Pharmacokinetics of recombinant factor XIII in young children with congenital FXIII deficiency and comparison with older patients

Abstract

Congenital factor XIII (FXIII) deficiency is a rare bleeding disorder, which in its severe form is associated with a significant bleeding phenotype, requiring regular prophylactic therapy. A recently developed recombinant FXIII (rFXIII) has demonstrated safety and efficacy in children aged ≥6 years and adults (mentor1 trial). This article describes the mentor4 trial, which has assessed the pharmacokinetics (PK) and safety of rFXIII in younger children (1 to <6 years) with congenital FXIII deficiency, and compares extrapolated PK parameters with the mentor1 trial. Six children with congenital FXIII A-subunit deficiency received a single, 35 IU kg(-1) rFXIII dose. PK properties were similar in all the children, with a mean area under the concentration vs. 30-day time curve of 248.6 IU h(-1) mL(-1) , maximal FXIII activity (30 min) of 0.67 IU mL(-1) , and mean 30-day trough of 0.21 IU mL(-1) . All patients maintained FXIII activity above the lower target level (0.1 IU mL(-1) ). rFXIII half-life was 15.1 days (range, 10-25). No safety findings of clinical concern were observed. PK properties of rFXIII were similar in patients from both trials. The study demonstrated that a single dose of 35 IU kg(-1) rFXIII maintained plasma FXIII levels above 0.1 IU mL(-1) over a 30-day period in young children with congenital FXIII deficiency, and is, therefore, likely to provide adequate prophylaxis in this age group. The study extends the previous findings of the mentor1 trial and confirms that no dose adjustment is required for different age groups with congenital FXIII deficiency.

Keywords: children; congenital FXIII deficiency; pharmacokinetics; prophylaxis; recombinant FXIII; safety.