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Safety and Efficacy of Turoctocog Alfa in Prevention and Treatment of Bleeds in Previously Untreated Children With Haemophilia A (guardian™4)

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: NCT01493778
Recruitment Status : Completed
First Posted : December 16, 2011
Results First Posted : October 30, 2018
Last Update Posted : January 14, 2020
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Brief Summary:
This trial is conducted in Asia, Europe and North America. The purpose of the trial is to evaluate the safety and efficacy of turoctocog alfa in prevention and treatment of bleeds in previously untreated children with haemophilia A.

Condition or disease Intervention/treatment Phase
Congenital Bleeding Disorder Haemophilia A Drug: turoctocog alfa Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Turoctocog Alfa in Prevention and Treatment of Bleeds in Paediatric Previously Untreated Patients With Haemophilia A
Actual Study Start Date : September 17, 2012
Actual Primary Completion Date : August 16, 2017
Actual Study Completion Date : December 5, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding Hemophilia

Arm Intervention/treatment
Experimental: turoctocog alfa Drug: turoctocog alfa
Patients will be scheduled to receive treatment with turoctocog alfa for at least 100 exposure days. In most cases, treatment will be given at home with intravenous (i.v., into the vein) self-injection by the parent/caregiver/support person.




Primary Outcome Measures :
  1. Incidence Rate of Factor VIII Inhibitors (Above or Equal to 0.6 BU (Bethesda Units)/mL) for the Main Phase of the Trial [ Time Frame: From Visit 2 (21 days after screening) to Visit 5 (50-55 exposure day) ]
    The incidence rate (percentage of participants with inhibitors) of inhibitors defined as inhibitor titres ≥0.6 BU for main phase of the trial.


Secondary Outcome Measures :
  1. Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None [ Time Frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial ]
    The haemostatic effect of turoctocog alfa was summarised by frequency tables containing count of all bleeds and assessed on a predefined four point scale: Excellent, Good, Moderate and None. The analysis was based on the total number of bleeds and their response to treatment. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.

  2. Annualised Bleeding Rate (ABR) [ Time Frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial ]
    Annualised bleeding rate defined as number of bleeds in total per patient per year following treatment were estimated by a Poisson model allowing for over-dispersion. The Poisson estimate is presented with a 95% confidence interval (CI). The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.

  3. Number of Turoctocog Alfa (N8) Injections Required Per Bleed [ Time Frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial ]
    The number of injections of turoctocog alfa (N8) required per bleed was calculated as the number of injections of turoctocog alfa used in the time period from start of the bleed to stop of the bleed. The mean number of turoctocog alfa injections required to stop the bleed is presented. The analysis was based on the total number of bleeds. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.

  4. Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Month [ Time Frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial ]
    Mean total consumption of turoctocog alfa (N8) used for treatment (includes all injections given: prevention, treatment of bleeds and during surgery) per patient per month. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.

  5. Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Year [ Time Frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial ]
    Mean total consumption of turoctocog alfa (N8) used for treatment (includes all injections given: prevention, treatment of bleeds and during surgery) per patient per year. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.

  6. Consumption of Turoctocog Alfa (N8) (IU/kg/Bleed) Per Bleed [ Time Frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial ]
    Mean consumption of turoctocog alfa (N8) used for treatment of bleed from start to stop of bleed. The analysis was based on number of bleeds. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.

  7. Consumption of Turoctocog Alfa (N8) (IU/kg/Months) for Bleed Prevention [ Time Frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial ]
    Mean consumption of turoctocog alfa (N8) used for preventive treatment per month per patient. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.

  8. Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) Reported During the Trial Period [ Time Frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial ]
    Number of adverse events and serious adverse events per patient years of exposure. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial (exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.

  9. Incidence Rate of Clinically Relevant Inhibitors Defined as an Inhibitor Titre (≥ 0.6 BU/mL) Combined With a Decreased Recovery (<66% of Expected Level) [ Time Frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial ]
    The incidence rates (number of patients with new inhibitor in the period/number of participants at risk, expressed in percentage) of clinically relevant inhibitors were defined as an inhibitor titre (≥ 0.6 BU) combined with a decreased recovery (<66% of expected level). Incidence rate of clinically relevant inhibitors according to the type of assay used is presented. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation) and the combined main and extension phase (from Visit 2 to end of trial).

  10. Incidence Rate of High-titre Inhibitors Defined as Inhibitor Titre ≥ 5 BU (Bethesda Units)/mL) [ Time Frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial ]
    Incidence rate (number of patients with new inhibitor in the period/number of participants at risk, expressed in percentage) of high-titre inhibitors defined as inhibitor titre ≥ 5 BU (Bethesda Units)/mL). The inhibitors were evaluated for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation) and the combined main and extension phase (from Visit 2 to end of trial).

  11. Change in Total Scores for Parent Reported Treatment Satisfaction [ Time Frame: Visit 3 (10th-15th ED); Visit 5 (50th-55th ED); End of trial (within 8 weeks of their last scheduled visit in the extension phase) ]

    The caregivers/parent reported treatment satisfaction is assessed by the parents using the haemophilia satisfaction questionnaire (HEMO-SAT). The questionnaire contained questions related to treatment that covered 6 domains (ease and convenience, efficacy, burden, specialist, centre and general satisfaction). Adults completing the questionnaire could achieve a score from 0 to 100, with lower scores reflecting greater treatment satisfaction. The scale range for each of the 6 domains was 0-100 with lower scores reflecting greater treatment satisfaction.

    The scores of the domains at visit 3 (10th-15th ED), visit 5 (50th-55th ED) and end of trial (EoT) are presented.


  12. Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Month Per Patient) [ Time Frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial ]
    Resource utilisation and caregiver burden are analysed in terms of average number of days absent from work and use of mobility aids (e.g. wheelchair or crutches) as a consequence of bleeds. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.

  13. Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Year Per Patient) [ Time Frame: From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial ]
    Resource utilisation and caregiver burden are analysed in terms of average number of days of absence from work and use of mobility aids (e.g. wheelchair or crutches) as a consequence of bleeds. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.



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Ages Eligible for Study:   up to 6 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age below 6 years
  • Informed consent obtained before any trial-related activities (trial-related activities are any procedure that would not have been performed during normal management of the patient)
  • Male patients diagnosed with congenital severe haemophilia A (FVIII level equal to or below 1%)
  • No prior use of purified clotting factor products (previous exposure, equal to or less than 5 ED to blood components, e.g. cryoprecipitate, fresh frozen plasma, is accepted) including commercially available NovoEight® /Novoeight®

Exclusion Criteria:

  • Known or suspected allergy to hamster protein or intolerance to trial product(s) or related products
  • Previous participation in this trial defined as withdrawal after administration of trial product
  • Congenital or acquired coagulation disorders other than haemophilia A
  • Any history of Factor VIII inhibitor
  • Ongoing treatment or planned treatment during the trial with immunomodulatory agents (e.g. intravenous immunoglobulin (IVIG), routine systemic corticosteroids)

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): NCT01493778


Locations
Show Show 69 study locations
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
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Study Director: Global Clinical Registry (GCR, 1452) Novo Nordisk A/S
  Study Documents (Full-Text)

Documents provided by Novo Nordisk A/S:

Additional Information:
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Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01493778    
Other Study ID Numbers: NN7008-3809
U1111-1119-6116 ( Other Identifier: WHO )
2011-001033-16 ( EudraCT Number )
P/50/2010 ( Other Identifier: EMA (PDCO) )
JapicCTI-142544 ( Other Identifier: JAPIC )
CTR20150455 ( Registry Identifier: ChinaDrugTrials )
First Posted: December 16, 2011    Key Record Dates
Results First Posted: October 30, 2018
Last Update Posted: January 14, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hemostatic Disorders
Hemophilia A
Blood Coagulation Disorders
Blood Coagulation Disorders, Inherited
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Vascular Diseases
Cardiovascular Diseases
Factor VIII
Coagulants