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

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Takeda Contact; Phone Number: +1-877-825-3327; Email: medinfoUS@takeda.com

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Not yet recruiting
    • Hospital Universitario Austral
    • Contact: Site Contact; Phone Number: 541147085000; Email: emicarricondo@gmail.com
    • Principal Investigator: Silvio Ariel Emiliano Carricondo
  • Buenos Aires, Argentina
    • Not yet recruiting
    • Clinica Zabala
    • Contact: Site Contact; Phone Number: 5491162650104; Email: hhferro@gmail.com
    • Principal Investigator: Hugo Ferro
• Austria
  • Vienna, Austria
    • Recruiting
    • AKH- Medizinische Universitat Wien
    • Contact: Site Contact; Phone Number: 4314040044100; Email: paul.knobl@meduniwien.ac.at
    • Principal Investigator: Paul Knobl
• Greece
  • Athens, Greece
    • Recruiting
    • General Hospital of Athens Laiko
    • Contact: Site Contact; Phone Number: 302132060961; Email: ppanayi@med.uoa.gr
    • Principal Investigator: Panayiotis Panayiotidis
  • Patra, Greece
    • Recruiting
    • University Hospital of Patra
    • Contact: Site Contact; Phone Number: 302613603247; Email: argiris.symeonidis@yahoo.gr
    • Principal Investigator: Anargyros Symeoinidis
  • Thessaloniki, Greece
    • Recruiting
    • General Hospital of Thessaloniki "G. Papanikolaou"
    • Contact: Site Contact; Phone Number: 302313307533; Email: ioannamarilena@gmail.com
    • Principal Investigator: Ioanna Sakellari
• Italy
  • Milan, Italy
    • Recruiting
    • Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico
    • Principal Investigator: Flora Peyvandi
    • Contact: Site Contact; Phone Number: 390255035414; Email: flora.peyvandi@policlinico.mi.it
  • Torino, Italy
    • Recruiting
    • Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
    • Principal Investigator: Alessandra Borchiellini
    • Contact: Site Contact; Phone Number: 116335329; Email: aborchiellini@cittadeallasalute.to.it
• Poland
  • Warszawa, Poland
    • Not yet recruiting
    • Instytut Hematologii i Transfuzjologii
    • Principal Investigator: Jerzy Windyga
    • Contact: Site Contact; Phone Number: 482234961581; Email: jwindyga@ihit.waw.pl
• Spain
  • Barakaldo, Spain
    • Recruiting
    • Hospital De Cruces
    • Contact: Site Contact; Phone Number: 34946006000; Email: miriam.varapampliega@osakidetza.eus
    • Principal Investigator: Miriam Vara Pampliega
  • Madrid, Spain
    • Recruiting
    • Hospital General Universitario Gregorio Marañon
    • Contact: Site Contact; Phone Number: 34915868443; Email: crisizquierdo3@yahoo.es
    • Principal Investigator: Cristina Pascual Izquierdo
  • Sevilla, Spain
    • Recruiting
    • Hospital Universitario Virgen del Rocio
    • Principal Investigator: Maria Eva Mingot Castellano
    • Contact: Site Contact; Phone Number: 34955013260; Email: mariae.mingot.sspa@juntadeandalucia.es
  • Valencia, Spain
    • Recruiting
    • Hospital Universitari i Politecnic La Fe
    • Principal Investigator: Javier de la rubia
    • Contact: Site Contact; Phone Number: 34961245875; Email: delarubia_jav@gva.es
  • Valencia, Spain
    • Recruiting
    • Hospital Universitario Dr. Peset
    • Contact: Site Contact; Phone Number: 34963189168; Email: fernandez_migzar@gva.es
    • Principal Investigator: Miguel Fernandez Zarzoso
• United Kingdom
  • Liverpool, United Kingdom
    • Recruiting
    • Royal Liverpool University Hospital
    • Contact: Site Contact; Phone Number: 441517063397; Email: tina.dutt@liverpoolft.nhs.uk
    • Principal Investigator: Tina Dutt
• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • Recruiting
      • University of Florida Shands
      • Contact: Site Contact; Phone Number: 352-262-7165; Email: ZUMBEMS@medicine.efl.edu
      • Principal Investigator: Marc Zumberg
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Not yet recruiting
      • Brigham and Women's Hospital
      • Contact: Site Contact; Phone Number: 617-732-5840; Email: alanger@bwh.harvard.edu
      • Principal Investigator: Arielle Langer
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota
      • Principal Investigator: Marshall Mazepa
      • Contact: Site Contact; Phone Number: 612-626-0665; Email: mmazepa@umn.edu
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University if Minnesota Med CAR
      • Contact: Site Contact; Phone Number: 612-626-3757; Email: verce001@umn.edu
      • Principal Investigator: Gregory Vercellotti
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Rutgers University
      • Contact: Site Contact; Phone Number: 732-235-7678; Email: as2872@rwjms.rutgers.edu
      • Principal Investigator: Ashwin Sridharan
  • New York
    • New York, New York, United States, 10021
      • Recruiting
      • Weill Cornell Medical College New York Presbyterian Hospital
      • Principal Investigator: Maria De Sancho
      • Contact: Site Contact; Phone Number: 646-962-2065; Email: mtd2002@med.cornell.edu
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Principal Investigator: Thomas Ortel
      • Contact: Site Contact; Phone Number: 919-684-5350; Email: thomas.ortel@duke.edu
    • Greenville, North Carolina, United States, 27834
      • Recruiting
      • Leo Jenkins Cancer Center/ECU School of Medicine
      • Contact: Site Contact; Phone Number: 252-744-3556; Email: lilesd@ecu.edu
      • Principal Investigator: Darla Liles
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University
      • Contact: Site Contact; Phone Number: 614-293-2887; Email: spero.cataland@osumc.edu
      • Principal Investigator: Spero Cataland
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Not yet recruiting
      • University of Utah
      • Contact: Site Contact; Phone Number: 801-585-2626; Email: yazan.abou-ismail@hsc.utah.edu
      • Principal Investigator: Yazan Abou-Ismail
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Versiti Clinical Trials and Research Office
      • Contact: Site Contact; Phone Number: 414-937-6826; Email: lisakreuziger@versiti.org
      • Principal Investigator: Lisa Baumann Kreuziger

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria

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

1. Participant has received more than 2 pre-study PEX prior to randomization.
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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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: 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

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 thromboembolic events and treatment-related bleeding events.	Through study completion, approximately 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 (≥150,000/microliter [μL]) that is followed by a confirmatory platelet count of ≥150,000/μL 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
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
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
Time to Clinical Response (Acute Phase)		Through study completion, approximately 12 weeks
Occurrence of Refractoriness (Acute Phase)		Through study completion, approximately 12 weeks
Time to First On-Study PEX to Achieve Clinical Response		Through study completion, approximately 12 weeks
Number of Days of On-study PEX in Participants Who Achieved Clinical Response (Acute Phase)		Through study completion, approximately 12 weeks
Total Volume of Plasma Administered (Acute Phase)		Through study completion, approximately 12 weeks
Occurrence of Treatment Failure	Treatment failure is defined as failure to achieve or maintain clinical response, including refractory iTTP and recurrent iTTP.	Through study completion, approximately 12 weeks
Occurrence of Immune-Mediated Thrombotic Thrombocytopenic Purpura (iTTP) Recurrence, 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
Time to iTTP Recurrence, Exacerbation, or Relapse		Through study completion, approximately 12 weeks
Occurrence of any one of the following events: Clinical Recurrence, iTTP-Related Death, or Major Thromboembolic Event From Time of First IP Administration Through Study Completion		Through study completion, approximately 12 weeks
Time to Occurrence of Any One of the Following Events: Clinical Recurrence, iTTP-Related Death, or Major Thromboembolic Event From Time of First IP Administration Through Study Completion		Through study completion, approximately 12 weeks
Change From Baseline in Lactate Dehydrogenase [LDH] Levels at Clinical Response and Study Completion		Through study completion, approximately 12 weeks
Change From Baseline in Troponin Levels at Clinical Response and Study Completion		Through study completion, approximately 12 weeks
Achievement of Clinical Remission	Clinical remission is defined as achieving and maintaining clinical response for ≥30 days.	Through study completion, approximately 12 weeks
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
ADAMTS13 Activity Level Resulting From TAK-755 Administration in Acute and Post-Acute Phases		Through study completion, approximately 12 weeks
Von Willebrand Factor (VWF) Antigen Level Resulting From TAK-755 Administration in Acute and Post-Acute Phases		Through study completion, approximately 12 weeks
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

• To obtain more information on the study, click here/on this link.

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2023
• Primary Completion (Estimated): March 15, 2025
• Study Completion (Estimated): March 15, 2025

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): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Drug Therapy; Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP)
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Hematologic Diseases; Hemorrhage; Blood Coagulation Disorders; Skin Manifestations; Thrombocytopenia; Blood Platelet Disorders; Thrombophilia; Thrombotic Microangiopathies; Cytopenia; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombotic Thrombocytopenic
• Other Study ID Numbers: TAK-755-2001; 2022-001940-36 (EudraCT Number)

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