Trial Outcomes & Findings for Efficacy and Safety of NNC-0156-0000-0009 During Surgical Procedures in Subjects With Haemophilia B (NCT NCT01386528)

Last Updated: 2017-08-23

Results Overview

Haemostatic effect during surgery was evaluated immediately after surgery (last stitch) using a fourpoint response scale: \- Four-point response scale: Excellent, good, moderate, poor. The evaluation was done by the surgeon, anaesthesiologist and/or investigator based on experience as follows: 1. Excellent: Better than expected/predicted in this type of procedure. 2. Good: As expected in this type of procedure. 3. Moderate: Less than optimal for the type of procedure but haemostatic response maintained without change of treatment regimen. 4. Poor: Bleeding due to inadequate therapeutic response with adequate dosing, change of regimen required.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

13 participants

Primary outcome timeframe

At the day of surgery

Results posted on

2017-08-23

Participant Flow

The study was conducted at 10 sites in 8 countries : Italy (1 site), Malaysia (1 site), Romania (1 site), South Africa (1 site), Taiwan (1 site), Turkey (1 SIte), UK (2 sites), US (2 sites).

Patients enrolled in the present trial were recruited from the pivotal trial (NN7999-3747) or the extension trial (NN7999-3775). In addition, new patients were recruited into the present trial.

Participant milestones

Participant milestones
Measure	Nonacog Beta Pegol New patients as well as transferred patients from the pivotal trial (NN7999-3747) or the extension trial(NN7999-3775) received nonacog beta pegol at screening and followed a preventive treatment regimen with nonacog beta pegol until one week before the day of surgery. No more than 4 hours prior to the planned surgical procedure, all patients received a single bolus injection of 80 U/kg of nonacog beta pegol. Postoperatively, the patients received fixed doses of 40 U/kg repeated at the investigator's discretion aiming for no less than the FIX levels recommended by the World Federation of Hemophilia. Nonacog beta pegol was administered intravenously. The new patients were dosed once with 40 U/kg nonacog beta pegol at screening.From the day after surgery (Day 1) and through Day 6, nonacog beta pegol dosing was adjusted to aim for a FIX activity level of approximately 0.50 U/mL.
Overall Study STARTED	13
Overall Study COMPLETED	13
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy and Safety of NNC-0156-0000-0009 During Surgical Procedures in Subjects With Haemophilia B

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nonacog Beta Pegol n=13 Participants New patients as well as transferred patients from the pivotal trial (NN7999-3747) or the extension trial(NN7999-3775) received nonacog beta pegol at screening and followed a preventive treatment regimen with nonacog beta pegol until one week before the day of surgery. No more than 4 hours prior to the planned surgical procedure, all patients received a single bolus injection of 80 U/kg of nonacog beta pegol. Postoperatively, the patients received fixed doses of 40 U/kg repeated at the investigator's discretion aiming for no less than the FIX levels recommended by the World Federation of Hemophilia. Nonacog beta pegol was administered intravenously. The new patients were dosed once with 40 U/kg nonacog beta pegol at screening.From the day after surgery (Day 1) and through Day 6, nonacog beta pegol dosing was adjusted to aim for a FIX activity level of approximately 0.50 U/mL.
Age, Categorical <=18 years	1 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	39 years FULL_RANGE 12.6 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: At the day of surgery

Population: The full analysis set consisted of all patients exposed to nanacog beta pegol.

Outcome measures

Outcome measures
Measure	Nonacog Beta Pegol n=13 Participants New patients as well as transferred patients from the pivotal trial (NN7999-3747) or the extension trial(NN7999-3775) received nonacog beta pegol at screening and followed a preventive treatment regimen with nonacog beta pegol until one week before the day of surgery. No more than 4 hours prior to the planned surgical procedure, all patients received a single bolus injection of 80 U/kg of nonacog beta pegol. Postoperatively, the patients received fixed doses of 40 U/kg repeated at the investigator's discretion aiming for no less than the FIX levels recommended by the World Federation of Hemophilia. Nonacog beta pegol was administered intravenously. The new patients were dosed once with 40 U/kg nonacog beta pegol at screening.From the day after surgery (Day 1) and through Day 6, nonacog beta pegol dosing was adjusted to aim for a FIX activity level of approximately 0.50 U/mL.
Haemostatic Effect During Surgery Evaluated by the Four-point Response Scale (Excellent, Good, Moderate, Poor) Excellent	10 Haemostatic responses
Haemostatic Effect During Surgery Evaluated by the Four-point Response Scale (Excellent, Good, Moderate, Poor) Good	3 Haemostatic responses
Haemostatic Effect During Surgery Evaluated by the Four-point Response Scale (Excellent, Good, Moderate, Poor) Moderate	0 Haemostatic responses
Haemostatic Effect During Surgery Evaluated by the Four-point Response Scale (Excellent, Good, Moderate, Poor) Poor	0 Haemostatic responses

SECONDARY outcome

Timeframe: During surgery (the time from knife to skin until last stitch) and post-operative period (day 1 to day 13)

Population: The full analysis set consisted of all patients exposed to nanacog beta pegol.

Mean consumption of nonacog beta pegol (U/kg) used for treatment per patient before surgery, during surgery (the time from knife to skin until last stitch) and post-operative period.

Outcome measures

Outcome measures
Measure	Nonacog Beta Pegol n=13 Participants New patients as well as transferred patients from the pivotal trial (NN7999-3747) or the extension trial(NN7999-3775) received nonacog beta pegol at screening and followed a preventive treatment regimen with nonacog beta pegol until one week before the day of surgery. No more than 4 hours prior to the planned surgical procedure, all patients received a single bolus injection of 80 U/kg of nonacog beta pegol. Postoperatively, the patients received fixed doses of 40 U/kg repeated at the investigator's discretion aiming for no less than the FIX levels recommended by the World Federation of Hemophilia. Nonacog beta pegol was administered intravenously. The new patients were dosed once with 40 U/kg nonacog beta pegol at screening.From the day after surgery (Day 1) and through Day 6, nonacog beta pegol dosing was adjusted to aim for a FIX activity level of approximately 0.50 U/mL.
Consumption of NNC-0156-0000-0009 (U/kg Body Weight)	328.2 U/Kg Standard Deviation 113.1

SECONDARY outcome

Timeframe: during surgery (the time from knife to skin until last stitch) and post-operative period (day 1 to day 13)

Population: The full analysis set consisted of all patients exposed to nanacog beta pegol.

Mean quantity of transfusion during surgery (the time from knife to skin until last stitch) and the postoperative period (Day 1-13).None of the patients required transfusions beyond Day 6 hence no values presented for days 7-13.

Outcome measures

Outcome measures
Measure	Nonacog Beta Pegol n=13 Participants New patients as well as transferred patients from the pivotal trial (NN7999-3747) or the extension trial(NN7999-3775) received nonacog beta pegol at screening and followed a preventive treatment regimen with nonacog beta pegol until one week before the day of surgery. No more than 4 hours prior to the planned surgical procedure, all patients received a single bolus injection of 80 U/kg of nonacog beta pegol. Postoperatively, the patients received fixed doses of 40 U/kg repeated at the investigator's discretion aiming for no less than the FIX levels recommended by the World Federation of Hemophilia. Nonacog beta pegol was administered intravenously. The new patients were dosed once with 40 U/kg nonacog beta pegol at screening.From the day after surgery (Day 1) and through Day 6, nonacog beta pegol dosing was adjusted to aim for a FIX activity level of approximately 0.50 U/mL.
Transfusion Requirements (Fulfilling Transfusion Criteria) During surgery	275 mL Standard Deviation 35.4
Transfusion Requirements (Fulfilling Transfusion Criteria) Post surgery through day 6	266.7 mL Standard Deviation 28.9

SECONDARY outcome

Timeframe: 0, 1 hour, 24 hours.

Population: The full analysis set consisted of all patients exposed to nanacog beta pegol.

The mean pre-surgery and post surgery haemoglobin level.

Outcome measures

Outcome measures
Measure	Nonacog Beta Pegol n=13 Participants New patients as well as transferred patients from the pivotal trial (NN7999-3747) or the extension trial(NN7999-3775) received nonacog beta pegol at screening and followed a preventive treatment regimen with nonacog beta pegol until one week before the day of surgery. No more than 4 hours prior to the planned surgical procedure, all patients received a single bolus injection of 80 U/kg of nonacog beta pegol. Postoperatively, the patients received fixed doses of 40 U/kg repeated at the investigator's discretion aiming for no less than the FIX levels recommended by the World Federation of Hemophilia. Nonacog beta pegol was administered intravenously. The new patients were dosed once with 40 U/kg nonacog beta pegol at screening.From the day after surgery (Day 1) and through Day 6, nonacog beta pegol dosing was adjusted to aim for a FIX activity level of approximately 0.50 U/mL.
Haemoglobin Pre- and Post-surgery Start prior to surgery	8.98 mmol/L Standard Deviation 0.67
Haemoglobin Pre- and Post-surgery Start 1 hour post-surgery	8.37 mmol/L Standard Deviation 0.78
Haemoglobin Pre- and Post-surgery Start 24 hours post surgery	7.99 mmol/L Standard Deviation 1.13

SECONDARY outcome

Timeframe: during the trial period (2-8 weeks prior to day of surgery (transferred subjects) or 2-4 weeks prior to day of surgery (new subjects) until 4 weeks after post-operative period (day 1 to day 13)

Population: The safety analysis set consisted of all patients exposed to nanacog beta pegol.

The number of adverse events per patient years of exposure, reported during the trial period. Number is the only available option here, the data presented are rate of AEs.

Outcome measures

Outcome measures
Measure	Nonacog Beta Pegol n=13 Participants New patients as well as transferred patients from the pivotal trial (NN7999-3747) or the extension trial(NN7999-3775) received nonacog beta pegol at screening and followed a preventive treatment regimen with nonacog beta pegol until one week before the day of surgery. No more than 4 hours prior to the planned surgical procedure, all patients received a single bolus injection of 80 U/kg of nonacog beta pegol. Postoperatively, the patients received fixed doses of 40 U/kg repeated at the investigator's discretion aiming for no less than the FIX levels recommended by the World Federation of Hemophilia. Nonacog beta pegol was administered intravenously. The new patients were dosed once with 40 U/kg nonacog beta pegol at screening.From the day after surgery (Day 1) and through Day 6, nonacog beta pegol dosing was adjusted to aim for a FIX activity level of approximately 0.50 U/mL.
Incidence of Adverse Events (AEs)	12.12 events per patient year of exposure

SECONDARY outcome

Timeframe: During the trial period (2-8 weeks prior to day of surgery (transferred subjects) or 2-4 weeks prior to day of surgery (new subjects) until 4 weeks after post-operative period (day 1 to day 13)

Population: The safety analysis set consisted of all patients exposed to nanacog beta pegol.

The number of serious adverse events per patient years of exposure, reported during the trial period. Number is the only available option here, the data presented are rate of AEs.

Outcome measures

Outcome measures
Measure	Nonacog Beta Pegol n=13 Participants New patients as well as transferred patients from the pivotal trial (NN7999-3747) or the extension trial(NN7999-3775) received nonacog beta pegol at screening and followed a preventive treatment regimen with nonacog beta pegol until one week before the day of surgery. No more than 4 hours prior to the planned surgical procedure, all patients received a single bolus injection of 80 U/kg of nonacog beta pegol. Postoperatively, the patients received fixed doses of 40 U/kg repeated at the investigator's discretion aiming for no less than the FIX levels recommended by the World Federation of Hemophilia. Nonacog beta pegol was administered intravenously. The new patients were dosed once with 40 U/kg nonacog beta pegol at screening.From the day after surgery (Day 1) and through Day 6, nonacog beta pegol dosing was adjusted to aim for a FIX activity level of approximately 0.50 U/mL.
Incidence of Serious Adverse Events (SAE)	0 Events per patient year of exposure

SECONDARY outcome

Timeframe: During the trial period (2-8 weeks prior to day of surgery (transferred subjects) or 2-4 weeks prior to day of surgery (new subjects) and every 4 weeks after post-operative period (day 1 to day 13)

Population: The full analysis set consisted of all patients exposed to nanacog beta pegol.

Number of patients with inhibitory antibodies

Outcome measures

Outcome measures
Measure	Nonacog Beta Pegol n=13 Participants New patients as well as transferred patients from the pivotal trial (NN7999-3747) or the extension trial(NN7999-3775) received nonacog beta pegol at screening and followed a preventive treatment regimen with nonacog beta pegol until one week before the day of surgery. No more than 4 hours prior to the planned surgical procedure, all patients received a single bolus injection of 80 U/kg of nonacog beta pegol. Postoperatively, the patients received fixed doses of 40 U/kg repeated at the investigator's discretion aiming for no less than the FIX levels recommended by the World Federation of Hemophilia. Nonacog beta pegol was administered intravenously. The new patients were dosed once with 40 U/kg nonacog beta pegol at screening.From the day after surgery (Day 1) and through Day 6, nonacog beta pegol dosing was adjusted to aim for a FIX activity level of approximately 0.50 U/mL.
Incidence of Inhibitors Against FIX (Coagulation Factor Nine)	0 patients

Adverse Events

Nonacog Beta Pegol

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Nonacog Beta Pegol n=13 participants at risk New patients as well as transferred patients from the pivotal trial (NN7999-3747) or the extension trial(NN7999-3775) received nonacog beta pegol at screening and followed a preventive treatment regimen with nonacog beta pegol until one week before the day of surgery. No more than 4 hours prior to the planned surgical procedure, all patients received a single bolus injection of 80 U/kg of nonacog beta pegol. Postoperatively, the patients received fixed doses of 40 U/kg repeated at the investigator's discretion aiming for no less than the FIX levels recommended by the World Federation of Hemophilia. Nonacog beta pegol was administered intravenously. The new patients were dosed once with 40 U/kg nonacog beta pegol at screening.From the day after surgery (Day 1) and through Day 6, nonacog beta pegol dosing was adjusted to aim for a FIX activity level of approximately 0.50 U/mL.
Blood and lymphatic system disorders Anaemia	7.7% 1/13 • Number of events 1 • AEs from screening visit (day 0) and until post treatment follow-up period. Patients not continuing in the extension trial attended a follow-up visit 4 weeks ± 2 weeks after the last dose of nonacog beta pegol. The safety analysis set consisted of all patients exposed to nanacog beta pegol.
Eye disorders Conjunctival haemorrhage	7.7% 1/13 • Number of events 1 • AEs from screening visit (day 0) and until post treatment follow-up period. Patients not continuing in the extension trial attended a follow-up visit 4 weeks ± 2 weeks after the last dose of nonacog beta pegol. The safety analysis set consisted of all patients exposed to nanacog beta pegol.
Gastrointestinal disorders Epigastric discomfort	7.7% 1/13 • Number of events 1 • AEs from screening visit (day 0) and until post treatment follow-up period. Patients not continuing in the extension trial attended a follow-up visit 4 weeks ± 2 weeks after the last dose of nonacog beta pegol. The safety analysis set consisted of all patients exposed to nanacog beta pegol.
Injury, poisoning and procedural complications Excoriation	7.7% 1/13 • Number of events 1 • AEs from screening visit (day 0) and until post treatment follow-up period. Patients not continuing in the extension trial attended a follow-up visit 4 weeks ± 2 weeks after the last dose of nonacog beta pegol. The safety analysis set consisted of all patients exposed to nanacog beta pegol.
General disorders Face oedema	7.7% 1/13 • Number of events 1 • AEs from screening visit (day 0) and until post treatment follow-up period. Patients not continuing in the extension trial attended a follow-up visit 4 weeks ± 2 weeks after the last dose of nonacog beta pegol. The safety analysis set consisted of all patients exposed to nanacog beta pegol.
Injury, poisoning and procedural complications Fall	7.7% 1/13 • Number of events 1 • AEs from screening visit (day 0) and until post treatment follow-up period. Patients not continuing in the extension trial attended a follow-up visit 4 weeks ± 2 weeks after the last dose of nonacog beta pegol. The safety analysis set consisted of all patients exposed to nanacog beta pegol.
Vascular disorders Haemorrhage	7.7% 1/13 • Number of events 1 • AEs from screening visit (day 0) and until post treatment follow-up period. Patients not continuing in the extension trial attended a follow-up visit 4 weeks ± 2 weeks after the last dose of nonacog beta pegol. The safety analysis set consisted of all patients exposed to nanacog beta pegol.
Vascular disorders Hypertension	7.7% 1/13 • Number of events 1 • AEs from screening visit (day 0) and until post treatment follow-up period. Patients not continuing in the extension trial attended a follow-up visit 4 weeks ± 2 weeks after the last dose of nonacog beta pegol. The safety analysis set consisted of all patients exposed to nanacog beta pegol.
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	7.7% 1/13 • Number of events 1 • AEs from screening visit (day 0) and until post treatment follow-up period. Patients not continuing in the extension trial attended a follow-up visit 4 weeks ± 2 weeks after the last dose of nonacog beta pegol. The safety analysis set consisted of all patients exposed to nanacog beta pegol.
Gastrointestinal disorders Nausea	7.7% 1/13 • Number of events 1 • AEs from screening visit (day 0) and until post treatment follow-up period. Patients not continuing in the extension trial attended a follow-up visit 4 weeks ± 2 weeks after the last dose of nonacog beta pegol. The safety analysis set consisted of all patients exposed to nanacog beta pegol.
Gastrointestinal disorders Oral mucosal erythema	7.7% 1/13 • Number of events 1 • AEs from screening visit (day 0) and until post treatment follow-up period. Patients not continuing in the extension trial attended a follow-up visit 4 weeks ± 2 weeks after the last dose of nonacog beta pegol. The safety analysis set consisted of all patients exposed to nanacog beta pegol.
Musculoskeletal and connective tissue disorders Pain in extremity	7.7% 1/13 • Number of events 1 • AEs from screening visit (day 0) and until post treatment follow-up period. Patients not continuing in the extension trial attended a follow-up visit 4 weeks ± 2 weeks after the last dose of nonacog beta pegol. The safety analysis set consisted of all patients exposed to nanacog beta pegol.
Skin and subcutaneous tissue disorders Pruritus	7.7% 1/13 • Number of events 1 • AEs from screening visit (day 0) and until post treatment follow-up period. Patients not continuing in the extension trial attended a follow-up visit 4 weeks ± 2 weeks after the last dose of nonacog beta pegol. The safety analysis set consisted of all patients exposed to nanacog beta pegol.
General disorders Pyrexia	7.7% 1/13 • Number of events 1 • AEs from screening visit (day 0) and until post treatment follow-up period. Patients not continuing in the extension trial attended a follow-up visit 4 weeks ± 2 weeks after the last dose of nonacog beta pegol. The safety analysis set consisted of all patients exposed to nanacog beta pegol.
Investigations Serum ferritin increased	7.7% 1/13 • Number of events 1 • AEs from screening visit (day 0) and until post treatment follow-up period. Patients not continuing in the extension trial attended a follow-up visit 4 weeks ± 2 weeks after the last dose of nonacog beta pegol. The safety analysis set consisted of all patients exposed to nanacog beta pegol.
Metabolism and nutrition disorders Type 2 diabetes mellitus	7.7% 1/13 • Number of events 1 • AEs from screening visit (day 0) and until post treatment follow-up period. Patients not continuing in the extension trial attended a follow-up visit 4 weeks ± 2 weeks after the last dose of nonacog beta pegol. The safety analysis set consisted of all patients exposed to nanacog beta pegol.
Gastrointestinal disorders Vomiting	7.7% 1/13 • Number of events 1 • AEs from screening visit (day 0) and until post treatment follow-up period. Patients not continuing in the extension trial attended a follow-up visit 4 weeks ± 2 weeks after the last dose of nonacog beta pegol. The safety analysis set consisted of all patients exposed to nanacog beta pegol.

Additional Information

Global Clinical Registry (GCR, 1452)

Novo Nordisk A/S

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER