A Study of Recombinant Von Willebrand Factor (rVWF) With or Without ADVATE in Children With Severe Von Willebrand Disease (VWD)

This is an interventional treatment trial for Von Willebrand Disease Read More

Inclusion Criteria:

• Diagnosis of severe von Willebrand disease (VWD) (defined as von Willebrand factor: ristocetin cofactor [VWF:RCo] less than [<] 20 percent [%]):

  • Type 1 (VWF:RCo <20 International Units per deciliter [IU/dL]); or
  • Type 2A (VWF:RCo <20 IU/dL), Type 2B (as diagnosed by genotype), Type 2N (Factor VIII coagulation activity [FVIII:C] <10 % and historically documented genetics), Type 2M; or
  • Type 3 (VWF:Ag less than or equal to [=<] 3 IU/dL).
• Age 0 to <18 years at the time of Screening.
• The participant has provided assent (if appropriate) and legally authorized representative(s) has provided informed consent.
• If female of childbearing potential, participant presents with a negative serum pregnancy test.
• If applicable, participant agrees to employ adequate birth control measures for the duration of the study.
• The participant and/or the legally authorized representative are willing and able to comply with the requirements of the protocol, which should also be confirmed based on a pre-screening evaluation held between the Investigator and the Sponsor, to ensure no eminent risk is present that could challenge the participants compliance with the study requirements.

Additional inclusion criteria for both previously treated participants and participants undergoing surgery are as follows:

• Unable to tolerate or are inadequately responsive to deamino-delta-D-arginine vasopressin (DDAVP).
• The participant has had a minimum of 1 documented bleed requiring VWF coagulation factor replacement therapy (i.e. treatment with a VWF product) during the previous 12 months prior to enrollment and overall historically 3 or more exposure days (EDs) to VWF replacement therapy.

Additional inclusion criterion for previously untreated participants are as follows:

- The participant has not received prior VWF coagulation factor replacement therapy.

Exclusion Criteria:

• Diagnosis of pseudo-VWD or another hereditary or acquired coagulation disorder (eg, qualitative and quantitative platelet disorders or elevated prothrombin time [PT]/international normalized ratio [INR] greater than [>] 1.4).
• History or presence of a VWF inhibitor at Screening.
• History or presence of a Factor VIII (FVIII) inhibitor with a titer greater than or equal [>=] 0.4 Bethesda units (BU) (by Nijmegen assay) or >=0.6 BU (by Bethesda assay).
• Documented history of a VWF: RCo half-life <6 hours.
• Known hypersensitivity to any of the components of the study drug, such as mouse or hamster proteins.
• Medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis/asthma, food allergies, or animal allergies.
• Medical history of a thromboembolic event.
• Human immunodeficiency virus (HIV) positive, with an absolute CD4 count <200/ cubic millimeter (mm^3).
• In the judgment of the Investigator, the participant has another clinically significant concomitant disease (e.g. uncontrolled hypertension, cancer) that may pose additional risks for the participant.
• Diagnosis of significant liver disease, as evidenced by, but not limited to, any of the following: serum alanine aminotransferase (ALT) of 5 times the upper limit of normal; hypoalbuminemia; portal vein hypertension (e.g. presence of otherwise unexplained splenomegaly, history of esophageal varices) or liver cirrhosis classified as Child B or C.
• Diagnosis of renal disease, with a serum creatinine level >=2.5 milligram per deciliter (mg/dL).
• Immunomodulatory drug treatment other than anti-retroviral chemotherapy (e.g. α-interferon, or corticosteroid agents at a dose equivalent to hydrocortisone greater than 10 milligram per day [mg/day] (excluding topical treatment [e.g. ointments, nasal sprays]), within 30 days prior to signing the informed consent (or assent, if appropriate).
• If female, participant is pregnant or lactating at the time informed consent (or assent, if appropriate) is obtained.
• Participant has participated in another clinical study involving an investigational product (IP), other than rVWF with or without ADVATE, or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP other than rVWF or investigational device during the course of this study.
• Participant's legal representative is a family member or employee of the Investigator.