E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Atherosclerosis |
Atherosclerose |
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E.1.1.1 | Medical condition in easily understood language |
A disease of the arteries characterized by the deposition of fatty material beneath their inner walls |
Een ziekte van de slagaderen waarbij vettig materiaal zich op hoopt onder de binnenwand van de slagader. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is, to determine whether short term anti-IgE treatment with an anti-IgE monoclonal antibody (omalizumab) can limit intraplaque mast cell activation in atherosclerotic plaques. |
Het primaire doel is om vast te stellen of kortdurende anti-IgE behandeling met een anti-IgE monoklonaal antilichaam (omalizumab) mestcel activatie in atherosclerotische plaque kan remmen. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to compare the following outcomes between the two treatment groups:
(1) Local inflammatory status of atherosclerotic plaque (measuring T-cell subsets, M1/M2 macrophages, neutrophils and B-cells)
(2) Plasma tryptase levels
(3) Infection parameters (complete bloodcount, hsCRP, IL-1beta and IL-6)
(4) Plaque characterization (e.g. necrotic area, cellular compostion and stability parameters)
(5) Serum IgE levels
(6) Basophil activation status
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De secundaire doelen zijn om de volgende uitkomsten te vergelijken tussen de beide groepen:
(1) Lokale inflammatoire status van de atherosclerotische plaque (meten van T-cell subsets, M1/M2 macrofagen, neutrofielen en B-cellen)
(2) Plasma tryptase spiegels
(3) Infectieparameters (volledig bloedbeeld, hsCRP, IL-1beta en IL-6)
(4) Plaque karakteristieken (zoals necrose, cellulaire samenstelling en stabiliteit parameters)
(5) Serum IgE spiegel
(6) Basofiele activatie status
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
(1) Patient is 18 years of age or older
(2) Patient is able and willing to give their consent and sign an informed consent
(3) Symptomatic or asymptomatic carotid artery stenosis based on atherosclerosis of at least 50% calculated by using criteria equivalent to the NASCET method
(4) Revascularization through carotid endarterectomy is indicated by multidisciplinary panel |
Om in aanmerking te komen voor deelname aan dit onderzoek, moet aan de volgende criteria worden voldaan:
(1) De patiënt is 18 jaar of ouder
(2) De patiënt is in staat en bereid om zijn toestemming te geven en een toestemmingsformulier te tekenen.
(3) De patiënt heeft een symptomatische of asymptomatische stenose van de carotis van minstens 50% berekend op basis van criteria die gelijkwaardig zijn aan de NASCET methode.
(4) De indicatie tot re-vascularisatie middels een carotis endarterectomie is gesteld door een multidisciplinair team tijdens een multidisciplinair overleg.
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E.4 | Principal exclusion criteria |
A potential subject who meets any of the following criteria will be excluded from participation in this study:
(1) Previous anaphylactic reaction (e.g. food allergy, medication such as antibiotics etc.)
(2) Previous CEA or CAS in the ipsilateral artery
(3) Patients with severe asthma or chronic urticaria which are treated or have been treated with omalizumab s.c.
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Een potentiële studie-kandidaat die voldoet aan een van de volgende criteria zal worden geëxcludeerd van participatie in dit onderzoek:
(1) Eerdere anafylactische reactie (bv anafylactische reactie op een voedsel- of medicatieallergie)
(2) Eerdere CEA of CAS in de ipsilaterale carotis
(3) Patiënten met ernstig allergisch astma of chronische galbulten welke worden behandeld of werden behandeld met omalizumab subcutaan.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is activated mast cell as the percentage of the total mast cell (CD45+CD117+FcεR+ cells) count, determined by flow cytometry. Normal unactivated mast cells are positive for the markers CD45, CD117 and FcεR. In addition, activated mast cells are positive for IgE and the activationmarkers CD203c and CD63. The primary study parameter is the % of mast cell activation determined by flow cytometry. |
Het primaire eindpunt is hoeveelheid geactiveerde mestcellen als een percentage van de totale hoeveelheid mestcellen. Normale niet geactiveerde mestcellen zijn positief voor de markers, CD45, CD117 en FcεR. Behalve voor deze markers zijn geactiveerde mestcellen ook positief voor IgE en de activatiemarkers CD203C en CD63. De primaire studie parameter is het percentage van mest cel activatie gemeten door flowcytometrie. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint will be assesed in the atherosclerotic plaque which be collected during the carotid endarterectomy (+ 3 days after the administration of study medication). |
Het primaire eindpunt zal worden bepaald in de atherosclerotische plaque, welke wordt verzameld gedurende de carotis endarterectomie (+3 dagen na toediening studiemedicatie) |
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E.5.2 | Secondary end point(s) |
Secondary endpoints are (endpoints will be compared between treatment groups and for point 2,3,5 and 6 between baseline and day 3):
(1) Local inflammatory status of atherosclerotic plaque (measuring T-cell subsets, M1/M2 macrophages, neutrophils and B-cells counts)
(2) Plasma tryptase levels
(3) Level of infection parameters (complete blooudcount, hsCRP, IL-1beta and IL-6)
(4) Plaque characterization (using histology)
(5) Serum IgE levels
(6) Basophil activation status
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Secundaire uitkomstmaten zijn (de uitkomstmaten worden vergeleken tussen de beide behandelingsgroepen en voor punten 2,3,5 en 6 tussen baseline en dag 3):
(1) Lokale inflammatoire status van de atherosclerotische plaque (meten van T-cell subsets, M1/M2 macrofagen, neutrofielen en B-cellen)
(2) Plasma tryptase spiegels
(3) Infectieparameters (volledig bloedbeeld, hsCRP, IL-1beta en IL-6)
(4) Plaque karakteristieken (zoals necrose, cellulaire samenstelling en stabiliteit parameters)
(5) Serum IgE spiegel
(6) Basofiele activatie status
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Blood based secondary endpoints will be assesed with blood samples from baseline and 3 days after administration of study medication.
Plaque based secondary endpoints will be assesed using the plaque which is acquired by carotid endarterectomy.
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Secundaire uitkomstmaten in bloed worden beoordeeld met bloed samples van de baseline en 3 dagen na toediening van studie medicatie.
Secundaire uitkomstmaten in atherosclerotiche plaque worden beoordeeld in de atherosclerotische plaque welke wordt verkregen gedurende de carotis endarterectomie. |
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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 | No |
E.6.4 | Safety | No |
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) | 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 | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |