Bleeding Incidence in VWD Patients Undergoing On-Demand Treatment

Study Overview
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Brief Summary
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The purpose of this study is to prospectively obtain reliable data on the bleeding and treatment pattern of patients with VWD undergoing on-demand treatment with a VWF-containing product over a period of 6 months. The data obtained will be used as a basis for historical comparisons with the bleeding and treatment pattern obtained from a clinical study on the efficacy of prophylactic treatment with a VWF/FVIII concentrate.

Official Title
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A Prospective, Multicenter, Non-Interventional Study Evaluating the Bleeding Incidence in Patients With Von Willebrand Disease Undergoing On-Demand Treatment

Conditions
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Von Willebrand Diseases

Intervention / Treatment
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* Drug: Von Willebrand Factor-Containing Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who meet all of the following criteria are eligible for the study: Male or female patients aged ≥5.5 years at the time of enrolment VWD type 1 (baseline von Willebrand factor activity [VWF: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 frequent on-demand treatment with a VWF-containing product In female patients of child-bearing potential using hormonal contraception, the medication class should remain unchanged for the duration of their study participation Voluntarily given, fully informed written and signed consent obtained before collection of any patient data Exclusion Criteria: Patients who meet any of the following criteria are not eligible for the study: Patients currently on prophylaxis for VWD (except for perioperative prophylaxis) as well as patients having received treatment once a month for menstrual bleeding, but not for any other bleeds Patients whose VWD treatment is planned to be switched from on-demand to prophylactic treatment in the next 6 months History, or current suspicion, of VWF or FVIII inhibitors Medical history of a thromboembolic event within 6 months before enrolment Severe liver or kidney diseases as described in the medical records Female patients with an existing or suspected pregnancy or who are breast-feeding at the time of enrolment Change in hormonal contraception within 6 months before enrolment Cervical or uterine conditions causing abnormal uterine bleeding (including infection or dysplasia) Other coagulation disorders or bleeding disorders due to anatomical reasons Participation in an interventional clinical study during the 6-month of study period Inability to complete the patient diary to reliably evaluate the type, frequency, and treatment of BEs during the 6-month study period

Ages Eligible for Study
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Minimum Age: 66 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients undergoing treatment with a VWF-containing product<br>Patients with type 3, type 2 (except 2N), or severe type 1 VWD undergoing routine on-demand treatment with a VWF-containing product over a period of 6 months | Drug: Von Willebrand Factor-Containing Product<br>* Active substances: VWF concentrates, VWF/FVIII concentrates, Cryoprecipitate VWF-containing products licensed in each participating country<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Annualized Bleeding Rate (TABR) | The total annualized bleeding rate (TABR) will be calculated as the total number of spontaneous bleeds, traumatic BEs, and other BEs occurring in the time period between the start of data collection for each patient and the Study Completion Visit, divided by the duration (in years) between the start of data collection and the Study Completion Visit. Surgery periods, and BEs occurring within these surgery periods, will be excluded from the calculation of TABR. | Screening through study completion (6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spontaneous Annualized Bleeding Rate (SABR) | Spontaneous annualized bleeding rate (SABR), calculated in analogy with TABR. This includes all bleeding episodes that occurred spontaneously. | Screening through study completion (6 months) | 
| Consumption of the VWF-containing Product | Data on the consumption of the VWF-containing product (VWF/FVIII IU/kg per month per patient) used for routine on-demand treatment | Screening through study completion (6 months) | 
| Number of Bleeding Episodes (BEs) Based on a 4-point Efficacy Scale | The efficacy assessment of bleeding episodes at the end of a BE was evaluated on a 4 point scale by the patient/legal guardian (together with the Investigator in case of on-site treatment) including the four items 'excellent,' 'good,' moderate,' and 'none.' The assessment was excellent when bleeding was completely stopped within 3 days in case of minor bleed, within 7 days in case of major bleed, and within 10 days in case of gastrointestinal bleed; Good when bleeding was completely stopped, but time and/or dose slightly exceeded expectations ; Moderate when bleeding could be stopped only by significantly exceeding time and/or dose expectations; and None when bleeding could be stopped only by using other VWF-containing products. | Screening through study completion (6 months) | 
| Number of Surgery With Successful/Unsuccessful Efficacy Assessment | Effectiveness of VWF-containing product in surgical prophylaxis based on the proportion of surgeries successfully treated. Overall treatment efficacy will be assessed at the end of the postoperative period by the treating physician using predefined criteria of 'Excellent', 'Good', 'Moderate/Poor' or 'None'. | From start of surgery until end of post-operative period (within 8 days after surgery) | 
| Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) | QoL assessment based on the results from the PROMIS-29 survey to monitor and evaluate the physical, mental, and social health in all patients, using a scale of a minimum score of 0 and a maximum score of 10, with higher scores representing a better outcome. 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. PROMIS scores have a mean of 50 and standard deviation (SD) of 10 in a referent population. Full details of cut off points for each domain can be found here: https://www.healthmeasures.net/score-and-interpret/interpret-scores/promis/promis-score-cut-points | At screening visit | 
| Quality of Life (QoL) Assessed Using a 36-Item Short Form Health Survey, Version 2 (SF-36v2) | QoL assessment based on the results from the SF-36v2 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). Higher scores indicate better health status, and a mean score of 50 has been articulated as a normative value for all scales. | At screening visit | 
| Quality of Life (QoL) Assessed Using a 10-item Short Form Health Survey (SF-10) | QoL assessment based on the results from a SF-10 parent-completed questionnaire for patients ≥5.5 and <16 years of age, in order to score physical and psychosocial health. SF-10 uses norm-based scoring where scales have a standardized mean value of 50 and standard deviation of 10. | At screening | 
| Joint Health Status Assessed Using Hemophilia Joint Health Score (HJHS) | 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. Higher scores indicate worse joint health. | At screening | 
| Menstrual Bleeding Assessed Using Pictorial Blood Loss Assessment Chart (PBAC) Score | 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 eCRF. The PBAC records pad and tampon use (as either light [1 point], medium [5 points], or heavy [10 points] flow), clots (small [1 point] or large [5 points]), and flooding episodes (1 point each) which can be recorded as many times as necessary any day of the month. The PBAC is scored from 0 (no bleeding) onwards, with a score of >100 defining abnormal coagulation and heavy menstrual bleeding (corresponds to >80ml of blood loss per menstrual cycle). | Screening through study completion (6 months) | 
| Number of Participants With Adverse Drug Reactions (ADRs) Associated With Use of Wilate | Noxious and unintended reactions arising from the use of Wilate will be monitored throughout the study. | Screening through study completion (6 months) |