Immune Activation Imaging for COVID-19

Overseen By Kofi Asare

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: CellSight Technologies, Inc.

Disqualifiers: Pregnancy, Breastfeeding, Transplant, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new imaging agent called [18F]F-AraG (also known as VisAcT or 2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine) to determine its effectiveness in visualizing immune activity in individuals recovering from COVID-19. The researchers aim to understand immune system behavior after a COVID-19 infection using PET-CT scans. It suits those who have tested positive for COVID-19, are beyond the initial 14 days of symptoms, and have not yet received a COVID-19 vaccine. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team to get a clear answer.

What prior data suggests that this imaging technique is safe?

Research has shown that [18F]F-AraG, the treatment in this trial, is being studied to ensure its safety for humans. In an earlier study, 24 participants underwent [18F]F-AraG PET/CT imaging, and no significant side effects occurred. This suggests the treatment might be well-tolerated.

Since this trial is in an early phase, [18F]F-AraG has demonstrated some safety in previous research, but further testing is necessary. This is typical for treatments at this stage, indicating that while initial results are promising, more information is needed to fully understand its safety.

Participants considering joining the trial should know that studies have used the treatment without major safety concerns, but it is still under investigation. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike most treatments for COVID-19, which focus on reducing symptoms or viral load, [18F]F-AraG offers a unique approach by using a radiofluorinated imaging agent. This agent, known as VisAcT, is designed to visualize immune activation in the body. Researchers are excited about this treatment because it provides real-time insights into how the immune system is responding to COVID-19, potentially allowing for more personalized and timely interventions. This novel mechanism could help doctors better understand and manage the disease, leading to improved patient outcomes.

What evidence suggests that this imaging method is effective for COVID-19?

Research shows that [18F]F-AraG, which participants in this trial will receive, is a promising tool for tracking immune activity in the body. Studies have found that [18F]F-AraG can highlight areas where T-cells, a type of immune cell, are active. This is important for understanding immune system function. [18F]F-AraG resembles a compound used to treat diseases involving T-cells. Early results suggest it might reveal how the immune system responds after a COVID-19 infection. Using PET-CT scans, researchers can safely and easily identify active immune areas. This could be crucial for understanding COVID-19 recovery. ^{6 7 8 9 10}

Who Is on the Research Team?

Timothy J Henrich, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults over 18 who've recently had COVID-19, with symptoms starting at least 14 days ago or a positive test if asymptomatic. They must have certain blood cell counts and organ function levels, not be pregnant or breastfeeding, and agree to use two forms of birth control if applicable.

Inclusion Criteria

My kidneys are functioning well, with a creatinine clearance rate of 60 mL/min or higher.

I am older than 18 years.

Your absolute neutrophil count is higher than 1000 per cubic millimeter.

Exclusion Criteria

Pregnancy

I have had a stem cell or organ transplant from another person.

Breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants receive an intravenous microdose of [18F]F-AraG followed by whole-body PET-CT imaging

4 weeks

1 visit (in-person)

Optional Imaging Extension

Participants may receive a second optional [18F]F-AraG dose and PET-CT imaging

1 month to 1 year

1 visit (in-person, optional)

Follow-up

Participants are monitored for safety and effectiveness after imaging

5 months

What Are the Treatments Tested in This Trial?

Interventions

• [18F]F-AraG

Trial Overview The study tests an imaging agent called [18F]F-AraG using PET-CT scans to see how it distributes in the body after COVID-19 infection. Participants will receive up to two microdoses of the tracer; one mandatory scan followed by an optional second scan four months later.

How Is the Trial Designed?

Group I: [18F]F-AraG Experimental Treatment 1 Intervention

Radiofluorinated imaging agent, \[18F\]F-AraG (2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine) Trade name: VisAcT

Who Is Running the Clinical Trial?

CellSight Technologies, Inc.

Lead Sponsor

Trials

18

Recruited

320+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

COVID-19 vaccination can lead to increased glucose metabolism in lymph nodes and the spleen, as observed through [18F]-FDG PET/CT imaging, indicating a robust immune response.

Recognizing these immune activation patterns is crucial for nuclear physicians to differentiate between normal post-vaccination responses and potential pathological conditions in patients after receiving vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Response Visualized In Vivo by [18F]-FDG PET/CT after COVID-19 Vaccine. Seban, RD., Champion, L., Deleval, N., et al.[2021]

Folic acid-based radiopharmaceuticals, like 18F-AzaFol, can specifically target activated macrophages, which are crucial in the inflammatory response during COVID-19, potentially aiding in the identification of patients at risk for severe complications such as acute respiratory distress syndrome (ARDS).

In a preclinical study, 18F-AzaFol demonstrated effectiveness as an imaging tool for monitoring macrophage-driven lung diseases, and it has been safely used in a multicenter cancer trial, suggesting its potential for clinical application in COVID-19 management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can Nuclear Imaging of Activated Macrophages with Folic Acid-Based Radiotracers Serve as a Prognostic Means to Identify COVID-19 Patients at Risk? Müller, C., Schibli, R., Maurer, B.[2020]

The study demonstrated that the radiotracer [18F]DPA714 effectively visualizes inflammation in the lungs of SARS-CoV-2-infected rhesus monkeys, with increased uptake observed in pulmonary lesions and mediastinal lymph nodes as early as 2 days post-infection.

The findings suggest that [18F]DPA714 could serve as a valuable diagnostic tool for monitoring pulmonary inflammation in SARS-CoV-2 and potentially other viral respiratory infections, as it correlates with the activation of immune cells in the bloodstream.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel application of [18F]DPA714 for visualizing the pulmonary inflammation process of SARS-CoV-2-infection in rhesus monkeys (Macaca mulatta). Meijer, L., Böszörményi, KP., Bakker, J., et al.[2022]

The study utilized 124I-iodo-DPA-713 PET/CT imaging in a hamster model of SARS-CoV-2 infection to successfully visualize and quantify lung inflammation, showing that this imaging tool can effectively highlight areas of activated macrophages in pneumonic lesions.

Results indicated that male hamsters exhibited worse pulmonary disease and higher levels of macrophage activity compared to females, suggesting potential gender differences in immune response to COVID-19, which could inform future therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

124I-Iodo-DPA-713 Positron Emission Tomography in a Hamster Model of SARS-CoV-2 Infection. Ruiz-Bedoya, CA., Mota, F., Ordonez, AA., et al.[2023]

In a study of 31 COVID-19 patients who underwent FDG PET/CT scans, 41.9% had positive results, indicating that while the imaging technique has limited sensitivity for detecting COVID-19, it can identify patients at higher risk for severe symptoms and hospitalizations.

Patients with positive PET scans showed significantly higher rates of symptomatic infection (77%) and hospitalizations (46%), suggesting that FDG PET/CT may be useful in predicting the severity of COVID-19 in patients undergoing cancer care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDG PET/CT imaging features and clinical utility in COVID-19. Yeh, R., Elsakka, A., Wray, R., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39762664

Effectiveness of AZD7442 (Tixagevimab/Cilgavimab) for ... Our results suggest that AZD7442 300 mg reduced COVID-19 hospitalizations among immunocompromised individuals; however, the findings are limited by a lack ...

2. withpower.com withpower.com/trial/early-phase-1-covid-19-3-2021-ec07d

Immune Activation Imaging for COVID-19 Trial Overview The study tests an imaging agent called [18F]F-AraG using PET-CT scans to see how it distributes in the body after COVID-19 infection.

3. researchgate.net researchgate.net/publication/46256837_Synthesis_of_2'-Deoxy-2'-18FFluoro-9-b-D-Arabinofuranosylguanine_a_Novel_Agent_for_Imaging_T-Cell_Activation_with_PET

Deoxy-2′-[18F]Fluoro-9-β-D-Arabinofuranosylguanine: a ... 9-(β-D-Arabinofuranosyl)guanine (AraG) is a guanosine analog that has a proven efficacy in the treatment of T-cell lymphoblastic disease.

4. profiles.stanford.edu profiles.stanford.edu/benjamin-franc

Benjamin Lewis Franc - Stanford Profiles Here, we show that a novel PET radiotracer, 2'-deoxy-2'-[18F]fluoro-9-β-D-arabinofuranosylguanine ([18F]F-AraG), targeted toward two salvage kinase pathways ...

5. escholarship.org escholarship.org/search/?q=author%3ALevi%2C%20Jelena

Your search: "author:Levi, Jelena" Here, we evaluated the potential of 2'-deoxy-2'-18F-fluoro-9-β-d-arabinofuranosylguanine (18F-FAraG) PET imaging to noninvasively assess infiltrating T ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04283461

Safety and Immunogenicity Study of 2019-nCoV Vaccine ... This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of mRNA-1273 manufactured by ModernaTX, Inc.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10418298/

Multimodal Molecular Imaging Reveals Tissue-Based T Cell ... Multimodal molecular imaging reveals tissue-based T cell activation and viral RNA persistence for up to 2 years following COVID-19.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11337933/

Tissue-Based T Cell Activation and Viral RNA Persist for Up to ... [18F]F-AraG PET/CT imaging was performed on 24 participants from the UCSF-based Long-term Impact of Infection with Novel Coronavirus (LIINC) study (NCT04362150) ...

9. nature.com nature.com/articles/s42003-024-06494-x

[18F]F-AraG imaging reveals association between ... This study explicates a newfound connection between neuroinflammation and brown- and bone marrow adipose tissue.

10. malacards.org malacards.org/card/severe_acute_respiratory_syndrome

Severe Acute Respiratory Syndrome (SARS) Severe acute respiratory syndrome (SARS) is a rare pulmonary disease caused by the SARS-CoV coronavirus. It has an incubation period of 2 to 7 days and ...