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

Haemophilia A Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00245297
• Other study ID #: OMRI Lip-FVIII-05-1
• Status: Completed
• Phase: Phase 2
• First received: October 26, 2005
• Last updated: October 15, 2007
• Start date: October 2005
• Est. completion date: April 2006

Study information

• Verified date: October 2007
• Source: Recoly N.V.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Russia: Ministry of Health of the Russian Federation
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: April 2006
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Haemophilia A
• Hemophilia A

Intervention

Drug:
• Kogenate FS, reconstituted in a suspension of liposomes

Locations

Country	Name	City	State
Russian Federation	Center for Hematological Research, Department of Reconstructive Orthopedic Surgery	Moscow
Russian Federation	The Russian Academy of Medical Sciences, Haemophilia Center	Moscow
Russian Federation	Republic Haemophilia Center.	St. Petersburg

Sponsors (1)

Lead Sponsor	Collaborator
Recoly N.V.

Country where clinical trial is conducted

Russian Federation, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	In vivo recovery (IVR).		IVR will be performed at the first and last dose.