A Prospective, Multicenter, Non-Interventional Study Evaluating the Bleeding Incidence in Patients With Von Willebrand Disease Undergoing On-Demand Treatment
Conditions: Von Willebrand Diseases
Sponsor: Octapharma

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090-NISP-WIL-29-V05
DOC ID 3212 
STUDY PROTOCOL FOR A 
NON-INTERVENTIONAL STUDY 
A Prospective, Multicentre, Non-Interventional Study 
Evaluating the Bleeding Incidence 
in Patients with Von Willebrand Disease 
Undergoing On-Demand Treatment 
(WIL-29) 
Protocol version identifier 
05 
Protocol date 
05-Aug-2020 
Previous protocols: 
Original Protocol version 1.0, dated 28-Feb-2019 
Protocol version 2.0 ( AMD1); dated 08-Jul-2019 
EU PAS register number 
EUPAS29946 
Active substances 
VWF concentrates 
VWF/FVIII concentrates 
Cryoprecipitate 
Medicinal products 
VWF-containing products 
Product references 
VWF-containing products licensed in each participating 
country 
Procedure number 
n/a 
Marketing authorisation holders 
All marketing authorizations holders for VWF-contain-
ing products used as per local practice 
Joint PASS 
No 
Research question and objectives 
The primary objective of this study is to characterise the 
bleeding and treatment pattern of patients with type 3, 
type 2 (except 2N), or severe type 1 von Willebrand 
disease receiving routine on-demand treatment with a 
von Willebrand factor-containing product. 
Countries of study 
Belarus, Bulgaria, Croatia, Hungary, Lebanon, Russia, 
Ukraine, and USA 
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PROTOCOL SIGNATURES 
Version 05 
05-Aug-2020
Signature of the Qualified Person Pharmacovigilance or Delegate 
of the Marketing Authorisation Holder 
Balazs Toth 
Qualified Person Pharmacovigilance 
Drug Safety Physician 
Octapharma Pharmazeutika 
Produktionsges. m.b.H. 
Oberlaaer StraBe 235 
A-1100 Vienna
Austria
1 9 AUG 2020 
Signature 
Date 
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Signature of the Clinical Trial Manager at Octapharma Responsible for the Study 
Page3 of57 
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CONFIDENTIAL 
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Signature of the Clinical Project Manager at Octapharma Responsible for the Study 
Sylvia Werner 
Senior Director Clinical R&D - Haematology 
Octaphanna USA, Inc. 
l I 7 West Century Road 
Paramus, New Jersey 07652 
USA 
Signature 
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Date 
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Signature of the Co-ordinating Investigator 
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Version 05 
05-Aug-2020
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Table of Contents 
1 
LIST OF ABBREVIATIONS ....................................................................................... 9 
2 
RESPONSIBLE PARTIES ........................................................................................ 10 
3 
ABSTRACT ............................................................................................................ 11 
4 
AMENDMENTS AND UPDATES .............................................................................. 14 
5 
MILESTONES ........................................................................................................ 15 
6 
RATIONALE AND BACKGROUND .......................................................................... 16 
6.1 
VON WILLEBRAND DISEASE ...................................................................... 16 
6.2 
RATIONALE FOR CONDUCTING THE STUDY ............................................... 17 
7 
RESEARCH QUESTION AND OBJECTIVES ............................................................ 18 
7.1 
PRIMARY OBJECTIVE ................................................................................. 18 
7.2 
SECONDARY OBJECTIVES .......................................................................... 18 
8 
RESEARCH METHODS .......................................................................................... 19 
8.1 
STUDY DESIGN .......................................................................................... 19 
8.2 
STUDY ENDPOINTS .................................................................................... 19 
8.2.1 
Primary Endpoint ....................................................................... 19 
8.2.2 
Secondary Endpoints .................................................................. 19 
8.3 
STUDY POPULATION .................................................................................. 20 
8.3.1 
Number of Patients ..................................................................... 20 
8.3.2 
Inclusion Criteria ........................................................................ 20 
8.3.3 
Exclusion Criteria ....................................................................... 20 
8.4 
STUDY CONDUCT ...................................................................................... 21 
8.4.1 
Study Setting and Centres .......................................................... 21 
8.4.2 
Study Duration ........................................................................... 21 
8.4.3 
Patient Codes .............................................................................. 21 
8.4.4 
Study Conduct ............................................................................ 21 
8.4.5 
Patient Diaries ............................................................................ 22 
8.5 
VARIABLES ................................................................................................ 23 
8.5.1 
Demographic and Baseline Characteristics ................................ 23 
8.5.2 
Medical History and Prior Medications ..................................... 23 
8.5.3 
Bleeding Episode (BE) Data ...................................................... 23 
8.5.4 
Data on the Administration of VWF-Containing Product.......... 25 
8.5.5 
Assessment of the Effectiveness of Treatment of BEs............... 25 
8.5.6 
Data on Surgical Prophylaxis ..................................................... 25 
8.5.7 
Assessment of the Effectiveness of Surgical Prophylaxis.......... 27 
8.5.8 
Quality of Life ............................................................................ 27 
8.5.9 
Joint Health Status ...................................................................... 28 
8.5.10 
Pictorial Blood Assessment Chart .............................................. 28 
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8.6 
DATA SOURCES ......................................................................................... 28 
8.7 
DATA MANAGEMENT ................................................................................ 28 
8.8 
DATA ANALYSIS ........................................................................................ 28 
8.9 
QUALITY CONTROL ................................................................................... 29 
9 
PROTECTION OF HUMAN SUBJECTS .................................................................... 30 
9.1 
PATIENT INFORMATION AND INFORMED CONSENT .................................... 30 
9.2 
SUBMISSION OF STUDY DOCUMENTS TO IECS/IRBS, REGULATORY
AUTHORITIES, AND OTHER STAKEHOLDERS ............................................... 30 
9.3 
CONFIDENTIALITY OF PATIENT DATA ........................................................ 31 
10 MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE REACTIONS 32 
10.1 
SAFETY MONITORING ................................................................................ 32 
10.1.1 
Definition of Adverse Drug Reaction and Other Safety 
Information ................................................................................. 32 
10.1.2 
Reporting of Adverse Drug Reactions and Other Relevant Safety 
Information ................................................................................. 33 
10.1.3 
Method and Duration of Observation of the Study Areas after the 
Occurrence of ADRs .................................................................. 35 
11 PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS .............. 36 
11.1 
FINAL STUDY REPORT................................................................................ 36 
11.2 
PUBLICATION POLICY ................................................................................ 36 
12 REFERENCES ........................................................................................................ 37 
13 ANNEXES .............................................................................................................. 38 
Annex 1 
Case Safety Report Form .................................................................. 39 
Annex 2 
Contact Addresses of Local Safety Offices ....................................... 49 
Annex 3 
Pregnancy Form ................................................................................ 50 
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1 
LIST OF ABBREVIATIONS 
ADR 
Adverse Drug Reaction 
AE 
Adverse Event 
BE 
Bleeding Event 
CRO 
Contract Research Organization 
DDVAP 
Desmopressin (1-deamino-8-D-arginine vasopressin) 
eCRF 
Electronic Case Report Form 
EMA 
European Medicines Agency 
FVIII 
Factor VIII 
GPP 
Good Pharmacoepidemiologic Practices 
HCP 
Health-Care Provider 
ICH 
International Conference of Harmonization 
IEC/IRB 
Independent Ethics Committee/Institutional Review Board 
NIS 
Non-Interventional Study 
PROMIS 
Patient-Reported Outcomes Measurement Information System 
PTP 
Previously Treated Patients 
QoL 
Quality of Life 
SABR 
Spontaneous Annualised Bleeding Rate 
SADR 
Serious Adverse Drug Reaction 
SF-10 
10-Item Short Form Health Survey
SF-36v2 
36-Item Short Form Health Survey, version 2
SmPC 
Summary of Product Characteristics 
TABR 
Total Annualised Bleeding Rate 
VWD 
Von Willebrand Disease 
VWF 
Von Willebrand Factor 
VWF:Ac 
Von Willebrand Factor Activity 
VWF:RCo 
VWF Ristocetin Cofactor 
VWF:Gp1bM 
Assay to Determine VWF:Ac Based on Spontaneous Binding of VWF to a Gain-of-
Function Mutant Gp1b Fragment 
VWF:GP1bR 
Assay to Determine VWF:Ac Based on Ristocetin-Induced Binding of VWF to a Recom-
binant Wild-Type Gp1b Fragment 
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2 
RESPONSIBLE PARTIES 
The key parties responsible for the conduct of this study are listed in Table 1. A complete 
list of study sites and treating physicians enrolling patients into this study will be provided 
in the final study report. 
Table 1 
Key Parties Responsible for the Conduct of Study WIL-29 
Co-ordinating Investigator 
Robert F. Sidonio Jr., MD 
Aflac Cancer and Blood Disorders 
Emory University School of Medicine 
1760 Haygood Drive 
HSRB W340 
Atlanta, Georgia 30322, USA 
Clinical Trial Manager 
Mayte Schmid 
Clinical Trial Manager, CR&D Haematology 
Octapharma AG 
Seidenstrasse 2 
8853 Lachen 
Switzerland 
Clinical Project Manager 
Sylvia Werner 
Senior Director Clinical R&D – Haematology  
Octapharma USA, Inc. 
117 West Century Road  
Paramus, New Jersey 07652 
USA 
Data Management and Statistical Analysis 
Hans-Peter Hucke, PhD 
Biostatistician 
ERGOMED 
Im Mediapark 2 
50670 Köln 
Germany 
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3 
ABSTRACT 
Title of Study: 
A Prospective, Multicentre, Non-Interventional Study Evaluating the Bleeding Inci-
dence in Patients with Von Willebrand Disease Undergoing On-Demand Treatment 
(WIL-29) 
Rationale and Background: 
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. 
Research Question and Objectives: 
The primary objective of this study is to characterise the bleeding and treatment pattern of 
patients with type 3, type 2 (except 2N), or severe type 1 VWD undergoing routine on-
demand treatment with a VWF-containing product.  
The secondary objectives of this study are to: 

Determine the effectiveness of the VWF-containing product used in the treat-
ment of bleeding episodes (BEs)

Determine the effectiveness of the VWF-containing product used in surgical
prophylaxis

Assess the quality of life (QoL) of VWD patients undergoing on-demand treat-
ment with a VWF-containing product

Assess the safety of the VWF-containing product used for on-demand VWD
treatment
Study Design: 
This is a prospective, multicentre, international, non-controlled non-interventional study. 
Population: 
Patients who meet all of the following criteria are eligible for the study: 
1. Male or female patients aged ≥5.5 years at the time of enrolment
2. 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
3. Currently receiving on-demand treatment with a VWF-containing product
4. In female patients of child-bearing potential using hormonal contraception, the
medication class should remain unchanged during the period of participation in
the study
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5. Voluntarily given, fully informed written and signed consent before collection of
any patient data
Patients who meet any of the following criteria are not eligible for the study: 
1. Patients currently on prophylaxis for VWD (except for perioperative prophy-
laxis) as well as patients having received treatment once a month for menstrual
bleeding, but not for any other bleeds
2. Patients whose VWD treatment is planned to be switched from on-demand to
prophylactic treatment in the next 6 months
3. History, or current suspicion, of VWF or FVIII inhibitors
4. Medical history of a thromboembolic event within 6 months before enrolment
5. Severe liver or kidney diseases as described in the medical records
6. Female patients with an existing or suspected pregnancy or who are breast-feed-
ing at the time of enrolment
7. Change in hormonal contraception within 6 months before enrolment
8. Cervical or uterine conditions causing abnormal uterine bleeding (including in-
fection or dysplasia)
9. Other coagulation disorders or bleeding disorders due to anatomical reasons
10. Participation in an interventional clinical study during the 6-month of study pe-
riod
11. Inability to complete the patient diary to reliably evaluate the type, frequency,
and treatment of BEs during the 6-month study period
Variables: 
Collected variables comprise: 

Demographic and baseline characteristics

Medical history and prior medications

Hemophilia Joint Health Score (HJHS)

Bleeding episode data
–
BE type (spontaneous, traumatic, postoperative, menstrual, other)
–
BE site
–
BE severity (minor, major)
–
Date and time the BE first occurred or was first noticed
–
Date and time the BE ended
–
BE treated or not treated
–
Data on the administration of the VWF-containing product
–
Assessment of the effectiveness of treatment at the end of the BE

Data on the administration of the VWF-containing product
–
Name and batch number of VWF-containing product
–
Dates and times of injections of VWF-containing product
–
Doses of VWF-containing product in IU and IU/kg
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–
Purpose of injection with VWF-containing product (treatment of BE,
prophylaxis of recurrent bleeding, surgery, prophylaxis after surgery)

Assessment of the effectiveness of the treatment of BEs

PBAC data and scores (for female patients of child-bearing potential)

Data on surgical prophylaxis

Assessment of the effectiveness of surgical prophylaxis

Quality of life using the PROMIS-29, the 36-Item Short Form Health Survey,
version 2 (SF-36v2) for patients ≥16 years, and the SF-10 for patients ≥5.5 and
<16 years of age
Data Sources: 
The data source for the calculation of the bleeding rate will be the information docu-
mented in the patient diaries as well as the information collected based on the review of 
the patient’s medical records. 
Study Size: 
Overall, around 55 PTPs aged ≥5.5 years at the time of enrolment will be included into 
this NIS. Of the 55 patients, at least 6 patients should have type 3 VWD and at least 6 
patients should be ≥5.5 to <16 years of age. 
Data Analysis: 
All data will be analysed descriptively. 
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4 
AMENDMENTS AND UPDATES 
Any amendments will be submitted to the competent independent ethics committees (IECs) 
or institutional review boards (IRBs) as well as to competent regulatory authorities as re-
quired by national regulations (see Section 9.2). 
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5 
MILESTONES 
The milestones of this study are summarized in Table 2. 
Table 2 
Study Milestones and Planned Dates 
Milestone 
Planned date 
Start of data collection 
Q3 2019 
End of data collection 
Q1 2021 
Final study report 
Q2 2021 
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6 
RATIONALE AND BACKGROUND 
6.1 
VON WILLEBRAND DISEASE 
Inherited von Willebrand disease (VWD) is the most common inherited haemorrhagic dis-
order, with an estimated prevalence of 1 in every 1000 individuals of either sex. There is 
wide geno- and phenotypic variability of the disease, and not all patients with VWD require 
treatment. 
Three types of inherited VWD are known. Whereas type 1 and type 3 disease are character-
ised by a quantitative deficiency of von Willebrand factor (VWF), VWD type 2 arises from 
a qualitative deficiency of VWF. There are various subtypes within the three inherited types 
of VWD. VWD may also be acquired. 
Of the inherited forms, type 1 is the most common, accounting for 70–80% of cases, fol-
lowed by type 2, which affects approximately 20% of patients. Type 3, the most severe 
form of VWD characterised by a complete absence of VWF, is rare and affects about 1–3% 
of all patients [1]. 
Treatment of VWD depends on the type and severity of the disease. Whereas mild to mod-
erate forms of type 1 and type 2A disease often respond adequately to treatment with 
desmopressin (1-deamino-8-D-arginine vasopressin, DDAVP), DDAVP is contraindicated 
in type 2B and not effective in type 3 disease. Treatment with DDAVP may also be contra-
indicated for other clinical reasons or may be associated with significant side effects. 
The appropriate treatment for the patients in whom DDAVP is ineffective or contraindicated 
are VWF/factor VIII (FVIII) concentrates, which have become the mainstay of VWD treat-
ment. Cryoprecipitate, which is screened for viruses but not treated to inactivate them, is 
also rich in VWF, but is likely to be less safe than the viral-attenuated concentrates [2]. 
VWD affects all ethnic groups and both sexes. Women are more likely to experience symp-
toms of VWD and may pose a special treatment challenge because of the physiological 
events related to menstruation, pregnancy, and birth [3]. If untreated, pregnant women with 
VWD are at increased risk of postpartum bleeding. In women with VWD types 1 or 2, the 
levels of VWF and FVIII rise 2- to 3-fold during the second and third trimesters, but fall to 
baseline levels soon after delivery. By contrast, in VWD type 2B, the increase of the abnor-
mal VWF can cause or worsen thrombocytopenia. In women with VWD type 3, VWF and 
FVIII do not increase during pregnancy, so that administration of VWF-containing products 
may be required during pregnancy and at birth [3]. 
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6.2 
RATIONALE FOR CONDUCTING THE STUDY 
Bleeding disorders are a disease area in which good record-keeping is an essential compo-
nent of home-based care. Complete bleeding and treatment records are an essential tool of 
communication between patients and their health-care providers (HCPs), and they help 
HCPs monitor patients and medication use to ensure optimal treatment [4–6]. However, 
record-keeping varies considerably between treatment centres and countries, posing a chal-
lenge when retrospectively estimating bleeding rates in a reliable manner.  
The purpose of this study is to prospectively obtain reliable data on the bleeding and treat-
ment pattern of patients with VWD undergoing on-demand treatment with a VWF-contain-
ing 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 in a clinical study on the ef-
ficacy of prophylactic treatment with a VWF/FVIII concentrate. 
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7 
RESEARCH QUESTION AND OBJECTIVES 
7.1 
PRIMARY OBJECTIVE 
The primary objective of this study is to characterise the bleeding and treatment pattern of 
patients with type 3, type 2 (except 2N), or severe type 1 VWD undergoing routine on-
demand treatment with a VWF-containing product. 
7.2 
SECONDARY OBJECTIVES 
The secondary objectives of this study are to: 

Determine the effectiveness of the VWF-containing product used in the treatment
of bleeding episodes (BEs)

Determine the effectiveness of the VWF-containing product used in surgical
prophylaxis

Assess the quality of life (QoL) of VWD patients undergoing on-demand treatment
with a VWF-containing product

Assess the patients’ joint status using the Hemophilia Joint Health Score (HJHS)

Assess the menstrual bleeding intensity of female patients of child-bearing poten-
tial

Assess the safety of the VWF-containing product used for on-demand VWD treat-
ment
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8 
RESEARCH METHODS 
8.1 
STUDY DESIGN 
This is a prospective, multicentre, international, non-controlled non-interventional study 
(NIS). 
8.2 
STUDY ENDPOINTS 
8.2.1 
Primary Endpoint 
The primary endpoint of this NIS is to characterise the total annualised bleeding rate (TABR) 
of patients with type 3, type 2 (except 2N), or severe type 1 VWD undergoing routine on-
demand treatment with a VWF-containing product. 
The TABR will be calculated as the total number of spontaneous, traumatic and other BEs 
in the time period between the start of data collection for each patient and the Study Com-
pletion 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, 
as well as menstrual bleeds will be excluded from the calculation of TABR.  
8.2.2 
Secondary Endpoints 
The secondary endpoints of this study are the: 

Spontaneous annualised bleeding rate (SABR), calculated in analogy with TABR

Data on the consumption of the VWF-containing product (VWF/FVIII IU/kg per
month per patient) used for routine on-demand treatment

Effectiveness of VWF-containing product in the treatment of BEs based on the
proportion of successfully treated BEs

Effectiveness of surgical prophylaxis with VWF-containing product based on the
proportion of successfully treated surgeries

QoL based on the PROMIS-29 for all patients, SF-36v2 for patients ≥16 years, and
SF-10 for patients ≥5.5 and <16 years of age.

Hemophilia Joint Health Score (HJHS)

Pictorial Blood Loss Assessment Chart (PBAC) score

Safety of the patient’s VWF-containing product by monitoring adverse drug reac-
tions (ADRs) throughout the study
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8.3 
STUDY POPULATION 
8.3.1 
Number of Patients 
Overall, around 55 PTPs aged ≥5.5 years at the time of enrolment will be included into this 
NIS. Of the 55 patients, at least 6 patients should have type 3 VWD and at least 6 patients 
should be ≥5.5 to <16 years of age. 
8.3.2 
Inclusion Criteria 
Patients who meet all of the following criteria are eligible for the study: 
1. Male or female patients aged ≥5.5 years at the time of enrolment
2. 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
3. Currently receiving frequent on-demand treatment with a VWF-containing product
4. In female patients of child-bearing potential using hormonal contraception, the
medication class should remain unchanged for the duration of their study participa-
tion
5. Voluntarily given, fully informed written and signed consent obtained before col-
lection of any patient data
8.3.3 
Exclusion Criteria 
Patients who meet any of the following criteria are not eligible for the study: 
1. 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
2. Patients whose VWD treatment is planned to be switched from on-demand to
prophylactic treatment in the next 6 months
3. History, or current suspicion, of VWF or FVIII inhibitors
4. Medical history of a thromboembolic event within 6 months before enrolment
5. Severe liver or kidney diseases as described in the medical records
6. Female patients with an existing or suspected pregnancy or who are breast-feeding
at the time of enrolment
7. Change in hormonal contraception within 6 months before enrolment
8. Cervical or uterine conditions causing abnormal uterine bleeding (including infec-
tion or dysplasia)
9. Other coagulation disorders or bleeding disorders due to anatomical reasons
10. Participation in an interventional clinical study during the 6-month of study period
11. Inability to complete the patient diary to reliably evaluate the type, frequency, and
treatment of BEs during the 6-month study period
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8.4 
STUDY CONDUCT 
8.4.1 
Study Setting and Centres 
This study will be conducted in about 20 centres for the treatment of bleeding disorders 
world-wide. 
8.4.2 
Study Duration 
The overall study duration will be approximately 2 years. Each patient will be followed for 
around 6 months from the time of enrolment. The study will be considered completed at the 
time of database lock. 
8.4.3 
Patient Codes  
Each patient enrolled into this NIS will be uniquely identifiable by a patient code consisting 
of the study code, centre code, and patient number. The centre code is assigned to the study 
site by Octapharma. At each site, enrolled patients will be numbered consecutively. Once 
assigned to a patient, a patient number will not be reused. 
8.4.4 
Study Conduct 
Male or female patients aged ≥5.5 years at the time of enrolment with VWD type 1 (baseline 
von Willebrand factor activity [VWF:RCo], <30 IU/dL), 2A, 2B, 2M, or 3 according to 
medical history having been prescribed on-demand therapy with a VWF-containing product 
to control their bleeding will be included into this study after written informed consent has 
been obtained (see Section 9.1). 
Patient eligibility for enrolment will be determined at the Screening Visit, during which 
demographic and baseline data, the medical history, and prior medications will be recorded 
(see Section 8.5.1 and Section 8.5.2). Quality of life will also be assessed during the Screen-
ing Visit (see Section 8.5.8). 
Patients and/or their parents or legal guardians will be asked to keep a patient diary to doc-
ument any bleeding and treatment details as well as information on the patients’ medical 
condition, treatment side effects, other noteworthy medical events, and concomitant medi-
cations throughout the study (see Section 8.4.5). In addition, treating physicians should en-
quire, during each follow-up visit, about any safety-relevant events and concomitant medi-
cations taken. The treating physicians will assess the causal relationship of any safety-rele-
vant events and report these as ADRs or other relevant safety information as required.  
For women of child-bearing potential, bleeding information from each menstrual period in 
this study will be collected using the Pictorial Blood Assessment Chart (PBAC) (see Section 
8.5.10). 
Details on any surgical interventions patients may be undergoing while participating in this 
study will also be collected (see Section 8.5.6). 
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Patient treatment as well as all follow-up visits will take place as per the routine standard of 
care of each study site. The recommended schedule is for follow-up visits to take place at 
1, 3, and 6 months after the Screening Visit.  
The recommended flow chart of study visits and the variables that should be collected in 
this study are given in Table 3. The variables are described in detail in Section 8.5. 
Table 3 
Recommended Flow Chart of Study Visits and Data Collected During On-
Demand Treatment with a VWF-Containing Product 
For more 
information, 
see 
Section 
Screening 
Visit 
Follow-up 
visits at 
1, 3, and 6 
months 
Informed consent 
x 
Inclusion and exclusion criteria 
8.3 
x 
Demographic & baseline data, including pregnancy status and HJHS 
8.5.1 
x 
Medical history and prior medications, including VWD treatments and 
genetic testing history, if available 
8.5.2 
x 
Family history of VWD 
x 
Bleeding history in the previous 6 months in PTPs 
x 
History of VWF and FVIII inhibitors 
x 
Quality of life using PROMIS-29 and SF-36v2 or SF-10, as applicable 
8.5.8 
x 
Handing out patient diaries and PBAC instruction 
8.4.5, 8.5.10 
x 
Possible VWF/FVIII inhibitor testing, if inhibitors suspected* 
x 
Collection of patient diary pages 
8.4.5 
x 
Obtaining PBAC data and scores 
8.5.10 
x 
Details on potential surgical interventions 
8.5.6, 8.5.7 
x 
Adverse drug reaction (ADR) monitoring 
10 
x 
Concomitant medications 
x 
HJHS = Hemophilia Joint Health Score, PBAC = Pictorial Blood Assessment Chart 
*As per routine standard of care at each treatment centre.
8.4.5 
Patient Diaries 
Documenting treatment and bleeding data is an integral part of home treatment for VWD. 
In this study, enrolled patients will be provided with a patient diary during the Screening 
Visit. Patients will be asked to complete their diaries and to bring them along to each follow-
up visit. The completed diary pages will be collected by the treating physician, and the in-
formation recorded will be transcribed to the electronic Case Report Forms (eCRFs). The 
patient diaries are considered source data, and the original diary pages will be included in 
the patient’s medical record. 
The following data should be recorded in the patient diary: 

Bleeding episode data (see Section 8.5.3)

Data on the administration of the VWF-containing product (see Section 8.5.4)

Assessment of the effectiveness of the treatment of BEs (see Section 8.5.5)

Any medications taken, or other treatments received (e.g., physical therapy, blood
transfusions), by the patient throughout the duration of the study
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8.5 
VARIABLES 
8.5.1 
Demographic and Baseline Characteristics 
The demographic and baseline characteristics are age, ethnic origin, height, weight, AB0 
blood group (if derivable from the patient’s medical history), and pregnancy and breast-
feeding status. 
In addition, the Hemophilia Joint Health Score (HJHS, see Section 8.5.9) will be obtained. 
Also, target joint(s), defined as having had 3 or more spontaneous BEs into a single joint in 
6 consecutive months before the Screening Visit, will be recorded, if available. 
8.5.2 
Medical History and Prior Medications 
The medical history as well as prior and concomitant medications will be obtained by patient 
interview. Records of past diseases and treatments (e.g., hospital discharge letters) will be 
obtained for the study files, if available. 
VWF activity using VWF:RCo, VWF:Gp1bM, VWF:Gp1bR, or any other pertinent method 
will be recorded, as will VWF:Ag, the VWF multimer pattern for VWD type 2A, and the 
genotype for VWD type 2B, if available. 
In addition, the age at first treatment for VWD and information on on-demand treatment 
with VWF-containing product in the previous 6 months before enrolment will be collected. 
Patients should preferably have a record of at least 6 spontaneous BEs requiring treatment 
in the past 3 months before screening. If this is not the case, the investigator should assess 
whether the patient experiences frequent enough bleedings to be included in the study. 
For female patients of child-bearing potential, the birth control measures used within 
6 months before enrolment will be documented. For all female patients, any history of heavy 
menstrual bleeding will be recorded. 
8.5.3 
Bleeding Episode (BE) Data 
Study participants will be instructed by the investigator on recording BEs in their patient 
diaries. For any BE occurring during the study, whether treated or not, the following data 
will be recorded: 

BE type (spontaneous, traumatic, postoperative, menstrual, other)

BE site

BE severity (minor, major) (see Table 4)

Date and time the BE first occurred or was first noticed

Date and time the BE ended

BE treated or not treated

Data on the administration of the VWF-containing product (see Section 8.5.4)

Assessment of the effectiveness of treatment at the end of the BE (see Section
8.5.5)
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All of these parameters will be documented by the patient (together with the treating physi-
cian in case of on-site treatments) in the patient diary. Patients who experience a major BE 
should be treated at the treatment centre, if possible. 
Based on these data, the frequency of BEs and the TABR and SABR under on-demand 
treatment will be calculated. 
If the treatment of a BE in one bleeding site is interrupted for more than 48 hours, two 
separate BEs will have to be recorded; if, in addition to the original bleeding site, another 
bleeding site is affected, these events will be recorded as separate BEs at any time. 
The severity of menstrual bleeding will be categorized as either ‘minor or ‘major’. Thus, 
menstrual bleeding of regular intensity classified as minor will be considered normal. Heavy 
menstrual bleeding will be regarded as a BE of ‘major’ severity (see Table 4). 
BE severity will be assessed using the criteria given in Table 4. 
Table 4 
Definition of the Severity of Bleeding 
Type of bleeding 
Description 
Minor bleeding 

Mild haemarthrosis (mild swelling, ‘aura,’ pain, warmth of the skin over the joint,
change in range of motion, decrease in mobility and activity, slight difficulty in us-
ing the limb compared with baseline)

Superficial muscle bleed (pain and/or swelling and functional impairment com-
pared with baseline)

Soft-tissue bleeding (scrapes, superficial cuts such as those cause by shaving
razor, knife, or scissors, bleeding episodes that require frequent bandage
changes, cutaneous bleeds with numerous bruises >1 cm)

Oral bleeding (superficial mouth bleeds, oozing or bleeding related to tooth erup-
tion or extraction, spontaneous or after brushing/flossing, gum bleeding, bleeding
after bites to lip or tongue)

Most nose bleeds (i.e., those causing distress or interference with daily or social
activities)
Major bleeding 
Generally, 

requires hospitalization

causes incapacity, significant pain, and substantial decrease in range of motion of
affected joint (in case of joint bleeds)

includes symptomatic bleeding in a critical area or organ (such as intracranial,
intraspinal, intraocular, retroperitoneal, intraabdominal, intraarticular, or pericardial
bleeds), intramuscular bleeds with compartment syndrome, bleeds of the pel-
vic muscles, periorbital bleeds, gastrointestinal bleeds, other central nerv-
ous system bleeds, heavy menstrual bleeding,* bleeding in the area of the
neck, throat, or pharynx, major trauma, or bleeding causing a decrease in
haemoglobin levels by 20 g/L (1.24 mmol/L) or more.
*Heavy menstrual bleeding qualifies as ‘major bleeding’ and is defined as any
menstrual bleeding that
−
interferes with daily activities such as work, housework, exercise, or social
activities,
−
requires changing pads/tampons more frequently than hourly (referred to as
‘flooding’),
−
lasts 7 or more days,
−
includes the presence of clots >1 cm combined with a history of flooding, or
−
yields a PBAC score ≥185.
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8.5.4 
Data on the Administration of VWF-Containing Product 
The following parameters will be documented: 

Name and batch number of VWF-containing product

Dates and times of injections of VWF-containing product

Doses of VWF-containing product in IU and IU/kg

Purpose of injection with VWF-containing product (treatment of BE, prophylaxis
of recurrent bleeding, surgery, prophylaxis after surgery)
8.5.5 
Assessment of the Effectiveness of Treatment of BEs 
At the end of a BE, treatment effectiveness will be assessed by the patient (together with 
the treating physician in case of on-site treatment) using the predefined criteria detailed in 
Table 5. The assessment of the treatment effectiveness is not required for menstrual bleed-
ings. 
Table 5 
Effectiveness Assessment of the Treatment of BEs 
Excellent 
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 
Bleeding was completely stopped, but time and/or dose slightly exceeded expectations 
Moderate 
Bleeding could be stopped only by significantly exceeding time and/or dose expectations 
None 
Bleeding could be stopped only by using other VWF-containing products 
The proportion of BEs successfully treated with VWF-containing product will be eval-
uated for all BEs taken together and by BE severity. All effectiveness ratings assessed as 
either ‘excellent’ or ‘good’ will be considered ‘successfully treated.’ 
8.5.6 
Data on Surgical Prophylaxis 
Any surgeries taking place during the patients’ study participation should be reported and 
documented as outlined in the recommended flow chart of data collected during surgical 
prophylaxis (Table 6). 
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Table 6 
Recommended Flow Chart of Data Recorded During Surgical Prophylaxis 
Parameters 
For more 
infor-
mation, 
see 
Section 
Any time 
before 
surgery 
Within 
3 hours 
before 
surgery 
Surgery 
Post- 
operatively 
Intra- 
opera-
tively 
End 
[1] 
POP 
day 1 
Any 
POP 
day 
End of 
POP 
period 
[4] 
Body weight 
x 
Type of surgery (planned or emergency) 
x 
Location of surgery 
x 
Severity of surgery 
8.5.6.1 
x 
Duration of surgery 
x 
Blood loss & transfusions during surgery 
x 
Administration of VWF-containing product 
8.5.4 
x 
(x) 
(x) 
(x) 
(x) 
(x) 
FVIII:C plasma levels 
# 
(#) 
(#) [2] (#) [3] 
(#) 
(#) 
VWF:Ac and VWF:Ag plasma levels 
# 
(#) 
(#) [2] (#) [3] 
(#) 
(#) 
Vitals 
x 
x 
x 
Presence of wound haematomas 
x 
x 
x 
Efficacy assessment by treating physician 
8.5.7 
x 
Adverse drug reaction (ADR) monitoring 
10 
Throughout observation period 
Concomitant medications 
Throughout observation period 
POP = postoperative, FVIII:C = factor VIII procoagulant activity, VWF:Ac = VWF activity (VWF:RCo, VWF:Gp1bM, or 
VWF:GP1bR), VWF:Ag = von Willebrand factor antigen   
( ) Optional 
# Preferably before (≤30 min) and 30±15 minutes after administration of VWF-containing product, if these data are obtained 
as per standard of care 
[1] Defined as the time after the last surgical suture
[2] Preferably obtained within an hour after the last surgical suture, if these data are obtained as per standard of care
[3] For major surgeries, levels documented for first 3 postoperative doses, if these data obtained as per standard of care
[4] Defined as the time when patient returns to regular on-demand treatment
8.5.6.1 
Severity of Surgery 
Surgeries are defined as major if any of the following criteria are met: 

General or spinal anaesthesia required

Opening into the great body cavities required

Severe haemorrhage during surgery possible

Haemostatic therapy for at least 6 days required

Orthopaedic interventions involving joints (ankle, knee, hip, wrist, elbow, shoulder)

3rd molar extraction or extraction of ≥3 teeth

Surgeries/conditions in which the patient’s life is at stake
All other surgeries are classified as minor. 
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8.5.6.2 
Definitions of Surgery Periods and Time Points 

Preoperative is defined as the time period of up to 3 hours before the start of sur-
gery.

The end of surgery is defined as the time immediately after the last surgical su-
ture.

Postoperative is the period from the end of surgery to the time the patient returns
to on-demand treatment.

The end of the postoperative period is the time the patient returns to on-demand
treatment.
8.5.7 
Assessment of the Effectiveness of Surgical Prophylaxis 
An overall assessment of effectiveness will be made at the end of the postoperative period 
by the treating physician (Table 7). 
Table 7 
Effectiveness Assessment of Surgical Prophylaxis by Treating Physician 
Excellent 
Haemostasis similar to that of a haemostatically normal patient 
Good 
Mildly abnormal haemostasis in terms of quantity and/or quality (e.g., slight oozing) 
Moderate/poor 
Moderately abnormal haemostasis in terms of quantity and/or quality (e.g., moderate, 
controllable bleeding) 
None 
Severely abnormal haemostasis in terms of quantity and/or quality (e.g., severe haem-
orrhage that is difficult to control) 
All effectiveness ratings assessed as either ‘excellent’ or ‘good’ will be considered ‘suc-
cessfully treated’ surgeries. 
8.5.8 
Quality of Life 
For the assessment of QoL, the following instruments will be used: 

Patient-Reported Outcomes Measurement Information System (PROMIS)-29 [7–9]
for patients of all ages.  For patients aged ≥5.5 to <8 years, the questionnaires will
be completed by the patient’s parent/legal guardian. For patients ≥8 years, self-re-
porting will be used, if possible.

36-Item Short Form Health Survey, version 2 (SF-36v2, [10]) for patients ≥16
years

10-Item Short From Health Survey (SF-10, [11]) for patients ≥5.5 and <16 years of
age
The completeness of the questionnaire will be checked by the treating physician, and the 
data will be entered in the eCRF. 
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8.5.9 
Joint Health Status 
Joint health will be assessed using the Hemophilia Joint Health Score (HJHS) [12], which 
has been specifically validated for the assessment of clinical outcome in VWD [13]. Also, 
target joint(s), defined as having had 3 or more spontaneous BEs into a single joint in 6 
consecutive months before the Screening Visit, will be recorded, if available. 
8.5.10 
Pictorial Blood Assessment Chart 
Bleeding information from each menstrual period in this study will be collected using the 
Pictorial Blood Assessment Chart (PBAC) [14, 15]. The PBAC will be provided to all fe-
male patients of child-bearing potential. 
The investigator will train all relevant patients on how to complete the PBAC. At each study 
visit, the investigator will review the completed PBAC and also calculate the PBAC score. 
The data documented in the PBAC and the investigator-calculated final score will be rec-
orded in the eCRF. 
8.6 
DATA SOURCES 
The data source for the calculation of the bleeding rate will be the information documented 
in the patient diaries as well as the information collected based on the review of the patient’s 
medical records. 
8.7 
DATA MANAGEMENT 
The treating physician will document clinical data as per routine practice in the patients’ 
medical records and transfer information to the study-specific eCRF as required.  
If any errors in the eCRFs are found during data review, queries will be generated and sub-
mitted to the site personnel. Once the query has been answered, Data Management will 
review the new or changed data to ensure an appropriate response and close the query. 
8.8 
DATA ANALYSIS 
No formal sample size calculations were performed. The sample size of 55 patients was 
chosen based on feasibility and to allow data summaries to be produced. However, with a 
sample size of 55, a two-sided 95% confidence interval for the mean ABR will extend ±0.8 
from the observed mean, assuming that the standard deviation is 3 or less and the confidence 
interval is based on the large sample z statistic. 
The data will be analysed using descriptive statistical methods. Full details of the planned 
analyses will be given in a Statistical Analysis Plan, which will be completed before data 
analysis. 
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8.9 
QUALITY CONTROL 
To ensure data quality, the treating physician should review the patient diaries returned by 
the patient for completeness. Whenever any information is missing, the treating physician 
will contact the patient to obtain the information and document the contact and the infor-
mation obtained from the patient in the patient records. 
The data entered into the eCRF by the treating physician or delegated person will be verified 
against the source documents by study monitors. 
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9 
PROTECTION OF HUMAN SUBJECTS 
9.1 
PATIENT INFORMATION AND INFORMED CONSENT 
Freely given written informed consent for participation in this study will be obtained from 
all patients after the aims, methods, and other important aspects of this NIS that are relevant 
to the patient’s decision to participate have been adequately explained. 
The informed consent form must be signed, with the name and date noted by the patient, 
before the patient is exposed to any study-related procedure, including screening for eligi-
bility. For patients not qualified to give legal consent, written consent must be obtained from 
the patient’s parent(s) or legal guardian(s). Children old enough to understand the risks and 
benefits of the observational programme should also be informed and provide their written 
assent. 
The treating physician will explain that the patients are free to refuse to enter the study, or 
to withdraw from it at any time, without any consequences for their further care and without 
the need to justify. Also, the treating physician will complete the informed consent section 
of the eCRF for each patient enrolled. 
Patients and/or their parents or legal guardians will be informed that they are free to with-
draw their consent for participation in this NIS at any time during the study without any 
consequences for their further medical care and without the need to justify their decision. 
Also, patients and/or their parents or legal guardians will be informed that their medical 
(source) records may be reviewed by study monitors or other personnel involved in the 
conduct of the study, and that these persons are bound by strict confidentiality obligations. 
Patients will also be instructed as to the importance of cooperating with their treating phy-
sicians throughout the observational programme by carefully documenting any BEs and 
treatments in their study diaries and by attending all follow-up visits scheduled in agreement 
with their treating physicians. 
9.2 
SUBMISSION OF STUDY DOCUMENTS TO IECS/IRBS, REGULATORY AU-
THORITIES, AND OTHER STAKEHOLDERS 
In accordance with Good Pharmacoepidemiological Practices (GPP), the study will be ap-
proved by the competent IECs/IRBs. Also, the study protocol as well as any protocol 
amendments, a sample of the patient information and informed consent/assent forms, mate-
rials provided to the patients and/or their parents or legal guardians, and further requested 
information will be submitted to the appropriate IECs/IRB, regulatory authorities, and other 
stakeholders as required by national regulations. Before the first patient is enrolled into the 
study, any party (e.g., sponsor, treating physician, CRO) involved in notifying the relevant 
stakeholders should confirm in writing that all ethical and legal requirements have been met. 
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9.3 
CONFIDENTIALITY OF PATIENT DATA 
The treating physician will ensure that the patient’s confidentiality is preserved. In eCRFs 
or any other documents submitted to the Sponsor, the patients will not be identified by their 
names, but by a unique patient code. 
Documents not intended for submission to the Sponsor, i.e., a confidential patient identifi-
cation code list, original consent forms, and patient records, will be maintained by the treat-
ing physician in strict confidence. 
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10 
MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE
REACTIONS 
10.1 
SAFETY MONITORING 
Throughout this NIS, all adverse drug reactions and other relevant safety information be-
coming known or arising during treatment with any of the VWF-containing products used 
in this study and as defined below have to be documented and reported to Octapharma. 
10.1.1 
Definition of Adverse Drug Reaction and Other Safety Information 
Adverse Drug Reaction 
An adverse drug reaction (ADR) is a response to a medicinal product which is noxious and 
unintended [Directive 2001/83/EC Art. 1(11)]. 
‘Response’ here means that a causal relationship between a medicinal product and an ad-
verse event (AE) is at least a reasonable possibility [Guideline ICH-E2A]. 
ADRs may arise from the use of a product within or outside the terms of the marketing 
authorisation or from occupational exposure [Directive 2001/83/EC Art 101(1)]. Conditions 
of use outside the marketing authorisation include off-label use, overdose, misuse, abuse, 
and medication errors.  
Serious Adverse Drug Reaction 
A serious ADR (SADR) is an ADR that fulfils at least one of the following criteria: 

Results in death

Is life-threatening (this implies that the patient was at risk of death at the time of
the event; it does not refer to a reaction that hypothetically might have caused
death if more severe)

Requires in-patient hospitalisation or prolongation of existing in-patient hospitali-
sation (hospitalisation does not refer to the treatment of an ADR on an out-patient
status)

Results in persistent or significant disability/incapacity

Is a congenital anomaly/birth defect

Is a medically important event, e.g.,
–
Suspected transmission of an infectious agent via a medicinal product
–
Inhibitor development
–
Thromboembolic event
–
Other reactions that should be reported in an expedited manner, although they
did not immediately result in one of the above seriousness criteria, e.g., inten-
sive treatment in an emergency room or at home for allergic bronchospasm,
blood dyscrasias, or convulsions that do not result in hospitalisation
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Other Relevant Safety Information 
Other relevant safety information is any information relating to: 

Pregnancies or breast-feeding

Drug abuse (persistent, sporadic, or intentional excessive use of a medicinal prod-
uct inconsistent with the product’s summary of product characteristics (SmPC) or
prescribing information, or acceptable medical practice)

Misuse (situations where the medicinal product is intentionally and inappropriately
used not in accordance with the authorised product information)

Overdose (administration of a dose of a medicinal product given per administration
or cumulatively which is above the maximum recommended dose according to the
authorised product information)

Medication errors (prescribing or dispensing error)

Interactions with other medicinal products or devices

Occupational exposure (an exposure to a medicinal product as a result of one’s
professional or non-professional occupation) associated with any VWF concentrate
used during this study, even if no ADR occurred.
10.1.2 
Reporting of Adverse Drug Reactions and Other Relevant Safety Infor-
mation 
For information about possible ADRs and other relevant safety information associated with 
each product used during this study, refer to the local summary of product characteristics or 
prescribing information. 
Patients who carry out home treatment should be asked to inform their treating physicians 
about any relevant safety information as soon as they become aware of it. The treating phy-
sician will then assess the causal relationship of any events for ADRs and report these and 
other relevant drug safety information as required. 
ADRs in patients treated with Wilate 
All suspected (serious and non-serious) ADRs and other relevant safety information asso-
ciated with the administration of Wilate have to be reported in the Case Safety Report 
Form (CSRF) (see Section 13, Annex 1), which should be sent, by email, to the local safety 
units within one business day. The contact details of the local safety units are given in Sec-
tion 13, Annex 2. 
Quarterly a reconciliation shall be made between study team and local safety units to ensure 
all ADR and other safety relevant information have been completely forwarded to local 
safety units. 
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Information on all pregnancies occurring during the study period in patients treated with 
Wilate is to be collected in the Pregnancy Form (see Section 13, Annex 3) and sent to the  
local safety units (in Section 13, Annex 2.) 
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: 
ADRs in patients treated with VWF-containing product other than Wilate 
All suspected (serious and non-serious) ADRs and other relevant safety information asso-
ciated with the administration of any VWF-containing product other than Wilate used 
during this study have to be reported to the responsible parties in accordance with local 
regulations. 
All pregnancies occurring during the study period in patients treated with any VWF-
containing product other than Wilate have to be reported to the responsible party in ac-
cordance with local regulations. 
10.1.3 
Method and Duration of Observation of the Study Areas after the Occur-
rence of ADRs 
After an ADR is discovered, it should be monitored until it is resolved or until it is regarded 
as permanent. The outcome of the ADR should be documented and classified in one of the 
following categories: “Recovered, resolved,” ”Recovering, resolving,” “Not recovered, not 
resolved,” “Recovered, resolved with sequelae,” “Fatal,” or “Unknown.”  
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11 
PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RE-
SULTS
11.1 
FINAL STUDY REPORT 
A final study report will be prepared after completion of the study and submitted to relevant 
study stakeholders as required locally. 
11.2 
PUBLICATION POLICY 
The results of this study may be published or presented at scientific meetings. If this is 
envisaged by a physician, the physician agrees to inform the Sponsor and to submit all man-
uscripts or abstracts to the Sponsor prior to submission to an editorial board or scientific 
review committee. This will allow the Sponsor to protect proprietary information and to 
provide comments based on information that may not yet be available to the author. 
In accordance with standard editorial and ethical practice, the Sponsor will support publi-
cation of multicentre studies only in their entirety and not as individual centre data. Author-
ship will be determined by mutual agreement. 
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12 
REFERENCES 
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Rodeghiero F, Castaman G, Tosetto A (2009) How I treat von Willebrand disease.
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Castaman G, Goodeve A, Eikenboom J (2013) Principles of care for the diagnosis and
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Broderick CR, Herbert RD, Latimer J et al. (2012) Feasibility of short message service
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10.1111/hae.12170
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Ader DN (2007) Developing the Patient-Reported Outcomes Measurement Infor-
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Hays RD, Spritzer KL, Schalet BD et al. (2018) PROMIS®-29 v2.0 profile physical
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11. Saris-Baglama, R,DeRosa, M, Raczek, A, Bjorner, J,Turner-Bowker, D, Ware, J The
SF-10™ Health Survey for Children: A User’s Guide. QualityMetric Incorporated
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a pictorial chart. British Journal of Obstetrics and Gynaecology 97(8): 734–739
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ANNEXES 
Annex 1 
Case Safety Report Form .................................................................. 39 
Annex 2 
Contact Addresses of Local Safety Offices ....................................... 49 
Annex 3 
Pregnancy Form ................................................................................ 50 
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Annex 2 
Contact Addresses of Local Safety Offices 
Country 
Address 
Email 
Belarus 
Representative Office of Octapharma AG 
in the Republic of Belarus 
Dzerzhinski Av. 8 
Office 503 
220036 Minsk 
nadezhda.lagoiko@octapharma.se 
anna.jakubchyk@octapharma.se 
Bulgaria 
Pharmimport Pharma AD 
20, Frederic Joliot Curie str. 
1113 Sofia 
safety@pharmimport.bg 
Croatia 
Clinres Nova d.o.o., Ul. Milana Makanca 
(Makančeva) 10 
10000 Zagreb 
drugsafety@c-nova.com 
Hungary 
Octapharma Képviselet HWH kft 
1023 Budapest Harcsa u 2. 
hwh@t-online.hu 
Lebanon 
Octapharma Representative Office 
Amman 
Wasfi Al Tal St. Waha Circle 
Bldg 171 
Amman 11953 
rania.mufeed@octapharma.com 
Russia 
Octapharma Nordic AB (Sweden) 
Rep. Office in Moscow 
Denezhniy lane 11 
Building 1 
Moscow 
moscowPV@octapharma.com
Ukraine 
Merit Medical 
Simirenko street 27 of 77 
03134 Kiev 
pharmacovigilance@meritmedical.com.ua 
United States of 
America 
Octapharma USA, Inc. 
117 West Century Road 
Paramus, NJ 07652 
US1.DrugSafety@octapharma.com 
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