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

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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

Tracking Information
First Submitted Date  ICMJE April 8, 2011
First Posted Date  ICMJE April 11, 2011
Results First Submitted Date  ICMJE June 27, 2017
Results First Posted Date  ICMJE July 28, 2017
Last Update Posted Date July 28, 2017
Actual Study Start Date  ICMJE April 27, 2011
Actual Primary Completion Date March 31, 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 27, 2017)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 8, 2011)
  • 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 ]
  • 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 ]
Change History Complete list of historical versions of study NCT01333111 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2017)
  • 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.
  • 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.
  • 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).
  • 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.
  • 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).
  • 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).
  • 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).
  • 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).
  • 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.
  • Host Cell Proteins (HCP) Antibodies [ Time Frame: 28 weeks after treatment start on on-demand treatment ]
    Subjects who were positive for anti-HCP antibodies.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 8, 2011)
  • 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 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 ]
  • Number of Bleeding Episodes Per Patient During Routine Prophylaxis [ Time Frame: 52 weeks after treatment start for patients on prophylaxis ]
  • Factor IX Trough Levels [ Time Frame: 52 weeks after treatment start for patients on prophylaxis ]
  • Factor IX trough levels [ Time Frame: 28 weeks after treatment start on on-demand treatment ]
  • Incidence of Adverse Events (AEs) [ Time Frame: at 56 weeks ±2 weeks for patients on prophylaxis ]
  • Incidence of Adverse Events (AEs) [ Time Frame: at 32 weeks ±2 weeks for patients on on-demand treatment ]
  • Incidence of Serious Adverse Events (SAEs) [ Time Frame: at 56 weeks ±2 weeks for patients on prophylaxis ]
  • Incidence of Serious Adverse Events (SAEs) [ Time Frame: at 32 weeks ±2 weeks for patients on on-demand treatment ]
  • Host Cell Proteins (HCP) Antibodies [ Time Frame: 52 weeks after treatment start for patients on prophylaxis ]
  • Host Cell Proteins (HCP) Antibodies [ Time Frame: 28 weeks after treatment start on on-demand treatment ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of NNC-0156-0000-0009 in Haemophilia B Patients
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE
  • Congenital Bleeding Disorder
  • Haemophilia B
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • Experimental: Prophylaxis, high dose (trial duration 52 weeks)
    Intervention: Drug: nonacog beta pegol
  • Experimental: Prophylaxis, low dose (trial duration 52 weeks)
    Intervention: Drug: nonacog beta pegol
  • Experimental: On-demand (trial duration 28 weeks)
    Intervention: Drug: nonacog beta pegol
Publications * Collins PW, Young G, Knobe K, Karim FA, Angchaisuksiri P, Banner C, Gürsel T, Mahlangu J, Matsushita T, Mauser-Bunschoten EP, Oldenburg J, Walsh CE, Negrier C; paradigm 2 Investigators. Recombinant long-acting glycoPEGylated factor IX in hemophilia B: a multinational randomized phase 3 trial. Blood. 2014 Dec 18;124(26):3880-6. doi: 10.1182/blood-2014-05-573055. Epub 2014 Sep 26.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 5, 2012)
74
Original Estimated Enrollment  ICMJE
 (submitted: April 8, 2011)
68
Actual Study Completion Date  ICMJE March 31, 2013
Actual Primary Completion Date March 31, 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 13 Years to 70 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Canada,   Germany,   Hungary,   Italy,   Japan,   Macedonia, The Former Yugoslav Republic of,   Malaysia,   Netherlands,   Russian Federation,   South Africa,   Thailand,   Turkey,   United Kingdom,   United States
Removed Location Countries Puerto Rico
 
Administrative Information
NCT Number  ICMJE NCT01333111
Other Study ID Numbers  ICMJE NN7999-3747
2010-023069-24 ( EudraCT Number )
U1111-1119-6415 ( Other Identifier: WHO )
JapicCTI-111644 ( Other Identifier: Japic )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novo Nordisk A/S
Study Sponsor  ICMJE Novo Nordisk A/S
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Global Clinical Registry (GCR, 1452) Novo Nordisk A/S
PRS Account Novo Nordisk A/S
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP