Trial Outcomes & Findings for Safety and Efficacy of NNC-0156-0000-0009 in Haemophilia B Patients (NCT NCT01333111)

Last Updated: 2017-07-28

Results Overview

Inhibitors were analysed with either the Nijmegen modified factor IX Bethesda assay or a heat/cold Nijmegen modified factor IX Bethesda assay. Number of subjects who developed inhibitory antibodies against factor IX are reported.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

74 participants

Primary outcome timeframe

52 weeks after treatment start for patients on prophylaxis

Results posted on

2017-07-28

Participant Flow

Of the 40 sites that screened subjects, 39 sites enrolled subjects. The trial was therefore conducted at 39 sites in 13 countries, as follows: France (1); Germany (3); Italy (2); Japan (5); Macedonia (2); Malaysia (1) Netherlands (1); Russia (2); South Africa(1); Thailand (2); Turkey (3); United Kingdom (4) and United States (12).

Participant milestones

Participant milestones
Measure	Prophylaxis, Low Dose 10 U/kg (52 Weeks) Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 10 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.	Prophylaxis, High Dose 40 U/kg (52 Weeks) Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 40 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.	On-Demand (28 Weeks) Subjects enrolled in this on-demand arm were treated for bleeding episodes on demand with nonacog beta pegol during a period of 28 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.
Overall Study STARTED	30	29	15
Overall Study COMPLETED	28	26	13
Overall Study NOT COMPLETED	2	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Prophylaxis, Low Dose 10 U/kg (52 Weeks) Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 10 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.	Prophylaxis, High Dose 40 U/kg (52 Weeks) Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 40 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.	On-Demand (28 Weeks) Subjects enrolled in this on-demand arm were treated for bleeding episodes on demand with nonacog beta pegol during a period of 28 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.
Overall Study patient undergoing major surgery	0	2	0
Overall Study personal reasons	0	0	1
Overall Study unclassified	1	0	0
Overall Study withdrawal criteria	0	1	0
Overall Study Non-compliance	1	0	0
Overall Study Ineffective therapy	0	0	1

Baseline Characteristics

Safety and Efficacy of NNC-0156-0000-0009 in Haemophilia B Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Prophylaxis, Low Dose 10 U/kg (52 Weeks) n=30 Participants Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 10 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.	Prophylaxis, High Dose 40 U/kg (52 Weeks) n=29 Participants Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 40 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.	On-Demand (28 Weeks) n=15 Participants Subjects enrolled in this on-demand arm were treated for bleeding episodes on demand with nonacog beta pegol during a period of 28 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.	Total n=74 Participants Total of all reporting groups
Age, Continuous	32.4 years STANDARD_DEVIATION 13.9 • n=5 Participants	30 years STANDARD_DEVIATION 15.8 • n=7 Participants	32.4 years STANDARD_DEVIATION 12.0 • n=5 Participants	31.4 years STANDARD_DEVIATION 14.2 • n=4 Participants
Age, Customized <=17 years	7 Participants n=5 Participants	9 Participants n=7 Participants	2 Participants n=5 Participants	18 Participants n=4 Participants
Age, Customized 18-64 years	23 Participants n=5 Participants	19 Participants n=7 Participants	13 Participants n=5 Participants	55 Participants n=4 Participants
Age, Customized >=65 years	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	29 Participants n=7 Participants	15 Participants n=5 Participants	74 Participants n=4 Participants

PRIMARY outcome

Timeframe: 52 weeks after treatment start for patients on prophylaxis

Population: Full analysis set included all subjects exposed to nonacog beta pegol. Subjects in prophylaxis arm were included for this analysis.

Outcome measures

Outcome measures
Measure	Prophylaxis, Low Dose 10 U/kg (52 Weeks) n=30 Participants Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 10 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.	Prophylaxis, High Dose 40 U/kg (52 Weeks) n=29 Participants Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 40 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.
Incidence of Inhibitory Antibodies Against Factor IX Defined as Titre Equal to or Above 0.6 BU (Bethesda Units)	0 Number of subjects Interval 0.0 to 0.0	0 Number of subjects Interval 0.0 to 0.0

PRIMARY outcome

Timeframe: 28 weeks after treatment start on on-demand treatment

Population: Full analysis set included all subjects exposed to nonacog beta pegol. Subjects in on-demand arm were included for this analysis.

Outcome measures

Outcome measures
Measure	Prophylaxis, Low Dose 10 U/kg (52 Weeks) n=15 Participants Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 10 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.	Prophylaxis, High Dose 40 U/kg (52 Weeks) Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 40 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.
Incidence of Inhibitory Antibodies Against Factor IX Defined as Titre Equal to or Above 0.6 BU (Bethesda Units)	0 number of subjects	—

SECONDARY outcome

Timeframe: 52 weeks after treatment start for patients on prophylaxis

Population: Full analysis set included all subjects exposed to nonacog beta pegol. Subjects in prophylaxis arm were included for this analysis.

Haemostatic response after treatment of a bleed with nonacog beta pegol was evaluated on a 4 point scale as excellent, good, moderate or poor. A success rate was calculated based on counting good or excellent as successes and poor and moderate as failures. * Excellent - abrupt pain relief and/or clear improvement in objective signs of bleeding within 8 hours after a single injection * Good - noticeable pain relief and/or improvement in signs of bleeding within 8 hours after a single injection * Moderate - probable or slight beneficial effect within the first 8 hours after the first injection but requiring more than one injection within 8 hours * Poor - no improvement, or worsening of symptoms within 8 hours after two injections. The success rate and 95% confidence interval (CI) are reported here.

Outcome measures

Outcome measures
Measure	Prophylaxis, Low Dose 10 U/kg (52 Weeks) n=30 Participants Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 10 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.	Prophylaxis, High Dose 40 U/kg (52 Weeks) n=29 Participants Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 40 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.
Haemostatic Effect of NNC-0156-0000-0009 When Used for Prophylaxis of Bleeding Episodes, Assessed as Success/Failure Based on a Four-point Scale for Haemostatic Response	86.9 percentage of bleeding episodes Interval 76.5 to 93.1	97.1 percentage of bleeding episodes Interval 90.0 to 99.2

SECONDARY outcome

Timeframe: 28 weeks after treatment start on on-demand treatment

Population: Full analysis set included all subjects exposed to nonacog beta pegol. Subjects in on-demand arm were included for this analysis.

Outcome measures

Outcome measures
Measure	Prophylaxis, Low Dose 10 U/kg (52 Weeks) n=15 Participants Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 10 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.	Prophylaxis, High Dose 40 U/kg (52 Weeks) Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 40 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.
Haemostatic Effect of NNC-0156-0000-0009 When Used for Treatment of Bleeding Episodes, Assessed as Success/Failure Based on a Four-point Scale for Haemostatic Response	95.1 percentage of bleeding episodes Interval 87.0 to 98.2	—

SECONDARY outcome

Timeframe: 52 weeks after treatment start for patients on prophylaxis

Population: Full analysis set included all subjects exposed to nonacog beta pegol. Subjects in prophylaxis arm were included for this analysis.

The number of bleeding episodes per patient during routine prophylaxis was assessed using the individual annualised bleeding rates (spontaneous and traumatic bleeding episodes per patient per year).

Outcome measures

Outcome measures
Measure	Prophylaxis, Low Dose 10 U/kg (52 Weeks) n=30 Participants Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 10 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.	Prophylaxis, High Dose 40 U/kg (52 Weeks) n=29 Participants Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 40 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.
Number of Bleeding Episodes Per Patient During Routine Prophylaxis	2.93 bleeds/patient/year Inter-Quartile Range 5.41 • Interval 0.99 to 6.02	1.04 bleeds/patient/year Inter-Quartile Range 7.41 • Interval 0.0 to 4.0

SECONDARY outcome

Timeframe: 52 weeks after treatment start for patients on prophylaxis

Population: Full analysis set included all subjects exposed to nonacog beta pegol. Subjects in prophylaxis arm were included for this analysis.

The mean pre-dose factor IX levels was measured with the one-stage clotting assay during the trial. Lowest factor IX activity recorded during single-dose and steady state, immediately before next dose was given. The analysis was based on a mixed model on the log-transformed plasma factor IX activity with subject as a random effect. The estimated mean factor IX trough level was presented back-transformed to the natural scale.

Outcome measures

Outcome measures
Measure	Prophylaxis, Low Dose 10 U/kg (52 Weeks) n=30 Participants Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 10 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.	Prophylaxis, High Dose 40 U/kg (52 Weeks) n=29 Participants Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 40 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.
Factor IX Trough Levels	0.085 U/mL Interval 0.077 to 0.093	0.273 U/mL Interval 0.248 to 0.3

SECONDARY outcome

Timeframe: at 56 weeks ±2 weeks for patients on prophylaxis

Population: Safety analysis set included all subjects exposed to nonacog beta pegol. Subjects in prophylaxis arm were included for this analysis.

The incidence of adverse events were summarised by the rate of AEs (number of AEs per patient years of exposure \[PYE\]). Number of adverse events per PYE is number of adverse events /total time in trial. All adverse events reported are treatment emergent (any adverse events which occurred after trial product administration).

Outcome measures

Outcome measures
Measure	Prophylaxis, Low Dose 10 U/kg (52 Weeks) n=30 Participants Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 10 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.	Prophylaxis, High Dose 40 U/kg (52 Weeks) n=29 Participants Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 40 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.
Incidence of Adverse Events (AEs)	2.62 number of AEs per PYE	3.83 number of AEs per PYE

SECONDARY outcome

Timeframe: at 32 weeks ±2 weeks for patients on on-demand treatment

Population: Safety analysis set included all subjects exposed to nonacog beta pegol.Subjects in on-demand arm were included for this analysis.

The incidence of adverse events were summarised by the rate of AEs (number of AEs per PYE). Number of adverse events per PYE is number of adverse events /total time in trial. All adverse events reported are treatment emergent (any adverse events which occurred after trial product administration).

Outcome measures

Outcome measures
Measure	Prophylaxis, Low Dose 10 U/kg (52 Weeks) n=15 Participants Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 10 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.	Prophylaxis, High Dose 40 U/kg (52 Weeks) Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 40 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.
Incidence of Adverse Events (AEs)	4.14 number of AEs per PYE	—

SECONDARY outcome

Timeframe: at 56 weeks ±2 weeks for patients on prophylaxis

Population: Safety analysis set included all subjects exposed to nonacog beta pegol. Subjects in prophylaxis arm were included for this analysis.

SAE was defined as an AE that resulted in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalisation, persistent/significant disability/incapacity/congenital anomaly/birth defect. The incidence of SAEs were summarised by the rate of SAEs (number of SAEs per PYE). Number of SAEs per PYE is number of SAEs/total time in trial. All SAEs reported are treatment emergent (any serious adverse events which occurred after trial product administration).

Outcome measures

Outcome measures
Measure	Prophylaxis, Low Dose 10 U/kg (52 Weeks) n=30 Participants Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 10 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.	Prophylaxis, High Dose 40 U/kg (52 Weeks) n=29 Participants Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 40 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.
Incidence of Serious Adverse Events (SAEs)	0.03 number of SAEs per PYE	0.11 number of SAEs per PYE

SECONDARY outcome

Timeframe: at 32 weeks ±2 weeks for patients on on-demand treatment

Population: Safety analysis set included all subjects exposed to nonacog beta pegol. Subjects in on-demand arm were included for this analysis.

Outcome measures

Outcome measures
Measure	Prophylaxis, Low Dose 10 U/kg (52 Weeks) n=15 Participants Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 10 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.	Prophylaxis, High Dose 40 U/kg (52 Weeks) Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 40 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.
Incidence of Serious Adverse Events (SAEs)	0 number of SAEs per PYE	—

SECONDARY outcome

Timeframe: 52 weeks after treatment start for patients on prophylaxis

Population: Safety analysis set included all subjects exposed to nonacog beta pegol. Subjects in prophylaxis arm were included for this analysis.

Subjects who were positive for anti-Host Cell Protein (HCP) antibodies.

Outcome measures

Outcome measures
Measure	Prophylaxis, Low Dose 10 U/kg (52 Weeks) n=30 Participants Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 10 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.	Prophylaxis, High Dose 40 U/kg (52 Weeks) n=29 Participants Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 40 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.
Host Cell Proteins (HCP) Antibodies	0 number of subjects	1 number of subjects

SECONDARY outcome

Timeframe: 28 weeks after treatment start on on-demand treatment

Population: Safety analysis set included all subjects exposed to nonacog beta pegol. Subjects in on-demand arm were included for this analysis.

Subjects who were positive for anti-HCP antibodies.

Outcome measures

Outcome measures
Measure	Prophylaxis, Low Dose 10 U/kg (52 Weeks) n=15 Participants Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 10 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.	Prophylaxis, High Dose 40 U/kg (52 Weeks) Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 40 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.
Host Cell Proteins (HCP) Antibodies	0 number of subjects	—

Adverse Events

Prophylaxis, Low Dose 10 U/kg (52 Weeks)

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

Prophylaxis, High Dose 40 U/kg (52 Weeks)

Serious events: 3 serious events

Other events: 19 other events

Deaths: 0 deaths

On-Demand (28 Weeks)

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Prophylaxis, Low Dose 10 U/kg (52 Weeks) n=30 participants at risk Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 10 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.	Prophylaxis, High Dose 40 U/kg (52 Weeks) n=29 participants at risk Subjects were randomised to either prophylaxis 10 U/kg or 40 U/kg arm. Subjects in this arm received 40 U/kg nonacog beta pegol dose once weekly (every 7th day ± 24 hours) for a period of 52 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.	On-Demand (28 Weeks) n=15 participants at risk Subjects enrolled in this on-demand arm were treated for bleeding episodes on demand with nonacog beta pegol during a period of 28 weeks. Nonacog beta pegol was given as an intravenous bolus injection with the maximum injection rate at 4 mL/min. Mild and moderate bleeding episodes were treated with 40 U/kg. Severe bleeding episodes were treated with 80 U/kg.
Gastrointestinal disorders Abdominal pain	0.00% 0/30 • For the subjects treated with prophylaxis, adverse events were assessed for 52 weeks + 4 weeks. For the subjects treated on-demand, adverse events were assessed for 28 weeks + 4 weeks. Treatment-emergent adverse events were defined as any adverse events which occurred after trial product administration. Analysis was based on the safety analysis set.	3.4% 1/29 • Number of events 1 • For the subjects treated with prophylaxis, adverse events were assessed for 52 weeks + 4 weeks. For the subjects treated on-demand, adverse events were assessed for 28 weeks + 4 weeks. Treatment-emergent adverse events were defined as any adverse events which occurred after trial product administration. Analysis was based on the safety analysis set.	0.00% 0/15 • For the subjects treated with prophylaxis, adverse events were assessed for 52 weeks + 4 weeks. For the subjects treated on-demand, adverse events were assessed for 28 weeks + 4 weeks. Treatment-emergent adverse events were defined as any adverse events which occurred after trial product administration. Analysis was based on the safety analysis set.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/30 • For the subjects treated with prophylaxis, adverse events were assessed for 52 weeks + 4 weeks. For the subjects treated on-demand, adverse events were assessed for 28 weeks + 4 weeks. Treatment-emergent adverse events were defined as any adverse events which occurred after trial product administration. Analysis was based on the safety analysis set.	3.4% 1/29 • Number of events 1 • For the subjects treated with prophylaxis, adverse events were assessed for 52 weeks + 4 weeks. For the subjects treated on-demand, adverse events were assessed for 28 weeks + 4 weeks. Treatment-emergent adverse events were defined as any adverse events which occurred after trial product administration. Analysis was based on the safety analysis set.	0.00% 0/15 • For the subjects treated with prophylaxis, adverse events were assessed for 52 weeks + 4 weeks. For the subjects treated on-demand, adverse events were assessed for 28 weeks + 4 weeks. Treatment-emergent adverse events were defined as any adverse events which occurred after trial product administration. Analysis was based on the safety analysis set.
Gastrointestinal disorders Retroperitoneal haematoma	3.3% 1/30 • Number of events 1 • For the subjects treated with prophylaxis, adverse events were assessed for 52 weeks + 4 weeks. For the subjects treated on-demand, adverse events were assessed for 28 weeks + 4 weeks. Treatment-emergent adverse events were defined as any adverse events which occurred after trial product administration. Analysis was based on the safety analysis set.	0.00% 0/29 • For the subjects treated with prophylaxis, adverse events were assessed for 52 weeks + 4 weeks. For the subjects treated on-demand, adverse events were assessed for 28 weeks + 4 weeks. Treatment-emergent adverse events were defined as any adverse events which occurred after trial product administration. Analysis was based on the safety analysis set.	0.00% 0/15 • For the subjects treated with prophylaxis, adverse events were assessed for 52 weeks + 4 weeks. For the subjects treated on-demand, adverse events were assessed for 28 weeks + 4 weeks. Treatment-emergent adverse events were defined as any adverse events which occurred after trial product administration. Analysis was based on the safety analysis set.
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/30 • For the subjects treated with prophylaxis, adverse events were assessed for 52 weeks + 4 weeks. For the subjects treated on-demand, adverse events were assessed for 28 weeks + 4 weeks. Treatment-emergent adverse events were defined as any adverse events which occurred after trial product administration. Analysis was based on the safety analysis set.	3.4% 1/29 • Number of events 1 • For the subjects treated with prophylaxis, adverse events were assessed for 52 weeks + 4 weeks. For the subjects treated on-demand, adverse events were assessed for 28 weeks + 4 weeks. Treatment-emergent adverse events were defined as any adverse events which occurred after trial product administration. Analysis was based on the safety analysis set.	0.00% 0/15 • For the subjects treated with prophylaxis, adverse events were assessed for 52 weeks + 4 weeks. For the subjects treated on-demand, adverse events were assessed for 28 weeks + 4 weeks. Treatment-emergent adverse events were defined as any adverse events which occurred after trial product administration. Analysis was based on the safety analysis set.

Other adverse events

Additional Information

Global Clinical Regstry (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