Trial Outcomes & Findings for Evaluating the Haemostatic Effect of NNC 0129-0000-1003 During Surgical Procedures in Subjects With Haemophilia A. (NCT NCT01489111)

NCT ID: NCT01489111

Last Updated: 2020-08-10

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 36 participants
• Primary outcome timeframe: Assessed by the Investigator/surgeon at the day of surgery
• Results posted on: 2020-08-10

Participant Flow

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).

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.

Unit of analysis: Surgeries

Participant milestones

Measure	NNC 0129-0000-1003 (Turoctocog Alfa Pegol) 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 Study STARTED	36 53
Overall Study COMPLETED	35 49
Overall Study NOT COMPLETED	1 4

Reasons for withdrawal

Measure

NNC 0129-0000-1003 (Turoctocog Alfa Pegol) 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 Study Withdrawal criterion

1

Baseline Characteristics

The number of partiipants enrolled were 36 while the number of planned surgeries were 53.

Baseline characteristics by cohort

Measure	NNC 0129-0000-1003 (Turoctocog Alfa Pegol) n=53 Surgeries 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.
Age, Continuous	40.6 years STANDARD_DEVIATION 13.1 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants • The number of partiipants enrolled were 36 while the number of planned surgeries were 53.
Sex: Female, Male Male	36 Participants n=5 Participants • The number of partiipants enrolled were 36 while the number of planned surgeries were 53.
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants • The number of partiipants enrolled were 36 while the number of planned surgeries were 53.
Ethnicity (NIH/OMB) Not Hispanic or Latino	36 Participants n=5 Participants • The number of partiipants enrolled were 36 while the number of planned surgeries were 53.
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • The number of partiipants enrolled were 36 while the number of planned surgeries were 53.
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants • The number of partiipants enrolled were 36 while the number of planned surgeries were 53.
Race (NIH/OMB) Asian	5 Participants n=5 Participants • The number of partiipants enrolled were 36 while the number of planned surgeries were 53.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants • The number of partiipants enrolled were 36 while the number of planned surgeries were 53.
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants • The number of partiipants enrolled were 36 while the number of planned surgeries were 53.
Race (NIH/OMB) White	30 Participants n=5 Participants • The number of partiipants enrolled were 36 while the number of planned surgeries were 53.
Race (NIH/OMB) More than one race	0 Participants n=5 Participants • The number of partiipants enrolled were 36 while the number of planned surgeries were 53.
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • The number of partiipants enrolled were 36 while the number of planned surgeries were 53.

PRIMARY outcome

Timeframe: Assessed by the Investigator/surgeon at the day of surgery

Population: 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.

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.

Outcome measures

Measure	NNC 0129-0000-1003 (Turoctocog Alfa Pegol) n=49 Surgeries 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.
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 Excellent	25 Surgeries
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 Good	22 Surgeries
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 Moderate	2 Surgeries
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 None	0 Surgeries

SECONDARY outcome

Timeframe: During surgery, defined as the time from "knife to skin" until "last stitch"

Population: 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.

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

Outcome measures

Measure

NNC 0129-0000-1003 (Turoctocog Alfa Pegol) n=1 Surgeries 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.

Average Consumption of N8-GP During Surgery

20.7 IU/kg 0.0

SECONDARY outcome

Timeframe: During the post-operative period, days 1-6

Population: 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.

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.

Outcome measures

Measure	NNC 0129-0000-1003 (Turoctocog Alfa Pegol) n=2 bleeding episodes 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.
Haemostatic Effect of N8-GP During the Post-operative Period Days 1-6 Excellent	0 bleeding episodes
Haemostatic Effect of N8-GP During the Post-operative Period Days 1-6 Good	1 bleeding episodes
Haemostatic Effect of N8-GP During the Post-operative Period Days 1-6 Moderate	0 bleeding episodes
Haemostatic Effect of N8-GP During the Post-operative Period Days 1-6 None	0 bleeding episodes
Haemostatic Effect of N8-GP During the Post-operative Period Days 1-6 Missing	1 bleeding episodes

SECONDARY outcome

Timeframe: During the post-operative period, days 7-14

Population: 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.

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.

Outcome measures

Measure	NNC 0129-0000-1003 (Turoctocog Alfa Pegol) n=2 bleeding episodes 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.
Haemostatic Effect of N8-GP During the Post-operative Period Days 7-14 Excellent	1 bleeding episodes
Haemostatic Effect of N8-GP During the Post-operative Period Days 7-14 Good	1 bleeding episodes
Haemostatic Effect of N8-GP During the Post-operative Period Days 7-14 Moderate	0 bleeding episodes
Haemostatic Effect of N8-GP During the Post-operative Period Days 7-14 None	0 bleeding episodes

SECONDARY outcome

Timeframe: During the post-operative period, days 1-6

Population: 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.

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.

Outcome measures

Measure

NNC 0129-0000-1003 (Turoctocog Alfa Pegol) n=49 Surgeries 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.

Average Consumption of N8-GP During the Post-operative Period Days 1-6

33.0 IU/kg Standard Deviation 10.2

SECONDARY outcome

Timeframe: during the trial (2-5 weeks)

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

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.

Outcome measures

Measure

NNC 0129-0000-1003 (Turoctocog Alfa Pegol) n=36 Participants 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.

Incidence Rate of Inhibitors Against Factor VIII (FVIII) (≥0.6 BU/mL)

0 Participants

SECONDARY outcome

Timeframe: During surgery

Population: 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.

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

Outcome measures

Measure

NNC 0129-0000-1003 (Turoctocog Alfa Pegol) n=49 Surgeries 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.

Estimated Blood Loss During Surgery

322.6 mL Standard Deviation 745.0

SECONDARY outcome

Timeframe: Post-operative period, days 1-6

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

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

Outcome measures

Measure

NNC 0129-0000-1003 (Turoctocog Alfa Pegol) n=49 Surgeries 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.

Number of Transfusions During the Post-operative Period Days 1-6

9 blood transfusions

SECONDARY outcome

Timeframe: During the trial (2-5 weeks)

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

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

Outcome measures

Measure

NNC 0129-0000-1003 (Turoctocog Alfa Pegol) n=49 Surgeries 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.

Length of Stay in the Hospital

10.00 days Standard Deviation 8.9

SECONDARY outcome

Timeframe: During the trial (2-5 weeks)

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

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

Outcome measures

Measure

NNC 0129-0000-1003 (Turoctocog Alfa Pegol) n=49 Surgeries 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.

Number of Days in Intensive Care

0.02 days Standard Deviation 0.14

SECONDARY outcome

Timeframe: During the trial (2-5 weeks)

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

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).

Outcome measures

Measure

NNC 0129-0000-1003 (Turoctocog Alfa Pegol) n=53 Planned surgeries 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.

Adverse Events Reported During the Trial Period

127 adverse events

SECONDARY outcome

Timeframe: During the trial (2-5 weeks)

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

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).

Outcome measures

Measure

NNC 0129-0000-1003 (Turoctocog Alfa Pegol) n=53 planned surgeries 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.

Serious Adverse Events Reported During the Trial Period

5 serious adverse event

Adverse Events

NNC 0129-0000-1003 (Turoctocog Alfa Pegol)

Serious events: 4 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Measure	NNC 0129-0000-1003 (Turoctocog Alfa Pegol) n=53 participants at risk 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.
Vascular disorders Haemorrhage	1.9% 1/53 • Number of events 1 • 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 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.
Vascular disorders Ischaemia	1.9% 1/53 • Number of events 1 • 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 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.
Musculoskeletal and connective tissue disorders Mobility decreased	1.9% 1/53 • Number of events 1 • 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 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.
Gastrointestinal disorders Pancreatitis acute	1.9% 1/53 • Number of events 1 • 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 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.
Surgical and medical procedures Tooth extraction	1.9% 1/53 • Number of events 1 • 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 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.

Other adverse events

Measure	NNC 0129-0000-1003 (Turoctocog Alfa Pegol) n=53 participants at risk 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.
Investigations Alanine aminotransferase increased	5.7% 3/53 • Number of events 3 • 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 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.
Investigations C-reactive protein increased	9.4% 5/53 • Number of events 5 • 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 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.
Gastrointestinal disorders Constipation	20.8% 11/53 • Number of events 11 • 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 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.
Gastrointestinal disorders Diarrhoea	5.7% 3/53 • Number of events 3 • 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 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.
Investigations Haemoglobin decreased	9.4% 5/53 • Number of events 5 • 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 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.
Gastrointestinal disorders Nausea	11.3% 6/53 • Number of events 6 • 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 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.
Injury, poisoning and procedural complications Post procedural inflammation	5.7% 3/53 • Number of events 3 • 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 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.
Injury, poisoning and procedural complications Procedural pain	9.4% 5/53 • Number of events 5 • 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 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.
General disorders Pyrexia	7.5% 4/53 • Number of events 4 • 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 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.
Gastrointestinal disorders Vomiting	5.7% 3/53 • Number of events 3 • 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 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.

Additional Information

Clinical Reporting Anchor and Disclosure (1452)

Novo Nordisk A/S

Phone: (+1) 866-867-7178

Email: clinicaltrials@novonordisk.com

Results disclosure agreements

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

Restriction type: OTHER