A staged dose-finding and challenge/rechallenge study of Staphylococcus aureus nasal colonisation in healthy adults (ReSET)

Research summary

Study Design: Two stage,unblinded strain-randomised controlled human infection model: Stage I – A dose-finding study using a continual reassessment method to identify the optimal nasal challenge dose for two strains of S. aureus each required to achieve colonisation in 50-70% of challenged participants. Participants will receive decolonisation therapy prior to challenge. If a strain in Stage I fails to colonise successfully or fails to progress for any other scientific,logistical or safety reason,it may be replaced by another suitable strain,restarting the strain-specific dose-finding process. The responsibility of the final decision to declare a strain ‘failed’ will be with the Study Management Group (SMG) and informed by the CRM analysis. Up to four strains may be trialled. If only one strain ‘passes’ Stage I,then this will be the only strain progressing to Stage II. If no strains ‘pass’ Stage I,then the study will cease. Stage II – Assesses protection following rechallenge with the strains carried forward from Stage I. Up to two strains will be evaluated at the doses established in Stage I in a new expansion cohort. Participants will be randomised 1:1 to receive one of the two strains at the time of their primary challenge. Those who are successfully colonised will proceed to rechallenge after a washout period of approximately two months and second decolonisation procedures. Rechallenge will initially be homologous,where participants receive the same strain as their primary challenge. If interim analyses show protection against homologous rechallenge,the SMG may decide to include heterologous rechallenge,informed by interim analyses and rechallenge colonisation rates. If only one strain progresses to Stage II,then there will be no randomisation and no heterologous challenge. Study Interventions: Decolonisation therapy: Antiseptic wash and nasal antibiotic cream use prior to each challenge and at the conclusion of in-person follow up. Challenge: Administration of a pre-defined amount of S. aureus in liquid suspension (the inoculum) into the anterior nares. Antibiotics: At clinical investigator’s discretion,participants may receive antibiotics to treat clinical infection. First choice antibiotics include Flucloxacillin and Doxycycline,but alternative antibiotics may be used. Objectives: Stage I: To determine the safety of S. aureus primary challenge in humans Stage I co-primary: To determine the challenge doses required to achieve a 50-70% nasal colonisation rate with up to two strains of S. aureus Stage II: To determine the safety of S. aureus primary challenge and rechallenge in humans Stage II co-primary: To quantify the rate of S. aureus acquisition following primary challenge,homologous rechallenge ± heterologous rechallenge

Principal Investigator

Robert Shaw

Contact us

Email: raquel.lomas@ndm.ox.ac.uk

IRAS number

366748