TAK-755 for Purpura

Recruiting at 30 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

Trial Summary

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.

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

The research highlights the importance of ADAMTS13 activity in diagnosing and predicting outcomes for thrombotic thrombocytopenic purpura (TTP), suggesting that treatments targeting ADAMTS13, like TAK-755, could be effective in managing this condition. ^{1 2 3 4 5}

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

In a study with 15 patients, TAK-755 (also known as BAX 930) was well tolerated with no serious side effects, and no antibodies against the treatment were found. Additionally, animal studies showed no increased risk of bleeding, even at high doses. ^{6 7 8 9 10}

How is the drug TAK-755 unique in treating Purpura?

TAK-755 is unique because it is a recombinant form of the enzyme ADAMTS13, which helps break down von Willebrand factor to prevent excessive blood clotting, specifically targeting the underlying cause of thrombotic thrombocytopenic purpura (TTP). This approach directly addresses the enzyme deficiency that leads to TTP, unlike other treatments that may not target this specific mechanism. ^{1 3 4 11 12}

What is the purpose of this trial?

Thrombotic thrombocytopenic purpura (or TTP for short) is a condition where blood clots form in small blood vessels throughout the body. The clots can limit or block the flow of oxygen-rich blood to the body's organs, such as the brain, kidneys, and heart. As a result, serious health problems can develop. The increased clotting that occurs in TTP uses up the cells that help the blood to clot, called platelets. With fewer platelets available in the blood, bleeding problems can also occur. People who have TTP may bleed underneath the skin forming purple bruises, or purpura. TTP also can cause anemia, a condition in which red blood cells break apart faster than the body can replace them, leading to fewer red blood cells than in normal. TTP is caused by a lack of activity in the ADAMTS13 enzyme, a protein in the blood involved in controlling clotting of the blood. The ADAMTS13 enzyme breaks up another blood protein called von Willebrand factor that forms blood clots by clumping together with platelets. Some people are born with this condition, while others develop the condition during their life. Many people who are born with TTP experience frequent flare-ups that need to be treated right away. 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 effects of long-term treatment with TAK-755. Treatment will be given in 2 ways: 1. TAK-755 treatment given either every week or every other week to prevent acute TTP events from happening (the "prophylactic" cohort). 2. TAK-755 treatment given to control an acute TTP event when it happens (the "on-demand" cohort). Participants in the prophylactic cohort will receive treatment in the clinic or at home for up to approximately 3 years. They will visit the clinic at least every 12 weeks. Participants in the on-demand cohort will receive daily treatment for the acute TTP event until the flare-up has gotten better. They will have a follow-up visit at the clinic 4 weeks later.

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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

Findings from Research

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 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 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]

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]

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 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]

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]

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]

References

1. 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]

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. 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]

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

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

5. England 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. [2023]

6. England pubmed.ncbi.nlm.nih.gov

ADAMTS-13 assays in thrombotic thrombocytopenic purpura. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

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

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

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

9. Germany pubmed.ncbi.nlm.nih.gov

The spacer domain of ADAMTS13 contains a major binding site for antibodies in patients with thrombotic thrombocytopenic purpura. [2016]

10. England pubmed.ncbi.nlm.nih.gov

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

11. India pubmed.ncbi.nlm.nih.gov

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

12. Japan pubmed.ncbi.nlm.nih.gov

Measurement of ADAMTS13. [2020]