treatments. Preventive regimen: Subjects received turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day, 20−60 IU/kg three times weekly or 40−60 IU/kg BW once every third day or twice weekly. On-Demand regimen: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for the treatment of bleeds as they occurred and occasionally as preventive treatment.

Adults (≥18 years)

Arm description

Subjects (≥18 years) received turoctocog alfa (preventive or on-demand regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. Subjects coming from main trial were allowed to switch back before completion of 6 months on-demand regimen. Preventive regimen: Turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day,20−60 IU/kg 3 times weekly or 40−60 IU/kg once every third day or twice weekly. On-Demand: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for treatment of bleeds as they occurred and occasionally as preventive treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. The maximum treatment duration (27 Oct 2009 - 30 Jun 2016)

Arm type

Experimental

Investigational medicinal product name

Turoctocog alfa

Investigational medicinal product code

Other name

Recombinant Factor VIII

Pharmaceutical forms

Powder and solvent for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Turoctocog alfa was administered as a slow iv bolus injection at a rate of approximately 2 mL/min for all preventive doses and bleed treatments. Preventive regimen: Subjects received turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day, 20−60 IU/kg three times weekly or 40−60 IU/kg BW once every third day or twice weekly. On-Demand regimen: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for the treatment of bleeds as they occurred and occasionally as preventive treatment.

Number of subjects in period 1	Small children (0 - <6 years)	Older children (6 - <12 years)	Adolescents (12 - <18 years)	Adults (≥18 years)
Started	27	28	23	135
Completed	20	20	16	76
Not completed	7	8	7	59
Adverse event, non-fatal	-	-	-	2
Withdrawal criteria	-	1	3	9
Choose to join Pathfinder trial™ + other	7	7	3	46
Protocol deviation	-	-	1	2

Baseline characteristics

Top of page

Reporting group title

Small children (0 - <6 years)

Reporting group description

Subjects (0-<6 years) received turoctocog alfa (preventive or on-demand regimen). Subjects switched between regimens during the trial (main and on-demand sub-trial) upon investigators’ discretion. Subjects coming from main trial were allowed to switch back before completion of 6 months on-demand regimen. Preventive: Turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day,20−60 IU/kg 3 times weekly or 40−60 IU/kg once every third day or twice weekly. On-Demand: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for treatment of bleeds as they occurred and occasionally as preventive treatment. All subjects were offered participation until either turoctocog alfa was commercially available in the relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in the relevant country. The maximum treatment duration (27 Oct 2009 - 30 Jun 2016)

Reporting group title

Older children (6 - <12 years)

Reporting group description

Subjects (6-<12 years) received turoctocog alfa (preventive or on-demand regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. Subjects coming from main trial were allowed to switch back before completion of 6 months on-demand regimen. Preventive: Turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day,20−60 IU/kg 3 times weekly or 40−60 IU/kg BW once every third day or twice weekly. On-Demand: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for treatment of bleeds as they occurred and occasionally as preventive treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. The maximum treatment duration (27 Oct 2009 - 30 Jun 2016)

Reporting group title

Adolescents (12 - <18 years)

Reporting group description

Subjects (12-<18 years) received turoctocog alfa (preventive or on-demand regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. Subjects coming from main trial were allowed to switch back before completion of 6 months on-demand regimen.Preventive regimen: Turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day,20−60 IU/kg 3 times weekly or 40−60 IU/kg once every third day or twice weekly.On-Demand: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for treatment of bleeds as they occurred and occasionally as preventive treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. The maximum treatment duration (27 Oct 2009 - 30 Jun 2016)

Reporting group title

Adults (≥18 years)

Reporting group description

Subjects (≥18 years) received turoctocog alfa (preventive or on-demand regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. Subjects coming from main trial were allowed to switch back before completion of 6 months on-demand regimen. Preventive regimen: Turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day,20−60 IU/kg 3 times weekly or 40−60 IU/kg once every third day or twice weekly. On-Demand: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for treatment of bleeds as they occurred and occasionally as preventive treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. The maximum treatment duration (27 Oct 2009 - 30 Jun 2016)

Reporting group values	Small children (0 - <6 years)	Older children (6 - <12 years)	Adolescents (12 - <18 years)	Adults (≥18 years)	Total
Number of subjects	27	28	23	135	213
Age Categorical
Units: Subjects
Small children (0 - <6 years)	27	0	0	0	27
Older children (6 - <12 Years)	0	28	0	0	28
Adolescents (12 - <18 Years)	0	0	23	0	23
Adults (≥18 Years)	0	0	0	135	135
Age Continuous
Units: years
arithmetic mean (standard deviation)	4.6 ± 1.4	9 ± 1.8	14.9 ± 1.7	32 ± 11.5	-
Gender Categorical
Units: Subjects
Female	0	0	0	0	0
Male	27	28	23	135	213

Subject analysis set title

Small children (0 - <6 years)-Preventive regimen [Main trial]

Subject analysis set type

Full analysis

Subject analysis set description

Subjects (0-<6 years) in main trial received turoctocog alfa (Preventive regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. However during on-demand sub-trial, it was not possible for new subjects to switch to another regimen, subjects who did not comply with on-demand treatment regimen were to be withdrawn. Subjects coming from main trial were allowed to switch back to main trial before completion of 6 months on-demand treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or trial site was terminated by Novo Nordisk or relevant authority for any reason in relevant country. Maximum treatment duration (27 Oct 2009–30 Jun 2016). Preventive regimen: Turoctocog alfa as slow iv bolus injection 20−50 IU/kg once every second day, 20−60 IU/kg 3 times weekly or 40−60 IU/kg once every third day or twice weekly

Subject analysis set title

Older children (6 - <12 years)-Preventive regimen [Main trial]

Subject analysis set type

Full analysis

Subject analysis set description

Subjects (6-<12 years) in main trial received turoctocog alfa (Preventive regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. However during on-demand sub-trial, it was not possible for new subjects to switch to another regimen, subjects who did not comply with on-demand treatment regimen were to be withdrawn. Subjects coming from main trial were allowed to switch back to main trial before completion of 6 months on-demand treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. Maximum treatment duration (27 Oct 2009 – 30 Jun 2016). Preventive regimen: Turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day, 20−60 IU/kg three times weekly or 40−60 IU/kg once every third day or twice weekly.

Subject analysis set title

Adolescents (12 - <18 years) - Preventive regimen [Main trial]

Subject analysis set type

Full analysis

Subject analysis set description

Subjects (12-<18 years) in main trial received turoctocog alfa (Preventive regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. However during on-demand sub-trial, it was not possible for new subjects to switch to another regimen, subjects who did not comply with on-demand treatment regimen were to be withdrawn. Subjects coming from main trial were allowed to switch back to main trial before completion of 6 months on-demand treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. Maximum treatment duration (27 Oct 2009 – 30 Jun 2016). Preventive regimen: Turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day, 20−60 IU/kg three times weekly or 40−60 IU/kg once every third day or twice weekly.

Subject analysis set title

Adults (>= 18 years) - Preventive regimen [Main trial]

Subject analysis set type

Full analysis

Subject analysis set description

Subjects (>=18 years) in main trial received turoctocog alfa (Preventive regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. However during on-demand sub-trial, it was not possible for new subjects to switch to another regimen, subjects who did not comply with on-demand treatment regimen were to be withdrawn. Subjects coming from main trial were allowed to switch back to main trial before completion of 6 months on-demand treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. Maximum treatment duration (27 Oct 2009 – 30 Jun 2016). Preventive regimen: Turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day, 20−60 IU/kg three times weekly or 40−60 IU/kg once every third day or twice weekly.

Subject analysis set title

Adolescents (12-<18 years)-(On-Demand regimen [Main trial])

Subject analysis set type

Full analysis

Subject analysis set description

Subjects (12-<18 Years) in main trial received turoctocog alfa (on-demand regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. However during on-demand sub-trial, it was not possible for new subjects to switch to another regimen, subjects who did not comply with on-demand treatment regimen were to be withdrawn. Subjects coming from main trial were allowed to switch back before completion of 6 months on-demand treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. Maximum treatment duration (27 Oct 2009–30 Jun 2016). On-Demand regimen: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for treatment of bleeds as they occurred and occasionally as preventive treatment.

Subject analysis set title

Adults (>=18 years)-(On-Demand regimen [Main trial])

Subject analysis set type

Full analysis

Subject analysis set description

Subjects (≥18 Years) in main trial received turoctocog alfa (on-demand regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. However during on-demand sub-trial, it was not possible for new subjects to switch to another regimen, subjects who did not comply with on-demand treatment regimen were to be withdrawn. Subjects coming from main trial were allowed to switch back before completion of 6 months on-demand treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. Maximum treatment duration (27 Oct 2009 – 30 Jun 2016). On-Demand regimen: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for treatment of bleeds as they occurred and occasionally as preventive treatment.

Subject analysis set title

Adults (>=18 years)-(On-Demand regimen [Sub-trial])

Subject analysis set type

Full analysis

Subject analysis set description

Subjects (≥18 Years) in sub-trial received turoctocog alfa (on-demand regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. However during on-demand sub-trial, it was not possible for new subjects to switch to another regimen, subjects who did not comply with on-demand treatment regimen were to be withdrawn. Subjects coming from main trial were allowed to switch back before completion of 6 months on-demand treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. Maximum treatment duration (27 Oct 2009 – 30 Jun 2016). On-Demand regimen: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for treatment of bleeds as they occurred and occasionally as preventive treatment.

Subject analysis set title

Surgery sub-trial

Subject analysis set type

Full analysis

Subject analysis set description

All subjects who had possibility to undergo major and minor surgery were included in the surgery sub-trial. Either bolus and continuous infusion with turoctocog alfa were chosen during surgery. However, continuous infusion was selected only if subjects were scheduled for major elective surgery and if the centre had experience with the use of continuous infusion. All subjects received a preoperative loading dose of turoctocog alfa immediately prior to the surgical procedure. The dose was chosen according to the standard practice at the centre. Switching regimens from continuous infusion to bolus administration was possible at the investigator’s discretion during the surgery period.

Subject analysis sets values	Small children (0 - <6 years)-Preventive regimen [Main trial]	Older children (6 - <12 years)-Preventive regimen [Main trial]	Adolescents (12 - <18 years) - Preventive regimen [Main trial]	Adults (>= 18 years) - Preventive regimen [Main trial]	Adolescents (12-<18 years)-(On-Demand regimen [Main trial])	Adults (>=18 years)-(On-Demand regimen [Main trial])	Adults (>=18 years)-(On-Demand regimen [Sub-trial])	Surgery sub-trial
Number of subjects	27	28	23	129	1	8	14	17
Age Categorical
Units: Subjects
Small children (0 - <6 years)
Older children (6 - <12 Years)
Adolescents (12 - <18 Years)
Adults (≥18 Years)
Age Continuous
Units: years
arithmetic mean (standard deviation)	±	±	±	±	±	±	±	±
Gender Categorical
Units: Subjects
Female	0	0	0	0	0	0	0
Male	27	28	23	129	1	8	14

End points

Top of page

Reporting group title

Small children (0 - <6 years)

Reporting group description

Subjects (0-<6 years) received turoctocog alfa (preventive or on-demand regimen). Subjects switched between regimens during the trial (main and on-demand sub-trial) upon investigators’ discretion. Subjects coming from main trial were allowed to switch back before completion of 6 months on-demand regimen. Preventive: Turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day,20−60 IU/kg 3 times weekly or 40−60 IU/kg once every third day or twice weekly. On-Demand: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for treatment of bleeds as they occurred and occasionally as preventive treatment. All subjects were offered participation until either turoctocog alfa was commercially available in the relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in the relevant country. The maximum treatment duration (27 Oct 2009 - 30 Jun 2016)

Reporting group title

Older children (6 - <12 years)

Reporting group description

Subjects (6-<12 years) received turoctocog alfa (preventive or on-demand regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. Subjects coming from main trial were allowed to switch back before completion of 6 months on-demand regimen. Preventive: Turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day,20−60 IU/kg 3 times weekly or 40−60 IU/kg BW once every third day or twice weekly. On-Demand: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for treatment of bleeds as they occurred and occasionally as preventive treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. The maximum treatment duration (27 Oct 2009 - 30 Jun 2016)

Reporting group title

Adolescents (12 - <18 years)

Reporting group description

Subjects (12-<18 years) received turoctocog alfa (preventive or on-demand regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. Subjects coming from main trial were allowed to switch back before completion of 6 months on-demand regimen.Preventive regimen: Turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day,20−60 IU/kg 3 times weekly or 40−60 IU/kg once every third day or twice weekly.On-Demand: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for treatment of bleeds as they occurred and occasionally as preventive treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. The maximum treatment duration (27 Oct 2009 - 30 Jun 2016)

Reporting group title

Adults (≥18 years)

Reporting group description

Subjects (≥18 years) received turoctocog alfa (preventive or on-demand regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. Subjects coming from main trial were allowed to switch back before completion of 6 months on-demand regimen. Preventive regimen: Turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day,20−60 IU/kg 3 times weekly or 40−60 IU/kg once every third day or twice weekly. On-Demand: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for treatment of bleeds as they occurred and occasionally as preventive treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. The maximum treatment duration (27 Oct 2009 - 30 Jun 2016)

Subject analysis set title

Small children (0 - <6 years)-Preventive regimen [Main trial]

Subject analysis set type

Full analysis

Subject analysis set description

Subjects (0-<6 years) in main trial received turoctocog alfa (Preventive regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. However during on-demand sub-trial, it was not possible for new subjects to switch to another regimen, subjects who did not comply with on-demand treatment regimen were to be withdrawn. Subjects coming from main trial were allowed to switch back to main trial before completion of 6 months on-demand treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or trial site was terminated by Novo Nordisk or relevant authority for any reason in relevant country. Maximum treatment duration (27 Oct 2009–30 Jun 2016). Preventive regimen: Turoctocog alfa as slow iv bolus injection 20−50 IU/kg once every second day, 20−60 IU/kg 3 times weekly or 40−60 IU/kg once every third day or twice weekly

Subject analysis set title

Older children (6 - <12 years)-Preventive regimen [Main trial]

Subject analysis set type

Full analysis

Subject analysis set description

Subjects (6-<12 years) in main trial received turoctocog alfa (Preventive regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. However during on-demand sub-trial, it was not possible for new subjects to switch to another regimen, subjects who did not comply with on-demand treatment regimen were to be withdrawn. Subjects coming from main trial were allowed to switch back to main trial before completion of 6 months on-demand treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. Maximum treatment duration (27 Oct 2009 – 30 Jun 2016). Preventive regimen: Turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day, 20−60 IU/kg three times weekly or 40−60 IU/kg once every third day or twice weekly.

Subject analysis set title

Adolescents (12 - <18 years) - Preventive regimen [Main trial]

Subject analysis set type

Full analysis

Subject analysis set description

Subjects (12-<18 years) in main trial received turoctocog alfa (Preventive regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. However during on-demand sub-trial, it was not possible for new subjects to switch to another regimen, subjects who did not comply with on-demand treatment regimen were to be withdrawn. Subjects coming from main trial were allowed to switch back to main trial before completion of 6 months on-demand treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. Maximum treatment duration (27 Oct 2009 – 30 Jun 2016). Preventive regimen: Turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day, 20−60 IU/kg three times weekly or 40−60 IU/kg once every third day or twice weekly.

Subject analysis set title

Adults (>= 18 years) - Preventive regimen [Main trial]

Subject analysis set type

Full analysis

Subject analysis set description

Subjects (>=18 years) in main trial received turoctocog alfa (Preventive regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. However during on-demand sub-trial, it was not possible for new subjects to switch to another regimen, subjects who did not comply with on-demand treatment regimen were to be withdrawn. Subjects coming from main trial were allowed to switch back to main trial before completion of 6 months on-demand treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. Maximum treatment duration (27 Oct 2009 – 30 Jun 2016). Preventive regimen: Turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day, 20−60 IU/kg three times weekly or 40−60 IU/kg once every third day or twice weekly.

Subject analysis set title

Adolescents (12-<18 years)-(On-Demand regimen [Main trial])

Subject analysis set type

Full analysis

Subject analysis set description

Subjects (12-<18 Years) in main trial received turoctocog alfa (on-demand regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. However during on-demand sub-trial, it was not possible for new subjects to switch to another regimen, subjects who did not comply with on-demand treatment regimen were to be withdrawn. Subjects coming from main trial were allowed to switch back before completion of 6 months on-demand treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. Maximum treatment duration (27 Oct 2009–30 Jun 2016). On-Demand regimen: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for treatment of bleeds as they occurred and occasionally as preventive treatment.

Subject analysis set title

Adults (>=18 years)-(On-Demand regimen [Main trial])

Subject analysis set type

Full analysis

Subject analysis set description

Subjects (≥18 Years) in main trial received turoctocog alfa (on-demand regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. However during on-demand sub-trial, it was not possible for new subjects to switch to another regimen, subjects who did not comply with on-demand treatment regimen were to be withdrawn. Subjects coming from main trial were allowed to switch back before completion of 6 months on-demand treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. Maximum treatment duration (27 Oct 2009 – 30 Jun 2016). On-Demand regimen: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for treatment of bleeds as they occurred and occasionally as preventive treatment.

Subject analysis set title

Adults (>=18 years)-(On-Demand regimen [Sub-trial])

Subject analysis set type

Full analysis

Subject analysis set description

Subjects (≥18 Years) in sub-trial received turoctocog alfa (on-demand regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. However during on-demand sub-trial, it was not possible for new subjects to switch to another regimen, subjects who did not comply with on-demand treatment regimen were to be withdrawn. Subjects coming from main trial were allowed to switch back before completion of 6 months on-demand treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. Maximum treatment duration (27 Oct 2009 – 30 Jun 2016). On-Demand regimen: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for treatment of bleeds as they occurred and occasionally as preventive treatment.

Subject analysis set title

Surgery sub-trial

Subject analysis set type

Full analysis

Subject analysis set description

All subjects who had possibility to undergo major and minor surgery were included in the surgery sub-trial. Either bolus and continuous infusion with turoctocog alfa were chosen during surgery. However, continuous infusion was selected only if subjects were scheduled for major elective surgery and if the centre had experience with the use of continuous infusion. All subjects received a preoperative loading dose of turoctocog alfa immediately prior to the surgical procedure. The dose was chosen according to the standard practice at the centre. Switching regimens from continuous infusion to bolus administration was possible at the investigator’s discretion during the surgery period.

Primary: Frequency of development of FVIII inhibitors (≥0.6 BU/mL)

Top of page

End point title

Frequency of development of FVIII inhibitors (≥0.6 BU/mL)

End point description

The frequency of inhibitors was calculated as number of patients with inhibitors during the trial divided by number of patients in the trial. This endpoint was measured during the trial.

End point type

Primary

End point timeframe

After 90 months

End point values	Small children (0 - <6 years)	Older children (6 - <12 years)	Adolescents (12 - <18 years)	Adults (≥18 years)
Number of subjects analysed	27	28	23	135
Units: Proportion of subjects	0	0	0	0

Statistical analysis 1

Statistical analysis description

A one-sided 95% upper confidence limit was based on an exact calculation for a binomial distribution.

Comparison groups

Small children (0 - <6 years) v Older children (6 - <12 years) v Adolescents (12 - <18 years) v Adults (≥18 years)

Number of subjects included in analysis

213

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Incidence rate

Point estimate

0

Confidence interval

level

95%

sides

1-sided

lower limit

-

upper limit

1.4

Primary: Frequency of AE, SAE and MESI reported

Top of page

End point title

Frequency of AE, SAE and MESI reported ^[1]

End point description

In the protocol amendment 1, objectives and endpoints were updated to reflect changes in the pivotal trial (NN7008-3543) and to be consistent with the paediatric trial (NN7008-3545) and the Japanese trial (NN7008-3600). The primary endpoint "Frequency of AEs, SAE and MESI reported" was changed to secondary safety endpoint "Frequency of Adverse Events and Serious Adverse Events". This endpoint was planned to be measured during the trial.

End point type

Primary

End point timeframe

After 90 months

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint which was previously cited as primary endpoint was changed to secondary endpoint as a result of amendment 1. As a result, this endpoint was analysed as secondary endpoint (except for MESIs) using descriptive statistics.

End point values	Small children (0 - <6 years)	Older children (6 - <12 years)	Adolescents (12 - <18 years)	Adults (≥18 years)
Number of subjects analysed	0 ^[2]	0 ^[3]	0 ^[4]	0 ^[5]
Units: Number of events

Notes
[2] - The endpoint was not analysed (reason described in outcome description)
[3] - The endpoint was not analysed (reason described in outcome description)
[4] - The endpoint was not analysed (reason described in outcome description)
[5] - The endpoint was not analysed (reason described in outcome description)

No statistical analyses for this end point

Primary: Haemostatic response to turoctocog alfa (none, moderate, good or excellent) (surgery sub-trial)

Top of page

End point title

Haemostatic response to turoctocog alfa (none, moderate, good or excellent) (surgery sub-trial) ^[6]

End point description

Haemostatic response to turoctocog alfa (none, moderate, good or excellent) during and after surgery using a four-point response scale: none, moderate, good or excellent. The evaluation during surgery was done by the surgeon as follows: Excellent: blood loss less than expected; Good: blood loss as expected; Fair/Moderate: blood loss more than expected; None: uncontrolled bleeding. Haemostatic response after surgery was evaluated by investigator as follows: Excellent: good or better than expected in this type of patient and procedure; Good: minimal negative impact on quality of haemostasis; Fair/Moderate: less than optimal for the type of procedure, maintained without change of treatment regimen; None: bleeding due to inadequate therapeutic response with adequate dosing, change of regimen required. This endpoint is measured during the surgery sub-trial from the day of surgery until the end of post-surgical period.

End point type

Primary

End point timeframe

From the day of surgery until the end of post-surgical period.

Notes
[6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint was measured using a four-point response scale: none, moderate, good or excellent. There was no statistical analysis performed.

End point values	Surgery sub-trial
Number of subjects analysed	17
Units: Number of surgeries
During major surgery (Excellent)	10
During major surgery (Good)	8
During major surgery (Moderate)	0
During major surgery (None)	0
During minor surgery (Excellent)	3
During minor surgery (Good)	0
During minor surgery (Moderate)	0
During minor surgery (None)	0
After major surgery (Excellent)	10
After major surgery (Good)	8
After major surgery (Moderate)	0
After major surgery (none)	0
After minor surgery (Excellent)	3
After minor surgery (Good)	0
After minor surgery (Moderate)	0
After minor surgery (None)	0

No statistical analyses for this end point

Secondary: Frequency of adverse events and serious adverse events

Top of page

End point title

Frequency of adverse events and serious adverse events

End point description

The number of adverse events and serious adverse events reported during the main trial and the on-demand sub-trial (during 90 months).

End point type

Secondary

End point timeframe

After 90 months

End point values	Small children (0 - <6 years)	Older children (6 - <12 years)	Adolescents (12 - <18 years)	Adults (≥18 years)
Number of subjects analysed	27	28	23	135
Units: Number of events
Adverse events	180	204	240	636
Serious adverse events	6	8	6	27

No statistical analyses for this end point

Secondary: Annualised bleeding rate reported during the prevention period (only applicable for subjects in the preventive regimen)

Top of page

End point title

Annualised bleeding rate reported during the prevention period (only applicable for subjects in the preventive regimen)

End point description

The number of bleeding episodes per year reported during the prevention period (during 90 months).

End point type

Secondary

End point timeframe

After 90 months

End point values	Small children (0 - <6 years)-Preventive regimen [Main trial]	Older children (6 - <12 years)-Preventive regimen [Main trial]	Adolescents (12 - <18 years) - Preventive regimen [Main trial]	Adults (>= 18 years) - Preventive regimen [Main trial]
Number of subjects analysed	27	28	23	129
Units: Bleeding episodes/year
median (full range (min-max))	1.08 (0 to 12.12)	1.57 (0 to 10.8)	1.57 (0 to 6.01)	1.37 (0 to 17.82)

No statistical analyses for this end point

Secondary: Haemostatic response to turoctocog alfa (none, moderate, good or excellent) in treatment of bleeds

Top of page

End point title

Haemostatic response to turoctocog alfa (none, moderate, good or excellent) in treatment of bleeds

End point description

Haemostatic response to turoctocog alfa (none, moderate, good or excellent) in treatment of bleeds using a four-point response scale: none, moderate, good or excellent. The evaluation was done by patient, caregiver and/or investigator based on experience as follows: 1. Excellent: Abrupt pain relief and/or unequivocal improvement in objective signs of bleeding within approximately 8 hours after a single infusion 2. Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hours after an infusion, but possibly requiring more than 1 infusion for complete resolution. 3. Moderate: Probable or slight beneficial effect within approximately 8 hours after the first infusion; usually requiring more than 1 infusion. 4. None: No improvement, or worsening of symptoms. This endpoint is measured during the preventive and on-demand sub-trial (during 90 months).

End point type

Secondary

End point timeframe

After 90 months

End point values	Small children (0 - <6 years)-Preventive regimen [Main trial]	Older children (6 - <12 years)-Preventive regimen [Main trial]	Adolescents (12 - <18 years) - Preventive regimen [Main trial]	Adults (>= 18 years) - Preventive regimen [Main trial]	Adolescents (12-<18 years)-(On-Demand regimen [Main trial])	Adults (>=18 years)-(On-Demand regimen [Main trial])	Adults (>=18 years)-(On-Demand regimen [Sub-trial])
Number of subjects analysed	21	24	22	103	1	7	14
Units: Number of bleeds
Excellent	124	189	72	565	1	150	94
Good	62	103	103	382	6	22	105
Moderate	17	37	19	91	0	2	11
None	1	1	0	7	0	0	0
Not known	0	0	0	1	0	0	0
Missing	0	1	2	5	0	0	0

No statistical analyses for this end point

Secondary: The number of infusions of turoctocog alfa required per bleeding episode

Top of page

End point title

The number of infusions of turoctocog alfa required per bleeding episode

End point description

Number of infusions of turoctocog alfa that are required to stop the bleed, per bleeding episode (during 90 months).

End point type

Secondary

End point timeframe

After 90 months

End point values	Small children (0 - <6 years)-Preventive regimen [Main trial]	Older children (6 - <12 years)-Preventive regimen [Main trial]	Adolescents (12 - <18 years) - Preventive regimen [Main trial]	Adults (>= 18 years) - Preventive regimen [Main trial]	Adolescents (12-<18 years)-(On-Demand regimen [Main trial])	Adults (>=18 years)-(On-Demand regimen [Main trial])	Adults (>=18 years)-(On-Demand regimen [Sub-trial])
Number of subjects analysed	21	24	22	103	1	7	14
Units: Number of infusions
arithmetic mean (standard deviation)	1.8 ± 2.1	1.7 ± 1.6	1.8 ± 2.1	1.6 ± 3	1.3 ± 0.5	1.1 ± 0.4	1.4 ± 0.7

No statistical analyses for this end point

Secondary: Time to control of bleeding after the first dose of turoctocog alfa used for treatment of bleeds

Top of page

End point title

Time to control of bleeding after the first dose of turoctocog alfa used for treatment of bleeds

End point description

Time to stop of bleed from first dose of turoctocog alfa used for treatment of bleeds. This endpoint was measured during 90 months.

End point type

Secondary

End point timeframe

After 90 months

End point values	Small children (0 - <6 years)-Preventive regimen [Main trial]	Older children (6 - <12 years)-Preventive regimen [Main trial]	Adolescents (12 - <18 years) - Preventive regimen [Main trial]	Adults (>= 18 years) - Preventive regimen [Main trial]	Adolescents (12-<18 years)-(On-Demand regimen [Main trial])	Adults (>=18 years)-(On-Demand regimen [Main trial])	Adults (>=18 years)-(On-Demand regimen [Sub-trial])
Number of subjects analysed	21	24	22	103	1	7	14
Units: Hours
arithmetic mean (standard deviation)	12.63 ± 23.52	19.32 ± 44.91	19.57 ± 31.26	16.61 ± 39.45	10.96 ± 7.52	8.01 ± 8.2	17.95 ± 17.64

No statistical analyses for this end point

Secondary: Assessment of the actual consumption of turoctocog alfa (IU/kg BW/bleeding episode)

Top of page

End point title

Assessment of the actual consumption of turoctocog alfa (IU/kg BW/bleeding episode)

End point description

The mean consumption of turoctocog alfa used for treatment of a bleed from start to stop of a bleed. This endpoint was measured during 90 months.

End point type

Secondary

End point timeframe

After 90 months

End point values	Small children (0 - <6 years)-Preventive regimen [Main trial]	Older children (6 - <12 years)-Preventive regimen [Main trial]	Adolescents (12 - <18 years) - Preventive regimen [Main trial]	Adults (>= 18 years) - Preventive regimen [Main trial]	Adolescents (12-<18 years)-(On-Demand regimen [Main trial])	Adults (>=18 years)-(On-Demand regimen [Main trial])	Adults (>=18 years)-(On-Demand regimen [Sub-trial])
Number of subjects analysed	21	24	22	103	1	7	14
Units: IU/kg BW/bleeding episode
arithmetic mean (standard deviation)	75.9 ± 86.4	70.5 ± 72.4	56.6 ± 56.2	57.9 ± 157.3	37.6 ± 21.7	43 ± 11.1	44.9 ± 30.5

No statistical analyses for this end point

Secondary: Assessment of the actual consumption of turoctocog alfa for prevention (only applicable for subjects in the preventive regimen)

Top of page

End point title

Assessment of the actual consumption of turoctocog alfa for prevention (only applicable for subjects in the preventive regimen)

End point description

The mean consumption of turoctocog alfa used for treatment of a bleed from start to stop of a bleed during the preventive regimen (per month per subject). This endpoint was measured during 90 months.

End point type

Secondary

End point timeframe

After 90 months

End point values	Small children (0 - <6 years)-Preventive regimen [Main trial]	Older children (6 - <12 years)-Preventive regimen [Main trial]	Adolescents (12 - <18 years) - Preventive regimen [Main trial]	Adults (>= 18 years) - Preventive regimen [Main trial]
Number of subjects analysed	27	28	23	128
Units: IU/kg BW/month
arithmetic mean (standard deviation)	547.3 ± 106.9	501 ± 113.9	378.1 ± 113.3	390.2 ± 112

No statistical analyses for this end point

Secondary: Frequency of adverse events and serious adverse events

Top of page

End point title

Frequency of adverse events and serious adverse events

End point description

The number of adverse events and serious adverse events reported during the surgery sub-trial.

End point type

Secondary

End point timeframe

After 90 months

End point values	Surgery sub-trial
Number of subjects analysed	17
Units: Number of events
Adverse events	18
Serious adverse events	2

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

From screening (visit 1) starting after first exposure to Turoctocog alfa and until post treatment follow-up period

Adverse event reporting additional description

The safety analysis set consists of all patients exposed to turoctocog alfa

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

19.0

Reporting group title

Small children (0 - <6 Years)

Reporting group description

Subjects (0-<6 years) received turoctocog alfa (preventive or on-demand regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. Subjects coming from main trial were allowed to switch back before completion of 6 months on-demand regimen. Preventive: Turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day,20−60 IU/kg 3 times weekly or 40−60 IU/kg once every third day or twice weekly. On-Demand: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for treatment of bleeds as they occurred and occasionally as preventive treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. The maximum treatment duration (27 Oct 2009 - 30 Jun 2016)

Reporting group title

Older children (6 - <12 Years)

Reporting group description

Subjects (6-<12 years) received turoctocog alfa (preventive or on-demand regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. Subjects coming from main trial were allowed to switch back before completion of 6 months on-demand regimen. Preventive: Turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day,20−60 IU/kg 3 times weekly or 40−60 IU/kg BW once every third day or twice weekly. On-Demand: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for treatment of bleeds as they occurred and occasionally as preventive treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. The maximum treatment duration (27 Oct 2009 - 30 Jun 2016)

Reporting group title

Adolescents (12 - <18 Years)

Reporting group description

Subjects (12-<18 years) received turoctocog alfa (preventive or on-demand regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. Subjects coming from main trial were allowed to switch back before completion of 6 months on-demand regimen. Preventive regimen: Turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day,20−60 IU/kg 3 times weekly or 40−60 IU/kg once every third day or twice weekly. On-Demand: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for treatment of bleeds as they occurred and occasionally as preventive treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. The maximum treatment duration (27 Oct 2009 - 30 Jun 2016)

Reporting group title

Adults (≥18 Years)

Reporting group description

Subjects (≥18 years) received turoctocog alfa (preventive or on-demand regimen). Subjects switched between regimens during trial (main and on-demand sub-trial) upon investigators’ discretion. Subjects coming from main trial were allowed to switch back before completion of 6 months on-demand regimen. Preventive regimen: Turoctocog alfa as a slow iv bolus injection 20−50 IU/kg once every second day,20−60 IU/kg 3 times weekly or 40−60 IU/kg once every third day or twice weekly. On-Demand: Dose level aimed at a post injection level of at least 0.50 IU/mL of turoctocog alfa for treatment of bleeds as they occurred and occasionally as preventive treatment. All subjects were offered participation until either turoctocog alfa was commercially available in relevant country or until the trial, part of trial or a trial site was terminated by Novo Nordisk or a relevant authority for any reason in relevant country. The maximum treatment duration (27 Oct 2009 - 30 Jun 2016)

Serious adverse events	Small children (0 - <6 Years)	Older children (6 - <12 Years)	Adolescents (12 - <18 Years)	Adults (≥18 Years)
Total subjects affected by serious adverse events
subjects affected / exposed	5 / 27 (18.52%)	9 / 28 (32.14%)	6 / 23 (26.09%)	21 / 135 (15.56%)
number of deaths (all causes)	0	0	0	2
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic cancer metastatic
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Vascular disorders
Hypotension
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Immune system disorders
Food allergy
subjects affected / exposed	1 / 27 (3.70%)	0 / 28 (0.00%)	0 / 23 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Social circumstances
Physical assault
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	1 / 27 (3.70%)	0 / 28 (0.00%)	0 / 23 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Laryngeal stenosis
subjects affected / exposed	1 / 27 (3.70%)	0 / 28 (0.00%)	0 / 23 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Bipolar I disorder
subjects affected / exposed	0 / 27 (0.00%)	1 / 28 (3.57%)	0 / 23 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Schizophrenia
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Product issues
Device loosening
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Femur fracture
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Forearm fracture
subjects affected / exposed	0 / 27 (0.00%)	2 / 28 (7.14%)	0 / 23 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hand fracture
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Muscle strain
subjects affected / exposed	0 / 27 (0.00%)	1 / 28 (3.57%)	0 / 23 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Post procedural haemorrhage
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	1 / 23 (4.35%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin injury
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	1 / 23 (4.35%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Subdural haemorrhage
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Traumatic fracture
subjects affected / exposed	1 / 27 (3.70%)	0 / 28 (0.00%)	0 / 23 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Haemorrhage intracranial
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	1 / 23 (4.35%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Optic neuritis
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	1 / 23 (4.35%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Radial nerve palsy
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Pterygium
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Ascites
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	1 / 23 (4.35%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal haemorrhage
subjects affected / exposed	1 / 27 (3.70%)	0 / 28 (0.00%)	0 / 23 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peritoneal haemorrhage
subjects affected / exposed	0 / 27 (0.00%)	1 / 28 (3.57%)	0 / 23 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	2 / 135 (1.48%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Haematuria
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	1 / 23 (4.35%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal aneurysm
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Haemophilic arthropathy
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Muscle haemorrhage
subjects affected / exposed	0 / 27 (0.00%)	1 / 28 (3.57%)	0 / 23 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tendinous contracture
subjects affected / exposed	0 / 27 (0.00%)	1 / 28 (3.57%)	0 / 23 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	0 / 27 (0.00%)	1 / 28 (3.57%)	0 / 23 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Device related infection
subjects affected / exposed	0 / 27 (0.00%)	1 / 28 (3.57%)	0 / 23 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 27 (3.70%)	0 / 28 (0.00%)	0 / 23 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatitis C
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary sepsis
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Staphylococcal infection
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	2 / 135 (1.48%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Small children (0 - <6 Years)	Older children (6 - <12 Years)	Adolescents (12 - <18 Years)	Adults (≥18 Years)
Total subjects affected by non serious adverse events
subjects affected / exposed	23 / 27 (85.19%)	25 / 28 (89.29%)	20 / 23 (86.96%)	94 / 135 (69.63%)
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	1 / 27 (3.70%)	5 / 28 (17.86%)	4 / 23 (17.39%)	8 / 135 (5.93%)
occurrences all number	1	8	5	13
Fall
subjects affected / exposed	3 / 27 (11.11%)	4 / 28 (14.29%)	5 / 23 (21.74%)	7 / 135 (5.19%)
occurrences all number	6	19	8	8
Head injury
subjects affected / exposed	2 / 27 (7.41%)	1 / 28 (3.57%)	0 / 23 (0.00%)	0 / 135 (0.00%)
occurrences all number	2	1	0	0
Joint injury
subjects affected / exposed	0 / 27 (0.00%)	2 / 28 (7.14%)	2 / 23 (8.70%)	4 / 135 (2.96%)
occurrences all number	0	2	3	4
Laceration
subjects affected / exposed	2 / 27 (7.41%)	0 / 28 (0.00%)	2 / 23 (8.70%)	3 / 135 (2.22%)
occurrences all number	3	0	2	3
Ligament sprain
subjects affected / exposed	0 / 27 (0.00%)	5 / 28 (17.86%)	1 / 23 (4.35%)	4 / 135 (2.96%)
occurrences all number	0	19	1	5
Limb injury
subjects affected / exposed	1 / 27 (3.70%)	2 / 28 (7.14%)	4 / 23 (17.39%)	3 / 135 (2.22%)
occurrences all number	3	3	4	4
Muscle strain
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	2 / 23 (8.70%)	0 / 135 (0.00%)
occurrences all number	0	0	2	0
Skin abrasion
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	2 / 23 (8.70%)	0 / 135 (0.00%)
occurrences all number	0	0	2	0
Traumatic haematoma
subjects affected / exposed	2 / 27 (7.41%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences all number	2	0	0	1
Wound
subjects affected / exposed	2 / 27 (7.41%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences all number	2	0	0	1
Nervous system disorders
Headache
subjects affected / exposed	2 / 27 (7.41%)	3 / 28 (10.71%)	6 / 23 (26.09%)	17 / 135 (12.59%)
occurrences all number	4	8	29	46
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	2 / 27 (7.41%)	1 / 28 (3.57%)	1 / 23 (4.35%)	4 / 135 (2.96%)
occurrences all number	2	2	1	5
General disorders and administration site conditions
Chills
subjects affected / exposed	2 / 27 (7.41%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences all number	3	0	0	1
Pyrexia
subjects affected / exposed	4 / 27 (14.81%)	2 / 28 (7.14%)	5 / 23 (21.74%)	5 / 135 (3.70%)
occurrences all number	5	6	6	6
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	2 / 27 (7.41%)	1 / 28 (3.57%)	1 / 23 (4.35%)	4 / 135 (2.96%)
occurrences all number	3	1	1	4
Abdominal pain upper
subjects affected / exposed	1 / 27 (3.70%)	0 / 28 (0.00%)	2 / 23 (8.70%)	2 / 135 (1.48%)
occurrences all number	1	0	2	2
Dental caries
subjects affected / exposed	5 / 27 (18.52%)	1 / 28 (3.57%)	0 / 23 (0.00%)	3 / 135 (2.22%)
occurrences all number	5	1	0	4
Diarrhoea
subjects affected / exposed	5 / 27 (18.52%)	1 / 28 (3.57%)	2 / 23 (8.70%)	4 / 135 (2.96%)
occurrences all number	5	1	2	4
Dyspepsia
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	2 / 23 (8.70%)	3 / 135 (2.22%)
occurrences all number	0	0	2	3
Gastritis
subjects affected / exposed	0 / 27 (0.00%)	2 / 28 (7.14%)	0 / 23 (0.00%)	0 / 135 (0.00%)
occurrences all number	0	2	0	0
Nausea
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	2 / 23 (8.70%)	3 / 135 (2.22%)
occurrences all number	0	0	2	3
Tooth development disorder
subjects affected / exposed	2 / 27 (7.41%)	0 / 28 (0.00%)	0 / 23 (0.00%)	0 / 135 (0.00%)
occurrences all number	3	0	0	0
Tooth loss
subjects affected / exposed	0 / 27 (0.00%)	3 / 28 (10.71%)	0 / 23 (0.00%)	0 / 135 (0.00%)
occurrences all number	0	3	0	0
Toothache
subjects affected / exposed	0 / 27 (0.00%)	1 / 28 (3.57%)	3 / 23 (13.04%)	11 / 135 (8.15%)
occurrences all number	0	1	3	12
Vomiting
subjects affected / exposed	5 / 27 (18.52%)	2 / 28 (7.14%)	2 / 23 (8.70%)	6 / 135 (4.44%)
occurrences all number	5	2	4	6
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	7 / 27 (25.93%)	1 / 28 (3.57%)	4 / 23 (17.39%)	9 / 135 (6.67%)
occurrences all number	11	1	5	11
Nasal congestion
subjects affected / exposed	1 / 27 (3.70%)	0 / 28 (0.00%)	2 / 23 (8.70%)	5 / 135 (3.70%)
occurrences all number	1	0	3	5
Oropharyngeal pain
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	3 / 23 (13.04%)	14 / 135 (10.37%)
occurrences all number	0	0	3	16
Respiratory disorder
subjects affected / exposed	1 / 27 (3.70%)	2 / 28 (7.14%)	0 / 23 (0.00%)	2 / 135 (1.48%)
occurrences all number	5	4	0	2
Rhinitis allergic
subjects affected / exposed	5 / 27 (18.52%)	1 / 28 (3.57%)	2 / 23 (8.70%)	1 / 135 (0.74%)
occurrences all number	5	1	2	2
Skin and subcutaneous tissue disorders
Urticaria
subjects affected / exposed	3 / 27 (11.11%)	1 / 28 (3.57%)	1 / 23 (4.35%)	1 / 135 (0.74%)
occurrences all number	4	1	1	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 27 (0.00%)	1 / 28 (3.57%)	4 / 23 (17.39%)	19 / 135 (14.07%)
occurrences all number	0	2	7	29
Arthropathy
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	2 / 23 (8.70%)	6 / 135 (4.44%)
occurrences all number	0	0	2	8
Back pain
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	0 / 23 (0.00%)	12 / 135 (8.89%)
occurrences all number	0	0	0	13
Haemophilic arthropathy
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	2 / 23 (8.70%)	2 / 135 (1.48%)
occurrences all number	0	0	2	2
Myalgia
subjects affected / exposed	2 / 27 (7.41%)	0 / 28 (0.00%)	0 / 23 (0.00%)	4 / 135 (2.96%)
occurrences all number	2	0	0	4
Pain in extremity
subjects affected / exposed	2 / 27 (7.41%)	0 / 28 (0.00%)	1 / 23 (4.35%)	3 / 135 (2.22%)
occurrences all number	3	0	1	4
Synovitis
subjects affected / exposed	0 / 27 (0.00%)	0 / 28 (0.00%)	2 / 23 (8.70%)	1 / 135 (0.74%)
occurrences all number	0	0	3	1
Infections and infestations
Bronchitis
subjects affected / exposed	1 / 27 (3.70%)	2 / 28 (7.14%)	2 / 23 (8.70%)	3 / 135 (2.22%)
occurrences all number	3	2	2	3
Conjunctivitis
subjects affected / exposed	0 / 27 (0.00%)	4 / 28 (14.29%)	0 / 23 (0.00%)	6 / 135 (4.44%)
occurrences all number	0	4	0	6
Gastroenteritis
subjects affected / exposed	3 / 27 (11.11%)	2 / 28 (7.14%)	1 / 23 (4.35%)	5 / 135 (3.70%)
occurrences all number	3	2	1	5
Gastroenteritis viral
subjects affected / exposed	3 / 27 (11.11%)	0 / 28 (0.00%)	0 / 23 (0.00%)	0 / 135 (0.00%)
occurrences all number	5	0	0	0
Influenza
subjects affected / exposed	0 / 27 (0.00%)	2 / 28 (7.14%)	9 / 23 (39.13%)	9 / 135 (6.67%)
occurrences all number	0	5	13	9
Nasopharyngitis
subjects affected / exposed	1 / 27 (3.70%)	2 / 28 (7.14%)	5 / 23 (21.74%)	23 / 135 (17.04%)
occurrences all number	1	4	18	41
Pharyngitis
subjects affected / exposed	1 / 27 (3.70%)	7 / 28 (25.00%)	3 / 23 (13.04%)	9 / 135 (6.67%)
occurrences all number	2	24	9	15
Pharyngitis streptococcal
subjects affected / exposed	0 / 27 (0.00%)	2 / 28 (7.14%)	0 / 23 (0.00%)	0 / 135 (0.00%)
occurrences all number	0	2	0	0
Respiratory tract infection viral
subjects affected / exposed	2 / 27 (7.41%)	0 / 28 (0.00%)	0 / 23 (0.00%)	1 / 135 (0.74%)
occurrences all number	2	0	0	1
Rhinitis
subjects affected / exposed	2 / 27 (7.41%)	1 / 28 (3.57%)	2 / 23 (8.70%)	1 / 135 (0.74%)
occurrences all number	2	1	3	1
Sinusitis
subjects affected / exposed	5 / 27 (18.52%)	1 / 28 (3.57%)	4 / 23 (17.39%)	2 / 135 (1.48%)
occurrences all number	6	1	7	2
Tonsillitis
subjects affected / exposed	4 / 27 (14.81%)	2 / 28 (7.14%)	2 / 23 (8.70%)	2 / 135 (1.48%)
occurrences all number	8	2	6	7
Upper respiratory tract infection
subjects affected / exposed	5 / 27 (18.52%)	5 / 28 (17.86%)	2 / 23 (8.70%)	16 / 135 (11.85%)
occurrences all number	9	16	2	26
Varicella
subjects affected / exposed	3 / 27 (11.11%)	3 / 28 (10.71%)	0 / 23 (0.00%)	0 / 135 (0.00%)
occurrences all number	3	3	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

14 Apr 2010

1. One of the main reasons for amending the protocol was that the pivotal trial (NN7008-3543) was substantially amended based on responses from health authorities. Furthermore, the paediatric trial protocol (NN7008-3545) had been finalised. To make a smooth transfer of patients from the above mentioned trials into the present trial, the trial protocol was amended. 2. The sub-trial was originally intended for patients undergoing elective surgery with continuous infusion. This was changed to allow surgery with both bolus and continuous infusion. Furthermore, emergency surgery was also allowed with this amendment. 3. Objectives and endpoints were updated to reflect changes in the pivotal trial (NN7008-3543) and to be consistent with the paediatric trial (NN7008-3545) and the Japanese trial (NN7008-3600). 4. The dose intervals for preventive treatments were changed based on higher dose levels for paediatric patients. 5. The maximum daily dose that was allowed was increased from 150 IU/kg to 200 IU/kg. 6. Sections 5 and 8 of the protocol were updated for readability and understanding. Especially the surgery sections were updated. 7. The section describing inhibitor formation and handling of inhibitors was updated for readability and understanding. 8. Concomitant medication not allowed in the trial was clarified. 9. Definition of hospitalisation was changed in accordance with Food and Drug Administration’s (FDA) definition. 10. Medical events of special interest were thoroughly described in the safety section. 11. A stopping rule was added to the safety section.

02 Sep 2011

1. Change of the diary data entry from data management at Novo Nordisk to diary data entry at site performed by the investigator or delegated trial staff. 2. Clarification of the continuous infusion surgery procedure. 3. Update of the total number of patients, sites and countries. 4. Change in exclusion criteria to include withdrawn patients from previous trial if allowed in previous protocol. 5. Removal of lupus anticoagulant test from the assessment visits 6. Specification of when HIV test and hepatitis test were to be performed. 7. Change to the master patient information/informed consent form (ICF) to include PK-trial NN7008-3893, update of the number of patients, sites and countries, and specification of when HIV test and hepatitis test were to be performed. 8. Change to the master patient information/informed consent form to remove the possibility of having trial product shipped to the patients home by courier.

02 Sep 2011

To correct a typing error in the master subject information/informed consent form which changed the meaning of a sentence to the opposite.

19 Jul 2012

1. This amendment opened the possibility of transferring subjects into the pathfinder™ trials (these are trials with glycopegylated turoctocog alfa [N8-GP]) and the possibility of transferring subjects into and back from the NN7008-4015 trial. 2. PRO questionnaires HAEMO-A-QOL for adult patients at every second assessment visit. 3. Extension of the study from year 2013 until 2016. 4. Change of the MESI definition. 5. For severe bleeds patients were given the option of phoning or visiting the site. 6. An extra preventive treatment outside of scheduled preventive dose was allowed. 7. Whole blood transfusions were allowed during the surgery sub-trial.

05 Feb 2014

1. UTN number was added. 2. On-demand sub-trial added to collect data on efficacy in treatment of bleeds occurring in an on-demand treatment setting for 6 months. 3. Removal of withdrawal criteria # 15. 4. Statistical section and end-points updated to align with the analysis being done in other turoctocog alfa trials and to reflect analysis for the on-demand sub-trial 5. Interim analyses added to support submission and questions from authorities and to report results from the on-demand sub-trial. 6. Continuation into NN7008-3553 removed. 7. Safety section updated. 8. Severity of bleed clarified/updated. 9. Lab value at visit 1 for patients coming from NN7008-4015: patients coming from NN7008-4015 had the lab data transferred from NN7008-4015 to NN7008-3568 visit 1, however the lab sample panel was not completely the same, and the differences were highlighted with this amendment 10. Monitoring visits when last patient had had his last visit at site: as long time could occur between last patient at site until closure of site, it has been added that monitoring visit frequency does not have to be at least 12 weeks when the last patients has had his last visit at site. 11. Minor corrections and consistency updates. 12. Attachment I updated with new information. 13. Patient information/informed consent form were adapted accordingly.

27 Mar 2015

1. Two (2) new treatment regimens were added – once every third day and twice weekly regimens. 2. PK sub-trial in patients with high BMI (BMI ≥30 kg/m2) was added. 3. The statistical section was updated to include the latest Statistical Analysis Plan version 3.0 from 9-Feb-2012. 4. Signatory investigator was updated. 5. Patient Information/Informed Consent Form was adapted accordingly.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

http://www.ncbi.nlm.nih.gov/pubmed/27291066
http://www.ncbi.nlm.nih.gov/pubmed/26058730
http://www.ncbi.nlm.nih.gov/pubmed/27291066

For support, Contact us.

The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

European Medicines Agency © 1995-Sat Apr 20 01:29:34 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands