Shigella WRSS1 Vaccine Trial in Bangladesh

NCT02934178 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: VAC-049
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Diarrhea

Keywords

shigellosis; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Outcome Measures

Primary Outcomes (2)

• Maximum Severity of Reactogenicity by Vaccination

  All toddlers were monitored for evidence of immediate reactions, assessed for systemic reactogenicity (fever, irritability, decreased appetite, and decreased activity) and gastrointestinal (GI) symptoms (abdominal pain, nausea, vomiting, loose stool, diarrhea, dysentery, bloating, excess flatulence, constipation) during the 72 hours following each vaccine dose.

  72 hours after each vaccination (Day 3, Day 31, Day 59)

• Number of Participants With Adverse Events Occurring Within 28 Days After Any Vaccination by Maximum Severity

  All toddlers were monitored for the occurrence of any adverse event (AE) or serious adverse event (SAE). Toddlers visited the clinic for safety assessments approximately one month after each vaccination. Grades are based on maximum severity per participant.

  Up to 28 days after any vaccination (up to Day 84)

Secondary Outcomes (42)

• Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigens

  Days 0, 7, 35, and 63

• Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen

  Days 0, 7, 35, and 63

• Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen

  Days 0, 7, 35, and 63

• Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS)

  Days 0, 7, 35, and 63

• Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen

  Days 0, 7, 35, and 63

Study Arms (8)

Cohort 1: WRSS1 3 x 10³ CFU

EXPERIMENTAL

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

Biological: Shigella sonnei Strain WRSS1 Vaccine

Cohort 2: WRSS1 3 x 10⁴ CFU

EXPERIMENTAL

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

Biological: Shigella sonnei Strain WRSS1 Vaccine

Cohort 3: WRSS1 3 x 10⁵ CFU

EXPERIMENTAL

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

Biological: Shigella sonnei Strain WRSS1 Vaccine

Cohort 4: WRSS1 3 x 10⁶ CFU

EXPERIMENTAL

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

Biological: Shigella sonnei Strain WRSS1 Vaccine

Cohort 1: Placebo

PLACEBO COMPARATOR

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

Biological: Placebo

Cohort 2: Placebo

PLACEBO COMPARATOR

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

Biological: Placebo

Cohort 3: Placebo

PLACEBO COMPARATOR

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

Biological: Placebo

Cohort 4: Placebo

PLACEBO COMPARATOR

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

Biological: Placebo

Interventions

Shigella sonnei Strain WRSS1 Vaccine BIOLOGICAL

Live attenuated, oral Shigella WRSS1 vaccine

Cohort 1: WRSS1 3 x 10³ CFU; Cohort 2: WRSS1 3 x 10⁴ CFU; Cohort 3: WRSS1 3 x 10⁵ CFU; Cohort 4: WRSS1 3 x 10⁶ CFU

Placebo BIOLOGICAL

Sterile saline solution

Cohort 1: Placebo; Cohort 2: Placebo; Cohort 3: Placebo; Cohort 4: Placebo

Eligibility Criteria

• Age: 12 Months - 24 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Male or female children aged between 12 to 24 month of age at the time of vaccination
• General good health as determined by the screening evaluation no greater than 30 days before admission
• Father, mother or other legally acceptable representative (guardian) properly informed about the study, able to understand it and sign the informed consent form
• Normal bowel habits (\< 3 grade 1 or 2 stools each day; ≥ 1 grade 1 or 2 stools every 2 days)
• Free of obvious health problems as established by medical history and clinical examination before entering into the study.
• Parent or guardian available for the entire period of the study and reachable by study staff throughout the entire follow-up period.
• Signed Informed Consent from the Parent or legal guardian

You may not qualify if:

• Presence of a significant medical that in the opinion of the Investigator precludes participation in the study
• Known infection with human immunodeficiency virus (HIV)
• Presence in the serum of hepatitis A virus (HAV) or hepatitis C virus (HCV) antibody.
• History of congenital abdominal disorders, intussusception, abdominal surgery or any other congenital disorder.
• 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
• Clinically significant abnormalities on physical examination
• Clinically significant abnormalities in screening hematology, serum chemistry as determined by the PI or the PI in consultation with the Study Physician
• History of febrile illness within 48 hours prior to vaccination
• Known or suspected impairment of immunological function based on medical history and physical examination
• Prior receipt of any Shigella vaccine
• Fever at the time of immunization. Fever is defined as a temperature ≥ 37.5C (99.5F) on axillary, oral, or tympanic measurement
• History of known shigellosis, chronic diarrhea/dysentery in the past 2 months
• Current use of iron or zinc supplements within the past 7 days; current use of antacids (H2 blockers, omeprazol, OTC agents) or immunosuppressive drug
• Allergy to quinolone, sulfa, and penicillin classes of antibiotics
• Clinical evidence of active gastrointestinal illness

Sponsors & Collaborators

• PATH: lead
• International Centre for Diarrhoeal Disease Research, Bangladesh: collaborator

Study Sites (1)

Mirpur Field Office

Mirpur, Bangladesh

Location

MeSH Terms

Conditions

Diarrhea; Dysentery, Bacillary; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Bacterial Infections and Mycoses; Infections; Dysentery

Results Point of Contact

• Title: Jorge Flores
• Organization: PATH

jeflores@path.org

(202) 822-0033

Study Officials

• Rubhana Raqib, MD

  International Centre for Diarrhoeal Disease Research, Bangladesh

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2016
• First Posted: October 14, 2016
• Study Start: February 23, 2017
• Primary Completion: January 10, 2018
• Study Completion: January 10, 2018
• Last Updated: March 31, 2020
• Results First Posted: March 31, 2020

Record last verified: 2020-03

Locations

BA (1)