Imaging Immune Activation in COVID-19

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.

Study Overview

• Status: Recruiting
• Conditions: Covid19; SARS-CoV Infection
• Intervention / Treatment: Drug: [18F]F-AraG (2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine)

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 Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Timothy Henrich, MD; Phone Number: 6282065518; Email: timothy.henrich@ucsf.edu
• Study Contact Backup: Name: Leo Torres; Email: Leonel.torres@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94110
      • Recruiting
      • University of California, San Francisco
      • Sub-Investigator: Robert Flavel, MD
      • Contact: Timothy J Henrich, MD; Phone Number: 415-206-5518; Email: timothy.henrich@ucsf.edu
      • Principal Investigator: Timothy J Henrich, MD
      • Sub-Investigator: Henry F Vanbrocklin, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >18 years
• Ability to read and understand written informed consent document
• 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.
• > 14 days since onset of COVID-19 symptoms (or if no symptoms, from time of initial nucleic acid based diagnostic test).

• Laboratory evaluations obtained within 60 days prior to entry.

  • Platelet count ≥75,000/mm3
  • ANC >1000/mm3
  • Aspartate aminotransferase (AST) <3 x ULN
  • Alanine aminotransferase (ALT) <3 x ULN
  • Calculated creatinine clearance (CrCl) ≥60 mL/min as estimated by the Cockcroft-
  • Gault equation

Exclusion Criteria:

• Any medical condition that would compromise the imaging acquisition, in the opinion of the investigator
• 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)
• Participants who are breastfeeding
• 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).
• Participants who have had prior allogeneic stem cell or solid organ transplant.
• 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.
• Known SARS-CoV-2 shedding within 5 days of PET imaging.
• Previously diagnosed myelodysplasia syndrome or history of lymphoproliferative disease prior to study entry
• Active systemic autoimmune diseases not related to COVID-19.
• 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.
• Prior PET scan or therapeutic radiation within 1 year of study enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: VisAcT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[18F]F-AraG uptake in participants with convalescent COVID-19	To determine regional uptake of [18F]F-AraG in participants with convalescent COVID-19.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[18F]F-AraG uptake in participants with convalescent COVID-19 over time	To determine the anatomical distribution of [18F]F-AraG in participant with convalescent COVID-19 approximately 4 weeks and 5 months (optional) over time.	5 months
[18F]F-AraG uptake in participants with mild to severe COVID-19 symptoms	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	1 year
[18F]F-AraG uptake in female versus male participants	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.	1 year

Collaborators and Investigators

• Sponsor: CellSight Technologies, Inc.
• Collaborators: University of California, San Francisco
• Investigators: Principal Investigator: Timothy Henrich, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2021
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: March 23, 2021
• First Submitted That Met QC Criteria: March 23, 2021
• First Posted (Actual): March 24, 2021

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 27, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: [18F]F-AraG; PET-CT Imaging
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Severe Acute Respiratory Syndrome; COVID-19
• Other Study ID Numbers: 20-32477

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No