Trial Outcomes & Findings for Surveillance of Safety and Efficacy of Wilate in Patients With Von Willebrand Disease (NCT NCT01602419)

NCT ID: NCT01602419

Last Updated: 2021-01-19

Results Overview

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

• Recruitment status: COMPLETED
• Target enrollment: 120 participants
• Primary outcome timeframe: Throughout the duration of each patient's participation in the study (mean [± standard deviation (SD)]: 575 days [±326]; median [range]: 731 days [2-1185])
• Results posted on: 2021-01-19

Participant Flow

Participant milestones

Measure	Wilate A total of 120 patients were enrolled in this study. Of the 120 patients enrolled into the study, 9 were excluded because they had not received any treatment with Wilate, leaving 111 patients in the safety (SAF) population. Of these 111 patients, 7 did not have a confirmed diagnosis of von Willebrand Disease (VWD) and 2 had another bleeding disorder, leaving 102 patients in the intention-to-treat (ITT) population. Of these 102 patients, 11 were excluded from the efficacy (EFF) population for the reasons summarised below.
Overall Study STARTED	120
Overall Study SAF Population	111
Overall Study ITT Population	102
Overall Study EFF Population	91
Overall Study COMPLETED	91
Overall Study NOT COMPLETED	29

Reasons for withdrawal

Measure	Wilate A total of 120 patients were enrolled in this study. Of the 120 patients enrolled into the study, 9 were excluded because they had not received any treatment with Wilate, leaving 111 patients in the safety (SAF) population. Of these 111 patients, 7 did not have a confirmed diagnosis of von Willebrand Disease (VWD) and 2 had another bleeding disorder, leaving 102 patients in the intention-to-treat (ITT) population. Of these 102 patients, 11 were excluded from the efficacy (EFF) population for the reasons summarised below.
Overall Study Not treated with Wilate	9
Overall Study Adverse Drug Reaction	4
Overall Study Insurance issues	3
Overall Study Changed treatment centre	1
Overall Study Treatment centre closed	1
Overall Study Withdrawal by Subject	5
Overall Study Lost to Follow-up	6

Baseline Characteristics

Surveillance of Safety and Efficacy of Wilate in Patients With Von Willebrand Disease

Baseline characteristics by cohort

Measure	SAF Population n=111 Participants Of the 120 patients enrolled in this study, 111 received at least one dose of Wilate and were included in the SAF population
Age, Continuous Age at study entry	27 years n=5 Participants
Age, Continuous Age at diagnosis of VWD	13.5 years n=5 Participants
Sex: Female, Male Sex · Female	76 Participants n=5 Participants
Sex: Female, Male Sex · Male	35 Participants n=5 Participants
Race/Ethnicity, Customized Ethnic origin · Caucasian	89 Participants n=5 Participants
Race/Ethnicity, Customized Ethnic origin · Other	17 Participants n=5 Participants
Race/Ethnicity, Customized Ethnic origin · Asian	3 Participants n=5 Participants
Race/Ethnicity, Customized Ethnic origin · Black	1 Participants n=5 Participants
Race/Ethnicity, Customized Ethnic origin · Unknown	1 Participants n=5 Participants
Height	163 cm n=5 Participants
Weight	62 kg n=5 Participants
Body mass index	23.5 kg/m^2 n=5 Participants
Family history of Von Willebrand Disease (VWD) Yes	60 Participants n=5 Participants
Family history of Von Willebrand Disease (VWD) No	36 Participants n=5 Participants
Family history of Von Willebrand Disease (VWD) Unknown	15 Participants n=5 Participants
Time since diagnosis	5 years n=5 Participants
Type of VWD Type 1 VWD	50 Participants n=5 Participants
Type of VWD Type 2 VWD	32 Participants n=5 Participants
Type of VWD Type 3 VWD	20 Participants n=5 Participants
Type of VWD Not available	8 Participants n=5 Participants
Type of VWD Not applicable	1 Participants n=5 Participants
History of Von Willebrand Factor (VWF) inhibitor activity Yes	1 Participants n=5 Participants
History of Von Willebrand Factor (VWF) inhibitor activity No	83 Participants n=5 Participants
History of Von Willebrand Factor (VWF) inhibitor activity Unknown	27 Participants n=5 Participants
Known gene mutation Yes	12 Participants n=5 Participants
Known gene mutation No	49 Participants n=5 Participants
Known gene mutation Unknown	50 Participants n=5 Participants
Prestudy exposure to Factor VIII (FVIII)/Von Willebrand factor (VWF) products in exposure days (ED)s 0	37 Participants n=5 Participants
Prestudy exposure to Factor VIII (FVIII)/Von Willebrand factor (VWF) products in exposure days (ED)s < 150 EDs	57 Participants n=5 Participants
Prestudy exposure to Factor VIII (FVIII)/Von Willebrand factor (VWF) products in exposure days (ED)s ≥ 150 EDs	14 Participants n=5 Participants
Prestudy exposure to Factor VIII (FVIII)/Von Willebrand factor (VWF) products in exposure days (ED)s Not available	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Throughout the duration of each patient's participation in the study (mean [± standard deviation (SD)]: 575 days [±326]; median [range]: 731 days [2-1185])

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

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

Outcome measures

Measure	SAF Population n=111 Participants All patients treated with at least one dose of Wilate during the study.	Bleeding Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Incidence of Adverse Drug Reactions (ADRs) (%) Any adverse event	8 Participants	—	—	—	—	—
Incidence of Adverse Drug Reactions (ADRs) (%) Infections and infestations	1 Participants	—	—	—	—	—
Incidence of Adverse Drug Reactions (ADRs) (%) Nervous system disorders	1 Participants	—	—	—	—	—
Incidence of Adverse Drug Reactions (ADRs) (%) Cardiac disorders	3 Participants	—	—	—	—	—
Incidence of Adverse Drug Reactions (ADRs) (%) Vascular disorders	2 Participants	—	—	—	—	—
Incidence of Adverse Drug Reactions (ADRs) (%) Respiratory, thoracic and mediastinal disorders	2 Participants	—	—	—	—	—
Incidence of Adverse Drug Reactions (ADRs) (%) Gastrointestinal disorders	3 Participants	—	—	—	—	—
Incidence of Adverse Drug Reactions (ADRs) (%) Skin and subcutaneous tissue disorders	3 Participants	—	—	—	—	—
Incidence of Adverse Drug Reactions (ADRs) (%) General disorders & administration site conditions	5 Participants	—	—	—	—	—

PRIMARY outcome

Timeframe: During and immediately after each infusion of Wilate during the study.

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

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).

Outcome measures

Measure	SAF Population n=5494 Infusions All patients treated with at least one dose of Wilate during the study.	Bleeding n=709 Infusions Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery n=44 Infusions Wilate administered in the context of surgery.	Menstruation n=162 Infusions Wilate administered in the context of menstrual BEs.	Prevention n=88 Infusions Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Tolerability Assessment of Wilate Infusions by Reason for Administration Excellent	5393 Infusions	654 Infusions	42 Infusions	127 Infusions	38 Infusions	—
Tolerability Assessment of Wilate Infusions by Reason for Administration Satisfactory	97 Infusions	55 Infusions	1 Infusions	35 Infusions	50 Infusions	—
Tolerability Assessment of Wilate Infusions by Reason for Administration Unsatisfactory	4 Infusions	0 Infusions	1 Infusions	0 Infusions	0 Infusions	—

SECONDARY outcome

Timeframe: During and immediately after treatment of each BE.

Population: 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.

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.

Outcome measures

Measure	SAF Population n=136 Bleeding Episodes (BEs) All patients treated with at least one dose of Wilate during the study.	Bleeding n=127 Bleeding Episodes (BEs) Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery n=154 Bleeding Episodes (BEs) Wilate administered in the context of surgery.	Menstruation n=139 Bleeding Episodes (BEs) Wilate administered in the context of menstrual BEs.	Prevention n=48 Bleeding Episodes (BEs) Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs n=34 Bleeding Episodes (BEs) Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Patient and Investigator Efficacy Analysis Assessment of the Treatment of Bleeding Episodes (BEs) Good	36 Bleeding Episodes (BEs)	33 Bleeding Episodes (BEs)	32 Bleeding Episodes (BEs)	68 Bleeding Episodes (BEs)	17 Bleeding Episodes (BEs)	12 Bleeding Episodes (BEs)
Patient and Investigator Efficacy Analysis Assessment of the Treatment of Bleeding Episodes (BEs) Excellent	100 Bleeding Episodes (BEs)	94 Bleeding Episodes (BEs)	119 Bleeding Episodes (BEs)	69 Bleeding Episodes (BEs)	23 Bleeding Episodes (BEs)	14 Bleeding Episodes (BEs)
Patient and Investigator Efficacy Analysis Assessment of the Treatment of Bleeding Episodes (BEs) Moderate	0 Bleeding Episodes (BEs)	0 Bleeding Episodes (BEs)	3 Bleeding Episodes (BEs)	2 Bleeding Episodes (BEs)	8 Bleeding Episodes (BEs)	8 Bleeding Episodes (BEs)
Patient and Investigator Efficacy Analysis Assessment of the Treatment of Bleeding Episodes (BEs) None	0 Bleeding Episodes (BEs)	0 Bleeding Episodes (BEs)	0 Bleeding Episodes (BEs)	0 Bleeding Episodes (BEs)	0 Bleeding Episodes (BEs)	0 Bleeding Episodes (BEs)

SECONDARY outcome

Timeframe: At the end of the study for each patient (study duration: mean [±SD]: 805 days [±247]; median [range]: 797 days [144-1185]).

Population: 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 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).

Outcome measures

Measure	SAF Population n=17 Participants All patients treated with at least one dose of Wilate during the study.	Bleeding n=17 Participants Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Efficacy Analysis for the Prevention of Breakthrough Bleeds During Prophylaxis Excellent (<0.75 breakthrough bleeds per month)	15 Participants	12 Participants	—	—	—	—
Efficacy Analysis for the Prevention of Breakthrough Bleeds During Prophylaxis Good (0.75-1 breakthrough bleeds per month)	1 Participants	2 Participants	—	—	—	—
Efficacy Analysis for the Prevention of Breakthrough Bleeds During Prophylaxis Moderate (1-1.5 breakthrough bleeds per month)	0 Participants	1 Participants	—	—	—	—
Efficacy Analysis for the Prevention of Breakthrough Bleeds During Prophylaxis Poor (>1.5 breakthrough bleeds per month)	1 Participants	2 Participants	—	—	—	—

SECONDARY outcome

Timeframe: During and immediately after each surgery.

Population: 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.

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

Outcome measures

Measure	SAF Population n=51 Surgeries All patients treated with at least one dose of Wilate during the study.	Bleeding n=46 Surgeries Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Efficacy Analysis of Surgical Prophylaxis Excellent	47 Surgeries	40 Surgeries	—	—	—	—
Efficacy Analysis of Surgical Prophylaxis Good	3 Surgeries	6 Surgeries	—	—	—	—
Efficacy Analysis of Surgical Prophylaxis Moderate	1 Surgeries	0 Surgeries	—	—	—	—
Efficacy Analysis of Surgical Prophylaxis None	0 Surgeries	0 Surgeries	—	—	—	—

SECONDARY outcome

Timeframe: At the end of the study for each patient (study duration: mean [±SD]: 596 days [±336]; median [range]: 732 days [2-1185]).

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

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.

Outcome measures

Measure	SAF Population n=78 Participants All patients treated with at least one dose of Wilate during the study.	Bleeding n=86 Participants Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Overall Efficacy Assessment by Patient and Physician at the End of the Treatment Period Excellent	67 Participants	71 Participants	—	—	—	—
Overall Efficacy Assessment by Patient and Physician at the End of the Treatment Period Good	10 Participants	15 Participants	—	—	—	—
Overall Efficacy Assessment by Patient and Physician at the End of the Treatment Period Moderate	1 Participants	0 Participants	—	—	—	—
Overall Efficacy Assessment by Patient and Physician at the End of the Treatment Period None	0 Participants	0 Participants	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 575 days [±326]; median [range]: 731 days [2-1185]).

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

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

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

Outcome measures

Measure	SAF Population n=111 Participants All patients treated with at least one dose of Wilate during the study.	Bleeding Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Safety: Number of Exposure Days to Wilate	10 Exposure days Interval 1.0 to 512.0	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Optional antibody tests were performed at baseline and 3-4 days (preferable 7 days) after Wilate injection.

Population: 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.

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.

Outcome measures

Measure	SAF Population n=17 Participants All patients treated with at least one dose of Wilate during the study.	Bleeding n=20 Participants Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Safety: Frequency of VWF Inhibitors at Baseline and Follow up Positive confirmatory inhibitor results	1 Participants	4 Participants	—	—	—	—
Safety: Frequency of VWF Inhibitors at Baseline and Follow up Negative confirmatory inhibitor results	15 Participants	16 Participants	—	—	—	—
Safety: Frequency of VWF Inhibitors at Baseline and Follow up Confirmatory inhibitor results not done	1 Participants	0 Participants	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Optional antibody tests were performed at baseline and 3-4 days (preferable 7 days) after Wilate injection

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

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

Outcome measures

Measure	SAF Population n=1 Participants All patients treated with at least one dose of Wilate during the study.	Bleeding n=4 Participants Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Adverse Drug Reactions (ADRs)	0 Adverse drug reactions	0 Adverse drug reactions	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Optional thrombogenicity tests were performed at baseline and 1, 3 and 24 hours after each administration of Wilate.

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

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.

Outcome measures

Measure	SAF Population n=46 Participants All patients treated with at least one dose of Wilate during the study.	Bleeding n=46 Participants Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery n=46 Participants Wilate administered in the context of surgery.	Menstruation n=46 Participants Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Safety: Patients With Thrombogenicity Values >2 Times the Upper Limit of Normal (ULN) Number of patients	10 Participants	17 Participants	3 Participants	6 Participants	—	—
Safety: Patients With Thrombogenicity Values >2 Times the Upper Limit of Normal (ULN) No sample available	1 Participants	0 Participants	0 Participants	0 Participants	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 677 days [±264]; median [range]: 749 days [40-1052]).

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

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

Outcome measures

Measure	SAF Population n=206 Number of infusions All patients treated with at least one dose of Wilate during the study.	Bleeding Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Wilate Dosage Per Infusion for the Treatment of Acute Bleeding Episodes (BEs; On-demand)	31.7 IU/kg per infusion Interval 5.6 to 87.7	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 677 days [±264]; median [range]: 749 days [40-1052]).

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

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

n = number of BEs

Outcome measures

Measure	SAF Population n=136 Number of BEs All patients treated with at least one dose of Wilate during the study.	Bleeding Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Wilate Dosage for the Treatment of Acute Bleeding Episodes (BEs; On-demand) Per Bleeding Episode (BE)	33 IU/kg per BE Interval 8.2 to 625.0	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 553 days [±296]; median [range]: 713 days [125-840]).

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

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

n = number of BEs treated

Outcome measures

Measure	SAF Population n=56 Number of menstrual BEs All patients treated with at least one dose of Wilate during the study.	Bleeding Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Wilate Doses for the Treatment of Menstrual Bleeding Episodes (BEs)	79.1 IU/kg per menstrual BE Interval 10.0 to 339.8	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 761 days [±251]; median [range]: 773 days [144-1185]).

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).

Outcome measures

Measure	SAF Population n=25 Participants All patients treated with at least one dose of Wilate during the study.	Bleeding Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Exposure Days for Prophylactic Treatment With Wilate	145 Exposure days Interval 11.0 to 512.0	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 761 days [±251]; median [range]: 773 days [144-1185]).

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.

Outcome measures

Measure	SAF Population n=25 Participants All patients treated with at least one dose of Wilate during the study.	Bleeding Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Number of Infusions of Prophylactic Treatment With Wilate Per Week	2 Infusions per week Interval 0.5 to 4.2	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 761 days [±251]; median [range]: 773 days [144-1185]).

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

Outcome measures

Measure	SAF Population n=25 Participants All patients treated with at least one dose of Wilate during the study.	Bleeding Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Dosage for Prophylactic Treatment With Wilate Per Week	69.3 IU/kg per week Interval 8.2 to 298.6	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 761 days [±251]; median [range]: 773 days [144-1185]).

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).

Outcome measures

Measure	SAF Population n=4584 Number of infusions All patients treated with at least one dose of Wilate during the study.	Bleeding Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Dosage for Prophylactic Treatment With Wilate Per Infusion	31.3 IU/kg per infusion Interval 8.3 to 183.7	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 805 days [±247]; median [range]: 797 days [144-1185]).

Population: 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.

Outcome measures

Measure	SAF Population n=17 Participants All patients treated with at least one dose of Wilate during the study.	Bleeding Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Exposure Days for Prophylactic Wilate Treatment on a Continuous Basis	271 Exposure days Interval 36.0 to 512.0	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 805 days [±247]; median [range]: 797 days [144-1185]).

Population: 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.

Outcome measures

Measure	SAF Population n=17 Participants All patients treated with at least one dose of Wilate during the study.	Bleeding Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Number of Infusions Per Week for Prophylactic Wilate Treatment on a Continuous Basis	2.6 Infusions per week Interval 1.0 to 4.2	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 805 days [±247]; median [range]: 797 days [144-1185]).

Population: 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.

Outcome measures

Measure	SAF Population n=17 Participants All patients treated with at least one dose of Wilate during the study.	Bleeding Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Dosage for Prophylactic Wilate Treatment on a Continuous Basis	77.5 IU/kg per week Interval 19.3 to 201.3	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 805 days [±247]; median [range]: 797 days [144-1185]).

Population: 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.

Outcome measures

Measure	SAF Population n=4120 Number of infusions All patients treated with at least one dose of Wilate during the study.	Bleeding Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Dosage for Prophylactic Wilate Treatment Per Infusion on a Continuous Basis	31.3 IU/kg per infusion Interval 8.3 to 111.1	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 561 days [±251]; median [range]: 773 days [144-1185]).

Population: 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 = number of infusions

Outcome measures

Measure	SAF Population n=292 Number of infusions All patients treated with at least one dose of Wilate during the study.	Bleeding Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Dosage of Wilate Per Infusion for the Treatment of Breakthrough Bleeds	52.4 IU/kg per infusion Interval 8.3 to 125.0	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 561 days [±251]; median [range]: 773 days [144-1185]).

Population: Treatment of breakthrough bleeds (n=175) in the EFF-P population that 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.

Outcome measures

Measure	SAF Population n=175 No. of breakthrough bleeds All patients treated with at least one dose of Wilate during the study.	Bleeding Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Dosage of Wilate for the Treatment of Breakthrough Bleeds Per Breakthrough Bleed	55.4 IU/kg per breakthrough bleed Interval 8.3 to 1441.3	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 568 days [±349]; median [range]: 732 days [2-1185]).

Population: 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 orthopaedic surgery and 1 minor cardiovascular surgery)

Outcome measures

Measure	SAF Population n=384 Number of infusions All patients treated with at least one dose of Wilate during the study.	Bleeding Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Wilate Dosage Per Infusion for the Prevention of Bleeding During and After Surgery	27.8 IU/kg per infusion Interval 1.1 to 92.3	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 568 days [±349]; median [range]: 732 days [2-1185]).

Population: 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)

Outcome measures

Measure	SAF Population n=96 Number of treated surgeries All patients treated with at least one dose of Wilate during the study.	Bleeding Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Wilate Dosage Per Procedure for the Prevention of Bleeding During and After Surgery	69.2 IU/kg per procedure Interval 6.3 to 679.6	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 761 days [±251]; median [range]: 773 days [144-1185]).

Population: 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).

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.

Outcome measures

Measure	SAF Population n=17 Participants All patients treated with at least one dose of Wilate during the study.	Bleeding n=8 Participants Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Number of Patients With Breakthrough Bleeds During Prophylaxis	13 Participants	5 Participants	—	—	—	—

POST_HOC outcome

Timeframe: Optional thrombogenicity tests were performed at baseline and 1,3 and 24 hours after each administration of Wilate

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

Outcome measures

Measure	SAF Population n=10 Participants All patients treated with at least one dose of Wilate during the study.	Bleeding n=17 Participants Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery n=3 Participants Wilate administered in the context of surgery.	Menstruation n=6 Participants Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Thromboembolic Adverse Drug Reactions (ADRs)	0 number of adverse drug reactions	0 number of adverse drug reactions	0 number of adverse drug reactions	0 number of adverse drug reactions	—	—

POST_HOC outcome

Timeframe: Optional antibody tests were performed at baseline and 3-4 days (preferable 7 days) after Wilate injection

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

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

Outcome measures

Measure	SAF Population n=1 Participants All patients treated with at least one dose of Wilate during the study.	Bleeding n=4 Participants Wilate administered for the treatment of acute or breakthrough BEs (does not include menstrual BEs).	Surgery Wilate administered in the context of surgery.	Menstruation Wilate administered in the context of menstrual BEs.	Prevention Wilate administered for the purpose of preventing recurrent BEs in patients undergoing on-demand treatment or short-term prophylaxis in surgery only.	Investigator Assessment of Menstrual BEs Investigator assessment on the efficacy of Wilate in the treatment of menstrual BEs.
Clinical Symptoms of Von Willebrand Factor (VWF) Inhibition	0 Participants	0 Participants	—	—	—	—

Adverse Events

SAF Population

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	SAF Population n=111 participants at risk All patients who received at least one dose of Wilate during the study.
Infections and infestations Erythema Infectiosum	0.90% 1/111 • Number of events 1 • Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 575 days [±326]; median [range]: 731 days [2-1185]).
Nervous system disorders Paraesthesia	0.90% 1/111 • Number of events 1 • Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 575 days [±326]; median [range]: 731 days [2-1185]).
Cardiac disorders Palpitations	0.90% 1/111 • Number of events 1 • Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 575 days [±326]; median [range]: 731 days [2-1185]).
Cardiac disorders Tachycardia	2.7% 3/111 • Number of events 3 • Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 575 days [±326]; median [range]: 731 days [2-1185]).
Vascular disorders Flushing	0.90% 1/111 • Number of events 2 • Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 575 days [±326]; median [range]: 731 days [2-1185]).
Vascular disorders Hypotension	0.90% 1/111 • Number of events 1 • Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 575 days [±326]; median [range]: 731 days [2-1185]).
Respiratory, thoracic and mediastinal disorders Cough	0.90% 1/111 • Number of events 1 • Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 575 days [±326]; median [range]: 731 days [2-1185]).
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.8% 2/111 • Number of events 2 • Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 575 days [±326]; median [range]: 731 days [2-1185]).
Gastrointestinal disorders Nausea	1.8% 2/111 • Number of events 2 • Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 575 days [±326]; median [range]: 731 days [2-1185]).
Gastrointestinal disorders Salivary Hypersecretion	0.90% 1/111 • Number of events 1 • Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 575 days [±326]; median [range]: 731 days [2-1185]).
Gastrointestinal disorders Vomiting	0.90% 1/111 • Number of events 1 • Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 575 days [±326]; median [range]: 731 days [2-1185]).
Skin and subcutaneous tissue disorders Pruritus	0.90% 1/111 • Number of events 1 • Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 575 days [±326]; median [range]: 731 days [2-1185]).
Skin and subcutaneous tissue disorders Rash	0.90% 1/111 • Number of events 1 • Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 575 days [±326]; median [range]: 731 days [2-1185]).
Skin and subcutaneous tissue disorders Urticaria	0.90% 1/111 • Number of events 1 • Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 575 days [±326]; median [range]: 731 days [2-1185]).
General disorders Administration Site Reaction	0.90% 1/111 • Number of events 1 • Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 575 days [±326]; median [range]: 731 days [2-1185]).
General disorders Chest Discomfort	0.90% 1/111 • Number of events 1 • Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 575 days [±326]; median [range]: 731 days [2-1185]).
General disorders Drug Ineffective	0.90% 1/111 • Number of events 1 • Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 575 days [±326]; median [range]: 731 days [2-1185]).
General disorders Face Oedema	0.90% 1/111 • Number of events 1 • Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 575 days [±326]; median [range]: 731 days [2-1185]).
General disorders Fatigue	0.90% 1/111 • Number of events 1 • Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 575 days [±326]; median [range]: 731 days [2-1185]).
General disorders Injection Site Pain	0.90% 1/111 • Number of events 1 • Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 575 days [±326]; median [range]: 731 days [2-1185]).
General disorders Pyrexia	0.90% 1/111 • Number of events 1 • Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 575 days [±326]; median [range]: 731 days [2-1185]).

Additional Information

Sigurd Knaub/SVP CR&D Haematology

Octapharma AG

Phone: +41 55 4512141

Email: Sigurd.Knaub@octapharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place