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Trial to Evaluate the Pharmacokinetics and Safety Profile of BAY94-9027 Following Single and Multiple Dose Administration

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ClinicalTrials.gov Identifier: NCT01184820
Recruitment Status : Completed
First Posted : August 19, 2010
Last Update Posted : September 7, 2018
Sponsor:
Information provided by (Responsible Party):
Bayer

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.


Condition or disease Intervention/treatment Phase
Hemophilia A Biological: BAY94-9027 + Recombinant Factor VIII (Kogenate FS, BAY14-2222) Biological: BAY94-9027 + Recombinant Factor VIII (Kogenate FS, BAY14-2222)) Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
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
Actual Study Start Date : October 13, 2010
Actual Primary Completion Date : October 10, 2011
Actual Study Completion Date : October 10, 2011


Arm Intervention/treatment
Experimental: Arm 1 Biological: BAY94-9027 + Recombinant Factor VIII (Kogenate FS, BAY14-2222)
Single dose of Kogenate FS and 16 doses of BAY94-9027 given 2 times a week for 8 weeks. Both drugs to be given intravenously.

Experimental: Arm 2 Biological: BAY94-9027 + Recombinant Factor VIII (Kogenate FS, BAY14-2222))
Single dose of Kogenate FS and 9 doses of BAY94-9027 given once a week for 8 weeks. Both drugs to be given intravenously.




Primary Outcome Measures :
  1. Safety as assessed by measuring immunogenicity [ Time Frame: Up to 8 weeks ]
    Antibodies to FVIII, polyethylene glycol (PEG) and BAY94-9027

  2. Adverse events collection [ Time Frame: Up to 8 weeks ]
  3. Area under the plasma concentration vs time curve from time 0 to the last data point (AUC0-tlast) [ Time Frame: Up to 8 weeks ]
  4. Area under the plasma concentration vs time curve from zero to infinity after single (first) dose (AUC0-inf) [ Time Frame: Up to 8 weeks ]
  5. Maximum drug concentration in plasma (Cmax) [ Time Frame: Up to 8 weeks ]
  6. Half-life associated with the terminal slope (t1/2) [ Time Frame: Up to 8 weeks ]
  7. Time to reach maximum drug concentration in plasma after single (first) dose (Tmax) [ Time Frame: Up to 8 weeks ]
  8. Mean residence time (MRT) [ Time Frame: Up to 8 weeks ]
  9. Total body clearance (CL) [ Time Frame: Up to 8 weeks ]
    Total body clearance of drug from plasma (volume/time) or (volume/time/body weight) or ((volume/time)*(1.73/body surface area)) calculated after intravenous administration

  10. Apparent volume of distribution at steady state (Vss) [ Time Frame: Up to 8 weeks ]
    Based on the chromogenic, one-stage and PEG capture assays

  11. Incremental recovery of FVIII [ Time Frame: Up to 8 weeks ]
    Recovery was assessed using two different assays (chromogenic and one-stage assay)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01184820


Locations
United States, California
Davis, California, United States, 95616
United States, Massachusetts
Boston, Massachusetts, United States, 02115-6195
United States, Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
Syracuse, New York, United States, 13210
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer

Additional Information:
Publications of Results:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01184820     History of Changes
Other Study ID Numbers: 13401
First Posted: August 19, 2010    Key Record Dates
Last Update Posted: September 7, 2018
Last Verified: September 2018

Keywords provided by Bayer:
Pharmacokinetics
Safety

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants