Efficacy, PK and Safety Results of a Phase I/II Clinical Trial of Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP) in Previously Treated Patients with Haemophilia B (PROLONG - 9FP)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1121-1121 ◽  
Author(s):  
Uriel Martinowitz ◽  
Aaron Lubetsky ◽  
Elena Santagostino ◽  
Gantcho Jotov ◽  
Jacob Luboshitz ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Prophylactic Treatment ◽  
Factor Ix ◽  
Bleeding Rate ◽  
On Demand ◽  
Routine Prophylaxis ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Bleeding Episodes

Abstract Abstract 1121 Factor IX (FIX) replacement therapy is the standard of care for patients with haemophilia B. FIX products currently available have a relatively short half-life, requiring 2–3 times a week intravenous prophylactic treatment to achieve a significant bleeding reduction. A recombinant FIX albumin fusion protein (rIX-FP) was generated by genetic fusion of human recombinant albumin to rFIX to extend the half life of FIX. A Phase I/II open-label, multicenter, clinical study of rIX-FP has been completed in previously treated patients with severe hemophilia B (FIX ≤ 2%) as part of the PROLONG - 9FP clinical developmental program. The objectives of the study were to evaluate the prevention of bleeding episodes during once weekly prophylaxis and to assess the hemostatic efficacy of rIX-FP for the treatment of bleeding, in addition to safety and pharmacokinetic (PK) assessments. The study consisted of a 10 to 14 day PK evaluation period, and a 3 to 12 month safety and efficacy evaluation period, during which subjects received either on-demand or prophylaxis treatment. Subjects receiving weekly prophylactic treatment were initially treated with a dose based upon the subject's PK profile, bleeding phenotype, and physical activity level. The dose could be adjusted based on clinical outcome, while maintaining a 7 day treatment interval. Subjects receiving on-demand treatment were treated with a dose based upon the subject's PK profile and WFH recommendations for treatment of bleeding episodes. Seventeen study subjects from hemophilia treatment centers in Israel and Bulgaria participated in the study, 13 of whom received weekly prophylaxis treatment and 4 of whom received on-demand treatment. Following a single infusion of 25 IU/kg rIX-FP (n=13), the PK parameters (t1/2 = 94 hrs, AUC0-inf= 3414 hr*IU/dL) were comparable to those previously reported from the Phase I study (Blood prepublished Aug 2, 2012). In addition, rIX-FP maintained a baseline-corrected mean trough level of 3.8% and 2.7% at Day 7 and Day 14, respectively, after 25 IU/kg rIX-FP administration. There were no AEs considered as possibly related to rIX-FP. There were no allergic reactions, inhibitors to FIX or antibodies to rIX-FP reported. All 10 prophylaxis subjects who were previously receiving routine prophylaxis with FIX were maintained successfully on weekly treatment with rIX-FP for the entire study. Furthermore, three prophylaxis subjects who were previously treated on-demand were maintained successfully on weekly prophylaxis treatment with rIX-FP with at least 85% reduction in the annualized spontaneous and total bleeding rate compared to the annualized bleeding rate prior to study entry. All of the bleeding events were treated successfully, including approximately 90% of the events with a single infusion of rIX-FP. The mean weekly product consumption of rIX-FP (IUs) was reduced compared to the consumption of the previous FIX product (IUs). No subject was withdrawn from the study due to safety concerns or lack of hemostatic efficacy. This Phase I/II study has demonstrated the clinical efficacy of rIX-FP for once weekly routine prophylaxis to prevent spontaneous bleeding episodes and treatment of bleeding episodes, in addition to the excellent safety characteristics and improved PK profile. A detailed analysis of the efficacy of weekly routine prophylaxis and treatment of bleeding episodes, improved PK and safety properties of rIX-FP will be presented. Disclosures: Martinowitz: CSL Behring: Honoraria, Investigator for CSL clinical study of rIX-FP Other. Lubetsky:CSL Behring: Investigator for CSL clinical trial of rIX-FP Other. Santagostino:CSL Behring: Honoraria, Investigator for CSL Behring clinical trial of rIX-FP Other, Research Funding, Speakers Bureau. Jotov:CSL Behring: sub-investigator for CSL clinical trial of rIX-FP Other. Barazani-Brutman:CSL Behring: study coordinator for CSL Behring clinical trial of rIX-FP Other. Voigt:CSL Behring: Employment. Moises:CSL Behring: Employment. Jacobs:CSL Behring: Employment. Lissitchkov:CSL Behring: Investigator for CSL Behgring clinical trial of rIX-FP Other.

Latest Results From The PUP-GCP Clinical Trial: A Low Inhibitor Rate In Previously Untreated Patients With Severe Hemophilia A Treated With Octanate

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3596-3596
Author(s):  
Anna Klukowska ◽  
Martina Jansen ◽  
Vladimir Komrska ◽  
Pawel Laguna ◽  
Vladimir Vdovin ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Rating Scale ◽  
Hemophilia A ◽  
Severe Hemophilia ◽  
Observational Period ◽  
Adverse Event Profile ◽  
On Demand ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Bleeding Episodes

Abstract Background Octanate is a highly purified, double virus inactivated, human plasma-derived factor VIII (FVIII) concentrate with all coagulation FVIII bound to its natural stabilizer VWF in a VWF:RCo/FVIII:C ratio of approximately 0.4. Five prospective GCP studies with octanate were conducted in 77 previously treated patients (PTPs) with severe hemophilia A. None of these 77 PTPs developed an inhibitor while treated exclusively with octanate. Aim To assess the immunogenicity in previously untreated patients (PUPs), a prospective clinical trial has been initiated in 2000. This included 50 PUPs with severe hemophilia A for an observational period of 100 exposure days with octanate, for at least 6 months. Methods Patients with severe hemophilia A without previous exposure to FVIII or FVIII-containing products were enrolled. Efficacy and tolerability were assessed by a 4-point verbal rating scale. Inhibitors were assessed according to modified Bethesda method prior to treatment every 3-4 exposure days (ED 1-20), and after treatment every 10 EDs (ED 21-100), but at minimum every three months. Results Two of 50 (4%) subjects developed clinically relevant inhibitor titers over the course of the study. Another two displayed inhibitors that disappeared spontaneously without change of dose or dosing interval. All inhibitors developed under on-demand treatment and before ED 50. From the 50 subjects, 42 had exceeded 50 EDs at the time of this analysis. Octanate was well-tolerated and the adverse event profile was consistent with the population studied. The hemostatic efficacy in prophylaxis and treatment of bleeding episodes was generally rated as “excellent” and no complication was reported for any surgical treatment. Conclusion Despite frequent inhibitor testing and predominant on-demand treatment, the data indicate a low overall inhibitor rate for octanate in patients who exceeded 50 exposure days (4/42) of which only 2 (4.8%) were clinically relevant. Disclosures: Klukowska: Octapharma AG: Investigator Other. Jansen:Octapharma AG: Employment. Komrska:Octapharma AG: Investigator Other. Laguna:Octapharma AG: Investigator Other. Vdovin:Octapharma AG: Investigator Other. Knaub:Octapharma AG: Employment.

Efficacy and Safety Results of Prolong-9FP Clinical Program of Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP) in Previously Treated Patients with Hemophilia B

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 548-548 ◽  
Author(s):  
Elena Santagostino ◽  
Christine Voigt ◽  
Denise Wolko ◽  
Grace Cole ◽  
Yanyan Li ◽  
...  
Keyword(s):  
Day Treatment ◽  
Hemophilia B ◽  
Spontaneous Bleeding ◽  
Safety And Efficacy ◽  
On Demand ◽  
Routine Prophylaxis ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Bleeding Episodes

Abstract A fusion protein genetically linking recombinant human coagulation FIX with recombinant human albumin (rIX-FP) has been developed with an improved PK profile, thus improving hemophilia B treatment by allowing less frequent dosing. Two Phase 3 studies (CSL654-3001 and CSL654-3002) were completed. CSL654-3001 study evaluated safety and efficacy of rIX-FP for prophylaxis treatment (PT) of every 7-, 10- and 14-day and on-demand (ODT) of bleeding episodes in 63 previously treated patients (PTP), 12-61 years of age with hemophilia B (FIX ≤ 2%). Subjects in the on-demand arm received only ODT for 6 months and then switched to every 7-day PT. Subjects in the prophylaxis arm received every 7-day PT, and eligible subjects switched to every 10- or 14-day PT for approximately 12-18 months. Annualized spontaneous bleeding rates (AsBR) were compared between ODT and PT periods (in on-demand arm), and between 7-day PT and 10- or 14-day PT (in prophylaxis arm). CSL654-3002 study evaluated safety and efficacy of rIX-FP for weekly prophylaxis regimen in 27 previously treated patients younger than 12 years with hemophilia B (FIX ≤ 2%) for approximately 12 months. Annualized spontaneous bleeding rates (AsBR) were calculated. The median annualized spontaneous bleeding rate were all 0.00 for all treatment interval (7-day, 10-day or 14-day) and in both studies age groups (1-11 years and 12-65 years) during the two completed phase 3 studies. Seventy-six subjects from both studies continued their prophylaxis regimen in the on-going extension study. In addition, subjects (including children), switched to longer treatment intervals of 10-day, 3 times per month or 14-day or lowered their weekly prophylaxis dose. Nine subjects switched to 21-day treatment interval with 100 IU/kg rIX-FP. As of 28 July 2015, at least 50 subjects (PTP) had achieved 100 EDs without developing an inhibitor to FIX or antibodies to rIX-FP. The long term safety and efficacy of rIX-FP will be presented. This presentation includes the new information regarding the change to longer than 7-day treatment regimens in the extension study, among those subjects (1-61 years of age) that previously participated in the lead in studies. Conclusion: The Prolong - 9FP clinical programdemonstrated the clinical efficacy of rIX-FP for routine prophylaxis every 7-, 10- and 14-day treatment intervals. Routine prophylaxis once every 21 days may be effective in preventing bleeding episodes in a selected patient population. In addition, rIX-FP demonstrated favorable long-term safety and tolerability. Disclosures Santagostino: Novo Nordisk: Speakers Bureau; Bayer: Speakers Bureau; CSL Behring: Speakers Bureau; Baxter/Baxalta: Speakers Bureau; Pfizer: Research Funding, Speakers Bureau; Biogen/Sobi: Speakers Bureau; Biotest: Speakers Bureau; Kedrion: Speakers Bureau; Octapharma: Speakers Bureau; Roche: Speakers Bureau. Voigt:CSL Behring: Employment. Wolko:CSL Behring: Employment. Cole:CSL Behring: Employment. Li:CSL Behring: Employment. Jacobs:CSL Behring: Employment.

Efficacy, PK and Safety Results of Clinical Study Of Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) In Previously Treated Patients With Hemophilia B

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1109-1109 ◽  
Author(s):  
Aaron Lubetsky ◽  
Toshko Lissitchkov ◽  
Elena Santagostino ◽  
Gantcho Jotov ◽  
Tami Barazani-Brutman ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Half Life ◽  
Factor Ix ◽  
Hemophilia B ◽  
Bleeding Events ◽  
Spontaneous Bleeding ◽  
Previously Treated Patients ◽  
Bleeding Episodes ◽  
The Mean

Abstract Background The standard of care for patients with severe hemophilia B is replacement treatment with Factor IX (FIX) 2-3 times a week. A fusion protein genetically linking recombinant human coagulation FIX with recombinant human albumin (rIX-FP) was developed with the aim to extend the half-life of FIX. In the completed Phase I pharmacokinetic study, the mean half-life of rIX-FP was found to be over 5 times longer than the subjects’ previous FIX. Thus, rIX-FP has potential to prevent bleedings for longer periods, allowing reduction in the frequency of injections compared to standard FIX and to reduce the number of injections required to treat a single bleed. Aims This was a Phase I/II open-label, multicenter study of rIX-FP in previously treated patients 12-65 years of age with severe hemophilia B (FIX ≤ 2%). The study evaluated the safety and efficacy of rIX-FP, including prevention of bleeding episodes during weekly prophylaxis of rIX-FP. Methods After completion of a 14-day rIX-FP pharmacokinetic assessment, 13 subjects in the prophylaxis arm received weekly prophylaxis of rIX-FP for approximately 11 months, and 4 subjects in the on-demand arm received rIX-FP upon occurrence of bleeding events. The treatment doses were initially selected based upon the pharmacokinetic profile of rIX-FP and subject’s bleeding phenotype, and doses could be adjusted at the Investigator’s discretion. Results Seventeen subjects were enrolled from hemophilia treatment centers in Israel and Bulgaria; the mean age was 26 years (range 13 to 46 years). Following a single injection of 25 IU/kg rIX-FP (n=13), the mean FIX activity level was 3.75% and 2.67% above baseline at Day 7 and Day 14, respectively, and the mean half-life of rIX-FP was 95 hours (comparable to the previously reported Phase I data). Over the 11 month treatment period, rIX-FP demonstrated a good safety profile with a total of over 700 EDs. The treatment was well tolerated and no FIX inhibitor formation was observed. There was no AE considered to be related to treatment with rIX-FP. No subject was withdrawn from the study due to safety concerns or lack of hemostatic efficacy. All 13 prophylaxis subjects were successfully maintained on a weekly routine regimen of rIX-FP for the entire duration of the study, with annualized spontaneous bleeding rates of 1.255 and 1.134 (mean and median respectively). Furthermore, three prophylaxis subjects who received only on-demand treatment prior to study entry had greater than 80% reduction in the annualized bleeding rate compared to their annualized bleeding rate prior to study entry. All bleeding events were treated successfully with ≤ 2 injections of rIX-FP, with approximately 90% of bleeds treated with a single injection of rIX-FP. The mean weekly consumption of rIX-FP was reduced markedly compared to the subjects’ weekly consumption of the previous FIX product. Conclusion This Phase I/II study demonstrated the clinical efficacy of rIX-FP for once weekly routine prophylaxis to prevent spontaneous bleeding episodes and for the treatment of bleeding episodes. In addition, rIX-FP showed an excellent safety and an improved PK profile over currently marketed factor IX products. Disclosures: Lubetsky: CSL Behring: Investigator for CSL clinical trial of rIX-FP Other. Lissitchkov:CSL Behring: Investigator for CSL Behring clinical trial of rIX-FP Other. Santagostino:CSL Behring: Honoraria, Investigator for CSL Behring clinical trial of rIX-FP Other, Research Funding, Speakers Bureau. Jotov:CSL Behring: sub-investigator for CSL Begring trial of rIX-FP Other. Barazani-Brutman:CSL Behring: study coordinator for CSL Behring rIX-FP trials Other. Voigt:CSL Behring: Employment. Moises:CSL Behring: Employment. Jacobs:CSL Behring: Employment. Martinowitz:CSL Behring: Honoraria, Investigator for CSL rIX-FP trials Other, Speakers Bureau.

RESULTS OF AN OPEN, PROSPECTIVE, MULTICENTER, NONCOMPARATIVE STUDY OF THE PHARMACOKINETICS, EFFICACY AND SAFETY OF NONACOG ALFA IN PATIENTS AGED 6–12 YEARS WITH SEVERE AND MODERATE HEMOPHILIA B

2020 ◽  
Vol 99 (6) ◽  
pp. 190-198
Author(s):  
T.A. Andreeva ◽  
◽  
V.V. Lebedev ◽  
V.V. Vdovin ◽  
M.A. Timofeeva ◽  
...  
Keyword(s):  
Prophylactic Treatment ◽  
Study Drug ◽  
Factor Ix ◽  
Hemophilia B ◽  
Efficacy And Safety ◽  
Open Label ◽  
Time Curve ◽  
Entire Study ◽  
On Demand ◽  
Bleeding Episodes

Providing hemophilia patients with blood coagulation preparations is one of the priority tasks of the national health care system. In 2011, the first recombinant factor IX was created in Russia (rFIX, nonacog alpha, Innonafactor, GENERIUM JSC), that was previously studied for pharmacokinetic (PK) parameters, efficacy and safety in adult patients and adolescents over 12 years of age with severe and moderate hemophilia B. Objective of this open-label, prospective, multicenter, noncomparative clinical study was to study PK, efficacy and safety of Innonafactor in 12 patients aged 6 to 12 years with severe and moderate forms of hemophilia B (FIX activity less than 2%). The study included periods of screening, studies of PK parameters and treatment within 26±1 weeks, but not less than 50 days of administration of the studied drug. Nonacog alfa was administered in the study of PK parameters at a dose of 75 IU/kg, once, for prophylactic treatment – at a dose of 45±10 IU/kg, 2 times a week with an interval of 72–96 h. 30 minutes after administration of the studied drug, FIX activity increased to 73,93±13,35%, with a gradual decrease to 5,88±1,97% 72 hours after administration. The area under the «concentration ‒ time» curve in the section 0–72 h (AUC0–72) and with exponential extrapolation to infinity (AUC00‒∞) was 1573,41±407,16%*h and 1808,74 ± 437,59%*h respectively. Biological half-life (T1/2) was 28,11±8,60 hours. During preventive treatment there were 19 hemorrhagic episodes, 14 (74%) bleedings were post-traumatic and 5 (26%) bleedings were spontaneous. Mean number of bleeding episodes over the entire observation period was 1,9±1,4. Mean number of episodes of spontaneous bleeding that occurred within 72 hours after Innonafactor administration in patients with bleeding was 2,5±2,1. During the entire study period, patients received 942,5 thousand IU of the drug Innonafactor, 890,5 thousand IU were administered for prophylaxis and 52 thousand IU to stop bleeding on demand. Mean single dose of Innonafactor for prophylactic treatment was 46,24±5,86 IU/kg, for on-demand treatment – 49±13,1 IU/kg. Of the 19 registered bleeding episodes, 14 (73.7%) episodes required the administration of the studied drug; 5 (26,3%) bleedings stopped on their own. To stop one episode of bleeding, an average of 2,3±2,3 administration of nonacog alfa was required. At the end of the study, the proportion of hemophilia B patients with residual FIX activity of 2% or more was 92%. During the study, 14 adverse events (AEs) were registered in 7 (58,3%) patients. All reported AEs were not study drug related and did not require study drug withdrawal. Thromboembolic complications and immunogenic reactions were not registered. Thus, the data obtained indicate efficacy and safety of Innafactor both for prophylactic treatment and for on-demand treatment of bleeding in patients aged 6 to 12 years with severe and moderate hemophilia 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.

Pharmacokinetics, Efficacy and Safety of BAX326, a Novel Recombinant Factor IX: A Prospective, Controlled, Multicenter Study in Previously Treated Patients with Severe (FIX Level < 1%) or Moderately Severe (FIX Level ≤ 2%) Hemophilia B.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2222-2222
Author(s):  
Jerzy Windyga ◽  
Toshko Lissitchkov ◽  
Oleksandra Stasyshyn ◽  
Vasily Mamonov ◽  
Luminita Rusen ◽  
...  
Keyword(s):  
Research Funding ◽  
Prophylactic Treatment ◽  
Hemophilia B ◽  
Control Group ◽  
On Demand ◽  
Previously Treated ◽  
Bleeding Episodes ◽  
The Mean ◽  
Hemostatic Efficacy ◽  
Level 2

Abstract Abstract 2222 Hemophilia B is a congenital X-linked bleeding disorder whose severity is associated with diminished or absent levels of circulating FIX. Treatment with regular prophylactic FIX infusions has significant medical and quality of life benefits by maintaining adequate plasma levels of FIX for hemostasis approximating a non-diseased state. BAX326 nonacog gamma is a novel recombinant FIX (rFIX) that is manufactured without the addition of any materials of human or animal origin, and viral inactivation/reduction is achieved through solvent/detergent (S/D) treatment as well as 15nm nanofiltration. Pharmacokinetics, hemostatic efficacy and safety of BAX326 were assessed in a prospective clinical trial in patients aged 12 to 65 years with severe (FIX level < 1%) or moderately severe (FIX level ≤ 2%) hemophilia B, previously treated with plasma-derived and/or recombinant FIX concentrates. PK parameters were compared with a commercially-available rFIX used as an active control in a crossover design. Hemostatic efficacy of BAX326 administered twice weekly as prophylaxis was compared with a historical control group treated on-demand. A total of 86 patients were enrolled and 73 were treated with BAX326. All subjects treated had previous exposure to a FIX concentrate for ≥ 150 days prior to entry into the study. Subjects included in the PK analysis (n=28) received one 75 ± 5 IU/kg infusion with BAX326 and one infusion with commercial rFIX in random order prior to receiving prophylactic treatment at a dose range from 40 to 60 IU/kg two times a week with BAX326. An additional 31 subjects also received prophylactic treatment (21–67 exposure days), and 14 subjects received BAX326 on-demand (5–25 exposure days). More than 70% of subjects had 50 or more exposure days to BAX326 during the study. PK equivalence between BAX326 and the comparator rFIX was confirmed as the 90% confidence intervals of the ratio (BAX326/comparator rFIX) of the geometric mean of AUC 0–72 h/dose (1.063 [1.03; 1.09]) was fully contained in the margins for equivalence (0.8 to 1.25). The mean half-life (T1/2) of BAX326 was 26.70h ± 9.55, and incremental recovery (IR) was 0.87 ± 0.22 IU/dL: IU/kg. Repeated PK analysis after 6 months of prophylactic treatment confirmed the results of the initial values. Twice weekly prophylactic treatment with BAX326 was effective in preventing bleeding episodes, with a significantly lower (79%, p<0.001) annualized bleed rate (ABR) during prophylaxis (mean ABR 4.20) compared to an on-demand treatment in a historical control group (mean ABR 20.0). Among the 56 subjects on prophylaxis, 24 subjects (43%) did not bleed; the mean ABR for joint bleeds was 2.79, and 1.70 for spontaneous bleeds. Of 238 total acute bleeds, 201 (84.4%) were controlled with 1–2 infusions of BAX326. Hemostatic efficacy at resolution of bleed was rated excellent or good in 95.4% of all treated bleeding episodes. The efficacy as related to degree of severity of bleeding episodes was excellent or good in 96.8 % of minor bleeds, 95 % of moderate bleeds and 92.9 % of major bleeding episodes. BAX326 was safe and well-tolerated, with similar adverse reaction rates to the comparator rFIX. The safety assessments demonstrate the safety and tolerability of BAX326 in patients with moderately severe or severe hemophilia B. There were no product related SAEs, no inhibitory or binding FIX antibodies, no antibodies to CHO, and no allergic reactions or thrombotic events; AEs considered related to BAX326 (dysgeusia and pain in extremity) were transient and mild, and occurred with an overall incidence of 2.7%. There were no treatment-related AEs within 24 hours after infusion. Elevated pre- and post-infusion values for thrombogenic markers (TAT, F1.2 and D-dimer) in some subjects did not reveal any pattern indicative of clinically relevant thrombogenicity with either BAX326 or the comparator rFIX, and were not associated with AEs. These data indicate that BAX326 is safe and efficacious in treating bleeding episodes and in routine prophylaxis in patients aged 12 years and older with hemophilia B. None of the historical risk factors, such as hypersensitivity reactions, inhibitor formation or thrombotic events were observed and few related adverse events occurred. Disclosures: Windyga: Baxter: Research Funding. Lissitchkov:Baxter: Research Funding. Stasyshyn:Baxter: Research Funding. Mamonov:Baxter: Research Funding. Rusen:Baxter: Research Funding. Lamas:Baxter: Research Funding. Oh:Baxter: Employment. Chapman:Baxter: Employment. Fritsch:Baxter: Employment. Pavlova:Baxter: Employment. Wong:Baxter: Employment. Abbuehl:Baxter: Employment.

scholarly journals Safety, Immunogenicity, and Hemostatic Efficacy of Nonacog Gamma in Patients With Severe or Moderately Severe Hemophilia B: A Continuation Study

2020 ◽  
Vol 26 ◽  
pp. 107602962095083
Author(s):  
Jerzy Windyga ◽  
Oleksandra Stasyshyn ◽  
Toshko Lissitchkov ◽  
Vasily Mamonov ◽  
Margit Serban ◽  
...  
Keyword(s):  
Prophylactic Treatment ◽  
Phase 1 ◽  
Factor Ix ◽  
Hemophilia B ◽  
Severe Hemophilia ◽  
On Demand ◽  
Treatment Standard ◽  
Pediatric Study ◽  
Bleeding Episodes ◽  
Hemostatic Efficacy

This phase 3, prospective, open-label, multicenter, continuation study (NCT01286779) investigated the use of a recombinant factor IX (FIX), nonacog gamma (BAX 326, RIXUBIS®) in patients with severe or moderately severe hemophilia B. The study population included 85 patients transitioning from a phase 1/3 pivotal study (NCT01174446), a pediatric study (NCT01488994), and 30 newly recruited patients, naïve to nonacog gamma. Patients received nonacog gamma as prophylaxis treatment (standard, modified or PK-tailored) or on-demand, as determined by the investigator. Treatment was assessed for safety, immunogenicity, hemostatic efficacy and consumption. In this study, after ≥100 exposure days, nonacog gamma resulted in no treatment-related serious adverse events, and no patients developed inhibitory antibodies to FIX. Nonacog gamma was efficacious at controlling bleeding episodes, with an 89.1% overall hemostatic efficacy rating of excellent or good, and 56% of bleeds resolved with one infusion. The annualized bleeding rate was considerably lower during prophylactic treatment (median ABR of 1.3 in 108 patients) than during on-demand treatment (median ABR of 16.5 in 13 patients). These results show that in previously treated patients and nonacog gamma-naïve patients, long-term use of nonacog gamma had acceptable safety and tolerability, and was efficacious as a prophylactic treatment for the management of bleeding episodes. NCT01286779, EudraCT: 2010-022726-33

scholarly journals Safety and Efficacy of New Moroctocog Alfa Drug (Octofactor) in Prophylactic Treatment in Adolescent Patients with Severe and Moderate Hemophilia a

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4703-4703 ◽  
Author(s):  
Ekaterina Shiller ◽  
Vladimir Vdovin ◽  
Victor Petrov ◽  
Pavel Svirin ◽  
Tatiana Andreeva ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Prophylactic Treatment ◽  
Hemophilia A ◽  
Residual Activity ◽  
Severe Hemophilia ◽  
Efficacy Evaluation ◽  
Spontaneous Bleeding ◽  
On Demand ◽  
Number Of Patients ◽  
Bleeding Episodes

Abstract Efficacy and safety of a new domestically produced rFVIII-BDD (moroctocog alfa, Octofactor, CJSC "GENERIUM", Russia) was investigated in a controlled, open, prospective, multicenter clinical trial. After screening and a 4-days washout period 12 previously treated patients adolescents (age 12-18 years old) with severe hemophilia A (the activity of FVIII was less than 1%) were included in the clinical trial. The patients were given the moroctocog alfa as prophylactic treatment in a dose of 35±5 ME/kg 3 times per week during 21±1 weeks. Before participation in this clinical trial 2 pts had received treatment with another recombinant FVIII, 2 pts had therapy with pdFVIII and 8 pts had been treated with rFVIII and pdFVIII. The main criterion of drug efficacy was the incidence of spontaneous bleeding occurred within 48 hours after of the moroctocog alfa injection. The additional criteria were: · The severity of spontaneous bleeding occurred in 21 ± 1 week. · Number of injections needed for the one episode of bleeding according of its severity. · The total amount of drug administered over a period of prophylactic treatment and treatment "on demand". · The number of patients with severe hemophilia A with a residual activity of FVIII ≥1% in 48 hours after the injection on prophylactic therapy. During the follow up period (21±1 week) 17 bleeding episodes were registered, 2 of them (11,8%) were severe, 10 (58,8%) were moderate and 5 (29,4%) were mild (Tab.1). Number of bleeding episodes (spontaneous and traumatic) was 17 (1.55 in average). Number of spontaneous bleeding was 3 (17,6%), 1 of them was mild and 2 were moderate. The average number of injections that stop one bleeding episode was 1.7±0.8. The total amount of moroctocog alfa administered over a period was 1.502.000 ÌÅ for prophylactic treatment and 64.750 ÌÅ for "on demand" treatment. The number of patients with severe hemophilia A with a residual activity of FVIII ≥1% in 48 hours after injection on prophylactic therapy was 63,6% on visit 2, 90,09% on visit 3 and 81,1% on visit 4. The safety assessment was performed in 12 patients. There were 8 adverse events and 7 of them were not associated with drugs administration. There was one serious adverse effect, allergic reaction accompanied by arthralgia and cephalalgia. The patient was excluded from the trial without consequences for life and health. There were no infection transmissions and de novo inhibitor incident. The study showed that moroctocog alfa is effective and safe in prophylactic treatment and stopping of bleeding in adolescents with severe hemophilia A. Table 1. Efficacy evaluation Table 1. Efficacy evaluation Disclosures No relevant conflicts of interest to declare.

A Multicenter Pharmacosurveillance Study for the Evaluation of the Efficacy and Safety of Recombinant Factor VIII in the Treatment of Patients with Hemophilia A

1997 ◽  
Vol 78 (05) ◽  
pp. 1352-1356 ◽  
Author(s):  
Emel Aygören-Pürsün ◽  
Inge Scharrer ◽  
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Parvovirus B19 ◽  
Subjective Evaluation ◽  
Recombinant Factor Viii ◽  
Fviii Inhibitor ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Bleeding Episodes ◽  
Recombinant Fviii

SummaryIn this open multicenter study the safety and efficacy of recombinant factor VIII (rFVIII) was assessed in 39 previously treated patients with hemophilia A (factor VIII basal activity ≤15%).Recombinant FVIII was administered for prophylaxis and treatment of bleeding episodes and for surgical procedures. A total of 3679 infusions of rFVIII were given. Efficacy of rFVIII as assessed by subjective evaluation of response to infusion and mean annual consumption of rFVIII was comparable to that of plasma derived FVIII concentrates. The incremental recovery of FVIII (2.4 ± 0,83%/IU/kg, 2.12 ± 0.61%/IU/kg, resp.) was within the expected range. No clinical significant FVIII inhibitor was detected in this trial. Five of 16 susceptible patients showed a seroconversion for parvovirus B19. However, the results are ambiguous in two cases and might be explained otherwise in one further case. Thus, in two patients a reliable seroconversion for parvovirus B19 was observed.

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