Clinical trial NCT00485134: Shigella Flexneri 2a Invaplex 50 Vaccine Dose Finding and Assessment of Protection
Official title: Shigella Flexneri 2a Invaplex 50 Vaccine Dose Finding and Assessment of Protection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Shigellosis
Lead sponsor: U.S. Army Medical Research and Development Command
Sponsor class: FED
Collaborators: name: U.S. Army Office of the Surgeon General
First posted: 2007-06-12
Enrollment: 113
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

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.
* 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.

Primary outcomes:
measure: Post-challenge Diarrhea, Fever, and Blood in Stool Adverse Events by Study Group
timeFrame: 7 days after challenge
Secondary outcomes:
measure: Post-challenge Loose Stool Samples Occurrences by Study Group
timeFrame: 7 days after challenge
measure: Post-challenge Loose Stool Sample Volumes by Study Group
timeFrame: 7 days after challenge
measure: Post-challenge Loose Stool Sample Durations by Study Group
timeFrame: 7 days after challenge
measure: S. Flexneri 2a Related Non-diarrheal Clinical Outcomes by Study Group
timeFrame: 56 days post-challenge
measure: Number of Subjects Exhibiting an Immune Response to Invaplex 50 and/or LPS
timeFrame: 56 days post-vaccination in stage 1
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Center for Immunization Research (CIR) John Hopkins Bayview Medical Center
state: Maryland
city: Silver Spring
country: United States
facility: Department of Clinical Trials, WRAIR
state: Maryland
Study officials:
affiliation: Naval Medical Research Center
name: Mark Riddle, MD
role: PRINCIPAL_INVESTIGATOR
References: