Male paediatric subjects with Haemophilia A who develped high titre antibodies to human coagulation Factor VIII MedDRA version: 14.1 Level: LLT Classification code 10018941 Term: Haemophilia NOS System Organ Class: 100000004850
Conditions
Interventions
Product Name: Biostate
Pharmaceutical Form: Lyophilisate for solution for injection
Product Name: Biostate
Pharmaceutical Form: Lyophilisate and solvent for suspension for injection
Sponsors
CSL Behring GmbH
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Male subjects diagnosed with haemophilia A (::;2% FVIII level in the absence of factor replacement, according to their medical history). 2. Age 28 days to 5 and 5 and 5 and =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion Criteria: l.DThe subject has received IT! previously. 2.DSubjects with a historical peak inhibitor titre of ~200 BU/mL. 3.DConcomitant treatment with drugs with immunosuppressive side effects (eg, systemic cortlcosteroids), azathioprine, cyclophosphamide, high dose immunoglobulin or the use of a protein A column or plasmapheresis and interferons. 4.DHigh risk of cardiovascular, cerebrovascular, or other thromboembolic events (excluding catheter thrombosis) as judged by the investigator. 5. DSubjects who are human immunodeficiency virus (HIV)-l or HIV-2 positive (as reported in the medical records or determined at screening). 6.DThe subject has evidence or a history (within the previous 12 months) of abuse of any drug substance, licit or illicit. 7.DThe subject has a known or suspected hypersensitivity or has previous evidence of severe side effects to von Willebrand factor (VWF)/FVIII or FVIII concentrates or human albumin. S.DThe subject has participated in a clinical study or used an investigational compound (eg, a new chemical entity not approved for clinical use) in the past 3 months, unless the study was for haemophilia A and the subject developed an inhibitor (then, a wash-out period of at least 4 weeks must be applied), or is planning to enter such a study during the study period. 9.DSubjects or legal guardians/ representatives with suspected inability (eg, language problems) or unwillingness to comply with study procedures. 10.DThe subject has an acute or chronic medical condition other than haemophilia A, which may, in the opinion of the investigator, affect the conduct of the study. l1.DMental condition rendering the subject (or the subject's legally acceptable representative) unable to understand the nature, scope and possible consequences of the study). 12.DAny condition that is likely to interfere with evaluation of the investigational medicinal product (IMP) or satisfactory conduct of the study. 13.DEmployee at the study site, or spouse/partner or relative of the investigator or subinvestigators. Study Product, Dose, and Mode of Administration: The IMP Biostate will be intravenously (I.v.) administered at a daily dose of 200 international units (IU)/kg body weight (b.w.), preferably split into 2 doses of 100 IU/kg b.w. per day. For subjects with an undetectable inhibitor titre «0.6 BU/mL) at 2 consecutive assessments, tested at intervals of 2 weeks (±3 days), and normal recovery (~66% of predicted) for 6-S weeks, the daily Biostate dose will be reduced by 20 IU/kg b.w. (ie, by 10% of the initial daily ITI dose), if possible, every 2-4 weeks down to a dose of 100 IU/kg b.w., provided the recovery remains normal during that time (assessed weekly). After further gradual reduction of the dose and extension of the administration interval (at the discretion of the investigator), Biostate will be administered as prophylaxis at a daily dose of 50 IU/kg b.w, on 3 days per week (about every second day). Any daily dose'~100IU/kg b.w. should preferably be evenly split into 2 doses per day. Daily doses of 100 IU/kg b.w. or lower will be administered once daily. Bleeding complications during the tolerization period should be treated according to centre's standard of care. Study treatment should not be interrupted for surgical procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the proportion of subjects who achieve a complete response (success) following ITI treatment with Biostate.;Secondary Objective: Secondary Objective: To assess the safety of Biostate when administered to subjects with haemophilia A and inhibitors to FVIII in an ITI treatment regimen.;Primary end point(s): Study endpoints: Efficacy endpoints: eoResponse to ITI treatment: complete response (success), partial response (partial success), or ITI failure. eoFVIII inhibitor titre. eOTime to complete response (success). eOTime to inhibitor <0.6 BU/mL for the first time. Safety endpoints: eAdverse events (AEs). eClinical significant changes of laboratory testing (haematology, biochemistry) as judged by the investigator. eMarkers of activation of coagulation (thrombin-antithrombin complex [TAT]) above ULN eSymptomatic thromboembolic events including catheter thrombosis eFrequency and nature of bleeding events (severity and number of bleedings per patient). eCatheter-related complications (line infections). ePhysical examination and orthopaedic status. eClinically significant changes of Vital signs (blood pressure, heart rate, and body temperature). | — |
Countries
Austria, France, Germany, Greece, Italy
Contacts
Public ContactSimone Lang
CSL Behring GmbH
Outcome results
None listed