Clinical trial NCT01184820: Trial to Evaluate the Pharmacokinetics and Safety Profile of BAY94-9027 Following Single and Multiple Dose Administration
Official title: An Open-label Phase 1 Trial to Evaluate the Pharmacokinetics and Safety Profile of BAY94-9027 Following Single and Multiple Dose Administration in Two Cohorts of Previously Treated Male Subjects With Severe Hemophilia A
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hemophilia A
Keywords: Pharmacokinetics
Safety
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2010-08-19
Enrollment: 14
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to describe the pharmacokinetics (PK) of BAY94-9027(the test drug). Pharmacokinetics means that we will measure how well the study drug corrects the factor VIII levels in your blood and how long it takes for the levels to fall back to your baseline level. The study is also designed to determine if the pharmacokinetics of BAY94-9027 change following repeat dosing over 8 weeks, determine if BAY94-9027 is safe, tolerable, and effective for the treatment of severe hemophilia A and define the appropriate dose of BAY94-9027. Two doses of BAY94-9027 will be studied.

The first 8 subjects enrolled in the study (cohort 1) will receive a low dose (25 IU/kg) and will be treated 2 days a week for 8 weeks (total of 16 doses). The second 8 subjects (cohort 2) will receive a higher dose and will be treated 1 day a week for 8 weeks (total 8 doses). All subjects will receive a single dose of rFVIII (Bayer Kogenate FS) to determine the PK by measuring blood levels for 2 days before they start the study drug BAY94-9027. Factor VIII blood levels for BAY94-9027 will be measured for 7 days after the first and last dose to see describe the PK. Safety \& tolerability assessment include vital signs, coagulation and hematological parameter, clinical chemistry, measurement of FVIII inhibitor and polyethylene glycol (PEG) antibodies will be done during the course of the study.


Eligibility criteria: Inclusion Criteria:

* Male subjects with severe hemophilia A (documented plasma baseline Factor VIII level \<1 %)
* \>/= 18 but \</= 65 years of age
* Previously treated with Factor VIII concentrate(s) for a minimum of 150 exposure days (as supported by the subject's medical history)
* Immunocompetent with a CD4+ lymphocyte count \> 400/mm³
* Signed informed consent from subject

Exclusion Criteria:

* Documented history of inhibitor to Factor VIII with a titer \>/= 0.6 BU (Biological Unit), by the Nijmegen modified assay. However, subjects with a maximum historical titer of \</= 1.0 BU with the classical Bethesda assay on a single measurement but with at least 3 subsequent successive negative results (\< 0.6 BU) thereafter are eligible.
* Unable to stop Factor VIII treatment to complete a minimum 72 hour washout
* Current evidence of inhibitor to Factor VIII with a titer \>/= 0.6 BU, measured at the time of screening
* Abnormal renal function (serum creatinine \> 1.5 times the upper limit of the normal range)
* Total bilirubin \> 1.5 times the upper limit of the normal range
* Active hepatic disease (alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels \> 2 times the upper limit of the normal range)
* Any concomitant coagulation disorder other than hemophilia A (including lupus anticoagulant)
* Platelet count \< 100,000/mm³
* Within the last 3 months prior to study entry or during the study will be treated with an immunomodulating drug other than anti-retroviral chemotherapy (e.g., a interferon, steroids, rituximab, etc)
* Any subject who requires major surgery during study period. Minor procedures may be approved if discussed in advance with the medical expert.

Primary outcomes:
measure: Safety as assessed by measuring immunogenicity
timeFrame: Up to 8 weeks
measure: Adverse events collection
timeFrame: Up to 8 weeks
measure: Area under the plasma concentration vs time curve from time 0 to the last data point (AUC0-tlast)
timeFrame: Up to 8 weeks
measure: Area under the plasma concentration vs time curve from zero to infinity after single (first) dose (AUC0-inf)
timeFrame: Up to 8 weeks
measure: Maximum drug concentration in plasma (Cmax)
timeFrame: Up to 8 weeks
measure: Half-life associated with the terminal slope (t1/2)
timeFrame: Up to 8 weeks
measure: Time to reach maximum drug concentration in plasma after single (first) dose (Tmax)
timeFrame: Up to 8 weeks
measure: Mean residence time (MRT)
timeFrame: Up to 8 weeks
measure: Total body clearance (CL)
timeFrame: Up to 8 weeks
measure: Apparent volume of distribution at steady state (Vss)
timeFrame: Up to 8 weeks
measure: Incremental recovery of FVIII
timeFrame: Up to 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Davis
country: United States
state: California
city: Boston
country: United States
state: Massachusetts
city: Minneapolis
country: United States
state: Minnesota
city: Syracuse
country: United States
state: New York
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Coyle TE, Reding MT, Lin JC, Michaels LA, Shah A, Powell J. Phase I study of BAY 94-9027, a PEGylated B-domain-deleted recombinant factor VIII with an extended half-life, in subjects with hemophilia A. J Thromb Haemost. 2014 Apr;12(4):488-96. doi: 10.1111/jth.12506.