Imaging Immune Activation in COVID-19

Covid19 Clinical Trial

Official title:

Imaging Immune Activation in COVID-19

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04815096
• Other study ID #: 20-32477
• Status: Recruiting
• Phase: Early Phase 1
• Start date: April 15, 2021
• Est. completion date: October 1, 2024

Study information

• Verified date: September 2023
• Source: CellSight Technologies, Inc.
• Contact: Timothy Henrich, MD
• Phone: 6282065518
• Email: timothy.henrich[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: October 1, 2024
• Est. primary completion date: October 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• Covid19
• SARS-CoV Infection
• Severe Acute Respiratory Syndrome

Intervention

Drug:
• [18F]F-AraG (2'-deoxy-2'-fluoro-9-ß-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.

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
CellSight Technologies, Inc.	University of California, San Francisco

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	[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	[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
Secondary	[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
Secondary	[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