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

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.

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

Spontaneous annualized bleeding rate (SABR) calculated in analogy with TABR

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

Data on the consumption of Wilate (VWF/FVIII IU/kg per month and per week per patient) for prophylactic treatment

Incremental VWF:RCo IVR of Wilate over time (at baseline and at 1, 2, 3, 6, 9, and 12 months of treatment)

FVIII:C of Wilate in pediatric patients (at baseline PK visit) measured by chromogenic assay

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".

Data on the exposure days of Wilate prophylactic treatment

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.

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.

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.

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.

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.

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).