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

Hemophilia A Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02750085
• Other study ID #: myPKFiT™ Study
• Status: Active, not recruiting
• Start date: April 2016
• Est. completion date: December 2020

Study information

• Verified date: May 2020
• Source: The Hospital for Sick Children
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 39
• Est. completion date: December 2020
• Est. primary completion date: January 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Hemophilia A

Locations

Country	Name	City	State
n/a

Sponsors (9)

Lead Sponsor	Collaborator
Victor Blanchette	Montreal Children's Hospital of the MUHC, Queen's University, Royal Children's Hospital, Royal Prince Alfred Hospital, Sydney, Australia, St. Paul's Hospital, Sydney Children's Hospitals Network, The University Hospital Brno, University Hospital, Motol

Outcome

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