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 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

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.

Review of Data for Monoclonal Antibody-purified Plasma-derived Factor IX

2011 ◽  
Vol 07 (04) ◽  
pp. 257
Author(s):  
Massimo Morfini ◽  
Wolfhart Kreuz ◽  
◽  
Keyword(s):  
Monoclonal Antibody ◽  
Treatment Strategies ◽  
Coagulation Factor ◽  
Factor Ix ◽  
Recurrent Bleeding ◽  
Haemophilia B ◽  
On Demand ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Major Treatment

Haemophilia B is attributed to a mutation in the gene that produces coagulation factor IX (FIX), resulting in FIX deficiency. Treatment of haemophilia B currently consists of replacing the deficient FIX by intravenous administration of exogenous FIX. There are two major treatment strategies: prophylactic FIX administration (to prevent recurrent bleeding episodes in patients), and on-demand FIX administration (to control existing bleeding in patients when it occurs). Prothrombin complex concentrates (PCCs), which were initially used to treat haemophilia B patients, have been available for approximately 40 years. However, PCCs have been largely replaced by highly purified plasma-derived FIX and recombinant FIX, which have benefited from improvements in purification and viral inactivation, reduction or elimination methods. Monoclonal antibody-purified plasma-derived FIX (MAb pd-FIX) has been extensively evaluated in clinical trials and has proved to be safe and efficacious for surgical prophylaxis and for on-demand and prophylactic treatment in previously untreated and previously treated patients. While intermittent dosing is the conventional method of administration, MAb pd-FIX is also suitable for continuous intravenous infusion; this dosing method has been shown to result in normal haemostasis in patients with haemophilia B. This article reviews the data available for MAb pd-FIX.

Pharmacokinetic/Pharmacodynamic Assessment of Reformulated Recombinant Coagulation Factor IX in Adults and Children with Severe Hemophilia B

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1190-1190
Author(s):  
JM Korth-Bradley ◽  
Leonard A. Valentino ◽  
Pablo Rendo ◽  
Frank E. Shafer ◽  
Lynne Smith ◽  
...  
Keyword(s):  
Medical Center ◽  
Coagulation Factor ◽  
Factor Ix ◽  
Hemophilia B ◽  
Pharmacokinetic Data ◽  
Severe Hemophilia ◽  
Bleeding Events ◽  
On Demand ◽  
Coagulation Factor Ix ◽  
Weekly Group

Abstract Abstract 1190 Introduction: The goal of this study was to evaluate the efficacy and safety of two prophylaxis regimens of reformulated recombinant coagulation factor IX (rFIX-R), 100 IU/kg once weekly and 50 IU/kg twice weekly, compared with on-demand treatment in subjects with severe hemophilia B. Patients and Methods: Pharmacokinetic data were collected for 47 subjects aged 6 to 64 years with severe hemophilia B. Factor IX activity (FIX:C) measurements were made immediately before rFIX-R administration and at 0.5 hours post-administration of either 100 IU/kg or 50 IU/kg doses, to assess recovery before the initiation of each weekly regimen. Another FIX:C sample was collected at least 72 hours after dosing during each regimen. All samples were analyzed at local laboratories. Results: The mean prophylactic doses of rFIX-R administered were 86 ± 29 IU/kg in the 100 IU/kg once-weekly group and 53 ± 14 IU/kg in the 50 IU/kg twice-weekly group. The treatment comparison between the two prophylaxis regimens for annualized bleeding rate was not significant (LS mean = 2.0; 95% CI, −1.2 – 5.2; n=43), although both were significantly different from the on-demand treatment period (both, P<.0001). The number of new bleeding events in each group was 51 and 35, respectively, with only 12/51 new hemorrhages occurring within 72 hours of dosing in the 100 IU/kg once-weekly group compared with 29/35 in the 50 IU/kg twice-weekly group. The pharmacokinetic results are shown in the Table. The number (%) of observed trough plasma concentrations (Ctrough) that fell into the mild (>5%) range for hemophilia were 18 (45%) and 19 (48%) for the r-FIX-R 100 IU/kg once-weekly and 50 IU/kg twice-weekly groups, respectively. However, the severe phenotype was observed in 4 (10%) and 3 (7%) subjects, respectively. Conclusions: The pharmacokinetics of r-FIX-R are dose proportional. The C0.5hr increased in proportion to the dose administered. Recovery was consistent between the two prophylaxis regimens. Both regimens provided similar therapeutic results for Ctrough. The apparent difference in time after dose of new bleeding events between the 2 regimens is intriguing and deserves further study. Disclosures: Korth-Bradley: Pfizer Inc: Employment. Valentino:Inspiration Bioscience: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center, Honoraria; CSL Behring: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center; Pfizer: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center; NovoNordisk: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center, Honoraria; GTC Biotherapeutics: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center, Honoraria; Bayer Healthcare: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center, Honoraria; Baxter Bioscience: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center, Honoraria; Biogen: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center; Hemophilia and Thrombosis Research Society: Membership on an entity's Board of Directors or advisory committees, Past-President. Rendo:Pfizer Inc: Employment. Shafer:Pfizer Inc: Employment. Smith:Pfizer Inc: Employment. Baumann:Pfizer Inc: Employment. Charnigo:Pfizer Inc: Employment.

Sign in / Sign up

Export Citation Format

Share Document