Back to resultsSafety 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)
Primary Purpose
Congenital Bleeding Disorder, Haemophilia B
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
nonacog beta pegol
nonacog beta pegol
nonacog beta pegol
Sponsored by
About this trial
This is an interventional treatment trial for Congenital Bleeding Disorder
Eligibility Criteria
Inclusion Criteria:
- Previous participation in NN7999-3747 (NCT01333111) and/or NN7999-3773
Exclusion Criteria:
- Known history of FIX inhibitors based on existing medical records, laboratory report reviews and patient and LAR (legal acceptable representative) interviews
- Current FIX inhibitors above or equal to 0.6 BU (Bethesda Units)
- Congenital or acquired coagulation disorders other than haemophilia B
- Previous arterial thrombotic events (e.g. myocardial infarction and intracranial thrombosis) or previous deep venous thrombosis or pulmonary embolism (as defined by available medical records)
- Any disease (liver, kidney, inflammatory and mental disorders included) or condition which, according to the Investigator's (trial physician) judgement, could imply a potential hazard to the patient, interfere with trial participation, or interfere with trial outcome
Sites / Locations
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Prophylaxis, high dose (once weekly)
Prophylaxis, low dose (once weekly)
On-demand
Prophylaxis, high dose (every second week)
Arm Description
Outcomes
Primary Outcome Measures
Incidence of Inhibitory Antibodies Against FIX Defined as Titre Above or Equal to 0.6 BU (Bethesda Units)
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.
Secondary Outcome Measures
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)
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.
Number of Bleeding Episodes During Routine Prophylaxis
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.
FIX Trough Levels
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.
Incidence of Adverse Events (AEs)
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).
Incidence of Serious Adverse Events (SAEs)
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01395810
Brief Title
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
Acronym
paradigm™ 4
Official Title
Safety and Efficacy of NNC-0156-0000-0009 After Long-Term Exposure in Patients With Haemophilia B
Study Type
Interventional
2. Study Status
Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
April 15, 2012 (Actual)
Primary Completion Date
March 30, 2014 (Actual)
Study Completion Date
March 30, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novo Nordisk A/S
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This trial is conducted in Asia, Europe, Japan, North America and South Africa. The aim is to evaluate the safety and efficacy of nonacog beta pegol (NNC-0156-0000-0009) after long-term exposure in patients with haemophilia B.
This trial is an extension to trials NN7999-3747 (NCT01333111/paradigm™ 2) and NN7999-3773 (NCT01386528/paradigm™ 3).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congenital Bleeding Disorder, Haemophilia B
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
71 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Prophylaxis, high dose (once weekly)
Arm Type
Experimental
Arm Title
Prophylaxis, low dose (once weekly)
Arm Type
Experimental
Arm Title
On-demand
Arm Type
Experimental
Arm Title
Prophylaxis, high dose (every second week)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
nonacog beta pegol
Other Intervention Name(s)
NNC-0156-0000-0009
Intervention Description
One single dose administered intravenously (into the vein) once weekly. Patients will receive instruction on how to treat any bleeding episode they may experience.
Intervention Type
Drug
Intervention Name(s)
nonacog beta pegol
Other Intervention Name(s)
NNC-0156-0000-0009
Intervention Description
One single dose administered intravenously (into the vein). Patients will treat themselves with either a low or a high dose dependent on the severity of the bleeding episode.
Intervention Type
Drug
Intervention Name(s)
nonacog beta pegol
Other Intervention Name(s)
NNC-0156-0000-0009
Intervention Description
One single dose administered intravenously (into the vein) every second week. Patients will receive instruction on how to treat any bleeding episode they may experience.
Primary Outcome Measure Information:
Title
Incidence of Inhibitory Antibodies Against FIX Defined as Titre Above or Equal to 0.6 BU (Bethesda Units)
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
Secondary Outcome Measure Information:
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)
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
Title
Number of Bleeding Episodes During Routine Prophylaxis
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
Title
FIX Trough Levels
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
Title
Incidence of Adverse Events (AEs)
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
Title
Incidence of Serious Adverse Events (SAEs)
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
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
13 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Previous participation in NN7999-3747 (NCT01333111) and/or NN7999-3773
Exclusion Criteria:
Known history of FIX inhibitors based on existing medical records, laboratory report reviews and patient and LAR (legal acceptable representative) interviews
Current FIX inhibitors above or equal to 0.6 BU (Bethesda Units)
Congenital or acquired coagulation disorders other than haemophilia B
Previous arterial thrombotic events (e.g. myocardial infarction and intracranial thrombosis) or previous deep venous thrombosis or pulmonary embolism (as defined by available medical records)
Any disease (liver, kidney, inflammatory and mental disorders included) or condition which, according to the Investigator's (trial physician) judgement, could imply a potential hazard to the patient, interfere with trial participation, or interfere with trial outcome
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Global Clinical Registry (GCR, 1452)
Organizational Affiliation
Novo Nordisk A/S
Official's Role
Study Director
Facility Information:
Facility Name
Novo Nordisk Investigational Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027-6016
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198-5456
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07102
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Wien
ZIP/Postal Code
1090
Country
Austria
Facility Name
Novo Nordisk Investigational Site
City
Bron Cedex
ZIP/Postal Code
69677
Country
France
Facility Name
Novo Nordisk Investigational Site
City
Kremlin-Bicêtre
ZIP/Postal Code
94270
Country
France
Facility Name
Novo Nordisk Investigational Site
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
Novo Nordisk Investigational Site
City
Duisburg
ZIP/Postal Code
47051
Country
Germany
Facility Name
Novo Nordisk Investigational Site
City
Giessen
ZIP/Postal Code
35392
Country
Germany
Facility Name
Novo Nordisk Investigational Site
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Novo Nordisk Investigational Site
City
Athens
ZIP/Postal Code
GR-11527
Country
Greece
Facility Name
Novo Nordisk Investigational Site
City
Firenze
ZIP/Postal Code
50134
Country
Italy
Facility Name
Novo Nordisk Investigational Site
City
Milano
ZIP/Postal Code
20124
Country
Italy
Facility Name
Novo Nordisk Investigational Site
City
Kashihara-shi, Nara
ZIP/Postal Code
634 8522
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Kawasaki-shi, Kanagawa
ZIP/Postal Code
216-8511
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Nagoya-shi, Aichi
ZIP/Postal Code
466 8560
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Nishinomiya-shi
ZIP/Postal Code
663 8051
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Shinjuku-ku, Tokyo
ZIP/Postal Code
160 0023
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Suginami-ku, Tokyo
ZIP/Postal Code
167 0035
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Skopje
ZIP/Postal Code
1000
Country
Macedonia, The Former Yugoslav Republic of
Facility Name
Novo Nordisk Investigational Site
City
Kuala Lumpur
ZIP/Postal Code
50400
Country
Malaysia
Facility Name
Novo Nordisk Investigational Site
City
Utrecht
ZIP/Postal Code
3584 CX
Country
Netherlands
Facility Name
Novo Nordisk Investigational Site
City
Timisoara
State/Province
Timis
ZIP/Postal Code
300011
Country
Romania
Facility Name
Novo Nordisk Investigational Site
City
Moscow
ZIP/Postal Code
105077
Country
Russian Federation
Facility Name
Novo Nordisk Investigational Site
City
Saint-Petersburg
ZIP/Postal Code
191119
Country
Russian Federation
Facility Name
Novo Nordisk Investigational Site
City
Parktown Johannesburg
State/Province
Gauteng
ZIP/Postal Code
2193
Country
South Africa
Facility Name
Novo Nordisk Investigational Site
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Novo Nordisk Investigational Site
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Novo Nordisk Investigational Site
City
Taipei
ZIP/Postal Code
100
Country
Taiwan
Facility Name
Novo Nordisk Investigational Site
City
Bangkok
ZIP/Postal Code
10400
Country
Thailand
Facility Name
Novo Nordisk Investigational Site
City
Ankara
ZIP/Postal Code
06500
Country
Turkey
Facility Name
Novo Nordisk Investigational Site
City
Kayseri
ZIP/Postal Code
38010
Country
Turkey
Facility Name
Novo Nordisk Investigational Site
City
Konya
ZIP/Postal Code
42090
Country
Turkey
Facility Name
Novo Nordisk Investigational Site
City
Basingstoke
ZIP/Postal Code
RG24 9NA
Country
United Kingdom
Facility Name
Novo Nordisk Investigational Site
City
Cardiff
ZIP/Postal Code
CF14 4XW
Country
United Kingdom
Facility Name
Novo Nordisk Investigational Site
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
Facility Name
Novo Nordisk Investigational Site
City
London
ZIP/Postal Code
SE1 7EH
Country
United Kingdom
Facility Name
Novo Nordisk Investigational Site
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
Facility Name
Novo Nordisk Investigational Site
City
Oxford
ZIP/Postal Code
OX3 7LJ
Country
United Kingdom
12. IPD Sharing Statement
Citations:
Citation
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
Results Reference
background
PubMed Identifier
26970716
Citation
Young G, Collins PW, Colberg T, Chuansumrit A, Hanabusa H, Lentz SR, Mahlangu J, Mauser-Bunschoten EP, Negrier C, Oldenburg J, Patiroglu T, Santagostino E, Tehranchi R, Zak M, Karim FA. Nonacog beta pegol (N9-GP) in haemophilia B: A multinational phase III safety and efficacy extension trial (paradigm4). Thromb Res. 2016 May;141:69-76. doi: 10.1016/j.thromres.2016.02.030. Epub 2016 Mar 2.
Results Reference
result
PubMed Identifier
27352908
Citation
Chowdary P, Kearney S, Regnault A, Hoxer CS, Yee DL. Improvement in health-related quality of life in patients with haemophilia B treated with nonacog beta pegol, a new extended half-life recombinant FIX product. Haemophilia. 2016 Jul;22(4):e267-74. doi: 10.1111/hae.12995. Epub 2016 Jun 28.
Results Reference
result
Links:
URL
http://novonordisk-trials.com
Description
Clinical Trials at Novo Nordisk
Learn more about this trial
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
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