pathfinder™3: Evaluating the Haemostatic Effect of NNC 0129-0000-1003 During Surgical Procedures in Subjects With Haemophilia A.

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01489111
• Collaborator: (none)
• Enrollment: 36
• Locations: 70
• Arm: 1
• Actual Duration (Months): 76.2
• Patients Per Site: 0.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This trial is conducted globally. The aim of this trial is to evaluate the haemostatic effect of NNC 0129-0000-1003 during surgical procedures in subjects with haemophilia A.

Condition or Disease	Intervention/Treatment	Phase
Congenital Bleeding Disorder; Haemophilia A	Drug: turoctocog alfa pegol	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of NNC 0129-0000-1003 During Surgical Procedures in Patients With Haemophilia A
• Actual Study Start Date: Aug 3, 2012
• Actual Primary Completion Date: Dec 10, 2018
• Actual Study Completion Date: Dec 10, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Surgery	Drug: turoctocog alfa pegol; Bleeding preventive treatment administered i.v. before, during and after surgery. Individually adjusted doses.; Other Names: NNC 0129-0000-1003

Outcome Measures

Primary Outcome Measures

1. Haemostatic Effect During Surgery Evaluated by the Four-point Scale, Assessed by the Investigator/Surgeon at the Day of Surgery - Four-point Response Scale: Excellent, Good, Moderate or None [Assessed by the Investigator/surgeon at the day of surgery]

   Haemostatic effect during surgery was evaluated on a four-point response scale as 'none', 'moderate', 'good' and 'excellent'. This was assessed after completion of surgery (defined as "last stitch"). Excellent: Better than expected/predicted in this type of procedure. Good: As expected in this type of procedure. Moderate: Less than optimal for the type of procedure but haemostatic response maintained without change of treatment regimen. None: Bleeding due to inadequate therapeutic response with adequate dosing, change of regimen required.

Secondary Outcome Measures

1. Average Consumption of N8-GP During Surgery [During surgery, defined as the time from "knife to skin" until "last stitch"]

   Average consumption of N8-GP, during surgery is presented. The time during surgery is defined from 'knife to skin' until 'last stitch'.

2. Haemostatic Effect of N8-GP During the Post-operative Period Days 1-6 [During the post-operative period, days 1-6]

   Haemostatic effect during post-operative period days 1-6 as evaluated on a four-point response scale as 'none', 'moderate', 'good' and 'excellent'. Excellent: Better than expected/predicted in this type of procedure. Good: As expected in this type of procedure. Moderate: Less than optimal for the type of procedure but haemostatic response maintained without change of treatment regimen. None: Bleeding due to inadequate therapeutic response with adequate dosing, change of regimen required.

3. Haemostatic Effect of N8-GP During the Post-operative Period Days 7-14 [During the post-operative period, days 7-14]

   Haemostatic effect during post-operative period days 1-6 and days 7-14 was evaluated on a four-point response scale as 'none', 'moderate', 'good' and 'excellent'. Excellent: Better than expected/predicted in this type of procedure. Good: As expected in this type of procedure. Moderate: Less than optimal for the type of procedure but haemostatic response maintained without change of treatment regimen. None: Bleeding due to inadequate therapeutic response with adequate dosing, change of regimen required.

4. Average Consumption of N8-GP During the Post-operative Period Days 1-6 [During the post-operative period, days 1-6]

   Average consumption of N8-GP during post operative period days 1-6 is presented. Analysis population: Full analysis set included all subjects exposed to the trial drug (N8-GP) and completed surgery.

5. Incidence Rate of Inhibitors Against Factor VIII (FVIII) (≥0.6 BU/mL) [during the trial (2-5 weeks)]

   Incidence rate of inhibitors is the number of newly developed inhibitors per surgery. Development of FVIII inhibitors was measured by a validated Nijmegen modified Bethesda assay. A positive inhibitor test was defined as ≥0.6 bethesda unit. Number of participants with inhibitors at the end of trial is presented.

6. Estimated Blood Loss During Surgery [During surgery]

   The mean estimated blood loss following surgery is presented. Estimated blood loss (mL) was evaluated post surgery.

7. Number of Transfusions During the Post-operative Period Days 1-6 [Post-operative period, days 1-6]

   Number of blood product transfusions (transfusion of red blood cells) during the post-surgery period, Days 1-6 is presented.

8. Length of Stay in the Hospital [During the trial (2-5 weeks)]

   Mean number of days stayed at the hospital during the trial.

9. Number of Days in Intensive Care [During the trial (2-5 weeks)]

   Mean number of days in the intensive care due to surgery during the trial is presented.

10. Adverse Events Reported During the Trial Period [During the trial (2-5 weeks)]

    Number of adverse event during the trial is presented. This includes events from the first trial related activity after the patient has signed the informed consent and until the end of trial (earliest at day 14).

11. Serious Adverse Events Reported During the Trial Period [During the trial (2-5 weeks)]

    Number of serious adverse event during the trial is presented. This includes events from the first trial related activity after the patient has signed the informed consent and until the end of trial (earliest at day 14).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject.)

• Ongoing participation in the pathfinder™2 (NN7088-3859) or the pathfinderTM 4 (NN7088-3861) trial and having received greater than or equal to 5 doses of N8-GP

• Undergoing major surgery requiring daily monitoring of FVIII:C (FVIII activity) and wound status for at least 3 days

• The patient and/or Legally Acceptable Representative (LAR) is capable of assessing a bleeding episode, keeping an eDiary, capable of home treatment of bleeding episodes and otherwise capable of following the trial procedures

Exclusion Criteria:

• Known or suspected hypersensitivity to trial product including allergy to hamster protein or related products

• Previous withdrawal from the pathfinder™2 (NN7088-3859) or the pathfinderTM 4 (NN7088-3861) trial after administration of trial product, except interruption due to inclusion in this pathfinderTM 3 trial (NN7088-3860)

• The receipt of any investigational medicinal product (except N8-GP) within 30 days prior to enrolment into the trial. (For Brazil, only: Participation in a previous clinical trial within one year prior to screening for this trial (Visit 1), unless there is a direct benefit to the research subject, at the Investigator's discretion)

• FVIII inhibitors at least 0.6 BU (Bethesda Units)/mL at screening

• Previous arterial thrombotic events (e.g. myocardial infarction and intracranial thrombosis) or previous deep venous thrombosis or pulmonary embolism (as defined by available medical records)

• Immune modulating or chemotherapeutic medication

• Any disease (liver, kidney, inflammatory and mental disorders included) or condition which, according to the Investigator's judgement, could imply a potential hazard to the patient, interfere with trial participation or trial outcome

• Unwillingness, language or other barriers precluding adequate understanding and/or cooperation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Phoenix	Arizona	United States	85016-7710
2	Novo Nordisk Investigational Site	Long Beach	California	United States	90806
3	Novo Nordisk Investigational Site	Sacramento	California	United States	95817
4	Novo Nordisk Investigational Site	Torrance	California	United States	90502-2004
5	Novo Nordisk Investigational Site	Orlando	Florida	United States	32827
6	Novo Nordisk Investigational Site	Tampa	Florida	United States	33607
7	Novo Nordisk Investigational Site	Boise	Idaho	United States	83712
8	Novo Nordisk Investigational Site	Iowa City	Iowa	United States	52242
9	Novo Nordisk Investigational Site	New Orleans	Louisiana	United States	70118-5720
10	Novo Nordisk Investigational Site	Baltimore	Maryland	United States	21287
11	Novo Nordisk Investigational Site	Newark	New Jersey	United States	07102
12	Novo Nordisk Investigational Site	Cincinnati	Ohio	United States	452289
13	Novo Nordisk Investigational Site	Portland	Oregon	United States	97239
14	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania	United States	19134
15	Novo Nordisk Investigational Site	Charleston	South Carolina	United States	29425
16	Novo Nordisk Investigational Site	Nashville	Tennessee	United States	37232-9830
17	Novo Nordisk Investigational Site	Houston	Texas	United States	77030
18	Novo Nordisk Investigational Site	Norfolk	Virginia	United States	23507
19	Novo Nordisk Investigational Site	Spokane	Washington	United States	99204
20	Novo Nordisk Investigational Site	Camperdown	New South Wales	Australia	2050
21	Novo Nordisk Investigational Site	South Brisbane	Queensland	Australia	4101
22	Novo Nordisk Investigational Site	Parkville	Victoria	Australia	3052
23	Novo Nordisk Investigational Site	Campinas	Sao Paulo	Brazil	13081-970
24	Novo Nordisk Investigational Site	Sofia		Bulgaria	1756
25	Novo Nordisk Investigational Site	Split		Croatia	21 000
26	Novo Nordisk Investigational Site	Zagreb		Croatia	10 000
27	Novo Nordisk Investigational Site	København Ø		Denmark	2100
28	Novo Nordisk Investigational Site	Århus N		Denmark	8200
29	Novo Nordisk Investigational Site	Bron Cedex		France	69677
30	Novo Nordisk Investigational Site	Le Kremlin Bicetre		France	94270
31	Novo Nordisk Investigational Site	Nantes Cedex 1		France	44093
32	Novo Nordisk Investigational Site	Paris		France	75015
33	Novo Nordisk Investigational Site	Berlin		Germany	10249
34	Novo Nordisk Investigational Site	Bonn		Germany	53127
35	Novo Nordisk Investigational Site	Frankfurt/M.		Germany	60590
36	Novo Nordisk Investigational Site	Hannover		Germany	30625
37	Novo Nordisk Investigational Site	Homburg		Germany	66421
38	Novo Nordisk Investigational Site	München		Germany	80336
39	Novo Nordisk Investigational Site	Budapest		Hungary	H-1134
40	Novo Nordisk Investigational Site	Debrecen		Hungary	4012
41	Novo Nordisk Investigational Site	Tel-Hashomer		Israel	52621
42	Novo Nordisk Investigational Site	Milano		Italy	20124
43	Novo Nordisk Investigational Site	Udine		Italy	33100
44	Novo Nordisk Investigational Site	Vicenza		Italy	36100
45	Novo Nordisk Investigational Site	Kashihara-shi, Nara		Japan	634 8522
46	Novo Nordisk Investigational Site	Shinjuku-ku, Tokyo		Japan	160 0023
47	Novo Nordisk Investigational Site	Suginami-ku, Tokyo		Japan	167 0035
48	Novo Nordisk Investigational Site	Tokyo		Japan	108-8639
49	Novo Nordisk Investigational Site	Kuala Lumpur		Malaysia	50400
50	Novo Nordisk Investigational Site	Selangor Darul Ehsan		Malaysia	68000
51	Novo Nordisk Investigational Site	Groningen		Netherlands	9713 GZ
52	Novo Nordisk Investigational Site	Rotterdam		Netherlands	3015 CE
53	Novo Nordisk Investigational Site	Oslo		Norway	0027
54	Novo Nordisk Investigational Site	Madrid		Spain	28046
55	Novo Nordisk Investigational Site	Málaga		Spain	29010
56	Novo Nordisk Investigational Site	Malmö		Sweden	205 02
57	Novo Nordisk Investigational Site	Genève 14		Switzerland	1211
58	Novo Nordisk Investigational Site	Lausanne		Switzerland	1011
59	Novo Nordisk Investigational Site	Zürich		Switzerland	8091
60	Novo Nordisk Investigational Site	Changhua		Taiwan	500
61	Novo Nordisk Investigational Site	Taipei		Taiwan	100
62	Novo Nordisk Investigational Site	Adana		Turkey	01130
63	Novo Nordisk Investigational Site	Bornova-IZMIR		Turkey	35100
64	Novo Nordisk Investigational Site	Samsun		Turkey	55319
65	Novo Nordisk Investigational Site	Basingstoke		United Kingdom	RG24 9NA
66	Novo Nordisk Investigational Site	Cardiff		United Kingdom	CF14 4XW
67	Novo Nordisk Investigational Site	London		United Kingdom	NW3 2QG
68	Novo Nordisk Investigational Site	London		United Kingdom	SE1 7EH
69	Novo Nordisk Investigational Site	Oxford		United Kingdom	OX3 7LJ
70	Novo Nordisk Investigational Site	Sheffield		United Kingdom	S11 8RN

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 6, 2019

More Information

Additional Information:

• Clinical Trials at Novo Nordisk

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT01489111
• Other Study ID Numbers: NN7088-3860; U1111-1119-7326; 2011-001144-30; 132215
• First Posted: Dec 9, 2011
• Last Update Posted: Aug 10, 2020
• Last Verified: Jul 1, 2020

• Additional relevant MeSH terms: Hemostatic Disorders; Hemophilia A; Blood Coagulation Disorders

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 26 sites in 13 countries, as follows: Australia (1 site), Denmark (1 site), France (3 sites), Hungary (1 site), Israel (1 site), Italy (2 sites), Japan (2 sites), Malaysia (1 site), Netherlands (1 site), Switzerland (2 sites), Turkey (3 sites), United Kingdom (4 sites) and United States (4 sites).
Pre-assignment Detail	36 participants were screened and exposed to the trial product. A total of 53 surgeries were planned in these 36 participants and 49 surgeries were completed. The results are analysed and presented based on the number of surgeries instead of number of participants. Participants in this trial were also enrolled in the NN7088-3859 trial.

Arm/Group Title	NNC 0129-0000-1003 (Turoctocog Alfa Pegol)
Arm/Group Description	Subjects (from trial NN7088-3859) undergoing major surgery received bleeding preventive treatment with turoctocog alfa pegol (N8-GP) before, during and after surgery. The trial product was administered as a slow bolus intravenous injection. Dosing was done at the investigators' discretion (except a fixed dose of 50 IU/kg at screening visit). The dose level of N8-GP during this trial was chosen following the coagulation factor 8 (FVIII) activity levels recommended by World Federation of Hemophilia (WFH) guidelines. The WFH guidelines for desired FVIII levels in major surgery are as follows: pre-surgery (day 0): 80-100%; post-surgery days 1-3: 60-80%; days 4-6: 40-60%; days 7-14: 30-50%. All subjects were treated with doses between 20-75 IU/kg for treatment of a bleeding episode. The maximum dose to be administered to a subject within 24 hours was 200 IU/kg. The total duration of the trial was 2-5 weeks. Upon completion of this trial, subjects returned to trial NN7088-3859.
Period Title: Overall Study
STARTED	36
COMPLETED	35
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	NNC 0129-0000-1003 (Turoctocog Alfa Pegol)
Arm/Group Description	Subjects (from trial NN7088-3859) undergoing major surgery received bleeding preventive treatment with turoctocog alfa pegol (N8-GP) before, during and after surgery. The trial product was administered as a slow bolus intravenous injection. Dosing was done at the investigators' discretion (except a fixed dose of 50 IU/kg at screening visit). The dose level of N8-GP during this trial was chosen following the coagulation factor 8 (FVIII) activity levels recommended by World Federation of Hemophilia (WFH) guidelines. The WFH guidelines for desired FVIII levels in major surgery are as follows: pre-surgery (day 0): 80-100%; post-surgery days 1-3: 60-80%; days 4-6: 40-60%; days 7-14: 30-50%. All subjects were treated with doses between 20-75 IU/kg for treatment of a bleeding episode. The maximum dose to be administered to a subject within 24 hours was 200 IU/kg. The total duration of the trial was 2-5 weeks. Upon completion of this trial, subjects returned to trial NN7088-3859.
Overall Participants	36
Overall Surgeries	53
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.6 (13.1)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	36 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	36 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	5 13.9%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 2.8%
White	30 83.3%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Haemostatic Effect During Surgery Evaluated by the Four-point Scale, Assessed by the Investigator/Surgeon at the Day of Surgery - Four-point Response Scale: Excellent, Good, Moderate or None
Description	Haemostatic effect during surgery was evaluated on a four-point response scale as 'none', 'moderate', 'good' and 'excellent'. This was assessed after completion of surgery (defined as "last stitch"). Excellent: Better than expected/predicted in this type of procedure. Good: As expected in this type of procedure. Moderate: Less than optimal for the type of procedure but haemostatic response maintained without change of treatment regimen. None: Bleeding due to inadequate therapeutic response with adequate dosing, change of regimen required.
Time Frame	Assessed by the Investigator/surgeon at the day of surgery

Outcome Measure Data

Analysis Population Description

Full analysis set included all subjects exposed to the trial drug (N8-GP). 'Number Analyzed' = number of surgeries evaluated. 49 surgeries were evaluated in 35 participants.

Arm/Group Title	NNC 0129-0000-1003 (Turoctocog Alfa Pegol)
Arm/Group Description	Subjects (from trial NN7088-3859) undergoing major surgery received bleeding preventive treatment with turoctocog alfa pegol (N8-GP) before, during and after surgery. The trial product was administered as a slow bolus intravenous injection. Dosing was done at the investigators' discretion (except a fixed dose of 50 IU/kg at screening visit). The dose level of N8-GP during this trial was chosen following the coagulation factor 8 (FVIII) activity levels recommended by World Federation of Hemophilia (WFH) guidelines. The WFH guidelines for desired FVIII levels in major surgery are as follows: pre-surgery (day 0): 80-100%; post-surgery days 1-3: 60-80%; days 4-6: 40-60%; days 7-14: 30-50%. All subjects were treated with doses between 20-75 IU/kg for treatment of a bleeding episode. The maximum dose to be administered to a subject within 24 hours was 200 IU/kg. The total duration of the trial was 2-5 weeks. Upon completion of this trial, subjects returned to trial NN7088-3859.
Measure Participants	35
Measure Surgeries	49
Excellent	25
Good	22
Moderate	2
None	0

2. Secondary Outcome

Title	Average Consumption of N8-GP During Surgery
Description	Average consumption of N8-GP, during surgery is presented. The time during surgery is defined from 'knife to skin' until 'last stitch'.
Time Frame	During surgery, defined as the time from "knife to skin" until "last stitch"

Outcome Measure Data

Analysis Population Description

Full analysis set included all subjects exposed to the trial drug (N8-GP). 'Number Analyzed' = number of surgeries evaluated. N8-GP was administered during 1 surgery for 1 participant.

Arm/Group Title	NNC 0129-0000-1003 (Turoctocog Alfa Pegol)
Arm/Group Description	Subjects (from trial NN7088-3859) undergoing major surgery received bleeding preventive treatment with turoctocog alfa pegol (N8-GP) before, during and after surgery. The trial product was administered as a slow bolus intravenous injection. Dosing was done at the investigators' discretion (except a fixed dose of 50 IU/kg at screening visit). The dose level of N8-GP during this trial was chosen following the coagulation factor 8 (FVIII) activity levels recommended by World Federation of Hemophilia (WFH) guidelines. The WFH guidelines for desired FVIII levels in major surgery are as follows: pre-surgery (day 0): 80-100%; post-surgery days 1-3: 60-80%; days 4-6: 40-60%; days 7-14: 30-50%. All subjects were treated with doses between 20-75 IU/kg for treatment of a bleeding episode. The maximum dose to be administered to a subject within 24 hours was 200 IU/kg. The total duration of the trial was 2-5 weeks. Upon completion of this trial, subjects returned to trial NN7088-3859.
Measure Participants	1
Measure Surgeries	1
Number [IU/kg]	20.7 (0.0)

3. Secondary Outcome

Title	Haemostatic Effect of N8-GP During the Post-operative Period Days 1-6
Description	Haemostatic effect during post-operative period days 1-6 as evaluated on a four-point response scale as 'none', 'moderate', 'good' and 'excellent'. Excellent: Better than expected/predicted in this type of procedure. Good: As expected in this type of procedure. Moderate: Less than optimal for the type of procedure but haemostatic response maintained without change of treatment regimen. None: Bleeding due to inadequate therapeutic response with adequate dosing, change of regimen required.
Time Frame	During the post-operative period, days 1-6

Outcome Measure Data

Analysis Population Description

Full analysis set included all subjects exposed to the trial drug (N8-GP). 'Number Analyzed' = number of surgeries evaluated. 2 surgeries with 2 bleeding episodes were evaluated in 35 participants.

Arm/Group Title	NNC 0129-0000-1003 (Turoctocog Alfa Pegol)
Arm/Group Description	Subjects (from trial NN7088-3859) undergoing major surgery received bleeding preventive treatment with turoctocog alfa pegol (N8-GP) before, during and after surgery. The trial product was administered as a slow bolus intravenous injection. Dosing was done at the investigators' discretion (except a fixed dose of 50 IU/kg at screening visit). The dose level of N8-GP during this trial was chosen following the coagulation factor 8 (FVIII) activity levels recommended by World Federation of Hemophilia (WFH) guidelines. The WFH guidelines for desired FVIII levels in major surgery are as follows: pre-surgery (day 0): 80-100%; post-surgery days 1-3: 60-80%; days 4-6: 40-60%; days 7-14: 30-50%. All subjects were treated with doses between 20-75 IU/kg for treatment of a bleeding episode. The maximum dose to be administered to a subject within 24 hours was 200 IU/kg. The total duration of the trial was 2-5 weeks. Upon completion of this trial, subjects returned to trial NN7088-3859.
Measure Participants	35
Measure bleeding episodes	2
Excellent	0
Good	1
Moderate	0
None	0
Missing	1

4. Secondary Outcome

Title	Haemostatic Effect of N8-GP During the Post-operative Period Days 7-14
Description	Haemostatic effect during post-operative period days 1-6 and days 7-14 was evaluated on a four-point response scale as 'none', 'moderate', 'good' and 'excellent'. Excellent: Better than expected/predicted in this type of procedure. Good: As expected in this type of procedure. Moderate: Less than optimal for the type of procedure but haemostatic response maintained without change of treatment regimen. None: Bleeding due to inadequate therapeutic response with adequate dosing, change of regimen required.
Time Frame	During the post-operative period, days 7-14

Outcome Measure Data

Analysis Population Description

Full analysis set included all subjects exposed to the trial drug (N8-GP). 'Number Analyzed' = number of surgeries evaluated. 2 surgeries with 2 bleeding episodes were evaluated in 35 participants.

Arm/Group Title	NNC 0129-0000-1003 (Turoctocog Alfa Pegol)
Arm/Group Description	Subjects (from trial NN7088-3859) undergoing major surgery received bleeding preventive treatment with turoctocog alfa pegol (N8-GP) before, during and after surgery. The trial product was administered as a slow bolus intravenous injection. Dosing was done at the investigators' discretion (except a fixed dose of 50 IU/kg at screening visit). The dose level of N8-GP during this trial was chosen following the coagulation factor 8 (FVIII) activity levels recommended by World Federation of Hemophilia (WFH) guidelines. The WFH guidelines for desired FVIII levels in major surgery are as follows: pre-surgery (day 0): 80-100%; post-surgery days 1-3: 60-80%; days 4-6: 40-60%; days 7-14: 30-50%. All subjects were treated with doses between 20-75 IU/kg for treatment of a bleeding episode. The maximum dose to be administered to a subject within 24 hours was 200 IU/kg. The total duration of the trial was 2-5 weeks. Upon completion of this trial, subjects returned to trial NN7088-3859.
Measure Participants	35
Measure bleeding episodes	2
Excellent	1
Good	1
Moderate	0
None	0

5. Secondary Outcome

Title	Average Consumption of N8-GP During the Post-operative Period Days 1-6
Description	Average consumption of N8-GP during post operative period days 1-6 is presented. Analysis population: Full analysis set included all subjects exposed to the trial drug (N8-GP) and completed surgery.
Time Frame	During the post-operative period, days 1-6

Outcome Measure Data

Analysis Population Description

Full analysis set included all subjects exposed to the trial drug (N8-GP). 'Number Analyzed' = number of surgeries evaluated. 49 surgeries were evaluated in 35 participants.

Arm/Group Title	NNC 0129-0000-1003 (Turoctocog Alfa Pegol)
Arm/Group Description	Subjects (from trial NN7088-3859) undergoing major surgery received bleeding preventive treatment with turoctocog alfa pegol (N8-GP) before, during and after surgery. The trial product was administered as a slow bolus intravenous injection. Dosing was done at the investigators' discretion (except a fixed dose of 50 IU/kg at screening visit). The dose level of N8-GP during this trial was chosen following the coagulation factor 8 (FVIII) activity levels recommended by World Federation of Hemophilia (WFH) guidelines. The WFH guidelines for desired FVIII levels in major surgery are as follows: pre-surgery (day 0): 80-100%; post-surgery days 1-3: 60-80%; days 4-6: 40-60%; days 7-14: 30-50%. All subjects were treated with doses between 20-75 IU/kg for treatment of a bleeding episode. The maximum dose to be administered to a subject within 24 hours was 200 IU/kg. The total duration of the trial was 2-5 weeks. Upon completion of this trial, subjects returned to trial NN7088-3859.
Measure Participants	35
Measure Surgeries	49
Mean (Standard Deviation) [IU/kg]	33.0 (10.2)

6. Secondary Outcome

Title	Incidence Rate of Inhibitors Against Factor VIII (FVIII) (≥0.6 BU/mL)
Description	Incidence rate of inhibitors is the number of newly developed inhibitors per surgery. Development of FVIII inhibitors was measured by a validated Nijmegen modified Bethesda assay. A positive inhibitor test was defined as ≥0.6 bethesda unit. Number of participants with inhibitors at the end of trial is presented.
Time Frame	during the trial (2-5 weeks)

Outcome Measure Data

Analysis Population Description

Safety analysis set (SAS) included all patients exposed to trial drug (N8-GP).

Arm/Group Title	NNC 0129-0000-1003 (Turoctocog Alfa Pegol)
Arm/Group Description	Subjects (from trial NN7088-3859) undergoing major surgery received bleeding preventive treatment with turoctocog alfa pegol (N8-GP) before, during and after surgery. The trial product was administered as a slow bolus intravenous injection. Dosing was done at the investigators' discretion (except a fixed dose of 50 IU/kg at screening visit). The dose level of N8-GP during this trial was chosen following the coagulation factor 8 (FVIII) activity levels recommended by World Federation of Hemophilia (WFH) guidelines. The WFH guidelines for desired FVIII levels in major surgery are as follows: pre-surgery (day 0): 80-100%; post-surgery days 1-3: 60-80%; days 4-6: 40-60%; days 7-14: 30-50%. All subjects were treated with doses between 20-75 IU/kg for treatment of a bleeding episode. The maximum dose to be administered to a subject within 24 hours was 200 IU/kg. The total duration of the trial was 2-5 weeks. Upon completion of this trial, subjects returned to trial NN7088-3859.
Measure Participants	36
Number [Participants]	0 0%

7. Secondary Outcome

Title	Estimated Blood Loss During Surgery
Description	The mean estimated blood loss following surgery is presented. Estimated blood loss (mL) was evaluated post surgery.
Time Frame	During surgery

Outcome Measure Data

Analysis Population Description

Full analysis set included all subjects exposed to the trial drug (N8-GP). 'Number Analyzed' = number of surgeries evaluated. 49 surgeries were evaluated in 35 participants.

Arm/Group Title	NNC 0129-0000-1003 (Turoctocog Alfa Pegol)
Arm/Group Description	Subjects (from trial NN7088-3859) undergoing major surgery received bleeding preventive treatment with turoctocog alfa pegol (N8-GP) before, during and after surgery. The trial product was administered as a slow bolus intravenous injection. Dosing was done at the investigators' discretion (except a fixed dose of 50 IU/kg at screening visit). The dose level of N8-GP during this trial was chosen following the coagulation factor 8 (FVIII) activity levels recommended by World Federation of Hemophilia (WFH) guidelines. The WFH guidelines for desired FVIII levels in major surgery are as follows: pre-surgery (day 0): 80-100%; post-surgery days 1-3: 60-80%; days 4-6: 40-60%; days 7-14: 30-50%. All subjects were treated with doses between 20-75 IU/kg for treatment of a bleeding episode. The maximum dose to be administered to a subject within 24 hours was 200 IU/kg. The total duration of the trial was 2-5 weeks. Upon completion of this trial, subjects returned to trial NN7088-3859.
Measure Participants	35
Measure Surgeries	49
Mean (Standard Deviation) [mL]	322.6 (745.0)

8. Secondary Outcome

Title	Number of Transfusions During the Post-operative Period Days 1-6
Description	Number of blood product transfusions (transfusion of red blood cells) during the post-surgery period, Days 1-6 is presented.
Time Frame	Post-operative period, days 1-6

Outcome Measure Data

Analysis Population Description

Full analysis set included all subjects exposed to the trial drug (N8-GP). 'Number Analyzed' = number of surgeries evaluated.

Arm/Group Title	NNC 0129-0000-1003 (Turoctocog Alfa Pegol)
Arm/Group Description	Subjects (from trial NN7088-3859) undergoing major surgery received bleeding preventive treatment with turoctocog alfa pegol (N8-GP) before, during and after surgery. The trial product was administered as a slow bolus intravenous injection. Dosing was done at the investigators' discretion (except a fixed dose of 50 IU/kg at screening visit). The dose level of N8-GP during this trial was chosen following the coagulation factor 8 (FVIII) activity levels recommended by World Federation of Hemophilia (WFH) guidelines. The WFH guidelines for desired FVIII levels in major surgery are as follows: pre-surgery (day 0): 80-100%; post-surgery days 1-3: 60-80%; days 4-6: 40-60%; days 7-14: 30-50%. All subjects were treated with doses between 20-75 IU/kg for treatment of a bleeding episode. The maximum dose to be administered to a subject within 24 hours was 200 IU/kg. The total duration of the trial was 2-5 weeks. Upon completion of this trial, subjects returned to trial NN7088-3859.
Measure Participants	35
Measure Surgeries	49
Number [blood transfusions]	9

9. Secondary Outcome

Title	Length of Stay in the Hospital
Description	Mean number of days stayed at the hospital during the trial.
Time Frame	During the trial (2-5 weeks)

Outcome Measure Data

Analysis Population Description

Full analysis set included all subjects exposed to the trial drug (N8-GP). 'Number Analyzed' = number of surgeries evaluated.

Arm/Group Title	NNC 0129-0000-1003 (Turoctocog Alfa Pegol)
Arm/Group Description	Subjects (from trial NN7088-3859) undergoing major surgery received bleeding preventive treatment with turoctocog alfa pegol (N8-GP) before, during and after surgery. The trial product was administered as a slow bolus intravenous injection. Dosing was done at the investigators' discretion (except a fixed dose of 50 IU/kg at screening visit). The dose level of N8-GP during this trial was chosen following the coagulation factor 8 (FVIII) activity levels recommended by World Federation of Hemophilia (WFH) guidelines. The WFH guidelines for desired FVIII levels in major surgery are as follows: pre-surgery (day 0): 80-100%; post-surgery days 1-3: 60-80%; days 4-6: 40-60%; days 7-14: 30-50%. All subjects were treated with doses between 20-75 IU/kg for treatment of a bleeding episode. The maximum dose to be administered to a subject within 24 hours was 200 IU/kg. The total duration of the trial was 2-5 weeks. Upon completion of this trial, subjects returned to trial NN7088-3859.
Measure Participants	35
Measure Surgeries	49
Mean (Standard Deviation) [days]	10.00 (8.9)

10. Secondary Outcome

Title	Number of Days in Intensive Care
Description	Mean number of days in the intensive care due to surgery during the trial is presented.
Time Frame	During the trial (2-5 weeks)

Outcome Measure Data

Analysis Population Description

Full analysis set included all subjects exposed to the trial drug (N8-GP). 'Number Analyzed' = number of surgeries evaluated.

Arm/Group Title	NNC 0129-0000-1003 (Turoctocog Alfa Pegol)
Arm/Group Description	Subjects (from trial NN7088-3859) undergoing major surgery received bleeding preventive treatment with turoctocog alfa pegol (N8-GP) before, during and after surgery. The trial product was administered as a slow bolus intravenous injection. Dosing was done at the investigators' discretion (except a fixed dose of 50 IU/kg at screening visit). The dose level of N8-GP during this trial was chosen following the coagulation factor 8 (FVIII) activity levels recommended by World Federation of Hemophilia (WFH) guidelines. The WFH guidelines for desired FVIII levels in major surgery are as follows: pre-surgery (day 0): 80-100%; post-surgery days 1-3: 60-80%; days 4-6: 40-60%; days 7-14: 30-50%. All subjects were treated with doses between 20-75 IU/kg for treatment of a bleeding episode. The maximum dose to be administered to a subject within 24 hours was 200 IU/kg. The total duration of the trial was 2-5 weeks. Upon completion of this trial, subjects returned to trial NN7088-3859.
Measure Participants	35
Measure Surgeries	49
Mean (Standard Deviation) [days]	0.02 (0.14)

11. Secondary Outcome

Title	Adverse Events Reported During the Trial Period
Description	Number of adverse event during the trial is presented. This includes events from the first trial related activity after the patient has signed the informed consent and until the end of trial (earliest at day 14).
Time Frame	During the trial (2-5 weeks)

Outcome Measure Data

Analysis Population Description

Safety analysis set (SAS) included all patients exposed to trial drug (N8-GP). 'Number Analyzed' = number of surgeries evaluated.

Arm/Group Title	NNC 0129-0000-1003 (Turoctocog Alfa Pegol)
Arm/Group Description	Subjects (from trial NN7088-3859) undergoing major surgery received bleeding preventive treatment with turoctocog alfa pegol (N8-GP) before, during and after surgery. The trial product was administered as a slow bolus intravenous injection. Dosing was done at the investigators' discretion (except a fixed dose of 50 IU/kg at screening visit). The dose level of N8-GP during this trial was chosen following the coagulation factor 8 (FVIII) activity levels recommended by World Federation of Hemophilia (WFH) guidelines. The WFH guidelines for desired FVIII levels in major surgery are as follows: pre-surgery (day 0): 80-100%; post-surgery days 1-3: 60-80%; days 4-6: 40-60%; days 7-14: 30-50%. All subjects were treated with doses between 20-75 IU/kg for treatment of a bleeding episode. The maximum dose to be administered to a subject within 24 hours was 200 IU/kg. The total duration of the trial was 2-5 weeks. Upon completion of this trial, subjects returned to trial NN7088-3859.
Measure Participants	36
Measure Planned surgeries	53
Number [adverse events]	127

12. Secondary Outcome

Title	Serious Adverse Events Reported During the Trial Period
Description	Number of serious adverse event during the trial is presented. This includes events from the first trial related activity after the patient has signed the informed consent and until the end of trial (earliest at day 14).
Time Frame	During the trial (2-5 weeks)

Outcome Measure Data

Analysis Population Description

Safety analysis set (SAS) included all patients exposed to trial drug (N8-GP). 'Number Analyzed' = number of surgeries evaluated.

Arm/Group Title	NNC 0129-0000-1003 (Turoctocog Alfa Pegol)
Arm/Group Description	Subjects (from trial NN7088-3859) undergoing major surgery received bleeding preventive treatment with turoctocog alfa pegol (N8-GP) before, during and after surgery. The trial product was administered as a slow bolus intravenous injection. Dosing was done at the investigators' discretion (except a fixed dose of 50 IU/kg at screening visit). The dose level of N8-GP during this trial was chosen following the coagulation factor 8 (FVIII) activity levels recommended by World Federation of Hemophilia (WFH) guidelines. The WFH guidelines for desired FVIII levels in major surgery are as follows: pre-surgery (day 0): 80-100%; post-surgery days 1-3: 60-80%; days 4-6: 40-60%; days 7-14: 30-50%. All subjects were treated with doses between 20-75 IU/kg for treatment of a bleeding episode. The maximum dose to be administered to a subject within 24 hours was 200 IU/kg. The total duration of the trial was 2-5 weeks. Upon completion of this trial, subjects returned to trial NN7088-3859.
Measure Participants	36
Measure planned surgeries	53
Number [serious adverse event]	5

Adverse Events

Time Frame	From the first trial related activity (day 0) after the patient has signed the informed consent until the end of trial (earliest at day 14).
Adverse Event Reporting Description	Adverse events were reported for the safety analysis set (SAS) which includes all subjects exposed to trial drug (N8-GP). As one of the objectives of the trial was to evaluate safety of N8-GP when used for prevention and treatment of bleeding throughout the surgical period, the adverse events are analysed based on the number (units) of surgeries rather than number of participants. Therefore 'the number at risk' in this adverse events section refers to the number of planned surgeries.
Arm/Group Title	NNC 0129-0000-1003 (Turoctocog Alfa Pegol)
Arm/Group Description	Subjects (from trial NN7088-3859) undergoing major surgery received bleeding preventive treatment with turoctocog alfa pegol (N8-GP) before, during and after surgery. The trial product was administered as a slow bolus intravenous injection. Dosing was done at the investigators' discretion (except a fixed dose of 50 IU/kg at screening visit). The dose level of N8-GP during this trial was chosen following the coagulation factor 8 (FVIII) activity levels recommended by World Federation of Hemophilia (WFH) guidelines. The WFH guidelines for desired FVIII levels in major surgery are as follows: pre-surgery (day 0): 80-100%; post-surgery days 1-3: 60-80%; days 4-6: 40-60%; days 7-14: 30-50%. All subjects were treated with doses between 20-75 IU/kg for treatment of a bleeding episode. The maximum dose to be administered to a subject within 24 hours was 200 IU/kg. The total duration of the trial was 2-5 weeks. Upon completion of this trial, subjects returned to trial NN7088-3859.
All Cause Mortality
	NNC 0129-0000-1003 (Turoctocog Alfa Pegol)
	Affected / at Risk (%)	# Events
Total	0/53 (0%)
Serious Adverse Events
	NNC 0129-0000-1003 (Turoctocog Alfa Pegol)
	Affected / at Risk (%)	# Events
Total	4/53 (7.5%)
Gastrointestinal disorders
Pancreatitis acute	1/53 (1.9%)	1
Musculoskeletal and connective tissue disorders
Mobility decreased	1/53 (1.9%)	1
Surgical and medical procedures
Tooth extraction	1/53 (1.9%)	1
Vascular disorders
Haemorrhage	1/53 (1.9%)	1
Ischaemia	1/53 (1.9%)	1
Other (Not Including Serious) Adverse Events
	NNC 0129-0000-1003 (Turoctocog Alfa Pegol)
	Affected / at Risk (%)	# Events
Total	30/53 (56.6%)
Gastrointestinal disorders
Constipation	11/53 (20.8%)	11
Diarrhoea	3/53 (5.7%)	3
Nausea	6/53 (11.3%)	6
Vomiting	3/53 (5.7%)	3
General disorders
Pyrexia	4/53 (7.5%)	4
Injury, poisoning and procedural complications
Post procedural inflammation	3/53 (5.7%)	3
Procedural pain	5/53 (9.4%)	5
Investigations
Alanine aminotransferase increased	3/53 (5.7%)	3
C-reactive protein increased	5/53 (9.4%)	5
Haemoglobin decreased	5/53 (9.4%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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