TAK-330 for Blood Clotting Disorders

Recruiting at 58 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Takeda

Must be taking: Factor Xa inhibitors

Must not be taking: Procoagulants, Heparin

Disqualifiers: Recent MI, Stroke, Bleeding, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial compares two treatments for reversing blood thinners in patients needing urgent surgery. Both treatments help the blood clot normally again. One treatment is commonly used and has been studied extensively.

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.

What data supports the effectiveness of the treatment TAK-330 for blood clotting disorders?

Research shows that four-factor prothrombin complex concentrate (4F-PCC), which is part of TAK-330, is effective in managing severe bleeding in patients on warfarin and in various critical bleeding situations like trauma and liver failure. It has been proven to work better than plasma transfusions in these cases. ^{1 2 3 4 5}

Is TAK-330 (4F-PCC) generally safe for humans?

Four-factor prothrombin complex concentrate (4F-PCC), also known as TAK-330, has been used safely in humans for reversing the effects of blood thinners like warfarin in cases of severe bleeding. However, its safety for other uses is not fully understood, and more research is needed to confirm its safety in different conditions. ^{1 2 4 6 7}

How is the drug TAK-330 different from other treatments for blood clotting disorders?

TAK-330 is unique because it is a four-factor prothrombin complex concentrate (4F-PCC) that contains four essential blood clotting factors, making it effective for urgent reversal of blood thinners like warfarin. Unlike traditional plasma transfusions, 4F-PCC provides a more targeted and rapid response in managing critical bleeding situations. ^{1 2 3 4 7}

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

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 18 years old or older.

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.

Trial Timeline

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)

Treatment Details

Interventions

• 4F-PCC (Reversal Agent)
• PROTHROMPLEX TOTAL (Reversal Agent)
• SOC 4F-PCC (Reversal Agent)
• TAK-330 (Reversal Agent)

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.

Participant Groups

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+

Findings from Research

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]

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 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]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Clinical utilization of four-factor prothrombin complex concentrate: a retrospective single center study. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Roles of Four-Factor Prothrombin Complex Concentrate in the Management of Critical Bleeding. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Four-factor prothrombin complex concentrates in paediatric patients - a retrospective case series. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Comparison of Hemostatic Outcomes in Patients Receiving Fixed-Dose vs. Weight-Based 4-Factor Prothrombin Complex Concentrate. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Use of four-factor prothrombin complex concentrate (4F-PCC) for management of bleeding not associated with therapeutic anticoagulant use. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Four-factor prothrombin complex concentrate for life-threatening bleeds or emergent surgery: A retrospective evaluation. [2022]

7. United States 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. [2022]