TAK-755 for Thrombotic Thrombocytopenic Purpura

Recruiting at 34 trial locations

Overseen By Takeda Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Takeda

Must not be taking: Caplacizumab

Disqualifiers: HIV, Severe infection, Pregnancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing TAK-755, a medication, in adults with a rare blood disorder called iTTP. The goal is to see if TAK-755 can help manage their symptoms without needing additional treatments. Participants will receive the medication during an acute attack and for a period afterward.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants will receive TAK-755 and immunosuppressive therapy, so it's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug TAK-755 for treating Thrombotic Thrombocytopenic Purpura?

The research highlights the importance of ADAMTS13, a key component of TAK-755, in diagnosing and managing Thrombotic Thrombocytopenic Purpura (TTP). While the studies focus on diagnosis, they suggest that ADAMTS13 activity is crucial in understanding TTP, which indirectly supports the potential effectiveness of TAK-755 in treating this condition. ^{1 2 3 4 5}

Is TAK-755 (recombinant ADAMTS13) safe for humans?

In a study with 15 patients having severe congenital ADAMTS-13 deficiency, TAK-755 (also known as BAX 930) was well tolerated, with no serious side effects or immune reactions observed. Additionally, animal studies showed that even at high doses, TAK-755 did not increase bleeding risks, suggesting it is generally safe. ^{6 7 8 9 10}

How is the drug TAK-755 different from other treatments for thrombotic thrombocytopenic purpura (TTP)?

TAK-755 is unique because it is a recombinant form of the ADAMTS13 enzyme, which is crucial for breaking down large blood clotting proteins that can cause TTP. This drug directly addresses the enzyme deficiency that leads to TTP, offering a targeted approach compared to other treatments that may not specifically replace the missing enzyme. ^{1 3 11 12 13}

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

Adults diagnosed with iTTP who haven't had more than two plasma exchanges before the study can join. They must be willing to use effective birth control, follow study rules, and give consent. Those with severe allergies to TAK-755 components, recent other investigational treatments, or certain health conditions like unstable HIV cannot participate.

Inclusion Criteria

Participant must provide a signed informed consent form. A fully recognized proxy may be used per local laws for participants unable to provide consent.

I have been diagnosed with iTTP for the first time or it has come back.

I am using or agree to use effective birth control during the study.

Exclusion Criteria

Participant is pregnant or lactating.

I have a life-threatening illness with a life expectancy of less than 3 months.

I am currently suffering from a severe infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Acute Treatment

Participants receive TAK-755 and immunosuppressive therapy during their stay at the hospital until they achieve a clinical response

Variable (until clinical response)

Daily hospital visits

Post-Acute Treatment

Participants receive TAK-755 for up to 6 weeks after the acute phase

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• TAK-755

Trial Overview The trial tests TAK-755 in adults with iTTP to see if they can respond clinically without needing plasma exchange. Participants will receive TAK-755 along with immunosuppressive therapy during an acute attack and for up to six weeks after, totaling about three months of study involvement.

Participant Groups

Group I: TAK-755 Dose 2 in Both Acute and Post-Acute Phase Experimental Treatment 1 Intervention

TAK-755 Dose 2, IV infusion, in the acute phase until clinical response is achieved. All participants achieving clinical response will receive TAK-755 at Dose 2, for up to 6 weeks during the post-acute phase.

Group II: TAK-755 Dose 1 in Acute Phase and Dose 2 in Post-acute Phase Experimental Treatment 1 Intervention

TAK-755 Dose 1, IV infusion, in the acute phase until clinical response is achieved. All participants achieving clinical response will receive TAK-755 at Dose 2, for up to 6 weeks during the post-acute phase.

TAK-755 is already approved in United States, European Union, Japan for the following indications:

Approved in United States as TAK-755 for:

• Congenital Thrombotic Thrombocytopenic Purpura (cTTP)

Approved in European Union as TAK-755 for:

• Thrombotic thrombocytopenic purpura

Approved in Japan as TAK-755 for:

• Thrombotic thrombocytopenic purpura

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 254 patients with thrombotic microangiopathy (TMA), moderate ADAMTS13 deficiency (11%-40% activity) was linked to older age and more severe clinical conditions like sepsis and multiorgan failure.

While moderate ADAMTS13 deficiency was associated with higher 90-day mortality in initial analyses, it was not an independent predictor of poor outcomes, suggesting it reflects the severity of the disease rather than directly causing worse outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical features and outcomes in patients with thrombotic microangiopathy not associated with severe ADAMTS13 deficiency. Li, A., Bendapudi, PK., Uhl, L., et al.[2018]

In a study of 89 patients with thrombotic thrombocytopenic purpura (TTP), high levels of total bilirubin (TBIL) and D-dimer (D-D), along with a low PLASMIC score and absence of plasma exchange, were identified as significant risk factors for poor prognosis.

Conversely, low levels of ADAMTS13 were found to be a protective factor, and the combination of TBIL, D-D, and ADAMTS13 showed high predictive value for patient outcomes, with an area under the curve of 0.872, indicating strong prognostic capability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive Values of ADAMTS13, TBIL, and D-D for Prognosis of Patients with Thrombotic Thrombocytopenic Purpura. Liu, B., Zhang, X., Yu, X.[2023]

In a study of 28 patients with various forms of thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), reduced ADAMTS13 activity was significantly correlated with the diagnosis of idiopathic TTP, indicating its potential as a diagnostic marker.

Higher ADAMTS13 activity was associated with better clinical parameters, such as increased platelet counts and lower blood urea nitrogen and creatinine levels, suggesting that ADAMTS13 measurements could help assess the severity of these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic relevance of ADAMTS13 activity: evaluation of 28 patients with thrombotic thrombocytopenic purpura - hemolytic uremic syndrome clinical diagnosis. Vucelić, D., Miković, D., Rajić, Z., et al.[2019]

A laboratory-developed assay using ACTIFLUOR(™) reagents demonstrated the best accuracy for measuring ADAMTS13 activity, with a reportable range of 5% to 114% and low variability, making it a reliable option for clinical testing.

The modified TECHNOZYM(®) autoantibody assay showed good agreement with reference methods, indicating that these optimized assays can improve the diagnosis and management of thrombotic thrombocytopenic purpura.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validation of a panel of ADAMTS13 assays for diagnosis of thrombotic thrombocytopenic purpura: activity, functional inhibitor, and autoantibody test. Nakashima, MO., Zhang, X., Rogers, HJ., et al.[2019]

A new enzyme-linked immunosorbent assay (ELISA) for detecting ADAMTS13 antigen levels in plasma has been established, showing normal levels range from 740-1420 ng/ml, which helps differentiate between conditions like hereditary TTP and HUS.

In patients with acquired TTP, the presence of both free and autoantibody-bound ADAMTS13 complicates the interpretation of antigen levels, limiting the assay's predictive value for diagnosis and treatment despite its rapid determination capabilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relation between ADAMTS13 activity and ADAMTS13 antigen levels in healthy donors and patients with thrombotic microangiopathies (TMA). Rieger, M., Ferrari, S., Kremer Hovinga, JA., et al.[2019]

Recombinant ADAMTS13 (rADAMTS13) has been shown to effectively cleave harmful ultra-large von Willebrand factor (VWF) multimers, making it a promising treatment for thrombotic thrombocytopenic purpura (TTP) and potentially for vaso-occlusive crises in sickle cell disease (SCD).

Safety studies in monkeys and rats demonstrated that even at very high doses (over 100 times normal levels), rADAMTS13 did not increase the risk of bleeding, either alone or when combined with common antithrombotic medications, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absence of exaggerated pharmacology by recombinant ADAMTS13 in the rat and monkey. Rossato, P., Glantschnig, H., Leidenmühler, P., et al.[2023]

In a phase 1 study involving 15 patients with severe congenital ADAMTS-13 deficiency, the recombinant ADAMTS-13 (BAX 930) was found to be well tolerated with no serious adverse events or development of anti-ADAMTS-13 antibodies.

BAX 930 demonstrated dose-dependent pharmacokinetics, with increases in ADAMTS-13 activity and effective cleavage of von Willebrand factor observed within one hour of administration, indicating its potential efficacy in treating this deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura. Scully, M., Knöbl, P., Kentouche, K., et al.[2022]

In a study of 8,908 deliveries, the prevalence of Thrombotic Thrombocytopenic Purpura (TTP) among pregnant women with severe thrombocytopenia was found to be as high as 5%, highlighting the importance of diagnosing this condition due to its serious risks to both mother and baby.

Preventive plasma infusion during subsequent pregnancies in women with TTP significantly improved outcomes, leading to normal deliveries and better placental health, demonstrating the efficacy of early intervention in managing this rare but critical condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of obstetrical thrombotic thrombocytopenic purpura in a retrospective study within thrombocytopenic pregnant women. A difficult diagnosis and a treatable disease. Delmas, Y., Helou, S., Chabanier, P., et al.[2018]

A study involving 150 healthy volunteers in Singapore established reference ranges for ADAMTS13 levels, which are crucial for diagnosing and managing thrombotic thrombocytopenic purpura (TTP) and other thrombotic microangiopathies.

The findings showed that ADAMTS13 levels did not significantly differ by gender or age, providing a standardized reference that can improve clinical management and facilitate research collaborations in diverse populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reference range for ADAMTS13 antigen, activity and anti-ADAMTS13 antibody in the healthy adult Singapore population Tso, ACY., Sum, CLL., Ong, KH.[2022]

References

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

Clinical features and outcomes in patients with thrombotic microangiopathy not associated with severe ADAMTS13 deficiency. [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

Predictive Values of ADAMTS13, TBIL, and D-D for Prognosis of Patients with Thrombotic Thrombocytopenic Purpura. [2023]

3. Serbia pubmed.ncbi.nlm.nih.gov

Diagnostic relevance of ADAMTS13 activity: evaluation of 28 patients with thrombotic thrombocytopenic purpura - hemolytic uremic syndrome clinical diagnosis. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Validation of a panel of ADAMTS13 assays for diagnosis of thrombotic thrombocytopenic purpura: activity, functional inhibitor, and autoantibody test. [2019]

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

ADAMTS13 related markers and von Willebrand factor in plasma from patients with thrombotic microangiopathy (TMA). [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Relation between ADAMTS13 activity and ADAMTS13 antigen levels in healthy donors and patients with thrombotic microangiopathies (TMA). [2019]

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

ADAMTS13 and von Willebrand factor interactions. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Absence of exaggerated pharmacology by recombinant ADAMTS13 in the rat and monkey. [2023]

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

Platelet-delivered ADAMTS13 inhibits arterial thrombosis and prevents thrombotic thrombocytopenic purpura in murine models. [2022]

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

Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura. [2022]

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

Insights into ADAMTS13 structure: impact on thrombotic thrombocytopenic purpura diagnosis and management. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Incidence of obstetrical thrombotic thrombocytopenic purpura in a retrospective study within thrombocytopenic pregnant women. A difficult diagnosis and a treatable disease. [2018]

13. India pubmed.ncbi.nlm.nih.gov

Reference range for ADAMTS13 antigen, activity and anti-ADAMTS13 antibody in the healthy adult Singapore population [2022]