A Phase 1 Dose Escalating Study of a Prototype CS6 Subunit Vaccine With a Modified Heat-labile Enterotoxin From Enterotoxigenic Escherichia Coli (ETEC)
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 50
- Locations
- 2
- Primary Endpoint
- Number of Participants With Unsolicited Adverse Events
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 45 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy, adult, male or female, age 18 to 45 years (inclusive) at the time of enrollment.
- •Completion and review of comprehension test (achieved > 70% accuracy).
- •Signed informed consent document.
- •Available for the required follow-up period and scheduled clinic visits.
- •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
- •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.
- •Clinically significant abnormalities on physical examination.
- •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).
- •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.
- •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.
- •Positive blood test for Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV), human immunodeficiency virus (HIV)-1/
- •Clinically significant abnormalities on basic laboratory screening.
- •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
- •History of chronic skin disease (clinician judgement)
- •Acute skin infection/eruptions on the upper arms including fungal infections, severe acne or active contact dermatitis
- •Allergies that may increase the risk of AEs
- •Regular use (weekly or more often) of antidiarrheal, anti-constipation, or antacid therapy
- •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
- •History of microbiologically confirmed ETEC or cholera infection in the last 3 years
- •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)
- •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
- •Vaccination for or ingestion of ETEC, cholera, or E. coli heat labile toxin within 3 years prior to dosing
- •Occupation involving handling of ETEC or V. cholerae currently, or in the past 3 years
Outcomes
Primary Outcomes
Number of Participants With Unsolicited Adverse Events
Time Frame: From first vaccination to 28 days after the third vaccination, 71 days.
Adverse events were assessed for severity by the investigator according to the following: Mild (Grade 1): Does not interfere with routine activities Minimal level of discomfort Moderate (Grade 2): Interferes with routine activities Moderate level of discomfort Severe (Grade 3): Unable to perform routine activities Significant level of discomfort Potentially life-threatening (Grade 4): Hospitalization or emergency room (ER) visit for potentially life-threatening event
Number of Participants With Solicited Adverse Events
Time Frame: From first vaccination to 28 days after the third vaccination, 71 days.
Solicited adverse events included vaccine site pain, vaccine site pruritus, vaccine site rash/eruption, vaccine site swelling, vaccine site tenderness, fever, headache, diarrhea, arthralgia, myalgia, malaise, nausea, and vomiting. Adverse events were assessed for severity by the investigator according to the following: Mild (Grade 1): Does not interfere with routine activities, minimal level of discomfort Moderate (Grade 2): Interferes with routine activities, moderate level of discomfort Severe (Grade 3): Unable to perform routine activities, significant level of discomfort Potentially life-threatening (Grade 4): Hospitalization or emergency room (ER) visit for potentially life-threatening event
Secondary Outcomes
- Percentage of Participants With a Mucosal Immunologic Response to Coli Surface Antigen 6 (CS6)(Baseline (Day 1 pre-dose), Days 8 and 29 predose, and Day 50)
- Geometric Mean Titer of Antibody Lymphocyte Supernatant Anti-LT Immunoglobulin A Antibodies(Days 1, 8, 29, and 50)
- Percentage of Participants With a Serum Immunologic Response to Coli Surface Antigen 6 (CS6)(Baseline (Day 1 predose), Days 22 and 43 predose, and Day 70)
- Percentage of Participants With a Mucosal Immunologic Response to Labile Toxin(Baseline (Day 1 pre-dose), Days 8 and 29 predose, and Day 50)
- Geometric Mean Titer of Serum Anti-CS6 Immunoglobulin A Antibodies(Days 1, 22, and 43 pre-vaccination, and Day 70)
- Geometric Mean Titer of Antibody Lymphocyte Supernatant Anti-CS6 Immunoglobulin G Antibodies(Days 1, 8, 29 and 50)
- Geometric Mean Titer of Antibody Lymphocyte Supernatant Anti-CS6 Immunoglobulin A Antibodies(Days 1, 8, 29, and 50)
- Geometric Mean Titer of Serum Anti-CS6 Immunoglobulin G Antibodies(Days 1, 22, and 43 pre-vaccination, and Day 70)
- Percentage of Participants With a Serum Immunologic Response to Labile Toxin(Baseline (Day 1 predose), Days 22 and 43 predose, and Day 70)
- Geometric Mean Titer of Serum Anti-LT Immunoglobulin G Antibodies(Days 1, 22, and 43 pre-vaccination, and Day 70)
- Geometric Mean Titer of Serum Anti-LT Immunoglobulin A Antibodies(Days 1, 22, and 43 pre-vaccination, and Day 70)
- Geometric Mean Titer of Antibody Lymphocyte Supernatant Anti-LT Immunoglobulin G Antibodies(Days 1, 8, 29, and 50)