A Pilot Clinical Study of PET Scanning in Evaluation of Vaccine Reactogenicity (PETVACC)

This study forms part of an integrated, multi-study effort to identify potential biomarkers of reactogenicity to vaccines. We have selected PET-CT as it is in routine clinical use and has been serendipitously shown to image lymph nodes and injection site inflammation after immunisation.The study's objectives are exploratory:

1. To methodically characterise relative anatomical distribution and intensity of post-immunisation innate immune activation visualised by PET-CT after immunisation with adjuvanted and non-adjuvanted vaccines.
2. To correlate PET/CT changes with diary card recorded symptoms of reactogenicity.

Study Overview

• Status: Completed
• Conditions: Positron-Emission Tomography; Immunization Reaction
• Intervention / Treatment: Biological: Immunization

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Able to read and understand the informed consent form (ICF), and understand study procedures
2. Signed the ICF
3. Healthy male aged 18'Äì55 years inclusive
4. BMI 19'Äì27 kg/m2
5. Pre-immunised with hepatitis B vaccine on the basis of immunisation history if Fendrix or Engerix B is to be the study vaccine
6. Available for follow-up for the duration of the study
7. Is, in the opinion of the investigator, healthy on the basis of a medical history, symptom directed medical examination and vital signs
8. Have not undergone research radiation exposures, and agree to avoid such exposures, for 12 months before/after this study
9. Be willing to avoid vigorous exercise or contact sports between vaccination and PET scan (e.g. gym workouts, prolonged cycling, rowing, martial arts or rugby)

Exclusion Criteria:

1. History of hypersensitivity to any of the vaccine components or a history of any allergy that in the opinion of the investigator would contraindicate participant participation
2. Use of steroids or immunosuppressive/immunomodulating drugs either orally or parenterally within 3 months of the PET scan. (Topical/ocular/nasal/inhaled steroids are allowed.)
3. Expression of only TSPO with low-affinity to PBR28, on the basis of TSPO genotype
4. Currently participating in a clinical study with a drug or device
5. Any condition that, in the investigator'Äôs opinion, compromises the participant'Äôs ability to meet protocol requirements or to complete the study
6. Unable to read and speak English to a fluency level adequate for the full comprehension of procedures required in participation and consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fendrix; Fendrix (Hepatitis B surface antigen adjuvanted by AS04C containing 3­O­desacyl­4'­ monophosphoryl lipid A adsorbed on aluminium phosphate, GlaxoSmithKline; 0.5 mL. intramuscular. stat.	Biological: Immunization; Immunisation with one of four licensed vaccines
Experimental: Bexsero; Bexsero (Meningococcal group B subunit / Outer Membrane Vesicles, GlaxoSmithKline); 0.5 mL. intramuscular. stat.	Biological: Immunization; Immunisation with one of four licensed vaccines
Experimental: Fluad; Fluad (split virion inactivated seasonal trivalent influenza vaccine adjuvanted with MF59C, Northern Hemisphere 2016-17, Seqirus Vaccines and Diagnostics) 0.5 mL. intramuscular. stat.	Biological: Immunization; Immunisation with one of four licensed vaccines
Experimental: Seasonal Trivalent Influenza Vaccine; Seasonal Trivalent Influenza Vaccine ('ÄòSTIV'Äô, split virion inactivated, Northern Hemisphere 2016-17, Sanofi Pasteur); 0.5 mL. intramuscular. stat.	Biological: Immunization; Immunisation with one of four licensed vaccines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
18FDG-PET/CT imaging	Quantification of PET activity at injection site and draining lymph nodes	4 hours
18FDG- or 11C-PBR28-PET/CT imaging	Quantification of PET activity at injection site and draining lymph nodes	1 day
18FDG- or 11C-PBR28-PET/CT imaging	Quantification of PET activity at injection site and draining lymph nodes	3 days
18FDG- or 11C-PBR28-PET/CT imaging	Quantification of PET activity at injection site and draining lymph nodes	5 days
18FDG- or 11C-PBR28-PET/CT imaging	Quantification of PET activity at injection site and draining lymph nodes	7 days
18FDG-PET/CT imaging	Quantification of PET activity at injection site and draining lymph nodes	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diary card of reactogenicity	Recording of solicited and unsolicited adverse events after immunisation	0 to 10 days

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Imperial College Healthcare NHS Trust
• Investigators: Principal Investigator: David JM Lewis, MD, Imperial College Healthcare NHS Trust

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2016
• Primary Completion (Actual): September 3, 2020
• Study Completion (Actual): September 3, 2020

Study Registration Dates

• First Submitted: August 13, 2020
• First Submitted That Met QC Criteria: August 13, 2020
• First Posted (Actual): August 17, 2020

Study Record Updates

• Last Update Posted (Actual): September 9, 2020
• Last Update Submitted That Met QC Criteria: September 8, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: PETVACC; 191407 (IRAS project ID); 15/LO/2039 (Other Identifier: London 'Äì Surrey Borders Research Ethics Committee)

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