Clinical trial NCT05714969: A Study of TAK-755 (rADAMTS13) With Little to No Plasma Exchange (PEX) Treatment in Adults With Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Thrombotic Thrombocytopenic Purpura (TTP)
Keywords: Drug Therapy
Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP)
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Takeda Development Center Americas, Inc.
First posted: 2023-02-06
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Event of Special Interest (AESIs) After Receiving any Dose of Investigational Product (IP)
timeFrame: Through study completion, approximately 12 weeks
Secondary outcomes:
measure: Part 1: Achievement of Clinical Response Without On-Study Plasma Exchange (PEX)
timeFrame: Through study completion, approximately 12 weeks
measure: Part 2: Achievement of Platelet Response Without On-Study Plasma Exchange (PEX)
timeFrame: Through study completion, approximately 12 weeks
measure: Part 1: Achievement of Clinical Response With Zero or Minimal on-Study PEX
timeFrame: Through study completion, approximately 12 weeks
measure: Part 2: Achievement of Platelet Response With Zero or Minimal on-Study PEX
timeFrame: Through study completion, approximately 12 weeks
measure: Part 1: Achievement of Clinical Response Overall
timeFrame: Through study completion, approximately 12 weeks
measure: Part 2: Achievement of Platelet Response Overall
timeFrame: Through study completion, approximately 12 weeks
measure: Part 1: Time to Clinical Response (Acute Phase)
timeFrame: Through study completion, approximately 12 weeks
measure: Part 2: Time to Platelet Response (Acute Phase)
timeFrame: Through study completion, approximately 12 weeks
measure: Part 1: Occurrence of Refractoriness (Acute Phase)
timeFrame: Through study completion, approximately 12 weeks
measure: Part 1: Time to First On-Study PEX in Participants who Achieved Clinical Response
timeFrame: Through study completion, approximately 12 weeks
measure: Part 2: Time to First On-Study PEX in Participants who Achieved Platelet Response
timeFrame: Through study completion, approximately 12 weeks
measure: Part 1: Number of Days of On-study PEX in Participants to Achieve Clinical Response (Acute Phase)
timeFrame: Through study completion, approximately 12 weeks
measure: Part 2: Number of Days of On-study PEX in Participants to Achieve Platelet Response (Acute Phase)
timeFrame: Through study completion, approximately 12 weeks
measure: Part 1: Total Volume of Plasma Administered (Acute Phase) to Achieve Clinical Response
timeFrame: Through study completion, approximately 12 weeks
measure: Part 2: Total Volume of Plasma Administered (Acute Phase) to Achieve Platelet Response
timeFrame: Through study completion, approximately 12 weeks
measure: Part 1: Occurrence of Treatment Failure
timeFrame: Through study completion, approximately 12 weeks
measure: Part 2: Occurrence of Treatment Failure
timeFrame: Through study completion, approximately 12 weeks
measure: Part 1: Occurrence of Immune-Mediated Thrombotic Thrombocytopenic Purpura (iTTP) Recurrence (Following Clinical Response), Exacerbation, or Relapse (Post-acute Phase)
timeFrame: Through study completion, approximately 12 weeks
measure: Part 2: Occurrence of iTTP Recurrence (Following Platelet Response), Exacerbation, or Relapse (Post-acute Phase)
timeFrame: Through study completion, approximately 12 weeks
measure: Part 1: Time to iTTP Recurrence (Following Clinical Response), Exacerbation, or Relapse
timeFrame: Through study completion, approximately 12 weeks
measure: Part 2: Time to iTTP Recurrence (Following Platelet Response), Exacerbation, or Relapse
timeFrame: Through study completion, approximately 12 weeks
measure: 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
timeFrame: Through study completion, approximately 12 weeks
measure: 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
timeFrame: Through study completion, approximately 12 weeks
measure: 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
timeFrame: Through study completion, approximately 12 weeks
measure: 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
timeFrame: Through study completion, approximately 12 weeks
measure: Part 1: Change From Baseline in Lactate Dehydrogenase [LDH] Levels at Clinical Response and Study Completion
timeFrame: Through study completion, approximately 12 weeks
measure: Part 2: Change From Baseline in LDH Levels at Platelet Response and Study Completion
timeFrame: Through study completion, approximately 12 weeks
measure: Part 1: Change From Baseline in Troponin Levels at Clinical Response and Study Completion
timeFrame: Through study completion, approximately 12 weeks
measure: Part 2: Change From Baseline in Troponin Levels at Platelet Response and Study Completion
timeFrame: Through study completion, approximately 12 weeks
measure: Part 1: Achievement of Clinical Remission
timeFrame: Through study completion, approximately 12 weeks
measure: Part 2: Achievement of Clinical Remission
timeFrame: Through study completion, approximately 12 weeks
measure: 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
timeFrame: Through study completion, approximately 12 weeks
measure: Part 1 and 2: ADAMTS13 Activity Level Resulting From TAK-755 Administration in Acute and Post-Acute Phases
timeFrame: Through study completion, approximately 12 weeks
measure: Part 1: Von Willebrand Factor (VWF) Antigen Level Resulting From TAK-755 Administration in Acute and Post-Acute Phases
timeFrame: Through study completion, approximately 12 weeks
measure: Part 1: VWF Activity Level Resulting From TAK-755 Administration in Acute and Post-Acute Phases
timeFrame: Through study completion, approximately 12 weeks
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida Shands
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: New Brunswick
country: United States
facility: Rutgers University
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medical College New York Presbyterian Hospital
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greenville
country: United States
facility: Leo Jenkins Cancer Center/ECU School of Medicine
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Milwaukee
country: United States
facility: Versiti Clinical Trials and Research Office
state: Wisconsin
city: Vienna
country: Austria
facility: AKH- Medizinische Universitat Wien
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki "G. Papanikolaou"
city: Milan
country: Italy
facility: Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
city: Torino
country: Italy
facility: Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza di Torino
city: Barakaldo
country: Spain
facility: Hospital de Cruces
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: University College London Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: