TAK-755 for Purpura

Recruiting at 36 trial locations

Overseen By Takeda Contact

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Takeda

Must not be taking: Immunomodulatory drugs

Disqualifiers: Immune deficiency, Neurological events, Cardiovascular, 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

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

Compensation: Varies

Number of Visits: 13

77 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called TAK-755 for individuals with thrombotic thrombocytopenic purpura (TTP). TTP causes harmful blood clots and can lead to issues like bleeding and anemia (a low red blood cell count). TAK-755 works by replacing a missing enzyme to help prevent or manage TTP flare-ups. The trial will include two groups: one receiving regular treatment to prevent flare-ups and another receiving treatment only during flare-ups. Individuals diagnosed with severe congenital ADAMTS-13 deficiency and who have experienced frequent TTP flare-ups might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are taking immunomodulatory drugs (medications that modify the immune system), you must stop them at least 30 days before enrolling in the study, except for certain topical treatments and corticosteroids used with fresh frozen plasma.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that TAK-755 is generally safe for people with thrombotic thrombocytopenic purpura (TTP). One study demonstrated that TAK-755 had better safety results compared to standard treatments for similar conditions, with many patients experiencing no severe side effects.

Most side effects were mild, such as reactions at the infusion site, while serious side effects were rare. TAK-755 is the first treatment to directly address the root cause of TTP by replacing a missing enzyme in the blood. As this treatment nears the final stages of research, strong evidence supports its safety for patients.

For those considering participation in a clinical trial with TAK-755, it is important to know that it has been tested in many individuals and has shown promising safety results. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for TTP?

TAK-755 is unique because it offers a new approach to treating thrombotic thrombocytopenic purpura (TTP) by using a recombinant ADAMTS13 enzyme. Unlike the standard plasma exchange treatments that can be time-consuming and rely on donor plasma, TAK-755 directly replaces the missing enzyme that causes TTP. Researchers are excited about TAK-755 because it has the potential to provide more targeted treatment with fewer side effects and greater convenience, possibly reducing the need for frequent hospital visits. Additionally, it offers flexibility with both prophylactic and on-demand treatment options, allowing for tailored therapy based on the patient's needs.

What evidence suggests that TAK-755 might be an effective treatment for TTP?

Research has shown that TAK-755 holds promise for treating thrombotic thrombocytopenic purpura (TTP) by replacing the missing enzyme, ADAMTS13. In this trial, participants in the Prophylactic Cohort will receive TAK-755 to prevent TTP flare-ups, while those in the On-Demand Cohort will receive it during acute TTP events. Studies have found that TAK-755 effectively prevents and controls TTP flare-ups by maintaining normal blood clotting. In clinical trials, TAK-755 demonstrated good safety and effectiveness compared to the usual treatment for congenital TTP. This treatment meets a critical need by directly addressing the enzyme deficiency that causes TTP. Overall, TAK-755 offers a focused approach to managing TTP and reducing the frequency of sudden episodes. ^{1 3 4 6 7}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

This trial is for individuals aged 0-70 with severe congenital ADAMTS-13 deficiency, a condition leading to excessive blood clotting and bleeding issues. Participants must be in good health otherwise, not pregnant, agree to use birth control, and have no history of drug/alcohol abuse or immune deficiencies. They cannot have other TTP-like disorders or life-threatening reactions to similar treatments.

Inclusion Criteria

I have been diagnosed with severe congenital ADAMTS-13 deficiency.

My doctor says I am mostly active and can care for myself.

You are part of a specific program or study and had an allergic reaction to the standard preventive treatment.

Exclusion Criteria

You have had a severe allergic reaction to certain ingredients.

I am currently sick.

I have been diagnosed with a condition similar to TTP.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Prophylactic Treatment

Participants receive TAK-755 treatment every week or every other week to prevent acute TTP events

Up to approximately 3 years

Clinic visits every 12 weeks

On-Demand Treatment

Participants receive daily TAK-755 infusions during acute TTP events until resolution

Varies per event

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks after each acute event

1 follow-up visit

What Are the Treatments Tested in This Trial?

Interventions

• TAK-755

Trial Overview TAK-755 is being tested as a replacement therapy for the ADAMTS13 enzyme in patients with congenital thrombotic thrombocytopenic purpura (TTP). The study has two parts: one where TAK-755 is given regularly to prevent flare-ups ('prophylactic' cohort) and another where it's given during acute flare-ups ('on-demand' cohort).

How Is the Trial Designed?

Group I: Prophylactic Cohort: TAK-755 Experimental Treatment 1 Intervention

All participants will receive prophylactic treatment with 40 IU/kg TAK-755 intravenous (IV) infusions once every week or once every other week for the duration of the study. Participants who are naïve will receive an initial IV dose of 40 IU/kg TAK-755 to allow measurement of the pharmacokinetics of TAK-755, followed by prophylactic treatment with 40 IU/kg TAK-755 by IV infusion once every week or once every other week for the duration of the study.

Group II: On-Demand Cohort: TAK-755 Experimental Treatment 1 Intervention

Participants will receive daily IV infusions of TAK-755 when experiencing an acute thrombotic thrombocytopenic purpura (TTP) event until 2 days after the acute TTP event is resolved. Participants will receive 40 IU/kg TAK-755 on the first day, followed by 20 IU/kg on Day 2, and then 15 IU/kg daily until 2 days after the acute TTP event has resolved. Upon resolution of the acute TTP event, participants may choose to move to the prophylactic cohort of the study or discontinue entirely from the study.

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+

Shire

Industry Sponsor

Trials

457

Recruited

96,000+

Pierre S. Sayad

Shire

Chief Medical Officer

MD from Loma Linda University

Flemming Ornskov

Shire

Chief Executive Officer since 2013

PhD in Medicine from Aarhus University

Published Research Related to This Trial

In a study of 15 patients with thrombotic thrombocytopenic purpura (TTP), all patients had antibodies that inhibited the activity of ADAMTS13, which is crucial for processing von Willebrand factor, indicating a common underlying mechanism in TTP.

The research identified that the spacer domain of ADAMTS13 is a major binding site for these inhibitory antibodies, suggesting that targeting this domain could be important for developing therapies for TTP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The spacer domain of ADAMTS13 contains a major binding site for antibodies in patients with thrombotic thrombocytopenic purpura. Luken, BM., Turenhout, EA., Hulstein, JJ., et al.[2016]

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 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 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]

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]

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]

ADAMTS13 is a crucial enzyme that regulates blood clotting by cleaving von Willebrand factor, and its deficiency leads to thrombotic thrombocytopenic purpura (TTP), a serious blood disorder.

There is ongoing debate about the effectiveness of ADAMTS13 assays in diagnosing TTP, highlighting the need for improved diagnostic methods to better utilize these tests in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measurement of ADAMTS13. Tsai, HM.[2020]

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]

The TECHNOSCREEN® ADAMTS-13 activity screening test demonstrated high sensitivity (88.7%) and specificity (90.4%) for identifying thrombotic thrombocytopenic purpura (TTP) in a study of 220 patients, making it a reliable tool for early diagnosis.

This screening test is simpler and faster than traditional assays, allowing for quicker evaluation of ADAMTS-13 levels, which can facilitate timely treatment decisions in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multi-center evaluation of TECHNOSCREEN® ADAMTS-13 activity assay as a screening tool for detecting deficiency of ADAMTS-13. Moore, GW., Meijer, D., Griffiths, M., et al.[2023]

ADAMTS-13 is crucial for regulating the structure of von Willebrand factor (VWF) and plays a significant role in the development of thrombotic thrombocytopenic purpura (TTP), a serious condition that can lead to organ damage due to blood clots.

Recent advancements have led to the development of various laboratory assays for measuring ADAMTS-13 levels and its autoantibodies, which can help in diagnosing and managing TTP effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ADAMTS-13 assays in thrombotic thrombocytopenic purpura. Peyvandi, F., Palla, R., Lotta, LA., et al.[2023]

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]

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/174465/download

Clinical Review Memo - ADZYNMA Congenital thrombotic thrombocytopenic purpura (TTP) is an ultra-rare, life-threatening thrombotic disorder of the microcirculation caused ...

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.

7. chpw.org chpw.org/wp-content/uploads/content/provider-center/policies/ADAMTS13_Recombinant_-_krhn_Adzynma_Clinical_Coverage_Criteria_PM605.pdf

ADAMTS13, Recombinant-krhn (Adzynma) Clinical ... Diagnosis is confirmed with molecular genetic testing of the ADAMTS13 gene or by ADAMTS13 activity testing showing < 10% of normal activity.