144 Chapter 8 Concomitantly, reduced dosing of emicizumab, by 20‒96%, without treated bleeds has been reported [19]. Consequently, we hypothesized that reducing the dose of emicizumab to target a Ctrough of 30 µg/mL using individual pharmacokinetic (PK) is equally effective in the prevention of bleeding as conventional dosing. We designed the DosEmi study to investigate this hypothesis in a large cohort of adult and paediatric PwHA. Additional benefits from this intervention are less frequent injections or lower injection volumes. This is especially beneficial for children, as 66% used a local anaesthetic prior to injection to prevent pain at the injection site [15]. The DosEmi study will be conducted with intensive clinical and laboratory monitoring and is expected to result in significant healthcare savings and improved cost-effectiveness without loss of bleeding control. In this report, we publish the study protocol of the DosEmi study registered as EUCTR2021-004039-10-NL at https://trialsearch.who.int. This study is supported with a grant (Transformatiegelden) by the Dutch federation of academic hospitals (Nederlandse federatie van universitaire medische centra [NFU]). METHODS AND ANALYSIS Primary objective The primary objective of the DosEmi study is to determine whether individualized PKguided dosing of emicizumab targeting a Ctrough of 30 µg/mL is noninferior to conventional dosing of emicizumab in the prevention of treated bleeds in people with congenital haemophilia A. Eligibility A participant must meet the following inclusion criteria: confirmed diagnosis of congenital haemophilia A with a baseline FVIII activity of <6 IU/mL, aged >1 year, receiving conventional dosing of emicizumab dosed according to label (± 6 mg/kg per 4 weeks, rounded to entire vials) at 1‒4 weekly intervals for a duration of ≥12 months prior to inclusion and demonstrating good bleeding control defined as (i) no spontaneous joint/ muscle bleeds in the previous 6 months, and (ii) a maximum of two treated (traumatic) bleeds in the previous 6 months. Study design and setting The DosEmi study is a multi-center, prospective, open-label, crossover study. It was designed as a noninferiority study that was powered to detect a clinically relevant decrease of 15% (risk difference) in the proportion of patients without treated bleeds during follow-up (see Sample size). The crossover intervention was chosen to account for potential imbalanced baseline characteristics, which might occur at treatment start (e.g., instable joint health), and to ensure comparability in an open-label setting [20].
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