title: Results from a large multinational clinical trial (guardian™1) using prophylactic treatment with turoctocog alfa in adolescent and adult patients with severe haemophilia A: safety and efficacy.
abstract: Recombinant factor VIII (rFVIII) products provide a safe and efficacious replacement therapy for prophylaxis and treatment of bleeding episodes in patients with severe haemophilia A. This multinational, open-label, non-controlled trial investigated the safety and efficacy of turoctocog alfa, a new rFVIII product. The primary objective was to evaluate safety. A total of 150 patients (24 adolescents and 126 adults) with severe haemophilia A (FVIII activity ≤ 1%), with at least 150 exposure days (EDs) to any FVIII product and no history of inhibitors were enrolled, and 146 patients (97%) completed the trial. All patients received prophylaxis with turoctocog alfa for approximately 6 months and had a mean of 85 EDs during the trial. None of the patients developed FVIII inhibitors, there were no indications of early FVIII inhibitor development and no safety concerns were identified. A total of 225 adverse events were reported in 100 (67%) patients, with the most common being events associated with dosing procedures, headaches, and nasopharyngitis. A total of 499 bleeding episodes were reported during the trial, the majority (89%) were controlled with 1-2 infusions of turoctocog alfa. Based on patient reports, the success rate (defined as 'excellent' or 'good' haemostatic response) for treatment of bleeding episodes was 81%. The overall median annualized bleeding rate was 3.7 (interquartile range: 8.7) bleeds/patient/year. In conclusion, turoctocog alfa provides a new, safe and effective alternative for prophylaxis and treatment of bleeding episodes in patients with haemophilia A.
authors: Department of Internal Medicine, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA. steven-lentz@uiowa.edu
authors: S R
authors: SR
authors: Lentz
authors: M
authors: M
authors: Misgav
authors: M
authors: M
authors: Ozelo
authors: S Z
authors: SZ
authors: Salek
authors: D
authors: D
authors: Veljkovic
authors: M
authors: M
authors: Recht
authors: M
authors: M
authors: Cerqueira
authors: A
authors: A
authors: Tiede
authors: B
authors: B
authors: Brand
authors: M E
authors: ME
authors: Mancuso
authors: S
authors: S
authors: Seremetis
authors: A
authors: A
authors: Lindblom
authors: U
authors: U
authors: Martinowitz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005169:Factor VIII / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D006467:Hemophilia A / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; C577506:recombinant factor VIII N8; D005169:Factor VIII
keywords: haemophilia A; prophylaxis; recombinant factor VIII; turoctocog alfa