ShigellosisPhase 1/2NCT00485134
Shigella Flexneri 2a Invaplex 50 Vaccine Dose Finding and Assessment of Protection
A Phase 1/2 study testing 240 µg Shigella flexneri 2a Invaplex 50 vaccine, 480 µg Shigella flexneri 2a Invaplex 50 vaccine and 690 Shigella flexneri 2a Invaplex 50 vaccine in people with Shigellosis, run by U.S. Army Medical Research and Development Command at 2 sites in United States.
Trial summary
The purpose of this study is to select a safe and immunogenic dose of Invaplex 50 intranasal vaccine, and to assess protection of Invaplex 50 intranasal vaccine against diarrhea, dysentery, and fever following challenge with the Shigella flexneri 2a 2457T strain. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Shigellosis
- What is being tested?
- 240 µg Shigella flexneri 2a Invaplex 50 vaccine, 480 µg Shigella flexneri 2a Invaplex 50 vaccine and 690 Shigella flexneri 2a Invaplex 50 vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 113 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2007to Sep 2010
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 form.
- 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 two (2) months following study completion.
Who cannot join
- General Health
- Health problems affecting study participation from medical history specifically to include chronic medical conditions such as psychiatric conditions, diabetes mellitus and hypertension or any other condition requiring chronic daily therapy that would place the volunteer at increased risk - as determined by a study physician, current use of antihypertensive medications, or other medications that may interact with pseudoephedrine in the event it is required to treat rhinorrhea).
- Clinically significant abnormalities on physical examination.
- Use of immunosuppressive drugs such as corticosteroids or chemotherapeutics that may influence antibody development.
- Women currently nursing
- 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 throughout the duration of the study.
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- Positive blood test for HBsAG, HCV, HIV-1.
- Clinically significant abnormalities on basic laboratory screening.
- Immunosuppressive illness or IgA deficiency (below the normal limits).
- Research specific
- Presence of nasal polyps, ulcers, or deviated nasal septum (further defined in section 4.2).
- History of chronic sinusitis or chronic/seasonal rhinitis (further defined in section 4.2)
- History of rhinoplasty.
- History of reactive airway disease (asthma), chronic obstructive pulmonary disease, or chronic bronchitis.
- History of Bell's palsy.
- Current smoker or smoker in past 3 months ('smoker' defined as daily cigarette cigar, or pipe use for a period of at least 1 month).
- 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.
- Personal or family history of an inflammatory arthritis.
- Positive blood test for HLA-B27.
- Prior exposure to Shigella
- History of microbiologically confirmed Shigella infection.
- Received previous experimental Shigella vaccine or live Shigella challenge.
- Travel to countries where Shigella or other enteric infections are endemic (most of the developing world) within two years prior to dosing.
- Occupation involving handling of Shigella bacteria currently, or in the past 3 years.
- Serum IgG titer ≥ 2500 to Shigella LPS
- Additionally, subjects participating in stage 2 with any of the following will be excluded:
- Are employed as a food handler, daycare provider or work in a nursing home, or are in direct care of an immunocompromised person, a child <2 years of age or frail elderly.
- Significant abnormalities in pre-admission screening lab hematology, serum chemistry, urinalysis or EKG (EKG only in volunteers ≥40 years), as determined by PI or the PI in consultation with the medical monitor and sponsor.
- Allergy to ciprofloxacin on ampicillin (excluded if allergic to either).
- History of diarrhea in the 2 weeks prior to planned inpatient phase.
- Use of antibiotics during the 7 days before Shigella inoculation or proton pump inhibitors, H2 blockers, or antacids within 48 hours of inoculation.
- Inability to comply with inpatient rules and regulations.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Center for Immunization Research (CIR) John Hopkins Bayview Medical Center
Baltimore, Maryland, 21287
Department of Clinical Trials, WRAIR
Silver Spring, Maryland, 20910
About this study
The purpose of this study is to select a safe and immunogenic dose of Invaplex 50 intranasal vaccine, and to assess protection of Invaplex 50 intranasal vaccine against diarrhea, dysentery, and fever following challenge with the Shigella flexneri 2a 2457T strain.
- Conditions
- Shigellosis
- Being tested
- 240 µg Shigella flexneri 2a Invaplex 50 vaccine, 480 µg Shigella flexneri 2a Invaplex 50 vaccine, 690 Shigella flexneri 2a Invaplex 50 vaccine, Shigella challenge strain
- Medical subject headings
- Dysentery, Bacillary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
240 µg Shigella flexneri 2a Invaplex 50 vaccineBiological
Vaccines were administered intranasally on Days 0, 14, and 28. The investigational vaccine was supplied as 1 mL of a sterile, clear liquid in a 3 ml glass vial. Each vial contained 3.5 mg of protein and 567 μg of LPS. The pH was 8.9 and the buffer was 250 mM NaCl in 20 mM Tris.
480 µg Shigella flexneri 2a Invaplex 50 vaccineBiological
Vaccines were administered intranasally on Days 0, 14, and 28. The investigational vaccine was supplied as 1 mL of a sterile, clear liquid in a 3 ml glass vial. Each vial contained 3.5 mg of protein and 567 μg of LPS. The pH was 8.9 and the buffer was 250 mM NaCl in 20 mM Tris.
690 Shigella flexneri 2a Invaplex 50 vaccineBiological
Vaccines were administered intranasally on Days 0, 14, and 28. The investigational vaccine was supplied as 1 mL of a sterile, clear liquid in a 3 ml glass vial. Each vial contained 3.5 mg of protein and 567 μg of LPS. The pH was 8.9 and the buffer was 250 mM NaCl in 20 mM Tris.
Shigella challenge strainOther
Also called Shigella challenge material
300 colony forming units (CFU) of Shigella challenge strain, Shigella flexneri 2a strain 2457T
| Study group | Role | What they receive |
|---|---|---|
| Stage 1: Group A, Dolphin 240 µg | Experimental | 240 µg Shigella flexneri 2a Invaplex 50 vaccine. The investigational vaccine was supplied as 1 mL of a sterile, clear liquid in a 3 mL glass vial. Each vial contained 3.5 mg of protein and 567 μg of lipopolysaccharides (LPS). 230 μL of the formulated vaccine (or placebo, sterile saline) was added to a nasal spray applicator (DolphinTM). Receives: Biological: 240 µg Shigella flexneri 2a Invaplex 50 vaccine |
| Stage 1: Group B, Dolphin 480 µg | Experimental | 480 µg Shigella flexneri 2a Invaplex 50 vaccine. The investigational vaccine was supplied as 1 mL of a sterile, clear liquid in a 3 mL glass vial. Each vial contained 3.5 mg of protein and 567 μg of LPS. 230 μL of the formulated vaccine (or placebo, sterile saline) was added to a nasal spray applicator (DolphinTM). Receives: Biological: 480 µg Shigella flexneri 2a Invaplex 50 vaccine |
| Stage 1: Group C, Dolphin 690 µg | Experimental | 690 Shigella flexneri 2a Invaplex 50 vaccine. The investigational vaccine was supplied as 1 mL of a sterile, clear liquid in a 3 mL glass vial. Each vial contained 3.5 mg of protein and 567 μg of LPS. 230 μL of the formulated vaccine (or placebo, sterile saline) was added to a nasal spray applicator (DolphinTM). Receives: Biological: 690 Shigella flexneri 2a Invaplex 50 vaccine |
| Stage 1: Group D, Pipette 240 µg | Other | 240 µg Shigella flexneri 2a Invaplex 50 vaccine. The investigational vaccine was supplied as 1 mL of a sterile, clear liquid in a 3 mL glass vial. Each vial contained 3.5 mg of protein and 567 μg of LPS. These subjects received 200 μL the vaccine via electronic pipette. This group is for lot bridging only, not included in dose-finding study. Receives: Biological: 240 µg Shigella flexneri 2a Invaplex 50 vaccine |
| Stage 2: Immunized / Challenge | Other | The selected dose was to be administered with the Dolphin™ using the vaccination schedule from stage 1. Immunized and challenged with Shigella challenge strain approximately 42 days after receiving the last vaccination following a 90-minute fast. Receives: Other: Shigella challenge strain |
| Stage 2: Controls | Placebo comparator | A control was to be administered with the DolphinTM using the vaccination schedule from Stage 1. Non-immunized and challenged with Shigella challenge strain approximately 42 days after receiving the last vaccination following a 90-minute fast. Receives: Other: Shigella challenge strain |
What is being measured
The primary outcome is the main question the study is designed to answer.
Post-challenge Diarrhea, Fever, and Blood in Stool Adverse Events by Study Group
Fecal samples were collected through day 77 or until discharge (all stools collected for weighing/grading; maximum of 3 stools/day for culture; rectal swab obtained if no stool provided).
Measured: 7 days after challenge
Secondary outcomes (5)
Post-challenge Loose Stool Samples Occurrences by Study Group
Measured: 7 days after challenge
Post-challenge Loose Stool Sample Volumes by Study Group
Measured: 7 days after challenge
Post-challenge Loose Stool Sample Durations by Study Group
Measured: 7 days after challenge
S. Flexneri 2a Related Non-diarrheal Clinical Outcomes by Study Group
Measured: 56 days post-challenge
Number of Subjects Exhibiting an Immune Response to Invaplex 50 and/or LPS
Immune responder is defined as someone with both a serologic and an ASC response to either Invaplex 50 or LPS. Immune response defined as Serology: ≥ 4-fold increase in baseline serum titer antibody cecreting cells (ASC): ≥ 10 ASC per 106 peripheral blood mononuclear cells(PBMC).
Measured: 56 days post-vaccination in stage 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2007 (estimated)
- Study startMay 2007
- Primary completionJul 2009
- Study completionSep 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for ShigellosisStudies 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 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 113 participants (actual)
Sponsor and investigators
- Lead sponsor
- U.S. Army Medical Research and Development Command
- Sponsor type
- US federal agency
- Collaborators
- U.S. Army Office of the Surgeon General
- Responsible party
- Sponsor
- Investigators
- Mark Riddle, MD, Principal investigator, Naval Medical Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00485134
- Sponsor's protocol ID
- NMRC.2006.0007
- Other IDs
- HSRRB # A-14057, WRAIR 1328
- Status last verified
- Aug 2017
- First submitted
- 11 Jun 2007
- Last updated
- 11 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Shigella Flexneri 2a Invaplex 50 Vaccine Dose Finding and Assessment of Protection
- ClinicalTrials.gov ID
- NCT00485134
- Acronym / sponsor ID
- NMRC.2006.0007
- Conditions
- Shigellosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 113 participants (actual)
- Lead sponsor
- U.S. Army Medical Research and Development CommandUS federal agency
- Collaborators
- U.S. Army Office of the Surgeon General
- Study start
- May 2007
- Primary completion
- Jul 2009 (actual)
- Study completion
- Sep 2010 (actual)
- First posted
- 12 Jun 2007 (estimated)
- Results
- Posted 11 Sep 2017
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 this study is to select a safe and immunogenic dose of Invaplex 50 intranasal vaccine, and to assess protection of Invaplex 50 intranasal vaccine against diarrhea, dysentery, and fever following challenge with the Shigella flexneri 2a 2457T strain.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Stage 1: Group A, Dolphin 240 µg | Experimental | Biological: 240 µg Shigella flexneri 2a Invaplex 50 vaccine240 µg Shigella flexneri 2a Invaplex 50 vaccine. The investigational vaccine was supplied as 1 mL of a sterile, clear liquid in a 3 mL glass vial. Each vial contained 3.5 mg of protein and 567 μg of lipopolysaccharides (LPS). 230 μL of the formulated vaccine (or placebo, sterile saline) was added to a nasal spray applicator (DolphinTM). |
| Stage 1: Group B, Dolphin 480 µg | Experimental | Biological: 480 µg Shigella flexneri 2a Invaplex 50 vaccine480 µg Shigella flexneri 2a Invaplex 50 vaccine. The investigational vaccine was supplied as 1 mL of a sterile, clear liquid in a 3 mL glass vial. Each vial contained 3.5 mg of protein and 567 μg of LPS. 230 μL of the formulated vaccine (or placebo, sterile saline) was added to a nasal spray applicator (DolphinTM). |
| Stage 1: Group C, Dolphin 690 µg | Experimental | Biological: 690 Shigella flexneri 2a Invaplex 50 vaccine690 Shigella flexneri 2a Invaplex 50 vaccine. The investigational vaccine was supplied as 1 mL of a sterile, clear liquid in a 3 mL glass vial. Each vial contained 3.5 mg of protein and 567 μg of LPS. 230 μL of the formulated vaccine (or placebo, sterile saline) was added to a nasal spray applicator (DolphinTM). |
| Stage 1: Group D, Pipette 240 µg | Other | Biological: 240 µg Shigella flexneri 2a Invaplex 50 vaccine240 µg Shigella flexneri 2a Invaplex 50 vaccine. The investigational vaccine was supplied as 1 mL of a sterile, clear liquid in a 3 mL glass vial. Each vial contained 3.5 mg of protein and 567 μg of LPS. These subjects received 200 μL the vaccine via electronic pipette. This group is for lot bridging only, not included in dose-finding study. |
| Stage 2: Immunized / Challenge | Other | Other: Shigella challenge strainThe selected dose was to be administered with the Dolphin™ using the vaccination schedule from stage 1. Immunized and challenged with Shigella challenge strain approximately 42 days after receiving the last vaccination following a 90-minute fast. |
| Stage 2: Controls | Placebo comparator | Other: Shigella challenge strainA control was to be administered with the DolphinTM using the vaccination schedule from Stage 1. Non-immunized and challenged with Shigella challenge strain approximately 42 days after receiving the last vaccination following a 90-minute fast. |
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 form.
- 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 two (2) months following study completion.
Key exclusion criteria (33 listed)
- General Health
- Health problems affecting study participation from medical history specifically to include chronic medical conditions such as psychiatric conditions, diabetes mellitus and hypertension or any other condition requiring chronic daily therapy that would place the volunteer at increased risk - as determined by a study physician, current use of antihypertensive medications, or other medications that may interact with pseudoephedrine in the event it is required to treat rhinorrhea).
- Clinically significant abnormalities on physical examination.
- Use of immunosuppressive drugs such as corticosteroids or chemotherapeutics that may influence antibody development.
- Women currently nursing
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 |
|---|---|---|
| 240 µg Shigella flexneri 2a Invaplex 50 vaccineVaccines were administered intranasally on Days 0, 14, and 28. The investigational vaccine was supplied as 1 mL of a sterile, clear liquid in a 3 ml glass vial. Each vial contained 3.5 mg of protein and 567 μg of LPS. The pH was 8.9 and the buffer was 250 mM NaCl in 20 mM Tris. | Biological | Stage 1: Group A, Dolphin 240 µg, Stage 1: Group D, Pipette 240 µg |
| 480 µg Shigella flexneri 2a Invaplex 50 vaccineVaccines were administered intranasally on Days 0, 14, and 28. The investigational vaccine was supplied as 1 mL of a sterile, clear liquid in a 3 ml glass vial. Each vial contained 3.5 mg of protein and 567 μg of LPS. The pH was 8.9 and the buffer was 250 mM NaCl in 20 mM Tris. | Biological | Stage 1: Group B, Dolphin 480 µg |
| 690 Shigella flexneri 2a Invaplex 50 vaccineVaccines were administered intranasally on Days 0, 14, and 28. The investigational vaccine was supplied as 1 mL of a sterile, clear liquid in a 3 ml glass vial. Each vial contained 3.5 mg of protein and 567 μg of LPS. The pH was 8.9 and the buffer was 250 mM NaCl in 20 mM Tris. | Biological | Stage 1: Group C, Dolphin 690 µg |
| Shigella challenge strainAlso: Shigella challenge material300 colony forming units (CFU) of Shigella challenge strain, Shigella flexneri 2a strain 2457T | Other | Stage 2: Controls, Stage 2: Immunized / Challenge |
Primary outcome
Post-challenge Diarrhea, Fever, and Blood in Stool Adverse Events by Study Group
Time frame: 7 days after challenge
Fecal samples were collected through day 77 or until discharge (all stools collected for weighing/grading; maximum of 3 stools/day for culture; rectal swab obtained if no stool provided).
5 secondary outcomes
Post-challenge Loose Stool Samples Occurrences by Study Group
Time frame: 7 days after challenge
Post-challenge Loose Stool Sample Volumes by Study Group
Time frame: 7 days after challenge
Post-challenge Loose Stool Sample Durations by Study Group
Time frame: 7 days after challenge
S. Flexneri 2a Related Non-diarrheal Clinical Outcomes by Study Group
Time frame: 56 days post-challenge
Number of Subjects Exhibiting an Immune Response to Invaplex 50 and/or LPS
Time frame: 56 days post-vaccination in stage 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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 Riddle, MD principal investigator
Naval Medical Research Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 240 µg Shigella flexneri 2a Invaplex 50 vaccine, 480 µg Shigella flexneri 2a Invaplex 50 vaccine and 690 Shigella flexneri 2a Invaplex 50 vaccine in people with Shigellosis, run by U.S. Army Medical Research and Development Command at 2 sites 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 33 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 11 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 combined 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.
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?
Yes. Results are posted in the registry (first posted 11 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Post-challenge Diarrhea, Fever, and Blood in Stool Adverse Events by Study Group (time frame: 7 days after challenge). 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 11 Sep 2017.