Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A

被引：75

作者：

Mahlangu, Johnny ^{[1
]}

Kuliczkowski, Kazimierz ^{[2
]}

Karim, Faraizah Abdul ^{[3
]}

Stasyshyn, Oleksandra ^{[4
]}

Kosinova, Marina V. ^{[5
]}

Lepatan, Lynda Mae ^{[6
]}

Skotnicki, Aleksander ^{[7
]}

Boggio, Lisa N. ^{[8
]}

Klamroth, Robert ^{[9
]}

Oldenburg, Johannes ^{[10
]}

Hellmann, Andrzej ^{[11
]}

Santagostino, Elena ^{[12
]}

Baker, Ross I. ^{[13
]}

Fischer, Kathelijn ^{[14
]}

Gill, Joan C. ^{[15
,16
]}

P'Ng, Stephanie ^{[17
]}

Chowdary, Pratima ^{[18
,19
]}

Escobar, Miguel A. ^{[20
,21
]}

Khayat, Claudia Djambas ^{[22
]}

Rusen, Luminita ^{[23
]}

Bensen-Kennedy, Debra ^{[24
]}

Blackman, Nicole ^{[24
]}

Limsakun, Tharin ^{[24
]}

Veldman, Alex ^{[25
]}

St Ledger, Katie ^{[24
]}

Pabinger, Ingrid ^{[26
]}

机构：

[1] Univ Witwatersrand, Natl Hlth Lab Serv, Charlotte Maxeke Johannesburg Acad Hosp, Dept Mol Med & Haematol,Fac Hlth Sci, Johannesburg, South Africa

[2] Wroclaw Med Univ, Dept Hematol Blood Neoplasms & Bone Marrow Transp, Wroclaw, Poland

[3] Natl Blood Ctr, Hemophilia Clin, Kuala Lumpur, Malaysia

[4] Natl Acad Med Sci Ukraine, Inst Blood Pathol & Transfus Med, Lvov, Ukraine

[5] Kemerovo Reg Clin Hosp, Kemerovo, Russia

[6] Perpetual Succour Hosp, Cebu, Philippines

[7] Krakow Med Ctr, Krakow, Poland

[8] Rush Univ, Med Ctr, Hemophilia & Thrombophilia Ctr, Chicago, IL 60612 USA

[9] Vivantes Clin Friedrichshain, Berlin, Germany

[10] Univ Clin Bonn, Inst Expt Haematol & Transfus Med, Bonn, Germany

[11] Med Univ Gdansk, Dept Hematol & Transplantat, Gdansk, Poland

[12] Maggiore Hosp Policlin, IRCCS Ca Granda Fdn, A Bianchi Bonomi Hemophilia & Thrombosis Ctr, Milan, Italy

[13] Murdoch Univ, Western Australian Ctr Thrombosis & Haemostasis, Perth, WA, Australia

[14] Univ Med Ctr Utrecht, Van Creveldklin, Utrecht, Netherlands

[15] Blood Ctr Wisconsin, Milwaukee, WI USA

[16] Med Coll Wisconsin, Milwaukee, WI 53226 USA

[17] Royal Perth Hosp, Perth, WA, Australia

[18] Royal Free Hosp, Katharine Dormandy Haemophilia Ctr, London, England

[19] Royal Free Hosp, Thrombosis Unit, London, England

[20] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA

[21] Gulf States Hemophilia & Thrombophilia Ctr, Houston, TX USA

[22] Hotel Dieu France Hosp, Lebanon Dept Pediat, Beirut, Lebanon

[23] Sanador SRL, Bucharest, Romania

[24] CSL Behring, Clin Res & Dev, King Of Prussia, PA USA

[25] CSL Behring, Clin Res & Dev, Marburg, Germany

[26] Med Univ Vienna, Med Clin 1, Clin Div Haematol & Haemostaseol, Waehringer Guertel 18-20, A-1090 Vienna, Austria

来源：

BLOOD | 2016年 / 128卷 / 05期

关键词：

RECOMBINANT FACTOR-VIII; VON-WILLEBRAND-FACTOR; FC FUSION PROTEIN; TUROCTOCOG ALPHA; FULL-LENGTH; FVIII; PHARMACOKINETICS; ADHERENCE; LIFE;

D O I：

10.1182/blood-2016-01-687434

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Recombinant VIII (rVIII)-SingleChain is a novel B-domain-truncated recombinant factor VIII (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains. It was designed to have a higher binding affinity for von Willebrand factor (VWF). This phase 1/3 study investigated the efficacy and safety of rVIII-SingleChain in the treatment of bleeding episodes, routine prophylaxis, and surgical prophylaxis. Participants were >= 12 years of age, with severe hemophilia A (endogenous FVIII <1%). The participants were allocated by the investigator to receive rVIII-SingleChain in either an on-demand or prophylaxis regimen. Of the 175 patients meeting study eligibility criteria, 173 were treated with rVIII-SingleChain, prophylactically (N = 146) or on-demand (N = 27). The total cumulative exposure was 14 306 exposure days (EDs), with 120 participants reaching >= 50 EDs and 52 participants having >= 100 EDs. Hemostatic efficacy was rated by the investigator as excellent or good in 93.8% of the 835 bleeds treated and assessed. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.0, 2.4) and the median overall annualized bleeding rate (ABR) was 1.14 (Q1, Q3: 0.0, 4.2). Surgical hemostasis was rated as excellent/good in 100% of major surgeries by the investigator. No participant developed FVIII inhibitors. In conclusion, rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy in surgery and in the control of bleeding events, low ABR in patients on prophylaxis, and a favorable safety profile in this large clinical study. This trial was registered at www.clinicaltrials.gov as #NCT01486927.

引用

页码：630 / 637

页数：8

共 23 条

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