Shigella CVD 30000: Study of Responses to Vaccination With Shigella Vaccine

May 14, 2024 updated by: Wilbur Chen, MD, MS, University of Maryland, Baltimore

Phase 2b Study of the Safety, Immunogenicity, and Efficacy of a Monovalent Synthetic Carbohydrate-based Conjugate Vaccine (SF2a-TT15) for Protection Against Shigella Flexneri 2a Experimental Infection

The purpose of this study is to determine whether SF2a-TT15 (a monovalent synthetic carbohydrate-based conjugate Shigella vaccine) is safe and effective in the prevention of Shigella infection.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The purpose of this study is to determine whether SF2a-TT15 (a monovalent synthetic carbohydrate-based conjugate Shigella vaccine) is safe and effective in the prevention of Shigella infection. This will be a phase 2b, double-blind, placebo-controlled, single-center study, involving a vaccination phase and a challenge phase. The vaccination phase will consist of study participants that will be 1:1 randomized to receive either the vaccine or placebo. Two doses of blinded study product will be given by intramuscular route of administration, separated by approximately 4 weeks. The challenge phase will consist of an inpatient stay of approximately 12 days during which eligible study participants will ingest an oral inoculum of wild-type S flexneri 2a strain 2457T and then be monitored for illness and treated with antibiotics when the primary endpoint is reached or upon 5 days post-challenge, whichever comes first, or when deemed necessary. Upon satisfying discharge criteria, study participants will complete outpatient clinic follow-up visits through ~7 months after last dose of blinded study product (Day 237). The efficacy study will be enrolled through three cohorts of participants, each cohort consisting of approximately 30 subjects that will be involved in the vaccination phase and 22 subjects that will proceed with the challenge phase. There will be a fourth cohort of participants, consisting of 12 subjects, that will receive the vaccine in an open-label design-this cohort will provide serum samples which are intended to be used for generating serum standards for laboratory assays, as a part of ongoing and future clinical development of Shigella vaccines.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
58

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland, Baltimore, Center for Vaccine Development and Global Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Male or female of age 18-45 years
  • Provides written informed consent
  • Healthy, based on history, exam, and medications
  • Documented acceptable screening laboratory work, including:

WBC, ANC, Hg, Platelets Creatinine, ALT, Bili Serum IgA HIV, HBsAg, HCV Negative for HLA-B27 (this criterion does not apply to cohort 4) Stool culture urinalysis

  • Passing score on Comprehension Assessment Tool (greater than or equal to 70 percent correct answers)
  • Agrees not to participate in another interventional clinical trial during the study period
  • For females of child-bearing potential, must agree to acceptable birth control, 4 weeks before enrollment and through 4 weeks after last vaccination or challenge
  • Available for a 12-day inpatient stay (this criterion does not apply to cohort 4)

Exclusion Criteria:

  • Positive pregnancy test at screening or within 24 hours of study product dosing
  • Poor venous access, as defined by inability to obtain venous blood after 3 venipuncture attempts (this criterion does not apply to cohort 4)
  • Abnormal vital signs, defined as:

Systolic BP greater than 150 mmHg or Diastolic BP greater than 90 mmHg Resting heart rate greater than 100 Oral temperature greater than or equal to 100.4 degrees F

  • Persons with IgA deficiency (serum IgA less than 70 mg per dL
  • Serum S. flexneri 2a LPS igG titer greater than or equal to 2500
  • Received prior vaccines or had prior infection (natural or challenge) with ETEC or Shigella, within 5 years prior to enrollment
  • Symptoms of Traveler's diarrhea associated with travel to countries where Shigella or other enteric infections are endemic (most of the developing world) within 3 years prior to enrollment
  • History of chronic gastrointestinal illness, including sever dyspepsia, lactose intolerance, or other significant gastrointestinal tract disease
  • Use of antimicrobials within 2 weeks of each dose of vaccine or the challenge
  • Regular use (greater than or equal to weekly) of laxatives, anti-diarrheal agents, anti-constipation agents, or antacid therapies
  • History of major gastrointestinal surgery (uncomplicated laparoscopic appendectomy or cholecystectomy greater than 1 year prior is permitted)
  • Abnormal bowel pattern, defined by less than 3 stools per week or greater than 2 stools per day in the past 6 months
  • Use of oral, parenteral or high-dose inhaled steroids within 30 days of each dose of vaccine or the challenge
  • Use of any medication which might affect immune function within 30 days of each dose of vaccine or the challenge
  • Current medical condition which requires daily or weekly prescribed medications for control (as medication use is limited during the inpatient stay), may be an exclusion criterion if in the judgement of the investigator the potential for missed doses could represent a significant risk to the subject's health
  • History of reactive arthritis
  • Diagnosis of schizophrenia or other major psychiatric disease
  • History of seizure disorder within the last 5 years
  • History of alcohol or drug abuse within the last 5 years
  • Presence of immunosuppression
  • Known significant allergy (i.e., anaphylaxis) to ciprofloxacin, trimethoprim-sulfamethoxazole (Bactrim), or a tetanus-containing vaccine
  • 12-lead electrocardiogram with pathologic abnormalities (this criterion does not apply to cohort 4)
  • Occupation in food handling industry, living with, or care of very young children (less than 5 years old), elderly (greater than 65 years), or immunocompromised (this criterion does not apply to cohort 4)
  • Having any known legal obligations, court appearances, professional meetings, vacations, planned events, or other reasons which might interfere with a person's availability for a 12-day inpatient stay. (this criterion does no apply to cohort 4)
  • Any other criteria which, in the investigator's opinion, would compromise the safety of the study, the ability of a subject to participate, or the results of the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort 1: Shigella Vaccine or Placebo, Followed by Challenge
1:1 randomization to investigational Shigella vaccine or placebo (n=30). The majority of participants will then receive the Shigella challenge (n=22).
Biological: SF2a-TT15 Shigella Vaccine
0.5 mL of the vaccine is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29.
Other: Placebo
0.5 mL of normal saline is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29.
Biological: S. flexneri 2a strain 2457T Challenge Agent
Each participant will drink 120 mL of sodium bicarbonate buffer solution. Approximately 1 to 2 minutes later, the participant will ingest approximately 1500 cfu of S. flexneri 2a strain 2457T suspended in 30 mL of the bicarbonate buffer solution.
Experimental: Cohort 2: Shigella Vaccine or Placebo, Followed by Challenge
1:1 randomization to investigational Shigella vaccine or placebo (n=30). The majority of participants will then receive the Shigella challenge (n=22).
Biological: SF2a-TT15 Shigella Vaccine
0.5 mL of the vaccine is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29.
Other: Placebo
0.5 mL of normal saline is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29.
Biological: S. flexneri 2a strain 2457T Challenge Agent
Each participant will drink 120 mL of sodium bicarbonate buffer solution. Approximately 1 to 2 minutes later, the participant will ingest approximately 1500 cfu of S. flexneri 2a strain 2457T suspended in 30 mL of the bicarbonate buffer solution.
Experimental: Cohort 3: Shigella Vaccine or Placebo, Followed by Challenge
1:1 randomization to investigational Shigella vaccine or placebo (n=30). The majority of participants will then receive the Shigella challenge (n=22).
Biological: SF2a-TT15 Shigella Vaccine
0.5 mL of the vaccine is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29.
Other: Placebo
0.5 mL of normal saline is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29.
Biological: S. flexneri 2a strain 2457T Challenge Agent
Each participant will drink 120 mL of sodium bicarbonate buffer solution. Approximately 1 to 2 minutes later, the participant will ingest approximately 1500 cfu of S. flexneri 2a strain 2457T suspended in 30 mL of the bicarbonate buffer solution.
Experimental: Cohort 4: Shigella Vaccine Only, No Challenge
All volunteers receive the investigational Shigella vaccine (n=12). No Shigella challenge.
Biological: SF2a-TT15 Shigella Vaccine
0.5 mL of the vaccine is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Moderate-Severe Shigellosis Illness, With Challenge
Time Frame: 10 days after challenge
Count of participants with primary endpoint (Moderate-Severe Shigellosis)
10 days after challenge

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants Meeting Other Case Definitions and Endpoint Definitions
Time Frame: 10 days after challenge
10 days after challenge
Number of Participants With Anti-LPS Serum IgG ELISA Response
Time Frame: Days 29, 57 and 85
Anti-LPS serum IgG ELISA response, by response rates (proportion of 4-fold increases from baseline, Day 1)
Days 29, 57 and 85
Anti-LPS Serum IgG ELISA Response, by Titer
Time Frame: Days 1, 29, 57 and 85
Days 1, 29, 57 and 85
Serum Bactericidal Activity Response, by Response Rates (Proportion of 4-fold Increases From Baseline, Day 1)
Time Frame: Days 29, 57 and 85
Days 29, 57 and 85
Serum Bactericidal Activity Response, by Titer
Time Frame: Days 1, 29, 57 and 85
Days 1, 29, 57 and 85

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Maryland, Baltimore

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 2, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 24, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 25, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 3, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 3, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 4, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 20, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 14, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HP-00086278

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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