Evaluation of a Simple Pharmacokinetic Tool (myPKFiT™) to Guide Personalized Factor VIII Dosing in Patients With Hemophilia

Study Overview
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Brief Summary
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This is an investigator-initiated, industry-funded, multi-centre, international study that will be carried out prospectively at hemophilia treatment centres across Canada, the Czech Republic and Australia with SickKids as the coordinating site. The study will use a central laboratory not directly affiliated with any of the participating sites. Enrollment target is 50 participants, both adult and pediatric with severe hemophilia A receiving Advate, who will each complete a 2-point and 6-point pharmacokinetic (PK) sampling. The main aim is to compare the results of a 2 sample PK using clinically practical time points and myPKFiT™ (a web-based, population PK Bayesian tool) to a 6 sample population PK to determine whether the results obtained are in good agreement.

Official Title
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Evaluation of a Simple Pharmacokinetic Tool (myPKFiT™) to Guide Personalized Factor VIII Dosing in Patients With Hemophilia

Conditions
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Hemophilia A

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of Hemophilia A; Severe disease (FVIII <2%); Receiving ADVATE for prevention of bleeding (prophylaxis) or receiving ADVATE on demand and a candidate for prophylaxis; Body weight ≤120 kg; and ≥12kg; Exclusion Criteria: FVIII inhibitor positive (level of ≥0.6 Bethesda Units [BU] per mL using the Nijmegen modification of the Bethesda assay). Inhibitor status to be documented as negative prior to study enrollment according to the two most recent, consecutive inhibitor assays on record. If patients have < 50 exposure days, an assay will be completed centrally within a reasonable timeframe (approximately 8 weeks suggested) to make sure that they are negative. Body weight >120 kg or <12kg; Human immunodeficiency virus (HIV) positivity with cluster of differentiation 4 (CD4) count < 200 / microliter; Significant hepatic dysfunction, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 times upper limit of normal History of recent events that might affect FVIII half-life (e.g., infection, surgery or an invasive procedure) within 2 weeks of blood sampling.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 2-point and 6-point PK sampling<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Terminal half-life (t1/2) | 2-point PK sampling protocol against 6-point PK sampling protocol | 2 years | 
| area under the plasma concentration versus time curve (AUC) | 2-point PK sampling protocol against 6-point PK sampling protocol | 2 years | 
| Area under the moment curve (AUMC) | 2-point PK sampling protocol against 6-point PK sampling protocol | 2 years | 
| In vivo recovery (IVR) | 2-point PK sampling protocol against 6-point PK sampling protocol | 2 years | 
| Maximum concentration (Cmax) | 2-point PK sampling protocol against 6-point PK sampling protocol | 2 years | 
| Clearance (Cl) | 2-point PK sampling protocol against 6-point PK sampling protocol | 2 years | 
| Volume of distribution at steady state (Vss) | 2-point PK sampling protocol against 6-point PK sampling protocol | 2 years | 
| Mean residence time (MRT) | 2-point PK sampling protocol against 6-point PK sampling protocol | 2 years | 
| Time to factor VIII concentration of 1% over baseline | 2-point PK sampling protocol against 6-point PK sampling protocol | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemophilia A, pharmacokinetics, myPKFiT