Shigella WRSS1 Vaccine Trial in Bangladesh

NCT ID: NCT02934178

Last Updated: 2020-03-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-23
• Study Completion Date: 2018-01-10

Brief Summary

This is a research study of an experimental (investigational) live attenuated Shigella sonnei vaccine (WRSS1) to find a dose of the vaccine that is safe, tolerable, and develops an immune response. Shigella causes bloody and watery diarrhea, and infants and children living in developing countries experience the greatest consequences of this disease.

Detailed Description

The WRSS1 vaccine in will be given to healthy toddlers (12-24 months old). The first vaccination was given to toddlers in the inpatient unit and the second and third doses will be administered on an outpatient basis. A safety evaluation was performed after the first dose before enrolling subjects in subsequent cohorts to receive a higher vaccine dose.

After the study was initiated, its funder, the Bill and Melinda Gates Foundation (BMGF) made significant changes to the PATH Enteric Vaccine Initiative (EVI) portfolio and decided not to support the three higher-dose cohorts (Cohort 1, 2, and 3) planned as part of this study.

Conditions

Diarrhea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Cohort 1: WRSS1 3 x 10³ CFU

Healthy toddlers receiving 3 oral doses of 3 x 10³ colony-forming units (CFU) of Shigella sonnei Strain WRSS1 approximately 4 weeks apart.

Group Type: EXPERIMENTAL

Shigella sonnei Strain WRSS1 Vaccine

Intervention Type: BIOLOGICAL

Live attenuated, oral Shigella WRSS1 vaccine

Cohort 2: WRSS1 3 x 10⁴ CFU

Healthy toddlers receiving 3 oral doses of 3 x 10⁴ CFU of Shigella sonnei Strain WRSS1 approximately 4 weeks apart.

Group Type: EXPERIMENTAL

Shigella sonnei Strain WRSS1 Vaccine

Intervention Type: BIOLOGICAL

Live attenuated, oral Shigella WRSS1 vaccine

Cohort 3: WRSS1 3 x 10⁵ CFU

Healthy toddlers receiving 3 oral doses of 3 x 10⁵ CFU of Shigella sonnei Strain WRSS1 approximately 4 weeks apart.

Group Type: EXPERIMENTAL

Shigella sonnei Strain WRSS1 Vaccine

Intervention Type: BIOLOGICAL

Live attenuated, oral Shigella WRSS1 vaccine

Cohort 4: WRSS1 3 x 10⁶ CFU

Healthy toddlers receiving 3 oral doses of 3 x 10⁶ CFU of Shigella sonnei Strain WRSS1 approximately 4 weeks apart.

Group Type: EXPERIMENTAL

Shigella sonnei Strain WRSS1 Vaccine

Intervention Type: BIOLOGICAL

Live attenuated, oral Shigella WRSS1 vaccine

Cohort 1: Placebo

Healthy toddlers receiving 3 oral doses of placebo to match 3 x 10³ WRSS1 approximately 4 weeks apart.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Sterile saline solution

Cohort 2: Placebo

Healthy toddlers receiving 3 oral doses of placebo to match 3 x 10⁴ WRSS1 approximately 4 weeks apart.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Sterile saline solution

Cohort 3: Placebo

Healthy toddlers receiving 3 oral doses of placebo to match 3 x 10⁵ WRSS1 approximately 4 weeks apart.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Sterile saline solution

Cohort 4: Placebo

Healthy toddlers receiving 3 oral doses of placebo to match 3 x 10⁶ WRSS1 approximately 4 weeks apart.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Sterile saline solution

Interventions

Shigella sonnei Strain WRSS1 Vaccine

Live attenuated, oral Shigella WRSS1 vaccine

Intervention Type: BIOLOGICAL

Placebo

Sterile saline solution

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Male or female children aged between 12 to 24 month of age at the time of vaccination

2. General good health as determined by the screening evaluation no greater than 30 days before admission

3. Father, mother or other legally acceptable representative (guardian) properly informed about the study, able to understand it and sign the informed consent form

4. Normal bowel habits (< 3 grade 1 or 2 stools each day; ≥ 1 grade 1 or 2 stools every 2 days)

5. Free of obvious health problems as established by medical history and clinical examination before entering into the study.

6. Parent or guardian available for the entire period of the study and reachable by study staff throughout the entire follow-up period.

7. Signed Informed Consent from the Parent or legal guardian

Exclusion Criteria

1. Presence of a significant medical that in the opinion of the Investigator precludes participation in the study

2. Known infection with human immunodeficiency virus (HIV)

3. Presence in the serum of hepatitis A virus (HAV) or hepatitis C virus (HCV) antibody.

4. History of congenital abdominal disorders, intussusception, abdominal surgery or any other congenital disorder.

5. Participation in research involving another investigational product (defined as receipt of investigational product) 30 days before planned date of first vaccination or concurrently participating in another clinical study, at any time during the study period, in which the child has been or will be exposed to an investigational or a non-investigational product

6. Clinically significant abnormalities on physical examination

7. Clinically significant abnormalities in screening hematology, serum chemistry as determined by the PI or the PI in consultation with the Study Physician

8. History of febrile illness within 48 hours prior to vaccination

9. Known or suspected impairment of immunological function based on medical history and physical examination

10. Prior receipt of any Shigella vaccine

11. Fever at the time of immunization. Fever is defined as a temperature ≥ 37.5C (99.5F) on axillary, oral, or tympanic measurement

12. History of known shigellosis, chronic diarrhea/dysentery in the past 2 months

13. Current use of iron or zinc supplements within the past 7 days; current use of antacids (H2 blockers, omeprazol, OTC agents) or immunosuppressive drug

14. Allergy to quinolone, sulfa, and penicillin classes of antibiotics

15. Clinical evidence of active gastrointestinal illness

16. Prior receipt of a blood transfusion or blood products, including immunoglobulins

17. Presence of any significant systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, immunological, dermatological, neurological, cancer or autoimmune disease) as determined by medical history and/or physical examination which would endanger the participant's health or is likely to result in non-conformance to the protocol.

18. History of any neurologic disorders or seizures.

19. Acute disease at the time of enrolment

20. Medically significant malnutrition, defined as moderate malnutrition (wt-for-age z-score between -3.0 and -2.0) and severe malnutrition (wt-for-age z-score <-3.0 or edema)

21. Any conditions which, in the opinion of the investigator, might jeopardize the safety of study participants or interfere with the evaluation of the study objectives

22. Receipt of antimicrobial drugs for any reason or a fever ≥ 38C within 7 days before vaccination

23. History of diarrhea during the 7 days before vaccination.

24. Has any household member(s) who is immunocompromised or under the age of 1 year old.

25. Culture or polymerase chain reaction (PCR) positive for any Shigella strain

• Minimum Eligible Age: 12 Months
• Maximum Eligible Age: 24 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

International Centre for Diarrhoeal Disease Research, Bangladesh

OTHER

Sponsor Role: collaborator

PATH

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rubhana Raqib, MD

Role: PRINCIPAL_INVESTIGATOR

International Centre for Diarrhoeal Disease Research, Bangladesh

Locations

Mirpur Field Office

Mirpur, , Bangladesh

Countries

Bangladesh

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

VAC-049

Identifier Type: -

Identifier Source: org_study_id