- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03038243
Safety, Immunogenicity and Efficacy Study of Inactivated Whole Cell Shigella Flexneri 2a Vaccine With and Without dmLT in Adults
A Phase 2a/2b, Randomized, Double-blinded, Placebo-controlled, Trial to Assess the Safety, Immunogenicity and Efficacy of Inactivated Shigella Flexneri 2a Whole Cell (Sf2aWC) Vaccine Administered With and Without Double Mutant E. Coli Heat Labile Toxin (dmLT) in Healthy Adult Subjects
Study Overview
Status
Conditions
Detailed Description
Despite the public health burden of Shigella spp. on travelers, deployed soldiers and, most significantly, young children in the developing world, there is no licensed vaccine against Shigella. The rationale for using Shigella flexneri 2a whole cell killed vaccine (Sf2aWC), is that it is expected to be especially well tolerated by subjects. This is a single site, 2a/2b, double-blind, randomized, placebo-controlled, study in healthy adult subjects. Approximately 72 subjects will be enrolled into one of three vaccination groups: Sf2aWC 1011 Sf2aWC cells plus 10 µg dmLT (Group 1, n=24), 1011 Sf2WC cells alone (Group 2, n=24); or placebo (Group 4, n=24). The placebo preparation will be bicarbonate buffer.
After the vaccination phase subjects will be admitted by cohort on day 84 to an inpatient facility for 12 days to undergo challenge with approximately 1500 colony forming units (CFU) of wild type S. flexneri 2a strain 2457T (administered with NaHCO3 buffer). After 5 days of observation for clinical endpoints (or earlier and within 12 hours if they meet the definition of moderate-to-severe shigellosis as defined in the primary endpoints section below), subjects will receive a 5-day course of orally administered ciprofloxacin.
The primary objective of this study are to 1) evaluate, the safety and reactogenicity of 3 oral sequential doses of Sf2aWC with or without dmLT, 2) To measure the protective efficacy of 3 spaced doses of high-dose Sf2aWC vaccine with and without dmLT against moderate-to-severe shigellosis following experimental oral challenge with wild-type S. flexneri 2a 2457T
Study Type
Phase
- Phase 2
Contacts and Locations
Study Locations
-
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Maryland
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Baltimore, Maryland, United States, 21201
- Center for Vaccine Development (CVD), University of Maryland School of Medicine
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Healthy adults, male or female, age 18 to 45 years (inclusive) at the time of enrollment.
- General good health, without clinically significant medical history, physical examination findings or clinical laboratory abnormalities per clinical judgment of PI.
- 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 and knowledge of Shigella associated illness by passing a written examination (70% pass score).
- Availability for the study duration, including all planned follow-up visits.
Exclusion Criteria:
- Presence of a significant medical or psychiatric condition that in the opinion of the investigator precludes participation in the study. Some medical conditions that 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, or serum chemistry as determined by PI or PI in consultation with the Medical Officer and sponsor.
- Recent of a non-study vaccine or receipt of another investigational product (within 14 days before vaccination).
- Have household contacts who are <3 years old or >70 years old or infirm or immunocompromised (for reasons including corticosteroid therapy, HIV infection, cancer chemotherapy, or other chronic debilitating disease).
- Use of any medication that affects the immune function (e.g., corticosteroids and others) within 30 days preceding the first vaccination or planned use during the active study period.
- Symptoms of Traveler's diarrhea associated with travel to countries where Shigella or other enteric infections are endemic (most of the developing world) within 1 year prior to dosing.
- History of shigellosis or Shigella vaccination or challenge or a laboratory worker with known exposure to Shigella within the last 6 months
- Prior receipt of experimental Shigella vaccine or live Shigella challenge within 3 years.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort 1
Group 1, 2.25 x 10^11 Sf2aWC cells +10 µg dmLT Group 2, 2.25 x 10^11 Sf2WC cells Group 3, 2.0 grams of NaHCO3 dissolved in 150 mL of sterile water
|
2.25 x 10^11 Sf2aWC cells +10 µg dmLT administered orally on Days 0, 28, and 56
2.25 x 10^11 Sf2WC cells administered orally on Days 0, 28, and 56
2.0 grams of NaHCO3 dissolved in 150 mL of sterile water
|
Experimental: Cohort 2
Group 1, 2.25 x 10^11 Sf2aWC cells +10 µg dmLT Group 2, 2.25 x 10^11 Sf2WC cells Group 3, 2.0 grams of NaHCO3 dissolved in 150 mL of sterile water
|
2.25 x 10^11 Sf2aWC cells +10 µg dmLT administered orally on Days 0, 28, and 56
2.25 x 10^11 Sf2WC cells administered orally on Days 0, 28, and 56
2.0 grams of NaHCO3 dissolved in 150 mL of sterile water
|
Experimental: Cohort 3
Group 1, 2.25 x 10^11 Sf2aWC cells +10 µg dmLT Group 2, 2.25 x 10^11 Sf2WC cells Group 3, 2.0 grams of NaHCO3 dissolved in 150 mL of sterile water
|
2.25 x 10^11 Sf2aWC cells +10 µg dmLT administered orally on Days 0, 28, and 56
2.25 x 10^11 Sf2WC cells administered orally on Days 0, 28, and 56
2.0 grams of NaHCO3 dissolved in 150 mL of sterile water
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
solicited reactions, AEs, SAEs
Time Frame: first vaccination through 6 months post-3rd vaccination
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solicited reactions, AEs, SAEs assessed post-vaccination using targeted physical examinations, vital signs, and clinical laboratory tests
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first vaccination through 6 months post-3rd vaccination
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prevention of moderate to severe shigellosis
Time Frame: up to 24 hours
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prevention of moderate to severe shigellosis identified by diarrhea, fever, dysentery, and other signs/symptoms of enteric illness
|
up to 24 hours
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Wilbur Chen, MD, MS, University of Maryland School of Medicine
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Infections
- Gastrointestinal Diseases
- Gastroenteritis
- Intestinal Diseases
- Gram-Negative Bacterial Infections
- Bacterial Infections
- Bacterial Infections and Mycoses
- Enterobacteriaceae Infections
- Dysentery, Bacillary
- Dysentery
- Physiological Effects of Drugs
- Immunologic Factors
- Vaccines
Other Study ID Numbers
- VAC-047
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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