scholarly journals Results of a phase I/II open‐label, safety and efficacy trial of coagulation factor IX (recombinant), albumin fusion protein in haemophilia B patients

Haemophilia ◽  
2015 ◽  
Vol 21 (6) ◽  
pp. 784-790 ◽  
Author(s):  
U. Martinowitz ◽  
T. Lissitchkov ◽  
A. Lubetsky ◽  
G. Jotov ◽  
T. Barazani‐Brutman ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Phase I ◽  
Coagulation Factor ◽  
Factor Ix ◽  
Efficacy Trial ◽  
Open Label ◽  
Safety And Efficacy ◽  
Haemophilia B ◽  
Coagulation Factor Ix

Multicentre, randomized, open-label study of on-demand treatment with two prophylaxis regimens of recombinant coagulation factor IX in haemophilia B subjects

Haemophilia ◽  
2014 ◽  
Vol 20 (3) ◽  
pp. 398-406 ◽  
Author(s):  
L. A. Valentino ◽  
L. Rusen ◽  
I. Elezovic ◽  
L. M. Smith ◽  
J. M. Korth-Bradley ◽  
...  
Keyword(s):  
Coagulation Factor ◽  
Factor Ix ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Haemophilia B ◽  
On Demand ◽  
Coagulation Factor Ix

scholarly journals Long-acting recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in children

2016 ◽  
Vol 116 (10) ◽  
pp. 659-668 ◽  
Author(s):  
Hervé Chambost ◽  
Christoph Male ◽  
Thierry Lambert ◽  
Susan Halimeh ◽  
Tatiana Chernova ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Coagulation Factor ◽  
Factor Ix ◽  
Recombinant Fusion Protein ◽  
Severe Haemophilia ◽  
Spontaneous Bleeding ◽  
Haemophilia B ◽  
Coagulation Factor Ix ◽  
Routine Prophylaxis ◽  
Bleeding Episodes

SummaryA global phase 3 study evaluated the pharmacokinetics, efficacy and safety of a recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 27 previously treated male children (1–11 years) with severe and moderately severe haemophilia B (factor IX [FIX] activity ≤2 IU/dl). All patients received routine prophylaxis once every seven days for up to 77 weeks, and treated any bleeding episodes on-demand. The mean terminal half-life of rIX-FP was 91.4 hours (h), 4.3-fold longer than previous FIX treatment and clearance was 1.11 ml/h/kg, 6.4-fold slower than previous FIX treatment. The median (Q1, Q3) annualised spontaneous bleeding rate was 0.00 (0.00, 0.91) and was similar between the <6 years and ≥6 years age groups, with a weekly median prophylactic dose of 46 IU/kg. In addition, patients maintained a median trough level of 13.4 IU/dl FIX activity on weekly prophylaxis. Overall, 97.2 % of bleeding episodes were successfully treated with one or two injections of rIX-FP (95 % CI: 92 % to 99 %), 88.7 % with one injection, and 96 % of the treatments were rated effective (excellent or good) by the Investigator. No patient developed FIX inhibitors and no safety concerns were identified. These results indicate that rIX-FP is safe and effective for preventing and treating bleeding episodes in children with haemophilia B with weekly prophylaxis. Routine prophylaxis with rIX-FP at treatment intervals of up to 14 days are currently being investigated in children with severe and moderately severe haemophilia B. Clinicaltrials.gov (NCT01662531)

Successful in vivo propagation of factor IX-producing hepatocytes in mice: Potential for cell-based therapy in haemophilia B

2008 ◽  
Vol 99 (11) ◽  
pp. 883-891 ◽  
Author(s):  
Kohei Tatsumi ◽  
Miho Kataoka ◽  
Masaru Shibata ◽  
Hiroyuki Naka ◽  
Midori Shima ◽  
...  
Keyword(s):  
Coagulation Factor ◽  
Isolated Hepatocytes ◽  
Factor Ix ◽  
Blood Levels ◽  
Recipient Mouse ◽  
Cytoplasmic Staining ◽  
Haemophilia B ◽  
Cell Based Therapy ◽  
Coagulation Factor Ix

SummaryCell-based therapies using isolated hepatocytes have been proposed to be an attractive application in the treatment of haemophilia B due to the normal production of coagulation factor IX (FIX) in these particular cells. Current cell culture technologies have largely failed to provide adequate isolated hepatocytes, so the present studies were designed to examine a new approach to efficiently proliferate hepatocytes that can retain normal biological function, including the ability to synthesize coagulation factors like FIX. Canine or human primary hepatocytes were transplanted into urokinase-type plasminogen activatorsevere combined immunodeficiency (uPA/SCID) transgenic mice. Both donor hepatocytes from canines and humans were found to progressively proliferate in the recipient mouse livers as evidenced by a sharp increase in the circulating blood levels of species-specific albumin, which was correlated with the production and release of canine and human FIX antigen levels into the plasma. Histological examination confirmed that the transplanted canine and human hepatocytes were able to proliferate and occupy >80% of the host livers. In addition, the transplanted hepatocytes demonstrated strong cytoplasmic staining for human FIX, and the secreted coagulation factor IX was found to be haemostatically competent using specific procoagulant assays. In all, the results from the present study indicated that developments based on this technology could provide sufficient FIX-producing hepatocytes for cell-based therapy for haemophilia B.

scholarly journals Long-term safety and efficacy of extended-interval prophylaxis with recombinant factor IX Fc fusion protein (rFIXFc) in subjects with haemophilia B

2017 ◽  
Vol 117 (03) ◽  
pp. 508-518 ◽  
Author(s):  
K.John Pasi ◽  
Kathelijn Fischer ◽  
Margaret Ragni ◽  
Beatrice Nolan ◽  
David J. Perry ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Factor Ix ◽  
Safety And Efficacy ◽  
Haemophilia B ◽  
Treatment Groups ◽  
Fc Fusion Protein ◽  
Recombinant Factor Ix ◽  
Bleeding Episodes ◽  
Supplementary Material

SummaryThe safety, efficacy, and prolonged half-life of recombinant factor IX Fc fusion protein (rFIXFc) were demonstrated in the Phase 3 B-LONG (adults/adolescents ≥12 years) and Kids B-LONG (children <12 years) studies of subjects with haemophilia B (≤2 IU/dl). Here, we report interim, long-term safety and efficacy data from B-YOND, the rFIXFc extension study. Eligible subjects who completed B-LONG or Kids B-LONG could enrol in B-YOND. There were four treatment groups: weekly prophylaxis (20–100 IU/kg every 7 days), individualised prophylaxis (100 IU/kg every 8–16 days), modified prophylaxis (further dosing personalisation to optimise prophylaxis), and episodic (ondemand) treatment. Subjects could change treatment groups at any point. Primary endpoint was inhibitor development. One hundred sixteen subjects enrolled in B-YOND. From the start of the parent studies to the B-YOND interim data cut, median duration of rFIXFc treatment was 39.5 months and 21.9 months among adults/adolescents and children, respectively; 68/93 (73.1 %) adults/adolescents and 9/23 (39.1 %) children had ≥100 cumulative rFIXFc exposure days. No inhibitors were observed. Median annualised bleeding rates (ABRs) were low in all prophylaxis regimens: weekly (≥12 years: 2.3; <6 years: 0.0; 6 to <12 years: 2.7), individualised (≥12 years: 2.3; 6 to <12 years: 2.4), and modified (≥12 years: 2.4). One or two infusions were sufficient to control 97 % (adults/adolescents) and 95 % (children) of bleeding episodes. Interim data from B-YOND are consistent with data from B-LONG and Kids B-LONG, and confirm the longterm safety of rFIXFc, absence of inhibitors, and maintenance of low ABRs with prophylactic dosing every 1 to 2 weeks.Supplementary Material to this article is available online at www.thrombosis-online.com.

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