DiarrheaPhase 2NCT01060748
Safety and Efficacy Study of a Vaccine Against Enterotoxigenic Escherichia Coli (ETEC) to Prevent Moderate to Severe Diarrhea
A Phase 2 study testing ACE527 in people with Diarrhea, run by TD Vaccines A/S at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Diarrhea
- What is being tested?
- ACE527
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2010to Oct 2010
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 20Show fewer
- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
Center for Immunization Research (CIR)
Baltimore, Maryland, 21205
About this study
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.
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).
Read the 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.
- Conditions
- Diarrhea
- Being tested
- ACE527, Placebo
- Keywords
- Vaccination, Challenge, Diarrhea, ETEC illness, Travelers diarrhea, ETEC, Enterotoxigenic E.coli
- Medical subject headings
- Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACE527Biological
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.
PlaceboBiological
Placebo
| Study group | Role | What they receive |
|---|---|---|
| ACE527 | Experimental | 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. Receives: Biological: ACE527 |
| Placebo vaccine | Placebo comparator | 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. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Study Day 49 to 57
Secondary outcomes (14)
Number of subjects with severe diarrhea (if any)
Measured: Study Day 49 to 57
Number of subjects with diarrhea of any severity
Measured: Study Day 49 to 57
Mean total weight of grade 3-5 stools passed per subject
Measured: Study Day 49 to 57
Mean number of grade 3-5 stools per subject
Measured: Study day 49 to 57
Number of subjects with nausea, vomiting, anorexia, or abdominal pain/cramps rated as moderate to severe.
Measured: Study Day 0 to 77
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.
Measured: Last visit
Mean time to onset of diarrhea.
Measured: Study Day 49 to 57
Number of subjects with moderate to severe ETEC illness
Measured: Study Day 49 to 57
Number of colony forming unite (cfu) of the challenge strain per gram of stool
Measured: Study day 49 to 57
Number of subjects requiring early antibiotic treatment
Measured: Study Day 49 to 57
Number of subjects requiring IV fluids
Measured: Study Day 49 to 57
Systemic immune responses to the constituent strains of the vaccine
Measured: Selected Time Points
Mucosal immune responses to the constituent strains of the vaccine
Measured: Selected Time Points
The intestinal colonization by the three individual vaccine strains and challenge strain post-vaccination
Measured: Selected Time Points
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2010 (estimated)
- Study startMar 2010
- Primary completionOct 2010
- Study completionOct 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DiarrheaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- TD Vaccines A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Pierrel Research USA, Inc., Johns Hopkins Bloomberg School of Public Health
- Investigators
- Clayton Harro, MD, Principal investigator, CIR, Johns Hopkins School of Public Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01060748
- Sponsor's protocol ID
- ACE527-102
- Status last verified
- Mar 2011
- First submitted
- 28 Jan 2010
- Last updated
- 7 Mar 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01060748
- Acronym / sponsor ID
- ACE527-102
- Conditions
- Diarrhea
- Keywords
- Vaccination, Challenge, Diarrhea, ETEC illness, Travelers diarrhea, ETEC, Enterotoxigenic E.coli
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- TD Vaccines A/SIndustry (pharma, biotech, devices)
- Collaborators
- Pierrel Research USA, Inc., Johns Hopkins Bloomberg School of Public Health
- Study start
- Mar 2010
- Primary completion
- Oct 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 2 Feb 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ACE527 | Experimental | Biological: ACE527First 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. |
| Placebo vaccine | Placebo comparator | Biological: PlaceboFirst 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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ACE527ACE527 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. | Biological | ACE527 |
| PlaceboPlacebo | Biological | Placebo vaccine |
Primary outcome
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
14 secondary outcomes
Number of subjects with severe diarrhea (if any)
Time frame: Study Day 49 to 57
Number of subjects with diarrhea of any severity
Time frame: Study Day 49 to 57
Mean total weight of grade 3-5 stools passed per subject
Time frame: Study Day 49 to 57
Mean number of grade 3-5 stools per subject
Time frame: Study day 49 to 57
Number of subjects with nausea, vomiting, anorexia, or abdominal pain/cramps rated as moderate to severe.
Time frame: Study Day 0 to 77
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
Mean time to onset of diarrhea.
Time frame: Study Day 49 to 57
Number of subjects with moderate to severe ETEC illness
Time frame: Study Day 49 to 57
Number of colony forming unite (cfu) of the challenge strain per gram of stool
Time frame: Study day 49 to 57
Number of subjects requiring early antibiotic treatment
Time frame: Study Day 49 to 57
Number of subjects requiring IV fluids
Time frame: Study Day 49 to 57
Systemic immune responses to the constituent strains of the vaccine
Time frame: Selected Time Points
Mucosal immune responses to the constituent strains of the vaccine
Time frame: Selected Time Points
The intestinal colonization by the three individual vaccine strains and challenge strain post-vaccination
Time frame: Selected Time Points
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2011.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clayton Harro, MD principal investigator
CIR, Johns Hopkins School of Public Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ACE527 in people with Diarrhea, run by TD Vaccines A/S at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Mar 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2011.