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

Primary Purpose

Shigella Sonnei Dysenteries

Status

Withdrawn

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

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

Shigella flexneri 2a whole cell (Sf2aWC) vaccine

Placebo

About this trial

This is an interventional treatment trial for Shigella Sonnei Dysenteries focused on measuring Shigella, vaccine, shigellosis, dysentery, whole cell

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Arm Description

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

Outcomes

Primary Outcome Measures

solicited reactions, AEs, SAEs

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

prevention of moderate to severe shigellosis

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

Secondary Outcome Measures

Full Information

NCT ID

NCT03038243

First Posted

January 23, 2017

Last Updated

November 16, 2017

Sponsor

PATH

1. Study Identification

Unique Protocol Identification Number

NCT03038243

Brief Title

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

Official Title

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 Type

Interventional

2. Study Status

Record Verification Date

November 2017

Overall Recruitment Status

Withdrawn

Why Stopped

Lack of funding

Study Start Date

August 1, 2017 (Anticipated)

Primary Completion Date

December 31, 2018 (Anticipated)

Study Completion Date

December 31, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

PATH

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Shigella Sonnei Dysenteries

Keywords

Shigella, vaccine, shigellosis, dysentery, whole cell

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1

Arm Type

Experimental

Arm Description

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

Arm Title

Cohort 2

Arm Type

Experimental

Arm Description

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

Arm Title

Cohort 3

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

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

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Shigella flexneri 2a whole cell (Sf2aWC) vaccine

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

2.0 grams of NaHCO3 dissolved in 150 mL of sterile water

Primary Outcome Measure Information:

Title

solicited reactions, AEs, SAEs

Description

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

Time Frame

first vaccination through 6 months post-3rd vaccination

Title

prevention of moderate to severe shigellosis

Description

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

Time Frame

up to 24 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Wilbur Chen, MD, MS

Organizational Affiliation

University of Maryland, Baltimore

Official's Role

Principal Investigator

Facility Information:

Facility Name

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

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21201

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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