MOTIVATE (MOdern Treatment of Inhibitor-positiVe patiEnts with haemophilia A) begins patient recruitment

MOTIVATE is a multi-center study initiated by researchers to capture different approaches to the management of patients with hemophilia A and inhibitors. MOTIVATE is registered as a non-interventionist study in the United States ( NCT04023019 ) and as a pragmatic, low-intervention trial in Europe ( EudraCT No. 2019-003427-38 ).

Inhibitor development is the most serious complication related to hemophilia A treatment, since inhibitors neutralize FVIII activity rendering it ineffective in preventing and controlling bleeding. Induction of immune tolerance (ITI) can be achieved with prolonged and frequent administration of FVIII; this is the only proven strategy for the eradication of inhibitors. Although the bi-specific monoclonal antibody emicizumab offers an alternative to bridging or bypass agents to control bleeding in patients with inhibitors, neither emicizumab nor bridging agents eradicate inhibitors.

The objective of MOTIVATE is to document established and other novel inhibitor eradication strategies in order to assess the efficacy and safety of ITI, even if it is performed in conjunction with emicizumab prophylaxis. The study will also analyze the impact of different approaches. of treatment in the prevention of bleeding in patients with inhibitors. Three groups will be evaluated depending on the treatment:

• ITI (with recombinant FVIII derived from a human cell line, Nuwiq ® , or with one of the plasma derived FVIII: octanate ® or wilate ® )
• ITI (with Nuwiq ® , octanate ® or wilate ® ) and prophylaxis with emicizumab
• Routine prophylaxis with emicizumab, aPCC or rFVIIa without ITI

All three approaches may include bridging agents (aPCC or rFVIIa) if necessary to treat bleeding episodes or during surgery. Patients will be followed for up to five years, and may switch to another group if their treatment changes at the discretion of the local physician.

MOTIVATE includes several optional sub-studies such as analysis of bone and joint health biomarkers, thrombotic risk assessment, or analysis of genetic variants of the F8 gene . The aim of these is to better understand the factors associated with treatment outcomes and the impact of different therapeutic regimens.

MOTIVATE is chaired by two coordinating researchers, Dr. Carmen Escuriola-Ettingshausen, director of the Hämophilie-Zentrum Rhein Main in Mörfelden-Walldorf, Germany, and Dr. Robert F. Sidonio Jr , Associate Professor of Pediatrics and Director of Clinical Operations at Hemophilia at the Georgia Center for Bleeding and Clotting Disorders, Children's Healthcare of Atlanta , Emory University , Atlanta, Georgia , United States.

Dr. Sidonio commented: " It is very exciting that the recruitment of patients for MOTIVATE has started. We hope that the MOTIVATE study will provide valuable information about the actual experience of patients with hemophilia A who have developed inhibitors to FVIII ." Dr. Escuriola-Ettingshausen added: " We hope that the MOTIVATE data will more accurately reveal treatment decisions to help us optimize the management of each patient. The sub-studies also promise to greatly increase our understanding of inhibitors. and how we can influence patient outcomes . "

MOTIVATE aims to recruit a total of 120 patients of any age and with hemophilia A of any severity who have developed inhibitors against any FVIII product. MOTIVATE has the financial support of Octapharma AG (Lachen, Switzerland).