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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

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
Prophylaxis 10 IU/kg 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.
Prophylaxis 40 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.
Prophylaxis 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.
On-demand 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.

Participant Flow:   Overall Study
    Prophylaxis 10 IU/kg   Prophylaxis 40 IU/kg   Prophylaxis 80 IU/kg   On-demand
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 
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.



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set (FAS) consisted of all subjects exposed to nonacog beta pegol.

Reporting Groups
  Description
Prophylaxis 10 IU/kg 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.
Prophylaxis 40 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.
Prophylaxis 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.
On-demand 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 Total of all reporting groups

Baseline Measures
   Prophylaxis 10 IU/kg   Prophylaxis 40 IU/kg   Prophylaxis 80 IU/kg   On-demand   Total 
Overall Participants Analyzed 
[Units: Participants]
 18   48   0   5   71 
Age 
[Units: Years]
Mean (Standard Deviation)
 32.2  (13.6)   31.4  (14.4)      37.6  (15.4)   32.0  (14.2) 
Age, Customized 
[Units: Participants]
         
13 - 17 years   3   12      0   15 
18 - 70 years   15   36      5   56 
Sex: Female, Male 
[Units: Participants]
Count of 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% 


  Outcome Measures

1.  Primary:   Incidence of Inhibitory Antibodies Against FIX Defined as Titre Above or Equal to 0.6 BU (Bethesda Units)   [ Time Frame: From Day 1 up to 2 years ]

2.  Secondary:   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)   [ Time Frame: From Day 1 up to 2 years ]

3.  Secondary:   Number of Bleeding Episodes During Routine Prophylaxis   [ Time Frame: From Day 1 up to 2 years ]

4.  Secondary:   FIX Trough Levels   [ Time Frame: From Day 1 up to 2 years ]

5.  Secondary:   Incidence of Adverse Events (AEs)   [ Time Frame: From Day 1 up to 2 years ]

6.  Secondary:   Incidence of Serious Adverse Events (SAEs)   [ Time Frame: From Day 1 up to 2 years ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Global Clinical Registry (GCR, 1452)
Organization: Novo Nordisk A/S
e-mail: clinicaltrials@novonordisk.com


Publications of Results:
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