Study design for the phase 2 concizumab trials. (A) explorer5 (HA without inhibitors) and (B) explorer4 (HAwI/HBwI). Dose-escalation criteria: if a patient experienced ≥3 spontaneous bleeding episodes within the preceding 12 weeks of treatment with concizumab, the patient could be escalated to the next dose level. In explorer4, after completion of the main part, patients in the rFVIIa arm continuing on to the extension part of the trial were switched to daily prophylactic subcutaneous treatment with concizumab 0.15 mg/kg, with potential dose escalation as appropriate. ↑, Dose escalate to the next dose level, based on the dose-escalation criteria. R, randomization.