Hemophilia A MedDRA version: 18.0 Level: LLT Classification code 10053753 Term: Hemophilia A without inhibitors System Organ Class: 100000004850 MedDRA version: 18.0 Level: LLT Classification code 10060612 Term: Hemophilia A System Organ Class: 100000004850
Conditions
Interventions
Product Name: recombinant Factor VIII-Fc
Product Code: rFVIIIFc
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: efmoroctocog alfa
Current Sponsor code: BIIB031
Sponsors
Biogen Idec Research Ltd
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: To be eligible to participate in this study, candidates must meet the following eligibility criteria at the time of randomization, on Day 1: 1.Ability 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. Parental or guardian consent is required for subjects who are less than 18 years of age or unable to give consent, or as applicable per local laws. Subjects who are less than 18 years of age may provide assent in addition to the parental/guardian consent, if appropriate. 2.Male, age =12 years at the time of informed consent, and weighing at least 40 kg. 3.Have severe hemophilia A, defined as 200 mm3 if known as HIV antibody positive at screening. 10.Viral load of =65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: Candidates will be excluded from study entry if any of the following exclusion criteria exist at the time of randomization, on Day 1. 1.Subject is at high risk of bleeding during the 5-day period between the first and second injections for PK analyses, as per Investigator discretion. 2.Previous treatment with rFVIIIFc as study drug or commercial product. 3.Other coagulation disorder(s) in addition to hemophilia A. 4.History of hypersensitivity or anaphylaxis associated with any FVIII or IV immunoglobulin administration. 5.Currently taking (or likely to require during the study) acetylsalicylic acid (ASA), except for low-dose ASA as prophylaxis (other non steroidal anti-inflammatory drugs are permitted). 6.Concurrent systemic treatment with immunosuppressive drugs within 12 weeks prior to Day 1. Exceptions to this include: ribavirin for treatment of hepatitis C virus (HCV), and/or systemic steroids (a total of 2 courses of pulse treatments lasting no more than 7 days at a dose of =1 mg/kg within 12 weeks prior to Day 1) and/or inhaled steroids. 7.Major surgery within the previous 8 weeks. 8.Current enrollment, or enrollment within the past 30 days, in any other clinical trial involving investigational drugs. 9.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. 10.Abnormal renal function (serum creatinine >2.0 mg/dL) [test performed by the central laboratory and reviewed prior to randomization on Day 1]. 11.Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 × upper limit of normal (ULN) [test performed by the central laboratory and reviewed prior to randomization on Day 1]. 12.Serum total bilirubin >3 × ULN (test performed by the central laboratory and reviewed prior to randomization on Day 1). 13.Inability to comply with study requirements in the opinion of the Investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Blood samples for PK analysis will be collected at 0.5 hour (±5 minutes); 1 hour and 6 hours (±10 minutes); and 24, 48, 72, and 96 hours (±60 minutes) after each injection. ;Main Objective: The primary objective of the study is to characterize the PK of rFVIIIFc administered at vial strengths of 1000 and 3000 IU in subjects with severe hemophilia A.;Secondary Objective: The secondary objective of the study is to evaluate the safety of rFVIIIFc beyond the PK assessment for up to 6 months. ;Primary end point(s): The primary endpoints include the following PK parameters of rFVIIIFc: area under the concentration-time curve from time zero to infinity (AUCinf) and incremental recovery (IR, K value) as estimated from the FVIII activity data measured by aPTT clotting assay. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Blood samples for PK analysis will be collected at 0.5 hour (±5 minutes); 1 hour and 6 hours (±10 minutes); and 24, 48, 72, and 96 hours (±60 minutes) after each injection. Inhibitor Development will be measured at screening, pre dose, month 3 and month 6 or final study visit by Nijmegen-modified Bethesda assay.;Secondary end point(s): Secondary endpoints are as follows: •Secondary PK parameters will include, but are not limited to, the following: -Cmax, t½, CL, volume of distribution at steady state (Vss), and mean residence time (MRT) measured by aPTT clotting assay. -The same PK parameters as stated in the primary and secondary endpoints above measured by two stage chromogenic clotting assay. •Development of inhibitor as measured by the Nijmegen-modified Bethesda assay. | — |
Countries
Australia, South Africa, United Kingdom, United States
Outcome results
None listed