A clinical study involving people with severe haemophilia A to look athow two different strengths of an experimental replacement factor VIII protein (known asrFVIIIFc) are processed by the body and how safe it is to take.
- Conditions
- Hemophilia AMedDRA version: 18.0Level: LLTClassification code 10053753Term: Hemophilia A without inhibitorsSystem Organ Class: 100000004850MedDRA version: 18.0Level: LLTClassification code 10060612Term: Hemophilia ASystem Organ Class: 100000004850Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2013-003013-18-GB
- Lead Sponsor
- Biogen Idec Research Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 16
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 <1 IU/dL (<1%) endogenous FVIII as determined by one-stage clotting assay from the central laboratory at screening. If the screening result is =1%, then the severity of hemophilia A may be confirmed by documented historical evidence from a certified clinical laboratory demonstrating <1% FVIII:C as determined by the one-stage clotting assay from the medical record.
4.Previously treated subject, defined as having at least 150 documented prior EDs to any recombinant and/or plasma-derived FVIII and/or cryoprecipitate products (other than any use of rFVIIIFc – study drug or commercial product) at Day 1. Fresh frozen plasma treatment must not be considered in the count for documented EDs.
5.No history of a positive inhibitor test or clinical signs of decreased response to FVIII administrations. Family history of inhibitors will not exclude the subject.
6.No measurable inhibitor activity using the Nijmegen-modified Bethesda assay (=0.6 BU/mL is considered positive) at Screening.
7.Willingness and ability of the subject or a surrogate (a caregiver or a family member =18 years of age) to complete training in the use of the study electronic diary (eDiary) and to complete the eDiary in a timely manner throughout the study.
8.Platelet count =100,000 platelets/µL at screening (test performed by the central laboratory and reviewed prior to randomization on Day 1).
The following inclusion criteria refer to tests performed within 6 months prior to screening. If not available, the test should be conducted by the central laboratory, sampled at screening and reviewed prior to randomization on Day 1.
9.CD4 lymphocytes >200 mm3 if known as HIV antibody positive at screening.
10.Viral load of <400 copies/mL if known HIV antibody positive at screening.
Are the trial subjects under 18? yes
Number of subjects for this age range: 4
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 8
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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. <br>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:<br>•Secondary PK parameters will include, but are not limited to, the following:<br>-Cmax, t½, CL, volume of distribution at steady state (Vss), and mean residence time (MRT) measured by aPTT clotting assay.<br>-The same PK parameters as stated in the primary and secondary endpoints above measured by two stage chromogenic clotting assay.<br>•Development of inhibitor as measured by the Nijmegen-modified Bethesda assay.<br>