Clinical study to investigate the efficacy, pharmacokinetics, immunogenicity and safety of wilate in severe von Willebrand disease patients under the age of 6 years
Von Willebrand disease
Patients will be treated with the VWF/FVIII concentrate wilate, produced from the plasma of human donors, which is presented as a powder and solvent for intravenous injection containing nominally 500 IU or 1000 IU human VWF and human FVIII per vial. Treatments will be administered in the course of 1. Pharmacokinetic investigation (PK visit) - within 4 weeks after screening 2. Incremental recovery (IVR) visits to the study site (after 1, 2, 3, 6, 9, 12 months after the start of the prophylactic treatment phase) 3. Regular prophylactic treatment over 12 months (2-3 times per week) 4. Treatment of bleeding episodes on demand 5. Surgical interventions as surgical prophylaxis Wilate dosage for PK assessment: Single dose of 80 IU/kg body-weight (BW) - exact dose calculated according to the nominal potency, with 70–85 IU/kg BW as the acceptable range Wilate dosage recommendations for IVR visits and prophylactic treatment: 2–3 times per week at a recommended dose of 30–50 IU/kg BW over 12 months. The prophylactic dose and frequency for each patient will be determined by the responsible treating Investigator, based on the individual patient’s clinical condition. In case of unacceptably frequent breakthrough bleeding events (BEs) (i.e. two or more BEs within a 30-day period or one major BE), the dose of wilate will be increased by approximately 5 IU/kg BW (depending on the vial size of the additional vial(s) that need(s) to be injected) and/or the treatment frequency can be increased. Test product, dose, and mode of administration: The VWF/FVIII concentrate wilate, produced from the plasma of human donors, is presented as a powder and solvent for intravenous injection containing nominally 500 IU or 1000 IU human VWF and human FVIII per vial. At least three different wilate batches will be used. Wilate dosage for PK assessment: Single dose of 80 IU/kg body-weight (BW). The exact dose calculated according to the nominal potency should be administered, with 70–85 IU/kg BW
1. Patients aged <6 years at the time of screening 2. Type 3 (at least four patients), severe type 2 (except 2N) or severe type 1 VWD (and of which with VWF:RCo <20%) according to medical history, requiring substitution therapy with a VWF-containing product 3. Minimum body weight 12.5 kg at the time of screening 4. Voluntarily given, fully informed written and signed consent obtained before any study-related procedures are conducted (obtained from the patient’s parent(s)/legal guardian(s))
1. History, or current suspicion of VWF or FVIII inhibitors 2. Injection of DDAVP or VWF-containing product within 72 hours prior to inclusion 3. Medical history of a thromboembolic event 4. Platelet count <100,000/µl at screening (except for VWD type 2B) 5. Patients receiving, or scheduled to receive, immunosuppressant drugs (other than antiretroviral chemotherapy), such as prednisone (equivalent to >10 mg/day), or similar drugs 6. Treatment with any investigational medicinal product (IMP) in another interventional clinical study currently or within four weeks before enrolment 7. Other coagulation disorders or bleeding disorders 8. Known hypersensitivity to any of the components of the study drug