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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Thrombotic Thrombocytopenic Purpura (TTP)

Intervention / Treatment
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* Biological: TAK-755


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria 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. Key Exclusion Criteria Participant has received more than 2 pre-study PEX prior to randomization. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAK-755 Dose 1 in Acute Phase and Dose 2 in Post-acute Phase<br>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<br>* TAK-755 IV infusion<br>* Other names: BAX 930;|
| Experimental: TAK-755 Dose 2 in Both Acute and Post-Acute Phase<br>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<br>* TAK-755 IV infusion<br>* Other names: BAX 930;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Therapy, Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP)