E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Thrombotic 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; • 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.2.2 | Secondary objectives of the trial |
Exploratory objectives Some patients may undergo cranial MRI once prior to, and once again ~6 weeks after the start of study drug treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male or female; ≥18 to ≤75 years of age; Diagnosis of TMA based on presence of: Thrombocytopenia, defined as a platelet count <100 x 109 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. Patients who have again become acutely ill following recent treatment and achievement of a brief remission of acute TMA may be enrolled in the study if ALL of the following conditions are met: Disease activity in the patient is unabated (e.g., persistent thrombocytopenia and microangiopathic hemolytic anemia with ongoing neurological symptoms and/or troponin elevation); The last plasma exchange of the patient’s preceding course of treatment occurred at least 7 days prior; The patient did not undergo splenectomy during the preceding course of treatment; The new course of plasma exchange has not been ongoing for more than 3 days. |
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E.4 | Principal exclusion criteria |
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 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). Patients who have again become acutely ill following recent treatment and achievement of a brief remission of acute TMA may not be enrolled in the study if ANY of the following conditions are met: The last plasma exchange of the patient’s preceding course of treatment occurred less than 7 days prior; The patient underwent splenectomy during the preceding course of treatment; The new course of plasma exchange has been ongoing for more than 3 days. |
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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 | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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 |
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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
| 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 | 15 |
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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Last visit of the last subject |
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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 | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |