NCT02531685

Phase 1 Study of dmLT ID Vaccination in Healthy Adults

A Phase 1 Double-Blind Placebo-Control Dose Escalating Study to Evaluate the Safety and Immunogenicity of Double Mutant Heat-Labile Toxin LTR192G/L211A (dmLT) From Enterotoxigenic Escherichia Coli (ETEC) by Intradermal (ID) Vaccination in Healthy Adults

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 100 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

Summary

This study is to determine the safety and immunogenicity of an Enterotoxigenic Escherichia coli (ETEC) candidate vaccine, attenuated recombinant Double Mutant Heat-Labile Toxin (dmLT) from ETEC, administered by the Intradermal (ID) route. The sample size has been determined based on the historic sample, not on power calculations.The study will involve 99 subjects (83 vaccinees and 16 placebo controls) in 4 consecutive cohorts of 16 individuals each (13 vaccinees and 3 placebo controls) and the final cohort of 35 (31 vaccinees and 4 placebos) subjects. The primary objective is to assess the safety and tolerability of dmLT vaccine when administered in three doses intradermally over a range of dosages in healthy adult subjects.

Detailed description

This is a randomized, double-blinded, single site outpatient Phase 1 study in healthy adults to determine the safety and immunogenicity of an Enterotoxigenic Escherichia coli (ETEC) candidate vaccine, attenuated recombinant Double Mutant Heat-Labile Toxin (dmLT) from ETEC, administered by the Intradermal (ID) route. The sample size has been determined based on the historic sample, not on power calculations.The study will involve 99 subjects (83 vaccinees and 16 placebo controls) in 4 consecutive cohorts of 16 individuals each (13 vaccinees and 3 placebo controls) and the final cohort of 35 (31 vaccinees and 4 placebos) subjects. A total of 16 subjects (to retain 10 vaccinees and 1 placebo evaluable subjects) in each cohort 1-4 will initially be recruited, 13 subjects each will receive three separate doses of dmLT intradermally at 1, 22 and 43-day, and 3 subjects in each cohort will receive three doses of a placebo (saline) in a blinded fashion. Because of concerns of local reactogencity in cohort 3, cohort 4 will include a sentinel group of 6 subjects that is assessed prior to dosing the remaining 10 subjects. Proceeding to the remaining subjects will be based on review of safety data obtained from days 1-14 after the first dose in the sentinel subjects by the ISM, PI and MM. As this is an outpatient study, subjects will receive their vaccinations and remain in clinic for observation for a minimum of 30 minutes. Safety data will be reviewed by Safety Monitoring Team or Committee. Subjects may be replaced to ensure 10 evaluable subjects in each single cohort, as defined by receiving all 3 vaccine doses. If replacement subjects will be included if needed and they will be randomized per cohort as a single group to include 1 subject to receive placebo to maintain the blind and ensure there are one placebos in each cohort. Final confirmatory cohort will include up to 35 vaccinees randomly selected to receive either 1, 2 or 3 vaccine doses or placebo. The study duration is approximately 1.5-2 years, including 6 months of follow-up and approximately 9 months for subject duration. The primary objective is to assess the safety and tolerability of dmLT vaccine when administered in three intradermal doses over a range of dosages levels in healthy adult subjects. The secondary objectives are: 1. To assess long-term safety follow-up from immunization through 6 months post last vaccination; 2. Following ID administration of dmLT vaccine over a range of dosages levels evaluate dmLT-specific immune response by assays.

Conditions

• Gastroenteritis Escherichia Coli

Interventions

Type	Name	Description
OTHER	Placebo	Placebo: 0.9% Sodium Chloride injection.
BIOLOGICAL	Recombinant Double Mutant Heat-Labile Toxin LT(R192G/L211A) (dmLT) Oral enterotoxigenic Escherichia coli (ETEC) Vaccine	LT(R192G/L211A), or dmLT is formulated as a freeze-dried (lyophilized), white to off-white cake, containing 700mcg of vaccine protein in a 3 ml, multi-dose.

Timeline

• Start date: 2016-06-02
• Primary completion: 2020-05-04
• Completion: 2020-05-04
• First posted: 2015-08-24
• Last updated: 2020-10-26

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study