Clinical trial NCT04953884: Efficacy, PK, Immunogenicity and Safety of Wilate in Severe Von Willebrand Disease VWD) Patients <6 Years of Age
Official title: Clinical Study to Investigate the Efficacy, Pharmacokinetics, Immunogenicity and Safety of Wilate in Severe Von Willebrand Disease Patients Under the Age of 6 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Von Willebrand Disease
Lead sponsor: Octapharma
Sponsor class: INDUSTRY
First posted: 2021-07-08
Enrollment: 12
Sex: ALL
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The WIL-33 study aims to determine the efficacy, pharmacokinetics, immunogenicity and safety of wilate as routine prophylaxis in up to 12 paediatric patients (eight evaluable) with severe von Willebrand Disease VWD (defined as screening von Willebrand factor ristocetin cofactor activity \[VWF:RCo\] \<20%) under the age of 6 years, over a period of 12 months.


Eligibility criteria: Inclusion Criteria:

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 (any 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))

Exclusion Criteria:

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

Primary outcomes:
measure: Total annualised bleeding rate (tABR) during prophylactic treatment with wilate.
timeFrame: Up to 12 months of treatment
Secondary outcomes:
measure: Area under the curve (AUC) of wilate for VWF:Ac (VWF:RCo) and FVIII:C (OS) over time
timeFrame: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate
measure: AUC normalised for the administered dose (AUCnorm) of wilate for VWF:Ac (VWF:RCo) and FVIII:C (OS) over time
timeFrame: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate
measure: In vivo half-life (T1/2) of wilate for VWF:Ac (VWF:RCo) and FVIII:C (OS) over time
timeFrame: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate
measure: Maximum plasma concentration (Cmax) of wilate for VWF:Ac (VWF:RCo) and FVIII:C (OS) over time
timeFrame: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate
measure: Time to reach maximum plasma concentration (Tmax) of wilate for VWF:Ac (VWF:RCo) and FVIII:C (OS) over time
timeFrame: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate
measure: Mean residence time (MRT) of wilate for VWF:Ac (VWF:RCo) and FVIII:C (OS) over time
timeFrame: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate
measure: Volume of distribution (Vd) of wilate for VWF:Ac (VWF:RCo) and FVIII:C (OS) over time
timeFrame: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate
measure: Clearance (CL) of wilate for VWF:Ac (VWF:RCo) and FVIII:C (OS) over time
timeFrame: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate
measure: Incremental in-vivo recovery (IVR) of wilate for VWF:Ac (VWF:RCo) and FVIII:C (OS) over time
timeFrame: At baseline and at 1, 2, 3, 6, 9, and 12 months of treatment
measure: Efficacy of wilate in the prevention and treatment of spontaneous and traumatic breakthrough BEs based on their rate and the proportion of spontaneous and traumatic BEs successfully treated with wilate
timeFrame: Up to 12 months of treatment
measure: The overall efficacy of wilate in perioperative prophylaxis against excessive bleeding as assessed at the end of the postoperative period by the responsible treating investigator
timeFrame: Up to 12 months of treatment
measure: wilate consumption data for prophylactic treatment, for on-demand treatment and during surgical prophylaxis
timeFrame: Up to 12 months of treatment
measure: Incidence of VWF and FVIII inhibitors
timeFrame: Up to 12 months of treatment
measure: Incidence of thromboembolic events
timeFrame: Up to 12 months of treatment
measure: Joint Health Status determination by the use of the Hemophilia Joint Health Score, given the patient's age and constitutional development allow this assessment
timeFrame: At baseline and at 12 months of treatment
measure: Safety and tolerability of wilate assessed by monitoring adverse events (AEs) throughout the study
timeFrame: Up to 12 months of treatment
Other outcomes:
Locations:
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Ostrava
country: Czechia
facility: University Hospital Ostrava Department for Pediatric Medicine
city: Prague
country: Czechia
facility: University Hospital Motol, Department of Paediatric Haematology and Oncology
city: Duisburg
country: Germany
facility: Gerinnungszentrum Rhein-Ruhr Ambulanz und Fachlaboratorium für Gerinnungserkrankungen/Hämophilie
city: Chişinău
country: Moldova, Republic of
facility: IMSP Mother and Child Institute
city: Skopje
country: North Macedonia
facility: PHI University Clinic for Child Diseases
city: Moscow
country: Russian Federation
facility: FSBI National Research Medical Center of Pediatric Hematology, Oncology and Immunology
city: Moscow
country: Russian Federation
facility: Morozovskaya Children's Hospital
city: Lviv
country: Ukraine
facility: Danylo Halytsky Lviv National Medical University, Communal Institution of Lviv Regional Council "Western Ukrainian Specialized Children's Medical Centre"
Study officials:
References: