Dose Escalating Study of a Prototype CS6 Subunit Vaccine With a Modified Heat-labile Enterotoxin From Enterotoxigenic Escherichia Coli (ETEC)

NCT ID: NCT03404674

Last Updated: 2021-01-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-16
• Study Completion Date: 2019-03-26

Brief Summary

This study will evaluate the safety of a prototype Coli surface antigen 6 (CS6) subunit vaccine (CssBA) alone or in combination with Escherichia coli double mutant heat labile toxin (dmLT) given by intramuscular (IM) injection.

Detailed Description

This is an open-label clinical trial in which a total of 50 participants will receive three injections of either CssBA alone, dmLT alone or CssBA + dmLT. The vaccine will be administered via IM injection to alternating deltoid regions on days 1, 22, and 43. Each participant will receive the same dose at each vaccination dependent upon group assignment. Group A is considered a pilot group in which all 3 doses will be administered and participants monitored for safety 7 days after the third vaccination, prior to the enrollment of participants in Group B.

Conditions

Diarrhea

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Group A1: CssBA 5 ug

Participants received an intramuscular injection of 5 ug CssBA on days 1, 22, and 43.

Group Type: EXPERIMENTAL

CssBA

Intervention Type: BIOLOGICAL

Recombinant enterotoxigenic Escherichia coli (ETEC) surface antigen 6 containing modified structural subunits A and B

Group A2: DmLT 100 ng

Participants received an intramuscular injection of 100 ng DmLT on days 1, 22, and 43.

Group Type: EXPERIMENTAL

dmLT

Intervention Type: BIOLOGICAL

Escherichia coli double mutant heat-labile toxin with mutations at amino acids 192 and 211

Group B: CssBA 5 ug + DmLT 100 ng

Participants received an intramuscular injection of 5 ug CssBA + 100 ng dmLT on days 1, 22, and 43.

Group Type: EXPERIMENTAL

CssBA

Intervention Type: BIOLOGICAL

Recombinant enterotoxigenic Escherichia coli (ETEC) surface antigen 6 containing modified structural subunits A and B

dmLT

Intervention Type: BIOLOGICAL

Escherichia coli double mutant heat-labile toxin with mutations at amino acids 192 and 211

Group C: CssBA 5 ug + DmLT 500 ng

Participants received an intramuscular injection of 5 ug CssBA + 500 ng dmLT on days 1, 22, and 43.

Group Type: EXPERIMENTAL

CssBA

Intervention Type: BIOLOGICAL

Recombinant enterotoxigenic Escherichia coli (ETEC) surface antigen 6 containing modified structural subunits A and B

dmLT

Intervention Type: BIOLOGICAL

Escherichia coli double mutant heat-labile toxin with mutations at amino acids 192 and 211

Group D: CssBA 15 ug + DmLT 500 ng

Participants received an intramuscular injection of 15 ug CssBA + 500 ng dmLT on days 1, 22, and 43.

Group Type: EXPERIMENTAL

CssBA

Intervention Type: BIOLOGICAL

Recombinant enterotoxigenic Escherichia coli (ETEC) surface antigen 6 containing modified structural subunits A and B

dmLT

Intervention Type: BIOLOGICAL

Escherichia coli double mutant heat-labile toxin with mutations at amino acids 192 and 211

Group E: CssBA 45 ug + DmLT 500 ng

Participants received an intramuscular injection of 45 ug CssBA + 500 ng dmLT on days 1, 22, and 43.

Group Type: EXPERIMENTAL

CssBA

Intervention Type: BIOLOGICAL

Recombinant enterotoxigenic Escherichia coli (ETEC) surface antigen 6 containing modified structural subunits A and B

dmLT

Intervention Type: BIOLOGICAL

Escherichia coli double mutant heat-labile toxin with mutations at amino acids 192 and 211

Interventions

CssBA

Recombinant enterotoxigenic Escherichia coli (ETEC) surface antigen 6 containing modified structural subunits A and B

Intervention Type: BIOLOGICAL

dmLT

Escherichia coli double mutant heat-labile toxin with mutations at amino acids 192 and 211

Intervention Type: BIOLOGICAL

Other Intervention Names

spd_dsc16Bntd14CssBAB7A[His]₆

Eligibility Criteria

Inclusion Criteria

1. Healthy, adult, male or female, age 18 to 45 years (inclusive) at the time of enrollment.

2. Completion and review of comprehension test (achieved > 70% accuracy).

3. Signed informed consent document.

4. Available for the required follow-up period and scheduled clinic visits.

5. Women: Negative pregnancy test with understanding (through informed consent process) to not become pregnant during the study or within three (3) months following last vaccination.

Exclusion Criteria

1. Health problems (for example, intercurrent febrile illness, chronic medical conditions such as psychiatric conditions, diabetes mellitus, hypertension or any other condition that might place the subject at increased risk of adverse events) - study clinicians, in consultation with the PI, will use clinical judgment on a case-by-case basis to assess safety risks under this criterion. The PI will consult with the Research Monitor as appropriate.

2. Clinically significant abnormalities on physical examination.

3. Immunosuppressive drugs (use of systemic corticosteroids or chemotherapeutics that may influence antibody development) or illness (including immunoglobulin A [IgA] deficiency, defined by serum IgA < 7 mg/dL).

4. Women who are pregnant or planning to become pregnant during the study period plus three (3) months beyond the last received dose and currently nursing women.

5. Participation in research involving another investigational product (defined as receipt of investigational product or exposure to invasive investigational device) 30 days before planned date of first vaccination or anytime through the last study safety visit.

6. Positive blood test for Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV), human immunodeficiency virus (HIV)-1/2.

7. Clinically significant abnormalities on basic laboratory screening.

8. Exclusionary skin disease history/findings that would confound assessment or prevent appropriate local monitoring of adverse events (AEs), or possibly increase the risk of a local AE

9. History of chronic skin disease (clinician judgement)

10. Acute skin infection/eruptions on the upper arms including fungal infections, severe acne or active contact dermatitis

11. Allergies that may increase the risk of AEs

12. Regular use (weekly or more often) of antidiarrheal, anti-constipation, or antacid therapy

13. Abnormal stool pattern (fewer than 3 stools per week or more than 3 stools per day) on a regular basis; loose or liquid stools on other than an occasional basis

14. History of microbiologically confirmed ETEC or cholera infection in the last 3 years

15. Travel to countries where ETEC or V. cholerae or other enteric infections are endemic (most of the developing world) within 3 years prior to dosing (clinician judgement)

16. Symptoms consistent with Travelers' Diarrhea or concurrent with travel to countries where ETEC infection is endemic (most of the developing world) within 3 years prior to dosing, OR planned travel to endemic countries during the length of the study

17. Vaccination for or ingestion of ETEC, cholera, or E. coli heat labile toxin within 3 years prior to dosing

18. Occupation involving handling of ETEC or V. cholerae currently, or in the past 3 years

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Naval Medical Research Center

FED

Sponsor Role: collaborator

Walter Reed Army Institute of Research (WRAIR)

FED

Sponsor Role: collaborator

PATH

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tida K Lee, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Naval Medical Research Center

Locations

Walter Reed Army Institute of Research Clinical Trial Center

Silver Spring, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

VAC-050

Identifier Type: -

Identifier Source: org_study_id