Safety/Efficacy Study to Assess Whether FVIII/VWF Concentrate Can Induce Immune Tolerance in Haemophilia A Patients

Summary

The purpose of this study is to assess the role of a FVIII/VWF complex concentrate (Emoclot) in successfully inducing immune tolerance (I.T.I.) in patients with Haemophilia A with inhibitors, including patients at high risk of failure.

Timeline

Start

2015-01

Primary completion

2019-01

Completion

2020-01

Publications

• Background Gilles JG, Saint-Remy JMR. Recombinant and plasma-derived factor VIII are immunologically distinct in in vitro assays. Thromb Haemost 1995; 73:1213.
• Background Guerois C, Laurian Y, Rothschild C, Parquet-Gernez A, Duclos AM, Negrier C, Vicariot M, Fimbel B, Fressinaud E, Fiks-Sigaud M, et al. Incidence of factor VIII inhibitor development in severe hemophilia A patients treated only with one brand of highly purified plasma-derived concentrate. Thromb Haemost. 1995 Feb;73(2):215-8.
• Background Yee TT, Williams MD, Hill FG, Lee CA, Pasi KJ. Absence of inhibitors in previously untreated patients with severe haemophilia A after exposure to a single intermediate purity factor VIII product. Thromb Haemost. 1997 Sep;78(3):1027-9.
• Background Teitel JM. Safety of coagulation factor concentrates. Haemophilia. 1998 Jul;4(4):393-401. doi: 10.1046/j.1365-2516.1998.440393.x.
• Background Rokicka-Milewska R, Klukowska A, Dreger B, Beer H-J. Incidence of factor VIII inhibitor development in previously untreated Haemophilia A patients after exposure to a double viral inactivated factor VIII concentrate. Ann Hematol 1999; 78 (suppl 1)
• Background Aznar JA, Lorenzo JI, Molina R, Haya S, Querol F, Dasi MA. Zero incidence of inhibitor development in previously treated haemophilia A, HIV-negative patients upon exposure to a plasma-derived high-purity and double viral inactivated factor VIII concentrate. Haemophilia. 1998 Jan;4(1):21-4. doi: 10.1046/j.1365-2516.1998.00139.x.
• Background Smith MP, Rice KM, Savidge GF. Successful clinical use of a plasma-derived, dual virus inactivated factor VII concentrate incorporating solvent-detergent and dry heat treatment. Thromb Haemost. 1997 Feb;77(2):406-7. No abstract available.
• Background Sukhu K, Keeling DM, Giangrande PL. Variation in inhibitor reactivity in acquired haemophilia A with different concentrates. Clin Lab Haematol. 2000 Oct;22(5):287-90. doi: 10.1046/j.1365-2257.2000.00328.x.
• Background Gensana M, Altisent C. Aznar JA, Casana P, Hernandez F, Jorquera JI, Magallon M, Massot M, Puig L. Factor VIII inhibitors directed to the A2 domain and the light chain may also show less reactivity to FVIII complexed with VWF. World Federation of Haemophilia, The Hague, May 1998, (Abstract book).
• Background Suzuki T, Arai M, Amano K, Kagawa K, Fukutake K. Factor VIII inhibitor antibodies with C2 domain specificity are less inhibitory to factor VIII complexed with von Willebrand factor. Thromb Haemost. 1996 Nov;76(5):749-54.
• Background Gensana M, Altisent C, Aznar JA, Casana P, Hernandez F, Jorquera JI, Magallon M, Massot M, Puig L. Influence of von Willebrand factor on the reactivity of human factor VIII inhibitors with factor VIII. Haemophilia. 2001 Jul;7(4):369-74. doi: 10.1046/j.1365-2516.2001.00526.x.
• Background Berntorp E, Ekman M, Gunnarsson M, Nilsson IM. Variation in factor VIII inhibitor reactivity with different commercial factor VIII preparations. Haemophilia. 1996 Apr;2(2):95-9. doi: 10.1111/j.1365-2516.1996.tb00022.x.
• Background Kreutz W: Immune tolerance induction (ITI) in Haemophilia A-patients with inhibitors - the choice of concentrate affecting success. Haematologica 2001; 86 (S4):16-20
• Background Kreuz W, Steiner J, Auerswald G, Beeg T, Becker S. Successful immunetolerance therapy of FVIII-inhibitor in chldren after changing from high to intermediate purity FVIII concentrate. Ann Hematol 1996; 72 (suppl 1).
• Background Orsini F, Rotschild C, Beurrier P, Faradji A, Goudemand J, Polack B. Immune tolerance induction with highly purified plasma-derived factor VIII containing von Willebrand factor in hemophilia A patients with high-responding inhibitors. Haematologica. 2005 Sep;90(9):1288-90.
• Background Gringeri A, Musso R, Mazzucconi MG, Piseddu G, Schiavoni M, Pignoloni P, Mannucci PM; RITS-FITNHES Study Group. Immune tolerance induction with a high purity von Willebrand factor/VIII complex concentrate in haemophilia A patients with inhibitors at high risk of a poor response. Haemophilia. 2007 Jul;13(4):373-9. doi: 10.1111/j.1365-2516.2007.01484.x.
• Background Mauser-Bunschoten EP, Nieuwenhuis HK, Roosendaal G, van den Berg HM. Low-dose immune tolerance induction in hemophilia A patients with inhibitors. Blood. 1995 Aug 1;86(3):983-8.
• Background Hay CR, DiMichele DM; International Immune Tolerance Study. The principal results of the International Immune Tolerance Study: a randomized dose comparison. Blood. 2012 Feb 9;119(6):1335-44. doi: 10.1182/blood-2011-08-369132. Epub 2011 Nov 18.
• Background Haya S, Casaña P, Moret A, Cid RA, Cabrera N, Abad L, Aznar AJ. Immunotolerance Induction Treatments in Hemophilia. J.of Coagulation Disorders 2009; 1(1): 37-42.
• Background Colowick AB, Bohn RL, Avorn J, Ewenstein BM. Immune tolerance induction in hemophilia patients with inhibitors: costly can be cheaper. Blood. 2000 Sep 1;96(5):1698-702.
• Background Coppola A, Di Minno MN, Santagostino E. Optimizing management of immune tolerance induction in patients with severe haemophilia A and inhibitors: towards evidence-based approaches. Br J Haematol. 2010 Sep;150(5):515-28. doi: 10.1111/j.1365-2141.2010.08263.x. Epub 2010 Jun 22.

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