Recombinant Von Willebrand Factor for Von Willebrand Disease

Recruiting at 15 trial locations

Overseen By Takeda Contact

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Takeda

Must be taking: VWF products

Must not be taking: Immunomodulatory drugs

Disqualifiers: Coagulation disorders, VWF inhibitor, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 12 months

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness of a new treatment called vonicog alfa (Recombinant von Willebrand Factor, rVWF) for children with severe Von Willebrand Disease, a bleeding disorder. The treatment is administered twice a week for a year to determine if it controls bleeding better than existing options. Children who have been using specific Von Willebrand Factor (VWF) treatments and still experience bleeding episodes might be suitable candidates for this study. Participants must visit the study clinic five times during the treatment. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must have been on VWF products for at least 6-12 months before the trial, depending on your age. Also, you cannot have taken immunomodulatory drugs (except topical treatments) within 30 days before the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that recombinant von Willebrand Factor (rVWF), also known as vonicog alfa, is generally safe for individuals with von Willebrand Disease. In a European study, researchers found no new safety issues when using rVWF for either preventing or treating the condition. Another study also identified no major safety problems, confirming that rVWF is safe and effective for managing severe bleeding symptoms. These findings suggest that the treatment is well-tolerated by patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Recombinant von Willebrand Factor (rVWF) is unique because it offers a more targeted and consistent approach to treating Von Willebrand Disease compared to traditional plasma-derived von Willebrand Factor (pdVWF) treatments. Unlike pdVWF, which is derived from human plasma, rVWF is produced using recombinant DNA technology, reducing the risk of blood-borne pathogen transmission. This technology ensures a purer product with a more reliable supply, addressing some of the limitations associated with plasma-derived treatments. Researchers are excited about rVWF because it could provide a safer and more effective option for managing this bleeding disorder, particularly in younger patients who need long-term treatment.

What evidence suggests that recombinant von Willebrand factor could be an effective treatment for Von Willebrand Disease?

Research shows that recombinant von Willebrand Factor (rVWF), a treatment participants in this trial may receive, helps reduce bleeding in people with Von Willebrand Disease. Studies have found that using rVWF as a preventive treatment decreases the number of spontaneous bleeding episodes each year. This is particularly beneficial for those who previously required treatment only during bleeding episodes. Evidence also suggests that rVWF treatment can prevent an increase in bleeding episodes over time. Early results from previous studies support its use, demonstrating positive outcomes in managing bleeding related to this disease. ^{2 6 7 8 9}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

This trial is for children under 18 with severe Von Willebrand Disease (VWF:RCo <20 IU/dL) who have had previous VWF treatments. They must have a history of bleeding events controlled by VWF concentrate and be recommended for prophylactic treatment. Participants need reliable medical records of their condition, meet specific body weight criteria, and girls able to bear children must use effective birth control.

Inclusion Criteria

Participant has voluntarily provided assent (if appropriate) and the legally authorized representative(s) has provided informed consent

Participant and/or legally authorized representative is willing and able to comply with the requirements of the protocol

I am under 18 years old.

Exclusion Criteria

Participant is pregnant or lactating at the time of enrollment

Participant is a member of the study team or in a dependent relationship with one of the study team members

My doctor expects I have 15 months or less to live due to my illness.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vonicog alfa (rVWF) with an initial dose selected within the range of 40 to 60 IU/kg, intravenous infusions, twice-weekly for 12 months

12 months

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ADVATE
• Recombinant von Willebrand Factor (rVWF)

Trial Overview The study tests the effectiveness of a new medication called recombinant von Willebrand factor (rVWF) over 12 months in children with severe vWD who were previously treated with VWF products. The goal is to see if rVWF can prevent bleeding episodes better than past treatments.

How Is the Trial Designed?

Group I: Cohort 3: Participants With Age <6 years Experimental Treatment 2 Interventions

Participants with age \<6 years who have received OD therapy of VWF product or prophylactic treatment with a pdVWF product will receive vonicog alfa (rVWF) with an initial dose selected within the range of 40 to 60 IU/kg vonicog alfa (rVWF), intravenous infusions, twice-weekly for 12 months. Participants may receive vonicog alfa (rVWF) with or without ADVATE intravenous infusions, when indicated (as deemed necessary for breakthrough bleeding episode treatment and perioperative bleeding management).

Group II: Cohort 2: Participants With Age >=6 to <12 years Experimental Treatment 2 Interventions

Participants with age \>=6 to \<12 years who have received OD therapy of VWF product or prophylactic treatment with a pdVWF product will receive vonicog alfa (rVWF) with an initial dose selected within the range of 40 to 60 IU/kg vonicog alfa (rVWF), intravenous infusions, twice-weekly for 12 months. Participants may receive vonicog alfa (rVWF) with or without ADVATE intravenous infusions, when indicated (as deemed necessary for breakthrough bleeding episode treatment and perioperative bleeding management).

Group III: Cohort 1: Participants With Age >=12 to <18 years Experimental Treatment 2 Interventions

Participants with age greater than or equal to (\>=) 12 to less than (\<) 18 years who have received on-demand (OD) therapy or prophylactic treatment with a pdVWF product will receive vonicog alfa (rVWF) with an initial dose selected within the range of 40 to 60 international units per kilogram (IU/kg) vonicog alfa (rVWF), intravenous infusions, twice-weekly for 12 months. Participants may receive vonicog alfa (rVWF) with or without ADVATE intravenous infusions, when indicated (as deemed necessary for breakthrough bleeding episode treatment and perioperative bleeding management).

Who Is Running the Clinical Trial?

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Published Research Related to This Trial

The novel recombinant von Willebrand Factor (rVWF) has been FDA approved for routine prophylaxis to prevent bleeding episodes in patients with severe type 3 von Willebrand Disease (VWD), expanding its use beyond on-demand treatment.

Phase III trial results suggest that rVWF may have superior hemostatic potential compared to traditional plasma-derived VWF concentrates, likely due to its unique structure that includes ultra-large VWF multimers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of von Willebrand factor (recombinant) therapy for adult patients living with severe type 3 von Willebrand disease. Hancock, JM., Escobar, MA.[2023]

Vonicog alfa, a recombinant von Willebrand factor product approved in Japan, has shown efficacy and safety in treating von Willebrand disease (VWD) across various clinical scenarios, including on-demand treatment and prophylaxis during surgery.

Clinical studies confirm that vonicog alfa effectively controls bleeding and has a favorable safety profile, with minimal adverse events reported in cases such as treating recurrent nosebleeds and providing prophylaxis for pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Advances in the therapy for von Willebrand disease]. Nakayama, T.[2023]

In a post hoc analysis of a phase 3 trial involving 18 adults with type 3 von Willebrand disease, recombinant von Willebrand factor (rVWF) prophylaxis significantly reduced annualized bleeding rates by 91.6% in patients previously treated on-demand, indicating its high efficacy.

The safety profile of rVWF was favorable, with only one non-serious adverse event reported and no serious treatment-related adverse events or development of von Willebrand factor inhibitors, suggesting it is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylaxis with recombinant von Willebrand factor in patients with type 3 von Willebrand disease: Results of a post hoc analysis from a phase 3 trial. Leebeek, FWG., Peyvandi, F., Tiede, A., et al.[2023]

Recombinant von Willebrand factor (rVWF) maintains a non-degraded multimeric structure, including large (L) and ultra-large (UL) VWF multimers, which are absent in human plasma-derived VWF concentrates, potentially enhancing its hemostatic efficacy.

rVWF exhibits superior platelet-binding activity and faster platelet adhesion under shear stress compared to plasma-derived VWF concentrates, indicating its effectiveness in treating patients with severe von Willebrand disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structure and Function of Recombinant versus Plasma-Derived von Willebrand Factor and Impact on Multimer Pharmacokinetics in von Willebrand Disease. Gritsch, H., Schrenk, G., Weinhappl, N., et al.[2022]

Recombinant von Willebrand factor (rVWF) has a significantly longer mean residence time and half-life compared to plasma-derived VWF/factor VIII (pdVWF/FVIII) in patients with von Willebrand disease, indicating a prolonged therapeutic effect.

Simulations suggest that administering rVWF can maintain FVIII activity levels above 40 IU/dL for the entire 72-hour dosing interval, making it a potentially more effective treatment option for managing bleeding episodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic-Pharmacodynamic Comparison of Recombinant and Plasma-Derived von Willebrand Factor in Patients with von Willebrand Disease Type 3. Bauer, A., Friberg-Hietala, S., Smania, G., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03879135

NCT03879135 | A Study of Recombinant Von Willebrand ... The main aim of the study is to check effectiveness of rVWF (vonicog alfa) prophylaxis based on the annualized bleeding rate (ABR) of spontaneous (not ...

2. clinicaltrials.takeda.com clinicaltrials.takeda.com/study-detail/b48da778c86b4f5a?

TAK-577-3001 | Clinical Trial Summary The main aim of the study is to evaluate the effectiveness of prophylaxis with vonicog alfa (recombinant von Willebrand factor [rVWF]) in children.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35439298/

Recombinant von Willebrand factor prophylaxis in patients ... Findings suggest that rVWF prophylaxis can reduce treated spontaneous BEs in patients previously receiving on-demand VWF therapy and maintains at least the ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06433778

A Study on the Outcomes of Recombinant Von Willebrand ... Number of Participants With Bleeding Episodes Treated With rVWF, Bleeding episodes will be reported based on type, severity, location, treatment, and outcomes, ...

5. catalogues.ema.europa.eu catalogues.ema.europa.eu/node/3262/methodological-aspects

TAK-577-4005: Estimating Risk of Selected Adverse Events in ... The primary outcomes will assess the percentage of participants who experienced hypersensitivity reactions, thromboembolic events, and with VWF ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12499246/

Real-World Data from an EU Post-Authorization Safety Study Overall, no new safety signals were identified in this European real-world study when rVWF was used for the prevention or treatment of ...

7. fda.gov fda.gov/media/188621/download?attachment

September 5, 2025 Clinical Review Memo - VONVENDI No significant safety concerns. ATHN 9 is a Natural History Cohort Study of the Safety, Effectiveness, and Practice of Treatment for People with ...

8. ashpublications.org ashpublications.org/blood/article/126/17/2038/34434/Hemostatic-efficacy-safety-and-pharmacokinetics-of

Hemostatic efficacy, safety, and pharmacokinetics of a ... Key Points. rVWF:rFVIII is safe and hemostatically effective in severe VWD patients for a variety of bleeding symptoms.rVWF induces sustained stabilization.

9. clinicaltrials.takeda.com clinicaltrials.takeda.com/study-detail/a4acf130288f407e??page=1&idFilter=TAK-577-5001

TAK-577-5001 | Clinical Trial Summary This study is a retrospective chart review study and will collect data on real world use of vonicog alfa (Recombinant Von Willebrand Factor [rVWF]). Von ...