Assessing the effectiveness of a new pneumococcal vaccine in healthy adults

A Phase IV, Experimental Human Pneumococcal Challenge (EHPC) Model to Investigate Streptococcus Pneumoniae Serotype 3 (SPN3) Colonisation Following PCV15, a Double Blind Randomised Controlled Trial (DBRCT) in Healthy Participants Aged 18 - 50 Years in the UK.

This study is testing a new pneumococcal vaccine to see if it helps healthy adults aged 18-50 fight off an infection caused by a specific bacteria.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 106 (estimated)
• Ages: 18 Years to 50 Years
• Sex: All
• Sponsor: University of Oxford (Academic / other)
• Locations: 2 sites (Liverpool, North West and 1 other locations)
• Trial ID: NCT06731374 on ClinicalTrials.gov

What this trial studies

This Phase IV double-blind, placebo-controlled trial evaluates the effectiveness of the PCV15 vaccine against pneumococcal carriage in healthy adults aged 18-50. Participants will be randomly assigned to receive either the vaccine or a placebo, followed by an intranasal inoculation with Streptococcus pneumoniae serotype 3. The study will monitor the participants for 28 days to assess nasal colonization and immune response. Additionally, a small cohort will undergo nasal biopsies to further investigate the vaccine's effects.

Who should consider this trial

Good fit: Ideal candidates are healthy adults aged 18 to 50 who can comply with study procedures and provide informed consent.

Not a fit: Patients outside the age range of 18 to 50 or those with pre-existing health conditions that may require hospitalization during the study will not benefit.

Why it matters

Potential benefit: If successful, this vaccine could significantly reduce the incidence of pneumococcal disease in at-risk populations by enhancing immunity.

How similar studies have performed: Previous studies with pneumococcal vaccines have shown success, but this specific approach with PCV15 is novel.

Eligibility criteria

Inclusion Criteria:

1. Adults between 18 to 50 years old (inclusive) at the time of enrolment.
2. Medically healthy, such that according to investigator judgement, hospitalisation within the study period is not anticipated, and the participant appears likely to be able to remain a study participant through to the end of protocol-specified follow-up. Planned elective procedures for pre-existing conditions may be allowable.
3. Fluent spoken English - to ensure a comprehensive understanding of the research project and their proposed involvement.
4. Able to attend the scheduled visits and to comply with all study procedures, including internet access for the recording of electronic diary after inoculation.
5. Willing and able to give informed consent for participation in the study.
6. Willing to allow confirmation of past medical history either through provision of, or access to, a medical record summary or other medical documentation or allowing investigators to obtain a copy of their medical history from their GP practice or accessed via electronic patient records.
7. Willing to allow their GP and/or consultant, if appropriate, to be notified of participation in the study.
8. Willing to provide their national insurance number or passport number to be registered on The Over-Volunteering Prevention System (TOPS).
9. For participants of childbearing potential only: willing to use effective contraception for the duration of the study AND to have a pregnancy test on the day of screening and challenge.

Exclusion Criteria:

1. Research Participants:

   1. Participation in another research study, in which procedures performed could compromise the integrity of this study (such as significant volumes of blood taken), or are planning to do so within the trial period
   2. Currently a participant in a previous EHPC trial within the last 2 years or at the discretion of the study team
2. Vaccination (self-reported or confirmed from GP questionnaire or medical records/summary if deemed necessary at clinician discretion):

   1. Have had any previous pneumococcal vaccination in the past 5 years (including in a research study)
   2. Planned vaccination during the study
3. Allergy:

   1. Have an allergy to penicillin or amoxicillin (for main study cohort only)
   2. History of a bleeding disorder (e.g., Factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture
   3. Have previous anaphylaxis or severe adverse reaction to any component/excipient of the vaccine or to any vaccine
   4. Allergy to Lidocaine local anaesthetic (for nasal biopsy cohort only)
4. Health History (self-reported or confirmed from GP questionnaire or medical records/summary if deemed necessary): moderate ill health including but not limited to:

   1. Asplenia or dysfuction of the spleen
   2. Chronic respiratory disease (e.g. asthma \[on medication\], COPD, emphysema, bronchiectasis)
   3. Chronic heart disease (e.g. angina, ischaemic heart disease, chronic heart failure) \[controlled stable hypertension +/- angina may be included\].
   4. Chronic kidney disease (e.g. nephrotic syndrome, kidney transplant, on dialysis)
   5. Chronic liver disease (e.g. cirrhosis, biliary atresia, hepatitis)
   6. Chronic neurological conditions
   7. Connective tissue disease
   8. Dementia
   9. Diabetes mellitus (including diet controlled)
   10. Immunosuppression or history of receiving immunosuppressive therapy - at the discretion of the investigator
   11. Individuals with cochlear implants
   12. Individuals with major cerebrospinal fluid leaks (e.g. following trauma, major skull surgery, or requiring CSF shunt)
   13. Recurrent otitis media.
   14. History of significant unexplained bleeding after a surgical or dental procedure (for nasal biopsy participants only)
   15. Have any uncontrolled medical/surgical/mental health conditions at the discretion of the study doctor.
   16. Major pneumococcal illness requiring hospitalisation within the last 10 years.
   17. Significant mental health condition (e.g previous admissions in a psychiatric unit, at the discretion of the clinician) that would impair the participant's ability to participate in the study
5. Taking Medications:

   1. Any medication that may affect the immune system in the last 3 months (e.g. systemic steroids \[IM/IV\], Roaccutane, disease modifying anti-rheumatoid drugs)
   2. Long-term use of antibiotics (see also section of Temporary Exclusion Criteria)
   3. Use of any medication or other product (prescription or over-the-counter) for symptoms of rhinitis or nasal congestion within the last 1 month
   4. Use of any medication affecting blood clotting (any oral/injectable anticoagulants)
6. Female participants who are pregnant, lactating or intending on becoming pregnant during the study
7. Direct caring role or close contact with individuals at higher risk of infection (for main study cohort only):

   1. Children under 5 years of age
   2. Chronic ill health or immunosuppressed adults
   3. Older adults
8. Smoker:

   1. Current or ex-smoker (regular cigarettes/cigars/e-cigarette/vaping/smoking of recreational drugs) in the last 6 months
   2. Previous significant smoking history (more than 20 cigarettes per day for 20 years or the equivalent \[\>20 pack years\])
9. Suspected or known current alcohol or drug abuse, as per investigators discretion
10. Overseas travel during the follow-up period (from the time point of inoculation to antibiotic treatment or completion of the 28 day follow up period post inoculation)
11. Any other issue which, in the opinion of the study staff, may:

    1. Put the participant or their contacts at risk because of participation in the study
    2. Adversely affect the interpretation of the study results, or
    3. Impair the participant's ability to participate in the study
12. Study site staff or a partner or dependent child of study site staff

Where this trial is running

Liverpool, North West and 1 other locations

• Liverpool Vaccine Group — Liverpool, North West, United Kingdom (Recruiting)
• Oxford Vaccine Group — Oxford, Oxfordshire, United Kingdom (Recruiting)

Study contacts

• Principal investigator: Simon Drysdale, MRCPCH, PhD, PgDip PID, FRCPH — University of Oxford
• Study coordinator: Carla Solorzano-Gonzalez, PhD

Conditions Pneumococcal Disease; Pneumococcal Carriage; Streptococcus pneumoniae; Experimental Human Pneumococcal Challenge; Pneumococcal carriage; PCV15; VAXNEUVANCE; SPN3