Phase 2 Shigella Vaccine and Challenge

NCT04242264 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 17-0112
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 2

Brief Summary

This is a trial to evaluate the safety, reactogenicity, immunogenicity and efficacy of a 10\^6 cfu dose of an oral live-attenuated S. sonnei vaccine candidate, WRSs2, in up to 120 healthy males and non-pregnant females aged 18-49, inclusive. This is a two-phase study, an outpatient WRSs2 vaccination phase and an inpatient S. sonnei 53G challenge phase. After the initiation of the study, two participants had Grade 3 diarrhea and/or vomiting in the days following vaccination. The vaccination dose was reduced to 5X10\^5, enrollment was changed to 2 arms and randomized 2:1 (vaccine: placebo). Participants with morbid obesity were excluded and weight loss medications prohibited. The Primary Objective of this study is to estimate combined vaccine efficacy of 2 doses of WRSs2 (10\^6 cfu or 5X10\^5 cfu) in preventing shigellosis, following challenge with S. sonnei strain 53G.

Conditions

Immunisation; Shigella Infection

Keywords

Challenge; Double-blind; Efficacy; Healthy Adults; Immunogenicity; Live-attenuated Shigella sonnei Vaccine; Phase 2 Trial; Placebo-controlled; Protective efficacy; Randomized; Reactogenicity; Safety; Shigella sonnei 53G Challenge; WRSs2

Outcome Measures

Primary Outcomes (1)

• The Proportion of Participants With Shigellosis Following Challenge With Shigella Sonnei 53G Through Day 63 in the Pooled Group of Participants Receiving Two Doses of 10^6 Cfu or 5x10^5 Cfu of WRSs2 Compared to Participants Receiving Two Doses of Placebo.

  Following study vaccination on Days 1 and 29, participants were admitted to an inpatient facility and challenged with Shigella sonnei strain 53G on Day 57. From challenge through Day 63, all stools passed by challenged participants were graded for consistency, all grade 3-5\* stools were visually assessed for gross blood, and all gross blood-containing stools were confirmed via hemoccult test. A blinded endpoint review committee of independent Shigella experts determined whether shigellosis occurred for each participant based on number, weight, consistency, and hemoccult-positive status of stools, along with the presence of additional enteric symptoms. \*Stool consistency was graded according to the following scale: 1 = Normal stool (best outcome); 2 = Soft stool; 3 = Loose stool; 4 = Watery stool; 5 = Rice water (worst outcome).

  Day 57 through Day 63

Secondary Outcomes (20)

• The Proportion of Participants With Shigellosis Following Challenge With S. Sonnei 53G Through Day 63 in Participants Receiving 1 Dose of 10^6 Cfu, 2 Doses of 10^6 Cfu, or 2 Doses of 5x10^5 Cfu of WRSs2 Compared to Those Receiving Two Doses of Placebo.

  Day 57 through Day 65

• Number and Percentage of Participants With Solicited Systemic Adverse Events (AEs) Through 7 Days After Each Study Vaccination.

  Day 1 through Day 8, Day 29 through Day 36

• Number and Percentage of Participants With Vaccine-related Unsolicited AEs Through 28 Days Post Last Vaccination

  Day 1 through Day 57

• Number and Percentage of Participants With SAEs Through Study Day 180 or Until Resolution or Stabilization Even if This Extends Beyond the Study-reporting Period.

  Day 1 through Day 180

• Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G)

  Day 15, Day 29, Day 43, and Day 56

Study Arms (3)

Arm 1

EXPERIMENTAL

Vaccine: 1 ml of saline containing10\^6 or 5X10\^5 cfu of the WRSs2 vaccine in 30 ml of sterile normal saline administered orally on Day 1 and Day 29. Challenge: 1 ml of S. sonnei 53G challenge in 30 ml of sterile saline administered orally on Day 57. N=40

Biological: Shigella sonnei strain 53G; Biological: WRSs2

Arm 2

EXPERIMENTAL

Placebo + Vaccine: 30 ml of sterile normal saline placebo administered orally on Day 1 and 1 ml of saline containing 10\^6 cfu of the WRSs2 vaccine in 30 ml of sterile normal saline administered orally on Day 29. Challenge: 1 ml of S. sonnei 53G challenge in 30ml of sterile saline administered orally on Day 57. N=40

Other: Placebo; Biological: Shigella sonnei strain 53G; Biological: WRSs2

Arm 3

PLACEBO COMPARATOR

Placebo: 31 ml of sterile normal saline placebo administered orally on Day 1 and Day 29. Challenge: 1 ml of S. sonnei 53G challenge in 30 ml of sterile saline administered orally on Day 57. N=40

Other: Placebo; Biological: Shigella sonnei strain 53G

Interventions

Placebo OTHER

0.9% Sterile Normal Saline, USP

Arm 2; Arm 3

Shigella sonnei strain 53G BIOLOGICAL

1.5 x 10\^3 Colony Forming Units (cfu) Shigella sonnei 53G, a virulent strain of wildtype Shigella sonnei

Arm 1; Arm 2; Arm 3

WRSs2 BIOLOGICAL

10\^6 Colony Forming Units (cfu) dose of an oral live-attenuated Shigella sonnei vaccine candidate derived from a virulent S. sonnei strain Moseley (WRSs2)-a live, attenuated vaccine that has been manufactured under cGMP conditions at the WRAIR PBF

Arm 1; Arm 2

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provide informed consent prior to initiation of any study procedures.
• Are able to understand and comply with planned study procedures and be available for all study visits.
• Is 18-49 years of age inclusive and in sufficiently good health\* to be safely enrolled in this study as determined by medical history, medication use, and abbreviated physical exam.

You may not qualify if:

• Oral temperature is less than 100.4 degrees Fahrenheit.
• Pulse is 50 to 100 beats per minute (bpm), inclusive.
• Systolic blood pressure is 90 to 140 mmHg, inclusive.
• Diastolic blood pressure is 55 to 90 mmHg, inclusive.
• Females of childbearing potential\*\* may enroll if subject has practiced adequate contraception\*\*\* = / \> 30 days prior to enrollment and agrees to continue adequate contraception for the entire study.
• \*\*Child-bearing potential is defined as not sterilized via tubal ligation, bilateral oophorectomy, salpingectomy, hysterectomy, or successful Essure(R) placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or \<1 year of the last menses if menopausal.
• \*\*\*Adequate contraception includes; non-male sexual relationships, abstinence from sexual intercourse with a male partner, monogamous relationship with vasectomized partner who has been vasectomized for 180 days or more prior to the subject enrollment, barrier methods such as condoms or diaphragms with spermicide, effective intrauterine devices, NuvaRing(R), and licensed hormonal methods such as implants, injectables, or oral contraceptives ("the pill").
• Females of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to enrollment.
• Drug screen for opiates is negative.
• BMI (Body Mass Index) between 18 and 40kg/m\^2.
• Have any disease or medical condition that, in the opinion of the site principal investigator or appropriate sub-investigator, is a contraindication to study participation\*\*\*\*.
• \*\*\*\* Including acute or chronic disease or medical condition that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this trial. These include:
• History of inflammatory bowel disease (IBD) (including ulcerative colitis, Crohn's disease, indeterminate colitis, or celiac disease).
• Irritable bowel syndrome (IBS) within the past 12 months or any active uncontrolled gastrointestinal disorders or diseases as assessed by the investigator. Including: symptoms or evidence of active gastritis or gastroesophageal reflux disease, gastric surgery or gastric acid hyper-secretory disorders (e.g., Zollinger-Ellison syndrome), gastrointestinal obstruction, ileus, gastric retention, bowel perforation, toxic colitis, persistent infectious gastroenteritis, persistent or chronic diarrhea of unknown etiology, Clostridium difficile infection.
• Known active neoplastic disease (Non-melanoma, treated, skin cancers are permitted), a history of any hematologic malignancy, or have used anticancer chemotherapy/radiation therapy (cytotoxic) within 3 years prior to study enrollment.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (2)

The Hope Clinic of Emory University

Decatur, Georgia, 30030-1705, United States

Location

Cincinnati Children's Hospital Medical Center Vaccine Research Center

Cincinnati, Ohio, 45229-3039, 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: Robert W Frenck, Jr, M.D.
• Organization: Cincinnati Children's Hospital Medical Center

Robert.Frenck@cchmc.org

513-636-4463

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2020
• First Posted: January 27, 2020
• Study Start: October 12, 2022
• Primary Completion: March 11, 2024
• Study Completion: July 8, 2024
• Last Updated: April 24, 2025
• Results First Posted: April 24, 2025

Record last verified: 2023-12-07

Locations

US (2)