Severe haemophilia A Haematological Disorders Hereditary factor VIII deficiency
Conditions
Interventions
In the cross-over PK phase (part I), the PK properties of human-cl rhFVIII and Kogenate®/Helexate® will be studied: each one single treatment with 50 IU rFVIII/kg body weight (BW) will be given intrav
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. Aged greater than 18 and less than 65 years, male 3. Body weight 45 kg to 110 kg 4. Previously treated with FVIII concentrate, at least 150 exposure days (EDs) 5. Immunocompetent (CD4+ count greater than 200/µL) 6. Negative for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) or respective viral load less than 200 particles/µL 7. Freely given written informed consent
Exclusion criteria
Exclusion criteria: 1. Other coagulation disorder than haemophilia A 2. Present or past FVIII inhibitor activity (greater than 0.6 BU) 3. Severe liver or kidney disease (alanine aminotransferase [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. Participation in another clinical study currently or during the past month
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare the area under curve (AUC) of human-cl rhFVIII and Kogenate®/Helexate® for FVIII:C using both the chromogenic (CHR) and the one-stage (OS) assays and the actual potency of human-cl rhFVIII and Kogenate®/Helexate®. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Pharmacokinetic (PK) parameters: 1.1. In vivo half-life (T1/2), Cmax, Tmax, MRT, Vd, and CL, calculated for FVIII:C using both the CHR and the OS assays and the actual potency of human-cl rhFVIII and Kogenate®/Helexate® 1.2. In-vivo recovery calculated from the FVIII levels before and peak level obtained in the 0.25, 0.5, 0.75, or 1 hour post-infusion samples 2. Efficacy in prophylactic treatment: 2.1. Overall efficacy assessment after a total of 50 EDs and at the end of the study 2.2. The frequency of bleeds under prophylactic treatment 2.3. Study drug consumption data (FVIII IU/kg per month, per year) per subject and in total 2.4. Efficacy assessment of each IMP injection and an overall efficacy assessment at the end of each BE 2.5. Surgical prophylaxis: the overall efficacy assessment after the end of the surgical prophylactic treatment phase by the surgeon and haematologist 2.6. Average and maximum expected estimated blood loss compared to the actual estimated blood loss 3. Safety: clinical tolerability assessed by: 3.1. Monitoring vital signs: blood pressure, heart rate, respiratory rate and body temperature will be assessed at pre-defined time-points 3.2. Laboratory parameters: the following routine safety laboratory parameters will be tested at pre-defined time-points: 3.2.1. Haematological parameters: red blood cell count, white blood cell count, haemoglobin, haematocrit, and platelet count 3.2.2. Clinical chemistry: total bilirubin, alanine aminotransferase, aspartate transaminase, blood urea nitrogen, serum creatinine, lactate dehydrogenase (LDH) 3.2.3. Serum electrolytes: sodium, potassium, bicarbonate, calcium 3.2.4. Urine analysis: urine dipstick chemical analysis (leucocyturia, haematuria, proteinuria, glucose, ketones, bilirubin, nitrites ? if positive including microscopic examination) 3.3. Monitoring adverse events (AEs): at each study visit, all adverse events are documented by the Investigator. 3.4. Inhibitors against FVIII and anti-rhFVIII an | — |
Countries
Russian Federation
Outcome results
None listed