Safety, Immunogenicity and Efficacy Study of Inactivated Whole Cell Shigella Flexneri 2a Vaccine With and Without dmLT in Adults

NCT03038243 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: VAC-047
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a research study about an experimental (investigational) oral inactivated whole cell Shigella flexneri 2a killed vaccine (Sf2aWC) and an adjuvant called dmLT. Sf2aWC is a killed vaccine that is being made to prevent disease from Shigella., which causes bloody, watery diarrhea. An adjuvant is something that is added to a vaccine to make it work better. The purpose of the study is to see if the vaccine will protect people from Shigella infection with or without an adjuvant called dmLT. About 72 healthy adults, ages 18-45, will participate in this study. The study will compare 2 different vaccination groups and 1 control group. Volunteers have an equal chance to be in any of the 3 groups. Study procedures include: stool samples, blood samples and documenting side effects. Participants will be involved in study related procedures for about 6 months.

Conditions

Shigella Sonnei Dysenteries

Keywords

Shigella; vaccine; shigellosis; dysentery; whole cell

Outcome Measures

Primary Outcomes (2)

• solicited reactions, AEs, SAEs

  solicited reactions, AEs, SAEs assessed post-vaccination using targeted physical examinations, vital signs, and clinical laboratory tests

  first vaccination through 6 months post-3rd vaccination

• prevention of moderate to severe shigellosis

  prevention of moderate to severe shigellosis identified by diarrhea, fever, dysentery, and other signs/symptoms of enteric illness

  up to 24 hours

Study Arms (3)

Cohort 1

EXPERIMENTAL

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

Biological: Shigella flexneri 2a whole cell (Sf2aWC) vaccine and double mutant E. coli heat labile toxin (dmLT); Biological: Shigella flexneri 2a whole cell (Sf2aWC) vaccine; Other: Placebo

Cohort 2

EXPERIMENTAL

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

Biological: Shigella flexneri 2a whole cell (Sf2aWC) vaccine and double mutant E. coli heat labile toxin (dmLT); Biological: Shigella flexneri 2a whole cell (Sf2aWC) vaccine; Other: Placebo

Cohort 3

EXPERIMENTAL

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

Biological: Shigella flexneri 2a whole cell (Sf2aWC) vaccine and double mutant E. coli heat labile toxin (dmLT); Biological: Shigella flexneri 2a whole cell (Sf2aWC) vaccine; Other: Placebo

Interventions

Shigella flexneri 2a whole cell (Sf2aWC) vaccine and double mutant E. coli heat labile toxin (dmLT) BIOLOGICAL

2.25 x 10\^11 Sf2aWC cells +10 µg dmLT administered orally on Days 0, 28, and 56

Cohort 1; Cohort 2; Cohort 3

Shigella flexneri 2a whole cell (Sf2aWC) vaccine BIOLOGICAL

2.25 x 10\^11 Sf2WC cells administered orally on Days 0, 28, and 56

Cohort 1; Cohort 2; Cohort 3

Placebo OTHER

2.0 grams of NaHCO3 dissolved in 150 mL of sterile water

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• PATH: lead

Study Sites (1)

Center for Vaccine Development (CVD), University of Maryland School of Medicine

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Dysentery, Bacillary; Dysentery

Interventions

Vaccines

Condition Hierarchy (Ancestors)

Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Study Officials

• Wilbur Chen, MD, MS

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2017
• First Posted: January 31, 2017
• Study Start: August 1, 2017
• Primary Completion: December 31, 2018
• Study Completion: December 31, 2019
• Last Updated: November 20, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)