Medical Dictionary for Regulatory Activities (MedDRA) primary system organ class preferred term. Incidence rate = number of patients reporting the event / number of patients * 100

All patients who received at least one dose of Wilate during the study (SAF population).

Tolerability was assessed using a 3-point verbal rating scale (excellent; satisfactory; unsatisfactory) according to overall feeling during and after Wilate therapy and occurrence of ADRs.

Tolerability was assessed for infusions given for on-demand and prophylactic treatment, but not for infusions administered for surgeries or for the purpose of thrombogenicity assessment. In some instances, however, investigators also recorded the tolerability of infusions given for surgical prophylaxis. For infusions administered for surgeries, only those with available tolerability assessments are presented. Wilate infusion may have been administered to a patient for more than one reason and may be included in more than one category (e.g., if a patient was under Wilate prophylaxis, they could also receive Wilate for the treatment of a bleeding episode [BE] or surgery or menstruation).

The tolerability analysis was performed in the SAF population; however, not all of the 111 participants experienced bleeding or had surgery or menstruation.

Document the efficacy of Wilate in the treatment of acute BEs, breakthrough BEs in patients receiving prophylactic treatment, and menstrual BEs.

Efficacy was rated on a 4-point scale (excellent; good; moderate; none) according to overall haemostasis.

From all the patients in the EFF population, 58 patients experienced one or more evaluable BEs; 24 patients experienced acute BEs, 25 patients experienced breakthrough BEs and 9 experienced menstrual BEs.

Efficacy was rated on a 4-point scale (excellent; good; moderate; none) according to the number of breakthrough bleeds per month. The treatment regimen for prophylactic treatment was at the discretion of the investigator and differed for each patient, as did the duration of prophylactic treatment. The prophylaxis efficacy population (EFF-P) was subdivided into 2 groups, prophylaxis on a continuous basis (EFF-PC population) and prophylaxis on an intermittent basis (EFF-PI population). In total, 25 patients received Wilate for prophylaxis and of these, 17 patients received prophylaxis on a continuous basis, which was defined as: (1) patients having received continuous prophylaxis over a period of at least 3 months, with no treatment gaps longer than 14 days; or (2) patients having received continuous prophylaxis for at least 1 year with an average of 1 infusion/per week (these patients may have had gaps of more than 14 days).

The efficacy results for the 17 patients with continuous prophylaxis are described here (EFF-PC population).

Efficacy was rated on a 4-point scale (excellent; good; moderate; none) according to overall haemostasis during and after surgery.

All patients in the EFF population who underwent surgery under the cover of Wilate (efficacy subpopulation undergoing surgery (EFF-S) population), divided according to surgery type. Efficacy assessments were available for 51/52 minor and 46/46 major surgeries.

Patient and investigator assessment of the overall efficacy of Wilate performed at the end of the study for each patient. Efficacy was rated on a 4-point scale (excellent; good; moderate; none); criteria for assessment were not defined.

Overall efficacy assessments in the EFF population (n=91) were available from 78 patients, and investigator assessments were available for 86 patients.

Number of exposure days to Wilate was documented throughout the observation period

EDs = exposure days. IU = international unit. SD = standard deviation.

All patients who received at least one dose of Wilate during the study (SAF Population).

Optional testing for anti-VWF antibodies/VWF inhibitor was performed at the baseline and follow up visits. VWF inhibitor testing was only performed if anti-VWF antibody results were positive. VWF antibody testing was performed using an ELISA assay, and inhibitor testing using a Bethesda assay. Both assays were considered experimental, since no standardized laboratory assays were available. Results displayed here are for confirmatory inhibitor testing.

Data was analysed for all patients in the SAF population who underwent VWF inhibitor testing. Results were not available at all visits for all patients.

Patients with a positive inhibitor test were assessed for ADRs related to anti VWF antibody or inhibitor development

ADRs were assessed for all patients who has a positive VWF inhibitor testing result as described in outcome 8.

Thrombogenicity testing was optional. Thrombogenicity markers (prothrombin fragments 1 + 2; D-dimer) were evaluated at baseline and during follow up. Samples with prothrombin F1+2 and/or D-dimer values at least 2 times above the upper limit of normal were recorded as high.

A total of 47 patients were assessed over multiple visits. Results were not available at all visits for all patients.

The number of infusions and dosage of Wilate administered for the on-demand treatment of acute BEs was documented throughout the study.

n= number of infusions

Bleeding episodes (BEs) occurring in the efficacy on-demand (EFF-OD) population that included 25 patients. Menstrual BEs were excluded from this analysis.

The dosage of Wilate administered for the on-demand treatment of acute BEs was documented throughout the study.

n = number of BEs

Bleeding episodes (BEs) occurring in the efficacy on-demand (EFF-OD) population that included 25 patients.

Dosage of Wilate administered for treatment of menstrual BE's was documented throughout the study.

n = number of BEs treated

Nine patients from the EFF population had a total of 56 menstrual BEs treated with Wilate.

The treatment regimen for prophylactic treatment was at the discretion of the investigator and differed for each patient, as did the duration of prophylactic treatment. The prophylaxis efficacy population (EFF-P) was subdivided into 2 groups, prophylaxis on a continuous basis (EFF-PC population) and prophylaxis on an intermittent basis (EFF-PI population).

Patients receiving prophylactic treatment (n=25) on either a continuous basis (EFF-PC population) or an intermittent basis (EFF-PI population).

The treatment regimen for prophylactic treatment was at the discretion of the investigator and differed for each patient, as did the duration of prophylactic treatment. The prophylaxis efficacy population (EFF-P) was subdivided into 2 groups, prophylaxis on a continuous basis (EFF-PC population) and prophylaxis on an intermittent basis (EFF-PI population).

n = number of patients.

Patients receiving prophylactic treatment (n=25) on either a continuous basis (EFF-PC population) or an intermittent basis (EFF-PI population).

The treatment regimen for prophylactic treatment was at the discretion of the investigator and differed for each patient, as did the duration of prophylactic treatment. The prophylaxis efficacy population (EFF-P) was subdivided into 2 groups, prophylaxis on a continuous basis (EFF-PC population) and prophylaxis on an intermittent basis (EFF-PI population).

n = number of patients

Patients receiving prophylactic treatment (n=25) on either a continuous basis (EFF-PC population) or an intermittent basis (EFF-PI population).

The treatment regimen for prophylactic treatment was at the discretion of the investigator and differed for each patient, as did the duration of prophylactic treatment. The prophylaxis efficacy population (EFF-P) was subdivided into 2 groups, prophylaxis on a continuous basis (EFF-PC population) and prophylaxis on an intermittent basis (EFF-PI population).

Patients receiving prophylactic treatment (n=25) on either a continuous basis (EFF-PC population) or an intermittent basis (EFF-PI population).

Number and dosage of Wilate infusions administered as prophylactic treatment on a continuous basis were documented throughout the study.

The treatment regimen for prophylactic treatment was at the discretion of the investigator and differed for each patient, as did the duration of prophylactic treatment.

Patients receiving prophylactic Wilate (n=17) on a continuous basis (EFF-PC population).

Number and dosage of Wilate infusions administered as prophylactic treatment on a continuous basis were documented throughout the study.

The treatment regimen for prophylactic treatment was at the discretion of the investigator and differed for each patient, as did the duration of prophylactic treatment.

Patients receiving prophylactic Wilate (n=17) on a continuous basis (EFF-PC population).

Number and dosage of Wilate infusions administered as prophylactic treatment on a continuous basis were documented throughout the study.

The treatment regimen for prophylactic treatment was at the discretion of the investigator and differed for each patient, as did the duration of prophylactic treatment.

n = number of patients.

Patients receiving prophylactic Wilate (n=17) on a continuous basis (EFF-PC population).

Number and dosage of Wilate infusions administered as prophylactic treatment on a continuous basis were documented throughout the study.

The treatment regimen for prophylactic treatment was at the discretion of the investigator and differed for each patient, as did the duration of prophylactic treatment.

n = number of infusions.

Patients receiving prophylactic Wilate (n=17) on a continuous basis (EFF-PC population).

Number and dosage of Wilate infusions administered as treatment for breakthrough bleeds in patients receiving prophylactic treatment on a continuous or intermittent basis were documented throughout the study. n = number of infusions

The EFF-P population included 25 patients.

Number and dosage of Wilate infusions administered as treatment for breakthrough bleeds in patients receiving prophylactic treatment on a continuous or intermittent basis were documented throughout the study.

n = For 1 bleed in the EFF-PC population, the dose is unknown.

Treatment of breakthrough bleeds (n=175) in the EFF-P population that included 25 patients.

Number and dosage of Wilate infusions administered to prevent bleeding during and after surgery were documented throughout the study.

1. For 6 infusions, no dosage information is available
2. One minor surgical procedure was not treated with Wilate. For 2 of the 98 treated surgical procedures, no dosage information is available (i.e., 1 major orthopaedic surgery and 1 minor cardiovascular surgery)

Efficacy of Wilate for the prevention of bleeding during and after surgery was assessed in the efficacy surgery (EFF-S) population that included 62 patients.

Number and dosage of Wilate infusions administered to prevent bleeding during and after surgery were documented throughout the study.

1. For 6 infusions, no dosage information is available
2. One minor surgical procedure was not treated with Wilate. For 2 of the 98 treated surgical procedures, no dosage information is available (i.e., 1 major orthopedic surgery and 1 minor cardiovascular surgery)

Efficacy of Wilate for the prevention of bleeding during and after surgery was assessed in the efficacy surgery (EFF-S) population that included 62 patients.

Breakthrough bleeds in patients receiving Wilate as prophylactic treatment on a continuous (EFF-PC population) or intermittent (EFF-PI population) basis were documented throughout the study.

Patients who received Wilate as prophylaxis were sub-divided into those who received prophylaxis on a continuous basis (EFF-PC Population) and those who received prophylaxis on an intermittent basis (EFF-PI).

Patients with elevated F1 + F2 and/or D-dimer levels were monitored for thromboembolic ADRs

Thromboembolic ADRs were analysed for all patients who has elevated F1 + F2 and/or D-dimer levels >2 times the upper limit of normal as identified in outcome 11.

Patients with a positive inhibitor tests were assessed for clinical symptoms of VWF inhibition

Data was assessed for all patients in the SAF population who had a positive VWF inhibitor testing result as described in outcome 8.