Clinical trial NCT04874818: CD8+ T-cell PET/CT Imaging in COVID-19 Patients
Official title: [89Zr]Df-IAB22M2C Anti-CD8 Minibody PET/CT Imaging to Assess the in Vivo Distribution of CD8+ T-cells in COVID-19 Patients
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Lymphopenia Due to COVID-19
T-cell
PET Imaging
Keywords: COVID-19
lymphopenia
T-cells
PET imaging
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: ImaginAb, Inc.
First posted: 2021-05-06
Enrollment: 5
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population for this pilot study exists of 20 evaluable patients with a proven SARS-CoV2 infection admitted to the Infectious Diseases ward. Patients presenting in the Radboud University Medical Center will be considered for recruitment.

Brief summary: A subset of patients diagnosed with severe acute respiratory syndrome (SARS)-CoV2 infection present with lymphopenia. The degree of lymphopenia, and in particular reduced cluster of differentiation (CD)8+ T-cell numbers, is correlated with clinical deterioration and intensive care unit (ICU) admission. The underlying reasons for lymphopenia in coronavirus disease (COVID)-19 is currently unclear, We aim to assess differences in the in vivo distribution of CD8+ T-cells in patients with proven SARS-CoV2 presenting with lymphopenia or with normal lymphocyte counts, using Zirconium-89 (\[89Zr\])Df-IAB22M2C positron emission tomography (PET) imaging.

Detailed description: Rationale: A subset of patients diagnosed with SARS-CoV2 infection present with lymphopenia. The degree of lymphopenia, and in particular reduced CD8+ T-cell numbers, is strongly correlated with clinical deterioration and ICU admission .

The underlying reasons for lymphopenia in COVID-19 is currently unclear, but several hypotheses have been put forward; 1) sequestration of CD8+ T-cells in peripheral tissues (e.g. lung) either during the effector phase of their lifespan or passively by local chemotactic signals, 2) accelerated maturation and apoptosis either induced by storm of inflammatory cytokines or direct infection or 3) resulting from decreased lymphopoiesis induced by reduced levels of stem cell factor. The lack of data on in vivo distribution of CD8+ T-cells hampers a more thorough understanding of this critical prognostic factor.

Aim: We aim to assess differences in the in vivo distribution of CD8+ T-cells in patients with proven SARS-CoV2 presenting with lymphopenia or with normal lymphocyte counts, using \[89Zr\]Df-IAB22M2C PET/CT imaging.

Study design: This is a prospective, observational non-randomized pilot study in 20 patients with microbiologically proven SARS-CoV2 infection. All patients will undergo a whole body \[89Zr\]Df-IAB22M2C PET/CT scan.

Study population: Twenty patients ≥50 years of age with proven COVID-19, who are admitted to the ward will be included, patients will be stratified according to lymphocyte counts on admission to ensure an even distribution: presenting with lymphopenia (\<1.0 x10e9/L) (n=10) and with lymphocyte numbers within normal range (1.0 - 3.5 x10e9/L) (n=10).

Study procedure: All patients will undergo a \[89Zr\]Df-IAB22M2C PET/CT scan 21-27 hours post intravenous injection of 1.5mg protein dose labelled with 37 megabecquerel (MBq) (1 mCi) 89Zr; and one additional blood sample at the day of scanning.

Primary study objective: The primary objective of this study is 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 \[89Zr\]Df-IAB22M2C PET/CT imaging.

Secondary study objectives:

1. To assess the spatial correlation between \[89Zr\]Df-IAB22M2C uptake and abnormal findings on routine contrast-enhanced CT scan of the chest
2. To assess the correlation between in vivo biodistribution of \[89Zr\]Df-IAB22M2C and concurrent flowcytometric phenotypic and quantitative assessment of lymphocyte populations
3. To explore the correlation between in vivo biodistribution of \[89Zr\]Df-IAB22M2C and clinical course of disease

Eligibility criteria: Inclusion Criteria:

* a microbiologically proven SARS-CoV2 infection
* More than 50 years of age;
* Ability to provide written informed consent.

Exclusion Criteria:

* Contra-indication for PET: Pregnancy, Breast-feeding, Severe claustrophobia.
* Contra-indication for administration of iodine-containing contrast agents
* Other serious illness, e.g. history of malignancies or auto-immune disorders
* Known pre-existing lymphopenia from an unrelated other medical condition
* Estimated creatinine clearance ≤ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method) OR oligo-uric patients (\<400 mL/24hr)

Primary outcomes:
measure: The primary objective of this study is to quantify uptake of [89Zr]Df-IAB22M2C, as a surrogate for the presence of CD8+ T-cells, in major organ systems of patients with proven SARS-CoV-2 presenting with lymphopenia or with normal lymphocyte counts.
timeFrame: 18 months
Secondary outcomes:
measure: Based on imaging
timeFrame: 18 months
measure: Based on laboratory parameters
timeFrame: 18 months
measure: Based on clinical characteristics
timeFrame: 18 months
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud university medical center
state: Gelderland
Study officials:
References: