Study design for the phase 2 concizumab trials. (A) explorer4 (HAwI/HBwI). (B) explorer5 (HA). As shown in panel A, patients were randomized 2:1 to receive either prophylaxis with concizumab or on-demand treatment with rFVIIa for 24 weeks (main part). Patients who received rFVIIa during the main part were switched to concizumab prophylaxis during the extension part (56-94 weeks). As shown in panel B, all patients received concizumab prophylaxis during the main part (24 weeks) and extension part (52-102 weeks). Dose escalation criteria throughout both trials were ≥3 treatment-requiring spontaneous bleeding episodes within the 12 weeks before concizumab treatment during both the main and extension parts.