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)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 29
- 试验地点
- 36
- 主要终点
- Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Event of Special Interest (AESIs) After Receiving any Dose of Investigational Product (IP)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Part 1 is double-blind, randomization and Part 2 is open-label, single-arm.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(Part 1 and Part 2)
- •Participant must provide a signed informed consent form. A fully recognized proxy may be used per local laws for participants unable to provide consent.
- •Participant is 18 years or older at time of screening.
- •Participant has been diagnosed with de novo or relapsed iTTP.
- •Participant must be willing to fully comply with study procedures and requirements.
- •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.
排除标准
- •(Part 1 and Part 2)
- •Participant has received more than 2 pre-study PEX prior to randomization in Part 1 or first dose of investigational product in Part
- •Participant has been diagnosed with cTTP or another cause of thrombotic microangiopathy (TMA).
- •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.
- •Participant has received caplacizumab within 30 days prior to study enrollment.
- •Participant has had a previous iTTP event within the past 30 days.
- •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.
- •Participant has condition of severe immunodeficiency.
- •Participant has a severe systemic acute infection.
- •Participant has another underlying progressive fatal disease and/or life expectancy <3 months.
- •Participant is identified by the investigator as being unable or unwilling to cooperate with study procedures.
- •Participant is pregnant or lactating.
- •Participant has any condition in which methylprednisolone or other steroid equivalent is contraindicated as per prescribing information.
- •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.
研究组 & 干预措施
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.
干预措施: TAK-755 (Biological)
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.
干预措施: TAK-755 (Biological)
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.
干预措施: TAK-755 (Biological)
结局指标
主要结局
Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Event of Special Interest (AESIs) After Receiving any Dose of Investigational Product (IP)
时间窗: Through study completion, approximately 12 weeks
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.
次要结局
- Part 2: Time to Platelet Response (Acute Phase)(Through study completion, approximately 12 weeks)
- Part 1: Achievement of Clinical Response Without On-Study Plasma Exchange (PEX)(Through study completion, approximately 12 weeks)
- Part 2: Achievement of Platelet Response Without On-Study Plasma Exchange (PEX)(Through study completion, approximately 12 weeks)
- Part 1: Achievement of Clinical Response With Zero or Minimal on-Study PEX(Through study completion, approximately 12 weeks)
- Part 2: Achievement of Platelet Response With Zero or Minimal on-Study PEX(Through study completion, approximately 12 weeks)
- Part 1: Achievement of Clinical Response Overall(Through study completion, approximately 12 weeks)
- Part 2: Achievement of Platelet Response Overall(Through study completion, approximately 12 weeks)
- Part 1: Time to Clinical 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(Through study completion, approximately 12 weeks)
- Part 2: Occurrence of Treatment Failure(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)(Through study completion, approximately 12 weeks)
- Part 2: Occurrence of iTTP Recurrence (Following Platelet Response), Exacerbation, or Relapse (Post-acute Phase)(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(Through study completion, approximately 12 weeks)
- Part 2: Achievement of Clinical Remission(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)