Escherichia Coli InfectionPhase 1NCT01382095
Safety Study of Recombinant Vaccine to Prevent ETEC Diarrhea
A Phase 1 study testing Recombinant fimbrial adhesin dscCfaE and Modified E. coli heat labile enterotoxin LTR192G in people with Escherichia Coli Infection, run by U.S. Army Medical Research and Development Command at 1 site in United States.
Trial summary
The purpose of the study is to determine if immunization with a recombinant E. coli protein, dscCfaE, is safe and immunogenic when administered through the skin using a patch. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Escherichia Coli Infection
- What is being tested?
- Recombinant fimbrial adhesin dscCfaE and Modified E. coli heat labile enterotoxin LTR192G
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2011to Apr 2013
- Phase
- Phase 1
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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 study completion.
Who cannot join
- Health problems such as, chronic medical conditions such as psychiatric conditions, diabetes mellitus, hypertension or any other conditions that might place the volunteer at increased risk of adverse events. Study clinicians, in consultation with the principal investigator (PI), will use clinical judgment on a case-by-case basis to assess safety risks under this criterion. The PI will consult with the Medical 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 IgA deficiency).
- Women who are pregnant or planning to become pregnant during the study period plus 3 months beyond the last study safety visit 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 HBsAg, HCV, HIV-1.
Show all 19Show fewer
- Clinically significant abnormalities on basic laboratory screening.
- Immunosuppressive illness or IgA deficiency (below the normal limits).
- Exclusionary skin history/findings that would confound assessment or prevent appropriate local monitoring of adverse events (AEs), or possibly increase the risk of an AE.
- History of chronic skin disease (clinician judgment).
- History of atopy.
- 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 Enterotoxigenic E. coli (ETEC) or V. cholerae infection.
- Travel to countries where ETEC or V. cholerae or other enteric infections are endemic (most of the developing world) within two years prior to dosing (clinician judgment).
- Received previous experimental ETEC or V. cholerae vaccine or live ETEC or V. cholerae challenge.
- Occupation involving handling of ETEC or V. cholerae currently, or in the past 3 years.
Trial locations and contacts
1 site in 1 country.
United States1 site
Walter Reed Army Institute of Research Clinical Trial Center
Silver Spring, Maryland, 20910
About this study
Official title: A Phase 1 Dose-Escalating Study of dscCfaE, Co-Administered With and Without LTR192G, by Transcutaneous Immunization (TCI) in Healthy Adult U.S. Volunteers
The purpose of the study is to determine if immunization with a recombinant E. coli protein, dscCfaE, is safe and immunogenic when administered through the skin using a patch.
Read the detailed description
The purpose of the study is to determine if immunization with dscCfaE with or without a modified E. coli heat labile enterotoxin, LTR192G, is safe and immunogenic when administered transcutaneously using a skin wet-patch. If the vaccine is found safe and adequately immunogenic in humans, a phase 2b vaccination/challenge study would be undertaken to further evaluate vaccine safety and allow a preliminary assessment of efficacy. With favorable evidence for safety, immunogenicity, efficacy, complemented by advances in standard methodology to combine multiple adhesins with an appropriate LT enterotoxoid form, a multivalent vaccine would be constructed and evaluated for further clinical development.
- Conditions
- Escherichia Coli Infection
- Being tested
- Recombinant fimbrial adhesin dscCfaE, Modified E. coli heat labile enterotoxin LTR192G
- Keywords
- ETEC, Diarrhea, Vaccine
- Medical subject headings
- Escherichia coli Infections, Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant fimbrial adhesin dscCfaEBiological
Also called dscCfaE
10 ug on study days 0, 21 and 42
Recombinant fimbrial adhesin dscCfaEBiological
Also called dscCfaE
50 ug on study days 0, 21 and 42
Recombinant fimbrial adhesin dscCfaEBiological
Also called dscCfaE
250 ug on study days 0, 21 and 42
Modified E. coli heat labile enterotoxin LTR192GBiological
Also called LTR192G
50 ug on study days 0, 21 and 42
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Not described Receives: Biological: Recombinant fimbrial adhesin dscCfaE; Biological: Modified E. coli heat labile enterotoxin LTR192G |
| Group B-1 | Experimental | Not described Receives: Biological: Recombinant fimbrial adhesin dscCfaE; Biological: Modified E. coli heat labile enterotoxin LTR192G |
| Group B-2 | Experimental | Not described Receives: Biological: Recombinant fimbrial adhesin dscCfaE |
| Group C | Experimental | Not described Receives: Biological: Recombinant fimbrial adhesin dscCfaE; Biological: Modified E. coli heat labile enterotoxin LTR192G |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of adverse events
Adverse event monitoring will survey and specifically inquire about fever (oral temperature > 100.4 o F), malaise, headache, rash, pain, diarrhea, abdominal pain, extremity pain or swelling. Clinical definitions will be used to grade severity of symptoms in accordance to the severity scale below: Grade 0 = None Grade 1= Barely noticeable Grade 2= Noticeable, does not interfere with daily activities Grade 3=Interferes with daily activities Grade 4=Prevents daily activities
Measured: Days 0 - 180
Secondary outcomes (3)
Number of Seroconversion to LT and dscCfaE; defined as a > 4-fold increase in endpoint titer between pre-and post-vaccination samples.
Measured: Study Days 0 - 180
Number of Mucosal responses (fecal IgA); defined as a > 4-fold increase in endpoint titer after adjusting for total IgA.
Measured: Study Days 0 - 180
Number of positive IgA-ASC responses; defined as a > 2-fold increase over th e baseline value of the ASC per 10 6 PBMC, when the number of ASC is > 0.5 per 10 6 in the baseline sample
A positive IgA-ASC response will be defined as a > 2-fold increase over th e baseline value of the ASC per 10 6 PBMC, when the number of ASC is > 0.5 per 10 6 in the baseline sample. When the number of baseline ASCs is less than 0.5 per 10 6 PBMC, a subject will be considered a responder if the post-vaccination value is greater than 1.0 per 10 6 PBMC
Measured: Study Days 0 - 180
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2011 (estimated)
- Study startJul 2011
- Primary completionAug 2012
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Escherichia Coli InfectionStudies 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 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- U.S. Army Medical Research and Development Command
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Mark S. Riddle, MD, DrPH, Principal investigator, Naval Medical Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01382095
- Sponsor's protocol ID
- A-16682
- Other IDs
- NMRC.2011.0004, WRAIR 1804
- Status last verified
- Apr 2015
- First submitted
- 23 Jun 2011
- Last updated
- 27 Apr 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Dose-Escalating Study of dscCfaE, Co-Administered With and Without LTR192G, by Transcutaneous Immunization (TCI) in Healthy Adult U.S. Volunteers
- ClinicalTrials.gov ID
- NCT01382095
- Acronym / sponsor ID
- A-16682
- Conditions
- Escherichia Coli Infection
- Keywords
- ETEC, Diarrhea, Vaccine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- U.S. Army Medical Research and Development CommandUS federal agency
- Study start
- Jul 2011
- Primary completion
- Aug 2012 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 27 Jun 2011 (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.
The purpose of the study is to determine if immunization with a recombinant E. coli protein, dscCfaE, is safe and immunogenic when administered through the skin using a patch.
Detailed description
The purpose of the study is to determine if immunization with dscCfaE with or without a modified E. coli heat labile enterotoxin, LTR192G, is safe and immunogenic when administered transcutaneously using a skin wet-patch. If the vaccine is found safe and adequately immunogenic in humans, a phase 2b vaccination/challenge study would be undertaken to further evaluate vaccine safety and allow a preliminary assessment of efficacy. With favorable evidence for safety, immunogenicity, efficacy, complemented by advances in standard methodology to combine multiple adhesins with an appropriate LT enterotoxoid form, a multivalent vaccine would be constructed and evaluated for further clinical development.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Biological: Recombinant fimbrial adhesin dscCfaE, Biological: Modified E. coli heat labile enterotoxin LTR192G |
| Group B-1 | Experimental | Biological: Recombinant fimbrial adhesin dscCfaE, Biological: Modified E. coli heat labile enterotoxin LTR192G |
| Group B-2 | Experimental | Biological: Recombinant fimbrial adhesin dscCfaE |
| Group C | Experimental | Biological: Recombinant fimbrial adhesin dscCfaE, Biological: Modified E. coli heat labile enterotoxin LTR192G |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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 study completion.
Key exclusion criteria (19 listed)
- Health problems such as, chronic medical conditions such as psychiatric conditions, diabetes mellitus, hypertension or any other conditions that might place the volunteer at increased risk of adverse events. Study clinicians, in consultation with the principal investigator (PI), will use clinical judgment on a case-by-case basis to assess safety risks under this criterion. The PI will consult with the Medical 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 IgA deficiency).
- Women who are pregnant or planning to become pregnant during the study period plus 3 months beyond the last study safety visit 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.
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 |
|---|---|---|
| Recombinant fimbrial adhesin dscCfaEAlso: dscCfaE10 ug on study days 0, 21 and 42 | Biological | Group A |
| Recombinant fimbrial adhesin dscCfaEAlso: dscCfaE50 ug on study days 0, 21 and 42 | Biological | Group B-1, Group B-2 |
| Recombinant fimbrial adhesin dscCfaEAlso: dscCfaE250 ug on study days 0, 21 and 42 | Biological | Group C |
| Modified E. coli heat labile enterotoxin LTR192GAlso: LTR192G50 ug on study days 0, 21 and 42 | Biological | Group A, Group B-1, Group C |
Primary outcome
Number of adverse events
Time frame: Days 0 - 180
Adverse event monitoring will survey and specifically inquire about fever (oral temperature > 100.4 o F), malaise, headache, rash, pain, diarrhea, abdominal pain, extremity pain or swelling. Clinical definitions will be used to grade severity of symptoms in accordance to the severity scale below: Grade 0 = None Grade 1= Barely noticeable Grade 2= Noticeable, does not interfere with daily activities Grade 3=Interferes with daily activities Grade 4=Prevents daily activities
3 secondary outcomes
Number of Seroconversion to LT and dscCfaE; defined as a > 4-fold increase in endpoint titer between pre-and post-vaccination samples.
Time frame: Study Days 0 - 180
Number of Mucosal responses (fecal IgA); defined as a > 4-fold increase in endpoint titer after adjusting for total IgA.
Time frame: Study Days 0 - 180
Number of positive IgA-ASC responses; defined as a > 2-fold increase over th e baseline value of the ASC per 10 6 PBMC, when the number of ASC is > 0.5 per 10 6 in the baseline sample
Time frame: Study Days 0 - 180
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 27 Apr 2015.
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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.
Mark S. Riddle, MD, DrPH principal investigator
Naval Medical Research Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Recombinant fimbrial adhesin dscCfaE and Modified E. coli heat labile enterotoxin LTR192G in people with Escherichia Coli Infection, run by U.S. Army Medical Research and Development Command 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 5 inclusion and 19 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 27 Apr 2015. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Number of adverse events (time frame: Days 0 - 180). 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 27 Apr 2015.