Clinical Trial of the S. Flexneri-S. Sonnei Bivalent Conjugate Vaccine

A Randomized, Double-blind, Placebo-controlled Phase III Clinical Trial Evaluating the Protective Efficacy, Immunogenicity, and Safety of the S. Flexneri-S. Sonnei Bivalent Conjugate Vaccine in Infants and Children Aged 6 Months to 5 Years in Bangladesh

The goal of this clinical trial is to evaluate the protective efficacy of S. Flexneri-S. Sonnei bivalent conjugate vaccine against diarrhea caused by Shigella infection in infants and children aged 6 months to 5 years. Researchers will observe the incidence of diarrhea of any severity due to Shigella flexneri and Shigella sonnei infection 30 days after full immunization. The subjects will receive 2 doses of vaccination.

Study Overview

• Status: Active, not recruiting
• Conditions: Dysentery; Dysentery, Shigella
• Intervention / Treatment: Biological: S. Flexneri-S. Sonnei bivalent conjugate vaccine; Biological: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 8000
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka, Bangladesh, 1216
    • Icddr,B

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Infants and children aged 6 months to 5 years.
• Legal guardians voluntarily agree to participate in the study and sign an informed consent form.
• Legal guardians agree to comply with the requirements of the clinical trial protocol and are willing and able to participate in all planned follow-ups.
• The subject's guardian agrees that the subject should not abuse antibiotics. If needed，antibiotics should be used under the guidance of a doctor and avoid taking antibiotics on their own during the clinical trial.
• Based on medical history, physical examination, and the investigator's judgment, the subject is determined to be in good health.

Exclusion Criteria:

• History of confirmed bacterial dysentery in the past 6 months.
• Serious allergy to tetanus toxoid, history of severe allergies, fever above 39.5°C following previous vaccination with a prophylactic biological product.
• Currently suffering from serious intestinal diseases, symptoms of diarrhea, abdominal pain, or bloody purulent stools in the past 15 days.
• Diagnosed pathological jaundice currently.
• Confirmed diagnosis of thrombocytopenia or other coagulation disorders.
• Known or suspected immunological deficiencies (e.g., perianal abscesses indicating potential immune deficiency in infants and young children), long-term treatment (≥14 days) with immunosuppressants within half a year before vaccination (radiotherapy, chemotherapy, systemic corticosteroids ≥2 mg/kg/day, antimetabolites, cytotoxic drugs), or parents confirmed to have HIV infection.
• Receipt of immunoglobulins/blood products (except hepatitis B immunoglobulin) within 3 months before vaccination.
• Severe congenital anomalies (important organ function impairment), severe malnutrition, developmental disorders, severe hereditary diseases.

• Currently suffering from the following diseases:

  1. Severe liver or kidney diseases, cardiovascular diseases, malignant tumors, and other severe chronic diseases.
  2. Diagnosed serious infectious diseases, such as tuberculosis, viral hepatitis, etc.
  3. Severe asthma.
  4. Generalized rashes, dermatophytosis, skin suppuration, or blistering.
  5. Convulsions, epilepsy, encephalopathy, psychiatric disorders or family history of psychiatric disorders.
• Planning to participate or currently participating in other vaccine or drug clinical trials.
• Any condition that the investigators believe may affect the evaluation of the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vaccine group; 4000 subjects aged 6 months to 5 years are enrolled in this group.	Biological: S. Flexneri-S. Sonnei bivalent conjugate vaccine; Subjects receive two doses of the vaccine on the day of randomisation (day 0) and day 30.
Placebo Comparator: Placebo group; 4000 subjects aged 6 months to 5 years are enrolled in this group.	Biological: Placebo; Subjects receive two doses of the placebo on the day of randomisation (day 0) and day 30.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The protective efficacy of S. Flexneri-S. Sonnei bivalent conjugate vaccine	The efficacy will be assessed by comparing the incidence rate of laboratory-confirmed S. flexneri-associated or S. sonnei-associated diarrhea between the vaccinated group and the placebo group. Statistical Analysis: Protective efficacy(%)=(control group incidence (person-year incidence)- vaccine group incidence (person -year incidence))/control group incidence (person-year incidence)x100%	From day 30 post full immunization to the subsequent 24-month period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The protective efficacy against diarrhea cases with positive bacterial culture for Shigella species	Evaluation of the protective efficacy of the vaccine against diarrhea cases with positive bacterial culture for Shigella species.	From he first dose of immunization to 24-month period post full immunization.
Positive PCR testing for Shigella species	Evaluation of diarrhea cases with positive PCR testing for Shigella species	From day 30 post full immunization to the subsequent 24-month period.
IgG antibody seroconversion (fourfold increase) rate on day 30 post full immunization for subgroup 1.	Subjects in immunogenicity subgroup 1, vaccine serotype-specific Shigella flexneri and Shigella sonnei IgG antibody seroconversion (fourfold increase) rate on day 30 post full immunization.	The 30th day after two doses of the vaccine.
IgG antibody concentration on day 30 post full immunization for subgroup 1.	For subjects in immunogenicity subgroup 1, vaccine serotype-specific Shigella flexneri and Shigella sonnei antibody concentration on day 30 post full immunization.	The 30th day after two doses of the vaccine.
IgG antibody seroconversion (fourfold increase) rate on day 30 post full immunization for subgroup 2.	For subjects in immunogenicity subgroup 2, vaccine serotype-specific Shigella flexneri and Shigella sonnei IgG antibody seroconversion (fourfold increase) rate on day 30 post the first dose, day 30 post full immunization, half a year after the first immunization, and one year after the first immunization.	From 30 day to 1 year after the first immunization.
IgG antibody concentration on day 30 post full immunization for subgroup 2.	For subjects in immunogenicity subgroup 2, vaccine serotype-specific Shigella flexneri and Shigella sonnei antibody concentration on day 30 post the first dose, day 30 post full immunization, half a year after the first immunization, and one year after the first immunization.	From 30 day to 1 year after the first immunization.
AEs within 0-30 minutes after vaccination	The occurrence of any adverse events within 30 minutes after each dose of vaccine (number of instances, number of cases, incidence rate, and the relationship to the vaccine administration)	Within 30 minutes after each dose of vaccine
Solicited AEs within 0-7 days after vaccination	The occurrence of solicited adverse events from Day 0 to Day 7 after each vaccine dose (number of instances, number of cases, incidence rate, and the relationship to the vaccine administration)	Within 0-7 days after each vaccine dose.
Unsolicited AEs within 0-30 days after vaccination	The occurrence of unsolicited adverse events from Day 0 to Day 30 after each vaccine dose (number of instances, number of cases, incidence rate, and the relationship to the vaccine administration).	Within 0-30 days after each vaccination
SAE within 0-6 months after primary immunization	The occurrence of Serious Adverse Events (SAEs) from after the first dose to 6 months after complete immunization (number of instances, number of cases, incidence rate, and the relationship to the vaccine administration)	Within 0-6 months after primary immunization.

Collaborators and Investigators

• Sponsor: Beijing Zhifei Lvzhu Biopharmaceutical Co., Ltd
• Investigators: Study Chair: Lin Du, Beijing Zhifei Lvzhu Biopharmaceutical Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2025
• Primary Completion (Estimated): July 2, 2028
• Study Completion (Estimated): July 30, 2028

Study Registration Dates

• First Submitted: February 7, 2025
• First Submitted That Met QC Criteria: February 18, 2025
• First Posted (Actual): February 20, 2025

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: S. Flexneri-S. Sonnei bivalent conjugate vaccine
• Additional Relevant MeSH Terms: Intestinal Diseases; Infections; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Enterobacteriaceae Infections; Dysentery, Bacillary; Dysentery
• Other Study ID Numbers: PR-24079

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No