Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
Register:
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EUCTR |
Last refreshed on:
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6 November 2023 |
Main ID: |
EUCTR2018-003775-35-IT |
Date of registration:
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29/01/2021 |
Prospective Registration:
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No |
Primary sponsor: |
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Public title:
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A Phase 2, randomized, placebo-controlled, double-blind study of rADAMTS-13 (SHP655) in the treatment of patients with aTTP
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Scientific title:
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A Phase 2, multicenter, randomized, placebo-controlled, double-blind study in patients with acquired thrombotic thrombocytopenic purpura (aTTP) to evaluate the pharmacokinetics, safety, and efficacy of rADAMTS-13 (SHP655) administered in addition to standard of care (SoC) treatment - na |
Date of first enrolment:
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21/02/2020 |
Target sample size:
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33 |
Recruitment status: |
Not Recruiting |
URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-003775-35 |
Study type:
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Interventional clinical trial of medicinal product |
Study design:
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Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): yes
Therapeutic confirmatory - (Phase III): no
Therapeutic use (Phase IV): no
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Countries of recruitment
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Canada
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France
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Germany
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Italy
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Netherlands
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Spain
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Switzerland
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United Kingdom
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United States
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Contacts
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Name:
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Archana Savla
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Address:
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650 East Kenadall Street,
MA 02191
Cambridge
United States |
Telephone:
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000000 |
Email:
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archana.savla@takeda.com |
Affiliation:
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Baxalta US Inc. |
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Name:
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Archana Savla
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Address:
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650 East Kenadall Street,
MA 02191
Cambridge
United States |
Telephone:
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000000 |
Email:
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archana.savla@takeda.com |
Affiliation:
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Baxalta US Inc. |
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Key inclusion & exclusion criteria
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Inclusion criteria: 1. Subject or legally authorized representative voluntarily signs informed consent. For subjects unable to provide consent, a fully recognized medical proxy may be used according to local laws.
2. Subject is 18 to 75 years old at the time of screening.
3. Subject has been diagnosed with primary or secondary autoimmune aTTP based on the following criteria:
a. Thrombocytopenia [drop in platelet count =50% or platelet count < 100,000/µL];
¿ No more than 3 subjects per arm may be enrolled with a screening platelet count =50,000/ µL.
b. Microangiopathic hemolytic anemia [elevation of lactate dehydrogenase (LDH) >2-fold or by presence or increase of schistocytes in peripheral blood smear].
4. Willingness to fully comply with study procedures and requirements, and intention to initiate plasma exchange (PEX). Subjects may be provisionally entered into the trial and undergo randomization pending the results of the ADAMTS-13 activity, anti-ADAMTS-13 antibody, and genetic testing for cTTP.
5. If female of childbearing potential, subject presents with a negative pregnancy test and agrees to employ adequate birth control measures for the duration of the study. Sexually active males must use an accepted and effective method of contraception during the treatment and until a minimum of 16 days after the last dose administered. 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 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 3
Exclusion criteria: 1. Subject has been diagnosed with congenital TTP.
2. Subject has plasma ADAMTS-13 activity> 10% of normal.
3. Subject has been diagnosed with another cause of thrombotic microangiopathy (TMA) including: DIC, disseminated malignancy, malignant hypertension, hematopoietic stem cell transplantation, shiga toxin-related
and atypical HUS, drug toxicity (e.g. gemcitabine, mitomycin C, clopidogrel) and pregnancy-related thrombocytopenia syndromes (e.g. HELLP, eclampsia).
4. Subject has been exposed to another IP within 30 days prior to enrollment or is scheduled to participate in another clinical study involving IP or investigational device during the course of the study.
5. Subject has received caplacizumab within 3 months of study enrollment.
6. Subject is human immunodeficiency virus positive (HIV+) with unstable disease or CD4+ count =200 cells/mm3 within 3 months screening.
7. Subject has had a previous aTTP event in the past 30 days.
8. Subject has another underlying progressive fatal disease and/or life expectancy of less than 3 months.
9. Subject is identified by the investigator as being unable or unwilling to cooperate with study procedures.
10. 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.
11. If female, subject is pregnant or lactating.
12. Subject is a family member or employee of the Sponsor or investigator.
13. Any contraindication to PEX, methylprednisolone and/or rituximab as per prescribing information.
Age minimum:
Age maximum:
Gender:
Female: yes Male: yes
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Health Condition(s) or Problem(s) studied
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acquired thrombotic thrombocytopenic purpura (aTTP) MedDRA version: 20.0
Level: PT
Classification code 10043648
Term: Thrombotic thrombocytopenic purpura
System Organ Class: 10005329 - Blood and lymphatic system disorders
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Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
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Intervention(s)
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Product Name: Recombinant A Disintegrin And Metalloproteinase with Thrombospondin Type-1 Motifs 13 (rADAMTS13) Product Code: [SHP 655 (BAX 930)] Pharmaceutical Form: Powder and solvent for solution for injection INN or Proposed INN: apadamtase alfa Current Sponsor code: SHP655 Other descriptive name: BAX930 - RECOMBINANT HUMAN ADAMTS13 Concentration unit: IU international unit(s) Concentration type: equal Concentration number: 500- Pharmaceutical form of the placebo: Solution for infusion Route of administration of the placebo: Intravenous use
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Primary Outcome(s)
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Secondary Objective: PK/PD Objectives 1. Evaluate changes in levels of ADAMTS-13 binding and inhibitory autoantibodies in response to daily PEX, with or without SHP655 supplementation, during the acute episode and up to 30 days after the resolution of the TTP episode
2. Evaluate ADAMTS-13 activity levels in subjects up to 30 days after TTP episode remission
3. Specify dose(s) of SHP655 needed to achieve and maintain adequate plasma levels of rADAMTS-13
Safety/Efficacy Objectives 1. Assess the safety and immunogenicity of two regimens of SHP655 supplementation administered during an acute TTP episode in subjects undergoing PEX treatment and immunosuppressant therapy
2. Evaluate the occurrences of aTTP related complications, aTTP relapses, exacerbations and end-organ function improvement
3. Evaluate the time to aTTP related complications, aTTP relapses, exacerbations and end-organ function improvement
4. Evaluate the occurrence of procedure related adverse events
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Timepoint(s) of evaluation of this end point: Various time points throughout the study
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Primary end point(s): 1. ADAMTS-13 activity levels 2. Platelet count and LDH levels
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Main Objective: Co-Primary: 1. Assess the PK of ADAMTS-13 in aTTP subjects treated for an acute episode by daily plasma exchange (PEX), immunosuppressant therapy, with or without SHP655 supplementation 2. Study the PK/PD relationship between ADAMTS-13 levels and pathophysiological biomarkers, as well as clinical efficacy parameters
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Secondary Outcome(s)
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Timepoint(s) of evaluation of this end point: Various time points throughout the study
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Secondary end point(s): PK/PD Endpoints
1. The PK/PD temporal relationship of efficacy parameters (e.g., platelet count, LDH levels), as a function of ADAMTS-13 activity
2. The ADAMTS-13 binding and inhibitory autoantibody levels in response to daily PEX, with or without SHP655 supplementation, during the acute TTP episode and up to 30 days after resolution
3. ADAMTS-13 activity levels in subjects receiving additional SHP655 for up to 30 days after the resolution of the TTP episode
4. The relationship between ADAMTS-13 activity and end-organ disease status (e.g., renal, neurologic, and cardiac)
5. PK parameters such as incremental recovery, area under the curve, systemic and antibody induced clearance, maximum ADAMTS-13 activity between PEX or SHP 655 infusions, and trough levels prior PEX
6. Occurrence of ADAMTS-13 activity trough levels >10%
Safety/Efficacy endpoints
1. Time to normalization of platelet count, defined as platelet count = 150,000/µL, which must be confirmed by a second normal platelet count = 150,000/µL and LDH <2 ULN 48 hours following initial normalization
2. Occurrence of remission, defined as a normal platelet count and LDH <2 ULN for at least 48 hours following initial normalization of platelet count (acute episode period)
3. Time to first exacerbation (aTTP episode =30 days following remission)
4. Time to relapse (aTTP episode >30 days following remission)
5. Occurrence of exacerbation
6. Occurrence of relapse
7. Occurrence of major clinical events related to TTP including: a. Death, b. Stroke, c. MI
d. Organ dysfunction not normalized within the 90-day observation period; i. Chronic renal insufficiency, ii. Neurologic impairment, iii. Neurocognitive deficits.
8. Incidence of major clinical events related to PEX, including clinically relevant bleeding (modified ITP score) or thrombosis at the site of line insertion, adverse reactions to plasma, including citrate reactions, allergic reactions, and TRALI
9. Changes in the titer of binding and inhibitory antibodies to ADAMTS-13
10. Occurrence of antibodies to SHP655
11. Incidence of AEs and SAEs, and specifically product-related AEs and SAEs
12. Clinically relevant changes in vital signs, clinical chemistry, and hematology
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Secondary ID(s)
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2018-003775-35-GB
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SHP655-201
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Source(s) of Monetary Support
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Baxalta Innovations GmbH
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Ethics review
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Status: Approved
Approval date: 08/10/2019
Contact:
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