| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| congenital Thrombotic thrombocytopenic purpura (TTP) |
|
| E.1.1.1 | Medical condition in easily understood language |
| congenital Thrombotic thrombocytopenic purpura |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the long-term safety and tolerability of TAK-755 (rADAMTS-13) in terms of related treatment-emergent adverse events (TEAEs) and related serious adverse events (SAEs) in both the prophylactic and the on-demand cohorts. |
|
| E.2.2 | Secondary objectives of the trial |
1. To evaluate the efficacy prophylactic TAK-755 treatment t for the
prevention of acute TTP events.
2. To evaluate the efficacy of TAK-755 in controlling treatment and control of acute
thrombotic thrombocytopenic purpura (TTP) events.
3. To evaluate the proportion of subjects that require dose modification
and supplemental dose in the prophylactic cohort.
4. To evaluate the incidence of isolated TTP manifestations in subjects
receiving prophylactic treatment.
For more secondary objectives please refer to the Protocol. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title: An open-label, single dose, multicenter exploratory substudy to
assess the safety and bioavailability of TAK-755 (rADAMTS13) given by
subcutaneous administration in subjects with cTTP receiving
prophylactic treatment with TAK-755 in the Phase 3b continuation study
(TAK-755-3002)
Date: 12Apr2022
Exploratory Objectives:
1. To evaluate the safety and tolerability of TAK-755 administered
subcutaneously in terms of adverse
events (AEs) and serious adverse events (SAEs).
2. To assess the bioavailability of TAK-755 administered subcutaneously.
3. To evaluate the pharmacokinetics (PK) of ADAMTS13 for up to 14 days
after subcutaneous (SC) administration. |
|
| E.3 | Principal inclusion criteria |
Applies to Subjects who have completed the TAK-755 Phase 3 pivotal study
(Study 281102) in the prophylactic cohort
Subjects who have completed TAK-755 Study 281102 (in the prophylactic cohort who meet ALL of the following criteria are eligible for this study:
1. Subject or legally authorized representative has provided signed informed consent (≥18 years of age) and/or assent form (<18 years of age).
2. Subject is 0 to 70 years of age at the time of screening of the 281102 study.
3. Subject has been diagnosed with severe congenital ADAMTS-13 deficiency.
4. Subject does not display any severe TTP signs (platelet count <100,000/µL and elevation of LDH >2 × upper limit of normal [ULN]) at screening (prophylactic cohort only).
5. Subjects ≥16 years of age must have a Karnofsky score ≥70% and subjects <16 years of age must have a Lansky score ≥80%.
6. If female of childbearing potential, subject presents with a negative serum or urine pregnancy test confirmed not more than 7 days before the first IP administration and agrees to employ highly effective birth control measures for the duration of the study and to undergo quarterly pregnancy testing.
7. 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.
8. Subject is willing and able to comply with the requirements of the protocol.
Applies to naïve subjects and non-naïve on-demand cohort subjects Naïve subjects can only be enrolled in this continuation study after enrollment of the adult subjects in the prophylactic arm of the TAK-755 Phase 3 pivotal study (Study 281102) has been completed. . Naïve pediatric subjects can be enrolled after enrollment of the respective age
cohort into Study 281102 has been completed. The following criteria also applies to subjects who completed study 281101, but did not participate in 281102.The following criteria do not apply to subjects from the Expanded Access Program or subjects from 281102 who had an allergic reaction to SoC.See separate criteria below for study eligibility of EAP subjects and subjects from study 281102 who had an allergic reaction to SoC.Naïve subjects and subjects who were enrolled into the on-demand cohort of the TAK-755 Phase 3 pivotal study (281102) who meet ALL of the following criteria are eligible for this study:
1. Subject is naïve to TAK-755 or was enrolled into the on-demand cohort of the TAK-755 Study 281102 for treatment of an acute event but did not receive prophylactic treatment.
2. Subject or legally authorized representative has provided signed informed consent (≥18 years of age) and/or assent form (<18 years of age).
3. Subject is 0 to 70 years of age at the time of screening.
4. Subject has been diagnosed with severe congenital ADAMTS-13 deficiency defined as:
a. Confirmed by molecular genetic testing, documented in subject history or at screening, and
b. ADAMTS-13 activity <10% as measured by the fluorescence resonance energy transfer (FRETS)-Von Willebrand factor (VWF)73 assay, documented in subject history or at screening. Subjects currently receiving standard of care prophylactic therapy may exceed 10% ADAMTS 13 activity at screening.
5. Subjects currently receiving prophylactic therapy will be screened immediately prior to their usual prophylactic infusion.
6. Subject does not display any severe TTP signs (platelet count <100,000/µL and elevation of LDH >2 × ULN) at screening (prophylactic cohort only).
7. Subjects ≥16 years of age must have a Karnofsky score ≥70% and subjects <16 years of age must have a Lansky score ≥80%.
8. Subject is hepatitis C virus negative (HCV) as confirmed by antibody or polymerase chain reaction testing OR HCV positive (HCV+) if their disease is chronic but stable.
9. If female of childbearing potential, subject presents with a negative serum or urine pregnancy test confirmed not more than 7 days before the first IP administration and agrees to employ highly effective birth control measures for the duration of the study and to undergo quarterly pregnancy testing.
10. Sexually active males must use an accepted and effective method of contraception during treatment and until a minimum of 16 days after the last dose administered.
11. Subject is willing and able to comply with the requirements of the protocol.
Subjects from an Expanded Access Program or subjects in Study 281102
who had an allergic reaction to standard of care prophylactic treatment
Subjects from an Expanded Access Program or subjects in Study 281102
who had an allergic reaction to standard of care prophylactic treatment
must meet ALL of the following criteria.
1. Subject or legally authorized representative has provided signed
informed consent (≥18 years of age) and/or assent form (<18 years of
age), as applicable.
2. Subject is 0 to 70 years of age at the time of screening.
For more inclusion criteria please refer to the Protocol. |
|
| E.4 | Principal exclusion criteria |
The subject will be excluded from the study if any of the following exclusion criteria are met.
Applies to subjects who have completed TAK-755 Phase 3 pivotal study (Study 281102) and TAK 755 naïve subjects:
. Known life-threatening hypersensitivity reaction, including
anaphylaxis, to the parent molecule ADAMTS-13, hamster protein, or
other constituents of TAK-755.
2. Subject has presence of a functional ADAMTS-13 inhibitor at
screening.
3. In the opinion of the investigator, the subject has another clinically
significant concomitant disease that may pose additional risks for the
subject.
4. Subject is receiving or anticipates receiving another investigational
drug and/or interventional drug within 30 days before enrollment.
5. Subject is identified by the investigator as being unable or unwilling to
cooperate with study procedures.
6. 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.
7. Subject is a family member or employee of the sponsor or investigator
Applies to naïve subjects and non-naïve on-demand cohort subjects:
The following criteria do not apply to subjects from the Expanded Access
Program or subjects from 281102 who had an allergic reaction to SoC.
The following criteria also applies to subjects who completed study
281101, but did not participate in 281102.
1. Subject has been diagnosed with any other TTP-like disorder (microangiopathic hemolytic anemia), including immune-mediated TTP.
2. Known life-threatening hypersensitivity reaction, including anaphylaxis, to the parent molecule ADAMTS-13, hamster protein, or other constituents of TAK-755.
3. Subject has presence of a functional ADAMTS-13 inhibitor at screening.
4. Subject has a medical history of a genetic or acquired immune deficiency that would interfere with the assessment of product immunogenicity, including subjects who are human immunodeficiency virus positive with an absolute cluster of differentiation 4 (CD4) count <200/mm3 or who are receiving chronic immunosuppressive drugs.
5. Subject has a history of significant neurological events, such as major stroke, indicating that a relapse might have severe consequences, as judged by the investigator.
6. Subject has been diagnosed with severe cardiovascular disease (New York Heart Association classes 3 to 4).
7. Subject with end stage renal disease requiring chronic dialysis.
8. Subject has been diagnosed with hepatic dysfunction, as evidenced by, but not limited to, any of the following:
a. Serum alanine aminotransferase ≥2 × ULN
b. Severe hypoalbuminemia <24 g/L
c. Portal vein hypertension (eg, presence of otherwise unexplained splenomegaly, history of esophageal varices).
9. In the opinion of the investigator, the subject has another clinically significant concomitant disease that may pose additional risks for the subject.
10. Subject has been treated with an immunomodulatory drug, excluding topical treatment (eg, ointments, nasal sprays), within 30 days prior to enrollment. Use of corticosteroids in conjunction with administration of fresh frozen plasma to prevent allergic reactions is permitted.
11. Subject has an acute illness (eg, influenza, flu-like syndrome, allergic rhinitis/conjunctivitis, bronchial asthma) at the time of screening (prophylactic cohort only).
12. Subject is receiving or anticipates receiving another investigational drug and/or interventional drug within 30 days before enrollment.
13. Subject has a history of drug and/or alcohol abuse within the last 2 years.
14. Subject has a progressive fatal disease and/or life expectancy of ≤3 months.
15. Subject is identified by the investigator as being unable or unwilling to cooperate with study procedures
16. 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.
17. Subject is a family member or employee of the sponsor or investigator.
18. If female, subject is pregnant or lactating at the time of enrollment. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| There is no primary efficacy endpoint for this study, as the primary objective of the study is long-term safety. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Various timepoints throughout the study |
|
| E.5.2 | Secondary end point(s) |
The key secondary efficacy outcome measure is the incidence of acute
TTP events among subjects receiving TAK-755 prophylactically. Analyses
will be conducted using FAS for the prophylactic cohort. The number and
incidence rate of acute TTP events will be summarized by enrollment
status ("Naïve" or having completed the Phase 3 pivotal study [Study
281102]) and overall. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Various timepoints throughout the study |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 26 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Brazil |
| Canada |
| China |
| Colombia |
| India |
| Israel |
| Japan |
| Korea, Republic of |
| Taiwan |
| Thailand |
| United States |
| Austria |
| France |
| Poland |
| Sweden |
| Netherlands |
| Spain |
| Switzerland |
| Czechia |
| Germany |
| Italy |
| Belgium |
| Denmark |
| Hungary |
| Norway |
| Portugal |
| Russian Federation |
| Turkey |
| Ukraine |
| United Kingdom |
| Serbia |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
Print
