Recombinant Von Willebrand Factor for Von Willebrand Disease

Recruiting at 10 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

Trial Summary

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.

What data supports the idea that Recombinant Von Willebrand Factor for Von Willebrand Disease is an effective drug?

The available research shows that Recombinant Von Willebrand Factor (rVWF) is effective in treating Von Willebrand Disease (VWD). It has been approved by the FDA for controlling bleeding episodes and for routine prevention of bleeding in severe cases. Studies have confirmed its effectiveness and safety in various situations, such as on-demand treatment, surgery, and regular prevention. Unlike older treatments, rVWF does not carry the same risks of infection or allergic reactions, making it a safer option. Additionally, it has been shown to work well with minimal side effects in specific cases, like nosebleeds and childbirth. ^{1 2 3 4 5}

What safety data exists for recombinant von Willebrand factor treatment?

Recombinant von Willebrand factor (rVWF), also known as vonicog alfa, has been evaluated for safety and efficacy in several clinical studies. It has been approved for on-demand treatment, perioperative management, and routine prophylaxis in patients with von Willebrand disease (VWD). The safety of vonicog alfa has been confirmed through three phases of clinical studies, showing minimal adverse events. It is not exposed to the VWF-cleaving protease ADAMTS13, reducing the risk of proteolytic degradation. Overall, the treatment has shown effective bleeding control with minimal adverse events reported in specific cases. ^{1 2 3 4 5}

Is the drug Recombinant von Willebrand Factor (rVWF) a promising treatment for Von Willebrand Disease?

Yes, Recombinant von Willebrand Factor (rVWF) is a promising treatment for Von Willebrand Disease. It is effective in controlling bleeding and preventing bleeding episodes, especially in severe cases. It is not exposed to certain enzymes that can break it down, which helps it work better. It has been approved for use in various situations, including on-demand treatment, surgery, and regular prevention of bleeding, with minimal side effects reported. ^{1 2 3 4 5}

What is the purpose of this trial?

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.

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

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

I am under 18 years old.

My BMI is within the required range for my age group.

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

Exclusion Criteria

I have severe liver disease or cirrhosis.

Participant is pregnant or lactating at the time of enrollment

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

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Pharmacokinetic-Pharmacodynamic Comparison of Recombinant and Plasma-Derived von Willebrand Factor in Patients with von Willebrand Disease Type 3. [2023]

2. England pubmed.ncbi.nlm.nih.gov

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

3. New Zealand 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. [2022]

4. Japan pubmed.ncbi.nlm.nih.gov

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

5. England 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. [2023]