MOTIVATE, Study of Treating Hemophilia A With Inhibitors, Enrolls 1st US Patient

A first patient in the U.S. has enrolled in a multinational study to collect real-world data on different approaches in managing hemophilia A in people with inhibitors, with an aim of understanding how treatment decisions affect patients.

The investigator-led MOTIVATE study (NCT04023019; EudraCT No. 2019-003427-38) is recruiting up to 120 children and adults in the U.S. and Germany. Sites may also open in Canada.

“We are very excited that patient enrollment in MOTIVATE has begun in the US,” Robert Sidonio, MD, the study’s coordinating investigator in the U.S. and Canada, said in a press release.

“The data being collected will be invaluable in progressing our understanding of the efficacy and safety of different therapeutic regimens, bringing us closer to our goal of improving the standard of care for hemophilia A patients with inhibitors,” Sidonio added.

In addition to capturing different management approaches, MOTIVATE aims to document current immune tolerance induction practices (ITI), which are often used to prevent the development of inhibitors. The study will also compare the safety and efficacy of different treatment approaches, including ITI with and without preventive treatment with Hemlibra (emicizumab).

Inhibitors are neutralizing antibodies produced by the body’s immune system that target factor VIII (FVIII) — the blood clotting protein that is missing in hemophilia A patients and is usually replenished through replacement therapies. These inhibitors are one of the biggest challenges in FVIII replacement therapy, since their presence lowers treatment effectiveness, and in worst cases, renders it useless.

During the study, participants will be assigned to one of three groups based on the treatments they receive, and followed for up to five years.

One group will be given ITI with Nuwiq, octanate, or wilate (von Willebrand Factor), along with activated prothrombin complex concentrate (aPCC) or recombinant FVIIa (rFVIIa), which will be given as needed to treat bleeds. A second group will receive ITI with Nuwiq, octanate, or wilate, in combination with Hemlibra, along with aPCC or rFVIIa as needed. Those in a third patient group will receive routine prophylaxis with Hemlibra — and aPCC or rFVIIa as needed — without ITI.

The study’s main goals include assessing the proportion of patients whose FVIII inhibitor levels drop under 0.6 Bethesda units per milliliter; the proportion seeing their FVIII levels recover by at least 66% of the predefined reference value of 1.5% international units per kilogram of body weight; the proportion of patients in whom FVIII lasts at least six hours in circulation before its levels drop to half; and participants’ annualized bleeding rates.

Other study outcomes include the time to ITI, frequency of therapy use during ITI, and the rate of FVIII inhibitor relapse.

Investigators are also conducting six optional sub-studies within MOTIVATE. Some of these aim to analyze bone and joint health, assess the risk of blood clots, and analyze variations in patients’ F8 gene, which codes for the FVIII protein. These sub-studies are expected to provide further insights into the various factors associated with treatment outcomes, and how different treatment regimens might affect patient outcomes.

“Real-world data from MOTIVATE and its sub-studies will help us greatly to understand how to optimize treatment for hemophilia A patients with inhibitors to improve patient outcomes,” said Carmen Escuriola-Ettingshausen, MD, the study’s coordinating investigator outside North America.

MOTIVATE is being sponsored by Emory University, which is collaborating with Octapharma, the maker of Nuwiq, octanate, and wilate.