Phase 1 Study of dmLT ID Vaccination in Healthy Adults

NCT02531685 | Completed Phase 1 FDA Drug

• 2 other identifiers: 13-0013HHSN272201300022I
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Gastroenteritis Escherichia Coli

Keywords

dmLT; Enteric; Escherichia coli Infections; Shigella; Toxin LTR192G/L211A

Outcome Measures

Primary Outcomes (2)

• Occurrence of solicited adverse events (AEs)

  7 Days following each vaccination

• Occurrence of vaccine-related, non-solicited adverse events (AEs)

  Day 1 through 30 days following last vaccination

Secondary Outcomes (14)

• Occurrence of vaccine-related serious adverse events (SAEs)

  Day 1 through 6 months following last vaccination

• Occurrence of vaccine-related, non-solicited adverse events (AEs)

  Day 1 through 6 months after last vaccination

• Proportion of subjects with > / = 2-fold rise from the baseline in double mutant heat-labile toxin (dmLT)-specific toxin neutralization IgA-ALS titers at any time

  Day 1 through 56 days (Cohorts 1-4) or 6 months (Cohort 5) following last vaccination

• Proportion of subjects with > / = 2-fold rise from the baseline in double mutant heat-labile toxin (dmLT)-specific toxin neutralization IgG-ALS titers at any time

  Day 1 through 56 days (Cohorts 1-4) or 6 months (Cohort 5) following last vaccination

• Proportion of subjects with > / = 4 fold rise from the baseline double mutant heat-labile toxin (dmLT)-specific fecal IgA titers at any time

  Day 1 through 8 days (cohorts 5A and 5B) or 29 days (cohorts 1-4 and 5C) following last vaccination

Study Arms (5)

Cohort 1

EXPERIMENTAL

13 subjects receive 0.1 mcg dmLT intradermally on days 1, 22 and 43. 3 subjects receive placebo.

Other: Placebo; Biological: Recombinant Double Mutant Heat-Labile Toxin LT(R192G/L211A) (dmLT) Oral enterotoxigenic Escherichia coli (ETEC) Vaccine

Cohort 2

EXPERIMENTAL

13 subjects receive 0.3 mcg dmLT intradermally on days 1, 22 and 43. 3 subjects receive placebo.

Other: Placebo; Biological: Recombinant Double Mutant Heat-Labile Toxin LT(R192G/L211A) (dmLT) Oral enterotoxigenic Escherichia coli (ETEC) Vaccine

Cohort 3

EXPERIMENTAL

13 subjects receive 1.0 mcg dmLT intradermally on days 1, 22 and 43. 3 subjects receive placebo.

Other: Placebo; Biological: Recombinant Double Mutant Heat-Labile Toxin LT(R192G/L211A) (dmLT) Oral enterotoxigenic Escherichia coli (ETEC) Vaccine

Cohort 4

EXPERIMENTAL

A sentinel group of 5 subjects receive 2.0 mcg dmLT intradermally on days 1, 22, and 43. 1 subject receives placebo. Safety data from days 1-14 in sentinel will be reviewed and upon approval to proceed, 8 additional subjects receive 2.0 mcg dmLT intradermally on days 1, 22 and 43. 2 subjects receive placebo.

Other: Placebo; Biological: Recombinant Double Mutant Heat-Labile Toxin LT(R192G/L211A) (dmLT) Oral enterotoxigenic Escherichia coli (ETEC) Vaccine

Cohort 5

EXPERIMENTAL

Up to 31 subjects receive TBD mcg dmLT intradermally on days 1, 22 and 43. 4 subjects receive placebo.

Other: Placebo; Biological: Recombinant Double Mutant Heat-Labile Toxin LT(R192G/L211A) (dmLT) Oral enterotoxigenic Escherichia coli (ETEC) Vaccine

Interventions

Placebo OTHER

Placebo: 0.9% Sodium Chloride injection.

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Recombinant Double Mutant Heat-Labile Toxin LT(R192G/L211A) (dmLT) Oral enterotoxigenic Escherichia coli (ETEC) Vaccine BIOLOGICAL

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.

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female ages 18-45, inclusive.
• Provide written informed consent before initiation of any study procedures.
• Are in general good health.
• As defined by being without:
• significant medical illness,
• clinically significant physical examination findings, including vitals, as determined by the PI, and ---screening laboratory values outside the site's normal limits.
• Within 46 days of vaccination, have normal screening laboratories.
• Screening labs include white blood cells (WBCs) , hemoglobin (Hgb), platelets, absolute neutrophil count (ANC), sodium, potassium, bicarbonate, blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST).
• Have normal screening laboratories for urine protein. Trace protein is acceptable.
• Hemoglobin (Hgb) A1C \< 6.5 percent at screening.
• Agrees to complete all study visits and procedures and to provide a screening stool sample.
• Female subjects must be of non-childbearing potential or if of childbearing potential, must be using an effective method of birth control or must be abstinent.
• Non-childbearing potential is defined as surgically sterile or postmenopausal for \> one year.
• Effective methods of birth control include the use of hormonal or barrier birth control such as implants, injectable contraceptives, combined oral contraceptives, intrauterine devices \[IUDs\], cervical sponges, diaphragms, or condoms with spermicidal agents within 2 months of vaccination. Female subjects must be using an effective method of birth control or practice abstinence and must agree to continue such precautions during the study and for 30 days after the Day 43 study visit.
• A woman is eligible if she is monogamous with a vasectomized male.

You may not qualify if:

• Women who are pregnant or lactating or have a positive serum pregnancy test at screening or positive urine pregnancy test on vaccination days.
• Abnormal vital signs, defined as:
• Hypertension (systolic blood pressure \> 140 mm Hg or diastolic blood pressure \>90 mm Hg) at rest on 2 separate days.
• Palpated heart rate \< 55 or \> 100 beats/minute at rest on 2 separate days.
• If heart rate between 45 and 55, subjects may be enrolled with an EKG that demonstrates normal sinus rhythm and does not document conduction disorders.
• Oral Temperature \>= 38.0 Degrees Celsius (100.4 Degrees Fahrenheit).
• Symptoms of an acute self-limited illness, including an oral temperature \>= 38.0 Degrees Celsius (100.4 Degrees Fahrenheit), such as an upper respiratory infection or gastroenteritis within 7 days of administration of Double Mutant Heat-Labile Toxin (dmLT).
• Positive hepatitis C, or Human Immunodeficiency Virus (HIV) serology or positive hepatitis B serology not consistent with prior hepatitis B immunization.
• Have a positive urine drug screen for opiates.
• History of antimicrobial treatment in the 2 weeks before any administration of dmLT.
• Received previous experimental E. coli, Labile Toxin (LT), or cholera vaccines or live E. coli or Vibrio cholera challenges; or previous known infections with cholera or diarrheagenic E. coli.
• Abnormal routine bowel habits as defined by fewer than three stools per week or more than two stools per day in the past 6 months.
• History of chronic gastrointestinal illness.
• This includes severe dyspepsia (mild or moderate heartburn or epigastric pain occurring no more than three times per week is permitted), or other significant gastrointestinal tract disease.
• Regular use (weekly or more often) of laxatives, anti-diarrheal, anti-constipation, or antacid therapy.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center - Infectious Diseases

Cincinnati, Ohio, 45206-1613, United States

Location

Related Publications (1)

• Pasetti MF, Milletich PL, White JA, Butts J, Brady RC, Dickey MD, Ballou C, Maier N, Sztein MB, Baqar S, Louis Bourgeois A, Bernstein DI. Safety and immunogenicity in humans of enterotoxigenic Escherichia coli double mutant heat-labile toxin administered intradermally. NPJ Vaccines. 2025 Feb 1;10(1):23. doi: 10.1038/s41541-025-01071-7.

  PMID: 39893179 DERIVED

MeSH Terms

Conditions

Escherichia coli Infections; Dysentery, Bacillary

Interventions

Vaccines

Condition Hierarchy (Ancestors)

Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Dysentery; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2015
• First Posted: August 24, 2015
• Study Start: June 2, 2016
• Primary Completion: May 4, 2020
• Study Completion: May 4, 2020
• Last Updated: October 26, 2020

Record last verified: 2020-10-20

Locations

US (1)