Safety, efficacy and pharmacokinetics of rVIII‐SingleChain in children with severe hemophilia A: results of a multicenter clinical trial. (21st March 2017)

• Record Type: Journal Article
• Authors: Stasyshyn, O.; Djambas Khayat, C.; Iosava, G.; Ong, J.; Abdul Karim, F.; Fischer, K.; Veldman, A.; Blackman, N.; St. Ledger, K.; Pabinger, I.
• Is Part Of: Journal of thrombosis and haemostasis. Volume 15:Number 4(2017)
• Page Start: 636
• Page End: 644
• Publication Date: 2017-03-21
• Subjects: clinical trial -- factor VIII -- hemophilia A -- pediatric -- pharmacokinetics -- safety; Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.13647
• Languages: English
• ISSNs: 1538-7933

Abstract

Abstract : Essentials rVIII‐SingleChain is a novel recombinant factor VIII with covalently bonded heavy and light chains. Efficacy, safety and pharmacokinetics were studied in pediatric patients with severe hemophilia A. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00. rVIII‐SingleChain showed excellent hemostatic efficacy and a favorable safety profile. 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.