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

Status

UNKNOWN

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT02750085

Enrollment

Registered

2016-04-25

Start date

2016-04-30

Completion date

2020-12-31

Last updated

2020-05-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hemophilia A

Keywords

Hemophilia A, pharmacokinetics, myPKFiT

Brief summary

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.

Interventions

None listed

Study design

Observational model

CASE_ONLY

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Healthy volunteers

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.

Design outcomes

Primary

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

Outcome results