Safety and Efficacy Study of WRSS1, a Shigella Sonnei Vaccine Candidate

This study has been completed.
Sponsor:
Collaborators:
Mahidol University
Information provided by (Responsible Party):
U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier:
NCT01080716
First received: December 23, 2009
Last updated: September 4, 2012
Last verified: September 2012

December 23, 2009
September 4, 2012
April 2010
December 2010   (final data collection date for primary outcome measure)
  • Safety/Clinical tolerance [ Time Frame: Study Parts 1,2-Daily, days 0-13; day 14, 28, and 60 ] [ Designated as safety issue: Yes ]
    Frequency of any mild, moderate, and severe signs and symptoms associated with the vaccine such as nausea, vomiting, diarrhea, dysentery, fever, abdominal cramping, and dehydration, as well as any unexpected events. Frequency of significant clinical laboratory abnormalities
  • Immunogenicity [ Time Frame: Study Part 1-Study days 0,3,5,7,9,14, and 28 ] [ Designated as safety issue: No ]
    Frequency and increase in antigen-specific serum IgG, IgA, and IgM antibody titers to S. sonnei LPS and invaplex-protein antigens. Frequency and increase in antigen-specific fecal IgA antibody titer to S. sonnei LPS and invaplex-protein antigens (study day -1 or 0, study days 3,5,7,14, and 28). Frequency and increase in antigen-specific IgG, IgA, and IgM antibody secreting cells (ASC) and antibody titers in lymphocyte supernatant (ALS) to S. sonnei LPS and invaplex-protein antigens (study days 0,7, and 9).
  • Efficacy [ Time Frame: Study Part 2-Daily, Study days 0-5 ] [ Designated as safety issue: No ]
    Study Part 2-Frequency of Shigella induced clinical disease defined as one or more of diarrhea, dysentery or fever in vaccinees and controls following challenge with S. sonnei 53G
Same as current
Complete list of historical versions of study NCT01080716 on ClinicalTrials.gov Archive Site
  • Fecal shedding of vaccine [ Time Frame: Study Part 1-Daily, Study days 0-13 ] [ Designated as safety issue: No ]
    Frequency and duration of detectable fecal presence of WRSS1 by PCR and culture
  • Transmissibility of WRSS1 to placebo recipients [ Time Frame: Sutdy Part 1-Daily, Study days 0-13 ] [ Designated as safety issue: Yes ]
    Frequency of detectable fecal presence of WRSS1 in placebo recipients by PCR and culture
  • Change in clinical laboratory values [ Time Frame: Study Part 1-Study days 0,7,14, and 28 ] [ Designated as safety issue: Yes ]
    Frequency of clinical laboratory changes, both normal and abnormal.
  • Fecal shedding of vaccine [ Time Frame: Daily ] [ Designated as safety issue: No ]
    Frequency and duration of detectable fecal presence of WRSS1 by PCR and culture
  • Transmissibility of WRSS1 to placebo recipients [ Time Frame: Daily ] [ Designated as safety issue: Yes ]
    Frequency of detectable fecal presence of WRSS1 in placebo recipients by PCR and culture
  • Change in clinical laboratory values [ Time Frame: Daily ] [ Designated as safety issue: Yes ]
    Frequency of clinical laboratory changes, both normal and abnormal.
Not Provided
Not Provided
 
Safety and Efficacy Study of WRSS1, a Shigella Sonnei Vaccine Candidate
Safety, Immunogenicity, and Efficacy Studies of WRSS1, a Live Attenuated Shigella Sonnei Vaccine Candidate, in Healthy Thai Adults

This study is an inpatient trial to determine the safety, immunogenicity and efficacy of the WRSS1 candidate vaccine in healthy Thai adult volunteers. This study is designed as 2 parts.

  • Part 1 is a blinded, placebo-controlled inpatient trial in a total of 20 volunteers (14 vaccinees and 6 controls) to determine the safety and immunogenicity. Volunteers will be vaccinated with a single oral dose of 104 colony forming unit (cfu) of WRSS1 or placebo given with bicarbonate buffer.
  • Part 2 will be started approximately 60 days after WRSS1 vaccination. This part is an inpatient phase II efficacy trial involving a challenge with the S.sonnei 53G of 10 vaccinees from the first part and 10 naïve controls.
Not Provided
Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
  • Dysentery
  • Shigella
  • Diarrhea
  • Biological: WRSS1 vaccine
    Single, oral dose of WRSS1
  • Biological: Placebo vaccine
    Placebo vaccine
  • Experimental: WRSS1 vaccine
    WRSS1 is a live attenuated S. sonnei vaccine candidate derived from the Mosely strain of S.sonnei
    Intervention: Biological: WRSS1 vaccine
  • Placebo Comparator: Placebo vaccine
    Placebo
    Intervention: Biological: Placebo vaccine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
20
December 2010
December 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. 20-40 years old; male or female;
  2. General good health as determined by a screening evaluation no greater than 30 days before admission;
  3. Normal bowel habits (grade 1-2 stools - no more than one to two stools per day with at least one stool per 2 days;
  4. Sexually active females willing to use birth control (birth control pills, injection hormonal contraceptive, implant hormonal contraceptive, hormonal patch, IUD, sterilization for effective contraceptive methods, spermicidal products and barrier methods are considered acceptable)during the entire study (starting from study day -30) and for 3 months after completion of the study (approximately a total of 6 months) or sexually inactive females (no sexual contact). Volunteers who take birth control pills will be required to use additional contraceptive methods for the remaining days of the cycle after discharge from the VTC (alteration of gastrointestinal functions from the oral vaccine or challenge strain may lead to unpredictable efficacy of pills);
  5. Will be available and willing to continue participation in the second part of the study if he/she has been randomly selected;
  6. Pass the Assessment of Understanding of the consent form.

Exclusion Criteria:

  1. An acute or chronic medical condition or a clinically significant abnormality on physical exam that, in the opinion of the investigator, would render vaccination or challenge as unsafe;
  2. Current use of iron or zinc supplements within the past 7 days; current use of antacids (H2 blockers, omeprazole, OTC agents) or immunosuppressive drug;
  3. Unwillingness to follow the study procedures
  4. Currently breastfeeding, pregnant (βHCG +) or planning to become pregnant within 3 months after the completion of the study;
  5. Allergy to quinolone, sulfa, and penicillin classes of antibiotics;
  6. History of any of the following conditions within the past 10 years:

    • Arthritis (two or more episodes of joint pain and swelling),
    • Gastrointestinal disease (diagnosed by a doctor as having irritable bowel disease, Crohn's disease, ulcerative colitis (biopsy confirmed), celiac disease, stomach or intestinal ulcers), or
    • Dyspepsia (digestion or heartburn requiring medication more than once per week);
  7. Lifetime previous history of known/suspected Shigella diarrhea (except for volunteers who receive vaccines from Part 1) ;
  8. Lifetime history of, or active gallbladder disease;
  9. HLA B27 Ag (+); Anti-HIV (+); HBsAg(+); Anti HCV IgG Ab(+); abnormal screening tests judged to be clinically significant as judged by PI or sub-PI (Values are out of the acceptable abnormal range from the table in the protocol) other than mild anemia in females (Hct = 0.33-0.36);
  10. Lifetime history of participation in Shigella study (except for volunteers who receive vaccines from Part 1);
  11. Concurrent participation in another experimental vaccine or drug study within the past 30 days(except for volunteers who receive vaccines from part1);
  12. Serological positive for Shigella sonnei: anti-Shigella sonnei LPS IgG antibody titer in serum >800 (except for volunteers who receive vaccines from Part 1);
  13. Receipt of antimicrobial drugs for any reason or acute illness or fever >=38 oC within 7 days before vaccination or challenge;
  14. Individuals with household contacts that are immunocompromised;
  15. History of major abdominal surgery or laparotomy for any reason in the past 3 years, or abdominal scar of unclear origin;
  16. Presence of significant ova or parasite or Shigella bacteria in the stool;
  17. Receipt of any of the following (does not include the WRSS1 vaccine):

    • a licensed live, attenuated vaccine within the 30 days of challenge
    • a licensed subunit or killed vaccine within the 14 days of the challenge
    • a blood product, including immunoglobulin, in the 90 days before the challenge
Both
20 Years to 40 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Thailand
 
NCT01080716
A-15647, 09-0021, 1609
Yes
U.S. Army Medical Research and Materiel Command
U.S. Army Medical Research and Materiel Command
  • Mahidol University
  • National Institutes of Health (NIH)
Study Director: Ladaporn Bodhidatta, MD Department of Enteric Diseases, Armed Forces Research Institute of Medical Sciences
Principal Investigator: Punnee Pitisuttithum, MBBS Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University
Study Director: Carl Mason, MD Department of Enteric Diseases, Armed Forces Research Institute of Medical Sciences
U.S. Army Medical Research and Materiel Command
September 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP