Study of the Efficacy of Human Recombinant Factor VIII (Kogenate FS) Reconstituted in Pegylated Liposomes.

Each subject will receive treatment for three bleeding episodes ("wash-in", on demand injections) followed by a minimum 4 day wash-out. Following this each subject will be randomized to a specific treatment order. Each order consists of four identical blocks. In each block the following three injections will be given: 1 One prophylactic treatment (randomized solution for dissolution) 2 and 3. Two standard on-demand treatments for a spontaneous bleeding episode (standard Kogenate FS). Each block will be followed by a four day wash-out. In total each subject should receive 3+4x3=15 injections. It is estimated that each subject will be in the study for about 4 months. A treatment for a spontaneous bleeding episode may require more than one infusion.

Inclusion criteria

• Between 18 and 60 years of age
• Severe haemophilia A (≤ 1% of baseline Factor VIII activity)
• At least 250 treatment cumulative exposure-days (CEDs) to previous products
• At least 25 cumulative exposure-days (CEDs) to previous products during one year prior to study start
• If HIV positive, CD4 lymphocytes ≥ 400/µl
• Subjects on demand treatment, and with a minimum bleeding/treatment pattern of a four episodes per month, evenly distributed within each month, during the three month preceding study start
• Subjects who have given their written informed consent.

Exclusion criteria

• Inhibitors or history of inhibitors
• History of adverse reactions related to Factor VIII
• Platelet count <90,000 /µl
• Subjects on prophylaxis treatment
• Subjects with concomitant debilitating disease (e.g. cancer, non-controlled diabetes, heart insufficiency, renal failure)
• Subjects with known sensitivity to blood products
• Subjects who have participated in another Ethical Committee approved Clinical Trial (including medical device studies) within the past 30 days
• Subjects with a weight over 86 kg or below 50 kg
• Subjects who do not understand or are not willing to comply with the requirement of the study protocol
• Subjects who cannot differentiate a bleeding episode from other causes of joint pain