40K glycoPEGylated, recombinant FVIIa: 3-month, double-blind, randomized trial of safety, pharmacokinetics and preliminary efficacy in hemophilia patients with inhibitors

Journal of Thrombosis and Haemostasis

Volumn 11, Issue 7, 2013, Pages 1260-1268

  Ljung, R ^a   Karim, F A ^b   Saxena, K ^c   Suzuki, T ^d   Arkhammar, P ^e   Rosholm, A ^e   Giangrande, P ^f  

^a LUND UNIVERSITY   (Sweden)

^b National Blood Centre   (Malaysia)

^c BOSTON CHILDREN S HOSPITAL   (United States)

^d TOKYO MEDICAL UNIVERSITY   (Japan)

^e NOVO NORDISK A S   (Denmark)

^f CHURCHILL HOSPITAL   (United Kingdom)

Author keywords

Factor VII; Factor VIII; Hemophilia; Inhibitors; Safety

Indexed keywords

D DIMER; N 7 GP; RECOMBINANT BLOOD CLOTTING FACTOR 7A; TROPONIN T; UNCLASSIFIED DRUG;

ADOLESCENT; ADULT; AGED; ARTICLE; CHILD; CLINICAL ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; FOLLOW UP; HEMOPHILIA A; HEMOPHILIA B; HUMAN; IMMUNOGENICITY; INJECTION SITE REACTION; MALAISE; MULTICENTER STUDY; PARALLEL DESIGN; PATIENT SAFETY; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROSPECTIVE STUDY; RANDOMIZED CONTROLLED TRIAL; SCHOOL CHILD; STEADY STATE; TREATMENT DURATION;

FACTOR VII; FACTOR VIII; HEMOPHILIA; INHIBITORS; SAFETY;

ADOLESCENT; ADULT; ANTIBODIES; CHILD; COAGULANTS; DOUBLE-BLIND METHOD; FACTOR VIIA; HALF-LIFE; HEMOPHILIA A; HUMANS; MALE; PROSPECTIVE STUDIES; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84880198215     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/jth.12237     Document Type: Article

References (23)

1. World Federation of Hemophilia Report on the Annual Global Survey 2010. World Federation of Hemophilia. Available at: http://www1.wfh.org/publications/files/pdf-1427.pdf. Accessed 25 September 2012.
2. Ghosh S, Sen P, Pendurthi UR, Rao LV. Activity and regulation of glycoPEGylated factor VIIa analogs. J Thromb Haemost 2008; 6: 1525-33.
3. Sen P, Ghosh S, Ezban M, Pendurthi UR, Vijaya Mohan Rao L. Effect of glycoPEGylation on factor VIIa binding and internalization. Haemophilia 2010; 16: 339-48.
4. Stennicke HR, Ostergaard H, Bayer RJ, Kalo MS, Kinealy K, Holm PK, Sørensen BB, Zopf D, Bjørn SE. Generation and biochemical characterization of glycoPEGylated factor VIIa derivatives. Thromb Haemost 2008; 100: 920-8.
5. Plesner B, Westh P, Hvidt S, Nielsen AD. The molar hydrodynamic volume changes of factor VIIa due to GlycoPEGylation. J Pharm Biomed Anal 2011; 55: 597-602.
6. Hamidi M, Azadi A, Rafiei P. Pharmacokinetic consequences of pegylation. Drug Deliv 2006; 13: 399-409.
7. Webster R, Didier E, Harris P, Siegel N, Stadler J, Tilbury L, Smith D. PEGylated proteins: evaluation of their safety in the absence of definitive metabolism studies. Drug Metab Dispos 2007; 35: 9-16.
8. Sorensen BB, Kjalke M, Zopf D, Bjørn SE, Stennicke HR. Platelet-dependent activity of GlycoPEGylated rFVIIa. Blood 2007; 110: Abstract 3140.
9. Johansen PB, Bjørn SE, Agersø H, Thorup I, Hermit MB, Sørensen B, Stennicke HR, Ezban M, Tranholm M. Prolonged effect of GlycoPEGylated rFVIIa (40k-PEG-rFVIIa) in rabbits correlates to activity in plasma. Thromb Haemost 2010; 104: 157-64.
10. Holmberg H, Elm T, Karpf D, Tranholm M, Bjørn SE, Stennicke H, Ezban M. GlycoPEGylated rFVIIa (N7-GP) has a prolonged hemostatic effect in hemophilic mice compared with rFVIIa. J Thromb Haemost 2011; 9: 1070-2.
11. Møss J, Rosholm A, Laurén A. Safety and pharmacokinetics of a glycoPEGylated recombinant activated factor VII derivative: a randomized first human dose trial in healthy subjects. J Thromb Haemost 2011; 9: 1368-74.
12. Møss J, Stenmo C, Jimenez-Yuste V, Bottcher S, Fernandez I. Long-acting glycopegylated recombinant activated factor VII (LA-rFVIIa) is safe and shows a prolonged FVIIa half-life after single and multiple administrations in hemophilia A and B patients, making it suitable for development as prophylactic treatment of patients with hemophilia and inhibitors. Haemophilia 2010; 16 (Suppl. 4): 1-158. 07P16.
13. World Medical Association. Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects. World Medical Association. Available at: http://www.wma.net/en/30publications/10policies/b3/17c.pdf. Accessed 25 September 2012.
14. International Conference on Harmonisation. ICH Harmonised Tripartite Guideline. Guideline for Good Clinical Practice E6(R1). Available at: http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6_R1/Step4/E6_R1__Guideline.pdf. Accessed 25 September 2012.
15. Ministry of Health and Wealth Ordinance on Good Clinical Practice (GCP). MHW Ordinance No.28. http://www.rammellconsulting.files.wordpress.com/2011/05/jp-mhw-ordinance-28-1997-on-gcp.pdf. Accessed 6 June 2012.
16. Scharling B, Nielsen GG, Klitgaard T, Skovsted TA, Møss J, Segel S, Larsen LF. Comparison of coagulant activity of factor VII and activated factor VII activity assays when used for determination of recombinant activated factor VII levels in plasma. Blood Coagul Fibrinolysis 2007; 18: 677-84.
17. Bysted BV, Scharling B, Møller T, Hansen BL. A randomized, double-blind trial demonstrating bioequivalence of the current recombinant activated factor VII formulation and a new robust 25 degrees C stable formulation. Haemophilia 2007; 13: 527-32.
18. Fridberg MJ, Hedner U, Roberts HR, Erhardtsen E. A study of the pharmacokinetics and safety of recombinant activated factor VII in healthy Caucasian and Japanese subjects. Blood Coagul Fibrinolysis 2005; 16: 259-66.
19. Klitgaard T, Nielsen TG. Overview of the human pharmacokinetics of recombinant activated factor VII. Br J Clin Pharmacol 2008; 65: 3-11.
20. Lusher JM, Shapiro SS, Palascak JE, Rao AV, Levine PH, Blatt PM. Efficacy of prothrombin-complex concentrates in hemophiliacs with antibodies to factor VIII: a multicenter therapeutic trial. N Engl J Med 1980; 303: 421-5.
21. Fischer K, Collins P, Björkman S, Blanchette V, Oh M, Fritsch S, Schroth P, Spotts G, Ewenstein B. Trends in bleeding patterns during prophylaxis for severe haemophilia: observations from a series of prospective clinical trials. Haemophilia 2011; 17: 433-8.
22. Konkle BA, Ebbesen LS, Erhardtsen E, Bianco RP, Lissitchkov T, Rusen L, Serban MA. Randomized, prospective clinical trial of recombinant factor VIIa for secondary prophylaxis in hemophilia patients with inhibitors. J Thromb Haemost 2007; 5: 1904-13.
23. Leissinger C, Gringeri A, Antmen B, Berntorp E, Biasoli C, Carpenter S, Cortesi P, Jo H, Kavakli K, Lassila R, Morfini M, Négrier C, Rocino A, Schramm W, Serban M, Uscatescu MV, Windyga J, Zülfikar B, Mantovani L. Anti-inhibitor coagulant complex prophylaxis in hemophilia with Inhibitors. N Engl J Med 2011; 365: 1684-92.