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

NCT04078022 | Completed Phase 2 Results FDA Drug

• 1 other identifier: HP-00086278
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Shigella

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Moderate-Severe Shigellosis Illness, With Challenge

  Count of participants with primary endpoint (Moderate-Severe Shigellosis)

  10 days after challenge

Secondary Outcomes (5)

• Number of Participants Meeting Other Case Definitions and Endpoint Definitions

  10 days after challenge

• Number of Participants With Anti-LPS Serum IgG ELISA Response

  Days 29, 57 and 85

• Anti-LPS Serum IgG ELISA Response, by Titer

  Days 1, 29, 57 and 85

• Serum Bactericidal Activity Response, by Response Rates (Proportion of 4-fold Increases From Baseline, Day 1)

  Days 29, 57 and 85

• Serum Bactericidal Activity Response, by Titer

  Days 1, 29, 57 and 85

Study Arms (4)

Cohort 1: Shigella Vaccine or Placebo, Followed by Challenge

EXPERIMENTAL

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; Other: Placebo; Biological: S. flexneri 2a strain 2457T Challenge Agent

Cohort 2: Shigella Vaccine or Placebo, Followed by Challenge

EXPERIMENTAL

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; Other: Placebo; Biological: S. flexneri 2a strain 2457T Challenge Agent

Cohort 3: Shigella Vaccine or Placebo, Followed by Challenge

EXPERIMENTAL

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; Other: Placebo; Biological: S. flexneri 2a strain 2457T Challenge Agent

Cohort 4: Shigella Vaccine Only, No Challenge

EXPERIMENTAL

All volunteers receive the investigational Shigella vaccine (n=12). No Shigella challenge.

Biological: SF2a-TT15 Shigella Vaccine

Interventions

SF2a-TT15 Shigella Vaccine BIOLOGICAL

0.5 mL of the vaccine is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29.

Cohort 1: Shigella Vaccine or Placebo, Followed by Challenge; Cohort 2: Shigella Vaccine or Placebo, Followed by Challenge; Cohort 3: Shigella Vaccine or Placebo, Followed by Challenge; Cohort 4: Shigella Vaccine Only, No Challenge

Placebo OTHER

0.5 mL of normal saline is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29.

Cohort 1: Shigella Vaccine or Placebo, Followed by Challenge; Cohort 2: Shigella Vaccine or Placebo, Followed by Challenge; Cohort 3: Shigella Vaccine or Placebo, Followed by Challenge

S. flexneri 2a strain 2457T Challenge Agent BIOLOGICAL

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.

Cohort 1: Shigella Vaccine or Placebo, Followed by Challenge; Cohort 2: Shigella Vaccine or Placebo, Followed by Challenge; Cohort 3: Shigella Vaccine or Placebo, Followed by Challenge

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

University of Maryland, Baltimore, Center for Vaccine Development and Global Health

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Dysentery, Bacillary

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Wilbur Chen
• Organization: University of Maryland, Baltimore Center for Vaccine Development and Global Health (CVD)

wchen@som.umaryland.edu

410-706-5328

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Frank M. Calia, MD Endowed Professor

Study Record Dates

• First Submitted: July 3, 2019
• First Posted: September 4, 2019
• Study Start: March 2, 2020
• Primary Completion: January 24, 2023
• Study Completion: January 25, 2024
• Last Updated: May 20, 2024
• Results First Posted: May 20, 2024

Record last verified: 2024-05

Locations

US (1)