Phase 3 Study of Recombinant Factor IX Fc Fusion Protein in Hemophilia B

被引：305

作者：

Powell, Jerry S. ^{[1
]}

Pasi, K. John ^{[2
]}

Ragni, Margaret V. ^{[3
,4
]}

Ozelo, Margareth C. ^{[5
]}

Valentino, Leonard A. ^{[6
]}

Mahlangu, Johnny N. ^{[7
]}

Josephson, Neil C. ^{[9
]}

Perry, David ^{[10
]}

Manco-Johnson, Marilyn J. ^{[11
,12
]}

Apte, Shashikant ^{[13
]}

Baker, Ross I. ^{[14
]}

Chan, Godfrey C. ^{[15
]}

Novitzky, Nicolas ^{[8
]}

Wong, Raymond S. ^{[16
]}

Krassova, Snejana ^{[17
]}

Allen, Geoffrey ^{[17
]}

Jiang, Haiyan ^{[17
]}

Innes, Alison ^{[17
]}

Li, Shuanglian ^{[17
]}

Cristiano, Lynda M. ^{[17
]}

Goyal, Jaya ^{[17
]}

Sommer, Jurg M. ^{[17
]}

Dumont, Jennifer A. ^{[17
]}

Nugent, Karen ^{[17
]}

Vigliani, Gloria

Brennan, Aoife ^{[17
]}

Luk, Alvin ^{[17
]}

Pierce, Glenn F. ^{[17
]}

机构：

[1] Univ Calif Davis, Davis, CA 95616 USA

[2] Barts & London Queen Marys Sch Med & Dent, Royal London Haemophilia Ctr, London, England

[3] Univ Pittsburgh, Pittsburgh, PA USA

[4] Hemophilia Ctr Western Penn, Pittsburgh, PA USA

[5] Univ Estadual Campinas, INCT Sangue Hemoctr UNICAMP, Campinas, SP, Brazil

[6] Rush Univ, Med Ctr, Chicago, IL 60612 USA

[7] Univ Witwatersrand, Haemophilia Comprehens Care Ctr, Natl Hlth Lab Serv, Charlotte Maxeke Johannesburg Acad Hosp, Johannesburg, South Africa

[8] Univ Cape Town, Sch Med, Comprehens Haemophilia Ctr, Groote Schuur Hosp, ZA-7925 Cape Town, South Africa

[9] Puget Sound Blood Ctr, Seattle, WA 98104 USA

[10] Addenbrookes Hosp, Cambridge, England

[11] Univ Colorado, Sch Med, Childrens Hosp, Aurora, CO USA

[12] Univ Colorado, Sch Med, Mt States Reg Hemophilia & Thrombosis Ctr, Aurora, CO USA

[13] Sahyadri Hosp, Dept Hematol, Mahara, India

[14] Murdoch Univ, Royal Perth Hosp, Ctr Thrombosis & Haemophilia, Perth, WA, Australia

[15] Univ Hong Kong, Dept Pediat & Adolescent Med, Hong Kong, Hong Kong, Peoples R China

[16] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China

[17] Biogen Idec Hemophilia, Cambridge, MA USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2013年 / 369卷 / 24期

关键词：

PREVIOUSLY TREATED PATIENTS; PHARMACOKINETIC PROPERTIES; PROLONGED ACTIVITY; FACTOR-VIII; PROPHYLAXIS; SAFETY; DEFICIENCY; INHIBITORS; MODERATE; DISEASE;

D O I：

10.1056/NEJMoa1305074

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BackgroundProphylactic factor replacement in patients with hemophilia B improves outcomes but requires frequent injections. A recombinant factor IX Fc fusion protein (rFIXFc) with a prolonged half-life was developed to reduce the frequency of injections required. MethodsWe conducted a phase 3, nonrandomized, open-label study of the safety, efficacy, and pharmacokinetics of rFIXFc for prophylaxis, treatment of bleeding, and perioperative hemostasis in 123 previously treated male patients. All participants were 12 years of age or older and had severe hemophilia B (endogenous factor IX level of 2 IU per deciliter, or 2% of normal levels). The study included four treatment groups: group 1 received weekly dose-adjusted prophylaxis (50 IU of rFIXFc per kilogram of body weight to start), group 2 received interval-adjusted prophylaxis (100 IU per kilogram every 10 days to start), group 3 received treatment as needed for bleeding episodes (20 to 100 IU per kilogram), and group 4 received treatment in the perioperative period. A subgroup of group 1 underwent comparative sequential pharmacokinetic assessments of recombinant factor IX and rFIXFc. The primary efficacy end point was the annualized bleeding rate, and safety end points included the development of inhibitors and adverse events. ResultsAs compared with recombinant factor IX, rFIXFc exhibited a prolonged terminal half-life (82.1 hours) (P<0.001). The median annualized bleeding rates in groups 1, 2, and 3 were 3.0, 1.4, and 17.7, respectively. In group 2, 53.8% of participants had dosing intervals of 14 days or more during the last 3 months of the study. In groups 1, 2 and 3, 90.4% of bleeding episodes resolved after one injection. Hemostasis was rated as excellent or good during all major surgeries. No inhibitors were detected in any participants receiving rFIXFc; in groups 1, 2, and 3, 73.9% of participants had at least one adverse event, and serious adverse events occurred in 10.9% of participants. These events were mostly consistent with those expected in the general population of patients with hemophilia. ConclusionsProphylactic rFIXFc, administered every 1 to 2 weeks, resulted in low annualized bleeding rates in patients with hemophilia B. (Funded by Biogen Idec; ClinicalTrials.gov number, NCT01027364.)

引用

页码：2313 / 2323

页数：11

共 41 条

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