The concomitant use of bypassing agents (BPAs) with emicizumab (Hemlibra®) as prophylaxis in patients with hemophilia A is being evaluated in a new multicenter, open-label, nonrandomized clinical trial. This therapeutic strategy is required for breakthrough bleeds or surgical procedures, but thrombotic events have been described.

“The aim of the UNEBI Study is to evaluate global coagulation function under treatment with emicizumab concomitantly with BPAs in [patients with hemophilia A] with [factor VIII, FVIII] inhibitor,” the authors said.

They will evaluate the usefulness of 3 methods to monitor the effects of BPAs in emicizumab-treated patients: rotational thromboelastometry, clot waveform analysis, and thrombin generation test.

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The study will enroll 60 patients with congenital hemophilia A aged over 4 years who have developed anti-FVIII antibodies (inhibitors) and are being treated or plan to be treated with emicizumab. Participants will be administered the recommended dose of 3 mg/kg of emicizumab via subcutaneous injection once weekly for the first 4 weeks.

The regimen will then follow 1 of the following protocols: 1.5 mg/kg once weekly, 3.0 mg/kg once every 2 weeks, or 6.0 mg/kg once every 4 weeks. The study plans to collect 20 events following the concomitant use of emicizumab and BPAs.

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“This study does not have a strict protocol for every concomitant use of BPAs, but when an event occurs, which means to collect blood samples before and after an infusion of BPA, a strict dosing protocol is mandatory,” the authors explained.

In the case of BPA administration, recombinant activated factor VII must be chosen and administered at an initial dose of 85±5 μg/kg.

The UNEBI Study was approved by the certified review board of Nara Medical University and started on March 6, 2020. The expected end date is September 30, 2023. Patients will be followed up every 6 months at 13 participating hospitals in Japan, and blood samples will be collected every 12 months.


Ogiwara K, Taki M, Suzuki T, et al. Assessment of global coagulation function under treatment with emicizumab concomitantly with bypassing agents in haemophilia A with inhibitor (UNEBI Study): multicentre open-label non-randomised clinical trial. BMJ Open. 2022;12(2):e056922. doi:10.1136/bmjopen-2021-056922