Safety Study of Live Shigella Vaccine in Bangladeshi Adults and Children
This is a research study about an experimental (investigational) oral Shigella 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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||A Randomized, Double-Blinded, Placebo-controlled, Dose-Escalation, Age-Descending Study to Assess the Safety and Tolerability of Live Attenuated, Oral Shigella WRSS1 Vaccine in Bangladeshi Adults and Children|
- Number of Serious adverse events (SAEs) [ Time Frame: 6 months after the 3rd vaccination ] [ Designated as safety issue: Yes ]
- Number of Adverse events leading to withdrawal [ Time Frame: 6 months after 3rd vaccination ] [ Designated as safety issue: Yes ]
- Number of solicited systemic and gastro-intestinal reactions [ Time Frame: 7 days after the first vaccination; 3 days after the second and third vaccination, as applicable ] [ Designated as safety issue: Yes ]Solicited reactogenicity includes loose stool, diarrhea, nausea, vomiting, generalized myalgia , malaise, abdominal pain, abdominal cramps, headache, bloating, constipation, fever, arthralgia, chills, dysentery, decreased appetite,excess flatulence, and reactive arthritis within one week after each vaccination. To be analyzed by severity and duration.
- any unsolicited AEs and SAEs judged as having a reasonable possibility that the study product caused the event [ Time Frame: 6 months after the 3rd vaccination ] [ Designated as safety issue: Yes ]
- Immunogenicity [ Time Frame: Baseline through 28 days (Cohorts A1/B1) or 84 days (Cohorts A2/A3/B2/B3) post-vaccination ] [ Designated as safety issue: No ]Antibody Lymphocyte Supernatant (ALS) assays and serology will be performed to assess the systemic and mucosal immunogenicity of the vaccine. Microbiology will be utilized to assess the shedding pattern of WRSS1.
|Study Start Date:||August 2013|
|Estimated Study Completion Date:||June 2015|
|Estimated Primary Completion Date:||February 2015 (Final data collection date for primary outcome measure)|
Experimental: Part A (Adults): Cohort A1
One oral dose of ~3x10^4 cfu WRSS1(10 participants) or placebo (3 participants)
Experimental: Part A (Adults): Cohort A2
Three oral doses of ~3x10^5 cfu WRSS1(10 participants) or placebo (3 participants)
Experimental: Part A (Adults): Cohort A3
Three oral doses of ~3x10^6 cfu WRSS1(10 participants) or placebo (3 participants)
Experimental: Part B (Children): Cohort B1
One oral dose of ~3x10^3 cfu WRSS1(12 participants) or placebo (4 participants)
Experimental: Part B (Children): Cohort B2
Three oral doses of ~3x10^4 cfu WRSS1(12 participants) or placebo (4 participants)
Experimental: Part B (Children): Cohort B3
Three oral doses of ~3x10^5 cfu WRSS1(12 participants) or placebo (4 participants)
This is a single site, double-blind, randomized, placebo-controlled, dose-escalation, age-descending study that will start testing the vaccine in healthy adults and move subsequently into school-age children. The study is designed as 2 parts, each part comprising 3 cohorts. The cohort receiving the lowest dose in Parts A and B will receive only one administration of vaccine or placebo; the subsequent two higher dose cohorts in Parts A and B will receive three administrations of vaccine or placebo. In each cohort, the first dose and immediate safety evaluation will be conducted at the icddr,b Inpatient Unit, where the participants will be admitted for observation for 72 hours. Follow-up visits for participants in A1 and B1 will take place on an outpatient basis at the Mirpur Field Office. Second and third vaccinations within A2, A3, B2, and B3 cohorts and all follow-up visits will take place on an outpatient basis at the Mirpur Field Office. Before enrolling participants in subsequent cohorts to receive a higher vaccine dose, or to move to the lower age group, the safety data from the previous cohort(s) (through Study Day 7) will be evaluated and reviewed by the Internal Protocol Safety Team (IPST) comprised of the study physician, the Medical Monitor from GVK, the principal investigator, and the Medical Monitor from PVS. Upon completion of the last adult cohort, the (DSMB -an advisory body to the Ethical Review Committee) will convene to review the cumulative safety data and IPST recommendation, and determine whether to proceed to Part B (children). Adverse events (AE)s will be graded according to standardized criteria. The immunogenicity outcome measures of interest include serum IgG and IgA antibodies by Antibodies in Lymphocyte Supernatant (ALS) assay against S. sonnei2a LPS, shedding profile of WRSS1, and vaccine-specific mucosal IgA responses.
The proposed study builds upon successful preliminary observations with this vaccine in the US, Israel and Thailand. While secondary objectives include studying the immunogenicity of the WRSS1 vaccine, the primary goal of the current trial is to establish a clear safety profile for the WRSS1 vaccine in adults and children 5-9 years old.The primary objective of the study is to evaluate the safety and tolerability of the vaccine; the secondary objective is to evaluate vaccine immunogenicity.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01813071
|Principal Investigator:||Rubhana Raqib, PhD||International Centre for Diarrhoeal Disease Research, Bangladesh|