E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Proven COVID-19. |
Bewezen COVID-19. |
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E.1.1.1 | Medical condition in easily understood language |
Proven coronavirus disease. |
Bewezen coronavirusziekte. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
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 |
We aim to assess differences in the in vivo distribution of CD8+ T-cells in patients with proven SARS-CoV-2 presenting with lymphopenia or with normal lymphocyte counts, using [89Zr]Zr-Df-IAB22M2C PET/CT imaging. Elucidating the pathophysiology underlying lymphopenia at early stages of disease development would allow to rationally design targeted interventions that aim to counteract the detrimental effects of lymphopenia in COVID-19 patients. |
We beogen verschillen te beoordelen in de in vivo verdeling van CD8+ T-cellen in patiënten met bewezen SARS-CoV-2 die zich presenteren met lymfopenie of met een normaal aantal lymfocyten met behulp van PET/CT beeldvorming met de tracer [89Zr]Zr-Df-IAB22M2C. Het verhelderen van de pathofysiologie van een onderliggende lymfopenie in de beginfase van de ziekte zou een rationale ontwikkeling van doelgerichte interventies mogelijk maken die erop gericht zijn om de negatieve effecten van deze lymfopenie in COVID-19 patiënten tegen te gaan. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives of this study will be:
Imaging related:
1) To assess the spatial correlation between [89Zr]Zr-Df-IAB22M2C uptake and abnormal findings on routine contrast-enhanced CT scan of the chest
Biomarker related:
2) To assess the correlation between in vivo biodistribution of [89Zr]Zr-Df-IAB22M2C and concurrent flowcytometric phenotypic and quantitative assessment of lymphocyte populations
Clinical outcome related:
3) To explore the correlation between in vivo biodistribution of [89Zr]Df-IAB22M2C and clinical course of disease
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Secundaire doelen van deze studie zijn:
Secondary objectives of this study will be:
Beeldvorming gerelateerd:
1) Het bepalen van de spatiele correlatie tussen [89Zr]Zr-Df-IAB22M2C opname en abnormale bevindingen op routine contrast-CT van de thorax
Biomarker gerelateerd:
2) Het bepalen van de correlatie tussen in vivo biodistributie van [89Zr]Zr-Df-IAB22M2C en fenotypering en kwantitatieve bepaling van lymfocytenpopulaties middels flowcytometrie
Klinisch beloop gerelateerd:
3) Ontdekken of er correlatie is tussen in vivo biodistributie van [89Zr]Zr-Df-IAB22M2C en het klinisch beloop van de ziekte |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All patients must meet all of the following criteria:
1. microbiologically proven SARS-CoV-19 infection;
2. More than or equal to 18 years of age;
3. Ability to provide written informed consent.
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Alle patiënten moeten aan onderstaande criteria voldoen:
1. microbiologisch bewezen SARS-CoV-2 infectie
2. leeftijd gelijk of ouder dan 18 jaar
3. In staat schriftelijk informed consent te geven.
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E.4 | Principal exclusion criteria |
A patient will be excluded from participation in the trial if one or more of the following criteria are met:
1. Contra-indication for PET; pregnancy, breast-feeding, severe claustrophobia
2. Contra-indication for administration of iodine-containing contrast agents
3. Other serious illness, e.g. history of malignancies or auto-immune disorders
4. Known pre-existing lymphopenia from an unrelated other medical condition
5. Estimated creatinine clearance ≤ 30mL/min according to the Cockcroft-Gault formula (or local institutional standard method) OR oligo-uric patients (<400mL/24hr)
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Een patiënt zal worden geexcludeerd van deelname aan de studie als ze voldoen aan een of meerdere van onderstaande criteria:
1. Contra-indicatie voor PET; zwangerschap, lactatie of ernstige claustrofobie
2. Contra-indicatie voor de toediening van jodium-houdende contrastmiddelen
3. Andere ernstige aandoeningen, bijv. voorgeschiedenis met maligniteiten of auto-immuun-afwijkingen
4. Bekende, eerder bestaande lymfopenie van een ongerelateerde medische aandoening
5. Geschatte kreatinineklaring ≤ 30mL/min op basis van de Cockcroft-Gault formule (of lokale institutionele standaardmethode) OF patiënten met oligurie (<400mL/24hr) |
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E.5 End points |
E.5.1 | Primary end point(s) |
The main study parameter is the whole body in vivo biodistribution of [89Zr]Df-IAB22M2C as quantified by PET/CT. All main organs will automatically be segmented using Siemens MIWBAS. The following parameters will be calculated and reported in a descriptive fashion: SUVmean ±SD, SUVmax ±SD and SUVpeak ±SD, total organ activity (% of total measured activity). Statistical tests to assess group differences will include the non-parametric Mann-Whitney U test per organ, since normal distribution cannot be assumed. Overall distribution profiles will be tested using Chi-square test. |
Het primaire eindpunt is de in vivo biodistributie van [89Zr]Zr-Df-IAB22M2C, zoals gekwantificeerd middels PET/CT. Alle belangrijke organen worden automatisch gesegmenteerd middels Siemens MIWBAS. De volgende parameters zullen worden berekend en gerapporteerd op een beschrijvende manier: SUVmean ±SD, SUVmax ±SD and SUVpeak ±SD, totale orgaanactiviteit (% van de totaal gemeten activiteit). Statistische testen om groepsverschillen te bepalen zullen de non-parametrische Mann-Whitney U-test per orgaan omvatten, aangezien een normale verdeling niet kan worden aangenomen. Overall verdelingsprofielen zullen worden getest middels de Chi-kwadraat test. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
LSLV.
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Na de laatste visite van de laatste deelnemer. |
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E.5.2 | Secondary end point(s) |
Secondary endpoints:
Imaging related:
1) Spatial correlation (per lung segment) with ground-glass opacities, consolidation and vascular thickening
Biomarker related:
2) Absolute and relative organ uptake of [89Zr]Df-IAB22M2C will be quantitatively correlated with concurrent levels of ferritin, D-dimer, CRP, as obtained per routine clinical care using Spearman non-parametric correlation.
3) Absolute and relative organ uptake of [89Zr]Df-IAB22M2C will be quantitatively correlated with total lymphocyte numbers, absolute and relative numbers of CD4+ and CD8+ T-cells using Spearman non-parametric correlation, as well as descriptively correlated with flowcytometric markers (PD-1, TIM-3, Granzyme B/CD127, phenotyping (CD45RA/CCR7, or CD62L/CD28) to establish effector memory/central memory, naïve and TEMRA subsets)
Clinical outcome related:
4) Absolute and relative organ uptake of [89Zr]Df-IAB22M2C will be correlated with the following clinical parameters: (time to) eventual ICU admission, length of ICU stay (days), mechanical ventilation parameters, oxygen demand, total length of hospital stay (days). |
Secundaire eindpunten:
Beeldvorming gerelateerd:
1) Spatiele correlatie (per longsegment) met matglasafwijkingen, consolidatie en vasculaire verdikking
Biomarker gerelateerd:
2) Absolute and relatieve orgaanopname van [89Zr]Df-IAB22M2C, kwantitatief gecorreleerd met gehalte ferritin, D-dimeer, CRP, gebruik makend van Spearman non-parametrische correlatie.
3) Absolute and relatieve orgaanopname van [89Zr]Df-IAB22M2C, kwantitatief gecorreleerd met totaal aantal lymfocyten, absolute and relatieve aantallen CD4+ and CD8+ T-cellen middels Spearman non-parametrische correlatie, alsook beschrijvend gecorreleerd met flowcytometrische markers (PD-1, TIM-3, Granzyme B/CD127, fenotypering (CD45RA/CCR7, or CD62L/CD28)
Klinische outcome gerelateerd:
4) Absolute and relatieve orgaanopname van [89Zr]Df-IAB22M2C, gecorreleerd met klinische parameters: (tijd tot) eventuele IC opname, duur IC opname (dagen), mechanische ventilatie parameters, zuurstofbehoefte, totale lengte van de ziekenhuisopname (dagen). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
LSLV. |
Na de laatste visite van de laatste deelnemer. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | 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
| 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 | No |
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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LSLV |
Laatste visite van de laatste deelnemer. |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |