E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acquired Thrombotic thrombocytopenic purpura |
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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. |
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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 | 18.0 |
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 |
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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 efficacy of caplacizumab in more rapidly restoring normal platelet counts as measure of prevention of further microvascular thrombosis. |
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E.2.2 | Secondary objectives of the trial |
-To evaluate prevention of recurrence of presenting TTP episode after cessation of daily PE, including prolongation of caplacizumab treatment beyond 30 days post-daily PE treatment based on clinical assessment of underlying disease and ADAMTS13 activity
-To evaluate mortality rate
-To evaluate the effect of caplacizumab on biomarkers for organ damage: LDH, cTnI, and serum creatinine. |
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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)
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 . |
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E.4 | Principal exclusion criteria |
1.Platelet count ≥100×109/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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to platelet count response defined as initial platelet count ≥ 150×109/L with subsequent stop of daily PE within 5 days. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1-Proportion of subjects with an exacerbation and/or relapse of TTP as well as the number of such events
2-Proportion of subjects with treatment-emergent clinically significant TTP-related events as well as the number of such events.
3-Area under the curve (AUC) of platelet count
4-Time to lactate dehydrogenase (LDH) ≤ 2 x upper limit of normal (ULN)
5-Time to cardiac Troponin I (cTnI) ≤ 1 x ULN
6-Time to serum creatinine ≤ 1 x ULN
7-Mortality Rate
8-(Serious)adverse events |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-During study drug treatment and during follow-up (FU)
2, 4, 5 &6- During the overall study period.
3- until Day 5
7-Initial daily PE period, full study drug treatment period, FU period and overall study period
8-During the overall study period
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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 | No |
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 | 3 |
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 |
New Zealand |
Spain |
Switzerland |
Turkey |
United Kingdom |
United States |
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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
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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 |