Clinical trial NCT00245297: Study of the Efficacy of Human Recombinant Factor VIII (Kogenate FS) Reconstituted in Pegylated Liposomes.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Haemophilia A
Keywords: Bleeding disorder
severe Haemophilia A
Prophylaxis
Lead sponsor: Recoly N.V.
Sponsor class: INDUSTRY
First posted: 2005-10-27
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: Bleeding free time following four single doses will be studies
Secondary outcomes:
measure: In vivo recovery (IVR).
timeFrame: IVR will be performed at the first and last dose.
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Center for Hematological Research, Department of Reconstructive Orthopedic Surgery
city: Moscow
country: Russian Federation
facility: The Russian Academy of Medical Sciences, Haemophilia Center
city: St. Petersburg
country: Russian Federation
facility: Republic Haemophilia Center.
Study officials:
affiliation: Recoly C/o InSpira Medical AB, Nasbyv 38, 13553 Tyreso Sweden
name: Jack Spira, MD. PhD.
role: STUDY_DIRECTOR
References:
citation: Baru M, Carmel-Goren L, Barenholz Y, Dayan I, Ostropolets S, Slepoy I, Gvirtzer N, Fukson V, Spira J. Factor VIII efficient and specific non-covalent binding to PEGylated liposomes enables prolongation of its circulation time and haemostatic efficacy. Thromb Haemost. 2005 Jun;93(6):1061-8. doi: 10.1160/TH04-08-0485.