Recombinant vWF Concentrate for Bleeding

Overseen By Keita Ikeda, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Virginia

Must not be taking: Anticoagulants

Disqualifiers: Thrombophilia, DVT, Liver failure, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for adults on ECMO (a machine that aids breathing and heart function) who experience severe bleeding. The study tests a single dose of recombinant von Willebrand Factor (Recombinant vWF Concentrate), which has shown promise in aiding proper blood clotting. The main goal is to assess the treatment's safety and how the body processes it. Participants should be adults on ECMO with serious bleeding issues and must not have taken blood thinners for at least four hours. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that participants stop taking systemic anticoagulation medications for at least 4 hours before joining. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that recombinant von Willebrand Factor (rVWF) is generally safe for treating bleeding conditions. Studies with patients who have von Willebrand disease, a bleeding disorder, indicate that rVWF is well-tolerated and effective in controlling bleeding. These studies found a low risk of allergic reactions and blood clots.

Additionally, a large safety study in the European Union confirmed similar results, showing that the risk of serious side effects is low. This suggests that rVWF can be a safe option for managing bleeding, even in patients with acquired von Willebrand syndrome, which is common in those on ECMO (a type of life support).

Overall, these findings reassure patients considering participation in clinical trials about the safety of rVWF. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for managing major bleeding, which often includes blood products like fresh frozen plasma or desmopressin, the recombinant von Willebrand Factor (vWF) concentrate is derived from recombinant technology, offering a more targeted approach. This treatment introduces a synthetic form of vWF, providing a consistent and pure active ingredient that can better address bleeding issues. Researchers are excited about this treatment because it offers precise dosing through intravenous administration, potentially reducing the risk of complications associated with traditional blood products.

What evidence suggests that recombinant vWF Concentrate might be an effective treatment for bleeding in ECMO patients?

Research shows that recombinant von Willebrand Factor (rVWF) can help reduce bleeding. Studies found that people who regularly received rVWF experienced 53% fewer bleeding episodes each year. This treatment is safe and effective for those with von Willebrand disease because it stabilizes an important blood protein needed for clotting. Early lab studies also suggest that adding rVWF to blood samples from patients on ECMO (a type of life support) improved platelet function, which is crucial for stopping bleeding. In this trial, ECMO patients with major bleeding will receive a single treatment with recombinant vWF, highlighting the potential of rVWF to help manage bleeding in these patients. ^{2 4 6 7 8}

Who Is on the Research Team?

Michael Mazzeffi, MD

Principal Investigator

UVA

Are You a Good Fit for This Trial?

This trial is for adults on ECMO with major bleeding who aren't on blood thinners for at least 4 hours. It's not for those with recent serious clots, vWF antibodies, low platelets or fibrinogen levels, high INR, liver failure, current trial participation, heparin allergy, inability to consent or pregnancy.

Inclusion Criteria

You are currently using a special machine to help your heart and lungs work.

You have had severe bleeding classified as grade 3 or higher according to CTCAE.

I haven't taken blood thinners for at least 4 hours.

Exclusion Criteria

Current participation in another clinical trial (interventional)

Your blood's clotting ability is too high.

Your fibrinogen levels are lower than 150 mg/dL.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

ECMO patients with major bleeding receive a single intravenous dose of recombinant von Willebrand Factor

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pharmacokinetic assessments and adverse event monitoring

30 days

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Recombinant vWF Concentrate

Trial Overview

The study tests a single dose of recombinant von Willebrand Factor (vWF) in adult ECMO patients with severe bleeding. The goal is to see if it's safe and how the body processes it. This phase I study aims to improve clotting by normalizing platelet adhesion.

How Is the Trial Designed?

Group I: Treatment with recombinant vWF Experimental Treatment 1 Intervention

ECMO patients with major bleeding who are enrolled in the trial will receive treatment with recombinant von Willebrand Factor a single time. The dose will be 50 IU/kg and the drug will be given intravenously.

Recombinant vWF Concentrate is already approved in United States, European Union for the following indications:

Approved in United States as Vonvendi for:

• Bleeding episodes in adults with von Willebrand disease

Approved in European Union as Veyvondi for:

• Bleeding episodes in adults with von Willebrand disease

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Published Research Related to This Trial

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]

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]

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 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]

A highly purified von Willebrand factor (vWF) concentrate was developed using a three-step chromatographic process, achieving over 10,000-fold purification from plasma and ensuring no detectable contaminants like fibrinogen or immunoglobulins.

The concentrate demonstrated a high capacity to correct platelet adhesion and has been clinically shown to be effective in treating patients with von Willebrand disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chromatographic preparation of a therapeutic highly purified von Willebrand factor concentrate from human cryoprecipitate. Burnouf-Radosevich, M., Burnouf, T.[2019]

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 clotting factor concentrates are effective treatments for hemostatic disorders like hemophilia A and B, as well as von Willebrand disease, offering new therapeutic options.

Ongoing research into the structure and function of plasma proteins may lead to innovative treatments, including second-generation clotting factors and gene therapy for hemophilia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Availability of clotting factor concentrates in genetically engineered form. van Aken, WG.[2019]

A plasma-derived von Willebrand factor concentrate was shown to be effective in treating severe von Willebrand disease, with 89% of treated bleeding episodes resulting in excellent or good outcomes.

The treatment was safe, with no thrombotic complications reported and no development of antibodies against VWF or FVIII in patients, indicating a favorable safety profile for this concentrate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of severe von Willebrand disease with a high-purity von Willebrand factor concentrate (Wilfactin): a prospective study of 50 patients. Borel-Derlon, A., Federici, AB., Roussel-Robert, V., 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]

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]

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