Enhancing the pharmacokinetic properties of recombinant factor VIII: First-in-human trial of glycoPEGylated recombinant factor VIII in patients with hemophilia A

Journal of Thrombosis and Haemostasis

Volumn 11, Issue 4, 2013, Pages 670-678

  Tiede, A ^a   Brand, B ^b   Fischer, R ^c   Kavakli, K ^d   Lentz, S R ^e   Matsushita, T ^f   Rea, C ^g   Knobe, K ^h   Viuff, D ^h  

^a HANNOVER MEDICAL SCHOOL   (Germany)

^b UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^c UNIVERSITY HOSPITAL GIESSEN   (Germany)

^d EGE UNIVERSITY   (Turkey)

^e UNIVERSITY OF IOWA   (United States)

^f NAGOYA UNIVERSITY HOSPITAL   (Japan)

^g ST THOMAS HOSPITAL   (United Kingdom)

^h NOVO NORDISK A S   (Denmark)

Author keywords

First in human; Half life prolongation; Hemophilia A; PEG; RFVIII

Indexed keywords

ANTITHROMBIN; D DIMER; FIBRINOGEN; PROTHROMBIN; RECOMBINANT BLOOD CLOTTING FACTOR 8;

ADULT; ADVERSE OUTCOME; AREA UNDER THE CURVE; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; DISEASE SEVERITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DOSE ESCALATION; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; FIBRINOGEN BLOOD LEVEL; HEADACHE; HEMOPHILIA A; HUMAN; MALE; MULTICENTER STUDY; PARTIAL THROMBOPLASTIN TIME; PRIORITY JOURNAL; PROTHROMBIN TIME; RADIOIMMUNOASSAY; SINGLE DRUG DOSE; TUBERCULOSIS;

AREA UNDER CURVE; DOSE-RESPONSE RELATIONSHIP, DRUG; FACTOR VIII; HALF-LIFE; HEMOPHILIA A; HUMANS; MALE; POLYETHYLENE GLYCOLS; RECOMBINANT PROTEINS;

EID: 84876182114     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/jth.12161     Document Type: Article

References (25)

1. Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker MR, Kilcoyne R, Ingram JD, Manco-Johnson ML, Funk S, Jacobson L, Valentino LA, Hoots WK, Buchanan GR, DiMichele D, Recht M, Brown D, Leissinger C, Bleak S, Cohen A, Mathew P, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med 2007; 357: 535-44.
2. Blanchette VS. Prophylaxis in the haemophilia population. Haemophilia 2010; 16(Suppl. 5): 181-8.
3. Löfqvist T, Nilsson IM, Berntorp E, Pettersson H. Haemophilia prophylaxis in young patients - a long-term follow-up. J Intern Med 1997; 241: 395-400.
4. Nilsson IM, Berntorp E, Löfqvist T, Pettersson H. Twenty-five years' experience of prophylactic treatment in severe haemophilia A and B. J Intern Med 1992; 232: 25-32.
5. Collins PW, Blanchette VS, Fischer K, Bjorkman S, Oh M, Fritsch S, Schroth P, Spotts G, Astermark J, Ewenstein B. Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A. J Thromb Haemost 2009; 7: 413-20.
6. World Federation of Hemophilia. Guidelines for the management of hemophilia. WFH. http://wfh.org/2/docs/Publications/Diagnosis_and_Treatment/Guidelines_Mng_Hemophilia.pdf. Accessed 6 September 2012.
7. Agerso H, Stennicke HR, Pelzer H, Olsen EN, Merricks EP, Defriess NA, Nichols TC, Ezban M. Pharmacokinetics and pharmacodynamics of turoctocog alfa and N8-GP in haemophilia A dogs. Haemophilia 2012; 18: 941-7.
8. Thim L, Vandahl B, Karlsson J, Klausen NK, Pedersen J, Krogh TN, Kjalke M, Petersen JM, Johnsen LB, Bolt G, Norby PL, Steenstrup TD. Purification and characterization of a new recombinant factor VIII (N8). Haemophilia 2010; 16: 349-59.
9. Martinowitz U, Bjerre J, Brand B, Klamroth R, Misgav M, Morfini M, Santagostino E, Tiede A, Viuff D. Bioequivalence between two serum-free recombinant factor VIII preparations (N8 and ADVATE(R)) - an open-label, sequential dosing pharmacokinetic study in patients with severe haemophilia A. Haemophilia 2011; 17: 854-9.
10. Committee for medicinal products for human use (CHMP). Guideline on the clinical investigation of recombinant and human plasma-derived factor VIII products. European Medicines Agency. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003614.pdf. Accessed 26 October 2012.
11. World Medical Association. Declaration of Helsinki: Ethical principles for medical research involving human subjects. World Medical Association. http://www.wma.net/en/30publications/10policies/b3/index.html. Accessed 6 September 2012.
12. International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use (ICH). Harmonised Tripartite Guideline: Guideline for Good Clinical Practice E6(R1). Step 4 version. ICH. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6_R1/Step4/E6_R1__Guideline.pdf. Accessed 6 September 2012.
13. Bjorkman S. Prophylactic dosing of factor VIII and factor IX from a clinical pharmacokinetic perspective. Haemophilia 2003; 9(Suppl. 1): 101-8.
14. Bolton-Maggs PH, Perry DJ, Chalmers EA, Parapia LA, Wilde JT, Williams MD, Collins PW, Kitchen S, Dolan G, Mumford AD. The rare coagulation disorders - review with guidelines for management from the United Kingdom Haemophilia Centre Doctors' Organisation. Haemophilia 2004; 10: 593-628.
15. Giles AR, Verbruggen B, Rivard GE, Teitel J, Walker I. A detailed comparison of the performance of the standard versus the Nijmegen modification of the Bethesda assay in detecting factor VIII:C inhibitors in the haemophilia A population of Canada. Association of Hemophilia Centre Directors of Canada. Factor VIII/IX Subcommittee of Scientific and Standardization Committee of International Society on Thrombosis and Haemostasis. Thromb Haemost 1998; 79: 872-5.
16. Verbruggen B, Novakova I, Wessels H, Boezeman J, van den Berg M, Mauser-Bunschoten E. The Nijmegen modification of the Bethesda assay for factor VIII:C inhibitors: improved specificity and reliability. Thromb Haemost 1995; 73: 247-51.
17. Gaberc-Porekar V, Zore I, Podobnik B, Menart V. Obstacles and pitfalls in the PEGylation of therapeutic proteins. Curr Opin Drug Discov Devel 2008; 11: 242-50.
18. Jevsevar S, Kunstelj M, Porekar VG. PEGylation of therapeutic proteins. Biotechnol J 2010; 5: 113-28.
19. Fishburn CS. The pharmacology of PEGylation: balancing PD with PK to generate novel therapeutics. J Pharm Sci 2008; 97: 4167-83.
20. Negrier C, Knobe K, Tiede A, Giangrande P, Moss J. Enhanced pharmacokinetic properties of a glycoPEGylated recombinant factor IX: a first human dose trial in patients with hemophilia B. Blood 2011; 118: 2695-701.
21. Webster R, Elliott V, Park BK, Walker D, Hankin M, Taupin P. PEG and PEG conjugates toxicity: towards an understanding of the toxicity of PEG and its relevance to PEGylated biologicals. In: Veronese FM, ed. PEGylated Protein Drugs: Basic Science and Clinical Applications. Switzerland: Birkhäuser Basel, 2009: 127-46.
22. Geraghty S, Dunkley T, Harrington C, Lindvall K, Maahs J, Sek J. Practice patterns in haemophilia A therapy - global progress towards optimal care. Haemophilia 2006; 12: 75-81.
23. Journeycake JM, Quinn CT, Miller KL, Zajac JL, Buchanan GR. Catheter-related deep venous thrombosis in children with hemophilia. Blood 2001; 98: 1727-31.
24. Neunert CE, Miller KL, Journeycake JM, Buchanan GR. Implantable central venous access device procedures in haemophilia patients without an inhibitor: systematic review of the literature and institutional experience. Haemophilia 2008; 14: 260-70.
25. Tarantino MD, Collins PW, Hay CR, Shapiro AD, Gruppo RA, Berntorp E, Bray GL, Tonetta SA, Schroth PC, Retzios AD, Rogy SS, Sensel MG, Ewenstein BM. Clinical evaluation of an advanced category antihaemophilic factor prepared using a plasma/albumin-free method: pharmacokinetics, efficacy, and safety in previously treated patients with haemophilia A. Haemophilia 2004; 10: 428-37.