Safety Study of Live Attenuated Oral Shigella (WRSS1) Vaccine in Bangladeshi Adults and Children

NCT01813071 | Completed Results DMC

• 2 other identifiers: VAC 008PR-12054
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 1

Brief Summary

This is a research study about an experimental (investigational) oral Shigella sonnei - Walter Reed S. sonnei (WRSS1). WRSS1 is a live vaccine that is being made to prevent disease from Shigella, which causes bloody, watery diarrhea. Infants and children living in developing countries experience the greatest consequences of this disease. The purpose of this study is to find a dose of the vaccine that is safe, tolerable, and develops an immune response. About 39 healthy adults, ages 18-39, and 48 healthy children, ages 5-9, will participate in this study. Once the vaccine is proven safe and tolerable in adults, then it will be tested in the children. This study will require volunteers to stay in the research facility for several nights for the first dose; they will not be required to stay overnight for the second and third doses. Participants will be assigned to receive 1 of 3 vaccine dose levels by mouth. Study procedures include: stool samples, blood samples and documenting side effects. Participants will be involved in study related procedures for about 8 months.

Conditions

Diarrhea

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Number and Percentage of Participants With Serious Adverse Events (SAEs)

  Based on maximum severity per participant over all serious adverse events (SAEs) within 6 months of any vaccination. A Serious Adverse Event, including serious suspected adverse reaction or serious adverse reaction as determined by the Investigator or the sponsor, was any event that results in any of the following outcomes: Inpatient hospitalization or prolongation of existing hospitalization , life-threatening AE that in the opinion of the investigator or sponsor put the participant at immediate risk of death, persistent or significant incapacity or substantial disruption, congenital abnormality or birth defect, a medically important event that may have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed or death.

  Day -1(admission day) through 6 months (Day 224 +/- 14 days) after the third vaccination for Cohorts A2,A3, B2, B3, B4, and after the first vaccination (Day 168 +/- 14 days) for Cohorts A1 and B1.

• Number and Percentage of Participants With Any Non-serious Unsolicited Adverse Events

  Based on subject count over all non-serious adverse events. An Adverse event was defined as any untoward medical occurrence in humans, whether or not considered drug related, that occurred during the conduct of a clinical trial. Any change in clinical status, ECGs, routine labs, x-rays, physical examinations, etc., that was considered clinically significant by the study investigator, was considered an AE. This definition also included an exacerbation or worsening of pre-existing conditions or events, inter-current illnesses, injuries, or vaccine or drug interaction, or worsening of abnormal clinical laboratory values. All AEs were assessed by the clinician using a protocol defined grading system.

  Day -1(admission day) through 6 months (Day 224 +/- 14 days) after the third vaccination for Cohorts A2,A3, B2, B3, B4, and after the first vaccination (Day 168 +/- 14 days) for Cohorts A1 and B1.

• Number and Percentage of Participants With Solicited Systemic and Intestinal Reactions

  Maximum severity per participant of any systemic or any gastrointestinal reactogenicity recorded within 7 days of any vaccination is reported. Solicited Systemic reactogenicity events assessed included fever, headache, malaise, generalized myalgia, arthralgia, chills, reactive arthritis and decreased appetite. Intestinal solicited reactogenicity events assessed included abdominal cramps, abdominal pain, nausea, vomiting, loose stool, diarrhea, dysentery, bloating, excess flatulence and constipation. Diarrhea and dysentery were assessed both during inpatient (first three day period post-vaccination) and outpatient ( post-vaccination days 4-7) periods post-vaccination 1. Vaccinations 2 and 3 did not have an inpatient admission period for any participants. Diarrhea severity was determined on the basis of stool number, grading and stool weight during the inpatient period and by stool number and grading only during the outpatient period.

  Day 0 through Day 7 after any vaccination

• Number and Percentage of Participants With Any Unsolicited AEs and SAEs Judged as Having a Reasonable Possibility That the Study Product Caused the Event

  Adverse event (AE) was defined as any untoward medical occurrence in humans, whether or not considered drug related, that occurs during the conduct of a clinical trial. A Serious Adverse Event (SAE) , including serious suspected adverse reaction or serious adverse reaction as determined by the Investigator or the sponsor, was any event that results in any of the following outcomes: Inpatient hospitalization or prolongation of existing hospitalization , life-threatening AE that in the opinion of the investigator or sponsor put the participant at immediate risk of death, persistent or significant incapacity or substantial disruption, congenital abnormality or birth defect, a medically important event that may have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed or death. Causality of the AE/SAE to the study drug was assessed by the Investigator as reasonable possibility that the study product caused the reported event.

  SAEs at any time and AEs after any vaccination until Day 168 (Cohort A1, B1) and Day 224 (all other Cohorts).

Secondary Outcomes (55)

• Number and Percentage of Participants With a 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Titers in Lymphocyte Supernatant (ALS)

  Day 7

• Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in ALS

  Day 35

• Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in ALS

  Day 63

• Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in ALS

  At any time (Day 7 to Day 63)

• Number and Percentage of Participants With a 4-fold Rise From Baseline in Immunoglobulin G (IgG ) IgG Antibodies in ALS

  Day 7

Study Arms (7)

Part A (Adults): Cohort A1

EXPERIMENTAL

One oral dose of \~3x10\^4 cfu WRSS1(10 participants) or placebo (3 participants)

Biological: WRSS1

Part A (Adults): Cohort A2

EXPERIMENTAL

Three oral doses of \~3x10\^5 cfu WRSS1(10 participants) or placebo (3 participants)

Biological: WRSS1

Part A (Adults): Cohort A3

EXPERIMENTAL

Three oral doses of \~3x10\^6 cfu WRSS1(10 participants) or placebo (3 participants)

Biological: WRSS1

Part B (Children): Cohort B1

EXPERIMENTAL

One oral dose of \~3x10\^3 cfu WRSS1(12 participants) or placebo (4 participants)

Biological: WRSS1

Part B (Children): Cohort B2

EXPERIMENTAL

Three oral doses of \~3x10\^4 cfu WRSS1(12 participants) or placebo (4 participants)

Biological: WRSS1

Part B (Children): Cohort B3

EXPERIMENTAL

Three oral doses of \~3x10\^5 cfu WRSS1(12 participants) or placebo (4 participants)

Biological: WRSS1

Part B (Children): Cohort B4

EXPERIMENTAL

Three oral doses of \~3x10\^6 cfu WRSS1(12 participants) or placebo (4 participants)

Biological: WRSS1

Interventions

WRSS1 BIOLOGICAL

Part A (Adults): Cohort A1; Part A (Adults): Cohort A2; Part A (Adults): Cohort A3; Part B (Children): Cohort B1; Part B (Children): Cohort B2; Part B (Children): Cohort B3; Part B (Children): Cohort B4

Eligibility Criteria

• Age: 5 Years - 39 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Healthy male or female adults from 18-39 years old, inclusive
• General good health as determined by the screening evaluation no greater than 30 days before admission
• 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.
• Available for the entire period of the study and reachable by study staff throughout the entire follow-up period
• Females of childbearing potential who are willing to take a serum pregnancy test at screening and urine pregnancy tests before each vaccination. Pregnancy tests must be negative before each vaccination. Females of childbearing potential must agree to use an efficacious hormonal or barrier method of birth control during the study. Abstinence is also acceptable.
• Signed Informed Consent

You may not qualify if:

• Presence of a significant medical or psychiatric condition that in the opinion of the Investigator precludes participation in the study
• Known infection with Hepatitis C or Human Immunodeficiency Virus (HIV)
• 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 participant 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, or urinalysis 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 ≥ 37.5 degrees Celsius (99.5 degrees Fahrenheit) on axillary, oral, or tympanic measurement
• Clinical evidence of active gastrointestinal illness
• Prior receipt of a blood transfusion or blood products, including immunoglobulins
• 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.
• History of any neurologic disorders or seizures.
• Acute disease at the time of enrolment

Sponsors & Collaborators

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

Study Sites (1)

Icddr,B

Dhaka, Bangladesh

Location

Related Publications (1)

• Sarker P, Mily A, Ara A, Haque F, Maier N, Wierzba TF, Walker RI, Venkatesan MM, Raqib R. Functional Antibodies and Innate Immune Responses to WRSS1, a Live Oral Shigella sonnei Vaccine Candidate, in Bangladeshi Adults and Children. J Infect Dis. 2021 Dec 20;224(12 Suppl 2):S829-S839. doi: 10.1093/infdis/jiab395.

  PMID: 34374425 DERIVED

MeSH Terms

Conditions

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

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: Jennifer O'Reilly
• Organization: PATH

joreilly@path.org

202-540-4510

Study Officials

• Rubhana Raqib, PhD

  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: not applicable
• 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: March 14, 2013
• First Posted: March 18, 2013
• Study Start: August 1, 2013
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: February 8, 2019
• Results First Posted: February 8, 2019

Record last verified: 2019-02

Locations

BA (1)