Recombinant factor XIII prophylaxis is safe and effective in young children with congenital factor XIII‐A deficiency: international phase 3b trial results

Abstract

Background Factor XIII deficiency is a rare, severe congenital bleeding disorder. Monthly prophylaxis with recombinant FXIII A-Subunit (rFXIII) has demonstrated favorable safety and efficacy in patients aged ≥ 6 years, and may similarly benefit younger children. Objective To evaluate the long-term safety and efficacy of rFXIII in children aged < 6 years with congenital FXIII A-subunit deficiency. Patients/methods Six children, who had previously completed a single-dose pharmacokinetic trial of rFXIII, received 35 IU kg rFXIII every 28 days (± 2 days) for a minimum of 52 weeks, and were evaluated for bleeding and adverse events. The Berichrom FXIII activity assay was used to monitor FXIII activity. Results The children, three girls and three boys, had an average age of 3.0 years (range: 1-4 years) at enrollment. The total treatment duration was 1.8-3.5 years, giving a total of 16.6 patient-years. No antibody development, thromboembolic events or allergic reactions occurred. There were 93 mild and seven moderate adverse events. Two adverse events (lymphopenia and gastroenteritis) were reported as probably or possibly related to rFXIII in two children. Two serious adverse events, unrelated to rFXIII, were reported in a single child, each related to head injury, and neither resulting in intracranial hemorrhage. The geometric mean FXIII activity trough was 0.19 IU mL . No bleeding episodes requiring treatment with an FXIII-containing hemostatic agent occurred during the trial; thus, the annualized bleeding rate was 0. Conclusions Consistent with data from older age groups, prophylaxis with rFXIII appears to be safe and effective in young children with congenital FXIII A-subunit deficiency.

Recombinant FXIII (rFXIII-A2) Prophylaxis Prevents Bleeding and Allows for Surgery in Patients with Congenital FXIII A-Subunit Deficiency

“…30 Despite that, a potential limitation was the low number of children/adolescents ( n = 16) participating in the mentor™2 trial; however, the current mentor™2 results support those from the mentor™5 trial, which showed efficacy and safety in six paediatric patients aged 1 to 4 years, in which rFXIII-A 2 prophylaxis was well tolerated and provided appropriate haemostatic coverage; the ABR was 0. 18 …”

“… 17 Similarly, the paediatric mentor™5 showed excellent efficacy and safety of prophylaxis with 35 IU/kg rFXIII-A 2 dosed every 4 weeks in patients aged <6 years. 18 Previous reports have shown similar pharmacokinetics (PK) in young children to that of older children and adults. 19 20 In the mentor™ programme to date, no patients treated with rFXIII-A 2 have developed FXIII-neutralizing antibodies (i.e., FXIII inhibitors).…”

Hemorrhagic Shock after Neonatal Circumcision: Severe Congenital Factor XIII Deficiency

“…Of these adverse events, 20 experienced a possible pathogen transmission, 12 a hypersensitivity reaction, 7 a possible thromboembolic event, and 5 developed a possible inhibitor [ 23 ]. For Tretten®, an international phase 3b trial exploring its safety and efficacy in pediatric patients with congenital factor XIII deficiency found that prophylaxis over 1.8–3.5 years dropped the annualized bleeding rate to zero with mostly mild adverse events [ 24 ]. Over the 16.6 patient years of the study, there were no thromboembolic events or hypersensitivity reactions observed [ 24 ].…”

“…For Tretten®, an international phase 3b trial exploring its safety and efficacy in pediatric patients with congenital factor XIII deficiency found that prophylaxis over 1.8–3.5 years dropped the annualized bleeding rate to zero with mostly mild adverse events [ 24 ]. Over the 16.6 patient years of the study, there were no thromboembolic events or hypersensitivity reactions observed [ 24 ]. Of note, during the study, two patients experienced a head injury and neither developed an intracranial hemorrhage [ 24 ].…”

Reducing Fibrinogen and Factor XIII Using Double-Filtration Plasmapheresis for Antibody-Mediated Rejection: Predictive Models

“…Similarly, a recent study reported on 6 children with factor XIII-A deficiency who had received once-monthly prophylaxis with recombinant factor XIII-A: the prophylaxis was well tolerated and no anti-FXIII antibodies were detected. Another study reported that prophylaxis was effective with an annualized bleeding rate of zero [23].…”