E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Anakinra treatment is expected to reduce the early and long term mortality of patients with Kawasaki Disease (KD), by a rapid and sustained effect on vascular inflammation |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
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 | 10023320 |
E.1.2 | Term | Kawasaki's disease |
E.1.2 | System Organ Class | 10047065 - Vascular 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 |
Assess the efficacy of anakinra (IL-1R1receptor antagonist) in patients on fever with KD who fail to respond to one infusion of IVIg (standard treatment).
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E.2.2 | Secondary objectives of the trial |
-To assess the efficacy of anakinra on disease activity -To assess the efficacy of anakinra on coronary lesions (eg: dilatation and aneurysm) -To assess the efficacy of anakinra on inflammation -To assess the safety and tolerability of anakinra
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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 |
-inflammatory biomarkers -gene expression profiling -endothelial cell activation markers -antibodies against anakinra |
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E.3 | Principal inclusion criteria |
1.Patients, male and female, ? 8 months (10kg) of life and ? 18 years old, with KD according to the American Heart Association definition for complete or incomplete KD. Fever ? 5 days and ? 4 of 5 main clinical signs: modification of the extremities, polymorphic exanthema, bilateral bulbar not exsudative conjunctivitis, erythema of the lips or oral cavity, and cervical lymph nodes usually unilateral > 1.5 cm in diameter. In the presence of less than 4 clinical criteria and 5 days of fever, the diagnosis of disease KD is proposed in case of coronary abnormalities (at least one dilated coronary artery with internal diameter ? 2,5 SD from the mean normalized for body surface area (Z score) as determined by echocardiography
2.Patients who failed to respond to standard therapy of KD:, e.g. Persistence or recrudescence of fever ? 38°C, 48 hours after the infusion of 2g/kg of IV Ig,
3.Patient, parents or legal guardian's written informed consent is required
4.Patient with health insurance
5Patient agrees to have effective contraception for the duration of participation in search
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E.4 | Principal exclusion criteria |
1.Preterm and neonates, pregnancy
2.Patients suspected with another diagnosis
3.Patients with overt concomitant bacterial infection
4.Patients previously treated with another biotherapy
5.Patients with any type of immunodeficiency or cancer
6.Patients with increased risk of TB infection
7.Recent tuberculosis infection or with active TB
8.Close contact with a patient with TB
9.Patients recently arrived less than 3 months from a country with high prevalence of TB
10. A chest radiograph suggestive of TB
11. Patients with end stage renal disease: NKF stages ?4; eGFR?29mL/min/1.73 m2 or diabetes mellitus or neutropenia <1500/mm3 or liver failure < 30 mL/min
12.Hypersensitivity to the active substance or to any of the excipients (citric acid and anhydrous; sodium chloride;disodium edetate dehydrate polysorbate 80; sodium hydroxide; water for injections)
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary statistical analysis of the proportion of patients succeeding to reach a body temperature <38°C within 24 hours of treatment by anakinra (even after dose escalation if any) at d15 will be purely descriptive through proportion of patients and its Agresti-Coull confidence interval at 95%. Based on the Intent-To-Treat principle, all included patients will be taken into account. |
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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 | No |
E.6.5 | Efficacy | No |
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) | Information not present in EudraCT |
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) | Information not present in EudraCT |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 | 1 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |