Efficacy, PK, Immunogenicity and Safety of Wilate in Severe Von Willebrand Disease VWD) Patients <6 Years of Age

Von Willebrand Disease Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04953884
• Other study ID #: WIL-33
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 28, 2021
• Est. completion date: December 2024

Study information

• Verified date: March 2024
• Source: Octapharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 12
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 5 Years

Eligibility

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

Related Conditions & MeSH terms

• Von Willebrand Disease
• Von Willebrand Diseases

Intervention

Drug:
• wilate
wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A

Locations

Country	Name	City	State
Czechia	University Hospital Ostrava Department for Pediatric Medicine	Ostrava
Czechia	University Hospital Motol, Department of Paediatric Haematology and Oncology	Prague
Germany	Gerinnungszentrum Rhein-Ruhr Ambulanz und Fachlaboratorium für Gerinnungserkrankungen/Hämophilie	Duisburg
Moldova, Republic of	IMSP Mother and Child Institute	Chisinau
North Macedonia	PHI University Clinic for Child Diseases	Skopje
Russian Federation	FSBI National Research Medical Center of Pediatric Hematology, Oncology and Immunology	Moscow
Russian Federation	Morozovskaya Children's Hospital	Moscow
Ukraine	Danylo Halytsky Lviv National Medical University, Communal Institution of Lviv Regional Council "Western Ukrainian Specialized Children's Medical Centre"	Lviv
United States	Tulane University	New Orleans	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
Octapharma

Countries where clinical trial is conducted

United States,  Czechia,  Germany,  Moldova, Republic of,  North Macedonia,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total annualised bleeding rate (tABR) during prophylactic treatment with wilate.		Up to 12 months of treatment
Secondary	Area under the curve (AUC) of wilate for VWF:Ac (VWF:RCo) and FVIII:C (OS) over time		At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate
Secondary	AUC normalised for the administered dose (AUCnorm) of wilate for VWF:Ac (VWF:RCo) and FVIII:C (OS) over time		At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate
Secondary	In vivo half-life (T1/2) of wilate for VWF:Ac (VWF:RCo) and FVIII:C (OS) over time		At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate
Secondary	Maximum plasma concentration (Cmax) of wilate for VWF:Ac (VWF:RCo) and FVIII:C (OS) over time		At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate
Secondary	Time to reach maximum plasma concentration (Tmax) of wilate for VWF:Ac (VWF:RCo) and FVIII:C (OS) over time		At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate
Secondary	Mean residence time (MRT) of wilate for VWF:Ac (VWF:RCo) and FVIII:C (OS) over time		At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate
Secondary	Volume of distribution (Vd) of wilate for VWF:Ac (VWF:RCo) and FVIII:C (OS) over time		At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate
Secondary	Clearance (CL) of wilate for VWF:Ac (VWF:RCo) and FVIII:C (OS) over time		At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate
Secondary	Incremental in-vivo recovery (IVR) of wilate for VWF:Ac (VWF:RCo) and FVIII:C (OS) over time		At baseline and at 1, 2, 3, 6, 9, and 12 months of treatment
Secondary	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	Assessed by the use of a 4-point ordinal haemostatic efficacy scale (excellent - good - moderate - none)	Up to 12 months of treatment
Secondary	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	Assessed by the use of a 4-point ordinal haemostatic efficacy scale (excellent - good - moderate - none)	Up to 12 months of treatment
Secondary	wilate consumption data for prophylactic treatment, for on-demand treatment and during surgical prophylaxis		Up to 12 months of treatment
Secondary	Incidence of VWF and FVIII inhibitors		Up to 12 months of treatment
Secondary	Incidence of thromboembolic events		Up to 12 months of treatment
Secondary	Joint Health Status determination by the use of the Hemophilia Joint Health Score, given the patient's age and constitutional development allow this assessment		At baseline and at 12 months of treatment
Secondary	Safety and tolerability of wilate assessed by monitoring adverse events (AEs) throughout the study		Up to 12 months of treatment