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Efficacy and Safety of NNC-0156-0000-0009 During Surgical Procedures in Subjects With Haemophilia B (paradigm™ 3)

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ClinicalTrials.gov Identifier: NCT01386528
Recruitment Status : Completed
First Posted : July 1, 2011
Results First Posted : July 24, 2017
Last Update Posted : August 23, 2017
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Congenital Bleeding Disorder
Haemophilia B
Intervention Drug: nonacog beta pegol
Enrollment 13
Recruitment Details The study was conducted at 10 sites in 8 countries : Italy (1 site), Malaysia (1 site), Romania (1 site), South Africa (1 site), Taiwan (1 site), Turkey (1 SIte), UK (2 sites), US (2 sites).
Pre-assignment Details Patients enrolled in the present trial were recruited from the pivotal trial (NN7999-3747) or the extension trial (NN7999-3775). In addition, new patients were recruited into the present trial.
Arm/Group Title Nonacog Beta Pegol
Hide Arm/Group Description New patients as well as transferred patients from the pivotal trial (NN7999-3747) or the extension trial(NN7999-3775) received nonacog beta pegol at screening and followed a preventive treatment regimen with nonacog beta pegol until one week before the day of surgery. No more than 4 hours prior to the planned surgical procedure, all patients received a single bolus injection of 80 U/kg of nonacog beta pegol. Postoperatively, the patients received fixed doses of 40 U/kg repeated at the investigator's discretion aiming for no less than the FIX levels recommended by the World Federation of Hemophilia. Nonacog beta pegol was administered intravenously. The new patients were dosed once with 40 U/kg nonacog beta pegol at screening.From the day after surgery (Day 1) and through Day 6, nonacog beta pegol dosing was adjusted to aim for a FIX activity level of approximately 0.50 U/mL.
Period Title: Overall Study
Started 13
Completed 13
Not Completed 0
Arm/Group Title Nonacog Beta Pegol
Hide Arm/Group Description New patients as well as transferred patients from the pivotal trial (NN7999-3747) or the extension trial(NN7999-3775) received nonacog beta pegol at screening and followed a preventive treatment regimen with nonacog beta pegol until one week before the day of surgery. No more than 4 hours prior to the planned surgical procedure, all patients received a single bolus injection of 80 U/kg of nonacog beta pegol. Postoperatively, the patients received fixed doses of 40 U/kg repeated at the investigator's discretion aiming for no less than the FIX levels recommended by the World Federation of Hemophilia. Nonacog beta pegol was administered intravenously. The new patients were dosed once with 40 U/kg nonacog beta pegol at screening.From the day after surgery (Day 1) and through Day 6, nonacog beta pegol dosing was adjusted to aim for a FIX activity level of approximately 0.50 U/mL.
Overall Number of Baseline Participants 13
Hide Baseline Analysis Population Description
The full analysis set consists of all patients exposed to nonacog beta pegol.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
<=18 years
1
   7.7%
Between 18 and 65 years
12
  92.3%
>=65 years
0
   0.0%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 13 participants
39
(15 to 56)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
Female
0
   0.0%
Male
13
 100.0%
1.Primary Outcome
Title Haemostatic Effect During Surgery Evaluated by the Four-point Response Scale (Excellent, Good, Moderate, Poor)
Hide Description

Haemostatic effect during surgery was evaluated immediately after surgery (last stitch) using a fourpoint response scale:

- Four-point response scale: Excellent, good, moderate, poor. The evaluation was done by the surgeon, anaesthesiologist and/or investigator based on experience as follows:

  1. Excellent: Better than expected/predicted in this type of procedure.
  2. Good: As expected in this type of procedure.
  3. Moderate: Less than optimal for the type of procedure but haemostatic response maintained without change of treatment regimen.
  4. Poor: Bleeding due to inadequate therapeutic response with adequate dosing, change of regimen required.
Time Frame At the day of surgery
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set consisted of all patients exposed to nanacog beta pegol.
Arm/Group Title Nonacog Beta Pegol
Hide Arm/Group Description:
New patients as well as transferred patients from the pivotal trial (NN7999-3747) or the extension trial(NN7999-3775) received nonacog beta pegol at screening and followed a preventive treatment regimen with nonacog beta pegol until one week before the day of surgery. No more than 4 hours prior to the planned surgical procedure, all patients received a single bolus injection of 80 U/kg of nonacog beta pegol. Postoperatively, the patients received fixed doses of 40 U/kg repeated at the investigator's discretion aiming for no less than the FIX levels recommended by the World Federation of Hemophilia. Nonacog beta pegol was administered intravenously. The new patients were dosed once with 40 U/kg nonacog beta pegol at screening.From the day after surgery (Day 1) and through Day 6, nonacog beta pegol dosing was adjusted to aim for a FIX activity level of approximately 0.50 U/mL.
Overall Number of Participants Analyzed 13
Measure Type: Number
Unit of Measure: Haemostatic responses
Excellent 10
Good 3
Moderate 0
Poor 0
2.Secondary Outcome
Title Consumption of NNC-0156-0000-0009 (U/kg Body Weight)
Hide Description Mean consumption of nonacog beta pegol (U/kg) used for treatment per patient before surgery, during surgery (the time from knife to skin until last stitch) and post-operative period.
Time Frame During surgery (the time from knife to skin until last stitch) and post-operative period (day 1 to day 13)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set consisted of all patients exposed to nanacog beta pegol.
Arm/Group Title Nonacog Beta Pegol
Hide Arm/Group Description:
New patients as well as transferred patients from the pivotal trial (NN7999-3747) or the extension trial(NN7999-3775) received nonacog beta pegol at screening and followed a preventive treatment regimen with nonacog beta pegol until one week before the day of surgery. No more than 4 hours prior to the planned surgical procedure, all patients received a single bolus injection of 80 U/kg of nonacog beta pegol. Postoperatively, the patients received fixed doses of 40 U/kg repeated at the investigator's discretion aiming for no less than the FIX levels recommended by the World Federation of Hemophilia. Nonacog beta pegol was administered intravenously. The new patients were dosed once with 40 U/kg nonacog beta pegol at screening.From the day after surgery (Day 1) and through Day 6, nonacog beta pegol dosing was adjusted to aim for a FIX activity level of approximately 0.50 U/mL.
Overall Number of Participants Analyzed 13
Mean (Standard Deviation)
Unit of Measure: U/Kg
328.2  (113.1)
3.Secondary Outcome
Title Transfusion Requirements (Fulfilling Transfusion Criteria)
Hide Description Mean quantity of transfusion during surgery (the time from knife to skin until last stitch) and the postoperative period (Day 1-13).None of the patients required transfusions beyond Day 6 hence no values presented for days 7-13.
Time Frame during surgery (the time from knife to skin until last stitch) and post-operative period (day 1 to day 13)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set consisted of all patients exposed to nanacog beta pegol.
Arm/Group Title Nonacog Beta Pegol
Hide Arm/Group Description:
New patients as well as transferred patients from the pivotal trial (NN7999-3747) or the extension trial(NN7999-3775) received nonacog beta pegol at screening and followed a preventive treatment regimen with nonacog beta pegol until one week before the day of surgery. No more than 4 hours prior to the planned surgical procedure, all patients received a single bolus injection of 80 U/kg of nonacog beta pegol. Postoperatively, the patients received fixed doses of 40 U/kg repeated at the investigator's discretion aiming for no less than the FIX levels recommended by the World Federation of Hemophilia. Nonacog beta pegol was administered intravenously. The new patients were dosed once with 40 U/kg nonacog beta pegol at screening.From the day after surgery (Day 1) and through Day 6, nonacog beta pegol dosing was adjusted to aim for a FIX activity level of approximately 0.50 U/mL.
Overall Number of Participants Analyzed 13
Mean (Standard Deviation)
Unit of Measure: mL
During surgery 275  (35.4)
Post surgery through day 6 266.7  (28.9)
4.Secondary Outcome
Title Haemoglobin Pre- and Post-surgery Start
Hide Description The mean pre-surgery and post surgery haemoglobin level.
Time Frame 0, 1 hour, 24 hours.
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set consisted of all patients exposed to nanacog beta pegol.
Arm/Group Title Nonacog Beta Pegol
Hide Arm/Group Description:
New patients as well as transferred patients from the pivotal trial (NN7999-3747) or the extension trial(NN7999-3775) received nonacog beta pegol at screening and followed a preventive treatment regimen with nonacog beta pegol until one week before the day of surgery. No more than 4 hours prior to the planned surgical procedure, all patients received a single bolus injection of 80 U/kg of nonacog beta pegol. Postoperatively, the patients received fixed doses of 40 U/kg repeated at the investigator's discretion aiming for no less than the FIX levels recommended by the World Federation of Hemophilia. Nonacog beta pegol was administered intravenously. The new patients were dosed once with 40 U/kg nonacog beta pegol at screening.From the day after surgery (Day 1) and through Day 6, nonacog beta pegol dosing was adjusted to aim for a FIX activity level of approximately 0.50 U/mL.
Overall Number of Participants Analyzed 13
Mean (Standard Deviation)
Unit of Measure: mmol/L
prior to surgery 8.98  (0.67)
1 hour post-surgery 8.37  (0.78)
24 hours post surgery 7.99  (1.13)
5.Secondary Outcome
Title Incidence of Adverse Events (AEs)
Hide Description The number of adverse events per patient years of exposure, reported during the trial period. Number is the only available option here, the data presented are rate of AEs.
Time Frame during the trial period (2-8 weeks prior to day of surgery (transferred subjects) or 2-4 weeks prior to day of surgery (new subjects) until 4 weeks after post-operative period (day 1 to day 13)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set consisted of all patients exposed to nanacog beta pegol.
Arm/Group Title Nonacog Beta Pegol
Hide Arm/Group Description:
New patients as well as transferred patients from the pivotal trial (NN7999-3747) or the extension trial(NN7999-3775) received nonacog beta pegol at screening and followed a preventive treatment regimen with nonacog beta pegol until one week before the day of surgery. No more than 4 hours prior to the planned surgical procedure, all patients received a single bolus injection of 80 U/kg of nonacog beta pegol. Postoperatively, the patients received fixed doses of 40 U/kg repeated at the investigator's discretion aiming for no less than the FIX levels recommended by the World Federation of Hemophilia. Nonacog beta pegol was administered intravenously. The new patients were dosed once with 40 U/kg nonacog beta pegol at screening.From the day after surgery (Day 1) and through Day 6, nonacog beta pegol dosing was adjusted to aim for a FIX activity level of approximately 0.50 U/mL.
Overall Number of Participants Analyzed 13
Measure Type: Number
Unit of Measure: events per patient year of exposure
12.12
6.Secondary Outcome
Title Incidence of Serious Adverse Events (SAE)
Hide Description The number of serious adverse events per patient years of exposure, reported during the trial period. Number is the only available option here, the data presented are rate of AEs.
Time Frame During the trial period (2-8 weeks prior to day of surgery (transferred subjects) or 2-4 weeks prior to day of surgery (new subjects) until 4 weeks after post-operative period (day 1 to day 13)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set consisted of all patients exposed to nanacog beta pegol.
Arm/Group Title Nonacog Beta Pegol
Hide Arm/Group Description:
New patients as well as transferred patients from the pivotal trial (NN7999-3747) or the extension trial(NN7999-3775) received nonacog beta pegol at screening and followed a preventive treatment regimen with nonacog beta pegol until one week before the day of surgery. No more than 4 hours prior to the planned surgical procedure, all patients received a single bolus injection of 80 U/kg of nonacog beta pegol. Postoperatively, the patients received fixed doses of 40 U/kg repeated at the investigator's discretion aiming for no less than the FIX levels recommended by the World Federation of Hemophilia. Nonacog beta pegol was administered intravenously. The new patients were dosed once with 40 U/kg nonacog beta pegol at screening.From the day after surgery (Day 1) and through Day 6, nonacog beta pegol dosing was adjusted to aim for a FIX activity level of approximately 0.50 U/mL.
Overall Number of Participants Analyzed 13
Measure Type: Number
Unit of Measure: Events per patient year of exposure
0
7.Secondary Outcome
Title Incidence of Inhibitors Against FIX (Coagulation Factor Nine)
Hide Description Number of patients with inhibitory antibodies
Time Frame During the trial period (2-8 weeks prior to day of surgery (transferred subjects) or 2-4 weeks prior to day of surgery (new subjects) and every 4 weeks after post-operative period (day 1 to day 13)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set consisted of all patients exposed to nanacog beta pegol.
Arm/Group Title Nonacog Beta Pegol
Hide Arm/Group Description:
New patients as well as transferred patients from the pivotal trial (NN7999-3747) or the extension trial(NN7999-3775) received nonacog beta pegol at screening and followed a preventive treatment regimen with nonacog beta pegol until one week before the day of surgery. No more than 4 hours prior to the planned surgical procedure, all patients received a single bolus injection of 80 U/kg of nonacog beta pegol. Postoperatively, the patients received fixed doses of 40 U/kg repeated at the investigator's discretion aiming for no less than the FIX levels recommended by the World Federation of Hemophilia. Nonacog beta pegol was administered intravenously. The new patients were dosed once with 40 U/kg nonacog beta pegol at screening.From the day after surgery (Day 1) and through Day 6, nonacog beta pegol dosing was adjusted to aim for a FIX activity level of approximately 0.50 U/mL.
Overall Number of Participants Analyzed 13
Measure Type: Number
Unit of Measure: patients
0
Time Frame AEs from screening visit (day 0) and until post treatment follow-up period. Patients not continuing in the extension trial attended a follow-up visit 4 weeks ± 2 weeks after the last dose of nonacog beta pegol.
Adverse Event Reporting Description The safety analysis set consisted of all patients exposed to nanacog beta pegol.
 
Arm/Group Title Nonacog Beta Pegol
Hide Arm/Group Description New patients as well as transferred patients from the pivotal trial (NN7999-3747) or the extension trial(NN7999-3775) received nonacog beta pegol at screening and followed a preventive treatment regimen with nonacog beta pegol until one week before the day of surgery. No more than 4 hours prior to the planned surgical procedure, all patients received a single bolus injection of 80 U/kg of nonacog beta pegol. Postoperatively, the patients received fixed doses of 40 U/kg repeated at the investigator's discretion aiming for no less than the FIX levels recommended by the World Federation of Hemophilia. Nonacog beta pegol was administered intravenously. The new patients were dosed once with 40 U/kg nonacog beta pegol at screening.From the day after surgery (Day 1) and through Day 6, nonacog beta pegol dosing was adjusted to aim for a FIX activity level of approximately 0.50 U/mL.
All-Cause Mortality
Nonacog Beta Pegol
Affected / at Risk (%)
Total   --/--    
Hide Serious Adverse Events
Nonacog Beta Pegol
Affected / at Risk (%) # Events
Total   0/13 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Nonacog Beta Pegol
Affected / at Risk (%) # Events
Total   9/13 (69.23%)    
Blood and lymphatic system disorders   
Anaemia  1  1/13 (7.69%)  1
Eye disorders   
Conjunctival haemorrhage  1  1/13 (7.69%)  1
Gastrointestinal disorders   
Epigastric discomfort  1  1/13 (7.69%)  1
Nausea  1  1/13 (7.69%)  1
Oral mucosal erythema  1  1/13 (7.69%)  1
Vomiting  1  1/13 (7.69%)  1
General disorders   
Face oedema  1  1/13 (7.69%)  1
Pyrexia  1  1/13 (7.69%)  1
Injury, poisoning and procedural complications   
Excoriation  1  1/13 (7.69%)  1
Fall  1  1/13 (7.69%)  1
Investigations   
Serum ferritin increased  1  1/13 (7.69%)  1
Metabolism and nutrition disorders   
Type 2 diabetes mellitus  1  1/13 (7.69%)  1
Musculoskeletal and connective tissue disorders   
Musculoskeletal discomfort  1  1/13 (7.69%)  1
Pain in extremity  1  1/13 (7.69%)  1
Skin and subcutaneous tissue disorders   
Pruritus  1  1/13 (7.69%)  1
Vascular disorders   
Haemorrhage  1  1/13 (7.69%)  1
Hypertension  1  1/13 (7.69%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 161
This is a single armed study having no comparator.
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 Registry (GCR, 1452)
Organization: Novo Nordisk A/S
EMail: clinicaltrials@novonordisk.com
Publications:
Escobar M, Colberg T, Karim F, Caliskan U, Chowdary P, Giangrande P, Giermasz A, Mancuso ME, Serban M, Tsay W, Zak M and Mahlangu J. Perioperative hemostatic management of major surgery in hemophilia B with long-acting recombinant glycopegylated factor IX: results from the paradigm™3 clinical trial. Journal of Thrombosis and Haemostasis (Abstracts) 2015; 13 (Supplement S2): 1-997 [OR348]
Layout table for additonal information
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01386528    
Other Study ID Numbers: NN7999-3773
2010-023070-40 ( EudraCT Number )
U1111-1121-4554 ( Other Identifier: WHO )
First Submitted: June 30, 2011
First Posted: July 1, 2011
Results First Submitted: June 21, 2017
Results First Posted: July 24, 2017
Last Update Posted: August 23, 2017