Clinical trial NCT02750085: Evaluation of a Simple Pharmacokinetic Tool (myPKFiT™) to Guide Personalized Factor VIII Dosing in Patients With Hemophilia
Official title: Evaluation of a Simple Pharmacokinetic Tool (myPKFiT™) to Guide Personalized Factor VIII Dosing in Patients With Hemophilia
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hemophilia A
Keywords: Hemophilia A
pharmacokinetics
myPKFiT
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
Collaborators: name: St. Paul's Hospital
name: Montreal Children's Hospital of the MUHC
name: Queen's University
name: University Hospital, Motol
name: The University Hospital Brno
name: Royal Children's Hospital
name: Sydney Children's Hospitals Network
name: Royal Prince Alfred Hospital, Sydney, Australia
First posted: 2016-04-25
Enrollment: 39
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with severe Hemophilia A

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Terminal half-life (t1/2)
timeFrame: 2 years
measure: area under the plasma concentration versus time curve (AUC)
timeFrame: 2 years
measure: Area under the moment curve (AUMC)
timeFrame: 2 years
measure: In vivo recovery (IVR)
timeFrame: 2 years
measure: Maximum concentration (Cmax)
timeFrame: 2 years
measure: Clearance (Cl)
timeFrame: 2 years
measure: Volume of distribution at steady state (Vss)
timeFrame: 2 years
measure: Mean residence time (MRT)
timeFrame: 2 years
measure: Time to factor VIII concentration of 1% over baseline
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: The Hospital for Sick Children
name: Victor S Blanchette, MD
role: PRINCIPAL_INVESTIGATOR
References: