Efficacy Study of IM Administered CssBA+dmLT Against Moderate-severe Diarrhea in Human Infection Model With ETEC Strain B7A in Healthy Adults

Summary

The study is designed to evaluate the safety, immunogenicity, and efficacy of the intramuscular administration of a CS6 based vaccine (CssBA) against ETEC co-administered with double mutant labile toxin (dmLT) in preventing moderate-severe diarrhea (MSD) following challenge with ETEC strain B7A in healthy adults. Approximately 72 adult participants, divided into 4 cohorts of 18, will be randomized 1:1 to receive vaccine (45 micrograms CssBA with 0.5 micrograms dmLT) or placebo (normal saline) on an outpatient basis. All participants will receive 3 intramuscular (IM) doses of vaccine or placebo at 3-week intervals (days 1, 22 and 43). Following vaccination, participants will be followed as outpatients for safety using a memory aid from the time of each vaccination through 7 days post each vaccination. Approximately 28 days (plus or minus 1 day) after receipt of the 3rd dose of study agent, participants meeting challenge criteria will be admitted to an inpatient unit and be administered an oral dose of 1 x 10\^10 cfu (colony-forming unit) of ETEC strain B7A. Five days after challenge, participants will be treated with ciprofloxacin, except in cases of known allergy or intolerance. Participants will be discharged from the inpatient unit when they have completed their 3-day antibiotic course and are able to care for themselves. After discharge from the inpatient unit, participants will return for clinic visits and have a phone visit to provide any updates on medication, medical history and AE/SAEs. The primary objectives are: 1) Estimate CssBA+dmLT efficacy in preventing moderate-severe diarrhea (MSD) following challenge with ETEC strain B7A in healthy adults. 2) Evaluate the safety of intramuscular injection of CssBA+dmLT.

Conditions

• Escherichia Infection

Interventions

OTHER

B7A (ETEC challenge strain)

A pathogenic strain of ETEC that can cause illness ranging from mild watery diarrhea to severe symptoms. The primary complication associated with an infection from this strain is dehydration.

BIOLOGICAL

CssBA

A CS6 based vaccine against ETEC (Enterotoxigenic Escherichia coli) in preventing moderate-severe diarrhea obtained via purification from a host E. coli expression strain, BL21(DE3), harboring a pET24a (+) plasmid containing the CssBA gene expressing the his-tagged CssBA protein.

BIOLOGICAL

dmLT

An E. coli double mutant heat labile toxin. This genetically attenuated strain is expressed from a plasmid (pLC403) in the E. coli expression strain JM83.

OTHER

Placebo

Placebo

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

  lead NIH

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

49 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-03-31

Primary Completion

2026-04-01

Completion

2026-04-01

FDA Drug

Yes

Countries

• United States

Study Locations