TAK-755 for Thrombotic Thrombocytopenic Purpura

Recruiting at 41 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

33 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of TAK-755, a recombinant enzyme therapy, for individuals with immune-mediated thrombotic thrombocytopenic purpura (iTTP). The researchers aim to determine how many participants can respond to the treatment without plasma exchange, a process that removes and replaces blood plasma. The study divides participants into groups receiving different doses during and after an acute iTTP attack. This trial may suit adults diagnosed with new or relapsed iTTP who are willing to follow the study procedures. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that TAK-755 is likely to be safe for humans?

Research has shown that TAK-755 has undergone safety testing in people with thrombotic thrombocytopenic purpura (TTP). Studies indicate that TAK-755, a lab-made protein, is generally well-tolerated. In trials for other TTP types, most participants did not experience serious side effects from TAK-755.

Another study compared TAK-755 to standard TTP treatments and found that TAK-755 works without causing more side effects than usual treatments. Additionally, the FDA has approved TAK-755 for use in congenital TTP, suggesting it is considered safe for that condition.

Overall, while TAK-755 is still being tested for immune-mediated TTP, past studies have shown it has a good safety record. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

TAK-755 is unique because it offers a new approach to treating Thrombotic Thrombocytopenic Purpura (TTP) by using an intravenous infusion with a potentially faster response time during the acute phase of the condition. Unlike the standard treatment options like plasma exchange and immunosuppressive therapy, TAK-755 is designed to target the underlying issues more directly, which might lead to quicker stabilization of platelet counts. Researchers are excited about TAK-755 because it could simplify the treatment process and reduce the need for intensive procedural interventions, offering a more streamlined and potentially more effective therapy for patients with TTP.

What evidence suggests that TAK-755 could be an effective treatment for iTTP?

Research shows that TAK-755, also known as apadamtase alfa, holds promise for treating thrombotic thrombocytopenic purpura (TTP). This treatment is a lab-made protein that replaces the missing ADAMTS13 enzyme, preventing blood clots. In this trial, participants will receive different doses of TAK-755 to evaluate its effectiveness in both acute and post-acute phases of TTP. Studies have found that TAK-755 effectively prevents and manages sudden TTP episodes, reducing the need for plasma exchange. Early results suggest that TAK-755 helps stabilize platelet levels, which is crucial for managing TTP. This treatment is also approved for congenital TTP, demonstrating a strong record of safety and effectiveness in similar conditions. ^{1 3 4 5 6}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Part 2: TAK-755 Dose 3 in Acute Phase and Dose 2 in Post-acute Phase Experimental Treatment 1 Intervention

TAK-755 Dose 3, IV infusion, in the acute phase until 48-hour platelet response is achieved. All participants achieving platelet response will receive TAK-755 at Dose 2, 4 times per week for Week 1 and 3 times per week for Week 2 and 3 during the post-acute phase based on investigator judgement as high-risk for developing iTTP recurrence.

Group II: Part 1: 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 III: Part 1: 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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05714969

NCT05714969 | A Study of TAK-755 (rADAMTS13) With ... The main aim of this study is to determine the percentage of participants with a clinical (Part 1) or platelet (Part 2) response without plasma exchange during ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38418772/

Apadamtase Alfa: First Approval This article summarizes the milestones in the development of apadamtase alfa leading to this first approval in the USA for congenital TTP. © 2024. The Author(s) ...

3. takeda.com takeda.com/newsroom/newsreleases/2022/takeda-announces-favorable-phase-3-safety-and-efficacy-results-of-tak-755-as-compared-to-standard-of-care-in-congenital-thrombotic-thrombocytopenic-purpura-cttp/

Takeda Announces Favorable Phase 3 Safety and Efficacy ... TAK-755 is the first and only recombinant ADAMTS13 protein in development. It provides targeted therapy to address an unmet medical need in patients with ...

4. fda.gov fda.gov/media/174318/download

ADZYNMA ADZYNMA is indicated for prophylactic or on-demand enzyme replacement therapy in adult and pediatric patients with congenital thrombotic.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04683003

NCT04683003 | A Study of TAK-755 in Participants With ... TAK-755 is a medicine that replaces ADAMTS13 and may prevent or control TTP flare-ups, called acute TTP events. The main aim of the study is to check for side ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10428421/

S305: PHASE 2 RANDOMIZED, PLACEBO-CONTROLLED ... Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare disorder caused by a severe ADAMTS13 deficiency, due to anti-ADAMTS13 autoantibodies.