Safety and Efficacy of Turoctocog Alfa (N8) in Prevention and On-demand Treatment of Bleeding Episodes in Subjects With Haemophilia A: An Extension to Trials NN7008-3543, NN7008-3545, NN7008-3600, NN7008-3893 and NN7008-4015

Study Overview
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Brief Summary
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This trial is conducted in Asia, Europe, Japan, Oceania, North America and South America. The aim of the trial is to investigate the safety and efficacy of turoctocog alfa (N8) in Haemophilia A patients. The trial is an extension to trials NN7008-3543 (start: March 2009, stop: September 2011) and NN7008-3545 (start: May 2010, stop: November 2011) and the pharmacokinetic trials NN7008-3600 (start: November 2010, stop: October 2011), NN7008-3893 (start: June 2011, stop: September 2011) and NN7008-4015 (start: August 2012, stop: March 2013).

Official Title
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Safety and Efficacy of N8 in Prevention and On-demand Treatment of Bleeding Episodes in Subjects With Haemophilia A

Conditions
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Congenital Bleeding Disorder, Haemophilia A

Intervention / Treatment
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* Drug: turoctocog alfa
* Drug: turoctocog alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed Consent obtained before any trial-related activities Completion of trial NN7008-3543 or paediatric trial NN7008-3545 or Japanese trial NN7008-3600 or pharmacokinetic trial NN7008-3893 or NN7008-4015 Exclusion Criteria: Previous participation in the current trial (defined as withdrawal) or withdrawn subjects from NN7008-3522, NN7008-3543, NN7008-3545, NN7008-3600, NN7008-3893 or NN7008-4015 after administration of trial product

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Turoctocog alfa<br> | Drug: turoctocog alfa<br>* The preventative treatment is administered intravenously (i.v.) at specific intervals either every second day or three times a week. Bleeding treatment will be administered if a bleed should occur.<br>Drug: turoctocog alfa<br>* Treatment is administered intravenously (i.v.) during bleeds and occasionally as a preventative treatment (e.g. before physical activity)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Development of FVIII Inhibitors (Greater Than or Equal to 0.6 Bethesda Units (BU)/mL) | The frequency of inhibitors was calculated as number of patients with inhibitors during the trial divided by number of patients in the trial. This endpoint was measured during the trial. | After 90 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Adverse Events and Serious Adverse Events | The number of adverse events and serious adverse events reported during the main trial and the on-demand sub-trial (during 90 months). | After 90 months | 
| Annualised Bleeding Rate Reported During the Prevention Period (Only Applicable for Subjects in the Preventive Regimen) | The number of bleeding episodes per year reported during the prevention period (during 90 months). | After 90 months | 
| Haemostatic Response to Turoctocog Alfa (None, Moderate, Good or Excellent) in Treatment of Bleeds. | Haemostatic response to turoctocog alfa (none, moderate, good or excellent) in treatment of bleeds using a four-point response scale: none, moderate, good or excellent. The evaluation was done by patient, caregiver and/or investigator based on experience as follows: 1. Excellent: Abrupt pain relief and/or unequivocal improvement in objective signs of bleeding within approximately 8 hours after a single infusion 2. Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hours after an infusion, but possibly requiring more than 1 infusion for complete resolution. 3. Moderate: Probable or slight beneficial effect within approximately 8 hours after the first infusion; usually requiring more than 1 infusion. 4. None: No improvement, or worsening of symptoms. This endpoint is measured during the preventive and on-demand sub-trial (during 90 months). | After 90 months |