Hemlibra in Mild Hemophilia A

Summary

This is a single arm, phase 4, prospective, open-label, United States single-center study to determine the hemostatic characteristics of Hemlibra (emicizumab) as measured by coagulation laboratory parameters in the mild hemophilia A male patient population with endogenous altered FVIII (baseline FVIII activity of \>5% to 30%). The safety and hemostatic efficacy of Hemlibra (emicizumab) in this patient population will be investigated. Secondary outcomes will assess changes in joint health and quality of life in treated patients.

Timeline

Start

2022-07-25

Primary completion

2025-07

Completion

2027-07

Publications

• Results Batorova A, Holme P, Gringeri A, Richards M, Hermans C, Altisent C, Lopez-Fernandez M, Fijnvandraat K; European Haemophilia Treatment Standardisation Board. Continuous infusion in haemophilia: current practice in Europe. Haemophilia. 2012 Sep;18(5):753-9. doi: 10.1111/j.1365-2516.2012.02810.x. Epub 2012 Apr 25.
• Results Blanchette VS, Key NS, Ljung LR, Manco-Johnson MJ, van den Berg HM, Srivastava A; Subcommittee on Factor VIII, Factor IX and Rare Coagulation Disorders of the Scientific and Standardization Committee of the International Society on Thrombosis and Hemostasis. Definitions in hemophilia: communication from the SSC of the ISTH. J Thromb Haemost. 2014 Nov;12(11):1935-9. doi: 10.1111/jth.12672. Epub 2014 Sep 3. No abstract available.
• Results Centers for Disease Control and Prevention (2014). Hemophilia Data & Statistics Retrieved April 22, 2014, from http://www.cdc.gov/ncbddd/hemophilia/data.html
• Results Franchini M, Favaloro EJ, Lippi G. Mild hemophilia A. J Thromb Haemost. 2010 Mar;8(3):421-32. doi: 10.1111/j.1538-7836.2009.03717.x. Epub 2009 Dec 7.
• Results Franchini M, Mannucci PM. Hemophilia A in the third millennium. Blood Rev. 2013 Jul;27(4):179-84. doi: 10.1016/j.blre.2013.06.002. Epub 2013 Jun 28.
• Results Franchini M, Mannucci PM. Inhibitor eradication with rituximab in haemophilia: where do we stand? Br J Haematol. 2014 Jun;165(5):600-8. doi: 10.1111/bjh.12829. Epub 2014 Mar 15.
• Results Gringeri A, Leissinger C, Cortesi PA, Jo H, Fusco F, Riva S, Antmen B, Berntorp E, Biasoli C, Carpenter S, Kavakli K, Morfini M, Negrier C, Rocino A, Schramm W, Windyga J, Zulfikar B, Mantovani LG. Health-related quality of life in patients with haemophilia and inhibitors on prophylaxis with anti-inhibitor complex concentrate: results from the Pro-FEIBA study. Haemophilia. 2013 Sep;19(5):736-43. doi: 10.1111/hae.12178. Epub 2013 Jun 4.
• Results Hay CR. Factor VIII inhibitors in mild and moderate-severity haemophilia A. Haemophilia. 1998 Jul;4(4):558-63. doi: 10.1046/j.1365-2516.1998.440558.x.
• Results Kempton CL, Allen G, Hord J, Kruse-Jarres R, Pruthi RK, Walsh C, Young G, Soucie JM. Eradication of factor VIII inhibitors in patients with mild and moderate hemophilia A. Am J Hematol. 2012 Sep;87(9):933-6. doi: 10.1002/ajh.23269. Epub 2012 Jun 26.
• Results Mahlangu J, Oldenburg J, Paz-Priel I, Negrier C, Niggli M, Mancuso ME, Schmitt C, Jimenez-Yuste V, Kempton C, Dhalluin C, Callaghan MU, Bujan W, Shima M, Adamkewicz JI, Asikanius E, Levy GG, Kruse-Jarres R. Emicizumab Prophylaxis in Patients Who Have Hemophilia A without Inhibitors. N Engl J Med. 2018 Aug 30;379(9):811-822. doi: 10.1056/NEJMoa1803550.
• Results Makris M, Oldenburg J, Mauser-Bunschoten EP, Peerlinck K, Castaman G, Fijnvandraat K; subcommittee on Factor VIII, Factor IX and Rare Bleeding Disorders. The definition, diagnosis and management of mild hemophilia A: communication from the SSC of the ISTH. J Thromb Haemost. 2018 Dec;16(12):2530-2533. doi: 10.1111/jth.14315. Epub 2018 Nov 15. No abstract available.
• Results National Institutes of Health (2014). What Is Hemophilia? Retrieved April 22, 2014, from https://www.nhlbi.nih.gov/health/health-topics/topics/hemophilia/
• Results Oldenburg J, Mahlangu JN, Kim B, Schmitt C, Callaghan MU, Young G, Santagostino E, Kruse-Jarres R, Negrier C, Kessler C, Valente N, Asikanius E, Levy GG, Windyga J, Shima M. Emicizumab Prophylaxis in Hemophilia A with Inhibitors. N Engl J Med. 2017 Aug 31;377(9):809-818. doi: 10.1056/NEJMoa1703068. Epub 2017 Jul 10.
• Results Pezeshkpoor B, Gazorpak M, Berkemeier AC, Singer H, Pavlova A, Biswas A, Oldenburg J. In silico and in vitro evaluation of the impact of mutations in non-severe haemophilia A patients on assay discrepancies. Ann Hematol. 2019 Aug;98(8):1855-1865. doi: 10.1007/s00277-019-03691-1. Epub 2019 Apr 17.
• Results Pipe, S. (2018). Emicizumab subcutaneous dosing every 4 weeks is safe and efficacious in the control of bleeding in persons with haemophilia A with and without inhibitors - Results from the phase 3 HAVEN 4 study. World Federation of Hemophila World Congress Glasgow, Scotland.
• Results Prelog T, Dolnicar MB, Kitanovski L. Low-dose continuous infusion of factor VIII in patients with haemophilia A. Blood Transfus. 2016 Sep;14(5):474-80. doi: 10.2450/2015.0080-15. Epub 2015 Nov 16.
• Results Sengupta M, Sarkar D, Ganguly K, Sengupta D, Bhaskar S, Ray K. In silico analyses of missense mutations in coagulation factor VIII: identification of severity determinants of haemophilia A. Haemophilia. 2015 Sep;21(5):662-9. doi: 10.1111/hae.12662. Epub 2015 Apr 9.
• Results Shima, M., K. Nogami, S. Nagami, S. Yoshida, K. Yoneyama, A. Ishiguro, T. Suzuki and M. Taki (2018) Every 2 Weeks or Every 4 Weeks Subcutaneous Injection of Emicizumab in Pediatric Patients with Severe Hemophilia A without Inhibitors: A Multi-Center, Open-Label Study in Japan (HOHOEMI Study). Blood 132:1186-1186.
• Results World Federation of Hemophilia (2012). Guidelines for the management of hemophilia Retrieved February 16, 2015, from http://www1.wfh.org/publication/files/pdf-1472.pdf
• Results World Federation of Hemophilia (2012). World Federation of Hemophilia report on the annual global survey 2011 Retrieved December 20, 2016, from http://www1.wfh.org/publication/files/pdf-1488.pdf
• Results World Federation of Hemophilia (2013). World Federation of Hemophilia report on the annual global survey 2013 Retrieved February 5, 2015, from http://www1.wfh.org/publications/files/pdf-1591.pdf
• Results World Federation of Hemophilia (2016). World Federation of Hemophilia report on the annual global survey 2015 Retrieved December 20, 2016, from http://www1.wfh.org/publication/files/pdf-1669.pdf.
• Results World Federation of Hemophilia (2017). World Federation of Hemophilia Annual Global Survey Data Retrieved May 30, 2017, from https://www.wfh.org/en/resources/annual-global-survey
• Results Young G, Liesner R, Chang T, Sidonio R, Oldenburg J, Jimenez-Yuste V, Mahlangu J, Kruse-Jarres R, Wang M, Uguen M, Doral MY, Wright LY, Schmitt C, Levy GG, Shima M, Mancuso ME. A multicenter, open-label phase 3 study of emicizumab prophylaxis in children with hemophilia A with inhibitors. Blood. 2019 Dec 12;134(24):2127-2138. doi: 10.1182/blood.2019001869.

Drugs

Indications