Design of an international investigator-initiated study on MOdern Treatment of Inhibitor-positiVe pATiEnts with haemophilia A (MOTIVATE).

backgroundInhibitor development is the most serious treatment-related complication of replacement coagulation factor VIII (FVIII) therapy for patients with haemophilia A. Immune tolerance induction (ITI), which involves intensive and prolonged treatment with plasma-derived or recombinant FVIII, is the only clinically proven strategy for eradication of inhibitors. The bispecific antibody emicizumab is approved for use in patients with and without inhibitors to prevent bleeding but does not eliminate inhibitors. MOTIVATE (www.motivate-study.com) aims to capture different approaches to the treatment and management of patients with haemophilia A and inhibitors, document current ITI approaches from real-world clinical experience, and evaluate the efficacy and safety of ITI, emicizumab prophylaxis and ITI with emicizumab prophylaxis.

methodsThe investigator-initiated MOTIVATE study [ClinicalTrials.gov identifier: NCT04023019; EudraCT 2019-003427-38] will investigate in real-life clinical practice the management of patients with haemophilia A of any severity who have developed inhibitors to FVIII. All treatment is at the investigator's discretion. The following treatment approaches will be evaluated: Group 1 - ITI with Nuwiq

conclusionsIt is planned to enrol 120 patients who will be followed for up to 5 years. Optional sub-studies will explore factors that may influence ITI results as well as the impact of different treatment approaches on important aspects of patient health, including joint and bone health and the risk of thrombotic events.