Long COVID-19 [11C]CPPC Study

A Phase l Study to Assess the Safety and Tolerability of PET Imaging With [11 C]CPPC [5-cyano-N-( 4-( 4-[l l CJ me1hylpiperazin-l-yl)-2-(Piperidin-l-yl)Phenyl)Furan-2-carboxamide] Radioligand and Magnetic Resonance (MR) Imaging in Patients With Long COVID.

The goal of this study is to evaluate the safety of using the [5-cyano-N-(4-(4-[11C]Methylpiperazin-1-yl)-2-(Piperidin-1-yl)Phenyl)Furan-2-carboxamide] ([11C]CPPC) radiotracer in positron emission tomography (PET) imaging of people with history of COVID-19 infection, with and without symptoms. The investigators are also interested to see whether use of this radiotracer reveals imaging differences between patients with history of COVID-19 infection and still exhibiting symptoms or healthy patients with history of COVID-19 infection but exhibiting no current symptoms.

Study Overview

• Status: Recruiting
• Conditions: COVID Long-Haul
• Intervention / Treatment: Drug: [11C]CPPC Injection

Detailed Description

This is a Phase 1 study of safety and tolerability of an investigational radiotracer drug called [5-cyano-N-(4-(4-[11C]Methylpiperazin-1-yl)-2-(Piperidin-1-yl)Phenyl)Furan-2-carboxamide] ([11C]CPPC). A radiotracer is a substance that chemically marks certain structures in the body. In this case, [11C]CPPC highlights structures expressing colony stimulating factor receptor (CSF1R), a receptor that is expressed on microglial cells. A safety and tolerability study is looking to see if there are any unanticipated, possibly harmful, effects of the use of the radiotracer in humans. However, ultimately, the investigators would like to know if this drug can be used to make better images of the brain for patients with history of COVID-19 infection, which could help doctors better understand the disease and help take care of patients suffering from Long COVID symptoms. This study will use a radiotracer to look for a chemical receptor which may be affected in patients who report of Long COVID. After receiving the radiotracer, participants' brains will be scanned with a positron emission tomography (PET) imaging machine. Each participant will also undergo magnetic resonance imaging (MRI) without contrast, detailed cognitive testing and a neurological exam. This study will assess possible associations between COVID-19 infection, cognitive function, other neurological symptoms, and 11C-CPPC PET neuroimaging in subjects.

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Mehreen Nabi, MBBS; Phone Number: 4109296586; Email: mnabi1@jh.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins Outpatient Center
      • Contact: Mehreen Nabi, MBBS
      • Principal Investigator: Licia Luna, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Have the ability to understand the requirements of the study, provide written informed consent, understand and provide written authorization for the use and disclosure of Protected Health Information (PHI) [per Health Insurance Portability and Accountability Act (HIPAA) Privacy Ruling] and comply with the study procedures.
2. Documented history of COVID infection at least 6 - 12 months before enrollment.
3. Men and women at least 18 years old.
4. Women must have a negative serum pregnancy test and practice an acceptable method of contraception or be of non-childbearing potential (post-menopausal for at least 2 years or who have undergone hysterectomy, oophorectomy or surgical sterilization).
5. Geographic accessibility to the study center and the ability to travel to the clinic for study visits.
6. Agrees to the visit schedule as outlined in the informed consent.
7. Pre-study labs within normal range, or if abnormal, deemed not clinically significant by the site investigator.

Exclusion Criteria:

1. History of recent nosocomial infection.
2. History of chronic neurological disorder, such as epilepsy, or structural Central Nervous System (CNS) abnormality such as stroke or arteriovenous malformation.
3. History of head trauma with prolonged loss of consciousness (>10 minutes) or any neurological condition including stroke, seizure (excluding childhood febrile seizure), or visible structural abnormality on prior MRI.
4. Active or recent (in the past year) substance dependence (drugs-including nicotine, marijuana or alcohol).
5. Receipt of any investigational drug, device or biologic within 30 days of administration of study compound.
6. Use of anti-inflammatory medications, immunosuppressants, or benzodiazepines within 7 days of administration of study compound.

7. Any concomitant medical disease or condition limiting the safety to participate including, but not limited to:

   • Coagulopathy
   • Active infection
8. Contraindications to MRI scanning to include pacemakers, metallic implants/prosthesis or prohibitive claustrophobia, etc.
9. Contraindications to PET scanning to include pregnancy, etc.
10. Any medical condition that in the opinion of the study investigators would constitute a safety risk to the subject.
11. Any radiation exposure in the past calendar year that in combination with the radiation exposure from this study would exceed 5 rem.
12. Any history of learning disability or special education (due to the potential to affect performance on neuropsychological testing).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with history of COVID-19 infection and still experiencing symptoms (Long-COVID); Participants with a diagnosis of Long- COVID will receive a single dose of [11C]CPPC (370 megabecquerel (MBq) (X±1 mCi)) intravenously and subsequent positron emission tomography (PET) scan.	Drug: [11C]CPPC Injection; A single dose of [11C]CPPC (370 megabecquerel (MBq) (X±1 mCi)) intravenously and subsequent positron emission tomography (PET) scan. Other Name: [5-cyano-N-(4-(4-[11C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide]
Experimental: Healthy Participants with history of COVID-19 infection but not experiencing any symptoms.; Healthy participants (without any history of post-COVID symptoms) will receive a single dose of [11C]CPPC (370 megabecquerel (MBq) (X±1 mCi)) intravenously and subsequent positron emission tomography (PET) scan.	Drug: [11C]CPPC Injection; A single dose of [11C]CPPC (370 megabecquerel (MBq) (X±1 mCi)) intravenously and subsequent positron emission tomography (PET) scan. Other Name: [5-cyano-N-(4-(4-[11C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide]

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the safety and tolerability of one dose level of [11C]CPPC when administered intravenously.	Safety and tolerability will be determined by evaluation of spontaneously reported adverse events, clinical laboratory test results, physical, cognitive and neurologic exams and imaging (PET).	Baseline and up to 2 days follow-up after scan
Safety of use of [11C]CPPC in patients with Long-COVID and healthy participants with history of COVID-19 infection as assessed by a change in complete blood count (CBC) test.	Safety of use of [11C]CPPC in positron emission tomography (PET) neuroimaging of patients with Long-Covid and healthy participants with history of COVID-19 infection. Safety will be assessed by monitoring of the complete blood count (CBC) for a change from baseline that is outside of the normal range.	Baseline and up to 2 days follow-up after scan
Safety of use of [11C]CPPC in patients with Long-COVID and healthy participants with history of COVID-19 infection as assessed by a change in complete metabolic panel (CMP) test.	Safety of use of [11C]CPPC in positron emission tomography (PET) neuroimaging of patients with Long-COVID and healthy participants with history of COVID-19 infection. Safety will be assessed by a change in the CMP from baseline that is outside of the normal range	Baseline and up to 2 days follow-up after scan

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biodistribution of [11C]CPPC by PET imaging	Image analysis of PET imaging obtained of patients and healthy participants. The PET compartmental model fits will be applied to the regional time activity curves (TACs) will be first assessed visually before the relative goodness of fit will be assessed using the statistical F test.	1 day
Cognitive function as assessed by the NIH Toolbox Cognition Battery (NIHTB-CB)	NIH Toolbox Cognition Battery (NIHTB-CB), which is an iPad-based instrument assessing five cognitive sub-domains: Language, Executive Function, Episodic Memory, Processing Speed, and Working Memory. Score range 59 - 140, higher score means better cognition.	1 day
Neuro-psychological assessment as assessed by the The Rey-Osterrieth complex figure test (ROCF)	The Rey-Osterrieth complex figure test (ROCF) is a neuro-psychological assessment in which participants are asked to reproduce a complicated line drawing, first by copying it freehand (recognition), and then drawing from memory (recall). Scoring of drawings is based on the 36-point scoring system (0 being the worst score and 36 the best).	1 day
Global cognitive function as assessed by the Mini-Mental State Exam (MMSE)	The MMSE is a measure of global cognitive function, scores range from 0-30, a lower score indicates greater cognitive impairment.	1 day
Dementia as assessed by the Clinical Dementia Rating (CDR) scale	The Clinical Dementia Rating Dementia Staging Instrument minimum score = 0, maximum score = 18. Low scores indicate less problems.	1 day
Hospital Anxiety and Depression Scale (HADS) score	Scoring for the Hospital Anxiety and Depression scale is 0-21; Normal (0-7); Borderline Abnormal Case (8-10); and Abnormal Case (11-21) higher score indicates worse outcome.	1 day

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Radiological Society of North America
• Investigators: Principal Investigator: Licia Luna, M.D., Ph.D., Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: January 23, 2024
• First Submitted That Met QC Criteria: January 23, 2024
• First Posted (Actual): January 25, 2024

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Chronic Disease; Post-Infectious Disorders; COVID-19; Post-Acute COVID-19 Syndrome
• Other Study ID Numbers: IRB00361674

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