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 |
Atherosclerosis, vascular disease |
Aderverkalking, hart- en vaatziekten |
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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 |
To demonstrate that 89Zr-CER-001 penetrates into atherosclerotic plaques in patients by means of PET imaging. |
Aantonen dat 89Zr-CER-001 aankomt in atherosclerotische plaques van patiënten met PET-imaging |
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E.2.2 | Secondary objectives of the trial |
To evaluate whether the amount of 89Zr-CER-001 penetrating the plaque corresponds to athero-lesion severity. To evaluate whether the amount of 89Zr-CER-001 penetrating the plaque corresponds to plaque permeability. To evaluate whether the amount of 89Zr-CER-001 penetrating the plaque corresponds to the cholesterol efflux capacity
|
Onderzoeken of de hoeveelheid 89Zr-CER-001 die aankomt in de plaque correspondeert met de ernst van de atherosclerotische laesie Onderzoeken of de hoeveelheid 89Zr-CER-001 die aankomt in de plaque correspondeert met de permeabiliteit van de plaque Onderzoeken of de hoeveelheid 89Zr-CER-001 die aankomt in de plaque correspondeert met de cholesterol efflux capaciteit |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must meet the following criteria for study entry: - Adult patients (either gender) ≥ 50 years - Documented atherosclerotic vascular disease; defined as either peripheral arterial disease or documented aortic or carotid atherosclerosis on clinical vascular MRI or ultrasound - Clinically stable for at least 3 months prior to inclusion - Very high CV-risk (based on Framingham risk engine) |
- Volwassen patiënten (zowel mannen als vrouwen) ≥ 50 jaar - Gedocumenteerd vaatlijden: gedefineerd als perifeer vaatlijden of gedocmenteerde atherosclerose van de aorta of carotiden met MRI of echo - Ten minste 3 maanden klinisch stabiel voor de inclusie - Ernstig verhoogd risico op hart- en vaatziekten |
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E.4 | Principal exclusion criteria |
Patients are not eligible if they meet one of the criteria listed below: - Creatinine clearance < 50 ml/min (MDRD) 6 months prior to inclusion - Auto-immune disease/vasculitis, other active inflammatory diseases, proven or suspected bacterial infections. Recent (<1 month prior to inclusion) or ongoing serious infection requiring IV antibiotic therapy that could interfere with the conduct of the study in the opinion of the investigator - Known systemic disorders such as hepatic, renal, hematologic, and malignant diseases or any clinically significant medical condition that could interfere with the conduct of the study in the opinion of the investigator - Standard contra-indications to MRI, PET, and CT - Inability or unwillingness to comply with the protocol requirements, or deemed by investigator to be unfit for the study |
Patiënten komen niet in aanmerking als zij voldoen aan een van de volgende criteria: - Creatinineklaring < 50 ml/min (MDRD) 6 maanden voorafgaand aan de inclusie - Auto-immuunziekten/vasculitis, andere actieve inflammatoire ziekten, bewezen of verdenking op bacteriële infectie. Recente (< 1 maand voor inclusie) of actieve ernstige infectie, waarvoor IV behandeling met antibiotica nodig is, die invloed zou kunnen uitoefenen op het beloop van het onderzoek naar het oordeel van de onderzoeker - Bekende systemische aandoeningen zoals lever-, nier-, hematologische en maligne aandoeningen of een klinisch significante medische aandoening die invloed zouden kunnen uitoefenen op het beloop van het onderzoek naar de mening van de onderzoeker - Standaard contra-indicaties voor MRI, PET en CT - Niet het vermogen of de wil om te voldoe |
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E.5 End points |
E.5.1 | Primary end point(s) |
The CER-001 uptake in the plaque over time by means of PET imaging of the aorta and carotid arteries, reported as Standardized Uptake Value (SUV) of the plaque. |
De primaire uitkomstmaat is de 89Zr-CER-001 opname in de plaque gedurende een tijdsperiode, uitgedrukt als de Standardized Uptake Value (SUV), met behulp van PET-imaging. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PET-imaging will be performed after infusion of 89Zr-CER-001, at timepoints of 10 minutes after infusion, after 24 hours and after 72 hours. |
PET-scans zullen worden vervaardigd na infusie van 89Zr-CER-001 na 10 minuten, na 24 uur en na 72 uur. |
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E.5.2 | Secondary end point(s) |
Further quantification of CER-001 uptake at the plaque - 89Zr-CER-001 uptake in the plaque over time assessed as the Target to Background Ratio (TBR), via PET imaging - Difference between SUV and TBR at the level of the plaque and SUV and TBR of non-diseased arterial wall on PET
Relation between CER-001 uptake and plaque characteristics - Relation between SUV and TBR of the plaque on PET and structural plaque dimensions on MRI i.e. normalized wall index, vessel wall area. - Relation between SUV and TBR of the plaque and plaque permeability on DCE-MRI, i.e. Ktrans
Relationship between the CER-001 uptake in the plaque by means of PET imaging reported as SUV of the plaque and the cholesterol efflux capacity. |
Verdere kwantificatie van CER-001 opname in de plaque: - 89Zr-CER-001 opname in de plaque gedurende een tijdperiode, uitgedrukt als de Target to Background Ratio (TBR), met behulp van PET-imaging - Het verschil tussen SUV en TBR op plaque-niveau en het verschil van SUV en TBR op gezonde vaatwand, met behulp van PET-imaging
De relatie tussen CER-001 opname en plaque karakteristieken - De relatie tussen SUV en TBR van de plaque op de PET en structurele plaque afmetingen op MRI (bijv. normalized wall index, vessell wall area) - De relatie tussen SUV en TBR van de plaque en plaque permabiliteit op DCE-MRI (bijv. Ktrans)
De relatie tussen CER-001 opname in de plaque met behulp van PET-imaging en de cholesterol efflux capaciteit |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
In addition to the PET-scans performed, an MRI will be performed after patients have been screened. |
Naast de PET-scans zal er tevens een MRI worden vervaardigd nadat patiënten zijn gescreend. |
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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) | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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
| 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
|
The end of the study will have been reached after visit 4, in which the third/last PET-CT scan will be performed, 72 hours after the infusion of Zr89-CER-001. |
Het einde van het onderzoek wordt bereikt na visite 4, nadat de derde/laatste PET-CT scan is gemaakt, 72 uur nadat Zr89-CER-001 is toegediend. |
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |