The main aim of the study is to evaluate the effectiveness of prophylaxis with vonicog alfa (recombinant von Willebrand factor [rVWF]) in children. This study will enroll those participants who have been previously treated with VWF product or with a plasma-derived VWF (pdVWF) product. In this study, participants will be treated with vonicog alfa (rVWF) for 12 months.

During the study, participants will visit the study clinic 5 times after treatment initiation.

1. The participant has a documented diagnosis of severe VWD (baseline von Willebrand factor ristocetin cofactor activity [VWF:RCo] <20 international units per deciliter [IU/dL]) with a history of replacement therapy with VWF concentrate required to control bleeding and a diagnosis of VWD type 1, type 2 (2A, 2B, 2M, 2N), or type 3. Diagnosis is confirmed, as applicable, by genetic testing and/or by multimer analysis, which may be documented in participant's history or at screening.

2. The participant is <18 years of age at the time of screening.

3. Prescreening treatment requirements:

   1. The participant has been receiving OD therapy with VWF products for at least 12 months (for participants >=2 years of age) prior to screening, has experienced at least 1 VWF-treated bleeding event during (excluding menorrhagia/heavy menstrual bleeding [HMB], as applicable) in the last 12 months, and prophylactic treatment is recommended by the investigator (Prior OD participants); or
   2. The participant has been receiving prophylactic treatment with pdVWF products for at least 12 months prior to screening (for participants >=2 years of age) and switching to prophylaxis with vonicog alfa (rVWF) is recommended by the investigator (Switch participants).
   3. For participants <2 years of age, the required duration for prior OD therapy with VWF products or for prior prophylactic treatment with pdVWF products is at least 6 months. Prior OD participants <2 years of age should have experienced at least 1 VWF-treated bleeding event during the last 6 months based on medical records and be recommended to receive prophylactic treatment by the investigator.

4. For participants >=2 years of age, the participant has available records that reliably evaluate type, frequency, severity, and treatment of BEs for at least 12 months preceding enrollment. For participants <2 years of age, the participant has available records that reliably evaluate type, frequency, severity and treatment of BEs for at least 6 months preceding enrollment.

5. If >=12 years old at the time of screening, the participant has a body mass index (BMI) >=15 but <40 kilogram per square meter (kg/m^2). If >=2 to <12 years old at the time of screening, the participant has a BMI of >=5th and <95th percentile (per Centers for Disease Control and Prevention [CDC] clinical charts). For younger participants who are <2 years old, the "weight-for-age" clinical charts (5th to 95th percentile) provided by the CDC should be utilized to ensure the participant has a body weight of >=5th and <95th percentile based on gender (for clinical charts provided by CDC, refer to: https://www.cdc.gov/growthcharts/clinical\_charts.htm).

6. Female participants of childbearing potential (that is, had onset of menses/reached puberty) must have a negative blood/urine pregnancy test result at screening and agree to employ highly effective birth control measures for the duration of their participation in the study.

7. The participant has voluntarily provided assent (if appropriate) and the legally authorized representative(s) has provided informed consent.

8. The participant and/or legally authorized representative is willing and able to comply with the requirements of the protocol, which should also be confirmed based on a prescreening evaluation held between the investigator and the sponsor to ensure no eminent risk is present that could challenge the participant's compliance with the study requirements.

Exclusion Criteria:

1. The participant has been diagnosed with pseudo VWD or another hereditary or acquired coagulation disorder other than VWD (example, qualitative and quantitative platelet disorders or elevated prothrombin time/international normalized ratio 1.4).
2. The participant has a history or presence of a VWF inhibitor at screening.
3. The participant has a history or presence of an factor VIII (FVIII) inhibitor with a titer >=0.6 Bethesda units per milliliter (/mL).
4. The participant has a known hypersensitivity to any of the components of the study drugs, such as mouse or hamster proteins.
5. The participant has a medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis, mild asthma, food allergies, or animal allergies.
6. The participant has a medical history of a thromboembolic event.
7. The participant is human immunodeficiency virus (HIV)-positive with an absolute helper T cell (CD4) count <200 per cubic millimeter or microliter (/mm^3).
8. The participant has been diagnosed with significant liver disease per the investigator's medical assessment of the participant's current condition or medical history or as evidenced by, but not limited to, any of the following: serum alanine aminotransferase (ALT) greater than 5 times the upper limit of normal (ULN), hypoalbuminemia, portal vein hypertension (example, presence of otherwise unexplained splenomegaly, history of esophageal varices), or liver cirrhosis classified as Child-Pugh class B or C.
9. The participant has been diagnosed with renal disease, with a serum creatinine level >=2.5 milligram per deciliter (mg/dL).
10. The participant has a platelet count <100,000/mL at screening (because participants with type 2B VWD are considered eligible for this study, for participants with type 2B VWD, platelet count[s] at screening will be evaluated in consultation with the sponsor, taking into consideration historical trends in platelet counts and the investigator's medical assessment of the participants condition).
11. The participant has been treated with an immunomodulatory drug, excluding topical treatment (example, ointments, nasal sprays), within 30 days prior to signing the informed consent (or assent, if appropriate).
12. The participant is pregnant or lactating at the time of enrollment.
13. The participant has cervical or uterine conditions causing menorrhagia or metrorrhagia (including infection, dysplasia).
14. The participant has participated in another clinical study involving another 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.
15. The participant has not received OD or prophylactic treatment with a VWF product prior to this study.
16. The participant has a progressive fatal disease and/or life expectancy of less than 15 months.
17. The participant is unable to complete screening procedures and/or comply with the requirements of the protocol in the opinion of the investigator, based on the joint prescreening evaluation held between the investigator and the sponsor.
18. 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.
19. The participant is member of the study team or in a dependent relationship with one of the study team members, which includes close relatives (that is, children, partner/spouse, siblings, and parents) as well as employees.

Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.