A Phase 2b study of TAK-755 (rADAMTS13) with minimal to no plasma exchange in the treatment of patients with thrombotic thrombocytopenic Purpura.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Takeda Development Center Americas Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

27 Apr 2023 → 16 Apr 2026

Decision date (initial)

2024-09-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Takeda Development Center Americas, Inc.

External identifiers

EU CT number

2023-507787-39-00

EudraCT number

2022-001940-36

ClinicalTrials.gov

NCT05714969

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Safety, Pharmacokinetic

Assess the safety of TAK-755 in the treatment of iTTP

Secondary objectives 8

1. Assess the efficacy of TAK-755 in achieving clinical response with and without on-study PEX following an acute TTP event.
2. Assess treatment failures.
3. Assess the efficacy of TAK-755 in prevention of iTTP recurrence, exacerbation, and relapse (Part 1), or in prevention of recurrent thrombocytopenia (platelet levels <150,000/µL) requiring daily PEX or rescue therapy (Part 2).
4. Assess changes in organ damage biomarkers.
5. Evaluate the durability of clinical response (Part 1) or platelet response (Part 2).
6. Evaluate the ADAMTS13 antigen and activity over time.
7. Evaluate VWF antigen and activity over time.
8. Assess the efficacy of TAK-755 in achieving platelet response without on-study PEX following an acute iTTP event.

Conditions and MedDRA coding

Immune-mediated thrombotic thrombocytopenic purpura (iTTP)

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share 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.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

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 based on the following criteria: a. Thrombocytopenia [platelet count <100,000/μL]. b. Microangiopathic hemolytic anemia [elevation of LDH >2×ULN or by the presence or an increase of schistocytes in peripheral blood smear].
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.

Exclusion criteria 15

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 TMA, including: disseminated intravascular coagulation (DIC), disseminated malignancy, malignant hypertension, solid organ and hematopoietic stem cell transplantation, shiga toxin–related and atypical hemolytic uremic syndrome, drug toxicity (eg, gemcitabine, mitomycin C, clopidogrel) and pregnancy-related thrombocytopenia syndromes (eg, hemolysis, elevated liver enzymes and low platelets [HELLP]; eclampsia), serum creatinine >2.25 mg/dL, active cancer within the last year.
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 CD4+ count ≤200 cells/mm3 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 suffers from a mental condition rendering him/her unable to understand the nature, scope, and possible consequences of the study and/or evidence of an uncooperative attitude. However, a fully recognized medical proxy will be permitted to provide consent, under the circumstances that the participant is unable to provide consent due to the effects of iTTP.
12. Participant is pregnant or lactating
13. Participant is a family member or employee of the sponsor or investigator.
14. Participant has any condition in which methylprednisolone or other streroide equivalent is contraindicated as per prescribing information.
15. Participant has known life-threatening hypersensitivity reaction, including anaphylaxis, to the parent molecule ADAMTS13, CHO cell proteins, or other constituents of TAK-755.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of AEs, SAEs, and AESIs after receiving any dose of IP

Secondary endpoints 15

1. Achievement of clinical response without on-study PEX
2. Achievement of clinical response with on-study PEX
3. Time to clinical response
4. Occurrence of refractoriness
5. Time to first on-study PEX in participants who achieved clinical response.
6. Number of days of on-study PEX and total volume of plasma administered to achieve clinical response.
7. Occurrence of treatment failure (failure to achieve clinical response or experience iTTP recurrence).
8. Occurrence of iTTP recurrence (following clinical response), including exacerbation, or relapse
9. Time to iTTP recurrence (following clinical response), including, exacerbation, or relapse
10. 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.
11. 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.
12. Organ damage biomarkers change from baseline at (1) clinical response and (2) study completion • LDH • Troponin
13. Achievement of clinical remission (achievemnt of clinical response and no occurrence for ≥ 30 days).
14. ADAMTS13 antigen and activity levels resulting from TAK-755 administration in acute and post-acute phases
15. VWF antigen and activity levels resulting from TAK-755 administration in acute and post-acute phases.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Takeda Development Center Americas Inc.

Sponsor organisation

Takeda Development Center Americas Inc.

Address

500 Kendall Street

City

Cambridge

Postcode

02142-1108

Country

United States

Scientific contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Global Clinical Lead

Public contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Study Director Clinical Trial

Third parties 17

Locations

5 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 29 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications