A Study of TAK-755 in Participants With Congenital Thrombotic Thrombocytopenic Purpura

NCT04683003 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: TAK-755-30022020-003348-102024-513839-24-00
• Study Type: interventional
• Target: 77
• Locations: 11 countries
• Sites: 27

Brief Summary

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. 1.TAK-755 treatment given either every week or every other week to prevent acute TTP events from happening (the "prophylactic" cohort).
2. 2.TAK-755 treatment given to control an acute TTP event when it happens (the "on-demand" cohort).

Conditions

Thrombotic Thrombocytopenic Purpura (TTP)

Keywords

Congenital Thrombotic Thrombocytopenic Purpura (TTP)

Outcome Measures

Primary Outcomes (1)

• Incidence of Related Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  TEAE: any adverse event emerging or manifesting at or after the initiation of treatment with TAK-755 or any existing adverse event that worsens in either intensity or frequency following exposure to TAK-755. SAE: Signs, symptoms or outcomes which results in death, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, results in a congenital abnormality/birth defect, or is an important medical event.

  Throughout the study period of approximately 6 years

Secondary Outcomes (38)

• Number of Acute Thrombotic Thrombocytopenic Purpura (TTP) Events in Participants with Congenital Thrombotic Thrombocytopenic Purpura (cTTP) Undergoing Prophylactic Treatment with TAK-755

  Up to approximately 3 years

• Incidence Rate of Acute TTP Events in Participants with cTTP Undergoing Prophylactic Treatment with TAK-755

  Up to approximately 3 years

• Number of Acute TTP Events Resolved After Treatment with TAK-755 while Enrolled in the Study

  Throughout the study period of approximately 6 years

• Proportion of Acute TTP Events Resolved After Treatment with TAK-755 while Enrolled in the Study

  Throughout the study period of approximately 6 years

• Incidence of Acute TTP Events while Participants are on Their Final Dose and Dosing Regimen

  Throughout the study period of approximately 6 years

Study Arms (2)

Prophylactic Cohort: TAK-755

EXPERIMENTAL

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.

Biological: TAK-755

On-Demand Cohort: TAK-755

EXPERIMENTAL

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.

Biological: TAK-755

Interventions

TAK-755 BIOLOGICAL

TAK-755 IV infusion

Also known as: rADAMTS13; recombinant ADAMTS13; SHP-655; BAX 930

On-Demand Cohort: TAK-755; Prophylactic Cohort: TAK-755

Eligibility Criteria

• Age: 0 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants who have completed TAK-755 Phase 3 pivotal Study 281102 (NCT03393975) in the prophylactic cohort and who meet all of the following criteria are eligible for this study:
• Participants or legally authorized representative has provided signed informed consent \>=18 years of age and/or assent form \<18 years of age.
• Participant 0 to 70 years of age at the time of screening of the 281102 (NCT03393975) study.
• Participant has been diagnosed with severe congenital ADAMTS-13 deficiency.
• Participant does not display any severe thrombotic thrombocytopenic purpura (TTP) signs (platelet count \<100,000/ microliter (mcL) and elevation of lactate dehydrogenase (LDH) greater than (\>) 2 × ULN at screening (prophylactic cohort only).
• Participants \>=16 years of age must have a Karnofsky score \>= 70% and participants \<16 years of age must have a Lansky score \>=80%.
• If female of childbearing potential, participant presents with a negative serum or urine pregnancy test confirmed not more than 7 days before the first IP administration and agrees to employ adequate birth control measures for the duration of the study and to undergo quarterly pregnancy testing.
• Sexually active males must use an accepted and effective method of contraception during the treatment and until a minimum of 16 days after the last dose administered.
• Participant is willing and able to comply with the requirements of the protocol.
• All naïve participants and non-naïve on-demand cohort participants:
• Naïve participants can only be enrolled in this continuation after enrollment of the adult participants in the prophylactic arm of TAK-755 Phase 3 pivotal study 281102 (NCT03393975) has been completed. Naïve pediatric participants can be enrolled after enrollment of the respective age cohort into the pivotal Phase 3 study 281102 (NCT03393975) has been completed. The following criteria also applies to participants who completed study 281101 (NCT02216084), but did not participate in 281102 (NCT03393975).
• Naïve participants and participants who were enrolled into the on-demand cohort of theTAK-755 Phase 3 pivotal study 281102 (NCT03393975) who meet ALL of the following criteria are eligible for this study:
• Participant is naïve or was enrolled into the on-demand cohort of the TAK-755 Phase 3 pivotal study 281102 (NCT03393975) for treatment of an acute TTP event but did not receive prophylactic treatment.
• Participant or legally authorized representative has provided signed informed consent (\>=18 years of age) and/or assent form (\<18 years of age).
• Participant is 0 to 70 years of age at the time of screening.

You may not qualify if:

• Participants who have completed TAK-755 Phase 3 pivotal study (281102) (NCT03393975) and naïve participants and non-naïve on-demand cohort participants and participants from an Expanded Access Program or participants in Study 281102 (NCT03393975) who had an allergic reaction to standard-of-care prophylactic treatment. The following criteria also applies to participants who completed study 281101 (NCT02216084), but did not participate in 281102 (NCT03393975).
• Participant has been diagnosed with any other TTP-like disorder (microangiopathic hemolytic anemia), including immune-mediated TTP.
• Known life-threatening hypersensitivity reaction, including anaphylaxis, to the parent molecule ADAMTS-13, hamster protein, or other constituents of TAK-755.
• Participant has a presence of a functional ADAMTS-13 inhibitor at screening.
• Participant has a medical history of a genetic or acquired immune deficiency that would interfere with the assessment of product immunogenicity, including participants who are human immunodeficiency virus-positive with an absolute cluster of differentiation 4 (CD4) count \< 200/ cubic millimeter (mm\^3) or who are receiving chronic immunosuppressive drugs.
• Participant has a history of significant neurological events, such as major stroke, indicating that a relapse might have severe consequences, as judged by the investigator.
• Participant has been diagnosed with severe cardiovascular disease (New York Heart Association classes 3 to 4).
• Participant with end stage renal disease requiring chronic dialysis.
• Participant has been diagnosed with hepatic dysfunction, as evidenced by, but not limited to, any of the following:
• Serum alanine aminotransferase \>= 2 × ULN
• Severe hypoalbuminemia \<24 gram per liter (g/L)
• Portal vein hypertension (e.g., presence of otherwise unexplained splenomegaly, history of esophageal varices).
• In the opinion of the investigator, the participant has another clinically significant concomitant disease that may pose additional risks for the participant.
• Participant has been treated with an immunomodulatory drug, excluding topical treatment (e.g., ointments, nasal sprays), within 30 days prior to enrollment. Use of corticosteroids in conjunction with administration of fresh frozen plasma to prevent allergic reactions is permitted.
• Participant has an acute illness (e.g., influenza, flu-like syndrome, allergic rhinitis/conjunctivitis, bronchial asthma) at the time of screening (prophylactic cohort only).

Sponsors & Collaborators

• Takeda: lead
• Takeda Development Center Americas, Inc.: collaborator
• Shire: collaborator

Study Sites (27)

Childrens Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14203, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Mid Ohio Heart Clinic Inc

Dublin, Ohio, 43017, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

AKH - Medizinische Universität Wien

Vienna, 1090, Austria

Location

Beijing Children's Hospital

Beijing, Beijing Municipality, 100045, China

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

Tongji Hospital Affiliated to Tongji Medicine University

Wuhan, Hubei, 430030, China

Location

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsushe, 215006, China

Location

Institute of Hematology and Hospital of Blood Disease

Tianjin, Tianjin Municipality, 300021, China

Location

Hôpital Necker - Enfants Malades

Paris, Paris, 75015, France

Location

CHU Saint Etienne - Hôpital Nord

Saint-Priest-en-Jarez Cedex, Pays de la Loire Region, 42270, France

Location

Hôpital Saint-Antoine

Paris, 75012, France

Location

Hôpital Robert Debré- Paris

Paris, 75935, France

Location

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Universitaetsklinikum Jena, Klinik fuerKinder-und Jugendmedizin

Jena, 07747, Germany

Location

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)

Bergamo, Hubei, 24127, Italy

Location

Kyushu University Hospital

Fukuoka, Fukuoka, 812-8582, Japan

Location

Hyogo College of Medicine Hospital

Nishinomiya, Hyōgo, 663-8501, Japan

Location

Medical Hospital,Tokyo Medical and Dental University

Bunkyo City, Tokyo, 113-8519, Japan

Location

Samodzielny Publiczny Dzieciecy Szpital Kliniczny

Warsaw, 02-091, Poland

Location

Instytut Hematologii i Transfuzjologii

Warsaw, 02-776, Poland

Location

Complejo Hospitalario Universitario A Coruña

A Coruña, La Coruña, 15006, Spain

Location

Hospital de Cruces

Barakaldo, Vizcaya, 48903, Spain

Location

Inselspital -Universitaetsspital Bern

Bern, 3010, Switzerland

Location

University College London Hospitals

London, Greater London, NW12PG, United Kingdom

Location

Related Links

• Click here for more information about this trial in easy-to-understand language, including a Plain Language Summary of the results if the trial has been completed.
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MeSH Terms

Conditions

Purpura, Thrombotic Thrombocytopenic

Interventions

ADAMTS13 protein, human

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Thrombophilia; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2020
• First Posted: December 24, 2020
• Study Start: April 14, 2021
• Primary Completion (Estimated): March 16, 2027
• Study Completion (Estimated): March 16, 2027
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

DE (2); US (5); AU (1); JP (3); FR (4); ES (2); IT (1); CN (5); CH (1); GB (1); PL (2)