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

Congenital Bleeding Disorder Clinical Trial

— paradigm™ 4  

Official title:

Safety and Efficacy of NNC-0156-0000-0009 After Long-Term Exposure in Patients With Haemophilia B

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01395810
• Other study ID #: NN7999-3775
• Secondary ID: 2010-023072-17U1
• Status: Completed
• Phase: Phase 3
• Start date: April 15, 2012
• Est. completion date: March 30, 2014

Study information

• Verified date: April 2018
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: March 30, 2014
• Est. primary completion date: March 30, 2014
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 13 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Blood Coagulation Disorders
• Congenital Bleeding Disorder
• Haemophilia B
• Hemophilia A
• Hemophilia B
• Hemostatic Disorders

Intervention

Drug:
• nonacog beta pegol
One single dose administered intravenously (into the vein) once weekly. Patients will receive instruction on how to treat any bleeding episode they may experience.
• nonacog beta pegol
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.
• nonacog beta pegol
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.

Locations

Country	Name	City	State
Austria	Novo Nordisk Investigational Site	Wien
France	Novo Nordisk Investigational Site	Bron Cedex
France	Novo Nordisk Investigational Site	Kremlin-Bicêtre
Germany	Novo Nordisk Investigational Site	Bonn
Germany	Novo Nordisk Investigational Site	Duisburg
Germany	Novo Nordisk Investigational Site	Giessen
Germany	Novo Nordisk Investigational Site	Hannover
Greece	Novo Nordisk Investigational Site	Athens
Italy	Novo Nordisk Investigational Site	Firenze
Italy	Novo Nordisk Investigational Site	Milano
Japan	Novo Nordisk Investigational Site	Kashihara-shi, Nara
Japan	Novo Nordisk Investigational Site	Kawasaki-shi, Kanagawa
Japan	Novo Nordisk Investigational Site	Nagoya-shi, Aichi
Japan	Novo Nordisk Investigational Site	Nishinomiya-shi
Japan	Novo Nordisk Investigational Site	Shinjuku-ku, Tokyo
Japan	Novo Nordisk Investigational Site	Suginami-ku, Tokyo
Macedonia, The Former Yugoslav Republic of	Novo Nordisk Investigational Site	Skopje
Malaysia	Novo Nordisk Investigational Site	Kuala Lumpur
Netherlands	Novo Nordisk Investigational Site	Utrecht
Romania	Novo Nordisk Investigational Site	Timisoara	Timis
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Saint-Petersburg
South Africa	Novo Nordisk Investigational Site	Parktown Johannesburg	Gauteng
Spain	Novo Nordisk Investigational Site	Madrid
Spain	Novo Nordisk Investigational Site	Valencia
Taiwan	Novo Nordisk Investigational Site	Taipei
Thailand	Novo Nordisk Investigational Site	Bangkok
Turkey	Novo Nordisk Investigational Site	Ankara
Turkey	Novo Nordisk Investigational Site	Kayseri
Turkey	Novo Nordisk Investigational Site	Konya
United Kingdom	Novo Nordisk Investigational Site	Basingstoke
United Kingdom	Novo Nordisk Investigational Site	Cardiff
United Kingdom	Novo Nordisk Investigational Site	London
United Kingdom	Novo Nordisk Investigational Site	London
United Kingdom	Novo Nordisk Investigational Site	Manchester
United Kingdom	Novo Nordisk Investigational Site	Oxford
United States	Novo Nordisk Investigational Site	Augusta	Georgia
United States	Novo Nordisk Investigational Site	Baltimore	Maryland
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Iowa City	Iowa
United States	Novo Nordisk Investigational Site	Jacksonville	Florida
United States	Novo Nordisk Investigational Site	Los Angeles	California
United States	Novo Nordisk Investigational Site	Minneapolis	Minnesota
United States	Novo Nordisk Investigational Site	New York	New York
United States	Novo Nordisk Investigational Site	Newark	New Jersey
United States	Novo Nordisk Investigational Site	Omaha	Nebraska
United States	Novo Nordisk Investigational Site	San Francisco	California
United States	Novo Nordisk Investigational Site	Syracuse	New York
United States	Novo Nordisk Investigational Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Austria,  France,  Germany,  Greece,  Italy,  Japan,  Macedonia, The Former Yugoslav Republic of,  Malaysia,  Netherlands,  Romania,  Russian Federation,  South Africa,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

References & Publications (3)

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: — View 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

Young G, Collins PW, Colberg T, Chuansumrit A, Hanabusa H, Lentz SR, Mahlangu J, Mauser-Bunschoten EP, Négrier C, Oldenburg J, Patiroglu T, Santagostino E, Tehranchi R, Zak M, Karim FA. Nonacog beta pegol (N9-GP) in haemophilia B: A multinational phase II — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From Day 1 up to 2 years
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)	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.	From Day 1 up to 2 years
Secondary	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.	From Day 1 up to 2 years
Secondary	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.	From Day 1 up to 2 years
Secondary	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).	From Day 1 up to 2 years
Secondary	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).	From Day 1 up to 2 years

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