A Study of TAK-755 (rADAMTS13) With Little to No Plasma Exchange (PEX) Treatment in Adults With Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP)

A Phase 2b, Multicenter, Randomized, Double-blind Study of Safety and Efficacy of TAK-755 (rADAMTS13) With Minimal to No Plasma Exchange (PEX) in the Treatment of Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP)

This is a study of TAK-755 in adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP). 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 the study. Participants who have an acute attack of iTTP will receive TAK-755 and immunosuppressive therapy during their stay at the hospital until they achieve a clinical response in Part 1 or platelet response in Part 2. Participants will also be treated with TAK-755 for an additional time of up to 6 weeks after the acute phase. In total, participants will stay in the study for approximately 3 months.

Study Overview

• Status: Completed
• Conditions: Thrombotic Thrombocytopenic Purpura (TTP)
• Intervention / Treatment: Biological: TAK-755

Detailed Description

This study consists of 2-parts. Part 1 is a double-blind, randomized study in which participants were randomized 1:1, in a blinded fashion, into 2 TAK-755 dose groups. Part 1, randomization was stratified based on whether the participant had received pre-study PEX and on the participant's Glasgow Coma Scale. Part 2 is an open-label study in which participants with iTTP experiencing an acute iTTP episode will be enrolled and assigned to a single-arm treatment.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Akh - Medizinische Universität Wien
• Greece
  • Thessaloniki, Greece, 57010
    • General Hospital of Thessaloniki "G. Papanikolaou"
• Italy
  • Milan, Italy, 20122
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Torino, Italy, 10126
    • Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
• Spain
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
  • Sevilla
    • Seville, Sevilla, Spain, 41010
      • Hospital Universitario Virgen del Rocio
  • Vizcaya
    • Barakaldo, Vizcaya, Spain, 48903
      • Hospital de Cruces
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, NW1 2PG
      • University College London Hospital
  • Merseyside
    • Liverpool, Merseyside, United Kingdom, L7 8XP
      • Royal Liverpool University Hospital
• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida - Shands
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Clinical Research Unit
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers University
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Greenville, North Carolina, United States, 27858
      • Leo Jenkins Cancer Center/ECU School of Medicine
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Health Sciences Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Versiti Wisconsin, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria (Part 1 and Part 2)

1. Participant must provide a signed informed consent form. A fully recognized proxy may be used per local laws for participants unable to provide consent.
2. Participant is 18 years or older at time of screening.
3. Participant has been diagnosed with de novo or relapsed iTTP.
4. Participant must be willing to fully comply with study procedures and requirements.
5. Female participants of childbearing potential must present with a negative pregnancy test and agree to employ highly effective birth control measures for duration of study. Sexually active male participants must agree to use an effective method of contraception for the duration of the study.

Key Exclusion Criteria (Part 1 and Part 2)

1. Participant has received more than 2 pre-study PEX prior to randomization in Part 1 or first dose of investigational product in Part 2.
2. Participant has been diagnosed with cTTP or another cause of thrombotic microangiopathy (TMA).
3. Participant has been exposed to another investigational product within 30 days prior to enrollment or is scheduled to participate in another clinical study involving investigational product or investigational device during the course of the study.
4. Participant has received caplacizumab within 30 days prior to study enrollment.
5. Participant has had a previous iTTP event within the past 30 days.
6. Participant is positive for human immunodeficiency virus (HIV) with unstable disease or cluster of differentiation (CD)4+ count ≤200 cells/mm^3 within 3 months of screening.
7. Participant has condition of severe immunodeficiency.
8. Participant has a severe systemic acute infection.
9. Participant has another underlying progressive fatal disease and/or life expectancy <3 months.
10. Participant is identified by the investigator as being unable or unwilling to cooperate with study procedures.
11. Participant is pregnant or lactating.
12. Participant has any condition in which methylprednisolone or other steroid equivalent is contraindicated as per prescribing information.
13. Participant has known life-threatening hypersensitivity reaction, including anaphylaxis, to the parent molecule ADAMTS13, Chinese hamster ovary (CHO) cell proteins, or other constituents of TAK-755.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: TAK-755 Dose 1 in Acute Phase and Dose 2 in Post-acute Phase; 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.	Biological: TAK-755; TAK-755 IV infusion; Other Names: rADAMTS13; SHP-655; recombinant ADAMTS13; BAX 930
Experimental: Part 1: TAK-755 Dose 2 in Both Acute and Post-Acute Phase; 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.	Biological: TAK-755; TAK-755 IV infusion; Other Names: rADAMTS13; SHP-655; recombinant ADAMTS13; BAX 930
Experimental: Part 2: TAK-755 Dose 3 in Acute Phase and Dose 2 in Post-acute Phase; 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.	Biological: TAK-755; TAK-755 IV infusion; Other Names: rADAMTS13; SHP-655; recombinant ADAMTS13; BAX 930

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Event of Special Interest (AESIs) After Receiving any Dose of Investigational Product (IP)	An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. 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. Adverse events of special interest include major thrombotic events and treatment-related bleeding events.	Through study completion, approximately 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Achievement of Clinical Response Without On-Study Plasma Exchange (PEX)	Clinical response is defined as normalization of platelets and no clinical evidence of new or progressive ischemic organ injury. Normalization of platelets: First occurrence of normal platelet count (greater than or equal to [>=]150,000/microliter [mcL]) that is followed by a confirmatory platelet count of >=150,000/mcL and a lactate dehydrogenase (LDH) <1.5×upper limit of normal (ULN) at 48±12 hours after the first occurrence.	Through study completion, approximately 12 weeks
Part 2: Achievement of Platelet Response Without On-Study Plasma Exchange (PEX)	Platelet response is defined as first occurrence of normal platelet count (>=150,000/mcL) that is followed by a confirmatory platelet count of >=150,000/mcL at 48±12 hours after the first occurrence.	Through study completion, approximately 12 weeks
Part 1: Achievement of Clinical Response With Zero or Minimal on-Study PEX	The number of PEX administered considered Zero when no PEX is administered and considered Minimal when 1 to 3 PEX are administered.	Through study completion, approximately 12 weeks
Part 2: Achievement of Platelet Response With Zero or Minimal on-Study PEX	The number of PEX administered considered Zero when no PEX is administered and considered Minimal when 1 to 3 PEX are administered.	Through study completion, approximately 12 weeks
Part 1: Achievement of Clinical Response Overall	Overall indicates clinical response regardless of whether on-study PEX is administered, or the number of PEX administered.	Through study completion, approximately 12 weeks
Part 2: Achievement of Platelet Response Overall	Overall indicates platelet response regardless of whether on-study PEX is administered, or the number of PEX administered.	Through study completion, approximately 12 weeks
Part 1: Time to Clinical Response (Acute Phase)		Through study completion, approximately 12 weeks
Part 2: Time to Platelet Response (Acute Phase)		Through study completion, approximately 12 weeks
Part 1: Occurrence of Refractoriness (Acute Phase)		Through study completion, approximately 12 weeks
Part 1: Time to First On-Study PEX in Participants who Achieved Clinical Response		Through study completion, approximately 12 weeks
Part 2: Time to First On-Study PEX in Participants who Achieved Platelet Response		Through study completion, approximately 12 weeks
Part 1: Number of Days of On-study PEX in Participants to Achieve Clinical Response (Acute Phase)		Through study completion, approximately 12 weeks
Part 2: Number of Days of On-study PEX in Participants to Achieve Platelet Response (Acute Phase)		Through study completion, approximately 12 weeks
Part 1: Total Volume of Plasma Administered (Acute Phase) to Achieve Clinical Response		Through study completion, approximately 12 weeks
Part 2: Total Volume of Plasma Administered (Acute Phase) to Achieve Platelet Response		Through study completion, approximately 12 weeks
Part 1: Occurrence of Treatment Failure	Treatment failure is defined as failure to achieve clinical response, or experience iTTP recurrence.	Through study completion, approximately 12 weeks
Part 2: Occurrence of Treatment Failure	Treatment failure is defined as failure to achieve platelet response, or experience iTTP recurrence.	Through study completion, approximately 12 weeks
Part 1: Occurrence of Immune-Mediated Thrombotic Thrombocytopenic Purpura (iTTP) Recurrence (Following Clinical Response), Exacerbation, or Relapse (Post-acute Phase)	iTTP recurrence comprised of exacerbation or relapse. Clinical exacerbation: Occurs <30 days after achieving initial clinical response (i.e., before clinical remission) and recurrent thrombocytopenia (platelet levels <150,000/μL), with or without clinical evidence of new or progressive ischemic organ damage, requiring daily PEX or rescue therapy. Clinical relapses: Occurs >=30 days after achieving initial clinical response (i.e., after clinical remission) and recurrent thrombocytopenia (platelet levels <150,000/μL), with or without clinical evidence of new or progressive ischemic organ damage, requiring daily PEX or rescue therapy.	Through study completion, approximately 12 weeks
Part 2: Occurrence of iTTP Recurrence (Following Platelet Response), Exacerbation, or Relapse (Post-acute Phase)	iTTP recurrence comprised of exacerbation or relapse. Clinical exacerbation: Occurs <30 days after achieving initial platelet response (i.e., before clinical remission) and recurrent thrombocytopenia (platelet levels <150,000/μL), with or without clinical evidence of new or progressive ischemic organ damage, requiring daily PEX or rescue therapy. Clinical relapses: Occurs >=30 days after achieving initial platelet response (i.e., after clinical remission) and recurrent thrombocytopenia (platelet levels <150,000/μL), with or without clinical evidence of new or progressive ischemic organ damage, requiring daily PEX or rescue therapy.	Through study completion, approximately 12 weeks
Part 1: Time to iTTP Recurrence (Following Clinical Response), Exacerbation, or Relapse		Through study completion, approximately 12 weeks
Part 2: Time to iTTP Recurrence (Following Platelet Response), Exacerbation, or Relapse		Through study completion, approximately 12 weeks
Part 1: Occurrence of Any One of the Following Events: Clinical Recurrence (Following Clinical Response), iTTP-Related Death, or Major Thrombotic Event From Time of First IP Administration Through Study Completion		Through study completion, approximately 12 weeks
Part 2: Occurrence of Any One of the Following Events: Clinical Recurrence (Following Platelet Response), iTTP-Related Death, or Major Thrombotic Event From Time of First IP Administration Through Study Completion		Through study completion, approximately 12 weeks
Part 1: Time to Occurrence of Any One of the Following Events: Clinical Recurrence (Following Clinical Response), iTTP-Related Death, or Major Thrombotic Event From Time of First IP Administration Through Study Completion		Through study completion, approximately 12 weeks
Part 2: Time to Occurrence of Any One of the Following Events: Clinical Recurrence (Following Platelet Response), iTTP-Related Death, or Major Thrombotic Event From Time of First IP Administration Through Study Completion		Through study completion, approximately 12 weeks
Part 1: Change From Baseline in Lactate Dehydrogenase [LDH] Levels at Clinical Response and Study Completion		Through study completion, approximately 12 weeks
Part 2: Change From Baseline in LDH Levels at Platelet Response and Study Completion		Through study completion, approximately 12 weeks
Part 1: Change From Baseline in Troponin Levels at Clinical Response and Study Completion		Through study completion, approximately 12 weeks
Part 2: Change From Baseline in Troponin Levels at Platelet Response and Study Completion		Through study completion, approximately 12 weeks
Part 1: Achievement of Clinical Remission	Clinical remission is defined as achieving clinical response and no recurrence for >=30 days.	Through study completion, approximately 12 weeks
Part 2: Achievement of Clinical Remission	Clinical remission is defined as achieving platelet response and no recurrence for >=30 days.	Through study completion, approximately 12 weeks
Part 1 and 2: A Disintegrin and Metalloproteinase With Thrombospondin Motifs 13 (ADAMTS13) Antigen Level Resulting From TAK-755 Administration in Acute and Post-Acute Phases		Through study completion, approximately 12 weeks
Part 1 and 2: ADAMTS13 Activity Level Resulting From TAK-755 Administration in Acute and Post-Acute Phases		Through study completion, approximately 12 weeks
Part 1: Von Willebrand Factor (VWF) Antigen Level Resulting From TAK-755 Administration in Acute and Post-Acute Phases		Through study completion, approximately 12 weeks
Part 1: VWF Activity Level Resulting From TAK-755 Administration in Acute and Post-Acute Phases		Through study completion, approximately 12 weeks

Collaborators and Investigators

• Sponsor: Takeda
• Collaborators: Takeda Development Center Americas, Inc.
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• Click here to ask Takeda's chatbot for comprehensive and easy-to-understand information about clinical trials - even across products and indications - in your local language.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2023
• Primary Completion (Actual): April 16, 2026
• Study Completion (Actual): April 16, 2026

Study Registration Dates

• First Submitted: January 24, 2023
• First Submitted That Met QC Criteria: January 24, 2023
• First Posted (Actual): February 6, 2023

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Drug Therapy; Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP)
• Additional Relevant MeSH Terms: Cytopenia; Pathologic Processes; Hemorrhage; Skin Manifestations; Hematologic Diseases; Blood Coagulation Disorders; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Thrombocytopenia; Thrombophilia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hemic and Lymphatic Diseases; Purpura, Thrombotic Thrombocytopenic; ADAMTS13 protein, human
• Other Study ID Numbers: TAK-755-2001; 2023-507787-39-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Time Frame: NOTE: IPD Sharing Time Frame has not been entered.
• IPD Sharing 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
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No