NCT03404674

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Jan 2018

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 10, 2018

Completed
6 days until next milestone

Study Start

First participant enrolled

January 16, 2018

Completed
3 days until next milestone

First Posted

Study publicly available on registry

January 19, 2018

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 26, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 26, 2019

Completed
1.8 years until next milestone

Results Posted

Study results publicly available

January 6, 2021

Completed
Last Updated

January 6, 2021

Status Verified

November 1, 2020

Enrollment Period

1.2 years

First QC Date

January 10, 2018

Results QC Date

December 10, 2020

Last Update Submit

December 10, 2020

Conditions

Diarrhea

Keywords

ETECEscherichia colienteric

Outcome Measures

Primary Outcomes (2)

  • Number of Participants With Solicited Adverse Events

    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

    From first vaccination to 28 days after the third vaccination, 71 days.

  • Number of Participants With Unsolicited Adverse Events

    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

    From first vaccination to 28 days after the third vaccination, 71 days.

Secondary Outcomes (12)

  • 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 Serum Immunologic Response to Labile Toxin

    Baseline (Day 1 predose), Days 22 and 43 predose, and Day 70

  • 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

  • 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 G Antibodies

    Days 1, 22, and 43 pre-vaccination, and Day 70

  • +7 more secondary outcomes

Study Arms (6)

Group A1: CssBA 5 ug

EXPERIMENTAL

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

Biological: CssBA

Group A2: DmLT 100 ng

EXPERIMENTAL

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

Biological: dmLT

Group B: CssBA 5 ug + DmLT 100 ng

EXPERIMENTAL

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

Biological: CssBABiological: dmLT

Group C: CssBA 5 ug + DmLT 500 ng

EXPERIMENTAL

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

Biological: CssBABiological: dmLT

Group D: CssBA 15 ug + DmLT 500 ng

EXPERIMENTAL

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

Biological: CssBABiological: dmLT

Group E: CssBA 45 ug + DmLT 500 ng

EXPERIMENTAL

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

Biological: CssBABiological: dmLT

Interventions

CssBABIOLOGICAL

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

Also known as: spd_dsc16Bntd14CssBAB7A[His]₆
Group A1: CssBA 5 ugGroup B: CssBA 5 ug + DmLT 100 ngGroup C: CssBA 5 ug + DmLT 500 ngGroup D: CssBA 15 ug + DmLT 500 ngGroup E: CssBA 45 ug + DmLT 500 ng
dmLTBIOLOGICAL

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

Group A2: DmLT 100 ngGroup B: CssBA 5 ug + DmLT 100 ngGroup C: CssBA 5 ug + DmLT 500 ngGroup D: CssBA 15 ug + DmLT 500 ngGroup E: CssBA 45 ug + DmLT 500 ng

Eligibility Criteria

Age18 Years - 45 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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)-1/2.
  • Clinically significant abnormalities on basic laboratory screening.
  • 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
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Walter Reed Army Institute of Research Clinical Trial Center

Silver Spring, Maryland, 20910, United States

Location

MeSH Terms

Conditions

DiarrheaEscherichia coli Infections

Condition Hierarchy (Ancestors)

Signs and Symptoms, DigestiveSigns and SymptomsPathological Conditions, Signs and SymptomsEnterobacteriaceae InfectionsGram-Negative Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfections

Results Point of Contact

Title
Rahsan Erdem
Organization
PATH
rerdem@path.org
202-540-4546

Study Officials

  • Tida K Lee, MD, PhD

    Naval Medical Research Center

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
SEQUENTIAL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 10, 2018

First Posted

January 19, 2018

Study Start

January 16, 2018

Primary Completion

March 26, 2019

Study Completion

March 26, 2019

Last Updated

January 6, 2021

Results First Posted

January 6, 2021

Record last verified: 2020-11

Locations

US(1)