NCT06290089

Pre-Study of Wild Type Enterotoxigenic E. Coli (ETEC) Strain for Verification of a Planned Challenge Dose

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: Scandinavian Biopharma AB · Industry
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

Summary

This was an open-label, single-site pre-study designed to evaluate the safety, tolerability, and infectivity of wild-type Enterotoxigenic Escherichia coli (ETEC) strain E24377A in healthy adults. The aim was to estimate the incidence of moderate and severe diarrhea following oral challenge with approximately 4 × 10⁹ colony forming units (cfu) of the strain. A total of 23 participants were enrolled and monitored in an inpatient setting after receiving a single challenge dose. Clinical signs, symptoms, and stool output were assessed over 120 hours. This challenge model was developed to support a future controlled human infection study (CHIM) evaluating an oral inactivated ETEC vaccine.

Detailed description

This was an open-label, single-center pre-study designed to evaluate the safety, tolerability, and infectivity of wild-type Enterotoxigenic Escherichia coli (ETEC) strain E24377A in healthy adults. The goal was to estimate the incidence of moderate and severe diarrhea following challenge with approximately 4 × 10⁹ colony forming units (cfu) of the strain. This challenge model was intended to inform a subsequent controlled human infection model (CHIM) study assessing the efficacy of the oral inactivated tetravalent ETEC vaccine ETVAX® (containing LCTBA and dmLT). Up to 30 healthy adult subjects were planned to be enrolled; 23 were ultimately challenged at the Center for Immunization Research (CIR), Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, USA. Participants underwent screening, then entered an inpatient unit on Day -1. On Day 1, they received a single oral dose of strain E24377A (lot 0807) suspended in 30 mL sodium bicarbonate buffer, preceded by 120 mL of buffer to reduce gastric acidity. During the inpatient period, subjects were monitored at least three times daily for vital signs, signs and symptoms of ETEC illness, and stool output. All stools were collected, weighed, graded, and cultured. Stools were graded on a 5-point scale: Grade 1 = firm/formed; Grade 2 = soft/formed; Grade 3 = thick liquid; Grade 4 = thin liquid; Grade 5 = clear/watery. Loose stools were defined as Grade 3-5. Diarrhea was defined as ≥2 loose stools (Grade 3-5) within a 24-hour period. Severity was categorized as: Mild: 2-3 Grade 3-5 stools and ≤400 g in 24 h Moderate: 4-5 Grade 3-5 stools or \>400-800 g Severe: ≥6 Grade 3-5 stools or \>800 g An independent adjudication committee determined whether episodes were attributable to ETEC and whether participants met the primary endpoint. Participants received ciprofloxacin 500 mg twice daily for 3 days starting on Day 6, or earlier if needed. Discharge occurred after meeting microbiological and clinical criteria, with follow-up visits on Day 29 (clinic) and Day 180 (phone). Secondary and exploratory endpoints included stool frequency and weight, symptom scores, microbiological shedding, and immunologic assessments (serum, fecal, and ALS IgA/IgG, memory B cells, transcriptomics, and biomarkers of intestinal/systemic inflammation). Safety endpoints included adverse events through Day 29 and serious adverse events through Day 180.

Conditions

• ETEC Diarrhea

Interventions

Type	Name	Description
OTHER	Enterotoxigenic E. coli (ETEC) strain	Challenge strain

Timeline

• Start date: 2024-02-12
• Primary completion: 2024-02-17
• Completion: 2024-09-13
• First posted: 2024-03-04
• Last updated: 2025-07-18
• Results posted: 2025-07-16

Locations

1 site across 1 country: United States