TAK-330 for Blood Clotting Disorders

Recruiting at 60 trial locations

Overseen By Sean Campbell, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Takeda

Must be taking: Factor Xa inhibitors

Must not be taking: Procoagulants, Heparin

Disqualifiers: Recent MI, Stroke, Bleeding, 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: 3

Duration: 1 day

328 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called TAK-330 (also known as Human Prothrombin Complex) for individuals needing urgent surgery while taking medication that affects blood clotting, specifically Factor Xa inhibitors like rivaroxaban, apixaban, or edoxaban. The goal is to determine if TAK-330 manages bleeding during surgery more effectively than the current standard treatment, 4F-PCC. Participants will be randomly assigned to receive either TAK-330 or the standard treatment before surgery. Those taking a Factor Xa inhibitor and requiring urgent surgery due to a high risk of bleeding might be a good fit. Participants will need to stay in the hospital for the trial and will have a follow-up via phone or video call after 30 days. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that you are currently on a Factor Xa inhibitor like rivaroxaban, apixaban, or edoxaban. Some medications, like certain procoagulant drugs and heparin, are restricted before and during the trial.

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

Previous studies have shown that TAK-330 is well-tolerated by people. Research indicates that this treatment, which includes human clotting factors, is generally safe. Some participants reported side effects, but these were mostly mild and manageable.

For example, some patients experienced minor reactions at the injection site, similar to other treatments using human clotting factors. TAK-330 is being compared to a standard treatment called 4F-PCC, which is already used in hospitals and known to be safe.

Both treatments aim to assist with blood clotting during urgent surgeries. Safety remains a priority in these studies, and both treatments have been researched to ensure they are safe for people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

TAK-330 is unique because it offers a potential new approach to managing blood clotting disorders. Unlike standard treatments, TAK-330 can be specifically dosed and adjusted during surgery based on the surgeon's assessment, which may provide more precise control over blood clotting. Additionally, TAK-330 is administered as an intravenous infusion, allowing for rapid action, which is particularly useful in surgical settings where timing is crucial. Researchers are excited about TAK-330 because it could offer a more tailored and responsive treatment option compared to current standard care practices.

What evidence suggests that this trial's treatments could be effective for blood clotting disorders?

Research has shown that TAK-330, one of the treatments in this trial, can effectively reverse the effects of blood thinners known as Factor Xa inhibitors. One study demonstrated that TAK-330 helped return blood clotting to normal within 30 minutes, crucial for patients needing emergency surgery. This treatment works quickly and effectively to stop excessive bleeding. TAK-330 provides important proteins needed for blood to clot, often low in people taking blood thinners, making it a promising option for those requiring a fast-acting countermeasure. Participants in this trial will receive either TAK-330 or SOC 4F-PCC, another treatment option, to assess their effectiveness in managing blood clotting disorders. ^{1 2 3 5 6}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

Adults on oral Factor Xa inhibitors needing urgent surgery with high bleeding risk can join. They must have a negative pregnancy test if applicable, and either took their last dose of the inhibitor within 15 hours or show elevated anti-FXa levels. Excluded are those with certain clotting/bleeding disorders, severe organ failure, recent use of heparin or other trials, breastfeeding women, imminent death prognosis, recent major cardiovascular events or active major bleeding.

Inclusion Criteria

I need urgent surgery and have a high bleeding risk due to recent Factor Xa inhibitor use.

Participant or legally authorized representative willing to sign e-consent/written informed consent form

I am currently taking a blood thinner medication like rivaroxaban.

Exclusion Criteria

I am being treated with PROTHROMPLEX TOTAL as standard care.

You have a history of IgA deficiency with allergic reactions and antibodies to IgA.

I haven't had a stroke, heart attack, severe blood clotting issues, or been hospitalized for severe COVID-19 in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive TAK-330 or SOC 4F-PCC prior to surgery for anticoagulation reversal

1 day

1 visit (in-person, hospitalization)

Surgery/Invasive Procedure

Participants undergo urgent surgery or invasive procedure with monitoring for hemostasis

1 day

1 visit (in-person, hospitalization)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including telehealth/phone call follow-up

30 days

1 visit (telehealth/phone call)

What Are the Treatments Tested in This Trial?

Interventions

• 4F-PCC
• PROTHROMPLEX TOTAL
• SOC 4F-PCC
• TAK-330

Trial Overview The trial is testing TAK-330 against standard treatment (4F-PCC) for reversing anticoagulation from Factor Xa inhibitors in patients requiring urgent surgery. Participants will be randomly assigned to one of these treatments before their procedure and followed up via telehealth after 30 days.

How Is the Trial Designed?

Group I: TAK-330 25 IU/kg Experimental Treatment 1 Intervention

Participants will receive TAK-330, 25 international unit per kilogram (IU/kg) single intravenous infusion on Day 1 (prior to surgery) as an initial dose and an additional dose of 25 IU/kg TAK-330 can be administered during the surgery if deemed necessary by the surgeon. The total dose of TAK-330 administered to the participant should not exceed 50 IU/kg or 5,000 IU, whichever is smaller.

Group II: SOC 4F-PCC Active Control 1 Intervention

Participants will receive 4F-PCC (excluding Prothromplex Total and activated 4F-PCC) as standard of care (SOC) on Day 1 (prior to surgery). The dose and infusion speed of the SOC 4F-PCC will be based on local institutional protocols. An additional dose of SOC 4F-PCC not exceeding total dose of 50 IU/kg or 5,000 IU, whichever is smaller can be given during the surgery if required.

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

Takeda Development Center Americas, Inc.

Industry Sponsor

Trials

58

Recruited

10,800+

Published Research Related to This Trial

4F-PCC is an effective hemostatic agent for reversing warfarin effects and has shown promise in treating various acquired coagulopathies, such as bleeding after cardiac surgery and trauma, based on several randomized trials.

While 4F-PCC has advantages over traditional plasma transfusions, optimal dosing for conditions beyond vitamin K antagonist reversal is still being researched, highlighting the need for further studies to clarify its safety and efficacy in these critical situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Roles of Four-Factor Prothrombin Complex Concentrate in the Management of Critical Bleeding. Tanaka, KA., Shettar, S., Vandyck, K., et al.[2022]

In a study of 16 pediatric patients aged 0-16 who received four-factor prothrombin complex concentrates (PCCs) over five years, significant improvements in prothrombin time (PT) were observed, particularly in those who had timely bloodwork for vitamin K antagonist (VKA) reversal.

The efficacy and safety of PCCs in children appear comparable to those reported in adults, although one thrombotic event was noted, with uncertain causation, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Four-factor prothrombin complex concentrates in paediatric patients - a retrospective case series. Noga, T., Bruce, AA., Blain, H., et al.[2018]

In a study involving 11 Japanese patients needing urgent vitamin K antagonist reversal, administration of 4F-PCC led to rapid increases in plasma levels of vitamin K-dependent coagulation factors and proteins C and S, with increases of over 100% in the bleeding group and 70% in the surgical group within 30 minutes.

The treatment was well tolerated, with no adverse thromboembolic events linked to elevated plasma levels, indicating that 4F-PCC is effective and safe for reversing anticoagulation in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Coagulation Factor Plasma Levels Following Administration of a 4-Factor Prothrombin Complex Concentrate for Rapid Vitamin K Antagonist Reversal in Japanese Patients. Yasaka, M., Brainsky, A., Zhang, P., et al.[2022]

In a study of 93 adult patients receiving four-factor prothrombin complex concentrate (4F-PCC), 11.8% developed thromboembolism within 14 days, highlighting a significant thromboembolic risk associated with its use, especially in patients with certain risk factors like heparin-induced thrombocytopenia and recent major surgery.

4F-PCC effectively corrected INR levels in patients reversing warfarin, with 71.4% achieving correction at first draw and 87.3% within 24 hours, although 25.5% experienced INR rebound, particularly in those not receiving vitamin K.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Four-factor prothrombin complex concentrate for life-threatening bleeds or emergent surgery: A retrospective evaluation. Sin, JH., Berger, K., Lesch, CA.[2022]

In a study of 72 patients, a fixed dose of approximately 2000 factor IX units of 4F-PCC was found to be as effective as weight-based dosing for achieving hemostasis in patients on warfarin or direct factor Xa inhibitors, with clinically effective hemostasis rates of 91.2% for fixed dosing compared to 78.9% for weight-based dosing.

The fixed-dose regimen not only maintained efficacy but also resulted in significant cost savings for healthcare facilities, without increasing the risk of adverse events or affecting hospital stay length.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Hemostatic Outcomes in Patients Receiving Fixed-Dose vs. Weight-Based 4-Factor Prothrombin Complex Concentrate. Kim, C., Cottingham, L., Eberwein, K., et al.[2022]

In a study of 76 adult patients receiving 4F-PCC for bleeding not related to anticoagulation, the treatment led to significant reductions in the need for blood components and improved coagulation parameters (PT, INR, aPTT).

Despite the benefits, 11% of patients experienced thromboembolic complications, highlighting the need for careful monitoring when using 4F-PCC in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of four-factor prothrombin complex concentrate (4F-PCC) for management of bleeding not associated with therapeutic anticoagulant use. Uttaro, E., Young, MR., Falvey, J., et al.[2023]

In a study of 184 patients at a trauma center, 4F-PCC was primarily used to manage severe bleeding, with 74% of cases involving active bleeding, and it was most commonly administered to patients on warfarin for atrial fibrillation.

While 4F-PCC was effective in reversing bleeding, 4.9% of patients experienced thrombotic events within 90 days, and the mortality rate was notably higher for off-label uses (37.7%) compared to on-label uses (19.1%), indicating a need for further research on its safety and efficacy in these contexts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utilization of four-factor prothrombin complex concentrate: a retrospective single center study. Naeem, Z., Allan, S., Hernandez, A., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01159210?cond=Factor%20VII%20deficiency&rank=8

Efficacy and Safety of Prothromplex Total (Prothrombin ... The purpose of the study is to assess the efficacy and safety of Prothromplex Total as a treatment for the immediate reversal of oral anticoagulant therapy with ...

2. clinicaltrials.takeda.com clinicaltrials.takeda.com/study-detail/61ba5ab5f571d4002a64b4aa

A Study of TAK-330 to Reverse the Effects of Factor Xa ... The aim of this study is to find out the effects of TAK-330 compared with four-factor prothrombin complex concentrate (4F-PCC) as part of standard treatment.

3. clinicaltrialsregister.eu clinicaltrialsregister.eu/ctr-search/rest/download/result/attachment/2010-019250-41/1/8924

Prothromplex Total Page 1 of 7 Full Clinical Study Report ... • To assess in-vivo recovery of clotting factors II, VII, IX and X at 30 ±. 5 minutes after administration of Prothromplex Total. • To assess ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25613927/

An international, multicenter, prospective study of a ... Of 59 subjects analyzed, all achieved normalization of INR (≤ 1.3) within 30 ± 5 minutes of infusion, demonstrating effective anticoagulant reversal. IVRs of ...

5. clinicaltrialsregister.eu clinicaltrialsregister.eu/ctr-search/trial/2021-004138-12/AT

Clinical Trials Register Human Coagulation Factors II, VII, IX, and X. D.3.9.2, Current sponsor code, TAK-330. D.3.9.3, Other descriptive name, HUMAN PROTHROMBIN COMPLEX.

6. assets-dam.takeda.com assets-dam.takeda.com/image/upload/v1651148870/HCMS-JOBS/Prothromplex_TOTAL_administration_guide_isgupe.pdf

Who is Prothromplex TOTAL for? Presentation: Prothromplex TOTAL vials contain human prothrombin complex (human coagulation factors II, VII, IX, X) powder and solvent.