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Safety and Efficacy of NNC-0156-0000-0009 After Long-Term Exposure in Patients With Haemophilia B: An Extension to Trials NN7999-3747 and NN7999-3773 (paradigm™ 4)

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ClinicalTrials.gov Identifier: NCT01395810
Recruitment Status : Completed
First Posted : July 18, 2011
Results First Posted : May 9, 2018
Last Update Posted : May 9, 2018
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Congenital Bleeding Disorder
Haemophilia B
Intervention Drug: nonacog beta pegol
Enrollment 71

Recruitment Details The trial was conducted at 41 sites in 15 countries as follows: France: 1 site; Germany: 3 sites; Italy: 2 sites; Japan: 4 sites; Macedonia: 2 sites; Malaysia: 1 site; Netherlands: 1 site; Romania: 1 site, Russia: 1 site; South Africa: 1 site; Taiwan: 1 site, Thailand: 2 sites; Turkey: 3 sites; United Kingdom: 5 sites; United States: 13 sites
Pre-assignment Details A total of 71 unique subjects were dosed during this trial. During the trial, subjects were free to switch between treatment arms if agreed between the investigator and the subject. Subjects who switched arms were represented in multiple arms.
Arm/Group Title Prophylaxis 10 IU/kg Prophylaxis 40 IU/kg Prophylaxis 80 IU/kg On-demand
Hide Arm/Group Description Subjects were given 10 IU/kg weekly nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an intravenous (i.v.) bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg. Subjects were given 40 IU/kg weekly nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg. Subjects were dosed with 80 IU/kg every second week. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg. Subjects in the on-demand group were administered with the single dose of 40 IU/kg of nonacog beta pegol. The recommended dose for treatment of a mild or moderate bleeding episode, for example a joint bleed, was a single dose of 40 IU/kg nonacog beta pegol. If there was no observed effect of 40 IU/kg, the investigator was to be contacted prior to administration of the second dose of 40 IU/kg. The recommended dose for severe bleeds was 80 IU/kg nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject.
Period Title: Overall Study
Started 18 48 0 5
After Switching the Arms [1] 21 [2] 52 [3] 2 [4] 5
Completed 16 44 0 5
Not Completed 2 4 0 0
Reason Not Completed
Adverse Event             0             1             0             0
Lack of Efficacy             0             1             0             0
Withdrawal criteria             0             2             0             0
Unclassified             2             0             0             0
[1]
Patients were free to switch between treatment arms if agreed between investigator and patient
[2]
18 subjects started in this arm and additional 3 subjects from 40 IU/kg switched to this arm
[3]
48 subjects started in this arm, 3 subjects in 10 IU/kg+1 subject in on-demand switched to this arm
[4]
No subjects started in this arm initially, 2 patients in 40 IU/kg arm switched to this arm.
Arm/Group Title Prophylaxis 10 IU/kg Prophylaxis 40 IU/kg Prophylaxis 80 IU/kg On-demand Total
Hide Arm/Group Description Subjects were given 10 IU/kg weekly nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg. Subjects were given 40 IU/kg weekly nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg. Subjects were dosed with 80 IU/kg every second week. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg. Subjects in the on-demand group were administered with the single dose of 40 IU/kg of nonacog beta pegol. The recommended dose for treatment of a mild or moderate bleeding episode, for example a joint bleed, was a single dose of 40 IU/kg nonacog beta pegol. If there was no observed effect of 40 IU/kg, the investigator was to be contacted prior to administration of the second dose of 40 IU/kg. The recommended dose for severe bleeds was 80 IU/kg nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Total of all reporting groups
Overall Number of Baseline Participants 18 48 0 5 71
Hide Baseline Analysis Population Description
The full analysis set (FAS) consisted of all subjects exposed to nonacog beta pegol.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 18 participants 48 participants 0 participants 5 participants 71 participants
32.2  (13.6) 31.4  (14.4) 37.6  (15.4) 32.0  (14.2)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 18 participants 48 participants 0 participants 5 participants 71 participants
13 - 17 years 3 12 0 15
18 - 70 years 15 36 5 56
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 48 participants 0 participants 5 participants 71 participants
Female
0
   0.0%
0
   0.0%
0
0
   0.0%
0
   0.0%
Male
18
 100.0%
48
 100.0%
0
5
 100.0%
71
 100.0%
1.Primary Outcome
Title Incidence of Inhibitory Antibodies Against FIX Defined as Titre Above or Equal to 0.6 BU (Bethesda Units)
Hide Description

The primary endpoint was incidence of inhibitors against coagulation factor nine (FIX) defined as titre

≥0.6 Bethesda unit (BU). Number of subjects who developed inhibitors against FIX are reported.

Time Frame From Day 1 up to 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set consisted of all subjects exposed to nonacog beta pegol. Subjects who switched arms were represented in multiple columns.
Arm/Group Title Prophylaxis 10 IU/kg Prophylaxis 40 IU/kg Prophylaxis 80 IU/kg On-demand
Hide Arm/Group Description:
Subjects were given 10 IU/kg weekly nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg.
Subjects were given 40 IU/kg weekly nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg.
Subjects were dosed with 80 IU/kg every second week. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg.
Subjects in the on-demand group were administered with the single dose of 40 IU/kg of nonacog beta pegol. The recommended dose for treatment of a mild or moderate bleeding episode, for example a joint bleed, was a single dose of 40 IU/kg nonacog beta pegol. If there was no observed effect of 40 IU/kg, the investigator was to be contacted prior to administration of the second dose of 40 IU/kg. The recommended dose for severe bleeds was 80 IU/kg nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject.
Overall Number of Participants Analyzed 21 52 2 5
Measure Type: Number
Unit of Measure: Patients with inhibitory antibodies
0 0 0 0
2.Secondary Outcome
Title Haemostatic Effect of Nonacog Beta Pegol When Used for Treatment of Bleeding Episodes, Assessed as Success/Failure Based on a Four-point Scale for Haemostatic Response (Excellent, Good, Moderate, Poor)
Hide Description The haemostatic effect was evaluated by a four-point scale where an "excellent" or "good" outcome translated into a successful treatment, and a "moderate" or "poor" outcome was considered a treatment failure. The values mentioned below do not include bleeds with missing response.
Time Frame From Day 1 up to 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set consisted of all subjects exposed to nonacog beta pegol. Subjects who switched arms were represented in multiple columns.
Arm/Group Title Prophylaxis 10 IU/kg Prophylaxis 40 IU/kg Prophylaxis 80 IU/kg On-demand Total
Hide Arm/Group Description:
Subjects were given 10 IU/kg weekly nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg.
Subjects were given 40 IU/kg weekly nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg.
Subjects were dosed with 80 IU/kg every second week. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg.
Subjects in the on-demand group were administered with the single dose of 40 IU/kg of nonacog beta pegol. The recommended dose for treatment of a mild or moderate bleeding episode, for example a joint bleed, was a single dose of 40 IU/kg nonacog beta pegol. If there was no observed effect of 40 IU/kg, the investigator was to be contacted prior to administration of the second dose of 40 IU/kg. The recommended dose for severe bleeds was 80 IU/kg nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject.
Subjects received nonacog beta pegol as prophylaxis treatment or on-demand treatment. Subjects in the prophylaxis treatment received either 10 IU/kg once weekly, 40 IU/kg once weekly or 80 IU/kg once every second week. Subjects in the on-demand group were administered with a single dose of 40 IU/kg of nonacog beta pegol. Subjects with on-demand treatment and prophylaxis treatments who experienced a bleeding episode were to be treated with single dose of 40 IU/kg unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects were free to switch between treatment arms if agreed between the investigator and the subject.
Overall Number of Participants Analyzed 21 52 2 5 71
Overall Number of Units Analyzed
Type of Units Analyzed: Bleeding episodes
35 98 1 73 207
Measure Type: Number
Unit of Measure: Percentage of bleeding episodes
Success 97.1 94.8 100 93.2 94.6
Failure 2.9 5.2 0 6.8 5.4
3.Secondary Outcome
Title Number of Bleeding Episodes During Routine Prophylaxis
Hide Description Annualized bleeding rate is the total number of bleeding episodes/total exposure time. It is analysed by a Poisson regression model with dose as a factor allowing for over-dispersion and using treatment duration as an offset. Median annualized bleeding rate is the median of individual annualized bleeding rates. Numbers are based on the treatment arm at the time of each bleed.
Time Frame From Day 1 up to 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set consisted of all subjects exposed to nonacog beta pegol. Subjects who switched arms were represented in multiple columns.
Arm/Group Title Prophylaxis 10 IU/kg Prophylaxis 40 IU/kg Prophylaxis 80 IU/kg
Hide Arm/Group Description:
Subjects were given 10 IU/kg weekly nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg.
Subjects were given 40 IU/kg weekly nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg.
Subjects were dosed with 80 IU/kg every second week. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg.
Overall Number of Participants Analyzed 21 52 2
Median (Inter-Quartile Range)
Unit of Measure: bleeds/patient/year
1.36
(0.00 to 2.23)
1.00
(0.00 to 2.03)
0
(0 to 0)
4.Secondary Outcome
Title FIX Trough Levels
Hide Description During the trial, the pre-dose FIX levels was measured with the one-stage clotting assay. Measurements taken at least 5 days and no more than 10 days after last dose as well as at least 14 days after last bleeding episode were included in this analysis. The mean FIX trough levels were estimated based on the mixed effects model on the log-transformed plasma concentration with subject as a random effect. The mean FIX trough level was presented back-transformed to the natural scale.
Time Frame From Day 1 up to 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set consisted of all subjects exposed to nonacog beta pegol. This endpoint was analysed only for the prophylaxis arms (i.e.,10 IU/kg, 40 IU/kg). No pre-dose measurements were collected for patients on 80 IU/kg every second week prophylaxis.
Arm/Group Title Prophylaxis 10 IU/kg Prophylaxis 40 IU/kg
Hide Arm/Group Description:
Subjects were given 10 IU/kg weekly nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg.
Subjects were given 40 IU/kg weekly nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg.
Overall Number of Participants Analyzed 21 52
Mean (95% Confidence Interval)
Unit of Measure: IU/mL
0.098
(0.080 to 0.119)
0.213
(0.189 to 0.241)
5.Secondary Outcome
Title Incidence of Adverse Events (AEs)
Hide Description AEs were summarized by frequency of events and frequency of patients with any event. Incidence of AEs was expressed as number of AEs per subject years of exposure (total number of events /total time in trial).
Time Frame From Day 1 up to 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set consisted of all subjects who were exposed to nonacog beta pegol. Subjects who switched arms were represented in multiple columns.
Arm/Group Title Prophylaxis 10 IU/kg Prophylaxis 40 IU/kg Prophylaxis 80 IU/kg On-demand
Hide Arm/Group Description:
Subjects were given 10 IU/kg weekly nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg.
Subjects were given 40 IU/kg weekly nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg.
Subjects were dosed with 80 IU/kg every second week. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg.
Subjects in the on-demand group were administered with the single dose of 40 IU/kg of nonacog beta pegol. The recommended dose for treatment of a mild or moderate bleeding episode, for example a joint bleed, was a single dose of 40 IU/kg nonacog beta pegol. If there was no observed effect of 40 IU/kg, the investigator was to be contacted prior to administration of the second dose of 40 IU/kg. The recommended dose for severe bleeds was 80 IU/kg nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject.
Overall Number of Participants Analyzed 21 52 2 5
Measure Type: Number
Unit of Measure: Events per subject year of exposure
2.4 1.9 0 3.2
6.Secondary Outcome
Title Incidence of Serious Adverse Events (SAEs)
Hide Description AEs were summarized by frequency of events and frequency of patients with any event. Incidence of serious AEs was expressed as number of serious AEs per subject years of exposure (total number of events /total time in trial).
Time Frame From Day 1 up to 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis set consisted of all subjects exposed to nonacog beta pegol. Subjects who switched arms were represented in multiple columns.
Arm/Group Title Prophylaxis 10 IU/kg Prophylaxis 40 IU/kg Prophylaxis 80 IU/kg On-demand
Hide Arm/Group Description:
Subjects were given 10 IU/kg weekly nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg.
Subjects were given 40 IU/kg weekly nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg.
Subjects were dosed with 80 IU/kg every second week. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg.
Subjects in the on-demand group were administered with the single dose of 40 IU/kg of nonacog beta pegol. The recommended dose for treatment of a mild or moderate bleeding episode, for example a joint bleed, was a single dose of 40 IU/kg nonacog beta pegol. If there was no observed effect of 40 IU/kg, the investigator was to be contacted prior to administration of the second dose of 40 IU/kg. The recommended dose for severe bleeds was 80 IU/kg nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject.
Overall Number of Participants Analyzed 21 52 2 5
Measure Type: Number
Unit of Measure: Events per subject year of exposure
0.1 0.1 0 0
Time Frame Adverse Events (AEs) from baseline visit (visit 1) and until one week after last treatment with nonacog beta pegol (±2 days) (up to 2 years)
Adverse Event Reporting Description The safety analysis set consists of all patients exposed to nonacog beta pegol.
 
Arm/Group Title Prophylaxis 10 U/kg Prophylaxis 40 U/kg Prophylaxis 80 U/kg On-demand
Hide Arm/Group Description Subjects were given 10 IU/kg weekly nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an intravenous (i.v.) bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg. Subjects were given 40 IU/kg weekly nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg. Subjects were dosed with 80 IU/kg every second week. Subjects were free to switch between treatment arms if agreed between the investigator and the subject. Administration of the appropriate volume of nonacog beta pegol was given as an i.v. bolus injection. The maximum injection rate was 4 mL/min. Subjects on prophylaxis who experienced a bleeding episode were to treat the bleeding episode with a single dose of 40 IU/kg, unless the bleeding episode was severe in which case it was to be treated with 80 IU/kg. Subjects in the on-demand group were administered with the single dose of 40 IU/kg of nonacog beta pegol. The recommended dose for treatment of a mild or moderate bleeding episode, for example a joint bleed, was a single dose of 40 IU/kg nonacog beta pegol. If there was no observed effect of 40 IU/kg, the investigator was to be contacted prior to administration of the second dose of 40 IU/kg. The recommended dose for severe bleeds was 80 IU/kg nonacog beta pegol. Subjects were free to switch between treatment arms if agreed between the investigator and the subject.
All-Cause Mortality
Prophylaxis 10 U/kg Prophylaxis 40 U/kg Prophylaxis 80 U/kg On-demand
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Prophylaxis 10 U/kg Prophylaxis 40 U/kg Prophylaxis 80 U/kg On-demand
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/21 (4.76%)      5/52 (9.62%)      0/2 (0.00%)      0/5 (0.00%)    
Gastrointestinal disorders         
Faecaloma  1  1/21 (4.76%)  1 0/52 (0.00%)  0 0/2 (0.00%)  0 0/5 (0.00%)  0
Infections and infestations         
Gastroenteritis  1  0/21 (0.00%)  0 1/52 (1.92%)  1 0/2 (0.00%)  0 0/5 (0.00%)  0
Post procedural infection  1  0/21 (0.00%)  0 1/52 (1.92%)  1 0/2 (0.00%)  0 0/5 (0.00%)  0
Injury, poisoning and procedural complications         
Femur fracture  1  0/21 (0.00%)  0 1/52 (1.92%)  1 0/2 (0.00%)  0 0/5 (0.00%)  0
Road traffic accident  1  0/21 (0.00%)  0 1/52 (1.92%)  1 0/2 (0.00%)  0 0/5 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Hepatocellular carcinoma  1  0/21 (0.00%)  0 1/52 (1.92%)  1 0/2 (0.00%)  0 0/5 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Prophylaxis 10 U/kg Prophylaxis 40 U/kg Prophylaxis 80 U/kg On-demand
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/21 (38.10%)      8/52 (15.38%)      0/2 (0.00%)      5/5 (100.00%)    
Eye disorders         
Asthenopia  1  0/21 (0.00%)  0 0/52 (0.00%)  0 0/2 (0.00%)  0 1/5 (20.00%)  1
Gastrointestinal disorders         
Dental caries  1  2/21 (9.52%)  2 0/52 (0.00%)  0 0/2 (0.00%)  0 0/5 (0.00%)  0
General disorders         
Chest discomfort  1  0/21 (0.00%)  0 0/52 (0.00%)  0 0/2 (0.00%)  0 1/5 (20.00%)  1
Influenza like illness  1  1/21 (4.76%)  1 1/52 (1.92%)  1 0/2 (0.00%)  0 1/5 (20.00%)  1
Pain  1  0/21 (0.00%)  0 1/52 (1.92%)  1 0/2 (0.00%)  0 1/5 (20.00%)  3
Swelling  1  0/21 (0.00%)  0 0/52 (0.00%)  0 0/2 (0.00%)  0 1/5 (20.00%)  1
Infections and infestations         
Bronchitis  1  0/21 (0.00%)  0 0/52 (0.00%)  0 0/2 (0.00%)  0 1/5 (20.00%)  1
Influenza  1  4/21 (19.05%)  6 0/52 (0.00%)  0 0/2 (0.00%)  0 0/5 (0.00%)  0
Nasopharyngitis  1  3/21 (14.29%)  5 4/52 (7.69%)  5 0/2 (0.00%)  0 0/5 (0.00%)  0
Upper respiratory tract infection  1  0/21 (0.00%)  0 0/52 (0.00%)  0 0/2 (0.00%)  0 1/5 (20.00%)  3
Urinary tract infection  1  0/21 (0.00%)  0 0/52 (0.00%)  0 0/2 (0.00%)  0 1/5 (20.00%)  1
Injury, poisoning and procedural complications         
Ligament sprain  1  0/21 (0.00%)  0 3/52 (5.77%)  5 0/2 (0.00%)  0 0/5 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Joint range of motion decreased  1  0/21 (0.00%)  0 0/52 (0.00%)  0 0/2 (0.00%)  0 1/5 (20.00%)  1
Muscle spasms  1  0/21 (0.00%)  0 0/52 (0.00%)  0 0/2 (0.00%)  0 1/5 (20.00%)  1
Nervous system disorders         
Headache  1  2/21 (9.52%)  2 1/52 (1.92%)  2 0/2 (0.00%)  0 0/5 (0.00%)  0
Psychiatric disorders         
Libido decreased  1  0/21 (0.00%)  0 0/52 (0.00%)  0 0/2 (0.00%)  0 1/5 (20.00%)  1
Respiratory, thoracic and mediastinal disorders         
Cough  1  2/21 (9.52%)  2 1/52 (1.92%)  1 0/2 (0.00%)  0 1/5 (20.00%)  1
Skin and subcutaneous tissue disorders         
Rash  1  0/21 (0.00%)  0 0/52 (0.00%)  0 0/2 (0.00%)  0 1/5 (20.00%)  1
Vascular disorders         
Hypertension  1  0/21 (0.00%)  0 0/52 (0.00%)  0 0/2 (0.00%)  0 1/5 (20.00%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17
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
Name/Title: Global Clinical Registry (GCR, 1452)
Organization: Novo Nordisk A/S
Other Publications:
Young G, Collins P, Tehranchi R, Chuansumrit A, Hanabusa H, Lentz SR, Mahlangu J, Mauser-Bunschoten E, Negrier C, Oldenburg J, Patiroglu T, Santagostino E, Zak M, Abdul Karim F. Safety and efficacy of nonacog beta pegol (N9-GP) for prophylaxis and treatment of bleeding episodes in previously-treated patients with hemophilia B: results from an extension trial. American Society of Hematology - 56th Annual Meeting (ASH) in San Francisco, CA, US
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01395810     History of Changes
Other Study ID Numbers: NN7999-3775
2010-023072-17 ( EudraCT Number )
U1111-1121-5408 ( Other Identifier: WHO )
JapicCTI-121812 ( Registry Identifier: JAPIC )
First Submitted: June 30, 2011
First Posted: July 18, 2011
Results First Submitted: November 28, 2017
Results First Posted: May 9, 2018
Last Update Posted: May 9, 2018