Background: Gonorrhoea remains a major global public health concern, with rising antimicrobial resistance underscoring the urgent need for an effective vaccine. GonoVac, a native outer membrane vesicle (nOMV) vaccine, has demonstrated immunogenicity and efficacy in preclinical studies. This first-in-human Phase I trial will evaluate the safety, tolerability, and immunogenicity of GonoVac administered with and without aluminium hydroxide (Al(OH)₃) in healthy UK adults.
Methods: GON001 is UK a dual-centre, first-in-human Phase I clinical trial sponsored by the University of Oxford and funded by UK Medical Research Council. The study will enrol healthy adults aged 18–35 years and comprises two stages; Stage 1 employs an open-label, non-randomised sentinel dose-escalation design with six GonoVac groups (n=3–6 per group) receiving escalating doses (12.5, 25, or 50 µg) with or without Al(OH)₃. Stage 2 implements a double-blind, randomised, adaptive cohort expansion design (n=45), including two GonoVac groups selected based on maximum tolerated dose in Stage 1 and a comparator group receiving 4CMenB (BexseroTM). All participants will receive three intramuscular doses of vaccine at 0, 3, and 6 months, with follow-up to 9 months post-first vaccination.
Results: The primary objective of the study is to assess vaccine safety as measured by solicited and unsolicited adverse events. The secondary objective is to assess the relationship between GonoVac dose and humoral immune response as assessed by serum IgG and serum bactericidal assay activity. Exploratory objectives include detailed characterisation of vaccine induced humoral and cellular responses in PBMC, mucosal antibody responses in nasal, vaginal and oropharyngeal samples and serum antibody avidity.
Conclusion: This Phase I study will provide the first human data for GonoVac, informing optimal dosing, the need for co-formulation with Al(OH)₃ and further clinical development pathway.