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.
Keywords
Haemophilia - prophylaxis - longer- acting factor VIII - pegylated liposome
