A long-term, multi-center clinical study of recombinant human factor VIII BAY w 6240) in treatment of hemophilia A.

弘, 福井; 和夫, 森; 正明, 石川; 昭, 柴田; 芳右, 高橋; 道男, 藤巻; 勝幸, 福武; 公人, 腰原; 忠俊, 木下; 明子, 中山; 英永, 浜; 稔, 稲垣; 秀次, 花房; 屋純一, 三間; 英彦, 斎藤; 忠, 神谷; 純樹, 高松; 茂, 白川; 克巳, 出口; 章, 吉岡; 緑倫, 嶋; 幸二郎, 安永; 進, 大久保; 慶一郎, 吉岡; 清二, 木下; 栄三, 垣下; 恭治, 西田; 聡, 白幡

doi:10.3925/jjtc1958.37.593

Cited by 18 publications

(24 citation statements)

References 6 publications

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“…The present Stage III investigation found that in vivo recoveries did not change significantly after 24 weeks of treatment with rFVIII–FS. These values are similar to those observed during the clinical evaluation of Kogenate ® in Japanese patients with haemophilia A, reported as 68.2–77.5% over a 25‐week period [5]. Therefore, in vivo recovery of rFVIII–FS was similar to that of Kogenate ® .…”

Section: Discussionsupporting

confidence: 86%

“…Both trials had similar patient numbers and demographics (age, body weight, and severity of haemophilia A). The haemostatic efficacy for the two formulations appeared to be similar, as a rating of ‘excellent’ and ‘good’ was reported for 82.9% of rFVIII–FS and 81.2% of Kogenate ® infusions; likewise, ratings for treatment of bleeding episodes were 98.0% and 98.8%, respectively [5]. Furthermore, in home therapy of North American and European patients with haemophilia A, 93.5% of all bleeding episodes were effectively treated with one or two infusions, and patients rated treatment responses as excellent or good in 80.5% of episodes [14].…”

Section: Discussionmentioning

confidence: 94%

“…In addition, the human plasma‐derived products used in the manufacture of Kogenate ® or rFVIII–FS, HPPS and albumin, are derived from Cohn fractions V and IV‐I which have never been implicated in viral transmission. Kogenate ® , developed by Bayer Corporation (Berkeley, CA, USA) and approved in 25 countries, has confirmed safety and efficacy for the treatment of haemophilia A [4–6].…”

Section: Introductionmentioning

confidence: 99%

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Safety and efficacy of a new recombinant FVIII formulated with sucrose (rFVIII–FS) in patients with haemophilia A: a long‐term, multicentre clinical study in Japan

Yoshioka¹,

Shima²,

Fukutake³

et al. 2001

Haemophilia

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The recombinant full-length FVIII product Kogenate has been reformulated using sucrose (rFVIII-FS) instead of human serum albumin as a stabiliser in purification and formulation. The in vivo recovery, haemostatic efficacy, and safety of rFVIII-FS were investigated in 20 previously treated patients with severe or moderate haemophilia A for > or = 24 weeks. In vivo recoveries of 73.5 +/- 16.3%, 78.4 +/- 16.1%, and 82.8 +/- 23.9% after the initial infusion of 50 IU kg(-1) rFVIII-FS and at weeks 12 and 24, respectively, showed no significant changes over time. A total of 1115 infusions (mean dose 24.1 +/- 8.4 IU kg(-1)) were included in the analysis of haemostatic efficacy. One (80.5%) or two (8.2%) infusions achieved adequate haemostasis in 88.7% of all bleeding episodes, and haemostatic efficacy was judged 'excellent' or 'good' in 749 of 764 episodes (98.0%). The haemostatic efficacy was judged as 'excellent' or 'good' in 924 of 1115 (82.9%) infusions. Twenty-one adverse events were observed in 12 patients in the total 1541 infusions included in the safety analysis. Causality with respect to rFVIII-FS could not be ruled out in three events in one HIV-negative patient: elevated CD4(%), decreased CD8(%), and elevated CD4/CD8 ratio. No FVIII inhibitor development was observed in any patient. ELISA assay testing for antibodies to rFVIII, baby hamster kidney cell (BHK) protein, and murine IgG were all negative. These results show that rFVIII-FS is a safe and effective for long-term treatment of patients with haemophilia A.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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Safety and efficacy of a new recombinant FVIII formulated with sucrose (rFVIII–FS) in patients with haemophilia A: a long‐term, multicentre clinical study in Japan

Yoshioka¹,

Shima²,

Fukutake³

et al. 2001

Haemophilia

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“…Binding antibodies against FVIII have recently been reported in 34% (5% with titres ≥1:80) of haemophilia patients without inhibitors and with a prevalence of 19% (2% with titres ≥1:80) in healthy individuals, indicating that the clinical significance of these has not been substantiated [26], and the presence of self-reactive anti-bodies against FIX in health volunteers is currently being investigated [39]. Increases in antibodies to CHO cell-derived components have been reported in patients treated with recombinant CHO-derived antihaemophilic factors [40]. In this trial, no specific antibodies to CHO protein or rFurin were detected in any subject.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics, efficacy and safety of BAX326, a novel recombinant factor IX: a prospective, controlled, multicentre phase I/III study in previously treated patients with severe (FIX level <1%) or moderately severe (FIX level ≤2%) haemophilia B

Windyga

Lissitchkov²,

Stasyshyn

et al. 2013

Haemophilia

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BAX326 is a recombinant factor IX (rFIX; nonacog gamma) manufactured without the addition of any materials of human or animal origin, and with two viral inactivation steps (solvent/detergent treatment and 15 nm nanofiltration). The aim of this prospective trial was to investigate the pharmacokinetics, haemostatic efficacy and safety of BAX326 in previously treated patients aged 12-65 years with severe or moderately severe haemophilia B. BAX326 was safe and well tolerated in all 73 treated subjects; adverse events considered related to treatment (2.7% incidence, all non-serious) were transient and mild, and no hypersensitivity reactions, inhibitor formation or thrombotic events were observed. Pharmacokinetic (PK) equivalence (n = 28) between BAX326 and a licensed rFIX was confirmed in terms of the ratio of geometric mean AUC(0-72) h per dose. Twice-weekly prophylaxis [mean duration 6.2 (±0.7) months; 1.8 (±0.1) infusions per week, 49.5 (±4.8) IU kg(-1) per infusion] was effective in preventing bleeding episodes, with a significantly lower (79%, P < 0.001) annualized bleed rate (4.2) compared to an on-demand treatment in a historical control group (20.0); 24 of 56 subjects on prophylaxis (43%) did not bleed throughout the study observation period. Of 249 total acute bleeds, 211 (84.7%) were controlled with one to two infusions of BAX326. Haemostatic efficacy at resolution of bleed was rated excellent or good in 96.0% of all treated bleeding episodes. The results of this study indicate that BAX326 is safe and efficacious in treating bleeds and routine prophylaxis in patients aged 12 years and older with haemophilia B.

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“…Brackmann [32] pioneered immune tolerance induction 20 years ago when he treated 21 patients attending his center in Bonn by using FVIII concentrate in doses of 100 U/kg twice a day with FEIBA. Two of his pa tients died of intracranial hemorrhages, 4 dropped from the program but 15 were successfully treated to either a total Inhibitors occur in patients treated with cryoprecipitate, intermediate or high purity products [14][15][16][17][18][19]. It appears that at least three key factors play a role in determining induc tion of inhibitors: severity of disease, age of onset, and ex posure days [20][21][22].…”

Section: Management Options Inhibitors and Prevalencementioning

confidence: 99%

Induction of Immune Tolerance, the Future of the Registry

Ewing¹

1996

Vox Sanguinis

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Factor VIII (FVIII) inhibitors are IgG antibodies that neutralize the procoagulant activity of FVIII, rendering hemorrhages difficult to manage. There may exist a genetic predisposition with consequent imbalance of T and B cell function. Efforts at inhibitor eradication in the last 20 years have produced a multitude of immune tolerance induction (IIT) protocols with variable outcome. Data derived from the International Registry indicate that inhibitor titer at outset of IIT and dose of FVIII concentrate used are important predictors of success. Future Registry activities should identify optimally standardized IIT regimens designed on the basis of patient likelihood to achieve tolerance and should provide further understanding of T and B cell interaction in the treatment process.

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A long-term, multi-center clinical study of recombinant human factor VIII BAY w 6240) in treatment of hemophilia A.

Cited by 18 publications

References 6 publications

Safety and efficacy of a new recombinant FVIII formulated with sucrose (rFVIII–FS) in patients with haemophilia A: a long‐term, multicentre clinical study in Japan

Safety and efficacy of a new recombinant FVIII formulated with sucrose (rFVIII–FS) in patients with haemophilia A: a long‐term, multicentre clinical study in Japan

Pharmacokinetics, efficacy and safety of BAX326, a novel recombinant factor IX: a prospective, controlled, multicentre phase I/III study in previously treated patients with severe (FIX level <1%) or moderately severe (FIX level ≤2%) haemophilia B

Induction of Immune Tolerance, the Future of the Registry

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