rVWF IN PROPHYLAXIS

Takeda

Status and phase: Completed; Phase 3

Conditions: Von Willebrand Disease

Treatments: Biological: von Willebrand factor (Recombinant); Biological: Antihemophilic Factor (Recombinant)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02973087

2016-001478-14 (EudraCT Number)

071301

Details and patient eligibility

About

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).

Enrollment: 29 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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29 participants in 1 patient group

All Study Participants

Experimental group

Description:

Participants will receive prophylaxis with rVWF in two cohorts: on-demand (OD) cohort (previously treated with OD) and pdVWF switch cohort (participants switching from prophylactic treatment with pdVWF).

Treatment:

Biological: Antihemophilic Factor (Recombinant)

Biological: von Willebrand factor (Recombinant)