Treatment of Congenital Fibrinogen Deficiency; Global Development Plan for a Double Virus Inactivated Fibrinogen Concentrate

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4636-4636
Author(s):  
Bruce A. Schwartz ◽  
Sigurd Knaub
Keyword(s):  
Development Plan ◽  
Minor Trauma ◽  
Efficacy And Safety ◽  
Fibrinogen Concentrate ◽  
Global Development ◽  
Inherited Disorders ◽  
Human Fibrinogen ◽  
Pediatric Study ◽  
Adolescent Patients ◽  
Bleeding Episodes

Abstract Abstract 4636 Congenital afibrinogenaemia and hypofibrinogenaemia are rare inherited disorders occurring in homozygotic patients with an estimated incidence of 1 in 106. Patients present with frequent severe bleeding episodes since birth or early childhood. Bleeding may occur after a minor trauma or a small surgical intervention, into the skin, mucosa, muscles, gastrointestinal tract, or the brain. Therapeutic substitution with human fibrinogen concentrate can correct the haemostatic defect and arrest the bleeding in patients with these fibrinogen deficiencies. Octafibrin is a highly purified, lyophilized, human plasma fibrinogen concentrate, without added albumin. Octafibrin is double virus inactivated using 2 dedicated virus inactivation/removal steps, solvent/detergent treatment, and nanofiltration. A plan for the global development of Octafibrin has been prepared taking into account discussions with European Regulators and the FDA. This plan also involves discussions with the European pediatric committee (PDCO) which oversees the inclusion of pediatric subjects into drug development under the new EMA guidelines. The development plan calls for a prospective, randomized, open label, multinational, pivotal PK comparison of Octafibrin to an existing marketed product in 18 adult and adolescent patients, including comparison of a surrogate efficacy endpoint measured by TEG. In a second study the efficacy and safety of the product in bleeding and invasive procedures will be assessed in 24 adult and adolescent patients. Finally a pediatric PK, efficacy and safety study in patients below 6 years will be performed but because of the rarity of these patients this study will not need to be completed before review and approval by the regulatory agencies. Clinical studies are planned to be started later this year. A double virus inactivated, plasma derived fibrinogen concentrate (Octafibrin) will be globally developed in an ultra rare congenital disease after harmonized discussions with EU and US regulators. Pivotal comparative PK data and interim efficacy and safety data will be available at time of regulatory submissions while the finalization of the pediatric study is deferred. Effective management of congenital fibrinogen deficiencies in bleeding situations is necessary for the prevention of potentially life-threatening bleeding episodes. This clinical program will help to confirm that fibrinogen substitution is able to successfully control bleeding, increase the fibrinogen plasma levels, and reduce the amount of transfusions needed with allogeneic blood products. In addition, it will give additional information on the tolerability and overall safety profile of fibrinogen replacement therapy. Disclosures: Schwartz: Octapharma: Employment. Knaub:Octapharma: Employment.

scholarly journals Efficacy and Safety of Human Fibrinogen Concentrate for the Treatment of Patients with Congenital Fibrinogen Deficiency: Combined Results of the FORMA-02 and FORMA-04 Clinical Trials

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 11-12
Author(s):  
Claudia Djambas Khayat ◽  
Irina Kruzhkova ◽  
Cristina Solomon ◽  
Bruce A. Schwartz ◽  
Flora Peyvandi
Keyword(s):  
Pediatric Patients ◽  
Efficacy And Safety ◽  
Fibrinogen Concentrate ◽  
Surgical Prophylaxis ◽  
Bleeding Events ◽  
Phase 3 ◽  
Human Fibrinogen ◽  
Patients Âgés ◽  
Bleeding Episodes ◽  
Hemostatic Efficacy

Introduction: Congenital fibrinogen deficiency (CFD) is a rare disorder which results from a complete lack (afibrinogenemia) or low levels (hypofibrinogenemia) of functional fibrinogen. Treatment with human fibrinogen concentrate (HFC) can treat bleeding episodes and prevent blood loss in surgical treatment in patients with CFD. Herein we report combined data from two clinical studies on the efficacy and safety of HFC for the treatment of bleeding episodes (BEs) and surgical prophylaxis in adult, adolescent and pediatric patients. Methods: Both FORMA-02 and FORMA-04 were multinational, multicenter, prospective, open-label, uncontrolled Phase 3 studies for the use of HFC in adult and pediatric patients with CFD. They reported the hemostatic efficacy and safety of human fibrinogen concentrate (HFC: Fibryga® Octapharma) for on-demand treatment of BEs and surgical prophylaxis using objective criteria. Efficacy was assessed by the trial investigators and adjudicated by an independent data monitoring and end-point adjudication committee (IDMEAC). All adverse events (AEs) and serious AEs were recorded. Results: The two studies included a total of 39 patients who received HFC. The median (range) age across both studies was 17 (1-54) years, with 14 pediatric (aged 0-11), 6 adolescent (aged 12-18) and 19 adult patients (aged >18). Treatment of Bleeding Events 32 patients received HFC for the treatment of 99 bleeding events (BEs), 97 minor and 4 major. Of these, 72 were spontaneous, and 27 were due to trauma. 10 BEs occurred in pediatric patients (8 minor, 2 major), and 89 in adult/adolescents (87 minor, 2 major). The mean (±SD) total dose per BE was 65.51 mg/kg (±26.47) for adult/adolescent patients (ages 12-54) and 93.78 (±64.60) for pediatric patients (ages 0-11). Investigator-assessed and IDMEAC rated hemostatic efficacy are shown in Table 1. Overall hemostatic efficacy was rated as success (rating of excellent or good) for 99.0% of BEs by the IDMEAC. Treatment efficacy results were comparable when analyzed by age subgroup of adult (≥18 years), adolescent (>12-<18 years) and in two groups of pediatric patients (<6 years and 6-12 years). Surgical prophylaxis A total of 12 patients received HFC across 15 surgeries (13 minor and 2 major), 3 in pediatric patients (major: splenectomy; minor: circumcision and pulpectomy), and 12 in adults/adolescents (major: eye enucleation with socket reconstruction; minor: knee radioisotope synovectomy [n=2], dental extraction [n=3], circumcision [n=2], excision of circumcision scar bud, root canal operation, skin biopsy, and debridement of superficial necrosis). Mean (±SD) loading dose administered prior to surgery was 77.39 (±20.22) in adult/adolescent patients and 78.50 mg/kg (±27.96) for pediatric patients. Seven surgeries required multiple infusions, with the two major surgeries requiring 5 and 7 maintenance infusions, and the five minor surgeries requiring median (range) 3 (1-4) maintenance infusions. Intra- and post-operative hemostatic efficacy for all surgeries is shown in Table 1. Overall hemostatic efficacy of all the procedures was rated 100% successful by both the investigator and IDMEAC assessment. Safety A total of 101 AEs occurred in 23 patients (59.0%), including 16 serious AEs in 6 patients. Of these, 5 AEs in 4 patients were considered to be possibly related to treatment. These included a mild skin reaction (itchiness and redness), ischemia due to digital microthrombi, peripheral phlebitis of the upper limbs, and a portal vein thrombosis following splenectomy. No allergic/hypersensitivity reactions or deaths were observed during either of the studies. Conclusions: HFC treatment was shown to be efficacious for on-demand treatment of BEs and perioperative prophylaxis in this rare CFD population, across two Phase 3 clinical trials. Efficacy was comparable for adult, adolescent and pediatric patients. A favorable safety profile was seen for the treatment of patients with congenital afibrinogenemia with HFC. Disclosures Djambas Khayat: Octapharma: Research Funding. Kruzhkova:Octapharma: Current Employment. Solomon:Octapharma: Current Employment. Schwartz:Octapharma: Current Employment. Peyvandi:Octapharma: Research Funding. OffLabel Disclosure: On label use: Fibryga for treatment of bleeding episodes Off label use: Use of Fibryga as surgical prophylaxis in the US

scholarly journals Efficacy and safety of a new human fibrinogen concentrate in patients with congenital fibrinogen deficiency: an interim analysis of a Phase III trial

Transfusion ◽  
2017 ◽  
Vol 58 (2) ◽  
pp. 413-422 ◽  
Author(s):  
Toshko Lissitchkov ◽  
Bella Madan ◽  
Claudia Djambas Khayat ◽  
Nadezhda Zozulya ◽  
Cecil Ross ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Fibrinogen Concentrate ◽  
Human Fibrinogen ◽  
Phase Iii Trial

scholarly journals Clinical pharmacology, efficacy and safety study of a triple‐secured fibrinogen concentrate in adults and adolescent patients with congenital fibrinogen deficiency

2019 ◽  
Vol 17 (4) ◽  
pp. 635-644 ◽  
Author(s):  
Claudia Djambas Khayat ◽  
Mohamed El Khorassani ◽  
Thierry Lambert ◽  
Valérie Gay ◽  
Malika Barthez‐Toullec ◽  
...  
Keyword(s):  
Clinical Pharmacology ◽  
Efficacy And Safety ◽  
Fibrinogen Concentrate ◽  
Safety Study ◽  
Adolescent Patients

Pharmacokinetic (PK) Comparison of Two Fibrinogen Concentrates for the Treatment of Congenital Fibrinogen Deficiency

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2817-2817
Author(s):  
Bruce A. Schwartz ◽  
Savita Rangarajan ◽  
Flora Peyvandi ◽  
Mehran Karimi ◽  
Sigurd Knaub
Keyword(s):  
Single Dose ◽  
Cardiac Complications ◽  
P Value ◽  
Severe Bleeding ◽  
Minor Trauma ◽  
Fibrinogen Concentrate ◽  
Open Label ◽  
Human Fibrinogen ◽  
Parameter Ratio ◽  
A Minor

Patients with congenital afibrinogenaemia and hypofibrinogenaemia, experience frequent severe bleeding episodes starting at birth or early childhood. Bleeding may occur after a minor trauma or a small surgical intervention, into the skin, mucosa, muscles, gastrointestinal tract, or the brain. Therapeutic substitution with human fibrinogen concentrate can correct the haemostatic defect and arrest the bleeding in patients with these fibrinogen deficiencies. Octafibrin is plasma derived, highly purified, lyophilized, fibrinogen concentrate, which has been double virus safeguarded using two dedicated virus inactivation/removal steps. In this study, the (PK) profile of this new concentrate is compared to a commercially available product (Haemocomplettan® P/RiaSTAPTM). This ongoing study is a prospective, randomized, open-label, multinational, crossover PK comparison of Octafibrin to an existing marketed product with planned interim data in 9 adult and adolescent patients, including comparison of a surrogate efficacy endpoint Maximum Clot Firmness (MCF) measured by ROTEM®. The study includes a crossover design where both products are given a single dose in a randomized fashion separated by an observation period and washout of any fibrinogen product prior to infusion. Patients are confirmed afibrinogenemic with baseline fibrinogen activity plasma level of < 0.20. All fibrinogen and MCF testing was performed in a central lab using validated methods. Nine patients completed the study until the end of May 2014. There have been no reports of adverse events (AE) related to the infusion of this novel concentrate. Comparable PK profiles between the products were seen but in key parameters, Normalized Aria Under the Curve (AUCnorm) (h·mg/mL/(mg/kg) Octafibrin 0.994, Haemocomplettan® P/RiaSTAPTM 0.731 p-value 0.014) and clearance (mL/h/kg Octafibrin 0.522, Haemocomplettan® P/RiaSTAPTM 0.594 p-value 0.033), significant differences were observed between the groups. Comparable haemostatic efficacy of Octafibrin and Haemocomplettan® P/RiaSTAPTM was demonstrated based on their ability to significantly increase MCF. Mean (± SD) Fibrinogen Levels (g/L) during PK Assessment after Octafibrin and Haemocomplettan® P/RiaSTAPTM Administration, Standardized to 70 mg/kg (PK Population, n=9) Figure 1 Figure 1. Ratios of Octafibrin Relative to Haemocomplettan® P/RiaSTAPTM for AUC and AUCnorm (PK Population, N=9) Table 1 Baseline Characteristics of Patients with and without Cardiac Complications in TTP Fibrinogen activity Parameter ratio Mean 90% CI of mean ratio p-value AUC 139.11 79.25, 246.13 0.0173 AUCnorm 139.96 80.26, 245.94 0.0144 In conclusion, this study showed in general a comparable PK profile for Octafibrin and Haemocomplettan® P/RiaSTAPTM in patients with congenital fibrinogen deficiency. Octafibrin showed a significantly higher AUCnorm and lower clearance than the comparator. The haemostatic efficacy of Octafibrin, as measured by change in MCF as a surrogate parameter, was similar to that of the licensed comparator used in this study, and there was no related AE or SAE for Octafibrin after single-dose administration. Disclosures Schwartz: Octapharma: Employment. Knaub:Octapharma: Employment.

scholarly journals Efficacy and Pharmacokinetics of a New Fibrinogen Concentrate in Treating Acute Bleeding in Adolescent Patients with Congenital Fibrinogen Deficiency

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2501-2501
Author(s):  
Flora Peyvandi ◽  
Bruce A. Schwartz ◽  
Sigurd Knaub
Keyword(s):  
Bleeding Event ◽  
Advisory Board ◽  
Severe Bleeding ◽  
Fibrinogen Concentrate ◽  
Open Label ◽  
Serious Adverse Events ◽  
Human Fibrinogen ◽  
Adolescent Patients ◽  
Congenital Afibrinogenemia ◽  
Hemostatic Efficacy

Abstract Introduction: Individuals with congenital afibrinogenemia can experience frequent and/or severe bleeding episodes (BE). Human fibrinogen concentrate (HFC) can correct the hemostatic defect and arrest bleeding. We investigated the efficacy, safety and pharmacokinetics (PK) of a new highly purified, double virus-inactivated HFC (Fibryga, Octapharma) in adolescent patients. Methods: Data were analyzed from two multinational, prospective, open-label studies. FORMA-01 studied the PK of the new HFC vs. comparator (Haemocomplettan P), as well as surrogate efficacy and safety, after single infusion of 70 mg/kg. Surrogate efficacy was defined as thromboelastometric maximum clot firmness (MCF). FORMA-02 was a Phase 3 study in which the primary endpoint was the hemostatic efficacy of the new HFC for on-demand treatment of the first bleeding event. A 4-point objective scale, which was adjudicated by an Independent Data Monitoring and Endpoint Adjudication Committee (IDMEAC), was used for evaluation of efficacy. In addition, MCF and safety were evaluated for all BEs that occurred during the study period. Results: Data were available for 12 patients aged 12-17 years with afibrinogenemia. FORMA-01 included 5 patients aged 12-17 years (1 was excluded due to a protocol deviation); PK data for new HFC vs. comparator are shown in Table 1. For comparison, in adults from the same study AUCnorm was also larger and clearance slower for new HFC vs. comparator (both p=0.0027). At 1 h following infusion of new HFC or comparator, mean±SD MCF (n=6) increased from 0 mm to 9.0±2.0 and 8.8±2.6 mm, respectively (9.9±3.3 and 10.4±4.9 mm in adults). In FORMA-02, 6 adolescent patients received new HFC individually dosed for treatment of a BE. Hemostatic efficacy for treatment of the first BE was rated as excellent for all patients (success: 100%; 90% CI: 0.655-1.000). When taking all BEs into account (n=23), efficacy was again classed as excellent for all patients. Mean MCF increased by 4.83±0.98 mm from baseline to 1 h after first infusion (7.06±3.36 mm in adults). There were no related serious adverse events, severe allergic, hypersensitivity reactions, or thromboembolic events, and no inhibitory anti-fibrinogen antibodies were detected. Conclusions: This analysis of data from two prospective studies demonstrated favorable efficacy, safety, and PK parameters of the new HFC in adolescents with afibrinogenemia. PK parameters were broadly comparable with those of the comparator HFC. After infusion of the new HFC, MCF increased statistically significantly and hemostatic efficacy was rated excellent in all patients. No safety concerns relating to the new HFC were identified in these study patients. Disclosures Peyvandi: Ablynx: Other: Member of Advisory Board, Speakers Bureau; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Octapharma US: Honoraria; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Octapharma US: Honoraria; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Kedrion: Consultancy; Kedrion: Consultancy; Kedrion: Consultancy; Kedrion: Consultancy; Grifols: Speakers Bureau; Kedrion: Consultancy; Grifols: Speakers Bureau; Grifols: Speakers Bureau; Novo Nordisk: Speakers Bureau; Novo Nordisk: Speakers Bureau; Grifols: Speakers Bureau; Grifols: Speakers Bureau; Roche: Speakers Bureau; Novo Nordisk: Speakers Bureau; Roche: Speakers Bureau; Novo Nordisk: Speakers Bureau; Novo Nordisk: Speakers Bureau; Roche: Speakers Bureau; Shire: Speakers Bureau; Shire: Speakers Bureau; Roche: Speakers Bureau; Roche: Speakers Bureau; Shire: Speakers Bureau; Sobi: Speakers Bureau; Shire: Speakers Bureau; Sobi: Speakers Bureau; Sobi: Speakers Bureau; Shire: Speakers Bureau; Octapharma US: Honoraria; Sobi: Speakers Bureau; Sobi: Speakers Bureau; Octapharma US: Honoraria; Octapharma US: Honoraria. Schwartz:Octapharma US: Employment. Knaub:Octapharma AG: Employment.

Pharmacokinetic (PK) Comparison of Two Fibrinogen Concentrates in Patients with Congenital Fibrinogen Deficiency: Final Analysis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4680-4680 ◽  
Author(s):  
Cecil Ross ◽  
Savita Rangarajan ◽  
Mehran Karimi ◽  
Bruce A. Schwartz ◽  
Sigurd Knaub ◽  
...  
Keyword(s):  
Single Dose ◽  
Area Under The Curve ◽  
Final Analysis ◽  
Primary Objective ◽  
P Value ◽  
Severe Bleeding ◽  
Minor Trauma ◽  
Fibrinogen Concentrate ◽  
Open Label ◽  
Human Fibrinogen

Abstract Introduction Patients with congenital afibrinogenaemia and hypofibrinogenaemia, experience frequent severe bleeding episodes starting at birth or early childhood. Bleeding may occur after a minor trauma or a small surgical intervention, into the skin, mucosa, muscles, gastrointestinal tract, or the brain. Therapeutic substitution with human fibrinogen concentrate can correct the haemostatic defect and arrest the bleeding in patients with these fibrinogen deficiencies. Octafibrin is a plasma derived, highly purified, lyophilized, fibrinogen concentrate, which has been double virus safeguarded using two dedicated virus inactivation/removal steps. In this study, the (PK) profile of this new concentrate is compared to a commercially available product. Methods This study was a prospective, randomized, open-label, multinational, crossover PK comparison of Octafibrin to an existing marketed product (Haemocomplettan¨ P/RiaSTAPTM) in adult and adolescent afibrinogenemic patients, including comparison of a surrogate efficacy endpoint Maximum Clot Firmness (MCF) measured by ROTEM¨. Patients were randomized to either product and received a single dose of 70mg/kg b.w. and blood samples were collected over 14 days followed by an observational period up to 45 days. Afibrinogenemia was confirmed by baseline fibrinogen activity plasma level of < 0.20. All fibrinogen and MCF testing was performed in a central lab using validated methods. Primary objective was to show bioequivalence between both products based on the Normalized Area Under the Curve (AUCnorm). Results Twenty two adult and adolescent patients were included in the final analysis. Mean AUCnorm) for Octafibrin was 1.62, and for the marketed concentrate 1.35 (hákgág/L/mg) and mean clearance 0.67 and 0.82 mL/h/kg, respectively. Both showed a statistically significant differences between the groups (see figure and table below). Other PK parameter were comparable between the products. Comparable haemostatic efficacy of the two products was demonstrated based on their ability to significantly increase MCF from baseline. There were no reports of adverse events (AE) related to the infusion of this novel concentrate. Conclusions In conclusion, this study showed a statistically significantly higher AUCnorm and lower clearance for Octafibrin compared to the comparator. Other PK parameters were in general comparable. Change in MCF compared to baseline as a surrogate efficacy parameter, was similar to that of the licensed comparator used in this study, and there was no related AE or SAE for Octafibrin after single-dose administration. Table. Ratios of Octafibrin Relative to Haemocomplettan¨ P/RiaSTAPTM for AUC and AUCnorm (PK Population, N=22) Fibrinogen activity Parameter ratio Mean 90% CI of mean ratio p-value AUC 1.34 (1.23, 1.41) <0.0001 AUCnorm 1.21 (1.25, 1.44) 0.0002 Figure Mean (± SD) Fibrinogen Levels (g/L) during PK Assessment after Octafibrin and Haemocomplettan¨ P/RiaSTAPTM Administration, Standardized to 70 mg/kg (PK Population, n=22) Figure. Mean (± SD) Fibrinogen Levels (g/L) during PK Assessment after Octafibrin and Haemocomplettan¨ P/RiaSTAPTM Administration, Standardized to 70 mg/kg (PK Population, n=22) Disclosures Ross: Octapharma: Other: Investigator. Rangarajan:Octapharma: Other: Investigator. Karimi:Octapharma: Other: Investigator. Schwartz:Octapharma: Employment. Knaub:Octapharma: Employment. Peyvandi:LFB, Kedrion, Novonordisk, Bayer, Roche, CSL Behring.: Consultancy, Honoraria, Research Funding; Octapharma: Other: Investigator.

Efficacy and Safety of Once-daily Tiotropium Respimat®Add-on Therapy over 1 Year in Adolescent Patients with Moderate Symptomatic Asthma

PEDIATRICS ◽  
2016 ◽  
Vol 137 (Supplement 3) ◽  
pp. 203A-203A
Author(s):  
Lyndon Mansfield ◽  
Petra Moroni-Zentgraf ◽  
Michael Engel ◽  
Mandy Avis ◽  
Reinhold Lühmann ◽  
...  
Keyword(s):  
Efficacy And Safety ◽  
Once Daily ◽  
Adolescent Patients ◽  
Symptomatic Asthma

scholarly journals Efficacy and safety of the drug Octofactor in prophylactic treatment in patients with severe haemophilia A

2018 ◽  
Vol 5 (3) ◽  
pp. 60-73 ◽  
Author(s):  
T. A. Andreeva ◽  
V. Yu. Zorenko ◽  
I. L. Davydkin ◽  
V. N. Konstantinova ◽  
O. E. Zalepukhina ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Bleeding Episode ◽  
Coagulation Factor ◽  
Preventive Treatment ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Efficacy And Safety ◽  
Spontaneous Bleeding ◽  
Bleeding Episodes ◽  
Blood Coagulation Factor Viii

Relevance.The development of a new recombinant blood coagulation factor VIII preparation is a promising step towards optimizing the treatment of hemophilia A. An introduction of a new medication into clinical practice precedes a clinical trials to evaluate the efficacy and safety.Materials and methods.The efficacy and safety of the domestic recombinant B-domain deleted blood coagulation factor VIII (FVIII) (moroctocog alfa, Octofactor®, JSC “GENERIUM”) were studied in the preventive treatment of 31 patients aged 21 to 52 years with severe haemophilia A. The Octofactor was administered in doses of 40 ± 5 IU/kg 3 times per week at intervals of at least 48 hours for 21 ± 1 weeks.Results.The efficacy of therapy was evaluated in 30 patients, since 1 patient refused to participate in the trial after the first injection of the study medication. There were registered 43 episodes of bleeding among 11 patients in the course of the preventive treatment with Octofactor. The average number of bleeding episodes was 1.4 ± 2.58. There were 43 bleeding episodes, 9 (20.9 %) of them were posttraumatic, 34 (79.1 %) of them were spontaneous. The average number of the spontaneous bleeding episodes (a major criterion of the efficacy) was 1.13 ± 2.19, which showed a low incidence of exacerbations of the hemorrhagic syndrome in the course of preventive treatment with Octofactor. Among all registered bleeding episodes there were 6 (14 %) mild episodes, 37 (86 %) moderate episodes. Among all spontaneous bleedings there were 6 mild episodes (17.6 %), 28 (82.4 %) moderate episodes. All posttraumatic bleedings were moderate. The vast majority (36, or 83.7 %) of bleeding episodes were stopped with administration of the Octofactor. The average number of administrations of the Octofactor for arresting 1 bleeding episode was 1.2 ± 0.56, for 1 spontaneous bleeding episode – 1.2 ± 0.59. On average, it was required to administer 3534.9 ± 2329.02 IU of the Octofactor to stop 1 episode of bleeding. In the vast majority of patients with severe hemophilia A (83.3–86.7 %),  the remaining activity FVIII was 1 % or more after the administration of the Octofactor in 48 hours. The total amount of the Octofactor, introduced for the prevention of bleeding, was 6,107,000 IU, to stop bleeding – 152,000 IU. The safety of therapy was evaluated in 31 patients. There were recorded 25 adverse events (AE) in 17 patients. Among them the laboratory ones prevailed in 23 (92 %) cases, which is not associated with the use of the trial medication. There were noted nausea and an unpleasant aftertaste in the mouth in 1 patient during the first administration of the Octofactor, and therefore he refused to continue to participate in the trial. Causality 2 AE with the study drug was regarded as definite. Such AE are expected and described in the instructions to the preparation. All AE were not serious and mild and resolved without outcomes. There were no presented thromboembolic events and immunogenic reactions.Conclusions.The obtained data testify to the efficacy and safety of the Octofactor both for preventive measures and for stopping bleeding in adult patients with severe hemophilia A.

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