Safety, Tolerability, and Pharmacokinetics Study of Turoctocog Alfa Pegol Injected Under the Skin in Patients With Haemophilia A

Study Overview
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Brief Summary
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The trial is conducted in Asia, Europe and North America. The aim of the study is to evaluate the safety of administration under the skin of turoctocog alfa pegol (SC N8-GP) in patients with severe haemophilia A.

Official Title
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Safety, Tolerability, and Pharmacokinetics Study of Single and Multiple Subcutaneous Doses of Turoctocog Alfa Pegol in Patients With Haemophilia A

Conditions
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Congenital Bleeding Disorder, Haemophilia A

Intervention / Treatment
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* Drug: turoctocog alfa pegol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male, age above or equal to 18 years at the time of signing informed consent,(part A). Male, age above or equal to 12 years at the time of signing informed consent,(part B). Diagnosis of congenital haemophilia A based on medical records (FVIII activity <1%). History of more than 150 exposure days to any FVIII containing products. Exclusion Criteria: Previous participation in this trial. Participation is defined as signed informed consent. (Patients who have completed part A are allowed to also participate in part B. If so, a separate informed consent covering part B must be signed.) Immune compromised patients due to human immunodeficiency virus (HIV) infection (defined as viral load greater than or equal to 400.000 copies/mL and/or cluster of differentiation 4+ (CD4+) lymphocyte count less than or equal to 200/μL performed at screening or defined by medical records no older than 6 months) Any history of FVIII inhibitors (defined by medical records within 8 years of randomisation) Inhibitors to FVIII (greater than or equal to 0.6 Bethesda unit (BU)) at screening, measured by Nijmegen modified Bethesda method at central laboratory.

Ages Eligible for Study
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Minimum Age: 12 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: N8-GP s.c.<br> | Drug: turoctocog alfa pegol<br>* Part A: Participants will receive a single dose of turoctocog alfa pegol, administered subcutaneously (under the skin), at a dose of 12.5, 25 or 50 U/kg. Part B: Participants will receive a daily dose of turoctocog alfa pegol, as identified in Part A, as a subcutaneous (under the skin) injection for a period of 3 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events | Count and % of Adverse events | Day 0-Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Calculated based on plasma FVIII activity measured in blood. | 0-144 hours | 
| Incidence of FVIII inhibitors above or equal to 0.6 BU | Count of presence of inhibitors | Day 0-Day 28 | 
| Area under the activity time curve from 0 to infinity | Calculated based on plasma FVIII activity measured in blood. | 0-144 hours | 
| Area under the activity time curve from 0 to t | Calculated based on plasma FVIII activity measured in blood. | 0-144 hours | 
| Area under the activity time curve from 0 to last | Calculated based on plasma FVIII activity measured in blood. | 0-144 hours | 
| tmax- time to maximal FVIII activity | Calculated based on plasma FVIII activity measured in blood. | 0-144 hours | 
| Cmin -the minimal FVIII activity | Calculated based on plasma FVIII activity measured in blood. | 0-144 hours | 
| tmin - time to minimal FVIII activity | Calculated based on plasma FVIII activity measured in blood. | 0-144 hours | 
| Css, min - the minimum FVIII activity at steady state | Calculated based on plasma FVIII activity measured in blood. | 0-144 hours | 
| Css, max - the maximal FVIII activity at steady state | Calculated based on plasma FVIII activity measured in blood. | 0-144 hours | 
| Css - the mean FVIII activity at steady state | Calculated based on plasma FVIII activity measured in blood. | 0-144 hours | 
| Racc - accumulation ratio | Calculated based on plasma FVIII activity measured in blood. | 0-144 hours | 
| t½ - terminal half-life | Calculated based on plasma FVIII activity measured in blood. | 0-144 hours | 
| CL - total plasma clearance of drug after intravenous administration | Calculated based on plasma FVIII activity measured in blood. | 0-144 hours | 
| Vz -apparent volume of distribution during terminal phase | Calculated based on plasma FVIII activity measured in blood. | 0-144 hours | 
| Vss - apparent volume of distribution during steady state | Calculated based on plasma FVIII activity measured in blood. | 0-144 hours | 
| MRT - mean residence time | Calculated based on plasma FVIII activity measured in blood. | 0-144 hours | 
| Injection site reactions | Count of reactions | Day 0 - day 28 | 
| Number of treatment requiring bleeding episodes | Count of episodes | Day 0 - day 120 | 
| Consumption of FVIII | Measured in IU | Day 0 - day 120 | 
| Change in Coagulation parameters, fibrinogen | Measured in g/L | Day 0, day 7 | 
| Change in Coagulation parameters, antithrombin | Measured in % | Day 0, day 7 | 
| Change in Coagulation parameters, international normalised ratio | Measured in INR | Day 0, day 7 | 
| Change in Coagulation parameters, activated partial thromboplastin time | Measured in sec. | Day 0, day 7 | 
| Change in Coagulation parameters, von Willebrand Factor | Measured in % | Day 0, day 7 |