immune-mediated thrombotic thrombocytopenic purpura (iTTP) MedDRA version: 20.0 Level: SOC Classification code 10005329 Term: Blood and lymphatic system disorders System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Product Name: Recombinant A Disintegrin And Metalloproteinase with Thrombospondin Type-1 Motifs 13 (rADAMTS13)
Product Code: TAK-755
Pharmaceutical Form: Powder and solvent for solution for injecti
Sponsors
Takeda Development Center Americas, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject must provide a signed informed consent form. A fully recognized proxy may be used per local laws for subjects unable to provide consent. 2. Subject is 18 years or older at time of screening. 3. Subject has been diagnosed with de novo or relapsed iTTP based on the following criteria: a. Thrombocytopenia [platelet count 2×ULN or by the presence or an increase of schistocytes in peripheral blood smear]. 4. Subject must be willing to fully comply with study procedures and requirements. 5. Female subjects 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 subjects must agree to use an effective method of contraception for the duration of the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 35 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. Subject has received more than 2 pre-study PEX prior to randomization. 2. Subject 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. Subject 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. Subject has received caplacizumab within 30 days prior to study enrollment. 5. Subject has had a previous iTTP event within the past 30 days. 6. Subject is positive for human immunodeficiency virus (HIV) with unstable disease or CD4+ count =200 cells/mm3 within 3 months of screening. 7. Subject has condition of severe immunodeficiency. 8. Subject has a severe systemic acute infection. 9. Subject has another underlying progressive fatal disease and/or life expectancy <3 months. 10. Subject is identified by the investigator as being unable or unwilling to cooperate with study procedures. 11. Subject 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 subject is unable to provide consent due to the effects of iTTP. 12. Subject is pregnant or lactating. 13. Subject is a family member or employee of the sponsor or investigator. 14. Subject has any condition in which methylprednisolone or other streroide equivalent is contraindicated as per prescribing information. 15.Subject has known life-threatening hypersensitivity reaction, including anaphylaxis, to the parent molecule ADAMTS13, CHO cell proteins, or other constituents of TAK-755.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assess the safety of TAK-755 in the treatment of iTTP;Secondary Objective: 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. 4. Assess changes in organ damage biomarkers. 5. Evaluate the durability of clinical response. 6. Evaluate the ADAMTS13 antigen and activity over time. 7. Evaluate VWF antigen and activity over time. ;Primary end point(s): Incidence of AEs, SAEs, and AESIs after receiving any dose of IP;Timepoint(s) of evaluation of this end point: Variable time point | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 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 subjects who achieved clinical response. 6.Number of days of PEX and total volume of plasma administered. 7.Occurrence of treatment failure. 8.Occurrence of iTTP recurrence, exacerbation, or relapse. 9.Time to iTTP recurrence, exacerbation, or relapse. 10.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. 11.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. 12.Organ damage biomarkers change from baseline at (1) clinical response and (2) study completion • LDH • Troponin 13.Achievement of clinical remission (maintaining clinical response 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.;Timepoint(s) of evaluation of this end point: Variable time points | — |
Countries
Argentina, Austria, Canada, France, Germany, Greece, Israel, Italy, Poland, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactStudy Director
Takeda Development Center Americas, Inc.
Outcome results
None listed