E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Thromobotic microangiopathy (TMA) disorders |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009731 |
E.1.2 | Term | Coagulation disorder |
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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 the ability of ARC1779 Injection to improve clinical outcome by protecting brain, heart, and kidney from damage due to formation of disseminated platelet thrombi in the microcirculation; To evaluate the overall safety and tolerability of ARC1779 Injection; |
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E.2.2 | Secondary objectives of the trial |
To assess the concentration-response of ARC1779 for efficacy- and safety-related effects; To assess the concentration-response relationships among ARC1779 pharmacokinetic (PK) and pharmacodynamic (PD) parameters. |
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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 |
ALTRI SOTTOSTUDI: I pazienti possono anche partecipare ai sottostudi di acquisizione di immagini del SNC e del cuore. I pazienti che partecipano al sottostudio di acquisizione di immagini del SNC saranno sottoposti a RM craniale una volta prima dellinizio del trattamento con il farmaco dello studio e ancora una volta circa 6 settimane dopo linizio del trattamento con il farmaco dello studio. Analogamente, i pazienti con una diagnosi di IMA (sulla base di risultati positivi delle troponine e/o ECG) che partecipano al sottostudio di acquisizione di immagini cardiache saranno sottoposti a RM del cuore una volta prima dellinizio del trattamento con il farmaco dello studio e ancora una volta circa 6 settimane dopo linizio del trattamento con il farmaco dello studio.
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E.3 | Principal inclusion criteria |
Patients who meet the following criteria are eligible for this study: Male or female; 18 to 75 years of age; Diagnosis of TMA based on presence of: Thrombocytopenia, defined as a platelet count <100 x 10^9 per liter; Microangiopathic hemolytic anemia, defined by negative findings on direct antiglobin test, and evidence of accelerated red blood cell (RBC) production and destruction); AND Absence of a clinically apparent alternative explanation for thrombocytopenia and anemia, e.g., disseminated intravascular coagulation (DIC), eclampsia, HELLP syndrome, Evans syndrome; Females: non-pregnant and commit to use of effective, redundant methods of contraception (i.e., for both self and male partner) throughout the study and for at least 30 days after discontinuation of study drug treatment; Males: commit to use of a medically acceptable contraceptive (abstinence or use of a condom with spermicide) throughout the study and for at least 30 days after discontinuation of study drug treatment; Not received an unlicensed investigational agent (drug, device, or blood-derived product) within 30 days prior to randomization, and may not receive such an investigational agent in the 30 days post-randomization (note: investigational use for treatment of TMA of a licensed immunomodulator, e.g., rituximab, is permitted at any time relative to randomization); Capable of understanding and complying with the protocol, and he/she (or a legal representative) must have signed the informed consent document prior to performance of any study-related procedures. |
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E.4 | Principal exclusion criteria |
Patients who meet the following criteria are NOT eligible for this study: Females: pregnant or <24 hours post-partum, or breastfeeding; History of bleeding diathesis or evidence of active abnormal bleeding within the previous 30 days; Disseminated malignancy or other co-morbid illness limiting life expectancy to &#8804;3 months independent of the TMA disorder. Diagnosis other than TMA which can account for the findings of thrombocytopenia and hemolytic anemia (e.g., DIC, HELLP syndrome, Evans syndrome); Diagnosis of DIC verified by laboratory values for D-dimer, fibrinogen, prothrombin time (PT), and activated partial thromboplastin time (aPTT). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Composite of clinical events and biomarker evidence for injury to the target organs commonly affected by TMA, i.e. brain, heart and kidney. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
lo studio prevede un disegno dose-crescente |
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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.8.3 |
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 | 16 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
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 | Information not present in EudraCT |
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 |
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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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l`ultima visita dell`ultimo paziente |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |