The medical condition to be investigated is Hemophilia B, or Christmas disease. Hemophilia B is a deficiency in the clotting FIX and is a recessively inherited coagulation disorder due to an X-chromosome mutation carried by females and expressed mainly by males, affecting approximately 80,000 people worldwide. MedDRA version: 14.1 Level: LLT Classification code 10053754 Term: Hemophilia B without inhibitors System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: rFIXFc
Product Code: rFIXFc
Pharmaceutical Form: Powder and solvent for solution for injection
Other descriptive name: FIXFc
Concentration unit: IU international unit(s)
Concentration ty
Sponsors
Biogen Idec Hemophilia Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: To be eligible to participate in this study, candidates must meet the following eligibility criteria at Screening: 1-Able to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations. If the subject is younger than 18 years old, then a parent or guardian needs to sign the informed consent form (ICF) and the subject needs to sign the assent form as consistent with local authorities" 2. Male and =12 years of age and weigh at least 40 kg 3. Have severe hemophilia B defined as =2 IU/dL (=2%) endogenous FIX activity as determined from the central laboratory at the time of screening. If the screening result is >2%, then the severity of hemophilia B may be confirmed by documented historical evidence from a certified clinical laboratory demonstrating =2% FIX:C from the medical record or from a documented genotype known to produce severe hemophilia B; 4. Be a previously treated subject, defined as having at least 100 prior EDs to any recombinant or plasma-derived FIX product (fresh frozen plasma treatment must not be considered in the count of the documented EDs) 5. Have had bleeding events and/or treatment with FIX during the prior 12 weeks, as documented in the subjects’ medical record 6. =8 bleeds in the 52 weeks prior to enrollment on the study if currently treating with an on-demand regimen 7. A platelet count =100,000 cells/µL 8. Immunocompetent as determined by the investigator’s review of the subject’s medical history 9. Viral load of =65 years) F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Candidates will be excluded from study entry if any of the following exclusion criteria exist at Screening: 1. Prior history of, or currently detectable inhibitor as defined by the reporting laboratory (family history of inhibitors will not exclude the subject. A positive inhibitor value is =0.6 BU/mL (=1.0 BU/mL only for laboratories with a historical lower sensitivity cut-off for inhibitor detection of 1.0 BU/mL). 2. Other coagulation disorder(s) in addition to hemophilia B; 3. Prior history of anaphylaxis associated with any FIX or IV immunoglobulin administration 4. Abnormal renal function defined as serum creatinine >2.0 mg/dL 5. Active hepatic disease defined as an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 5 times the upper limit of normal 6. For the Sequential PK subgroup receiving BeneFIX: allergy to Chinese Hamster proteins 7.Any concurrent clinically significant major disease that, in the opinion of the Investigator, makes the subject unsuitable for enrollment 8. Subjects who are unable or unwilling to refrain from taking additional prophylactic doses of FIX prior to sports activity or increased physical activity 9. Concurrent systemic treatment with immunosuppressant drugs within the last 12 weeks prior to the study entry (Exceptions: ribavirin, treatment of hepatitis C virus [HCV] and HIV and/or systemic steroids [a total of 2 pulse treatments within 7 days =1mg/kg] and/or inhaled steroids) 10. Current enrollment within the past 30 days in any other clinical study involving investigational drugs. 11. Unable to enter accurate and timely information regarding injections and bleeding episodes into an electronic patient diary and without adequate parental/caregiver support to manage this (per the Investigator’s judgment).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): •Safety and tolerability endpoints include clinically notable changes from baseline in laboratory values and the incidence of AEs, including the incidence of inhibitor development. •The primary efficacy endpoint is the number of bleeding episodes (spontaneous and traumatic) with rFIXFc per subject annualized over the study period (comparison between Arms 1, 2 vs 3) ;Main Objective: The primary objectives of the study are: • To evaluate the safety and tolerability of rFIXFc • To evaluate the efficacy of rFIXFc in all treatment arms: • To evaluate the effectiveness of prophylaxis over on-demand therapy by comparing the annualized number of bleeding episodes between subjects receiving rFIXFc on each prevention regimen (Arm 1 and Arm 2) and subjects receiving rFIXFc on an on-demand regimen (Arm 3) ;Secondary Objective: The secondary objectives of the study are: To evaluate and assess the PK parameter estimates of rFIXFc and BeneFIX at baseline in the Sequential PK subgroup as well as rFIXFc at Week 26 (± 1 week) To evaluate subjects’ response to treatment To evaluate rFIXFc consumption ;Timepoint(s) of evaluation of this end point: Through-out treatment period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Assessments of response to treatment with rFIXFc for bleeding episodes, using the 4 point bleeding response scale •Physicians’ global assessments of subjects’ response to treatment with rFIXFc, using a 4 point scale •Total annualized rFIXFc consumption per subject •Dose per injection for Arm 1 •Dosing interval for subjects in Arm 2 •The number of annualized spontaneous bleeding episodes (joint, soft tissue, and muscle) per subject •The number of annualized joint bleeding episodes (spontaneous and traumatic) per subject •Time from last injection of rFIXFc to the bleeding episode •Number of injections and dose per injection of rFIXFc required to stop a bleeding episode (joint, soft tissue, and muscle) •Quality-of-Life (QoL) via Haemo-QoL or Haem-A-QoL questionnaires for Arms 1 and 2. For Arm 4: •Investigators’/Surgeons’ assessments of subjects’ response to surgery with rFIXFc, using a 4-point scale •Number of injections and dose per injection required to maintain hemostasis during the surgical period •Estimated blood loss during surgery •Number of transfusions required for surgery For Sequential PK Subgroup: •Pharmacokinetic Endpoints - Endpoints for pharmacodynamic (PD)/PK assessments will include but not be limited to activity/concentration at maximum (Amax/ Cmax), half-life (t½), clearance (CL), volume of distribution (Vd), area under the curve (AUC), mean residence time (MRT), in vivo recovery, and incremental recovery calculated from the FIX activity/ rFIXFc concentration data. In addition, the time to 1% above baseline will be estimated from the FIX activity profiles. Population PK endpoints are CL and Vd and may include other PK parameters. •Additional Safety Endpoints - The following safety measurements will be assessed: i Vital signs in the PK part of treatment Arm 1 ii Prothrombin split fragments 1+ 2 (F 1+2) iii D dimer iv Thrombin-antithrombin complex (TAT) ;Timepoint(s) of evaluation of this end point: Through-out | — |
Countries
Australia, Belgium, Brazil, Canada, China, France, Germany, Hong Kong, India, Italy, Japan, Poland, Russian Federation, South Africa, Sweden, United Kingdom, United States
Contacts
Public ContactCTA Haemophilia Contact group
Biogen Idec Hemophilia Inc
Outcome results
None listed