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

Primary Purpose

Hemophilia A

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

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

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

About this trial

This is an interventional basic science trial for Hemophilia A focused on measuring Pharmacokinetics, Safety

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm 1

Arm 2

Arm Description

Outcomes

Primary Outcome Measures

Safety as assessed by measuring immunogenicity

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

Adverse events collection

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

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

Maximum drug concentration in plasma (Cmax)

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

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

Mean residence time (MRT)

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

Apparent volume of distribution at steady state (Vss)

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

Incremental recovery of FVIII

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

Secondary Outcome Measures

Full Information

NCT ID

NCT01184820

First Posted

July 13, 2010

Last Updated

September 6, 2018

Sponsor

Bayer

1. Study Identification

Unique Protocol Identification Number

NCT01184820

Brief Title

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

2. Study Status

Record Verification Date

September 2018

Overall Recruitment Status

Completed

Study Start Date

October 13, 2010 (Actual)

Primary Completion Date

October 10, 2011 (Actual)

Study Completion Date

October 10, 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bayer

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hemophilia A

Keywords

Pharmacokinetics, Safety

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm 1

Arm Type

Experimental

Arm Title

Arm 2

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

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

Intervention Description

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

Intervention Name(s)

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

Intervention Description

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 Measure Information:

Title

Safety as assessed by measuring immunogenicity

Description

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

Time Frame

Up to 8 weeks

Title

Adverse events collection

Time Frame

Up to 8 weeks

Title

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

Time Frame

Up to 8 weeks

Title

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

Time Frame

Up to 8 weeks

Title

Maximum drug concentration in plasma (Cmax)

Time Frame

Up to 8 weeks

Title

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

Time Frame

Up to 8 weeks

Title

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

Time Frame

Up to 8 weeks

Title

Mean residence time (MRT)

Time Frame

Up to 8 weeks

Title

Total body clearance (CL)

Description

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

Time Frame

Up to 8 weeks

Title

Apparent volume of distribution at steady state (Vss)

Description

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

Time Frame

Up to 8 weeks

Title

Incremental recovery of FVIII

Description

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

Time Frame

Up to 8 weeks

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bayer Study Director

Organizational Affiliation

Bayer

Official's Role

Study Director

Facility Information:

City

Davis

State/Province

California

ZIP/Postal Code

95616

Country

United States

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115-6195

Country

United States

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55455

Country

United States

City

Syracuse

State/Province

New York

ZIP/Postal Code

13210

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

24843882

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.

Results Reference

result

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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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