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

Study Overview
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Brief Summary
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Primary efficacy endpoint: To study whether there is a difference in the length of the bleeding free periods between infusion of FVIII that is reconstituted with 22.1, 12.6, or 4.2 mg of pegylated liposomes per kg bwt compared with standard formulation. Safety endpoint: To study the safety and tolerability of Kogenate FS reconstituted with Pegylated liposomes

Detailed Description
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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.

Official Title
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A Patient-Blinded, Randomized, Comparative, Multicenter, Crossover, (Liposome) Dose Finding Study of the Efficacy of Human Recombinant Factor VIII (Kogenate FS) Reconstituted in Pegylated Liposomes.

Conditions
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Haemophilia A

Intervention / Treatment
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* Drug: Kogenate FS, reconstituted in a suspension of liposomes


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Kogenate FS, reconstituted in a suspension of liposomes|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary efficacy parameter is the number of bleeding free days (without a bleeding/treatment) between a randomized prophylactic infusion and following on demand injection. |  | Bleeding free time following four single doses will be studies | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In vivo recovery (IVR). |  | IVR will be performed at the first and last dose. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bleeding disorder, severe Haemophilia A, Prophylaxis