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

PATH

Status and phase: Completed; Phase 1

Conditions: Diarrhea

Treatments: Biological: dmLT; Biological: CssBA

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT03404674

VAC-050

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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50 participants in 6 patient groups

Group A1: CssBA 5 ug

Experimental group

Description:

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

Treatment:

Biological: CssBA

Group A2: DmLT 100 ng

Experimental group

Description:

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

Treatment:

Biological: dmLT

Group B: CssBA 5 ug + DmLT 100 ng

Experimental group

Description:

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

Treatment:

Biological: CssBA

Biological: dmLT

Group C: CssBA 5 ug + DmLT 500 ng

Experimental group

Description:

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

Treatment:

Biological: CssBA

Biological: dmLT

Group D: CssBA 15 ug + DmLT 500 ng

Experimental group

Description:

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

Treatment:

Biological: CssBA

Biological: dmLT

Group E: CssBA 45 ug + DmLT 500 ng

Experimental group

Description:

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

Treatment:

Biological: CssBA

Biological: dmLT