A Pilot Clinical Study of PET Scanning in Evaluation of Vaccine Reactogenicity

Study Overview
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Brief Summary
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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: 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. To correlate PET/CT changes with diary card recorded symptoms of reactogenicity.

Official Title
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A Pilot Clinical Study of PET Scanning in Evaluation of Vaccine Reactogenicity

Conditions
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Positron-Emission Tomography, Immunization Reaction

Intervention / Treatment
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* Biological: Immunization


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to read and understand the informed consent form (ICF), and understand study procedures Signed the ICF Healthy male aged 18'Äì55 years inclusive BMI 19'Äì27 kg/m2 Pre-immunised with hepatitis B vaccine on the basis of immunisation history if Fendrix or Engerix B is to be the study vaccine Available for follow-up for the duration of the study Is, in the opinion of the investigator, healthy on the basis of a medical history, symptom directed medical examination and vital signs Have not undergone research radiation exposures, and agree to avoid such exposures, for 12 months before/after this study 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: 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 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.) Expression of only TSPO with low-affinity to PBR28, on the basis of TSPO genotype Currently participating in a clinical study with a drug or device Any condition that, in the investigator'Äôs opinion, compromises the participant'Äôs ability to meet protocol requirements or to complete the study Unable to read and speak English to a fluency level adequate for the full comprehension of procedures required in participation and consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fendrix<br>Fendrix (Hepatitis B surface antigen adjuvanted by AS04C containing 3¬≠O¬≠desacyl¬≠4'¬≠ monophosphoryl lipid A adsorbed on aluminium phosphate, GlaxoSmithKline; 0.5 mL. intramuscular. stat. | Biological: Immunization<br>* Immunisation with one of four licensed vaccines<br>|
| Experimental: Bexsero<br>Bexsero (Meningococcal group B subunit / Outer Membrane Vesicles, GlaxoSmithKline); 0.5 mL. intramuscular. stat. | Biological: Immunization<br>* Immunisation with one of four licensed vaccines<br>|
| Experimental: Fluad<br>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<br>* Immunisation with one of four licensed vaccines<br>|
| Experimental: Seasonal Trivalent Influenza Vaccine<br>Seasonal Trivalent Influenza Vaccine ('ÄòSTIV'Äô, split virion inactivated, Northern Hemisphere 2016-17, Sanofi Pasteur); 0.5 mL. intramuscular. stat. | Biological: Immunization<br>* Immunisation with one of four licensed vaccines<br>|

What is the study measuring?
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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 |