Investigation of the Pharmacokinetics of Turoctocog Alfa in Subjects With Haemophilia A

Study Overview
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Brief Summary
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This trial is conducted in Europe. The aim of the trial is to investigate the pharmacokinetics (the exposure of the trial drug in the body) of four lots of turoctocog alfa (a human recombinant coagulation factor VIII (FVIII)) in subjects with haemophilia A.

Official Title
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Multi-centre, Open-labelled Trial Investigating the Pharmacokinetics of Four Lots of Turoctocog Alfa 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. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial Male subjects with the diagnosis of severe haemophilia A (FVIII<1%) from age 18 years Documented history of at least 150 exposure days to any other FVIII products (prevention or treatment of bleeds) Immunocompetent (HIV (Human Immunodeficiency Virus) positive subjects should have CD4+ (Cluster of differentiation 4; a glycoprotein expressed on the surface) lymphocyte count >200/microL) Exclusion Criteria: Detectable inhibitors to FVIII (above or equal to 0.6 Bethesda Units (BU)) History of FVIII inhibitors Severe current hepatic dysfunction or severe hepatic disease during the last 12 months Known or suspected allergy to trial product (FVIII) or related products Subjects receiving immune modulating medication or immune tolerance induction (ITI) regimens Body mass index (BMI) above 30 kg/m^2

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lot A<br>Each subject will receive two single doses of turocotocog alfa from two lots of trial product on two separate days. | Drug: turoctocog alfa<br>* Trial product, 2000 IU/vial will be administered as an i.v. (intravenous) bolus injection.<br>|
| Experimental: Lot B<br>Each subject will receive two single doses of turocotocog alfa from two lots of trial product on two separate days. | Drug: turoctocog alfa<br>* Trial product, 2000 IU/vial will be administered as an i.v. (intravenous) bolus injection.<br>|
| Experimental: Lot C<br>Each subject will receive two single doses of turocotocog alfa from two lots of trial product on two separate days. | Drug: turoctocog alfa<br>* Trial product, 2000 IU/vial will be administered as an i.v. (intravenous) bolus injection.<br>|
| Experimental: Lot D<br>Each subject will receive two single doses of turocotocog alfa from two lots of trial product on two separate days. | Drug: turoctocog alfa<br>* Trial product, 3000 IU/vial will be administered as an i.v. (intravenous) bolus injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose normalised area under the curve (AUC/actual dose) based on chromogenic assay |  | up to 48 hours after i.v. administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose normalised area under the FVIII activity-time curve (AUC/actual dose) based on one stage clot assay |  | up to 48 hours after i.v. administration | 
| Incremental recovery (IR30min) (defined as the peak FVIII level recorded 30 min after injection and reported as[IU/mL]/[IU/kg]) |  | up to 48 hours after i.v. administration | 
| Area under the FVIII activity-time curve (AUC) |  | up to 48 hours after i.v. administration | 
| Terminal half-life of FVIII (t½) |  | up to 48 hours after i.v. administration | 
| Clearance of FVIII (CL) |  | up to 48 hours after i.v. administration | 
| Incidence of adverse events (AEs) including FVIII inhibitors |  | After approximately 3 months (at end of trial) |