Imaging Immune Activation in COVID-19
Study Details
Study Description
Brief Summary
This is a single center, single arm exploratory imaging study involving up to two intravenous microdoses of [18F]F-AraG (the second tracer dose is optional) followed by whole-body PET-CT imaging in participants with convalescent COVID-19. Up to 20 participants will be enrolled over an accrual period of approximately 24 months. Each participant will undergo one PET-CT scan following 50 +/- 10 minutes uptake following a single bolus injection of [18F]F-AraG in order to determine the tissue distribution of tracer in pariticpants with recent SARS-CoV-2 infection. A second optional [18F]F-AraG dose and PET-CT will be offered approximately 4 months following the initial imaging time point.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Detailed Description
This is a single center exploratory imaging study involving up to two intravenous microdoses of [18F]F-AraG (the second tracer dose is optional) followed by whole-body PET-CT imaging in participants 18 years of age and older with recent SARS-CoV-2 diagnosis and COVID-19 at least 14 days following onset of symptoms. The primary objective is to determine the anatomical distribution of [18F]F-AraG in participant with convalescent COVID-19 approximately 4 weeks and 5 months (optional, 4 months following first PET imaging visit) following onset of symptoms (N = 20). Tracer activity will also be compared with sex and age-matched uninfected historical control participants enrolled in prior studies. Up to 20 participants will be enrolled in this study who will be identified in the UCSF LIINC longitudinal COVID-19 cohort study. Each participant will undergo one PET-CT scan following 50 +/- 10 minutes uptake following a single bolus injection of [18F]F-AraG. A second optional [18F]F-AraG dose and PET-CT will be offered approximately 4 months following the initial imaging time point.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: [18F]F-AraG Radiofluorinated imaging agent, [18F]F-AraG (2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine) Trade name: VisAcT |
Drug: [18F]F-AraG (2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine)
[18F]F-AraG is a radiolabeled high affinity substrate for deoxyguanosine kinase (dGK) and a low affinity substrate for deoxycytidine kinase (dCK), which are over-expressed in activated T cells.
Other Names:
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Outcome Measures
Primary Outcome Measures
- [18F]F-AraG uptake in participants with convalescent COVID-19 [4 weeks]
To determine regional uptake of [18F]F-AraG in participants with convalescent COVID-19.
Secondary Outcome Measures
- [18F]F-AraG uptake in participants with convalescent COVID-19 over time [5 months]
To determine the anatomical distribution of [18F]F-AraG in participant with convalescent COVID-19 approximately 4 weeks and 5 months (optional) over time.
- [18F]F-AraG uptake in participants with mild to severe COVID-19 symptoms [1 year]
To compare maximum SUV (SUVmax) and the mean SUV (SUVmean) from regions of interest (ROI; e.g. lungs, lymph node chains,) between convalescent COVID-19 individuals with mild (N=10) to those with moderate to severe initial disease (N=10) at each imaging timepoint
- [18F]F-AraG uptake in female versus male participants [1 year]
To compare maximum SUV (SUVmax) and the mean SUV (SUVmean) from regions of interest (ROI; e.g. lungs, lymph node chains,) between male and female participants with convalescent COVID-19 at each imaging time point.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age >18 years
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Ability to read and understand written informed consent document
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Have a recent diagnosis of SARS-CoV-2 infection as defined by a prior positive SARS-CoV-2 nucleic acid-based diagnostic test performed in a clinical laboratory on one or more nasopharyngeal or respiratory secretion samples.
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14 days since onset of COVID-19 symptoms (or if no symptoms, from time of initial nucleic acid based diagnostic test).
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Laboratory evaluations obtained within 60 days prior to entry.
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Platelet count ≥75,000/mm3
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ANC >1000/mm3
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Aspartate aminotransferase (AST) <3 x ULN
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Alanine aminotransferase (ALT) <3 x ULN
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Calculated creatinine clearance (CrCl) ≥60 mL/min as estimated by the Cockcroft-
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Gault equation
Exclusion Criteria:
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Any medical condition that would compromise the imaging acquisition, in the opinion of the investigator
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Participants who are pregnant (female participants of childbearing age will be tested prior to injection of imaging agent at entry visit/initial visit - positive test will exclude from further participation in the study)
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Participants who are breastfeeding
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Female participants of reproductive potential (defined as women who have not been post-menopausal for at least 24 consecutive months (i.e., who have had menses within the preceding 24 months), or women who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy) must have a negative urine or serum pregnancy test with a sensitivity of at least 25 mIU/mL performed within 24 hours prior to PET imaging. Females of reproductive potential will need to be on 2 forms of birth control (excluding withdrawal or timing methods).
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Participants who have had prior allogeneic stem cell or solid organ transplant.
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Screening absolute neutrophil count <1,000 cells/mm3, platelet count <75,000 cells/mm3, hemoglobin < 8 mg/dL, estimated creatinine clearance <60 mL/minute, aspartate aminotransferase >3 x ULN, alanine aminotransferase >3 x ULN.
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Known SARS-CoV-2 shedding within 5 days of PET imaging.
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Previously diagnosed myelodysplasia syndrome or history of lymphoproliferative disease prior to study entry
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Active systemic autoimmune diseases not related to COVID-19.
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COVID-19 vaccine prior to the first PET imaging session. Participants may receive COVID-19 vaccination after the first PET imaging session and the optional second PET scan, with the scan being performed at least 2 weeks following the most recent vaccine dose.
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Prior PET scan or therapeutic radiation within 1 year of study enrollment.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California, San Francisco | San Francisco | California | United States | 94110 |
Sponsors and Collaborators
- CellSight Technologies, Inc.
- University of California, San Francisco
Investigators
- Principal Investigator: Timothy Henrich, MD, University of California, San Francisco
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 20-32477