Safety and Efficacy Study of a Vaccine Against Enterotoxigenic Escherichia Coli (ETEC) to Prevent Moderate to Severe Diarrhea
Primary Purpose
Diarrhea
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ACE527
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Diarrhea focused on measuring Vaccination, Challenge, Diarrhea, ETEC illness, Travelers diarrhea, ETEC, Enterotoxigenic E.coli
Eligibility Criteria
Inclusion criteria:
- Male or female age ≥18 and ≤ 50 years.
- General good health, without clinically significant medical history, physical examination findings or clinical laboratory abnormalities per clinical judgment of PI.
- Negative serum pregnancy test before first (visit V0) and before challenge (visit C0) for female subjects of childbearing potential. Females of childbearing potential must agree to use an efficacious hormonal or barrier method of birth control during the study. Abstinence is acceptable. Female subjects unable to bear children must have this documented (e.g. tubal ligation or hysterectomy) or must have negative pregnancy tests.
- Willingness to participate in the study after all aspects of the protocol have been explained and written informed consent obtained.
- Completion of a training session and demonstrated comprehension of the protocol procedures, knowledge of ETEC-associated illness, and by passing a written examination.
- Availability for the study duration, including all planned follow-up visits.
Exclusion criteria:
- Presence of a significant medical or psychiatric condition which in the opinion of the investigator precludes participation in the study. Some medical conditions which are adequately treated and stable would not preclude entry into the study. These conditions might include stable asthma controlled with inhalers or mild hypertension stably controlled with a single agent.
- Significant abnormalities in screening hematology, serum chemistry or urinalysis as determined by PI or PI in consultation with the MM and sponsor.
- Presence in the serum of HIV antibody, HBsAg, or HCV antibody.
- Evidence of IgA deficiency (serum IgA < 7 mg/dl or limit of detection of assay).
- Evidence of current excessive alcohol consumption or drug dependence.
- Evidence of impaired immune function.
- BMI <19, >34
- Recent vaccination or receipt of an investigational product (within 30 days before vaccination).
- Intention to donate blood or blood products for one month following the completion of study participation (note: The Red Cross will not allow blood donations for 1 year following participation in an investigational research study).
- Any other criteria which, in the investigator's opinion, would compromise the ability of the subject to participate in the study, the safety of the study, or the results of the study
- Working as a food handler, in child-care or as a healthcare worker with direct patient contact.
- Have household contacts who are <2 years old or >80 years old or infirm or immunocompromised (for reasons including corticosteroid therapy, HIV infection, cancer chemotherapy, or other chronic debilitating disease).
- Abnormal stool pattern (fewer than 3 per week or more than 3 per day).
- Regular use of laxatives, antacids, or other agents to lower stomach acidity.
- Use of any medication known to affect the immune function (e.g., corticosteroids and others) within 30 days preceding the first vaccination or planned use during the active study period.
- Known allergy to two of the following antibiotics: quinolones, trimethoprim-sulfamethoxazole, and penicillin.
- Symptoms consistent with Traveler's Diarrhea concurrent with travel to countries where ETEC infection is endemic (most of the developing world) within two years prior to dosing, OR planned travel to endemic countries during the length of the study.
- Vaccination for or ingestion of ETEC, cholera, or LT toxin within 3 years prior to dosing.
- Use of antibiotics during the 7 days before dosing or proton pump inhibitors, H2 blockers or antacids within 48 hours prior to dosing.
- History of diarrhea in the 7 days prior to vaccination (outpatient diarrhea is defined as ≥ 3 unformed loose stools in 24 hours).
Sites / Locations
- Center for Immunization Research (CIR)
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
ACE527
Placebo vaccine
Arm Description
First cohort: ACE527 vaccine doses of 9 x 10E10 cfu on study day 0 and 21 on an outpatient basis. Second cohort: ACE527 vaccine dose of 9 x 10E10 cfu on study day 0 and 21 on an outpatient basis.
First cohort: Placebo vaccine on study day 0 and 21 on an outpatient basis. Second cohort: Placebo vaccine on study day 0 and 21 on an outpatient basis.
Outcomes
Primary Outcome Measures
Severe diarrhea: ≥6 grade 3-5 stools in 24 hrs, or >800g of grade 3-5 stools in 24 hrs and moderate diarrhea: 4-5 grade 3-5 stools in 24 hrs or 401-800g of grade 3-5 stools in 24 hrs
Secondary Outcome Measures
Number of subjects with severe diarrhea (if any)
Number of subjects with diarrhea of any severity
Mean total weight of grade 3-5 stools passed per subject
Mean number of grade 3-5 stools per subject
Number of subjects with nausea, vomiting, anorexia, or abdominal pain/cramps rated as moderate to severe.
Number of subjects who indicate they would have reduced their daily activity if they had been vacationing or traveling for business because of their ETEC illness.
Mean time to onset of diarrhea.
Number of subjects with moderate to severe ETEC illness
Number of colony forming unite (cfu) of the challenge strain per gram of stool
Number of subjects requiring early antibiotic treatment
Number of subjects requiring IV fluids
Systemic immune responses to the constituent strains of the vaccine
Mucosal immune responses to the constituent strains of the vaccine
The intestinal colonization by the three individual vaccine strains and challenge strain post-vaccination
Full Information
NCT ID
NCT01060748
First Posted
January 28, 2010
Last Updated
March 4, 2011
Sponsor
TD Vaccines A/S
Collaborators
Pierrel Research USA, Inc., Johns Hopkins Bloomberg School of Public Health
1. Study Identification
Unique Protocol Identification Number
NCT01060748
Brief Title
Safety and Efficacy Study of a Vaccine Against Enterotoxigenic Escherichia Coli (ETEC) to Prevent Moderate to Severe Diarrhea
Official Title
Development of a Polyvalent Vaccine Against Enterotoxigenic Escherichia Coli (ETEC)Protective Efficacy of the Deletion-Attenuated, Multi-valent ACE527 Against Challenge With a Prototype Strain of Enterotoxigenic E.Coli Expressing LT and ST Enterotoxins and CFA/I (Strain H10407) in Human Challenge Model.
Study Type
Interventional
2. Study Status
Record Verification Date
March 2011
Overall Recruitment Status
Completed
Study Start Date
March 2010 (undefined)
Primary Completion Date
October 2010 (Actual)
Study Completion Date
October 2010 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
TD Vaccines A/S
Collaborators
Pierrel Research USA, Inc., Johns Hopkins Bloomberg School of Public Health
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a research study about an experimental (investigational) vaccine called ACE527. ACE527 is a vaccine that is being made to prevent disease from a germ called enterotoxigenic Escherichia coli (ETEC). This germ causes diarrhea, largely in children living in developing countries and in travelers to those countries. One purpose of this study is to see if the vaccine is safe and develops an immune response. Another purpose is to see if it prevents people from getting sick when exposed to the ETEC germ. This ETEC germ is also experimental (investigational).
Detailed Description
This is a single-center, double-blind, placebo-controlled, Phase II vaccination and challenge study designed to assess the protective efficacy of the ACE 527 vaccine, as well as collect expanded safety and immunogenicity data. The study will be carried out in two phases. In the initial vaccination phase, up to 72 subjects will be randomized 1:1 to receive either ACE527 or placebo on an outpatient basis. Vaccine and placebo preparations will be given orally. Following vaccination, subjects will be followed as out-patients for safety using diary card surveillance, for vaccine shedding by qualitative stool culture (i.e. presence or absence) and for the development of local and systemic antibody responses to the ACE527 vaccine strains. In the subsequent inpatient challenge phase, up to 56 vaccinated subjects will be admitted as inpatients and challenged with the ETEC strain, H10407. The challenge dose will be administered orally.After challenge, subjects will be monitored for diarrhea and other signs/symptoms of enteric illness by daily medical checks, vital sign determinations, grading and weighing of all stools. Monitoring for fecal shedding of the challenge ETEC strain H10407 will occur daily, after challenge, while in-patient. Local and systemic antibody responses to the challenge ETEC strain H10407 will also be assessed. All subjects will be treated with Abx.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diarrhea
Keywords
Vaccination, Challenge, Diarrhea, ETEC illness, Travelers diarrhea, ETEC, Enterotoxigenic E.coli
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
70 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ACE527
Arm Type
Experimental
Arm Description
First cohort: ACE527 vaccine doses of 9 x 10E10 cfu on study day 0 and 21 on an outpatient basis.
Second cohort: ACE527 vaccine dose of 9 x 10E10 cfu on study day 0 and 21 on an outpatient basis.
Arm Title
Placebo vaccine
Arm Type
Placebo Comparator
Arm Description
First cohort: Placebo vaccine on study day 0 and 21 on an outpatient basis.
Second cohort: Placebo vaccine on study day 0 and 21 on an outpatient basis.
Intervention Type
Biological
Intervention Name(s)
ACE527
Intervention Description
ACE527 comprises a mixture of three live, attenuated ETEC strains; ACAM2025 (CFA/I+ and LTB+), ACAM2022 (CS5+, CS6+ and LTB+), and ACAM2027 (CS1+, CS2+, CS3+ and LTB+). The vaccine is administered orally as a two-dose regimen, at 9x1010 cfu, on Days 0 and 21, in 200 ml CeraVacx buffer. The required volume of each vaccine strain, supplied as a frozen suspension, is mixed into the buffer solution prior to dosing.
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Severe diarrhea: ≥6 grade 3-5 stools in 24 hrs, or >800g of grade 3-5 stools in 24 hrs and moderate diarrhea: 4-5 grade 3-5 stools in 24 hrs or 401-800g of grade 3-5 stools in 24 hrs
Time Frame
Study Day 49 to 57
Secondary Outcome Measure Information:
Title
Number of subjects with severe diarrhea (if any)
Time Frame
Study Day 49 to 57
Title
Number of subjects with diarrhea of any severity
Time Frame
Study Day 49 to 57
Title
Mean total weight of grade 3-5 stools passed per subject
Time Frame
Study Day 49 to 57
Title
Mean number of grade 3-5 stools per subject
Time Frame
Study day 49 to 57
Title
Number of subjects with nausea, vomiting, anorexia, or abdominal pain/cramps rated as moderate to severe.
Time Frame
Study Day 0 to 77
Title
Number of subjects who indicate they would have reduced their daily activity if they had been vacationing or traveling for business because of their ETEC illness.
Time Frame
Last visit
Title
Mean time to onset of diarrhea.
Time Frame
Study Day 49 to 57
Title
Number of subjects with moderate to severe ETEC illness
Time Frame
Study Day 49 to 57
Title
Number of colony forming unite (cfu) of the challenge strain per gram of stool
Time Frame
Study day 49 to 57
Title
Number of subjects requiring early antibiotic treatment
Time Frame
Study Day 49 to 57
Title
Number of subjects requiring IV fluids
Time Frame
Study Day 49 to 57
Title
Systemic immune responses to the constituent strains of the vaccine
Time Frame
Selected Time Points
Title
Mucosal immune responses to the constituent strains of the vaccine
Time Frame
Selected Time Points
Title
The intestinal colonization by the three individual vaccine strains and challenge strain post-vaccination
Time Frame
Selected Time Points
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion criteria:
Male or female age ≥18 and ≤ 50 years.
General good health, without clinically significant medical history, physical examination findings or clinical laboratory abnormalities per clinical judgment of PI.
Negative serum pregnancy test before first (visit V0) and before challenge (visit C0) for female subjects of childbearing potential. Females of childbearing potential must agree to use an efficacious hormonal or barrier method of birth control during the study. Abstinence is acceptable. Female subjects unable to bear children must have this documented (e.g. tubal ligation or hysterectomy) or must have negative pregnancy tests.
Willingness to participate in the study after all aspects of the protocol have been explained and written informed consent obtained.
Completion of a training session and demonstrated comprehension of the protocol procedures, knowledge of ETEC-associated illness, and by passing a written examination.
Availability for the study duration, including all planned follow-up visits.
Exclusion criteria:
Presence of a significant medical or psychiatric condition which in the opinion of the investigator precludes participation in the study. Some medical conditions which are adequately treated and stable would not preclude entry into the study. These conditions might include stable asthma controlled with inhalers or mild hypertension stably controlled with a single agent.
Significant abnormalities in screening hematology, serum chemistry or urinalysis as determined by PI or PI in consultation with the MM and sponsor.
Presence in the serum of HIV antibody, HBsAg, or HCV antibody.
Evidence of IgA deficiency (serum IgA < 7 mg/dl or limit of detection of assay).
Evidence of current excessive alcohol consumption or drug dependence.
Evidence of impaired immune function.
BMI <19, >34
Recent vaccination or receipt of an investigational product (within 30 days before vaccination).
Intention to donate blood or blood products for one month following the completion of study participation (note: The Red Cross will not allow blood donations for 1 year following participation in an investigational research study).
Any other criteria which, in the investigator's opinion, would compromise the ability of the subject to participate in the study, the safety of the study, or the results of the study
Working as a food handler, in child-care or as a healthcare worker with direct patient contact.
Have household contacts who are <2 years old or >80 years old or infirm or immunocompromised (for reasons including corticosteroid therapy, HIV infection, cancer chemotherapy, or other chronic debilitating disease).
Abnormal stool pattern (fewer than 3 per week or more than 3 per day).
Regular use of laxatives, antacids, or other agents to lower stomach acidity.
Use of any medication known to affect the immune function (e.g., corticosteroids and others) within 30 days preceding the first vaccination or planned use during the active study period.
Known allergy to two of the following antibiotics: quinolones, trimethoprim-sulfamethoxazole, and penicillin.
Symptoms consistent with Traveler's Diarrhea concurrent with travel to countries where ETEC infection is endemic (most of the developing world) within two years prior to dosing, OR planned travel to endemic countries during the length of the study.
Vaccination for or ingestion of ETEC, cholera, or LT toxin within 3 years prior to dosing.
Use of antibiotics during the 7 days before dosing or proton pump inhibitors, H2 blockers or antacids within 48 hours prior to dosing.
History of diarrhea in the 7 days prior to vaccination (outpatient diarrhea is defined as ≥ 3 unformed loose stools in 24 hours).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clayton Harro, MD
Organizational Affiliation
CIR, Johns Hopkins School of Public Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Center for Immunization Research (CIR)
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
12. IPD Sharing Statement
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Safety and Efficacy Study of a Vaccine Against Enterotoxigenic Escherichia Coli (ETEC) to Prevent Moderate to Severe Diarrhea
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