Safety and Efficacy of Turoctocog Alfa Pegol (N8-GP) in Previously Untreated Patients With Haemophilia A

Study Overview
=================
Brief Summary
-----------------
This trial is conducted globally. The aim of the trial is to investigate the safety and efficacy of turoctocog alfa pegol (N8-GP) in previously untreated patients (PUPs) with haemophilia A.

Official Title
-----------------
An Open-label Single-arm Multicentre Non-controlled Phase 3a Trial Investigating Safety and Efficacy of N8-GP in Prophylaxis and Treatment of Bleeding Episodes in Previously Untreated Paediatric Patients With Severe Haemophilia A

Conditions
-----------------
Congenital Bleeding Disorder, Haemophilia A

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial Male, age below 6 years of age at the time of signing informed consent Diagnosis of severe haemophilia A (FVIII activity level 1%) based on medical records or central laboratory results No prior use of purified clotting factor products (5 previous exposures to blood components is acceptable) Exclusion Criteria: Any history of FVIII inhibitor (defined by medical records) - Known or suspected hypersensitivity to trial product or related products Previous participation in this trial. Participation is defined as first dose administered of trial product Receipt of any investigational medicinal product within 30 days before screening Congenital or acquired coagulation disorder other than haemophilia A Any chronic disorder or severe disease which, in the opinion of the Investigator, might jeopardise the patient's safety or compliance with the protocol Patient's parent(s')/legally acceptable representative (LAR(s')) mental incapacity, unwillingness to cooperate, or a language barrier precluding adequate understanding and cooperation

Ages Eligible for Study
-----------------
Minimum Age: 0 Years
Maximum Age: 6 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 50 EDs (exposure days)<br> | Drug: turoctocog alfa pegol<br>* For intravenous (i.v.) injection. Frequency and dosage (20-75 U/kg) dependent on whether given as treatment for bleeding episode or as prophylaxis<br>* Other names: N8-GP;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of inhibitory antibodies against coagulation factor VIII (FVIII) |  | When the first 50 PUP have reached at least 50 exposure dates. (Expected to reach between 6 - 18 months) | 
| Incidence of inhibitory antibodies against coagulation factor VIII (FVIII) |  | At the end of the trial. End of trial will be up to 4 years after the patient has reached 100 exposure dates. (Expected to reach between 12 - 60 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of adverse events including serious adverse events and medical events of special interest |  | When the first 50 PUPs have reached at least 50 exposure days, and at end of trial. End of trial will be up to 4 years after the first patient has reached 100 exposure days | 
| Incidence of confirmed high titre inhibitors (defined as inhibitor titre above 5 Bethesda Units (BU) |  | When the first 50 PUPs have reached at least 50 exposure days, and at end of trial. End of trial will be up to 4 years after the first patient has reached 100 exposure days | 
| Number of breakthrough bleeding episodes during prophylaxis with turoctocog alfa pegol (N8-GP) (annualised bleeding rate) |  | When the first 50 PUPs have reached at least 50 exposure days, and at end of trial. End of trial will be up to 4 years after the first patient has reached 100 exposure days | 
| Haemostatic effect of N8-GP in treatment of bleeding episodes, assessed by a predefined 4-point haemostatic response scale (excellent, good, moderate and none) |  | When the first 50 PUPs have reached at least 50 exposure days, and at end of trial. End of trial will be up to 4 years after the first patient has reached 100 exposure days | 
| Consumption of N8-GP for prophylaxis (number of injections and U/Kg per month and per year) |  | When the first 50 PUPs have reached at least 50 exposure days, and at end of trial. End of trial will be up to 4 years after the first patient has reached 100 exposure days | 
| Consumption of N8-GP for treatment of bleeding episodes (number of injections and U/Kg required per bleeding episode) |  | When the first 50 PUPs have reached at least 50 exposure days, and at end of trial. End of trial will be up to 4 years after the first patient has reached 100 exposure days | 
| Total consumption of N8-GP per patient (prevention and treatment of bleeding episodes) per month and annualised value |  | When the first 50 PUPs have reached at least 50 exposure days, and at end of trial. End of trial will be up to 4 years after the first patient has reached 100 exposure days | 
| Outcome of immune tolerance induction (ITI), assessed by a predefined 4-point ITI outcome scale (success, partial success, failure, other) |  | When the first 50 PUPs have reached at least 50 exposure days, and at end of trial. End of trial will be up to 4 years after the first patient has reached 100 exposure days |