SUMMARY: Background rVIII-SingleChain is a novel B-domain truncated recombinant factor VIII (rFVIII) comprised of covalently bonded FVIII heavy and light chains, demonstrating a high binding affinity to von Willebrand factor. Objectives This phase III study investigated the safety, efficacy and pharmacokinetics of rVIII-SingleChain in previously treated pediatric patients < 12 years of age with severe hemophilia A. Patients/Methods Patients could be assigned to prophylaxis or on-demand therapy by the investigator. For patients assigned to prophylaxis, the treatment regimen and dose were based on the bleeding phenotype. For patients receiving on-demand therapy, dosing was guided by World Federation of Hemophilia recommendations. The primary endpoint was treatment success, defined as a rating of 'excellent' or 'good' on the investigator's clinical assessment of hemostatic efficacy for all treated bleeding events. Results The study enrolled 84 patients (0 to < 6 years, n = 35; ≥ 6 to < 12 years, n = 49); 81 were assigned to prophylaxis and three to an on-demand regimen. Patients accumulated a total of 5239 exposure days (EDs), with 65 participants reaching > 50 EDs. In the 347 bleeds treated and evaluated by the investigator, hemostatic efficacy was rated as excellent or good in 96.3%. The median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.00, 2.20), and the median annualized bleeding rate was 3.69 (Q1, Q3: 0.00, 7.20) across all prophylaxis regimens. No participant developed an inhibitor. Conclusions rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy and a favorable safety profile in a clinical study in children < 12 years of age with severe hemophilia A.
OBJECTIVES: The aim of this extension study was to investigate the long-term safety and efficacy of rVIII-SingleChain prophylaxis in ≥200 previously treated patients (PTPs) with hemophilia A with ≥100 exposure days (EDs).
METHODS: In total, 222 patients were enrolled, of which 204 rolled over from prior rVIII-SingleChain studies. The median age was 21 years (range, 2-65 years), including 155 patients ≥12 years and 67 patients <12 years. Patients continued with their previously assigned dose and regimen, or switched at the investigator's discretion. Patients were treated for a mean duration of 31 months (range, 1-47 months), the mean ED was 342 (standard deviation, 135.5), and 212 (95.5%) patients achieved >100 EDs. When the study ended, most patients were on either a prophylaxis regimen of 34.9 (17-62) IU/kg, 3×/week (N = 88; 39.6%), or 37.2 (13-65) IU/kg, 2×/week regimen (N = 72; 32.4%).
RESULTS: Hemostatic efficacy was rated excellent or good in 87.1% of assessed bleeds. The median (range) annualized bleeding rate was 1.21 (0.0-42.6), and the annualized spontaneous bleeding rate (AsBR) was 0.32 (0.0-33.0) for prophylaxis regimens. Median AsBR was similar for patients treated 3×/week and 2×/week (0.31 and 0.30, respectively). Surgical hemostatic efficacy was rated excellent or good in 100% of surgeries. No inhibitors, anaphylactic reactions, or thromboembolic events were reported in PTPs.
CONCLUSION: These results confirm the safety and efficacy of rVIII-SingleChain as a long-term prophylaxis treatment modality for PTPs with severe hemophilia A.