The current investigator-driven, open-label, crossover, phase 4 DosEmi study is being conducted to assess the noninferiority of pharmacokinetic-guided reduced emicizumab dosing compared with conventional dosing among individuals with hemophilia A from all hemophilia centers located in The Netherlands.
The study protocol of DosEmi has been published recently in the journal BMJ Open.
Although prophylaxis with emicizumab effectively prevents bleeding in this patient population, use of the agent is a burden for national healthcare budgets and thus may limit access to the drug. Patients with hemophilia A, who have a deficiency in coagulation factor VIII (FVIII), usually experience spontaneous or provoked bleeds, which occur mainly in major joints and are associated with chronic arthropathy.
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Emicizumab dosing, which is based on an individual’s body weight, is typically administered at fixed intervals of 7, 14, or 28 days, leading to mean plasma levels of 55±15 μg/mL. Several studies, however, have suggested that the use of a pharmacokinetic-guided minimal effective concentration of 30 μg/mL may be equally as beneficial as the higher doses typically used for the prevention of bleeds.
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The primary study objective of DosEmi is to establish whether individualized pharmacokinetic-guided dosing of emicizumab that targets a Ctrough of 30 μg/mL is noninferior to the use of conventional dosing for preventing treated bleeds among patients with congenital hemophilia A. To participate in DosEmi, individuals must fulfill the following criteria:
- Confirmed diagnosis of congenital hemophilia A with a baseline FVIII activity of less than 6 IU/mL
- Be 1 or more years of age
- Currently be receiving conventional emicizumab doses (±6 mg/kg per 4 weeks at individualized 1 to 4 weekly intervals for ≥12 weeks prior to study inclusion) with good bleeding control (ie, no spontaneous joint/muscle bleeds in prior 6 months and ≤2 treated bleeds in the last 6 months)
The following comparisons will be performed in each participant:
- Comparator: 6 months of conventional dosing of emicizumab
- Intervention: 12 months of individualized pharmacokinetic-guided emicizumab dosing to attain a target Ctrough of 30 μg/mL
The researchers are seeking to enroll 95 participants in an effort to account for any possible dropouts. The primary study outcome is the percentage of patients without treated bleeds during 6 months of conventional therapy (ie, comparator) vs 6 months of individualized pharmacokinetic-guided dosing (ie, intervention). Secondary outcomes include the following:
- Proportion of participants without treated bleeds in the follow-up periods of 12 months in the conventional vs intervention groups.
- Percentage of patients without any spontaneous joint/muscle bleeds in the 6 and 12 months on conventional vs individualized pharmacokinetic-guided dosing.
- Annualized bleed rates of treated bleeds in the conventional vs intervention arms.
“The study provides a unique opportunity to evaluate alternative emicizumab dosing strategies in a safe and well-controlled clinical setting,” the researchers noted. “Participation in the DosEmi study is expected to reduce the pain associated with emicizumab injections,” they concluded.
Reference
Donners A, van der Zwet K, Egberts ACG, et al. DosEmi study protocol: a phase IV, multicentre, open-label, crossover study to evaluate non-inferiority of pharmacokinetic-guided reduced dosing compared with conventional dosing of emicizumab in people with haemophilia A. BMJ Open. Published online June 26, 2023. doi:10.1136/bmjopen-2023-072363
