Second interim analysis results from the STASEY trial: A single-arm, multicentre, open-label, phase III clinical trial to evaluate the safety and tolerability of emicizumab prophylaxis in persons with haemophilia A (PwHA) with FVIII inhibitors

Objective Emicizumab, a subcutaneously administered, bispecific monoclonal antibody, bridges activated factor (F)IX and FX, replacing the function of missing activated FVIII in persons with haemophilia A (PwHA), thereby restoring haemostasis. Here we report updated interim results from STASEY (NCT03191799), a study of emicizumab prophylaxis in PwHA with FVIII inhibitors.

Material and Methods Following ethics committee approval and informed consent, PwHA aged ≥12 years with FVIII inhibitors (N = 195; intent-to-treat population) received emicizumab 3 mg/kg per week for 4 weeks, followed by 1.5 mg/kg per week. Study duration was 2 years. The primary objective was safety (adverse events [AEs], including thromboembolic events [TEs] and hypersensitivity); secondary objectives included efficacy (annualised bleed rates [ABRs]).

Results At data cut-off (20 May 2019), 193 PwHA had received emicizumab and were evaluable for safety; median age (range) was 28.0 (12–80) years; median (range) treatment duration was 50.9 (1.1–88.1) weeks. Emicizumab was well tolerated ([Table 1]). Emicizumab-related AEs were reported in 33 PwHA; the most common were injection-site reactions, occurring in 22/193 (11.4 %) PwHA. Two AEs were classified as TEs: ST-elevation myocardial infarction (STEMI; n = 1) and hypertrophic clot following tooth extraction caused by multiple doses of antifibrinolytic combined with rFVIIa (n = 1). The 55-year-old PwHA with STEMI had several risk factors, including a history of smoking, hypertension and family history of coronary heart disease. He did not receive bypassing agents and continued emicizumab without dose adjustment; the treating physician assessed the event as unrelated to emicizumab. One previously reported fatality (polytrauma), was assessed as unrelated to emicizumab. Three PwHA received activated prothrombin complex concentrate and 32 received rFVIIa, with no associated thrombotic microangiopathy or arterial/venous TEs. Ten PwHA (5.2 %) developed anti-drug antibodies, none with neutralising potential (by pharmacokinetic/clinical assessment); they continued on 1.5 mg/kg per week emicizumab with no increased bleeding. ABRs remained low ([Table 2]).

Conclusion No new safety signals were identified; these data confirm the safety results from the HAVEN clinical program.

Tab 1. Safety Summary (Safety-Evaluable Population)

Tab 2. Efficacy Summary (Intent-to-Treat Population)

Publication History

Article published online:
18 June 2021