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

Bayer

Status and phase: Completed; Phase 1

Conditions: Hemophilia A

Treatments: Biological: Recomb. Factor VIII (Kogenate FS Liposome, BAY79-4980); Biological: Recombinant Factor VIII (Kogenate FS, BAY14-2222)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00629837

LipLong

11876

Details and patient eligibility

About

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.

Enrollment: 27 patients

Sex: Male

Ages: 12 to 60 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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27 participants in 4 patient groups

Arm 1

Experimental group

Treatment:

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

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

Arm 2

Experimental group

Treatment:

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

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

Arm 3

Active Comparator group

Treatment:

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

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

Arm 4

Active Comparator group

Treatment:

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

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