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

NCT ID: NCT01184820

Last Updated: 2018-09-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-13
• Study Completion Date: 2011-10-10

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.

Conditions

Hemophilia A

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Arm 1

Group Type: EXPERIMENTAL

BAY94-9027 + Recombinant Factor VIII (Kogenate FS, BAY14-2222)

Intervention Type: BIOLOGICAL

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.

Arm 2

Group Type: EXPERIMENTAL

BAY94-9027 + Recombinant Factor VIII (Kogenate FS, BAY14-2222))

Intervention Type: BIOLOGICAL

Single dose of Kogenate FS and 9 doses of BAY94-9027 given once a week for 8 weeks. Both drugs to be given intravenously.

Interventions

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.

Intervention Type: 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.

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

Davis, California, United States

Boston, Massachusetts, United States

Minneapolis, Minnesota, United States

Syracuse, New York, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 24843882 (View on PubMed)

Other Identifiers

13401

Identifier Type: -

Identifier Source: org_study_id