Thromb Haemost 2008; 100(03): 429-434
DOI: 10.1160/TH08-03-0133
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Evaluation of liposomal dose in recombinant factor VIII reconstituted with pegylated liposomes for the treatment of patients with severe haemophilia A

Jack Spira
1   Recoly Curaçao, Netherlands Antilles
,
Olga P. Plyushch
2   Center for Hematological Research, The Russian Academy of Medical Sciences, Moscow, Russia
,
Tatyana A. Andreeva
3   City Haemophilia Center, Saint Petersburg, Russia
,
Rosa N. Khametova
2   Center for Hematological Research, The Russian Academy of Medical Sciences, Moscow, Russia
› Author Affiliations
Further Information

Publication History

Received 04 March 2008

Accepted after minor revision 27 June 2008

Publication Date:
22 November 2017 (online)

Summary

Patients with haemophilia A treated prophylactically require frequent factor VIII (FVIII) infusions for bleed protection. Recombinant sucrose-formulated FVIII (rFVIII-FS) with pegylated liposomes (PEGLip-rFVIII-FS) was previously shown to extend the bleed-free period after prophylactic infusion versus rFVIII-FS using two doses of FVIII with a fixed amount of liposomal diluent. This randomised, subject-blinded, four-way crossover study evaluated the efficacy and safety of PEGLip-rFVIII-FS using various quantities of pegylated liposomes with a fixed FVIII dose. Adults with severe haemophilia A were randomised to one of four treatment arms. Each arm had four treatment segments, with each segment consisting of a prophylactic infusion followed by on-demand infusions. The prophylactic infusions used a fixed dose of 35 IU/kg rFVIII-FS, but varied in the amount of pegylated liposomes used for reconstitution (4.2, 12.6, or 22.1 mg/kg of body weight or water as a control). On-demand infusions all used 35 IU/kg rFVIII-FS. After treatment of spontaneous bleeds and a wash-out, subjects crossed to another treatment segment (i.e. another PEGLip-rFVIII-FS dose or control).Sixteen subjects enrolled in and completed the study. Mean number of bleed-free days after prophylactic infusion increased from 7.8 days for control rFVIII-FS to 8.7, 10.8, and 10.9 days for PEGLip-rFVIII-FS reconstituted in 4.2, 12.6, and 22.1 mg/kg of pegylated liposomes, respectively. The difference in bleed-free days approached but did not achieve statistical significance in this small study population. No drug-related adverse events or inhibitors were reported. This study helps establish the optimal concentration of liposomes in PEGLip-rFVIII-FS to prolong the post-infusion bleed-free period.

 
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