rVWF +/− ADVATE for Von Willebrand Disease

Recruiting at 38 trial locations

Overseen By Takeda Contact

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Baxalta now part of Shire

Must be taking: VWF products

Must not be taking: Immunomodulatory drugs

Disqualifiers: Pseudo-VWD, 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: Unknown

Duration: 12-18 months

31 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment for children with severe von Willebrand disease, a condition that affects blood clotting and can cause frequent bleeding. The study evaluates how well the treatment, vonicog alfa (a recombinant von Willebrand factor), works alone or with another drug, ADVATE (an antihemophilic factor), to control bleeding episodes over 12-18 months. Children who have experienced severe bleeding episodes in the past year and are not suitable for other treatments might be a good fit for this trial. Participants will have regular follow-ups at clinics or through phone calls to monitor their progress. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on immunomodulatory drugs (medications that affect the immune system) other than anti-retroviral chemotherapy, you may need to stop them 30 days before joining the study.

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

Research has shown that vonicog alfa, a lab-made version of von Willebrand factor (rVWF), is generally safe for people with von Willebrand Disease (VWD). In studies for VONVENDI®, a brand of rVWF, common side effects included headache and fever, with no new safety concerns identified. Real-world studies from Europe also reported no new safety issues for rVWF.

For ADVATE®, used with vonicog alfa in this study, safety information primarily comes from its use in people with hemophilia A. It is generally well-tolerated, with common side effects being mild, such as headache or dizziness. However, ADVATE® is not specifically used for von Willebrand disease.

Overall, both treatments have demonstrated a good safety record in studies, but discussing any concerns with a healthcare provider remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they leverage recombinant technology to produce von Willebrand factor (rVWF) and antihemophilic factor (ADVATE), which are essential for blood clotting. Unlike traditional plasma-derived options, these recombinant factors are produced synthetically, eliminating the risk of viral transmission. Additionally, the treatment protocol offers flexibility with on-demand dosing for non-surgical bleeding and tailored infusion schedules for various types of surgery, potentially improving patient outcomes by providing more precise control over bleeding episodes. This approach could simplify the management of Von Willebrand Disease by reducing reliance on human-derived products and enhancing safety and efficacy.

What evidence suggests that this trial's treatments could be effective for Von Willebrand Disease?

Research shows that vonicog alfa, a lab-made version of von Willebrand factor (rVWF), helps reduce bleeding in people with severe von Willebrand disease (VWD). Studies have found a 53% decrease in yearly bleeding episodes for patients using rVWF regularly. A combined review of clinical trials rated 96% of treatments as excellent or good. Vonicog alfa replaces the missing or faulty von Willebrand factor, aiding blood clotting. In this trial, participants may receive rVWF for non-surgical bleeding episodes or during surgical procedures. While ADVATE, a factor VIII product, is mainly used for hemophilia A, it can also stabilize factor levels in VWD, potentially managing bleeding episodes. Participants in this trial may receive rVWF with or without ADVATE, depending on the treatment arm. ^{1 2 6 7 8}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

Children under 18 with severe hereditary von Willebrand disease (VWD) can join this trial. They must have had at least one bleed requiring treatment in the past year and agree to follow study rules. Girls who can have babies must test negative for pregnancy and use birth control.

Inclusion Criteria

I have been diagnosed with severe von Willebrand disease.

I've had a bleeding episode in the last year despite treatment with DDAVP.

I have never received VWF coagulation factor replacement therapy.

Exclusion Criteria

Pregnant or lactating female participants at the time of informed consent

I have had a blood clot in the past.

I haven't taken any immune system modifying drugs in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vonicog alfa for non-surgical bleeding episodes over a 12 to 18-month period

12-18 months

Regular follow-ups at clinics or via telephone

Surgery

Participants undergo elective or emergency surgery with specific infusion protocols

Varies by surgery type

Pre-operative and post-operative visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

Throughout the study duration of approximately 8.5 years

What Are the Treatments Tested in This Trial?

Interventions

• Antihemophilic Factor (Recombinant)
• von Willebrand factor (Recombinant)

Trial Overview The trial is testing recombinant von Willebrand Factor (rVWF), alone or with ADVATE, to treat bleeding in kids with VWD. Over 12-18 months, doctors will give treatments based on their usual practice while checking effectiveness and side effects.

How Is the Trial Designed?

Group I: On-demand Treatment Experimental Treatment 2 Interventions

Participants will receive vonicog alfa (recombinant von Willebrand factor \[rVWF\]) treatment for non-surgical bleeding episodes over a 12 to 18-month period.

Group II: Emergency Surgery Experimental Treatment 2 Interventions

Within 3 hours prior to surgery. Minor surgery: infuse every 12-24 hours for at least 48 hours based on post-operative dosing. Oral Surgery: infuse at least once within first 8-12 hours post-surgery based on post-operative dosing. Major Surgery: infuse every 12-24 hours for at least first 96 hours post-surgery based on post-operative dosing.

Group III: Elective Surgery Experimental Treatment 2 Interventions

12-24 hours prior to surgery and within 3 hours of surgery. Minor surgery: infuse every 12-24 hours for at least 48 hours based on post-operative dosing. Oral Surgery: infuse at least once within first 8-12 hours post-surgery based on post-operative dosing. Major Surgery: infuse every 12-24 hours for at least first 96 hours post-surgery based on post-operative dosing.

Who Is Running the Clinical Trial?

Baxalta now part of Shire

Lead Sponsor

Trials

111

Recruited

9,100+

Flemming Ornskov

Baxalta now part of Shire

Chief Executive Officer since 2013

MD, MPH

Ludwig N. Hantson

Baxalta now part of Shire

Chief Medical Officer since 2015

PhD

Takeda Development Center Americas, Inc.

Industry Sponsor

Trials

58

Recruited

10,800+

Published Research Related to This Trial

In a study involving 91 adults with von Willebrand disease, recombinant von Willebrand factor (rVWF) effectively treated spontaneous and traumatic bleeds, achieving resolution in 14 out of 15 cases.

rVWF was also effective in preventing and treating surgery-related bleeds, with a resolution rate of 25 out of 58 surgeries, and no treatment-emergent adverse events were reported, indicating a strong safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes in Patients With von Willebrand Disease Receiving Recombinant von Willebrand Factor on Demand and in Surgical Settings: Chart Review. Sun, SX., Lowndes, S., Willock, R., et al.[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]

In a real-world study involving 111 patients with von Willebrand disease (VWD) across 31 centers in 11 countries, wilate was found to be safe and well tolerated, with 96.2% of infusions rated as 'excellent' by patients.

Wilate demonstrated high effectiveness in treating bleeding episodes and providing prophylaxis, with 100% of on-demand treatments rated as 'excellent' or 'good' by patients and investigators, and a median annualized bleeding rate of only 1.9 during prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Data on the Effectiveness and Safety of wilate for the Treatment of von Willebrand Disease. Sholzberg, M., Khair, K., Yaish, H., et al.[2021]

A recombinant von Willebrand factor (rVWF) was successfully used in a patient with von Willebrand disease type 2A to control severe gastrointestinal bleeding, demonstrating its efficacy in acute treatment.

After starting rVWF therapy, the patient experienced a significant reduction in bleeding symptoms and did not require any red blood cell transfusions for over 3 months, indicating its potential for both treatment and prophylaxis in managing bleeding episodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant von Willebrand factor for severe gastrointestinal bleeding unresponsive to other treatments in a patient with type 2A von Willebrand disease: a case report. Brown, R.[2018]

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]

In a phase 3 study involving patients with severe von Willebrand disease (VWD) undergoing surgery, recombinant von Willebrand factor (rVWF) demonstrated excellent or good hemostatic efficacy in 100% of cases, with 73.3% rated as excellent overall.

rVWF was well-tolerated, with most patients (89.4%) receiving it alone, achieving effective levels of endogenous factor VIII for up to 96 hours, and no severe allergic reactions were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3 study of recombinant von Willebrand factor in patients with severe von Willebrand disease who are undergoing elective surgery. Peyvandi, F., Mamaev, A., Wang, JD., et al.[2023]

Citations

1. advate.com advate.com/safety

Safety and Side Effects of ADVATE® Factor VIII Treatment ADVATE is a medicine used to prevent and control bleeding in adults and children with hemophilia A. ADVATE is not used to treat von Willebrand disease.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7496521/

Management of von Willebrand disease with a factor VIII‐poor ... They were treated for 743 bleeds and 140 surgeries including childbirth. Efficacy outcomes were excellent/good for 98.2% of 56 major surgeries and 94.0% of 67 ...

3. tandfonline.com tandfonline.com/doi/full/10.1080/17474086.2025.2504956

Real-world treatment patterns and outcomes in people with ... This retrospective chart review evaluated real-world effectiveness of prophylaxis with recombinant von Willebrand factor (rVWF) in all subtypes of VWD.

4. advatepro.com advatepro.com/safety-profile

ADVATE Safety Profile and Clinical Trial Data for HCPs *In clinical trials, ADVATE demonstrated the ability to help prevent bleeding episodes using a prophylaxis regimen. Indication: ADVATE is a recombinant ...

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

Hemostatic efficacy, safety, and pharmacokinetics of a ... These results show that rVWF was safe and effective in treating bleeds in VWD patients and stabilizes endogenous FVIII:C, which may eliminate the need for ...

6. vonvendipro.com vonvendipro.com/safety

Safety Data for VONVENDI® [von Willebrand factor ... Explore the safety profile and the most common adverse reactions observed in VONVENDI® clinical trials for patients with Von Willebrand Disease (VWD).

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4616237/

Hemostatic efficacy, safety, and pharmacokinetics of a ... These results show that rVWF was safe and effective in treating bleeds in VWD patients and stabilizes endogenous FVIII:C, which may eliminate the need for ...

8. advate.com advate.com/

Treat Hemophilia A with ADVATE® Antihemophilic Factor VIII ADVATE is a medicine used to prevent and control bleeding in adults and children with hemophilia A. ADVATE is not used to treat von Willebrand disease.