Previously treated patients with severe (FIX level < 1%) or moderately severe (FIX level = 2%) hemophilia B. MedDRA version: 14.0 Level: LLT Classification code 10018939 Term: Haemophilia B (Factor IX) System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: BAX326
Product Code: BAX326
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Nonacog alfa
CAS Number: 181054-95-5
Current Sponsor code: BAX 326
Oth
Sponsors
Baxter Innovations GmbH
Baxter Healthcare Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Subject is 12 to 65 years old at the time of screening. • Subject and/or legal representative has/have provided signed informed consent. • Subject has severe (FIX level =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • The subject has a history of FIX inhibitors with a titer = 0.6 Bethesda Units (BU) (as determined by the Nijmegen modification of the Bethesda assay or the assay employed in the respective local laboratory) at any time prior to screening. • The subject has a detectable FIX inhibitor at screening, with a titer =0.6 BU as determined by the Nijmegen modification of the Bethesda assay in the central laboratory. • The subject's weight is 120 kg. • The subject has a history of allergic reaction, eg, anaphylaxis, following exposure to FIX concentrate(s). • The subject has a known hypersensitivity to hamster proteins or rFurin. • The subject has evidence of an ongoing or recent thrombotic disease, fibrinolysis or disseminated intravascular coagulation (DIC). • The subject has an abnormal renal function (serum creatinine > 1.5 times the upper limit of normal). • The subject has severe chronic liver disease as evidenced by, but not limited to, any of the following: International Normalized Ratio (INR) greater than 1.4 hypoalbuminemia, portal vein hypertension including presence of otherwise unexplained splenomegaly and history of esophageal varices. • The subject has active hepatic disease with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels = 2 times the upper limit of normal. • The subject has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia B. • The subject’s platelet count is < 100,000/mL. • The subject has a clinically significant medical, psychiatric, or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect subject’s safety or compliance. • The subject is currently receiving, or is scheduled to receive during the course of the study, an immunomodulating drug (eg, corticosteroid agents at a dose equivalent to hydrocortisone greater than 10 mg/day, or a-interferon) other than anti-retroviral chemotherapy. • The subject has participated in another investigational study within 30 days of enrollment. Participation in study 050901 with Immunine is allowed. • The subject is a member of the team conducting this study or is in a dependent relationship with one of the study team members. Dependent relationships include close relatives (i.e., children, partner/spouse, siblings, parents) as well as employees of the investigator or site personnel conducting the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess BAX 326 pharmacokinetic (PK) parameters and to determine bioequivalence with BeneFIX, to evaluate its hemostatic efficacy, safety, immunogenicity, and changes in health-related quality of life (HR QoL);Secondary Objective: To compare the PK parameters of BAX 326 with those of BeneFIX To monitor incremental recovery (IR) of BAX 326 over time To evaluate the hemostatic efficacy of BAX 326 in the management and prevention of acute bleeding episodes for a period of 6 months To evaluate the hemostatic efficacy of BAX 326 in the treatment of acute bleeding episodes. To evaluate the safety in terms of BAX 326 related adverse events, immunogenicity for a minimum of 50 exposure days (EDs), thrombogenicity during the PK parts, as well as clinically significant changes in routine laboratory parameters (hematology/clinical chemistry) and vital signs. To evaluate changes in HR QoL and health resource use.;Primary end point(s): • PK: o Primary PK: AUC0-72 h/dose (area under the plasma concentration versus time curve from 0 to 72 hours post-infusion);Timepoint(s) of evaluation of this end point: PK: 0.5 - 72 hours post infusion. First dose at study start and 26 weeks of treatment (please refer to protocol page 31). | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Secondary PK: total AUC/dose, MRT, CL, IR, T1/2, Vss Hemostatic efficacy: Number of bleeding episodes beginning within 24 and 48 hours of an infusion as exploratory end point. Safety: Development of inhibitory and total bibding antibodies to FIX etc. (for more details see protocol), Health related and Quality of Life and Health Resource Use End Points: please refer to protocol.;Secondary end point(s): • Other PK parameters: o AUC0-8 /dose (area under the plasma concentration/time curve from time 0 to infinity) MRT (mean residence time), CL (clearance), IR, T1/2 (elimination phase half-life), Vss (Volume of distribution at steady state). o IR over time. • Hemostatic efficacy: o Treatment of bleeding episodes: number of infusions per bleeding episode, overall hemostatic efficacy rating. o Prophylaxis: annualized bleeding rate. o Consumption of BAX 326: number of infusions and weight-adjusted consumption per month and per year; weight-adjusted consumption per event (prophylaxis and on-demand). • Safety: o Development of inhibitory and total binding antibodies to factor IX o Development of antibodies to Chinese hamster ovary (CHO) proteins and recombinant furin (rFurin) o Occurrence of severe allergic reactions, eg, anaphylaxis o Occurrence of thrombotic events and clinically significant changes in thrombogenic markers during the PK parts of the study: prothrombin fragment 1.2 (F 1.2), thrombin-antithrombin III (TAT), D-dimer. o IP-related AEs o Clinically significant changes in routine laboratory parameters (hematology and clinical chemistry), and vital signs • HR QoL and pharmacoeconomic parameters o Changes in the following HR QoL parameters and health resource use • For subjects who are between 12 to 16 years of age: o Disease-specific: Haemo-QoL short version o Generic: PedsQL™ o Health utility: EQ-5D o General pain Assessment through a visual analog scale (VAS) o Health resource use • For s | — |
Countries
Argentina, Brazil, Bulgaria, Chile, Colombia, Czech Republic, Germany, Japan, Russian Federation, Spain, Sweden, Ukraine, United Kingdom, United States
Contacts
Public ContactGuido Wuerth, Clinical Operations
Baxter Innovations GmbH
Outcome results
None listed