Safety Study of Live Shigella Vaccine in Bangladeshi Adults and Children

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2013 by PATH
Sponsor:
Collaborator:
International Centre for Diarrhoeal Disease Research, Bangladesh
Information provided by (Responsible Party):
PATH
ClinicalTrials.gov Identifier:
NCT01813071
First received: March 14, 2013
Last updated: August 27, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention
Diarrhea
Biological: WRSS1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by PATH:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 87
Study Start Date: August 2013
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A (Adults): Cohort A1
One oral dose of ~3x10^4 cfu WRSS1(10 participants) or placebo (3 participants)
Biological: WRSS1
Experimental: Part A (Adults): Cohort A2
Three oral doses of ~3x10^5 cfu WRSS1(10 participants) or placebo (3 participants)
Biological: WRSS1
Experimental: Part A (Adults): Cohort A3
Three oral doses of ~3x10^6 cfu WRSS1(10 participants) or placebo (3 participants)
Biological: WRSS1
Experimental: Part B (Children): Cohort B1
One oral dose of ~3x10^3 cfu WRSS1(12 participants) or placebo (4 participants)
Biological: WRSS1
Experimental: Part B (Children): Cohort B2
Three oral doses of ~3x10^4 cfu WRSS1(12 participants) or placebo (4 participants)
Biological: WRSS1
Experimental: Part B (Children): Cohort B3
Three oral doses of ~3x10^5 cfu WRSS1(12 participants) or placebo (4 participants)
Biological: WRSS1

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   5 Years to 39 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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 or2 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

Exclusion Criteria:

  • Presence of a significant medical or psychiatric condition that in the opinion of the Investigator precludes participation in the study
  • Known infection with Hep C or 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 ≥ 37.5C (99.5F) 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
  • Evidence of current excessive alcohol consumption
  • Evidence of current illicit drug use or drug dependence
  • 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
  • History of any of the following conditions within the past 10 years:

    1. Arthritis (two or more episodes of joint pain and swelling)
    2. Gastrointestinal disease (diagnosed by a doctor as having irritable bowel disease, Crohn's disease, ulcerative colitis (biopsy confirmed), celiac disease, stomach or intestinal ulcers
    3. Dyspepsia (indigestion or heartburn requiring medication more than once per week)
    4. History of gallbladder disease
    5. History of chronic heart disease
  • 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
  • Receipt of antimicrobial drugs for any reason or a fever ≥ 38C within 7 days before vaccination
  • History of diarrhea during the 7 days before vaccination.
  • Has any household member(s) who is immunocompromised or under the age of 2 years old.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01813071

Contacts
Contact: Rubhana Raqib, PhD 880-2-8860523-32 Ext:2404 rubhana@icddrb.org

Locations
Bangladesh
Icddr,B Recruiting
Dhaka, Bangladesh
Principal Investigator: Rubhana Raqib, PhD         
Sponsors and Collaborators
PATH
International Centre for Diarrhoeal Disease Research, Bangladesh
Investigators
Principal Investigator: Rubhana Raqib, PhD International Centre for Diarrhoeal Disease Research, Bangladesh
  More Information

No publications provided

Responsible Party: PATH
ClinicalTrials.gov Identifier: NCT01813071     History of Changes
Other Study ID Numbers: VAC 008, PR-12054
Study First Received: March 14, 2013
Last Updated: August 27, 2013
Health Authority: United States: Food and Drug Administration
Bangladesh: icddr,b Ethical Review Committee (ERC)

Keywords provided by PATH:
Enterobacteriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Shigellosis

Additional relevant MeSH terms:
Diarrhea
Signs and Symptoms, Digestive
Signs and Symptoms

ClinicalTrials.gov processed this record on August 27, 2014