Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Efficacy of NNC-0156-0000-0009 in Haemophilia B Patients (paradigm™ 2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01333111
Recruitment Status : Completed
First Posted : April 11, 2011
Results First Posted : July 28, 2017
Last Update Posted : July 28, 2017
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Participant);   Primary Purpose: Treatment
Conditions Congenital Bleeding Disorder
Haemophilia B
Intervention Drug: nonacog beta pegol
Enrollment 74
Recruitment Details 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).
Pre-assignment Details  
Arm/Group Title Prophylaxis, Low Dose 10 U/kg (52 Weeks) Prophylaxis, High Dose 40 U/kg (52 Weeks) On-Demand (28 Weeks)
Hide Arm/Group Description 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. 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. 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.
Period Title: Overall Study
Started 30 29 15
Completed 28 26 13
Not Completed 2 3 2
Reason Not Completed
patient undergoing major surgery             0             2             0
personal reasons             0             0             1
unclassified             1             0             0
withdrawal criteria             0             1             0
Non-compliance             1             0             0
Ineffective therapy             0             0             1
Arm/Group Title Prophylaxis, Low Dose 10 U/kg (52 Weeks) Prophylaxis, High Dose 40 U/kg (52 Weeks) On-Demand (28 Weeks) Total
Hide Arm/Group Description 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. 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. 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 of all reporting groups
Overall Number of Baseline Participants 30 29 15 74
Hide Baseline Analysis Population Description
Full analysis set included all subjects exposed to nonacog beta pegol.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 30 participants 29 participants 15 participants 74 participants
32.4  (13.9) 30  (15.8) 32.4  (12.0) 31.4  (14.2)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 30 participants 29 participants 15 participants 74 participants
<=17 years 7 9 2 18
18-64 years 23 19 13 55
>=65 years 0 1 0 1
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 29 participants 15 participants 74 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
30
 100.0%
29
 100.0%
15
 100.0%
74
 100.0%
1.Primary Outcome
Title Incidence of Inhibitory Antibodies Against Factor IX Defined as Titre Equal to or Above 0.6 BU (Bethesda Units)
Hide Description 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.
Time Frame 52 weeks after treatment start for patients on prophylaxis
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all subjects exposed to nonacog beta pegol. Subjects in prophylaxis arm were included for this analysis.
Arm/Group Title Prophylaxis, Low Dose 10 U/kg (52 Weeks) Prophylaxis, High Dose 40 U/kg (52 Weeks)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 30 29
Measure Type: Number
Unit of Measure: Number of subjects
0 0
2.Primary Outcome
Title Incidence of Inhibitory Antibodies Against Factor IX Defined as Titre Equal to or Above 0.6 BU (Bethesda Units)
Hide Description 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.
Time Frame 28 weeks after treatment start on on-demand treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all subjects exposed to nonacog beta pegol. Subjects in on-demand arm were included for this analysis.
Arm/Group Title On-Demand (28 Weeks)
Hide Arm/Group Description:
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 Number of Participants Analyzed 15
Measure Type: Number
Unit of Measure: number of subjects
0
3.Secondary Outcome
Title 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
Hide Description

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.

Time Frame 52 weeks after treatment start for patients on prophylaxis
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all subjects exposed to nonacog beta pegol. Subjects in prophylaxis arm were included for this analysis.
Arm/Group Title Prophylaxis, Low Dose 10 U/kg (52 Weeks) Prophylaxis, High Dose 40 U/kg (52 Weeks)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 30 29
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of bleeding episodes
86.9
(76.5 to 93.1)
97.1
(90.0 to 99.2)
4.Secondary Outcome
Title 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
Hide Description

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.

Time Frame 28 weeks after treatment start on on-demand treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all subjects exposed to nonacog beta pegol. Subjects in on-demand arm were included for this analysis.
Arm/Group Title On-Demand (28 Weeks)
Hide Arm/Group Description:
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 Number of Participants Analyzed 15
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of bleeding episodes
95.1
(87.0 to 98.2)
5.Secondary Outcome
Title Number of Bleeding Episodes Per Patient During Routine Prophylaxis
Hide Description 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).
Time Frame 52 weeks after treatment start for patients on prophylaxis
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all subjects exposed to nonacog beta pegol. Subjects in prophylaxis arm were included for this analysis.
Arm/Group Title Prophylaxis, Low Dose 10 U/kg (52 Weeks) Prophylaxis, High Dose 40 U/kg (52 Weeks)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 30 29
Median (Inter-Quartile Range)
Unit of Measure: bleeds/patient/year
2.93
(0.99 to 6.02)
1.04
(0.00 to 4.00)
6.Secondary Outcome
Title Factor IX Trough Levels
Hide Description 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.
Time Frame 52 weeks after treatment start for patients on prophylaxis
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all subjects exposed to nonacog beta pegol. Subjects in prophylaxis arm were included for this analysis.
Arm/Group Title Prophylaxis, Low Dose 10 U/kg (52 Weeks) Prophylaxis, High Dose 40 U/kg (52 Weeks)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 30 29
Mean (95% Confidence Interval)
Unit of Measure: U/mL
0.085
(0.077 to 0.093)
0.273
(0.248 to 0.300)
7.Secondary Outcome
Title Incidence of Adverse Events (AEs)
Hide Description 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).
Time Frame at 56 weeks ±2 weeks for patients on prophylaxis
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all subjects exposed to nonacog beta pegol. Subjects in prophylaxis arm were included for this analysis.
Arm/Group Title Prophylaxis, Low Dose 10 U/kg (52 Weeks) Prophylaxis, High Dose 40 U/kg (52 Weeks)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 30 29
Measure Type: Number
Unit of Measure: number of AEs per PYE
2.62 3.83
8.Secondary Outcome
Title Incidence of Adverse Events (AEs)
Hide Description 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).
Time Frame at 32 weeks ±2 weeks for patients on on-demand treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all subjects exposed to nonacog beta pegol.Subjects in on-demand arm were included for this analysis.
Arm/Group Title On-Demand (28 Weeks)
Hide Arm/Group Description:
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 Number of Participants Analyzed 15
Measure Type: Number
Unit of Measure: number of AEs per PYE
4.14
9.Secondary Outcome
Title Incidence of Serious Adverse Events (SAEs)
Hide Description 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).
Time Frame at 56 weeks ±2 weeks for patients on prophylaxis
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all subjects exposed to nonacog beta pegol. Subjects in prophylaxis arm were included for this analysis.
Arm/Group Title Prophylaxis, Low Dose 10 U/kg (52 Weeks) Prophylaxis, High Dose 40 U/kg (52 Weeks)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 30 29
Measure Type: Number
Unit of Measure: number of SAEs per PYE
0.03 0.11
10.Secondary Outcome
Title Incidence of Serious Adverse Events (SAEs)
Hide Description 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).
Time Frame at 32 weeks ±2 weeks for patients on on-demand treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all subjects exposed to nonacog beta pegol. Subjects in on-demand arm were included for this analysis.
Arm/Group Title On-Demand (28 Weeks)
Hide Arm/Group Description:
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 Number of Participants Analyzed 15
Measure Type: Number
Unit of Measure: number of SAEs per PYE
0
11.Secondary Outcome
Title Host Cell Proteins (HCP) Antibodies
Hide Description Subjects who were positive for anti-Host Cell Protein (HCP) antibodies.
Time Frame 52 weeks after treatment start for patients on prophylaxis
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all subjects exposed to nonacog beta pegol. Subjects in prophylaxis arm were included for this analysis.
Arm/Group Title Prophylaxis, Low Dose 10 U/kg (52 Weeks) Prophylaxis, High Dose 40 U/kg (52 Weeks)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 30 29
Measure Type: Number
Unit of Measure: number of subjects
0 1
12.Secondary Outcome
Title Host Cell Proteins (HCP) Antibodies
Hide Description Subjects who were positive for anti-HCP antibodies.
Time Frame 28 weeks after treatment start on on-demand treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all subjects exposed to nonacog beta pegol. Subjects in on-demand arm were included for this analysis.
Arm/Group Title On-Demand (28 Weeks)
Hide Arm/Group Description:
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 Number of Participants Analyzed 15
Measure Type: Number
Unit of Measure: number of subjects
0
Time Frame 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.
Adverse Event Reporting Description Treatment-emergent adverse events were defined as any adverse events which occurred after trial product administration. Analysis was based on the safety analysis set.
 
Arm/Group Title Prophylaxis, Low Dose 10 U/kg (52 Weeks) Prophylaxis, High Dose 40 U/kg (52 Weeks) On-Demand (28 Weeks)
Hide Arm/Group Description 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. 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. 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.
All-Cause Mortality
Prophylaxis, Low Dose 10 U/kg (52 Weeks) Prophylaxis, High Dose 40 U/kg (52 Weeks) On-Demand (28 Weeks)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Prophylaxis, Low Dose 10 U/kg (52 Weeks) Prophylaxis, High Dose 40 U/kg (52 Weeks) On-Demand (28 Weeks)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/30 (3.33%)      3/29 (10.34%)      0/15 (0.00%)    
Gastrointestinal disorders       
Abdominal pain  1  0/30 (0.00%)  0 1/29 (3.45%)  1 0/15 (0.00%)  0
Retroperitoneal haematoma  1  1/30 (3.33%)  1 0/29 (0.00%)  0 0/15 (0.00%)  0
Injury, poisoning and procedural complications       
Hip fracture  1  0/30 (0.00%)  0 1/29 (3.45%)  1 0/15 (0.00%)  0
Skin and subcutaneous tissue disorders       
Skin ulcer  1  0/30 (0.00%)  0 1/29 (3.45%)  1 0/15 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Prophylaxis, Low Dose 10 U/kg (52 Weeks) Prophylaxis, High Dose 40 U/kg (52 Weeks) On-Demand (28 Weeks)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   21/30 (70.00%)      19/29 (65.52%)      11/15 (73.33%)    
Blood and lymphatic system disorders       
Eosinophilia  1  1/30 (3.33%)  1 2/29 (6.90%)  2 0/15 (0.00%)  0
Gastrointestinal disorders       
Constipation  1  0/30 (0.00%)  0 0/29 (0.00%)  0 1/15 (6.67%)  1
Mouth ulceration  1  0/30 (0.00%)  0 0/29 (0.00%)  0 1/15 (6.67%)  1
Nausea  1  1/30 (3.33%)  1 1/29 (3.45%)  2 1/15 (6.67%)  1
General disorders       
Fatigue  1  3/30 (10.00%)  3 2/29 (6.90%)  2 1/15 (6.67%)  1
Pyrexia  1  1/30 (3.33%)  2 2/29 (6.90%)  4 1/15 (6.67%)  1
Infections and infestations       
Influenza  1  4/30 (13.33%)  4 3/29 (10.34%)  5 1/15 (6.67%)  1
Lower respiratory tract infection  1  0/30 (0.00%)  0 0/29 (0.00%)  0 1/15 (6.67%)  1
Nasopharyngitis  1  7/30 (23.33%)  9 3/29 (10.34%)  4 0/15 (0.00%)  0
Paronychia  1  0/30 (0.00%)  0 0/29 (0.00%)  0 1/15 (6.67%)  1
Pharyngotonsillitis  1  0/30 (0.00%)  0 2/29 (6.90%)  2 0/15 (0.00%)  0
Upper respiratory tract infection  1  3/30 (10.00%)  4 3/29 (10.34%)  4 2/15 (13.33%)  2
Injury, poisoning and procedural complications       
Contusion  1  2/30 (6.67%)  2 2/29 (6.90%)  2 1/15 (6.67%)  1
Fall  1  1/30 (3.33%)  1 3/29 (10.34%)  4 0/15 (0.00%)  0
Laceration  1  1/30 (3.33%)  2 1/29 (3.45%)  1 1/15 (6.67%)  1
Overdose  1  0/30 (0.00%)  0 2/29 (6.90%)  2 0/15 (0.00%)  0
Thermal burn  1  0/30 (0.00%)  0 0/29 (0.00%)  0 1/15 (6.67%)  1
Investigations       
C-reactive protein increased  1  4/30 (13.33%)  4 0/29 (0.00%)  0 0/15 (0.00%)  0
Prothrombin level increased  1  0/30 (0.00%)  0 2/29 (6.90%)  4 0/15 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia  1  2/30 (6.67%)  2 1/29 (3.45%)  2 1/15 (6.67%)  2
Back pain  1  2/30 (6.67%)  2 0/29 (0.00%)  0 0/15 (0.00%)  0
Groin pain  1  0/30 (0.00%)  0 0/29 (0.00%)  0 1/15 (6.67%)  1
Musculoskeletal pain  1  0/30 (0.00%)  0 0/29 (0.00%)  0 1/15 (6.67%)  1
Myalgia  1  0/30 (0.00%)  0 0/29 (0.00%)  0 1/15 (6.67%)  1
Neck pain  1  0/30 (0.00%)  0 3/29 (10.34%)  3 0/15 (0.00%)  0
Pain in extremity  1  1/30 (3.33%)  1 3/29 (10.34%)  3 1/15 (6.67%)  1
Synovitis  1  0/30 (0.00%)  0 0/29 (0.00%)  0 1/15 (6.67%)  1
Tendonitis  1  0/30 (0.00%)  0 0/29 (0.00%)  0 1/15 (6.67%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Lipoma  1  0/30 (0.00%)  0 0/29 (0.00%)  0 1/15 (6.67%)  1
Nervous system disorders       
Headache  1  2/30 (6.67%)  2 3/29 (10.34%)  7 2/15 (13.33%)  3
Speech disorder developmental  1  0/30 (0.00%)  0 0/29 (0.00%)  0 1/15 (6.67%)  2
Psychiatric disorders       
Attention deficit/hyperactivity disorder  1  0/30 (0.00%)  0 0/29 (0.00%)  0 1/15 (6.67%)  1
Reproductive system and breast disorders       
Erectile dysfunction  1  0/30 (0.00%)  0 0/29 (0.00%)  0 1/15 (6.67%)  1
Respiratory, thoracic and mediastinal disorders       
Cough  1  0/30 (0.00%)  0 2/29 (6.90%)  3 0/15 (0.00%)  0
Epistaxis  1  0/30 (0.00%)  0 2/29 (6.90%)  6 0/15 (0.00%)  0
Oropharyngeal pain  1  0/30 (0.00%)  0 3/29 (10.34%)  3 1/15 (6.67%)  1
Rhinorrhoea  1  0/30 (0.00%)  0 0/29 (0.00%)  0 1/15 (6.67%)  1
Skin and subcutaneous tissue disorders       
Dermatitis  1  0/30 (0.00%)  0 0/29 (0.00%)  0 1/15 (6.67%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Clinical Regstry (GCR, 1452)
Organization: Novo Nordisk A/S
EMail: clinicaltrials@novonordisk.com
Layout table for additonal information
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01333111     History of Changes
Other Study ID Numbers: NN7999-3747
2010-023069-24 ( EudraCT Number )
U1111-1119-6415 ( Other Identifier: WHO )
JapicCTI-111644 ( Other Identifier: Japic )
First Submitted: April 8, 2011
First Posted: April 11, 2011
Results First Submitted: June 27, 2017
Results First Posted: July 28, 2017
Last Update Posted: July 28, 2017