Concizumab Prophylaxis in Paediatric Participants With Haemophilia A/b With Inhibitors in the Phase 3 Explorer10 Study: Efficacy, Safety and Pk/pd Results From the 32-week Cut-off
Year: 2026
Type: article
Abstract: Background Concizumab is an anti-tissue factor pathway inhibitor (TFPI) monoclonal antibody approved in the US, Europe and other countries for once-daily, subcutaneous prophylaxis for patients aged ≥12 years with haemophilia A/B with or without inhibitors. Aim To assess concizumab efficacy and safety in paediatric participants with haemophilia A/B with inhibitors (HAwI/HBwI) at the explorer10 (NCT05135559) 32-week cut-off. Methods Explorer10 is a multi-centre, non-randomised phase 3 study of male paediatric partici-pants (<12 years) who were concizumab-naïve (arm 1) or previously treated with concizumab via compassionate use (arm 2). Concizumab-naïve participants received a 1.0 mg/kg loading dose (Day 1), followed by 0.20 mg/kg daily from Day 2, with potential dose adjustment at 5–8 weeks to 0.15 or 0.25 mg/kg based on plasma concentration. The primary endpoint was the number of treated spontaneous/traumatic bleeding episodes during concizumab prophylaxis vs previous on-demand treatment (≥26 weeks; historical records) in arm 1. Cut-off was when all arm 1 par-ticipants completed week 32 or withdrew. Safety and PK/PD parameters were also evaluated. Informed consent was obtained and the study was approved by local ethics committees. Results In 24 participants, estimated mean ABR (95% CI) was 2.08 (1.27; 3.41) on concizumab prophylaxis vs 11.51 (7.75; 17.09) with previous on-demand treatment. The ABR ratio was 0.18 (0.11; 0.29; P < 0.001), representing an 82% ABR reduction and demonstrating superiority of con-cizumab prophylaxis. Concizumab plasma concentration remained stable over time, free TFPI levels decreased and remained stable, and the geometric mean thrombin peak increased to within the normal adult range. Concizumab was well tolerated, with no safety concerns identi-fied. Conclusion In paediatric HAwI/HBwI, concizumab prophylaxis was effective in bleed prevention compared with previous observations.
Institutions: Vilnius University, McMaster Children's Hospital, Novo Nordisk (Denmark), Hospital Universitario La Paz, Hospital La Paz Institute for Health Research, Ege University, National Health Laboratory Service, University of the Witwatersrand, Great Ormond Street Hospital, Great Ormond Street Hospital for Children NHS Foundation Trust, St. Marianna University School of Medicine, Institute of Child Health, University of Washington, Azienda Ospedaliero-Universitaria Careggi
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223104074