Recombinant Von Willebrand Factor for Von Willebrand Disease

Recruiting in Palo Alto (17 mi)

+10 other locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Takeda

Must be taking: VWF products

Must not be taking: Immunomodulatory drugs

Disqualifiers: Coagulation disorders, VWF inhibitor, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

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.

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.

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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.

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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.

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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.

Trial 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

Participant Groups

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.

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).

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Children's Health Care d/b/a Children's Minnesota Minneapolis, MN

Childrens Hospital of Michigan Detroit, MI

New York - Presbyterian/Weill Cornell Medical Center New York, NY

Medical University of South Carolina (MUSC) Charleston, SC

Who Is Running the Clinical Trial?

Takeda Lead Sponsor

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] Recombinant von Willebrand factor (rVWF, vonicog alfa, Vonvendi/Veyvondi, Takeda Pharmaceuticals USA, Lexington, MA) and several plasma-derived VWF/factor VIII (pdVWF/FVIII) concentrates are available for treating bleeding episodes in patients with von Willebrand disease (VWD).

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] Von Willebrand Factor (VWF) containing concentrates have been used for the treatment of von Willebrand Disease (VWD) for many years. Recently, however, a novel recombinant VWF (rVWF or vonicog alpha, VONVENDI [US], VEYVONDI [Europe]) has arrived to the market for the treatment of VWD. Initially, rVWF was approved by the U.S. Food and Drug Administration (FDA) for the on-demand treatment and control of bleeding episodes and for the perioperative management of bleeding for patients with VWD. More recently, however, the FDA has approved rVWF for routine prophylaxis to prevent bleeding episodes for those patients with severe type 3 VWD receiving on-demand therapy.

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] Recombinant von Willebrand factor (rVWF, vonicog alfa) is a purified VWF concentrate produced from Chinese hamster ovary cells. rVWF is not exposed to the VWF-cleaving protease ADAMTS13 and so is not subject to proteolytic degradation of large (L) and ultra-large (UL) VWF multimers by that enzyme.

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

[Advances in the therapy for von Willebrand disease]. [2023] Von Willebrand disease (VWD) is caused by quantitative or qualitative deficiencies in the von Willebrand factor (VWF). VWF concentrate replacement therapy is required in certain situations, such as severe VWD subtype or critical bleeding, even in mild VWD subtypes. A single plasma-derived factor VIII/VWF concentrate has been available for decades in Japan. However, it has a theoretical risk of infectious disease transmission, allergic reactions, and thrombosis. A recombinant VWF (vonicog alfa) was approved by the Japanese Pharmaceuticals and Medical Devices Agency in 2020. Vonicog alfa is the only VWF product that contains ultralarge multimer, suggesting both effective bleeding control and excessive platelet plug formation. The efficacy and safety of vonicog alfa have been confirmed by three phases of clinical studies for on-demand usage, elective surgery, and prophylaxis. We also have a successful experience with vonicog alfa with minimal adverse events in two cases (hemostatic treatment in a patient with recurrent epistaxis and prophylaxis for delivery in a pregnant woman).

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] To describe efficacy/safety of recombinant von Willebrand factor (rVWF) prophylaxis in patients with type 3 von Willebrand disease (VWD).