PREVENTING PNEUMOcoccal Disease Through Vaccination (Study 2) — Pneumo 2  

Streptococcus Pneumonia Clinical Trial

Official title: A Phase IV Double Blind Randomised Controlled Trial (DBRCT) to Investigate the Effect of PCV-13 and PPV-23 on Pneumococcal Colonisation Using the Experimental Human Pneumococcal Challenge (EHPC) Model in Healthy Adults

Status Recruiting

Clinical Trial Summary

To determine the effect of PCV-13 and PPV-23 vaccination versus control on experimental pneumococcal colonisation of 2 clades of serotypes 3 and 6B at 1 month and 6 months post vaccination respectively, using the EHPC model.

Clinical Trial Description

Streptococcus pneumoniae (SPN) is the leading cause of morbidity and mortality worldwide, causing community acquired pneumonia (CAP), bacterial meningitis and bacteremia. Pneumococcal infections cause over 1 million pneumonia deaths per year in children in the developing world and is a major burden of otitis media globally.

The LSTM Experimental Human Pneumococcal Challenge (EHPC) model is a unique method of measuring pneumococcal colonization of bacteria, understanding the effect of pneumococcal colonization on acquired immunity, and allows vaccines to be tested in adults to understand their effect on colonization in a manner which is cost-effective and uses much smaller numbers of participants compared to large phase III clinical trials.

Participants: Healthy adults aged 18-50 years of age (inclusive) will be recruited. A recruitment target of up to 516 participants with an approximate screen failure/dropout rate of 20% will ensure 410 participants complete Part A and 246 complete Part A & B of the trial.

Methods: Double blind randomized controlled trial (DBRCT) to investigate the effect of PCV-13 and PPV-23 vaccination on pneumococcal colonisation using the EHPC model in healthy adults. Participants will be randomised to 5 arms for Part A of the study that:

1. to receive PCV-13 vaccine IM and inoculation a month later with SPN3 clade 1a;

2. to receive PCV-13 vaccine IM and inoculation a month later with SPN3 clade 2;

3. to receive PPV-23 vaccine IM and inoculation a month later with SPN3 clade 1a;

4. to receive 0.9% saline for injection IM and inoculation a month later with SPN3 clade 1a or

5. to receive 0.9% saline for injection IM and inoculation a month later with SPN3 clade 2.

The last two 0.9% saline of injection groups represent the placebo control groups. The SPN3 (2 clades) is amoxicillin-susceptible. After challenge (inoculation) they will be followed up for 23 days where nasal, blood and urine samples will be taken. Part B of the trial will run 6 months post vaccination. Participants will be re-screened for safety prior to Part B to ensure they remain eligible. The 3 groups of participants detailed below from the Part A population will proceed to Part B of the trial:

1. Up to 104 of the participants that received PCV-13 in Part A (split across clades 1a and 2)

2. Up to 104 of the participants that received PPV-23 in Part A

3. Up to 104 of the participants that received 0.9% saline for injection in Part A (split across clades 1a and 2) The total number to proceed to Part B will be up to 312 to allow for 20% dropout / screen failure to ensure 246 complete part A & B. All Part B Participants will receive a second inoculation of amoxicillin-susceptible SPN6B at 6 months post-vaccine and will be followed up for 23 days in total where further samples will be taken (Trial Flow Chart and Table 2). All participants will take a 5-day course of amoxicillin three times a day (TDS) at the end of Part A to ensure experimental colonization clearance prior to Part B inoculation. Participants that are experimentally colonized at any point following the SPN6B challenge at 6 months (Part B) will take a 3-day course of amoxicillin TDS.

Randomization & Blinding: Participants will be randomized to receive PCV-13 vaccine and clade 1a (group 1), PCV-13 and clade 2 (group 2), PPV-23 vaccine and clade 1a (group 3), 0.9% saline for injection and clade 1a (group 4) or 0.9% saline for injection and clade 2 (group 5) vaccine in a ratio of 1:1:1:1:1 with up to 104 participants in each arm. Randomization will be computer-generated.

Randomization will occur in two cohorts:

1. Cohort I: 312 subjects for five groups 1:1:2:1:1 in block sizes of 6

2. Cohort II: 204 participants for four groups 1:1:0:1:1 in block sizes of 4 This will ensure that overall the randomization ratio is 1:1:1:1:1, but it will allow 312 participants from Cohort I, split equally across participants that have received PCV-13, PPV-23 and placebo to proceed to part B of the trial. ;

Related Conditions & MeSH terms

• Pneumonia, Pneumococcal
• Streptococcus Pneumonia

• NCT number: NCT04974294
• Study type: Interventional
• Source: Liverpool School of Tropical Medicine
• Contact: Kelly Davies
• Phone: +44 151 702 9391
• Email: kelly.davies@lstmed.ac.uk
• Status: Recruiting
• Phase: Phase 4
• Start date: July 28, 2021
• Completion date: December 31, 2023