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 | 20.0 |
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 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 presenting 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: LDH, 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 |
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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 ≥100×10E9/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. As per PEI Request: 13. Subjects with severe hepatic impairment 14. Subjects with severe chronic renal impairment 15. Subjects who are institutionalized due to regulatory or juridical order (according to AMG § 40) 16. Subjects involved in the planning and/or conduct of the study by Ablynx staff and/or staff at the study site or is employed by Ablynx (i.e., an employee, temporary contract worker or designee responsible for the conduct of the study), or who is an immediate family member (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the study at the clinical study site, or is directly affiliated with the study at the clinical study site. 17. Subjects with any cerebral bleeding as detected by magnetic resonance imaging (MRI) of the brain performed at screening. |
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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 ≥ 150×10E9/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 TTP-related death, a recurrence of TTP, or at least one treatment-emergent major thromboembolic event during the study drug treatment period (including 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 LDH ≤ 1 x upper limit of normal (ULN), and - Time to cTnI ≤ 1 x ULN, and - Time to serum creatinine ≤ 1 x ULN |
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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)
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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 | 9 |
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 |
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 |