Clinical Study to Investigate the Efficacy and Safety of Wilate During Prophylaxis in Previously Treated Patients With VWD

September 29, 2023 updated by: Octapharma

Clinical Study to Investigate the Efficacy and Safety of Wilate During Prophylaxis in Previously Treated Patients With Von Willebrand Disease (VWD)

This is a prospective, non-controlled, international, multi-center phase 3 study investigating the efficacy and safety of Wilate in previously treated adult patients with VWD, to obtain additional data on the safety and efficacy of Wilate in previously treated patients with VWD undergoing regular prophylaxis.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

43

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belarus
      • Gomel, Belarus, 290
        • Republican Research Center for Radiation Medicine and Human Ecology
  • Bulgaria
      • Sofia, Bulgaria
        • "Specialized Hospital for Active Treatment of Haematological Diseases" EAD, Sofia
      • Varna, Bulgaria, 9010
        • Pediatric Clinic of Haematology and Oncology
  • Croatia
      • Zagreb, Croatia, 10000
        • University hospital centre Zagreb
  • Hungary
      • Budapest, Hungary, 1134
        • Medical Centre Hungarian Defence Forces
      • Debrecen, Hungary, 4032
        • Debreceni Egyetem Klinikai Központ, Regionális Haemophilia és Thrombophilia Központ
  • Lebanon
      • Beirut, Lebanon
        • American University of Beirut Medical Center
      • Beirut, Lebanon, BP166830
        • Hotel Dieu de France Hospital
      • Tripoli, Lebanon
        • Nini Hospital
  • Russian Federation
      • Kirov, Russian Federation, 610027
        • Federal State Budgetary Scientific Institution Kirov Scientific-Research Institute of Hematology and Blood Transfusion of Federal
      • Moscow, Russian Federation, 119049
        • Morosovskaya Children Clinical Hospital, Moscow Health Department, Department of General Hematology with the Pathology of Hemostasis
  • Ukraine
      • Kyiv, Ukraine, 01135
        • State Institution "National Children's Specialized Hospital "OKHMATDYT" of the Ministry of Health of Ukraine," Center of Hemostasis Pathology
      • Lviv, Ukraine, 79035
        • Communal Nonprofit Enterprise "Western Ukrainian Specialized Children's Medical Center"of Lviv Regional Council
  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30329
        • Children's Healthcare of Atlanta

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Patients who meet all of the following criteria are eligible for the study:

  • Aged ≥6 years at the time of screening
  • VWD type 1 (baseline von Willebrand factor activity [VWF:Ristocetin Co-factor (RCo)] <30 IU/dL, 2A, 2B, 2M, or 3 according to medical history requiring substitution therapy with a VWF-containing product to control bleeding
  • Currently receiving on-demand treatment with a VWF-containing product with at least 1, and an average of ≥2, documented spontaneous BEs per month in the last 6 months, with at least 2 of these BEs requiring treatment with a VWF-containing product
  • Availability of records to reliably evaluate type, frequency, and treatment of BEs for at least 6 months of on-demand treatment before screening
  • Female patients of child-bearing potential must have a negative urine pregnancy test at screening and agree to use adequate birth control measures; in case hormonal contra-ception is used, the medication class should remain unchanged for the duration of the study
  • All patients to provide voluntarily given, fully informed written and signed consent obtained before any study-related procedures are conducted

Exclusion Criteria:

Patients who meet any of the following criteria are not eligible for the study:

  • Having received on-demand or prophylactic treatment with a VWF-containing product but having no records available to reliably evaluate the type, frequency, and treatment of BEs over a period of at least 6 months of on-demand treatment
  • History, or current suspicion, of VWF or FVIII inhibitors
  • Medical history of a thromboembolic event within 1 year before enrolment
  • Severe liver or kidney diseases (alanine aminotransferase [ALAT] and aspartate trans-aminase [ASAT] levels >5 times of upper limit of normal, creatinine >120 µmol/L)
  • Platelet count <100,000/µL at screening (except for VWD type 2B)
  • Body weight <20 kg at screening
  • Patients receiving, or scheduled to receive, immunosuppressant drugs (other than an-tiretroviral chemotherapy), such as prednisone (equivalent to >10 mg/day), or similar drugs
  • Pregnant or breast-feeding at the time of enrolment
  • Cervical or uterine conditions causing abnormal uterine bleeding (including infection, dysplasia)
  • Treatment with any IMP in another interventional clinical study currently or within 4 weeks before enrolment
  • Other coagulation disorders or bleeding disorders due to anatomical reasons
  • Known hypersensitivity to any of the components of the study drug

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: All patients
Patients with type 3, type 2 (except 2N), or severe type 1 VWD aged ≥6 years at screening receiving Wilate for prophylactic treatment.
Drug: Wilate

Produced from the plasma of human donors, Wilate is presented as a powder or solvent for intravenous injection containing normally 500 IU or 1000 IU human VWF and human FVIII per vial. The ratio between VWF ristocetin co-factor activity (VWF:RCo) and FVIII:C is 1:1. The product contains approximately 100 IU/ml human VWF when reconstituted with 5ml/10mL water for injection with 0.1% polysorbate 80.

The specific activity of Wilate is ≥67 IU VWF:RCo/mg protein. The injection or infusion rate should not exceed 2-3mL per minute.

Other Names:
  • von Willebrand factor / Factor VIII (plasma derived)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Annualized Bleeding Rate (TABR)
Time Frame: 12 months
The TABR was calculated as the total number of spontaneous bleeds, traumatic bleeds, and other bleeds (except menstrual bleeds) occurring in the time period between first dose of the investigational medicinal product (IMP) and the Study Completion Visit, divided by the duration (in years) between first dose of IMP and the Study Completion Visit.
12 months
Comparison of Total Annualized Bleeding Rates (TABR) During Prophylaxis Treatment in Study WIL-31 to On-demand Treatment in the Same Patient Population in the Preceding Study WIL-29
Time Frame: 12 Months
Estimated TABR number calculated using a negative binomial counting regression model. Comparison between this number calculated for studies WIL-29 (NCT04053699) and WIL-31. For the comparison of results from WIL-31 to WIL-29 an estimated total annualized bleeding rate was calculated for each cohort, and compared with a negative binomial counting model. As these were estimated rates, there is only one value for each cohort with no measure of spread
12 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Spontaneous Annualized Bleeding Rate (SABR)
Time Frame: 12 months
Spontaneous annualized bleeding rate (SABR) calculated in analogy with TABR
12 months
Comparison of Spontaneous Annualized Bleeding Rates (SABR) During Prophylaxis Treatment in Study WIL-31 to On-demand Treatment in the Same Patient Population in the Preceding Study WIL-29.
Time Frame: 12 Months
Estimated SABR number calculated using a negative binomial counting regression model. Comparison between this number calculated for studies WIL-29 (NCT04053699) and WIL-31. For the comparison of results from WIL-31 to WIL-29 an estimated total annualized bleeding rate was calculated for each cohort, and compared with a negative binomial counting model. As these were estimated rates, there is only one value for each cohort with no measure of spread
12 Months
Wilate Consumption for Prophylaxis (mFAS Population)
Time Frame: 12 months
Data on the consumption of Wilate (VWF/FVIII IU/kg per month and per week per patient) for prophylactic treatment
12 months
Incremental In Vivo Recovery (IVR) of Von Willebrand Factor Activity (VWF:RCo)
Time Frame: From baseline and 12-month visit
Incremental VWF:RCo IVR of Wilate over time (at baseline and at 1, 2, 3, 6, 9, and 12 months of treatment)
From baseline and 12-month visit
Incremental In Vivo Recovery (IVR) of FVIII
Time Frame: Baseline and 12-month visit
FVIII:C of Wilate in pediatric patients (at baseline PK visit) measured by chromogenic assay
Baseline and 12-month visit
Efficacy of Wilate in the Treatment of Breakthrough Bleeding Events (BEs)
Time Frame: 12 months
Treatment efficacy will be assessed at the end of a BE by the patient using predefined criteria of 'Excellent', 'Good', 'Moderate' or 'None'. All effectiveness ratings assessed as either "excellent" or "good" will be considered "successfully treated".
12 months
Wilate Exposure for Prophylaxis (mFAS Population)
Time Frame: 12 months
Data on the exposure days of Wilate prophylactic treatment
12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy Rating for Wilate in Surgical Prophylaxis
Time Frame: 12 months
Efficacy will be assessed by the surgeon at the end of surgery and by the hematologist at the end of the postoperative period using predefined criteria of 'Excellent', 'Good', 'Moderate' or 'None'. In addition, an overall assessment using the 'Excellent', 'Good', 'Moderate' or 'None' scale taking both the intra- and postoperative assessments into account will be made at the end of the postoperative period by the investigator based on an algorithm.
12 months
Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29)
Time Frame: 12 months
QoL assessment based on the results from the PROMIS-29 (Patient-Reported Outcomes Measurement Information System) survey, which monitors and evaluates the physical, mental, and social health in all patients. The survey covers seven domains from the most relevant areas of self-reported health (depression, anxiety, physical function, pain interference, fatigue, sleep disturbance and ability to participate in social roles and activities) for the majority of people with chronic illness, each domain using a scale of a minimum score of 0 and a maximum score of 10. Derived T-score values are presented with higher scores equalling higher levels of the outcome being measured (e.g. more fatigue, more physical function). T-scores were calculated using the scoring service from the HealthMeasures Assessment Center. For this T-score metric 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population.
12 months
Quality of Life (QoL) Assessed Using a 36-Item Short Form Health Survey, Version 2 (SF-36v2)
Time Frame: 12 months
QoL assessment based on the results from the SF-36v2 (Short Form Health Survey) questionnaire to measure functional health and well-being in patients ≥16 years. SF-36v2 ranks 8 different domains using a scale standardized with a scoring algorithm to obtain a score ranging from 0 to 100. The eight health domains include physical functioning (PF), role physical (RP), bodily pain (BP), general health problems (GH), vitality (VT), social functioning (SF), role emotional (RE) and general mental health (MH). Norm-based scoring is used for the SF-36, setting the general population mean to 50 and the SD to 10 for all scales. Scores typically range from 20 to 60, with higher scores indicating better health.
12 months
Quality of Life (QoL) Assessed Using a 10-Item Short Form Health Survey (SF-10)
Time Frame: 12 months
QoL assessment based on the results from a SF-10 parent-completed questionnaire for patients ≥6 and <16 years of age, in order to score physical and psychosocial health. Norm-based scoring is used for the SF-36, setting the general population mean to 50 and the SD to 10 for all scales. Scores typically range from 20 to 60, with higher scores indicating better health.
12 months
Joint Health Status Assessed Using Hemophilia Joint Health Score (HJHS)
Time Frame: Baseline and 12 months
Joint health status will be assessed using the Hemophilia Joint Health Score (HJHS), which has been specifically validated for the assessment of the clinical outcome in VWD. HJHS evaluates six index joints to produce a score between 0-124. The maximum score for an individual index joint is 20. Higher scores indicate worse joint health.
Baseline and 12 months
Menstrual Bleeding Assessed Using Pictorial Blood Loss Assessment Chart (PBAC) Score
Time Frame: 12 months
Bleeding information from each menstrual period while in this study will be collected using the Pictorial Blood Loss Assessment Chart (PBAC). The PBAC will be provided to all female patients of child-bearing potential. The data documented in the PBAC and the investigator-calculated final score will be recorded in the electronic case report form (eCRF). The PBAC score is from 0 onwards, with no theoretical maximum. A score of >100 defines abnormal coagulation and heavy menstrual bleeding (>80ml of blood loss per menstrual cycle).
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Octapharma

Investigators

  • Study Director: Cristina Solomon, Octapharma

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 18, 2020

Primary Completion (Actual)

April 23, 2022

Study Completion (Actual)

April 23, 2022

Study Registration Dates

First Submitted

August 9, 2019

First Submitted That Met QC Criteria

August 9, 2019

First Posted (Actual)

August 12, 2019

Study Record Updates

Last Update Posted (Actual)

October 25, 2023

Last Update Submitted That Met QC Criteria

September 29, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • WIL-31

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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