Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Enterotoxigenic Escherichia Coli (ETEC) ETVAX Vaccine Trial in Bangladesh (ETVAX/dmLT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02531802
Recruitment Status : Completed
First Posted : August 24, 2015
Results First Posted : September 12, 2018
Last Update Posted : September 12, 2018
Sponsor:
Collaborators:
Scandinavian Biopharma AB
International Centre for Diarrhoeal Disease Research, Bangladesh
Information provided by (Responsible Party):
PATH

Brief Summary:
The purpose of this study is to determine if the ETEC vaccine ETVAX with and without dmLT adjuvant is safe and immunogenic in adults, children, toddlers and infants in Bangladesh.

Condition or disease Intervention/treatment Phase
Escherichia Coli Diarrhea Biological: ETVAX Biological: dmLT Other: Bicarbonate Buffer Phase 1 Phase 2

Detailed Description:
This Phase I/II trial will serve to assess whether ETVAX is safe and provides mucosal as well as systemic immune responses against the key protective antigens when tested in different age-groups in Bangladesh. This study provides an opportunity to test the safety profile of a mucosal adjuvant, double-mutant LT (dmLT), in adults and children, as well as provide the opportunity to potentially assess the ability of dmLT to further enhance the mucosal and systemic antibody responses to key antigens in the ETVAX vaccine among age groups in developing country sites, like Bangladesh, that have proved refractory to oral immunization with enteric vaccines. In addition, this study also allows for the evaluation of the potential dose-sparing effect of dmLT when combined with a lower dose of vaccine. Finally, this clinical trial is considered an essential study along the critical path of the overall clinical development plan before determining whether the vaccine can be tested for protective efficacy in children in developing countries.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 475 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Randomized, Double-blind, Placebo-controlled, Dose-Escalation Study Evaluating the Safety, Tolerability, and Immunogenicity of an Oral Inactivated ETEC Vaccine (ETVAX) Alone and Together With dmLT Adjuvant in Descending Age Groups in Bangladesh
Study Start Date : October 2015
Actual Primary Completion Date : July 29, 2017
Actual Study Completion Date : July 29, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diarrhea

Arm Intervention/treatment
Experimental: Adult: ETVAX (Full)
Adult arm (18-45 year olds) receiving the full dose of ETVAX vaccine (10^11 inactivated E. coli bacteria) added to bicarbonate buffer solution administered orally on Day 0 and 14
Biological: ETVAX

Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of:

  • Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg
  • E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I)
  • E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3)
  • E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5)
  • E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6)

The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.


Other: Bicarbonate Buffer
Sodium bicarbonate buffer dissolved in 150 ml of potable water

Experimental: Adult: ETVAX (Full) + 10 ug dmLT
Adult arm (18-45 year olds) receiving the full dose of ETVAX vaccine (10^11 inactivated E. coli bacteria) with 10 ug dmLT added to bicarbonate buffer solution administered orally on Day 0 and 14
Biological: ETVAX

Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of:

  • Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg
  • E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I)
  • E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3)
  • E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5)
  • E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6)

The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.


Biological: dmLT
Varying dosages of dmLT, a derivative of wild-type enterotoxigenic Escherichia coli LT that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.
Other Name: double mutant heat labile toxin, LT(R192G/L211A)

Other: Bicarbonate Buffer
Sodium bicarbonate buffer dissolved in 150 ml of potable water

Placebo Comparator: Adult: Placebo
Adult arm (18-45 year olds) receiving a placebo on days 0 and 14
Other: Bicarbonate Buffer
Sodium bicarbonate buffer dissolved in 150 ml of potable water

Experimental: 24-59 months: ETVAX (1/4)
24-59 month old children receiving a quarter adult dose (2.5 x 10^10 inactivated E. coli bacteria) of ETVAX vaccine in bicarbonate buffer solution administered orally on Day 0 and 14
Biological: ETVAX

Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of:

  • Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg
  • E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I)
  • E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3)
  • E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5)
  • E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6)

The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.


Other: Bicarbonate Buffer
Sodium bicarbonate buffer dissolved in 150 ml of potable water

Experimental: 24-59 months: ETVAX (1/2)
24-59 month old children receiving a half adult dose of ETVAX vaccine (5 x 10^10 inactivated E. coli bacteria) in bicarbonate buffer solution administered orally on Day 0 and 14
Biological: ETVAX

Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of:

  • Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg
  • E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I)
  • E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3)
  • E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5)
  • E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6)

The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.


Other: Bicarbonate Buffer
Sodium bicarbonate buffer dissolved in 150 ml of potable water

Experimental: 24-59 months: ETVAX (full)
24-59 month old children receiving a full adult dose of ETVAX vaccine (10^11 inactivated E. coli bacteria) in bicarbonate buffer solution administered orally on Day 0 and 14
Biological: ETVAX

Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of:

  • Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg
  • E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I)
  • E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3)
  • E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5)
  • E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6)

The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.


Other: Bicarbonate Buffer
Sodium bicarbonate buffer dissolved in 150 ml of potable water

Experimental: 24-59 months: ETVAX (1/2) + 2.5 ug dmLT
24-59 month old children receiving a half adult dose of ETVAX vaccine (5 x 10^10 inactivated E. coli bacteria) plus 2.5 ug dmLT in bicarbonate buffer solution administered orally on Day 0 and 14
Biological: ETVAX

Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of:

  • Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg
  • E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I)
  • E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3)
  • E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5)
  • E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6)

The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.


Biological: dmLT
Varying dosages of dmLT, a derivative of wild-type enterotoxigenic Escherichia coli LT that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.
Other Name: double mutant heat labile toxin, LT(R192G/L211A)

Other: Bicarbonate Buffer
Sodium bicarbonate buffer dissolved in 150 ml of potable water

Experimental: 24-59 months: ETVAX (1/2) + 5 ug dmLT
24-59 month old children receiving a half adult dose of ETVAX vaccine (5 x 10^10 inactivated E. coli bacteria) plus 5 ug dmLT in bicarbonate buffer solution administered orally on Day 0 and 14
Biological: ETVAX

Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of:

  • Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg
  • E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I)
  • E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3)
  • E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5)
  • E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6)

The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.


Biological: dmLT
Varying dosages of dmLT, a derivative of wild-type enterotoxigenic Escherichia coli LT that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.
Other Name: double mutant heat labile toxin, LT(R192G/L211A)

Other: Bicarbonate Buffer
Sodium bicarbonate buffer dissolved in 150 ml of potable water

Experimental: 24-59 months: ETVAX (1/2) + 10 ug dmLT
24-59 month old children receiving a half adult dose of ETVAX vaccine (5 x 10^10 inactivated E. coli bacteria) plus 10 ug dmLT in bicarbonate buffer solution administered orally on Day 0 and 14
Biological: ETVAX

Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of:

  • Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg
  • E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I)
  • E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3)
  • E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5)
  • E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6)

The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.


Biological: dmLT
Varying dosages of dmLT, a derivative of wild-type enterotoxigenic Escherichia coli LT that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.
Other Name: double mutant heat labile toxin, LT(R192G/L211A)

Other: Bicarbonate Buffer
Sodium bicarbonate buffer dissolved in 150 ml of potable water

Placebo Comparator: 24-59 months: Placebo
24-59 month old children receiving a placebo of bicarbonate buffer solution administered orally on Day 0 and 14
Other: Bicarbonate Buffer
Sodium bicarbonate buffer dissolved in 150 ml of potable water

Experimental: 12-23 months: ETVAX (1/4)
12-23 month old children receiving a quarter adult dose of ETVAX vaccine (2.5 x 10^10 inactivated E. coli bacteria) in bicarbonate buffer solution administered orally on Day 0 and 14
Biological: ETVAX

Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of:

  • Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg
  • E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I)
  • E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3)
  • E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5)
  • E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6)

The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.


Other: Bicarbonate Buffer
Sodium bicarbonate buffer dissolved in 150 ml of potable water

Experimental: 12-23 months: ETVAX (1/2)
12-23 month old children receiving a half adult dose of ETVAX vaccine (5 x 10^10 inactivated E. coli bacteria) in bicarbonate buffer solution administered orally on Day 0 and 14
Biological: ETVAX

Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of:

  • Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg
  • E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I)
  • E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3)
  • E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5)
  • E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6)

The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.


Other: Bicarbonate Buffer
Sodium bicarbonate buffer dissolved in 150 ml of potable water

Experimental: 12-23 months: ETVAX (1/2) + 2.5 ug dmLT
12-23 month old children receiving a half adult dose of ETVAX vaccine (5 x 10^10 inactivated E. coli bacteria) plus 2.5 ug dmLT in bicarbonate buffer solution administered orally on Day 0 and 14
Biological: ETVAX

Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of:

  • Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg
  • E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I)
  • E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3)
  • E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5)
  • E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6)

The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.


Biological: dmLT
Varying dosages of dmLT, a derivative of wild-type enterotoxigenic Escherichia coli LT that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.
Other Name: double mutant heat labile toxin, LT(R192G/L211A)

Other: Bicarbonate Buffer
Sodium bicarbonate buffer dissolved in 150 ml of potable water

Experimental: 12-23 months: ETVAX (1/2) + 5 ug dmLT
12-23 month old children receiving a half adult dose of ETVAX vaccine (5 x 10^10 inactivated E. coli bacteria) plus 5 ug dmLT in bicarbonate buffer solution administered orally on Day 0 and 14
Biological: ETVAX

Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of:

  • Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg
  • E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I)
  • E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3)
  • E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5)
  • E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6)

The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.


Biological: dmLT
Varying dosages of dmLT, a derivative of wild-type enterotoxigenic Escherichia coli LT that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.
Other Name: double mutant heat labile toxin, LT(R192G/L211A)

Other: Bicarbonate Buffer
Sodium bicarbonate buffer dissolved in 150 ml of potable water

Placebo Comparator: 12-23 months: Placebo
12-23 month old children receiving a placebo of bicarbonate buffer solution administered orally on Day 0 and 14
Other: Bicarbonate Buffer
Sodium bicarbonate buffer dissolved in 150 ml of potable water

Experimental: 6-11 months: ETVAX (1/8)
6-11 month old children receiving an eighth of an adult dose of ETVAX vaccine in bicarbonate buffer solution administered orally on Day 0 and 14
Biological: ETVAX

Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of:

  • Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg
  • E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I)
  • E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3)
  • E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5)
  • E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6)

The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.


Other: Bicarbonate Buffer
Sodium bicarbonate buffer dissolved in 150 ml of potable water

Experimental: 6-11 months: ETVAX (1/4)
6-11 month old children receiving a quarter of an adult dose of ETVAX vaccine (2.5 x 10^10 inactivated E. coli bacteria) in bicarbonate buffer solution administered orally on Day 0 and 14
Biological: ETVAX

Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of:

  • Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg
  • E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I)
  • E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3)
  • E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5)
  • E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6)

The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.


Other: Bicarbonate Buffer
Sodium bicarbonate buffer dissolved in 150 ml of potable water

Experimental: 6-11 months: ETVAX (1/2)
6-11 month old children receiving a half of an adult dose of ETVAX vaccine (5 x 10^10 inactivated E. coli bacteria) in bicarbonate buffer solution administered orally on Day 0 and 14
Biological: ETVAX

Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of:

  • Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg
  • E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I)
  • E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3)
  • E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5)
  • E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6)

The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.


Other: Bicarbonate Buffer
Sodium bicarbonate buffer dissolved in 150 ml of potable water

Experimental: 6-11 months: ETVAX (1/4) + 2.5 ug dmLT
6-11 month old children receiving a quarter of an adult dose of ETVAX vaccine (2.5 x 10^10 inactivated E. coli bacteria) plus 2.5 ug dmLT in bicarbonate buffer solution administered orally on Day 0 and 14
Biological: ETVAX

Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of:

  • Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg
  • E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I)
  • E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3)
  • E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5)
  • E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6)

The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.


Biological: dmLT
Varying dosages of dmLT, a derivative of wild-type enterotoxigenic Escherichia coli LT that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.
Other Name: double mutant heat labile toxin, LT(R192G/L211A)

Other: Bicarbonate Buffer
Sodium bicarbonate buffer dissolved in 150 ml of potable water

Experimental: 6-11 month olds: ETVAX (1/4) + 5 ug dmLT
6-11 month old children receiving a quarter of an adult dose of ETVAX vaccine (2.5 x 10^10 inactivated E. coli bacteria) plus 5 ug dmLT in bicarbonate buffer solution administered orally on Day 0 and 14
Biological: ETVAX

Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of:

  • Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg
  • E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I)
  • E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3)
  • E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5)
  • E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6)

The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.


Biological: dmLT
Varying dosages of dmLT, a derivative of wild-type enterotoxigenic Escherichia coli LT that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.
Other Name: double mutant heat labile toxin, LT(R192G/L211A)

Other: Bicarbonate Buffer
Sodium bicarbonate buffer dissolved in 150 ml of potable water

Placebo Comparator: 6-11 month olds: Placebo
6-11 month old children receiving a placebo of bicarbonate buffer solution administered orally on Day 0 and 14
Other: Bicarbonate Buffer
Sodium bicarbonate buffer dissolved in 150 ml of potable water




Primary Outcome Measures :
  1. Number and Percentage of Participants Experiencing Solicited Events by Symptom and Maximum Severity [ Time Frame: 7 days after each vaccination (Day 7 and Day 21) ]
    Adverse events (AEs) were assessed post-vaccination using participant/parent/guardian interview (including memory aids), targeted physical examinations, vital signs and clinical laboratory tests and reactogenicity assessments which were completed following each vaccination. The solicited AEs of nausea (adults only), abdominal pain/stomach ache (adults and children 24-59 months only), fever, vomiting and diarrhea were evaluated daily for 7 days post vaccination.

  2. Number and Percentage of Participants Experiencing Unsolicited Adverse Events Related to Vaccine [ Time Frame: 6 months ± 14 days after the first dose ]
    Adverse events (AEs) were assessed post-vaccination using participant/parent/guardian interview (including memory aids), targeted physical examinations, vital signs and clinical laboratory tests and reactogenicity assessments which were completed following each vaccination. Unsolicited AEs were assessed through Day 42 and serious adverse events (SAEs) were assessed over the entire duration of the study.


Secondary Outcome Measures :
  1. Number and Percentage of Subjects With ≥Two-fold Increase in Antibody Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response After Either Vaccine Dose, by Antigen [ Time Frame: 19 days ]

    Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second). Antigen in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin


  2. Number and Percentage of Subjects With ≥Four-fold Increase in Antibody Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response After Either Vaccine Dose, by Antigen [ Time Frame: 19 days ]

    Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second). Antigen in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin


  3. Geometric Mean Titer (GMT) of Antibody Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response After Either Vaccine Dose, by Antigen [ Time Frame: 19 days ]

    Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second). Antigen in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin


  4. Geometric Mean Fold Change of Antibody Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response After Either Vaccine Dose, by Antigen [ Time Frame: 19 days ]

    Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second). Antigen in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin


  5. Number and Percentage of 6-11 Month Old Subjects With ≥Two-fold Increase in Fecal Secretory Immunoglobulin A (SIgA) Response, by Antigen [ Time Frame: 28 days ]

    Fecal secretion was measured on Day 7, Day 19, and Day 28; number in table is subjects experiencing a two-fold rise at any of these time points. Antigen in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin


  6. Number and Percentage of 6-11 Month Old Subjects With ≥Four-fold Increase in Fecal Secretory Immunoglobulin A (SIgA) Response, by Antigen [ Time Frame: 28 days ]

    Fecal secretion was measured on Day 7, Day 19, and Day 28; number in table is subjects experiencing a four-fold rise at any of these time points. Antigens in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin


  7. Geometric Mean Titer (GMT) of Fecal Secretory Immunoglobulin A (SIgA) Response 6-11 Month Old Subjects, by Antigen [ Time Frame: 28 days ]

    Fecal secretion was measured on Day 7, Day 19, and Day 28; number in table is based on the maximum value for each subject. Antigen in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin


  8. Geometric Mean Fold Change of Fecal Secretory Immunoglobulin A (SIgA) Response Among 6-11 Month Old Subjects, by Antigen [ Time Frame: 28 days ]

    Fecal secretion was measured on Day 7, Day 19, and Day 28; number in table is based on the maximum value for each subject. Antigen in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin


  9. Number and Percentage of Subjects With ≥Two-fold Increase in Plasma Immunoglobulin A (IgA) Response After Either Vaccine Dose, for Antigens in ETVAX [ Time Frame: 19 days ]

    Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second). Antigen in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin


  10. Number and Percentage of Subjects With ≥Four-fold Increase in Plasma Immunoglobulin A (IgA) Response After Either Vaccine Dose, for Antigens in ETVAX [ Time Frame: 19 days ]

    Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second). Antigen in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin


  11. Geometric Mean Titer (GMT) of Plasma Immunoglobulin A (IgA) Response After Either Vaccine Dose, for Antigens in ETVAX [ Time Frame: 19 days ]

    Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second). Antigen in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin


  12. Geometric Mean Fold Change in Plasma Immunoglobulin A (IgA) Response After Either Vaccine Dose, for Antigens in ETVAX [ Time Frame: 19 days ]

    Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second). Antigen in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin


  13. Number and Percentage of Adult Subjects With ≥Two-fold and ≥Four-fold Increase in Plasma Immunoglobulin A (IgA) Response After Either Vaccine Dose, for O78 Antigen [ Time Frame: 19 days ]
    Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second).

  14. Geometric Mean Titer (GMT) for Plasma Immunoglobulin A (IgA) Response After Either Vaccine Dose, for O78 Antigen, Among Adults [ Time Frame: 19 days ]
    Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second).

  15. Geometric Mean Fold Change in Plasma Immunoglobulin A (IgA) Response After Either Vaccine Dose, for O78 Antigen, Among Adults [ Time Frame: 19 days ]
    Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second).

  16. Number and Percentage of Subjects With ≥Two-fold and ≥Four-fold Increase in Plasma Immunoglobulin G (IgG) Response to E. Coli Heat-labile Enterotoxin (LTB) After Either Vaccine Dose [ Time Frame: 19 days ]
    Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second). B-subunit of the E. coli heat-labile enterotoxin (LTB) was one of the antigens in the ETVAX vaccine.

  17. Geometric Mean Titer (GMT) of Plasma Immunoglobulin G (IgG) Response to E. Coli Heat-labile Enterotoxin (LTB) After Either Vaccine Dose [ Time Frame: 19 days ]
    Measured 7 days after the first dose and 5 days after the second). B-subunit of the E. coli heat-labile enterotoxin (LTB) was one of the antigens in the ETVAX vaccine.

  18. Geometric Mean Fold Change of Plasma Immunoglobulin G (IgG) Response to E. Coli Heat-labile Enterotoxin (LTB) After Either Vaccine Dose [ Time Frame: 19 days ]
    Between baseline and after vaccination (measured 7 days after the first dose and 5 days after the second). B-subunit of the E. coli heat-labile enterotoxin (LTB) was one of the antigens in the ETVAX vaccine.

  19. Number of Antigen Responses in Antibody Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Experienced by Subjects [ Time Frame: 19 days ]
  20. Number of Antigen Responses in Plasma Immunoglobulin A (IgA) Experienced by Subjects [ Time Frame: 19 days ]
  21. Number and Percentage of 6-11 Month Old Subjects With ≥Two-fold Increase in Fecal Secretory Immunoglobulin A (SIgA) Response on Day 7, by Antigen [ Time Frame: 7 days ]

    Fecal secretion was measured on Day 0 and Day 7 (7 days after administration of first dose of vaccine). Antigens in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin


  22. Number and Percentage of 6-11 Month Old Subjects With ≥Four-fold Increase in Fecal Secretory Immunoglobulin A (SIgA) Response on Day 7, by Antigen [ Time Frame: 7 days ]

    Fecal secretion was measured on Day 0 and Day 7 (7 days after administration of first dose of vaccine). Antigens in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin


  23. Geometric Mean Titer (GMT) of Fecal Secretory Immunoglobulin A (SIgA) Response 6-11 Month Old Subjects on Day 7, by Antigen [ Time Frame: 7 days ]

    Fecal secretion was measured on Day 7 (7 days after administration of first dose of vaccine). Antigen in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin


  24. Geometric Mean Fold Change of Fecal Secretory Immunoglobulin A (SIgA) Response Among 6-11 Month Old Subjects on Day 7, by Antigen [ Time Frame: 7 days ]

    Fecal secretion was measured on Day 0 and Day 7 (7 days after administration of first dose of vaccine). Antigen in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin


  25. Number and Percentage of 6-11 Month Old Subjects With ≥Two-fold Increase in Fecal Secretory Immunoglobulin A (SIgA) Response on Day 19, by Antigen [ Time Frame: Day 19 ]

    Fecal secretion was measured on Day 0 and Day 19 (5 days after administration of second dose of vaccine). Antigen in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin


  26. Number and Percentage of 6-11 Month Old Subjects With ≥Four-fold Increase in Fecal Secretory Immunoglobulin A (SIgA) Response on Day 19, by Antigen [ Time Frame: 19 days ]

    Fecal secretion was measured on Day 0 and Day 19 (5 days after administration of second dose of vaccine). Antigens in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin


  27. Geometric Mean Titer (GMT) of Fecal Secretory Immunoglobulin A (SIgA) Response 6-11 Month Old Subjects on Day 19, by Antigen [ Time Frame: 19 days ]

    Fecal secretion was measured on Day 19 (5 days after administration of second dose of vaccine). Antigen in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin


  28. Geometric Mean Fold Change of Fecal Secretory Immunoglobulin A (SIgA) Response Among 6-11 Month Old Subjects on Day 19, by Antigen [ Time Frame: 19 days ]

    Fecal secretion was measured on Day 0 and Day 19 (5 days after administration of second dose of vaccine). Antigen in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin


  29. Number and Percentage of 6-11 Month Old Subjects With ≥Two-fold Increase in Fecal Secretory Immunoglobulin A (SIgA) Response on Day 28, by Antigen [ Time Frame: 28 days ]

    Fecal secretion was measured on Day 0 and Day 28 (2 weeks after administration of second dose of vaccine). Antigen in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin


  30. Number and Percentage of 6-11 Month Old Subjects With ≥Four-fold Increase in Fecal Secretory Immunoglobulin A (SIgA) Response on Day 28, by Antigen [ Time Frame: 28 days ]

    Fecal secretion was measured on Day 0 and Day 28 (2 weeks after administration of second dose of vaccine). Antigens in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin


  31. Geometric Mean Titer (GMT) of Fecal Secretory Immunoglobulin A (SIgA) Response 6-11 Month Old Subjects on Day 28, by Antigen [ Time Frame: 28 days ]

    Fecal secretion was measured on Day 28 (2 weeks after administration of second dose of vaccine). Antigen in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin


  32. Geometric Mean Fold Change of Fecal Secretory Immunoglobulin A (SIgA) Response Among 6-11 Month Old Subjects on Day 28, by Antigen [ Time Frame: 28 days ]

    Fecal secretion was measured on Day 0 and Day 28 (2 weeks after administration of second dose of vaccine). Antigen in ETVAX were:

    E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   6 Months to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Adults

Inclusion Criteria:

  1. Healthy male or female adults 18-45 years old, inclusive
  2. General good health as determined by the screening evaluation no greater than 7days before enrollment and vaccination
  3. Properly informed about the study, able to understand it and sign or thumb print the informed consent form
  4. Available for the entire period of the study and reachable by study staff throughout the entire follow-up period
  5. Females of childbearing potential who are willing to take a urine pregnancy test at screening and before the second vaccination. Pregnancy tests must be negative before each vaccination. Females of childbearing potential must agree to use an efficacious hormonal or barrier method of birth control during the study. Abstinence is also acceptable.
  6. Informed Consent (signature or thumb print provided, with witness signature)

Exclusion Criteria:

  1. Presence of any significant known systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, immunological, dermatological, neurological, cancer or autoimmune disease) as determined by medical history and/or physical examination which would endanger the participant's health or is likely to result in non-conformance to the protocol.
  2. History of congenital abdominal disorders, intussusception, abdominal surgery or any other congenital disorder or presence of a significant medical condition that in the opinion of the Investigator precludes participation in the study. Known or suspected impairment of immunological function based on medical history and physical examination. Clinical evidence of active gastrointestinal illness and acute disease at the time of enrollment
  3. Screening positive with hepatitis B antigen and/or hepatitis C antibodies
  4. Participation in research involving another investigational product (defined as receipt of investigational product) during the 30 days before planned date of first vaccination or concurrently participating in another clinical study at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational product
  5. Clinically significant abnormalities in screening hematology or serum chemistry, as determined by the Study Physician
  6. History of febrile illness within 48 hours prior to vaccination and fever at the time of immunization (fever is defined as a temperature ≥ 37.5 C (99.5 F) on axillary, oral, or tympanic measurement)
  7. Prior receipt of any cholera (e.g., Dukoral, Shanchol) or ETEC vaccine
  8. Prior receipt of a blood transfusion or blood products, including immunoglobulins
  9. Evidence of current illicit drug use or drug dependence
  10. Current use of iron or zinc supplements within the past 7 days; current use of antacids (H2 blockers, omeprazole, over-the-counter (OTC) agents) or immunosuppressive drug
  11. Any condition which, in the opinion of the investigator, might jeopardize the safety of study participants or interfere with the evaluation of the study objectives
  12. Receipt of antimicrobial drugs for any reason within 14 days before vaccination
  13. History of diarrhea during the 7 days before vaccination (see protocol definition of diarrhea)
  14. Culture positive for ETEC, Shigella, V. Cholerae or Salmonella within 7 days before vaccination.
  15. Acute disease at the time of enrollment or 3 days prior to enrollment
  16. History of chronic administration (defined as more than 14 days) of immunosuppressant medications, including corticosteroids.

Children, Toddlers and Infants Inclusion Criteria

  1. Healthy male or female infants/toddlers/children ages:

    • Part B: >24 and ≤59 months old at the time of enrollment
    • Part C: ≥12 and <24 months old at the time of enrollment
    • Part D: ≥6 and <12 months at the time of enrollment
  2. General good health as determined by the screening evaluation no greater than 7 days before enrollment and vaccination
  3. Parent properly informed about the study, able to understand it and sign or thumb print the informed consent form
  4. Parent and child available for the entire study period of the study and reachable by study staff throughout the entire follow-up period
  5. Informed Consent (signature or thumb of parent, with signature of witness, provided)

Exclusion Criteria

  1. Presence of any significant known systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, immunological, dermatological, neurological, cancer or autoimmune disease) as determined by medical history and/or physical examination which would endanger the participant's health or is likely to result in non-conformance to the protocol.
  2. History of congenital abdominal disorders, intussusception, abdominal surgery or any other congenital disorder or presence of a significant medical condition that in the opinion of the Investigator precludes participation in the study. Known or suspected impairment of immunological function based on medical history and physical examination. Clinical evidence of active gastrointestinal illness and acute disease at the time of enrollment
  3. Screening positive with hepatitis B antigen and/or hepatitis C antibodies
  4. Participation in research involving another investigational product (defined as receipt of investigational product) during the 30 days before planned date of first vaccination or concurrently participating in another clinical study at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational product
  5. Clinically significant abnormalities in screening hematology or serum chemistry, as determined by the Study Physician
  6. History of febrile illness within 48 hours prior to vaccination and fever at the time of immunization (fever is defined as a temperature ≥ 37.5 C (99.5 F) on axillary, oral, or tympanic measurement)
  7. Prior receipt of any cholera (e.g., Dukoral, Shanchol) or ETEC vaccine
  8. Prior receipt of a blood transfusion or blood products, including immunoglobulins
  9. Current use of iron or zinc supplements within the past 7 days; current use of antacids (H2 blockers, omeprazole, OTC agents) or immunosuppressive drug
  10. Any condition which, in the opinion of the investigator, might jeopardize the safety of study participants or interfere with the evaluation of the study objectives
  11. Receipt of antimicrobial drugs for any reason within 14 days before vaccination
  12. History of diarrhea during the 7 days before vaccination (see Protocol definition of diarrhea))
  13. Culture positive for ETEC, Shigella, V. cholerae, Salmonella or Rotavirus (the latter for all children <5 years of age) within 7 days of vaccination
  14. Acute disease at the time of enrollment or 3 days prior to enrollment
  15. Known or suspected impairment of immunological function based on medical history and physical examination
  16. Participant's parents/guardians not able, available or willing to accept active weekly follow-up by the study staff
  17. History of chronic administration (defined as more than 14 days) of immunosuppressant medications, including corticosteroids. Infants on inhaled or topical steroids may be permitted to participate in the study
  18. Any medical condition in the child/infant that, in the judgment of the investigator, would interfere with or serves as a contraindication to protocol adherence or a participant's parents' ability to give informed consent
  19. Medically significant malnutrition, defined as moderate malnutrition (wt-for-ht z-score between -3.0 and -2.0) and severe malnutrition (wt-for-ht z-score <-3.0 or edema)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02531802


Locations
Layout table for location information
Bangladesh
International Centre for Diarrheal Disease, Bangladesh (icddr,b)
Dhaka, Bangladesh, 1212
Sponsors and Collaborators
PATH
Scandinavian Biopharma AB
International Centre for Diarrhoeal Disease Research, Bangladesh
  Study Documents (Full-Text)

Documents provided by PATH:
Study Protocol  [PDF] June 1, 2015
Statistical Analysis Plan  [PDF] August 8, 2018

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: PATH
ClinicalTrials.gov Identifier: NCT02531802    
Other Study ID Numbers: VAC 014
First Posted: August 24, 2015    Key Record Dates
Results First Posted: September 12, 2018
Last Update Posted: September 12, 2018
Last Verified: September 2018
Keywords provided by PATH:
ETEC diarrhea
Escherichia Coli (ETEC)
Additional relevant MeSH terms:
Layout table for MeSH terms
Diarrhea
Signs and Symptoms, Digestive