Safety, efficacy and pharmacokinetics of rVIII-SingleChain in children with severe hemophilia A: results of a multicenter clinical trial.
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.



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.
Institute of Blood Pathology and Transfusion Medicine, National Academy of Medical Sciences of Ukraine, Lviv, Ukraine.
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Stasyshyn
Lebanon Department of Pediatrics, Hotel Dieu de France Hospital, Beirut, Lebanon.
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Djambas Khayat
JSC Scientific-Research Institute of Hematology and Transfusiology, Tbilisi, Georgia.
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Iosava
Brokenshire Integrated Health Ministries, Inc., Davao, Philippines.
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Ong
Hemophilia Clinic, National Blood Centre, Kuala Lumpur, Malaysia.
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Abdul Karim
Van Creveldkliniek, University Medical Center Utrecht, Utrecht, the Netherlands.
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Fischer
Clinical R&D, CSL Behring, Marburg, Germany.
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Veldman
Clinical R&D, CSL Behring, King of Prussia, PA, USA.
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Blackman
Clinical R&D, CSL Behring, King of Prussia, PA, USA.
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St Ledger
Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University Vienna, Vienna, Austria.
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Pabinger
D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005169:Factor VIII / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy*; D006470:Hemorrhage; D006487:Hemostasis / Q000187:drug effects; D006490:Hemostatics / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D061214:Patient Safety; D010372:Pediatrics; D010641:Phenotype; D011485:Protein Binding; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000737:chemistry
D006490:Hemostatics; D014841:von Willebrand Factor; C427184:recombinant factor VIII SQ; D005169:Factor VIII
clinical trial; factor VIII; hemophilia A; pediatric; pharmacokinetics; safety