Carriage to Assess Protection of New Pneumococcal Vaccines - PCV15

NCT06731374 | Recruiting Phase 4 DMC

• 2 other identifiers: OVG 2024/02MISP 101865
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 2

Brief Summary

Streptococcus pneumoniae (pneumococcus) is a bacterium that causes just under four million serious infections every year. It is normal for pneumococcus bacteria to live in the noses of healthy adults and children as part of the nasal microflora without causing harm. This is called "carriage". But the bacteria can still be passed on to other people. If they are at-risk, for example elderly, or very young, or have pre-existing health conditions, the pneumococcus bacteria can cause pneumonia, which can cause serious life-threatening illness. Pneumococcus bacteria are surrounded by a sugar capsule. But the capsule does not always have the same components. As a result, the bacteria are classified into more than 100 different types. To make them effective, the vaccines that are currently available contain the sugar capsules of the most common pneumococcal types that cause disease. One such vaccine - PCV13 - has been effective globally in protecting against pneumococcus disease. It works because it controls the "carriage" (how a person carries the bacteria in their nose) of 13 types of the bacteria. Vaccines giving protection against other types of the bacteria are also becoming available worldwide. PCV15 is similar to PCV13 and protects against two additional types of the bacteria so may offer more protection. This study, which lasts 2 months and is funded by Merck Sharp \& Dohme (MSD), aims to assess if using PCV15 can protect against "carriage". To do this, investigators will use a well-established method already used with more than 2,000 people safely in other research. This involves "challenging" volunteers by putting a small amount of the pneumococcus bacteria into their noses. In this study, before they are challenged, volunteers will either be vaccinated with the real PCV15 vaccine or a dummy ("placebo"). The Investigators will then be able to compare the two groups to find out who the vaccine protected and who it did not. After the study everyone who takes part and fit into certain criteria will be given antibiotics to clear the pneumococcus colonisation. They will also be regularly monitored during the study to ensure their safety. A very small number of volunteers will be asked to have a biopsy to collect tissue samples from inside their nose before and after being vaccinated with PCV15. This will help researchers to understand more about how the immune system responds to the vaccine. The information gain in this project will help the investigators to understand how exactly PCV15 vaccine protects people against pneumococcus. This means that this vaccine and future pneumococcal vaccines will be improved to protect many lives in future around the world.

Conditions

Pneumococcal Disease; Pneumococcal Carriage

Keywords

Streptococcus pneumoniae; Experimental Human Pneumococcal Challenge; Pneumococcal carriage; PCV15; VAXNEUVANCE; SPN3

Outcome Measures

Primary Outcomes (1)

• Presence or absence of experimental SPN3 colonisation acquisition

  Presence or absence of SPN3 bacteria detected by microbiological culture in nasal wash samples for 28 days after experimental SPN3 inoculation at 1-month post PCv15 vaccination compared with placebo.

  Days 2, 7, 14 and 28 following experimental challenge

Secondary Outcomes (3)

• Density of experimental SPN3 colonisation

  Days 2, 7, 14 and 28 following experimental challenge

• Duration of experimental SPN3 colonisation

  Days 2, 7, 14 and 28 following experimental challenge

• Vaccine-induced immune responses

  Days 7 and 23 following vaccination and 2, 7, 14 and 28 following experimental challenge

Study Arms (2)

PCV-15 Vaccination

EXPERIMENTAL

One dose (0.5 ml) of PCV-15 is to be given Intramuscularly (IM) into the deltoid region of the arm at day 0.

Biological: PCV15; Biological: Streptococcus pneumoniae serotype 3

Placebo

PLACEBO COMPARATOR

0.9% saline is to be given Intramuscularly (IM) into the deltoid region of the arm at day 0.

Biological: Streptococcus pneumoniae serotype 3; Biological: Placebo

Interventions

PCV15 BIOLOGICAL

VAXNEUVANCE (Merck, Sharp \& Dohme LLC, a subsidiary of Merck \& Co, Inc., Rahway, NJ, USA \[MSD\]) is a 15-valent PCV containing capsular polysaccharides from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 22F, and 33F adjuvanted with aluminium phosphate.

Also known as: VAXNEUVANCE

PCV-15 Vaccination

Streptococcus pneumoniae serotype 3 BIOLOGICAL

Streptococcus pneumoniae SPN3 (Clade Ia, strain LIV014-S3) - Single inoculation at 80,000 colony-forming unit (CFU)/naris, 28 days after vaccination.

Also known as: SPN3, pneumococcus serotype 3

PCV-15 Vaccination; Placebo

Placebo BIOLOGICAL

The placebo consists of 0.9% sodium chloride for injection

Also known as: Saline Placebo, 0.9% Sodium Chloride

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adults between 18 to 50 years old (inclusive) at the time of enrolment.
• 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.
• Fluent spoken English - to ensure a comprehensive understanding of the research project and their proposed involvement.
• Able to attend the scheduled visits and to comply with all study procedures, including internet access for the recording of electronic diary after inoculation.
• Willing and able to give informed consent for participation in the study.
• 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.
• Willing to allow their GP and/or consultant, if appropriate, to be notified of participation in the study.
• Willing to provide their national insurance number or passport number to be registered on The Over-Volunteering Prevention System (TOPS).
• 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.

You may not qualify if:

• Research Participants:
• 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
• Currently a participant in a previous EHPC trial within the last 2 years or at the discretion of the study team
• Vaccination (self-reported or confirmed from GP questionnaire or medical records/summary if deemed necessary at clinician discretion):
• Have had any previous pneumococcal vaccination in the past 5 years (including in a research study)
• Planned vaccination during the study
• Allergy:
• Have an allergy to penicillin or amoxicillin (for main study cohort only)
• 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
• Have previous anaphylaxis or severe adverse reaction to any component/excipient of the vaccine or to any vaccine
• Allergy to Lidocaine local anaesthetic (for nasal biopsy cohort only)
• Health History (self-reported or confirmed from GP questionnaire or medical records/summary if deemed necessary): moderate ill health including but not limited to:
• Asplenia or dysfuction of the spleen
• Chronic respiratory disease (e.g. asthma \[on medication\], COPD, emphysema, bronchiectasis)
• Chronic heart disease (e.g. angina, ischaemic heart disease, chronic heart failure) \[controlled stable hypertension +/- angina may be included\].

Sponsors & Collaborators

• University of Oxford: lead
• Liverpool School of Tropical Medicine, United Kingdom: collaborator
• Oxford University Hospitals NHS Trust: collaborator

Study Sites (2)

Liverpool Vaccine Group

Liverpool, North West, L7 8XZ, United Kingdom

RECRUITING

Oxford Vaccine Group

Oxford, Oxfordshire, OX3 7LE, United Kingdom

RECRUITING

Related Publications (1)

• Macedo BR, Solorzano C, Hyder-Wright A, Lustosa Martinelli J, Robinson H, Brito-Mutunayagam S, Urban BC, Codreanu T, Elterish F, Mitsi E, Howard A, El Safadi D, Tanha K, Liu X, Mazur O, Ramasamy MN, Collins A, Ferreira DM, Drysdale SB. Protocol for 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 in healthy participants aged 18-50 years in the UK (RATIONALE-15). BMJ Open. 2025 Nov 24;15(11):e106028. doi: 10.1136/bmjopen-2025-106028.

  PMID: 41290307 DERIVED

MeSH Terms

Conditions

Pneumococcal Infections

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Simon Drysdale, MRCPCH, PhD, PgDip PID, FRCPH

  University of Oxford

  PRINCIPAL INVESTIGATOR

• Daniela M Ferreira, PhD

  University of Oxford

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carla Solorzano-Gonzalez, PhD

CONTACT

+44 1865 611400; Carla.SolorzanoGonzalez@paediatrics.ox.ac.uk

Simon Drysdale

CONTACT

+44 1865 611400; info@ovg.ox.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2024
• First Posted: December 12, 2024
• Study Start: February 24, 2025
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 15, 2025

Record last verified: 2024-11

Locations

GB (2)