Prospective clinical study in children with severe haemophilia A to investigate clinical efficacy, immunogenicity, pharmacokinetics, and safety of Human-cl rhFVIII

Not Applicable

Completed

Conditions: Severe haemophilia A
Haematological Disorders
Haemophilia

Registration Number: ISRCTN71212110

Lead Sponsor: Octapharma AG (Switzerland)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Male

Target Recruitment: 60

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

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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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<br>2. Efficacy of on-demand treatment of breakthrough bleeding episodes

Secondary Outcome Measures

Name	Time	Method
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<br>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<br>3. The immunogenic potential of Human-cl rhFVIII is investigated by controlling the inhibitor titre<br>4. The efficacy of Human-cl rhFVIII in surgeries is assessed<br>5. The safety of Human-cl rhFVIII in terms of adverse event monitoring is assessed