Severe hemophilia A - defined as <1 IU/dL (<1%) endogenous FVIII MedDRA version: 14.1 Level: PT Classification code 10056493 Term: Haemophilia A without inhibitors System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 14.1 Level: LLT Classification code 10053753 Term: Hemophilia A without inhibitors System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 14.1 Level: LLT Classification code 10018937 Term: Haemophilia A Syste
Conditions
Interventions
Product Name: recombinant Factor VIII-Fc
Product Code: rFVIIIFc
Pharmaceutical Form: Powder and solvent for solution for infusion
Current Sponsor code: BIIB031
Other descriptive name: rFVIIIFc, recomb
Sponsors
Biogen Idec Hemophilia, Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Provide written informed consent and any authorizations required by local law (e.g., Protected Health Information [PHI]). Parental or guardian consent is required for subjects who are less than 18 years of age (or as per local regulations). Subjects less than 18 years of age (or as per local regulations) should consent to the study providing a signed assent form if required by local regulations. 2. Male, =12 years of age and weighing at least 40 kg 3. Have severe hemophilia A defined as 200 mm3, if known as human immunodeficiency virus (HIV) antibody positive 12. Viral load of =65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: 1. History of, or currently detectable inhibitor. A positive inhibitor value is =0.6 BU/mL (or any value greater than or equal to the lower sensitivity cut-off for laboratories with cut offs for inhibitor detection between 0.7 and 1.0 BU/mL). In addition, the following documentation should be provided: - at least 2 negative inhibitor tests prior to the screening test AND - within the past 5 years (or since the start of treatment with FVIII or cryoprecipitate, if available) absence of clinical suspicion of inhibitors (from medical records and patient history- no evidence of decreased therapeutic response due to inhibitor and normal FVIII recovery, as available). Family history of inhibitors will not exclude the subject. 2. Other coagulation disorder(s) in addition to hemophilia A 3. History of hypersensitivity or anaphylaxis associated with any FVIII or IV immunoglobulin administration 4. For the PK subgroup only: known hypersensitivity to mouse or hamster proteins 5. Currently taking (or likely to require during the study) acetylsalicylic acid (ASA) or ibuprofen (other non-steroidal anti-inflammatory drugs are permitted) 6. Concurrent systemic treatment with immunosuppressive drugs 12 weeks prior to Day 0 (Advate or rFVIIIFc). (Exceptions: ribavirin, treatment of hepatitis C virus [HCV] and HIV and/or systemic steroids [a total of 2 courses of pulse treatments within 7 days =1 mg/kg] and/or inhaled steroids) 7. Major surgery within the previous 8 weeks 8. Unable to enter accurate and timely information regarding injections and bleeding episodes into an EPD and without adequate parental/caregiver support to manage this (per the Investigator’s judgment) 9. Unable or unwilling to refrain from taking additional prophylactic doses of rFVIII prior to sports activities or an increase in physical activity 10. Current enrollment or enrollment within the past 30 days in any other clinical trial involving investigational drugs. 11. Any concurrent clinically significant major disease or other unspecified reasons that, in the opinion of the Investigator, makes the subject unsuitable for participation in the study The following exclusion criteria refer to tests by the central laboratory sampled at screening and reviewed prior to Day 0 (Advate or rFVIIIFc): 12. Abnormal renal function (serum creatinine >2.0 mg/dL) 13. Serum alanine transaminase (ALT) or aspartate aminotransferase (AST) >5x upper limit of normal (ULN) 14. Serum bilirubin >3x ULN
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the safety and tolerability of rFVIIIFc administered as a prophylaxis, weekly, on-demand, and surgical treatment regimen • To evaluate the efficacy of the rFVIIIFc tailored prophylaxis regimen (Arm 1) • To evaluate the efficacy of rFVIIIFc administered as an on demand (Arm 3) and surgical treatment regimen ;Secondary Objective: • To characterize the PK profile of rFVIIIFc and compare the PK of rFVIIIFc with the currently marketed product, Advate • To characterize the range of dose and schedules required to adequately prevent bleeding in a prophylaxis regimen; maintain hemostasis in a surgical setting; or to treat bleeding episodes in an on-demand, weekly treatment, or prophylaxis setting;Primary end point(s): For Safety and Tolerability: • Clinically notable changes from baseline in physical examinations and vital signs • Incidence of AEs, including clinically significant abnormal laboratory values • Incidence of inhibitor development using the Nijmegen-modified Bethesda assay For Efficacy: • Annualized number of bleeding episodes (spontaneous and traumatic) • Primary PK parameters are the following assessments of FVIII activity: dose-corrected area under the curve (AUC/dose), half-life, MRT, clearance (CL), and incremental recovery based on the one-stage clotting assay.;Timepoint(s) of evaluation of this end point: Through-out treatment period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Total annualized rFVIIIFc consumption per subject • Subjects’ individual assessments of response to treatment with rFVIIIFc for bleeding episodes, using a bleeding response scale • Investigators’ assessment of subjects’ response to treatment with rFVIIIFc for bleeding episodes treated in the clinic, using a bleeding response scale • Annualized number of spontaneous bleeding episodes (joint, soft tissue, and muscle) per subject • Annualized number of joint bleeding episodes (spontaneous and traumatic) per subject • Time from last injection of rFVIIIFc to a bleeding episode • Number of injections and dose per injection of rFVIIIFc required to resolve a bleeding episode (joint, soft tissue, and muscle) • Additional parameters for PK/pharmacodynamic (PD) assessments will include but not be limited to: AUC/dose, half-life, MRT, CL, and incremental recovery based on the two-stage chromogenic assay; volume of distribution (Vd), time at maximum activity (Tmax); and percent recovery for FVIII activity based on both the one-stage clotting assay and the two-stage chromogenic assay. • QoL via hemophilia-specific HRQoL questionnaire for children and parents (Haemo QoL; ages 13 to 16 years) or hemophilia-specific HRQoL questionnaire for adults (Haem-A-QoL; ages 17 years and above) For the Surgery Subgroup: • Investigators’/Surgeons’ assessments of subjects’ response to surgery with rFVIIIFc, using a bleeding response scale • Number of injections and dose per injection required to maintain hemostasis during the surgical period • Estimated blood loss during surgery • Number and type of blood component transfusions required during surgery;Timepoint(s) of evaluation of this end point: Through-out treatment period. End-points for surgery sub-group are all collected at the time of surgery. | — |
Countries
Australia, Austria, Belgium, Brazil, Canada, Chile, China, Denmark, France, Germany, Hong Kong, India, Israel, Italy, Japan, New Zealand, Poland, Portugal, Russian Federation, South Africa, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactCTA Haemophilia Contact
Biogen Idec Hemophilia, Inc
Outcome results
None listed