rVWF IN PROPHYLAXIS
Condition: Von Willebrand Disease
MeSH terms: Von Willebrand Diseases
Intervention: von Willebrand factor (Recombinant); Antihemophilic Factor (Recombinant)
Intervention description: OD participants will receive intravenous (IV) rVWF:RCo at an initial prophylactic dose of 50 +/- 10 International Unit per Kilogram (IU/kg) twice (two infusions) a week for at least 12 months up to 15 months and may be increased up to 80 IU/kg. pdVWF switch cohort participants will receive rVWF:RCo equivalent (± 10%) to the weekly VWF dose received during prophylactic treatment with pdVWF.; During prophylaxis period any bleeding episodes requiring substitution therapy with VWF concentrate to control bleeding will be treated with rVWF with or without ADVATE. Participants will receive rFVIII IV if necessary for OD treatment of breakthrough bleeds or for peri-operative. The dose will be according to the bleeding type and severity and it will be adjusted to the clinical response.
Intervention MeSH terms: Factor VIII
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this phase 3 study is to investigate the efficacy and safety, including
      immunogenicity, thrombogenicity and hypersensitivity reactions, as well as pharmacokinetics
      (PK), health related quality of life (HRQoL) and pharmacoeconomics of prophylactic treatment
      with recombinant von Willebrand factor (rVWF) (vonicog alfa) in adult participants with
      severe von Willebrand disease (VWD).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Participant has a documented diagnosis of severe von Willebrand disease (VWD)
             (baseline Von Willebrand factor: Ristocetin cofactor activity (VWF:RCo) less than (<)
             20 International Units/Deciliter [IU/dL]) with a history of requiring substitution
             therapy with von Willebrand factor concentrate to control bleeding

               1. Type 1 (VWF:RCo <20 IU/dL) or,

               2. Type 2A (as verified by multimer pattern), Type 2B (as diagnosed by genotype),
                  Type 2M or,

               3. Type 3 (Von Willebrand factor antigen (VWF:Ag) less than or equal to [< or =] 3
                  IU/dL).

          2. Diagnosis is confirmed by genetic testing and multimer analysis, documented in patient
             history or at screening.

          3. For on-demand patient group, participant currently receiving on-demand treatment for
             whom prophylactic treatment is recommended by the investigator.

          4. For Plasma derived von Willebrand factor (pdVWF) product switch patient group,
             participant has been receiving prophylactic treatment of pdVWF products for no less
             than 12 months prior to screening.

          5. For on-demand patient group, participant has greater than or equal to (>or=) 3
             documented spontaneous bleeds (not including menorrhagia) requiring von Willebrand
             factor (VWF) treatment during the past 12 months.

          6. Availability of records to reliably evaluate type, frequency and treatment of bleeding
             episodes during at least 12 months preceding enrollment. Up to 24 months retrospective
             data should be collected if available. Availability of dosing and factor consumption
             during 12 months (up to 24 months) of treatment prior to enrollment is required for
             pdVWF switch participants and is desired (but not a requirement) for on-demand
             participants.

          7. Participant is > or = 18 years old at the time of screening and has a body mass index
             > or = 15 but <40 kilogram per meter square (kg/m^2).

          8. If female of childbearing potential, participant presents with a negative blood/urine
             pregnancy test at screening and agrees to employ adequate birth control measures for
             the duration of the study.

          9. Participant is willing and able to comply with the requirements of the protocol.

        Exclusion Criteria:

          1. The participant has been diagnosed with Type 2N Von Willebrand disease (VWD), pseudo
             VWD, or another hereditary or acquired coagulation disorder other than VWD (eg
             qualitative and quantitative platelet disorders or prothrombin time [PT]/international
             normalized ratio [INR] greater than [>]1.4).

          2. The participant is currently receiving prophylactic treatment with more than 5
             infusions per week.

          3. The participant is currently receiving prophylactic treatment with a weekly dose
             exceeding 240 IU/kg.

          4. The participant has a history or presence of a VWF inhibitor at screening.

          5. The participant has a history or presence of a Factor VIII (FVIII) inhibitor with a
             titer ≥0.4 Bethesda units (BU) (by Nijmegen modified Bethesda assay) or > or = 0.6
             Bethesda Unit (BU) (by Bethesda assay).

          6. The participant has a known hypersensitivity to any of the components of the study
             drugs, such as to mouse or hamster proteins.

          7. The participant has a medical history of immunological disorders, excluding seasonal
             allergic rhinitis/conjunctivitis, mild asthma, food allergies or animal allergies.

          8. The participant has a medical history of a thromboembolic event.

          9. The participant is human immunodeficiency virus (HIV) positive with an absolute Helper
             T cell (CD4) count <200/ cubic millimeter (mm^3).

         10. The participant has been diagnosed with significant liver disease per investigator's
             medical assessment of the participant's current condition or medical history or as
             evidenced by any of the following: serum alanine aminotransferase (ALT) greater than 5
             times the upper limit of normal; hypoalbuminemia; portal vein hypertension (e.g.,
             presence of otherwise unexplained splenomegaly, history of esophageal varices).

         11. The participant has been diagnosed with renal disease, with a serum creatinine (CR)
             level > or = 2.5 milligram per deciliter (mg/dL).

         12. The participant has a platelet count <100,000/ milliliter (mL) at screening.

         13. The participant has been treated with an immunomodulatory drug, excluding topical
             treatment (e.g., ointments, nasal sprays), within 30 days prior to signing the
             informed consent.

         14. The participant is pregnant or lactating at the time of enrollment.

         15. Patient has cervical or uterine conditions causing menorrhagia or metrorrhagia
             (including infection, dysplasia).

         16. The participant has participated in another clinical study involving another
             Investigational product (IP) or investigational device within 30 days prior to
             enrollment or is scheduled to participate in another clinical study involving an IP or
             investigational device during the course of this study.

         17. The participant has a progressive fatal disease and/or life expectancy of less than 15
             months.

         18. The participant is scheduled for a surgical intervention.

         19. The participant is identified by the investigator as being unable or unwilling to
             cooperate with study procedures.

         20. The participant has a mental condition rendering him/her unable to understand the
             nature, scope and possible consequences of the study and/or evidence of an
             uncooperative attitude.

         21. The participant is in prison or compulsory detention by regulatory and/or juridical
             order.

         22. The participant is member of the study team or in a dependent relationship with one of
             the study team members which includes close relatives (i.e., children, partner/spouse,
             siblings and parents) as well as employees.