Severe haemophilia A Haematological Disorders Haemophilia
Conditions
Interventions
This study schedules two patient groups and two study phases. One patient group passes through both study phases, whereas the other patient group undergoes the second study phase only.
Study phase I
Sponsors
Octapharma AG (Switzerland)
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Must have severe haemophilia A (FVIII:C less than 1%; historical value as documented in subject records) 2. Previously treated with FVIII concentrate, at least 50 EDs 3. Immunocompetent (CD4+ count above greater than 200/µL) 4. Human immunodeficiency virus (HIV) negative or respective viral load less than 200 particles/µL or less than 400,000 copies/ml 5. Freely given written informed consent by parents or legal guardian 6. Aged between 2 and 12 years, males only
Exclusion criteria
Exclusion criteria: 1. Other coagulation disorder than haemophilia A 2. Present or past FVIII inhibitor activity (greater than 0.6 BU) 3. Target joints 4. Severe liver or kidney disease (alanine aminotranferase [ALAT] and aspartate aminotransferase [ASAT] levels greater than 5 times of upper limit of normal, creatinine greater than 120 µmol/L) 4. Receiving or scheduled to receive immuno-modulating drugs (other than anti-retroviral chemotherapy) such as alpha-interferon, prednisone (equivalent to greater than 10 mg/day), or similar drugs 5. Current participation in another clinical study 6. Participation in another interventional clinical study with administration of investigational medical product (IMP) in the course of the past 3 months, except studies investigating already registered FVIII products
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Efficacy of prophylactic treatment: the frequency of breakthrough bleeds under prophylactic treatment will be calculated. Study drug consumption data (FVIII IU/kg, extrapolated to monthly and yearly usage) both per subject and in total will be evaluated 2. Efficacy of on-demand treatment of breakthrough bleeding episodes | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Pharmacokinetic parameters: in 50% of the included patients the following pharmacokinetic parameters of Human-cl rhFVIII are determined and compared with the previously used FVIII concentrate: in vivo half-life (T1/2), AUC, Cmax, Tmax, MRT, Vd, and CL. These PK parameters will be calculated for FVIII:C using both the CHR and the OS assays and the actual potency of Human-cl rhFVIII 2. In-vivo recovery: will be calculated - also over time - from the FVIII levels before and peak level obtained in the 0.5 or 2 hours post-infusion samples 3. The immunogenic potential of Human-cl rhFVIII is investigated by controlling the inhibitor titre 4. The efficacy of Human-cl rhFVIII in surgeries is assessed 5. The safety of Human-cl rhFVIII in terms of adverse event monitoring is assessed | — |
Countries
Austria, Czech Republic, France, Germany, Poland, Romania, Russian Federation, Serbia, Turkey, United Kingdom
Outcome results
None listed