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

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.

Study Overview

• Status: Unknown
• Conditions: Hemophilia A

• Study Type: Observational
• Enrollment (Actual): 39

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with severe Hemophilia A

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
2-point and 6-point PK sampling

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Victor Blanchette
• Collaborators: Queen's University; Sydney Children's Hospitals Network; Royal Children's Hospital; Royal Prince Alfred Hospital, Sydney, Australia; Montreal Children's Hospital of the MUHC; University Hospital, Motol; St. Paul's Hospital; The University Hospital Brno
• Investigators: Principal Investigator: Victor S Blanchette, MD, The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2016
• Primary Completion (ACTUAL): January 1, 2019
• Study Completion (ANTICIPATED): December 1, 2020

Study Registration Dates

• First Submitted: April 7, 2016
• First Submitted That Met QC Criteria: April 20, 2016
• First Posted (ESTIMATE): April 25, 2016

Study Record Updates

• Last Update Posted (ACTUAL): May 15, 2020
• Last Update Submitted That Met QC Criteria: May 13, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: pharmacokinetics; Hemophilia A; myPKFiT
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A
• Other Study ID Numbers: myPKFiT™ Study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO