E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acquired Thrombotic thrombocytopenic purpura |
|
E.1.1.1 | Medical condition in easily understood language |
TTP is a rare condition in which the blood becomes “sticky” and forms clots within the blood vessels in different parts of the body. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10043648 |
E.1.2 | Term | Thrombotic thrombocytopenic purpura |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
|
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 |
For adults: To evaluate efficacy of caplacizumab in more rapidly
restoring normal platelet counts as measure of prevention of further
microvascular thrombosis.
For pediatric subjects: To report the efficacy, safety, PK and PD
properties and immunogenicity of caplacizumab in pediatric subjects
experiencing an acute episode of
acquired TTP |
|
E.2.2 | Secondary objectives of the trial |
- to evaluate the effect of study drug on a composite endpoint
consisting of TTP-related mortality, recurrence of TTP and major
thromboembolic events during study drug treatment.
- to evaluate the effect of study drug on prevention of recurrence of TTP
over the entire study period
- to evaluate the effect of study drug on refractoriness to treatment.
- to evaluate the effect of study drug on biomarkers of organ
damage: lactate dehydrogenase (LDH), cardiac troponin I (cTnI), and
serum creatinine
- to evaluate the effect of study drug on PE parameters (days of PE and
volume), days in intensive care unit (ICU), days in hospital
- to evaluate the effect of study drug on PE parameters (days of PE and
volume), days in intensive care unit (ICU), days in hospital |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Adult male or female ≥ 18 years of age at the time of signing the informed consent form (ICF) or Male or female child (aged ≥ 2 to < 12
years) or adolescent (aged ≥ 12 to <18 years) at the time of obtaining
informed consent/assent (as applicable)
2.Clinical diagnosis of acquired TTP (initial or recurrent), which includes thrombocytopenia and microscopic evidence of red blood cell fragmentation (e.g. schistocytes)
3.Requires initiation of daily PE treatment and has received PE treatment prior to randomization and prior to start of first dose of study drug for pediatric subjects. |
|
E.4 | Principal exclusion criteria |
1.Platelet count ≥100×10E9/L
2.Serum creatinine level >200 µmol/L in case platelet count is > 30×109/L
3.Known other causes of thrombocytopenia
4.Congenital TTP (known at the time of study entry)
5.Pregnancy or breast-feeding. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
For adults only: Time to platelet count response defined as initial platelet
count ≥ 150×10E9/L with subsequent stop of daily PE within 5 days.
Data of pediatric subjects will be analyzed separately from data of adult
subjects. No endpoints are defined for the pediatric subjects. Data will
be analyzed descriptively. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. Proportion of subjects with TTP-related death, a recurrence of TTP,
or at least one treatment-emergent major thromboembolic event during
the study drug treatment period (incl. extensions).
2. Proportion of subjects with a recurrence of TTP in the overall study
period (including 4 week FU period).
3. Proportion of subjects with refractory TTP, defined as absence of
platelet count doubling after 4 days of standard treatment, and LDH
>ULN
4. Time to normalization of all 3 of the following organ damage marker
levels:
- Time to lactate dehydrogenase(LDH) ≤ 1 x upper limit of
normal (ULN), and
- Time to cardiac Troponin l (cTnI) ≤ 1 x ULN, and
- Time to serum creatinine ≤ 1 x ULN |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. During the treatment period (ie daily PE period + post-daily PE
treatment period)
2. During the overall study period (including the FU period)
3. Will be evaluated during the daily PE period.
4. During the overall study period (including the FU period) |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
For children & adolescents open-label treatment with Caplacizumab |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 47 |
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 |
Austria |
Belgium |
Canada |
Czech Republic |
France |
Germany |
Hungary |
Israel |
Italy |
Netherlands |
Spain |
Switzerland |
Turkey |
United Kingdom |
United States |
|
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |