Protocol Version 2 (Amendment 1) - Refinement of Exclusion criteria 1 and 6 - The 1-Month and 2-Month Contacts were changed into formal study visits that also include an IVR assessment. - Between the 3- and 6-Month Visits, the 6- and 9-Month Visits, and the 9- and 12-Month Visits, monthly telephone contacts were added. - The Wilate dose for the first IVR assessment at the time of the Baseline IVR Visit was changed from 60±10 IU/kg BW to being each patient’s individually assigned prophylactic dose as used for subsequent visits. - Obtaining female patients’ history of heavy menstrual bleeding was added at screening. - The PROMIS-29 was added as an additional QoL assessment. - Assessment of joint status using the Hemophilia Joint Health Score (HJHS) and the documentation of target joints were added. - The Pictorial Blood Loss Assessment Chart was implemented and the PBAC score was added as a tool to estimate menstrual blood loss. - The minimum number of patients aged ≥6 to <17 years was increased from 2 to 4. - The methods of VWF:Ac determination to be used were clearly specified as being VWF:RCo and VWF:GpIbM. - A clarification was added that, if no mutation was identified in the VWF gene for patients with VWD Type 2B, additional genetic testing was to be performed to exclude pseudo-VWD.

Protocol Version 3 (Amendment 2): The protocol was amended to comply with FDA requests. - A PK assessment in pediatric patients was added as a secondary objective and a secondary endpoint. - The number of pediatric patients was increased from 4 to 10. - Patients with body weight <20 kg were excluded. - The protocol author and contact for SAE reporting was changed. - The possible interval between the Screening Visit and the Baseline IVR Visit was reduced from 30 days to 2 weeks. - The estimated start date of the study was changed from Q4 2019 to Q1 2020. - The definition of target joint assessment was extended to the Study Completion Visit. - In this protocol, seroconversion for Parvovirus B19 was to be reported as an AE.

Protocol Version 5 (Amendment 3) - VWF:Ag testing was removed - FVIII:C was added as a parameter in IVR assessments. - Inclusion criterion 3 was updated to allow for patients that switched to prophylaxis within the past 2 years and had reliable documentation of on-demand treatment before switching. - Menstrual bleeds excluded from calculation of TABR. -The annual rate of heavy (i.e., major) menstrual bleeds was added as an exploratory endpoint. -Clarification that the Screening and Baseline Visits could coincide in adults, but- must not coincide in children was added. - Standard anesthetic medication was not to be collected as concomitant medications. - The patient diary was handed out at screening, NOT baseline. - All patients were to use their previous product between screening and baseline. - Previous product was to be documented as concomitant medication. - BEs were to be documented under BEs. - Number of pregnancy tests were reduced. - Number of blood draws for hematology/chemistry were reduced. - Wilate consumption data added as secondary endpoint.

Protocol Version 7 (Amendment 4) - Increased number of patients to be enrolled, in order to get 25 evaluable patients, from 28 to 40. Increased number of pediatric patients from 4 to 6. -The following sentence added: If, after a dose increase, patients still experience more than 2 spontaneous bleeding episodes, the dosing interval should be shortened from 2 times per week to 3 times per week. - Added forbidden medication in Section 4.2 (consistent with other protocols). - Added that BUN or urea could be tested. - Corrected the “within 60 -/+5 min before infusion time point” to “within 60 min before infusion”.