Clinical trial NCT03404674: Dose Escalating Study of a Prototype CS6 Subunit Vaccine With a Modified Heat-labile Enterotoxin From Enterotoxigenic Escherichia Coli (ETEC)
Official title: A Phase 1 Dose Escalating Study of a Prototype CS6 Subunit Vaccine With a Modified Heat-labile Enterotoxin From Enterotoxigenic Escherichia Coli (ETEC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diarrhea
Keywords: ETEC
Escherichia coli
enteric
Lead sponsor: PATH
Sponsor class: OTHER
Collaborators: name: Naval Medical Research Center
name: Walter Reed Army Institute of Research (WRAIR)
First posted: 2018-01-19
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Number of Participants With Solicited Adverse Events
timeFrame: From first vaccination to 28 days after the third vaccination, 71 days.
measure: Number of Participants With Unsolicited Adverse Events
timeFrame: From first vaccination to 28 days after the third vaccination, 71 days.
Secondary outcomes:
measure: Percentage of Participants With a Serum Immunologic Response to Coli Surface Antigen 6 (CS6)
timeFrame: Baseline (Day 1 predose), Days 22 and 43 predose, and Day 70
measure: Percentage of Participants With a Serum Immunologic Response to Labile Toxin
timeFrame: Baseline (Day 1 predose), Days 22 and 43 predose, and Day 70
measure: Percentage of Participants With a Mucosal Immunologic Response to Coli Surface Antigen 6 (CS6)
timeFrame: Baseline (Day 1 pre-dose), Days 8 and 29 predose, and Day 50
measure: Percentage of Participants With a Mucosal Immunologic Response to Labile Toxin
timeFrame: Baseline (Day 1 pre-dose), Days 8 and 29 predose, and Day 50
measure: Geometric Mean Titer of Serum Anti-CS6 Immunoglobulin G Antibodies
timeFrame: Days 1, 22, and 43 pre-vaccination, and Day 70
measure: Geometric Mean Titer of Serum Anti-CS6 Immunoglobulin A Antibodies
timeFrame: Days 1, 22, and 43 pre-vaccination, and Day 70
measure: Geometric Mean Titer of Serum Anti-LT Immunoglobulin G Antibodies
timeFrame: Days 1, 22, and 43 pre-vaccination, and Day 70
measure: Geometric Mean Titer of Serum Anti-LT Immunoglobulin A Antibodies
timeFrame: Days 1, 22, and 43 pre-vaccination, and Day 70
measure: Geometric Mean Titer of Antibody Lymphocyte Supernatant Anti-CS6 Immunoglobulin G Antibodies
timeFrame: Days 1, 8, 29 and 50
measure: Geometric Mean Titer of Antibody Lymphocyte Supernatant Anti-CS6 Immunoglobulin A Antibodies
timeFrame: Days 1, 8, 29, and 50
measure: Geometric Mean Titer of Antibody Lymphocyte Supernatant Anti-LT Immunoglobulin G Antibodies
timeFrame: Days 1, 8, 29, and 50
measure: Geometric Mean Titer of Antibody Lymphocyte Supernatant Anti-LT Immunoglobulin A Antibodies
timeFrame: Days 1, 8, 29, and 50
Other outcomes:
Locations:
city: Silver Spring
country: United States
facility: Walter Reed Army Institute of Research Clinical Trial Center
state: Maryland
Study officials:
affiliation: Naval Medical Research Center
name: Tida K Lee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: