Treatment of Hemophilia A Patients With FVIII Inhibitors

  • Research type

    Research Study

  • Full title

    MOdern Treatment of Inhibitor-PositiVe PATiEnts with Haemophilia A – An International Low-Interventional Pragmatic Investigator Initiated Trial

  • IRAS ID

    272829

  • Contact name

    Mary Mathias

  • Contact email

    mary.mathias@gosh.nhs.uk

  • Sponsor organisation

    HZRM – Hämophilie-Zentrum Rhein Main GmbH

  • Eudract number

    2019-003427-38

  • ISRCTN Number

    ISRCTN00000000

  • Clinicaltrials.gov Identifier

    NCT04023019

  • Clinicaltrials.gov Identifier

    2019-003427-38, EudarCT number

  • Duration of Study in the UK

    8 years, 10 months, 0 days

  • Research summary

    Inhibitor 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 treatment with plasma-derived (pdFVIII) or recombinant FVIII (rFVIII), 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 aims to capture different approaches to the treatment and management of patients with haemophilia A and inhibitors, document current ITI approaches and evaluate the efficacy and safety of ITI, including ITI with emicizumab prophylaxis. MOTIVATE will include multiple sub-studies to assess long-term impact of treatments on joint and bone health and the risk for thrombosis.
    The investigator-initiated MOTIVATE trial – to be initiated in Europe and in North America – will evaluate the management of inhibitors in 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®, octanate® or wilate® and aPCC/rFVIIa if needed to treat bleeding episodes (BEs) or during surgery or for prophylaxis; Group 2 – ITI with Nuwiq®, octanate® or wilate® and emicizumab prophylaxis and aPCC/rFVIIa if needed to treat BEs or during surgery; Group 3 – routine prophylaxis with emicizumab without ITI and aPCC/rFVIIa if needed to treat BEs or during surgery. Participants are not randomised to any treatment group and may change groups during the study. It is planned to enrol 120 patients who will be followed for up to 5 years.

  • REC name

    North of Scotland Research Ethics Committee 2

  • REC reference

    20/NS/0048

  • Date of REC Opinion

    31 Mar 2020

  • REC opinion

    Favourable Opinion