A multi-centre, comparative, double blind, randomised cross-over trial investigating single dose pharmacokinetics and safety of turoctocog alfa pegol from the pivotal process and turoctocog alfa pegol from the commercial process in patients with severe haemophilia A

The manufacturing processes for turoctocog alfa which is an intermediate in the
production of turoctocog alfa pegol has been changed and moved to a new
production facility, where the manufacturing of turoctocog alfa pegol drug
substance is also conducted. The manufacturing process and facility for
turoctocog alfa pegol drug product are unchanged. The turoctocog alfa pegol
produced with the original process and which has been investigated in the
pivotal trials is hereafter denominated *turoctocog alfa pegol from the pivotal
process*. The turoctocog alfa pegol produced with the new manufacturing process
for turoctocog alfa and at the new facility is hereafter denominated
*turoctocog alfa pegol from the commercial process*. The rationale for
conducting this trial is to assess and compare the single-dose PK of turoctocog
alfa pegol from the pivotal process with turoctocog alfa pegol from the
commercial process in patients with severe haemophilia A.

Primary objective
To evaluate and compare the single-dose pharmacokinetic of turoctocog alfa
pegol from the pivotal process with turoctocog alfa pegol from the commercial
process, each given as intravenous administrations of 50 U/kg to patients with
severe haemophilia A

Secondary objective
To assess the safety of turoctocog alfa pegol from the pivotal process and
turoctocog alfa pegol from the commercial process after single intravenous
doses of 50 U/kg in patients with severe haemophilia A

This is a multi-centre, comparative, double-blind, randomised cross-over trial
investigating single dose pharmacokinetics and safety of turoctocog alfa pegol
from the pivotal process and turoctocog alfa pegol from the commercial process
in patients with severe haemophilia A.
Two batches of turoctocog alfa pegol will be evaluated in the trial, i.e. one
batch of turoctocog alfa pegol from the pivotal process (2000 U/vial) and one
batch of turoctocog alfa pegol from the commercial process (2000 U/vial). Both
products will be administered as intravenous injections at a dose of 50 U/kg.
Patients will receive each product in a randomised cross-over design for
comparison of the pharmacokinetics between turoctocog alfa pegol from the
pivotal process and turoctocog alfa pegol from the commercial process.
The trial will consist of 4 visits, including one screening visit (visit 1) and
one end-of-trial visit (visit 4). There will be two identical pharmacokinetic
sessions, each consisting of 5 days (visit 2 and 3). Patients must have
completed a turoctocog alfa pegol wash-out period of at least 7 days prior to
each pharmacokinetic session and must not be actively bleeding during the
pharmacokinetic sessions. Blood samples for pharmacokinetic analysis will be
collected pre-dose and at 10 time points up to 96 hours post-injection.

For each of the 2 pharmacokinetic sessions patients will administer an
intravenous injection of turoctocog alfa pegol (once from the pivotal and once
from the commercial process) at a dose of 50 U/kg. In between the visits, if
interval is planned to be longer than the 7 day wash-out period, turoctocog
alfa pegol from the pivotal process will be administered every 4th day at a
dose of 50 U/kg, or every 7th day at a dose of 75 U/kg in order to prevent
bleeding episodes. The dosing regimen is depending on the patients current
dosing regimen in the PathfinderTM2 trial, from which the patients are
recruited.

Currently available clinical data from the pathfinder* programme indicate that
turoctocog alfa pegol effectively arrests bleeding episodes and thereby has the
intended haemostatic potential. The key risks associated with turoctocog alfa
pegol administration are inhibitor development and allergic/hypersensitivity
reactions, which are well-known class effects for FVIII products.