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

NCT01184820 | Completed Phase 1

• 1 other identifier: 13401
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 4

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

Keywords

Pharmacokinetics; Safety

Outcome Measures

Primary Outcomes (11)

• Safety as assessed by measuring immunogenicity

  Antibodies to FVIII, polyethylene glycol (PEG) and BAY94-9027

  Up to 8 weeks

• Adverse events collection

  Up to 8 weeks

• Area under the plasma concentration vs time curve from time 0 to the last data point (AUC0-tlast)

  Up to 8 weeks

• Area under the plasma concentration vs time curve from zero to infinity after single (first) dose (AUC0-inf)

  Up to 8 weeks

• Maximum drug concentration in plasma (Cmax)

  Up to 8 weeks

• Half-life associated with the terminal slope (t1/2)

  Up to 8 weeks

• Time to reach maximum drug concentration in plasma after single (first) dose (Tmax)

  Up to 8 weeks

• Mean residence time (MRT)

  Up to 8 weeks

• Total body clearance (CL)

  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

  Up to 8 weeks

• Apparent volume of distribution at steady state (Vss)

  Based on the chromogenic, one-stage and PEG capture assays

  Up to 8 weeks

• Incremental recovery of FVIII

  Recovery was assessed using two different assays (chromogenic and one-stage assay)

  Up to 8 weeks

Study Arms (2)

Arm 1

EXPERIMENTAL

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

Arm 2

EXPERIMENTAL

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

Interventions

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

Arm 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bayer: lead

Study Sites (4)

Unknown Facility

Davis, California, 95616, United States

Location

Unknown Facility

Boston, Massachusetts, 02115-6195, United States

Location

Unknown Facility

Minneapolis, Minnesota, 55455, United States

Location

Unknown Facility

Syracuse, New York, 13210, United States

Location

Related Publications (1)

• 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.

  PMID: 24843882 RESULT

MeSH Terms

Conditions

Hemophilia A

Interventions

Factor VIII; F8 protein, human; BAY 14-2222

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2010
• First Posted: August 19, 2010
• Study Start: October 13, 2010
• Primary Completion: October 10, 2011
• Study Completion: October 10, 2011
• Last Updated: September 7, 2018

Record last verified: 2018-09

Locations

US (4)