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Safety and Efficacy of NNC-0156-0000-0009 in Haemophilia B Patients (paradigm™ 2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01333111
Recruitment Status : Completed
First Posted : April 11, 2011
Results First Posted : July 28, 2017
Last Update Posted : July 28, 2017
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Brief Summary:
This trial is conducted in Africa, Asia, Europe, Japan and North America. The aim of this trial is to evaluate the safety and efficacy, including pharmacokinetics (the rate at which the body eliminates the trial drug), of NNC-0156-0000-0009 (nonacog beta pegol) when used for treatment and prophylaxis of bleeding episodes in patients with haemophilia B.

Condition or disease Intervention/treatment Phase
Congenital Bleeding Disorder Haemophilia B Drug: nonacog beta pegol Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 74 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: A Multi-centre, Single-blind Trial Evaluating Safety and Efficacy, Including Pharmacokinetics, of NNC-0156-0000-0009 When Used for Treatment and Prophylaxis of Bleeding Episodes in Patients With Haemophilia B
Actual Study Start Date : April 27, 2011
Actual Primary Completion Date : March 31, 2013
Actual Study Completion Date : March 31, 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding

Arm Intervention/treatment
Experimental: Prophylaxis, high dose (trial duration 52 weeks) 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
Other Name: NNC-0156-0000-0009

Experimental: Prophylaxis, low dose (trial duration 52 weeks) 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
Other Name: NNC-0156-0000-0009

Experimental: On-demand (trial duration 28 weeks) Drug: nonacog beta pegol
Patients will treat themselves with either a low or a high dose dependent on the severity of the bleeding episode
Other Name: NNC-0156-0000-0009




Primary Outcome Measures :
  1. Incidence of Inhibitory Antibodies Against Factor IX Defined as Titre Equal to or Above 0.6 BU (Bethesda Units) [ Time Frame: 52 weeks after treatment start for patients on prophylaxis ]
    Inhibitors were analysed with either the Nijmegen modified factor IX Bethesda assay or a heat/cold Nijmegen modified factor IX Bethesda assay. Number of subjects who developed inhibitory antibodies against factor IX are reported.

  2. Incidence of Inhibitory Antibodies Against Factor IX Defined as Titre Equal to or Above 0.6 BU (Bethesda Units) [ Time Frame: 28 weeks after treatment start on on-demand treatment ]
    Inhibitors were analysed with either the Nijmegen modified factor IX Bethesda assay or a heat/cold Nijmegen modified factor IX Bethesda assay. Number of subjects who developed inhibitory antibodies against factor IX are reported.


Secondary Outcome Measures :
  1. Haemostatic Effect of NNC-0156-0000-0009 When Used for Prophylaxis of Bleeding Episodes, Assessed as Success/Failure Based on a Four-point Scale for Haemostatic Response [ Time Frame: 52 weeks after treatment start for patients on prophylaxis ]

    Haemostatic response after treatment of a bleed with nonacog beta pegol was evaluated on a 4 point scale as excellent, good, moderate or poor. A success rate was calculated based on counting good or excellent as successes and poor and moderate as failures.

    • Excellent - abrupt pain relief and/or clear improvement in objective signs of bleeding within 8 hours after a single injection
    • Good - noticeable pain relief and/or improvement in signs of bleeding within 8 hours after a single injection
    • Moderate - probable or slight beneficial effect within the first 8 hours after the first injection but requiring more than one injection within 8 hours
    • Poor - no improvement, or worsening of symptoms within 8 hours after two injections.

    The success rate and 95% confidence interval (CI) are reported here.


  2. Haemostatic Effect of NNC-0156-0000-0009 When Used for Treatment of Bleeding Episodes, Assessed as Success/Failure Based on a Four-point Scale for Haemostatic Response [ Time Frame: 28 weeks after treatment start on on-demand treatment ]

    Haemostatic response after treatment of a bleed with nonacog beta pegol was evaluated on a 4 point scale as excellent, good, moderate or poor. A success rate was calculated based on counting good or excellent as successes and poor and moderate as failures.

    • Excellent - abrupt pain relief and/or clear improvement in objective signs of bleeding within 8 hours after a single injection
    • Good - noticeable pain relief and/or improvement in signs of bleeding within 8 hours after a single injection
    • Moderate - probable or slight beneficial effect within the first 8 hours after the first injection but requiring more than one injection within 8 hours
    • Poor - no improvement, or worsening of symptoms within 8 hours after two injections.

    The success rate and 95% confidence interval (CI) are reported here.


  3. Number of Bleeding Episodes Per Patient During Routine Prophylaxis [ Time Frame: 52 weeks after treatment start for patients on prophylaxis ]
    The number of bleeding episodes per patient during routine prophylaxis was assessed using the individual annualised bleeding rates (spontaneous and traumatic bleeding episodes per patient per year).

  4. Factor IX Trough Levels [ Time Frame: 52 weeks after treatment start for patients on prophylaxis ]
    The mean pre-dose factor IX levels was measured with the one-stage clotting assay during the trial. Lowest factor IX activity recorded during single-dose and steady state, immediately before next dose was given. The analysis was based on a mixed model on the log-transformed plasma factor IX activity with subject as a random effect. The estimated mean factor IX trough level was presented back-transformed to the natural scale.

  5. Incidence of Adverse Events (AEs) [ Time Frame: at 56 weeks ±2 weeks for patients on prophylaxis ]
    The incidence of adverse events were summarised by the rate of AEs (number of AEs per patient years of exposure [PYE]). Number of adverse events per PYE is number of adverse events /total time in trial. All adverse events reported are treatment emergent (any adverse events which occurred after trial product administration).

  6. Incidence of Adverse Events (AEs) [ Time Frame: at 32 weeks ±2 weeks for patients on on-demand treatment ]
    The incidence of adverse events were summarised by the rate of AEs (number of AEs per PYE). Number of adverse events per PYE is number of adverse events /total time in trial. All adverse events reported are treatment emergent (any adverse events which occurred after trial product administration).

  7. Incidence of Serious Adverse Events (SAEs) [ Time Frame: at 56 weeks ±2 weeks for patients on prophylaxis ]
    SAE was defined as an AE that resulted in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalisation, persistent/significant disability/incapacity/congenital anomaly/birth defect. The incidence of SAEs were summarised by the rate of SAEs (number of SAEs per PYE). Number of SAEs per PYE is number of SAEs/total time in trial. All SAEs reported are treatment emergent (any serious adverse events which occurred after trial product administration).

  8. Incidence of Serious Adverse Events (SAEs) [ Time Frame: at 32 weeks ±2 weeks for patients on on-demand treatment ]
    SAE was defined as an AE that resulted in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalisation, persistent/significant disability/incapacity/congenital anomaly/birth defect. The incidence of SAEs were summarised by the rate of SAEs (number of SAEs per PYE). Number of SAEs per PYE is number of SAEs/total time in trial. All SAEs reported are treatment emergent (any serious adverse events which occurred after trial product administration).

  9. Host Cell Proteins (HCP) Antibodies [ Time Frame: 52 weeks after treatment start for patients on prophylaxis ]
    Subjects who were positive for anti-Host Cell Protein (HCP) antibodies.

  10. Host Cell Proteins (HCP) Antibodies [ Time Frame: 28 weeks after treatment start on on-demand treatment ]
    Subjects who were positive for anti-HCP antibodies.



Information from the National Library of Medicine

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Ages Eligible for Study:   13 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male patients with moderately severe or severe congenital haemophilia B with a factor IX activity of 2% or below according to medical records
  • History of at least 150 exposure days to other factor IX products
  • Patients currently treated on-demand with at least 6 bleeding episodes during the last 12 months or at least 3 bleeding episodes during the last 6 months, or patients currently on prophylaxis

Exclusion Criteria:

  • Known history of factor IX inhibitors based on existing medical records, laboratory report reviews and patient and legally acceptable representative (LAR) interviews
  • HIV (Human immunodeficiency virus) positive, with a viral load equal to or above 400,000 copies/mL and/or CD4+ lymphocyte count equal to or below 200/microL
  • 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)
  • Immune modulating or chemotherapeutic medication

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01333111


Locations
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United States, California
Novo Nordisk Investigational Site
Los Angeles, California, United States, 90027-6016
United States, Florida
Novo Nordisk Investigational Site
Jacksonville, Florida, United States, 32207
United States, Georgia
Novo Nordisk Investigational Site
Augusta, Georgia, United States, 30912
United States, Iowa
Novo Nordisk Investigational Site
Iowa City, Iowa, United States, 52242
United States, Maryland
Novo Nordisk Investigational Site
Baltimore, Maryland, United States, 21287
United States, Minnesota
Novo Nordisk Investigational Site
Minneapolis, Minnesota, United States, 55404
United States, Nebraska
Novo Nordisk Investigational Site
Omaha, Nebraska, United States, 68198-5456
United States, New Jersey
Novo Nordisk Investigational Site
Newark, New Jersey, United States, 07102
United States, New York
Novo Nordisk Investigational Site
New York, New York, United States, 10029
Novo Nordisk Investigational Site
Syracuse, New York, United States, 13210
United States, Pennsylvania
Novo Nordisk Investigational Site
Hershey, Pennsylvania, United States, 17033
United States, Texas
Novo Nordisk Investigational Site
Houston, Texas, United States, 77030
Canada, Alberta
Novo Nordisk Investigational Site
Edmonton, Alberta, Canada, T6G 2B7
France
Novo Nordisk Investigational Site
Kremlin-Bicêtre, France, 94270
Novo Nordisk Investigational Site
Lyon, France, 69003
Germany
Novo Nordisk Investigational Site
Bonn, Germany, 53127
Novo Nordisk Investigational Site
Duisburg, Germany, 47051
Novo Nordisk Investigational Site
Giessen, Germany, 35392
Novo Nordisk Investigational Site
Hannover, Germany, 30625
Hungary
Novo Nordisk Investigational Site
Budapest, Hungary, H-1134
Italy
Novo Nordisk Investigational Site
Firenze, Italy, 50134
Novo Nordisk Investigational Site
Milano, Italy, 20124
Japan
Novo Nordisk Investigational Site
Kawasaki-shi, Kanagawa, Japan, 216-8511
Novo Nordisk Investigational Site
Nagoya-shi, Aichi, Japan, 466 8560
Novo Nordisk Investigational Site
Nishinomiya-shi, Japan, 663 8051
Novo Nordisk Investigational Site
Shinjuku-ku, Tokyo, Japan, 160 0023
Novo Nordisk Investigational Site
Suginami-ku, Tokyo, Japan, 167 0035
Macedonia, The Former Yugoslav Republic of
Novo Nordisk Investigational Site
Skopje, Macedonia, The Former Yugoslav Republic of, 1000
Malaysia
Novo Nordisk Investigational Site
Kuala Lumpur, Malaysia, 50400
Netherlands
Novo Nordisk Investigational Site
Utrecht, Netherlands, 3584 CX
Russian Federation
Novo Nordisk Investigational Site
Moscow, Russian Federation, 105077
Novo Nordisk Investigational Site
Saint-Petersburg, Russian Federation, 191119
South Africa
Novo Nordisk Investigational Site
Parktown Johannesburg, Gauteng, South Africa, 2193
Thailand
Novo Nordisk Investigational Site
Bangkok, Thailand, 10400
Turkey
Novo Nordisk Investigational Site
Ankara, Turkey, 06500
Novo Nordisk Investigational Site
Kayseri, Turkey, 38010
Novo Nordisk Investigational Site
Konya, Turkey, 42090
United Kingdom
Novo Nordisk Investigational Site
Basingstoke, United Kingdom, RG24 9NA
Novo Nordisk Investigational Site
Cardiff, United Kingdom, CF14 4XW
Novo Nordisk Investigational Site
London, United Kingdom, NW3 2QG
Novo Nordisk Investigational Site
London, United Kingdom, SE1 7EH
Novo Nordisk Investigational Site
Manchester, United Kingdom, M13 9WL
Novo Nordisk Investigational Site
Oxford, United Kingdom, OX3 7LJ
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
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Study Director: Global Clinical Registry (GCR, 1452) Novo Nordisk A/S
Additional Information:
Publications:
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Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01333111    
Other Study ID Numbers: NN7999-3747
2010-023069-24 ( EudraCT Number )
U1111-1119-6415 ( Other Identifier: WHO )
JapicCTI-111644 ( Other Identifier: Japic )
First Posted: April 11, 2011    Key Record Dates
Results First Posted: July 28, 2017
Last Update Posted: July 28, 2017
Last Verified: June 2017
Additional relevant MeSH terms:
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Hemostatic Disorders
Hemophilia A
Hemophilia B
Blood Coagulation Disorders
Hemorrhage
Pathologic Processes
Blood Coagulation Disorders, Inherited
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Vascular Diseases
Cardiovascular Diseases