ETVAX Trial in the Gambia: Reported Protection Against Severe Childhood Diarrhea

Reported results suggest that the oral enterotoxigenic Escherichia coli (ETEC) vaccine candidate ETVAX showed efficacy signals against moderate-to-severe ETEC-associated diarrheal illness in young children in a phase 2b study, with the authors noting that the primary endpoint was not met.

A publication in The Lancet Infectious Diseases describes efficacy signals against moderate-to-severe ETEC-associated disease alongside observations on serious adverse events and immune responses.

The publication is described as a double-blind, randomized, placebo-controlled phase 2b trial conducted in The Gambia in 4,936 children. Participants were aged 6–18 months at enrollment and were assigned to receive either oral ETVAX or placebo. ETVAX was administered as three oral doses, and the report notes follow-up for up to two years with regular health assessments and sample collection. Overall, the described design focuses on infant and toddler dosing with longitudinal surveillance through early childhood.

In the reported efficacy analyses, investigators reported that the primary efficacy endpoint—vaccine efficacy against moderate-to-severe ETEC-positive diarrhoea excluding co-infections with Cryptosporidium spp, norovirus genogroup II, rotavirus, or Shigella spp—was 26.6% (95% CI −58.3 to 66.0; p=0.43). The report also describes 48.2% vaccine efficacy against moderate-to-severe ETEC-positive diarrhoea regardless of copathogens (p=0.053). In an exploratory analysis excluding enteroparasitic copathogens (Giardia lamblia and Cryptosporidium spp), vaccine efficacy was 80.6% (p=0.0092). The report also highlights an age-stratified analysis indicating efficacy of 67.8% (p=0.026) against moderate-to-severe ETEC-positive diarrhoea regardless of copathogens when the first dose was given before age 9 months.

Separately, the report states a 21.4% reduction in moderate-to-severe diarrhoea regardless of cause (p=0.032) and places that estimate alongside effects observed with rotavirus vaccines in low- and middle-income countries, without extending the comparison beyond that framing. These findings were presented as efficacy signals across the overall cohort and selected subgroup analyses.

On safety, the report states that no vaccine-related serious adverse events were observed among children in the study. It also reports that overall adverse events were similar between groups and includes reactogenicity and tolerability summaries (including vomiting within 30 minutes of dosing, which was infrequent and similar between groups). On immunogenicity, it describes that the vaccine generated clear immune responses to bacterial factors associated with disease, without adding mechanistic detail in the summary.

Looking ahead, the report describes development and next steps, stating that the Lancet Infectious Diseases paper supports advancing ETVAX into a multinational Phase 3 efficacy trial after evaluating the Gambian results together with earlier ETVAX studies.

Key Takeaways:

• The report describes a double-blind, randomized, placebo-controlled phase 2b study in The Gambia enrolling young children who received three oral doses and were followed longitudinally.
• Efficacy signals were reported for moderate-to-severe ETEC disease in secondary, exploratory, and age-stratified analyses, alongside a reported reduction in moderate-to-severe all-cause diarrhea discussed in relation to rotavirus vaccine effects; the authors note the primary endpoint was not met.
• No vaccine-related serious adverse events and clear immune responses were reported, and the account notes support to advance to a multinational Phase 3 efficacy trial.