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

Clinical Study to Investigate the Efficacy, Pharmacokinetics, Immunogenicity and Safety of Wilate in Severe Von Willebrand Disease Patients Under the Age of 6 Years

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Von Willebrand Disease
• Intervention / Treatment: Drug: wilate

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Ostrava, Czechia
    • University Hospital Ostrava Department for Pediatric Medicine
  • Prague, Czechia
    • University Hospital Motol, Department of Paediatric Haematology and Oncology
• Germany
  • Duisburg, Germany
    • Gerinnungszentrum Rhein-Ruhr Ambulanz und Fachlaboratorium für Gerinnungserkrankungen/Hämophilie
• Moldova, Republic of
  • Chişinău, Moldova, Republic of
    • IMSP Mother and Child Institute
• North Macedonia
  • Skopje, North Macedonia
    • PHI University Clinic for Child Diseases
• Russian Federation
  • Moscow, Russian Federation
    • FSBI National Research Medical Center of Pediatric Hematology, Oncology and Immunology
  • Moscow, Russian Federation
    • Morozovskaya Children's Hospital
• Ukraine
  • Lviv, Ukraine
    • Danylo Halytsky Lviv National Medical University, Communal Institution of Lviv Regional Council "Western Ukrainian Specialized Children's Medical Centre"
• United States
  • Louisiana
    • New Orleans, Louisiana, United States, 70118
      • Tulane University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 5 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: wilate treatment; PK: Single dose of 80 IU/kg body weight (BW). Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months. Minor haemorrhage: loading dose 30-50 IU/kg BW followed by a maintenance dose of 30-40 IU/kg BW every 12-24 hours to achieve von Willebrand factor activity (VWF:Ac) and FVIII:C trough levels of >30%. Major haemorrhage: loading dose 50-80 IU/kg BW followed by a maintenance dose of 30-50 IU/kg BW every 12-24 hours to achieve VWF:Ac and FVIII:C trough levels of >50%. Minor surgery: loading dose of 40-60 IU/kg BW followed by a maintenance dose of 20-30 IU/kg BW every 12- 24 hours for up to 3 days, to achieve VWF:Ac peak levels of 50% after loading dose and trough levels >30% during maintenance. Major surgery: loading dose of 60-80 IU/kg BW followed by a maintenance dose of 30-40 IU/kg BW every 12-24 hours for up to 6 days or longer, to achieve VWF:Ac peak levels of 100% after loading dose and trough levels >50% during maintenance

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Total annualised bleeding rate (tABR) during prophylactic treatment with wilate.	Up to 12 months of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
wilate consumption data for prophylactic treatment, for on-demand treatment and during surgical prophylaxis		Up to 12 months of treatment
Incidence of VWF and FVIII inhibitors		Up to 12 months of treatment
Incidence of thromboembolic events		Up to 12 months of treatment
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
Safety and tolerability of wilate assessed by monitoring adverse events (AEs) throughout the study		Up to 12 months of treatment
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

Collaborators and Investigators

• Sponsor: Octapharma

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2021
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: June 18, 2021
• First Submitted That Met QC Criteria: July 7, 2021
• First Posted (Actual): July 8, 2021

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Blood Platelet Disorders; Von Willebrand Diseases
• Other Study ID Numbers: WIL-33

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No