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Pharmacokinetics and Safety of a Single Intravenous Infusion of BAY 79-4980

Primary Purpose

Hemophilia A

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Recomb. Factor VIII (Kogenate FS Liposome, BAY79-4980)

Recombinant Factor VIII (Kogenate FS, BAY14-2222)

About this trial

This is an interventional treatment trial for Hemophilia A focused on measuring FVIII, Long acting, pk

Eligibility Criteria

12 Years - 60 Years (Child, Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

Males aged 12 to 60 years
Hemophilia A with plasma FVIII level less than 1% (severe hemophilia)
No history of FVIII inhibitor antibody formation and no current evidence of inhibitor antibody measured using the Nijmegen modified Bethesda assay (< 0.6 Nijmegen Bethesda Units [N.B.U.]/mL)
No signs or symptoms of an acute bleeding episode on the day of infusion
Four or more days without treatment with FVIII prior to the day of infusion
Subject (or the subject's legal representative) must provide written informed consent and authorization of use and disclosure of Protected Health Information (PHI)
Subjects must have been previously treated with FVIII concentrate for a total of at least 200 exposure days, including 20 exposure days in the previous 12 months. Previous treatment can have been with any type of rFVIII or plasma-derived FVIII concentrate

Exclusion Criteria:

Individuals with abnormal renal function (serum creatinine concentrations greater than 1.3 mg/dL) or active hepatic disease (persistent aspartate aminotransferase [AST] or alanine aminotransferase [ALT] increases to greater than five times the upper limit of normal).
Individuals with anemia, as defined by hemoglobin level less than 12 g/dL
Any individual with a past history of severe reaction(s) to FVIII products
Any individual on interferon treatment or who has received interferon within the previous 3 months
Any individual with thrombocytopenia (platelets greater than or equal to 100,000 cells/mm3) or known hematologic/bleeding problems other than hemophilia A
Any individual who is receiving or has received other experimental drugs within 3 months prior to study entry
Any individual with known dislipidemic disease or actively taking cholesterol lowering drugs for the treatment of hypercholesterolemia or hyperlipidemia (e.g., statins, cholesterol absorption inhibitors, bile acid sequestrants, nicotinic acid or fibrates) or individuals taking anaesthetic drugs
Any individual who requires pre-medication for FVIII infusions (e.g., antihistamines)
Any individual with high blood pressure (defined as diastolic blood pressure great than or equal to 100 mm/Hg)
Any patient who cannot forego FVIII treatment for at least 4 days prior to study entry or between study infusions due to a need for more frequent prophylactic treatment because of a pre-existing medical condition
Any patient with known allergy or severe reactions to liposomes or PEG
Individuals with any other known disease affecting hemostasis besides hemophilia A
Any patient who is not suitable for participation in this trial for any reason, according to the Investigator

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Arm Label

Arm 1

Arm 2

Arm 3

Arm 4

Arm Description

Outcomes

Primary Outcome Measures

To determine the pk profile after single administration of two doses of BAY 79-4980 (high and low: 35 IU FVIII/Kg reconstituted in 22 mg and 13 mg of liposomes/kg, respectively) compared to rFVIII-FS (35 IU/Kg reconstituted in 2.5 mL WFI/1000 IU) in PTPs

Secondary Outcome Measures

To determine the infusion tolerability of both BAY 79-4980 doses, by evaluation of vital signs and adverse events

To determine the safety of both BAY 79-4980 doses by measuring the effects on laboratory parameters - especially the lipid profile and adverse events

To determine the pk characteristics of liposomes - esp body clearance by measuring the major liposome component 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (POPC) and the non-biological liposome component, MPEG 2000 DSPE, as surrogate marker

To determine the activity of rFVIII over time (as determined by thrombin generation assay and the rotation thromboelastography [RoTEG] assay) for both doses of BAY 79-4980 compared to rFVIII-FS

Additional analyses of the number and timing of spontaneous bleeds after each study treatment will be assessed

Full Information

NCT ID

NCT00629837

First Posted

February 27, 2008

Last Updated

November 17, 2014

Sponsor

Bayer

1. Study Identification

Unique Protocol Identification Number

NCT00629837

Brief Title

Pharmacokinetics and Safety of a Single Intravenous Infusion of BAY 79-4980

Official Title

A Randomized, Double-blind, Cross-over Study to Determine the Pharmacokinetics and Safety of a Single Intravenous Infusion of BAY 79-4980 in Previously Treated Patients With Severe Hemophilia A

Study Type

Interventional

2. Study Status

Record Verification Date

November 2014

Overall Recruitment Status

Completed

Study Start Date

September 2005 (undefined)

Primary Completion Date

undefined (undefined)

Study Completion Date

March 2006 (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 primary objective of this study is to determine the pharmacokinetic profile after single administration of two doses of BAY 79-4980 (high and low: 35 IU FVIII/Kg reconstituted in 22 mg and 13 mg of liposomes/Kg, respectively) compared to rFVIII-FS (35 IU/Kg reconstituted in 2.5 mL WFI/1000 IU) in PTPs aged 12 to 60 years with severe hemophilia A.

6. Conditions and Keywords

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

Hemophilia A

Keywords

FVIII, Long acting, pk

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

27 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm 1

Arm Type

Experimental

Arm Title

Arm 2

Arm Type

Experimental

Arm Title

Arm 3

Arm Type

Active Comparator

Arm Title

Arm 4

Arm Type

Active Comparator

Intervention Type

Biological

Intervention Name(s)

Recomb. Factor VIII (Kogenate FS Liposome, BAY79-4980)

Intervention Description

Low dose of BAY 79-4980 [13mg of liposomes/kg] then cross over to rFVIII-FS (35 IU/kg reconstituted in 2.5 mL WFI / 1000 IU).

Intervention Type

Biological

Intervention Name(s)

Recomb. Factor VIII (Kogenate FS Liposome, BAY79-4980)

Intervention Description

High dose of BAY 79-4980 [22mg of liposomes/kg] then cross over to rFVIII-FS (35 IU/kg reconstituted in 2.5 mL WFI / 1000 IU)

Intervention Type

Biological

Intervention Name(s)

Recombinant Factor VIII (Kogenate FS, BAY14-2222)

Intervention Description

rFVIII-FS (35 IU/kg reconstituted in 2.5mL WFI /1000 IU) then cross over to low dose of BAY 79-4980 [13mg of liposomes/kg]

Intervention Type

Biological

Intervention Name(s)

Recombinant Factor VIII (Kogenate FS, BAY14-2222)

Intervention Description

rFVIII-FS (35 IU/kg reconstituted in 2.5mL WFI /1000 IU) then cross over to high dose of BAY 79-4980 [22mg of liposomes/kg]

Primary Outcome Measure Information:

Title

Time Frame

6 weeks

Secondary Outcome Measure Information:

Title

To determine the infusion tolerability of both BAY 79-4980 doses, by evaluation of vital signs and adverse events

Time Frame

6 weeks

Title

To determine the safety of both BAY 79-4980 doses by measuring the effects on laboratory parameters - especially the lipid profile and adverse events

Time Frame

6 weeks

Title

Time Frame

6 weeks

Title

To determine the activity of rFVIII over time (as determined by thrombin generation assay and the rotation thromboelastography [RoTEG] assay) for both doses of BAY 79-4980 compared to rFVIII-FS

Time Frame

6 weeks

Title

Additional analyses of the number and timing of spontaneous bleeds after each study treatment will be assessed

Time Frame

6 weeks

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

12 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Males aged 12 to 60 years Hemophilia A with plasma FVIII level less than 1% (severe hemophilia) No history of FVIII inhibitor antibody formation and no current evidence of inhibitor antibody measured using the Nijmegen modified Bethesda assay (< 0.6 Nijmegen Bethesda Units [N.B.U.]/mL) No signs or symptoms of an acute bleeding episode on the day of infusion Four or more days without treatment with FVIII prior to the day of infusion Subject (or the subject's legal representative) must provide written informed consent and authorization of use and disclosure of Protected Health Information (PHI) Subjects must have been previously treated with FVIII concentrate for a total of at least 200 exposure days, including 20 exposure days in the previous 12 months. Previous treatment can have been with any type of rFVIII or plasma-derived FVIII concentrate Exclusion Criteria: Individuals with abnormal renal function (serum creatinine concentrations greater than 1.3 mg/dL) or active hepatic disease (persistent aspartate aminotransferase [AST] or alanine aminotransferase [ALT] increases to greater than five times the upper limit of normal). Individuals with anemia, as defined by hemoglobin level less than 12 g/dL Any individual with a past history of severe reaction(s) to FVIII products Any individual on interferon treatment or who has received interferon within the previous 3 months Any individual with thrombocytopenia (platelets greater than or equal to 100,000 cells/mm3) or known hematologic/bleeding problems other than hemophilia A Any individual who is receiving or has received other experimental drugs within 3 months prior to study entry Any individual with known dislipidemic disease or actively taking cholesterol lowering drugs for the treatment of hypercholesterolemia or hyperlipidemia (e.g., statins, cholesterol absorption inhibitors, bile acid sequestrants, nicotinic acid or fibrates) or individuals taking anaesthetic drugs Any individual who requires pre-medication for FVIII infusions (e.g., antihistamines) Any individual with high blood pressure (defined as diastolic blood pressure great than or equal to 100 mm/Hg) Any patient who cannot forego FVIII treatment for at least 4 days prior to study entry or between study infusions due to a need for more frequent prophylactic treatment because of a pre-existing medical condition Any patient with known allergy or severe reactions to liposomes or PEG Individuals with any other known disease affecting hemostasis besides hemophilia A Any patient who is not suitable for participation in this trial for any reason, according to the Investigator

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

Orange

State/Province

California

ZIP/Postal Code

92868-3974

Country

United States

12. IPD Sharing Statement

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Pharmacokinetics and Safety of a Single Intravenous Infusion of BAY 79-4980

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