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.

Study Overview

• Status: Completed
• Conditions: Diarrhea; Dysentery; Shigella
• Intervention / Treatment: Biological: Part 1/Arm 1 of Study: WRSS1 vaccine; Biological: Part 1/Arm 2 of Study: Placebo vaccine; Biological: Part 2/Arm 1 of Study: S. sonnei 53G; Biological: Part 2/Arm 2 of Study: S. sonnei 53G

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10400
    • Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1/Arm 1 of Study: WRSS1 vaccine; WRSS1 is a live attenuated S. sonnei vaccine candidate derived from the Mosely strain of S.sonnei	Biological: Part 1/Arm 1 of Study: WRSS1 vaccine; Single, oral dose of WRSS1
Placebo Comparator: Part 1/Arm 2 of Study: Placebo vaccine; Placebo	Biological: Part 1/Arm 2 of Study: Placebo vaccine; Placebo vaccine
Experimental: Part 2/Arm 1 of Study: S. sonnei 53G; 10 volunteers from Study Arm 1/Part 1 (WRSS1 vaccine) plus 4 alternates from Arm 1/Part 1 are given 53G S. sonnei	Biological: Part 2/Arm 1 of Study: S. sonnei 53G; Subject from Part 1/Arm 1 of Study are given 53G S. sonnei
Active Comparator: Part 2/Arm 2 of Study: S sonnei 53G; 10 subjects (naïve controls) plus 4 alternates are give 53G S sonnei	Biological: Part 2/Arm 2 of Study: S. sonnei 53G; 10 naïve controls are given S. sonnei 53G

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	Overview of AEs highlighting all AEs, withdrawals and deaths related to AEs	Up to 12 months
Number of Participants With Shigella Induced Clinical Disease in Part 2	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. Transmissibility of disease will be evaluated by the presence of fecal shedding in control subjects.	0-5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Count of Subjects With Normal and Abnormal Clinical Laboratory Values During Parts 1 and 2 of Study	Count of subjects in Parts 1 and 2 with normal and abnormal clinical laboratory values after samples taken on days 1, 7, 14, and 28. Abnormal lab values are determined clinically significant by the PI	Days 1, 7, 14, and 28

Collaborators and Investigators

• Sponsor: U.S. Army Medical Research and Development Command
• Collaborators: National Institutes of Health (NIH); Mahidol University
• Investigators: 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

Publications and helpful links

General Publications

• Pitisuttithum P, Islam D, Chamnanchanunt S, Ruamsap N, Khantapura P, Kaewkungwal J, Kittitrakul C, Luvira V, Dhitavat J, Venkatesan MM, Mason CJ, Bodhidatta L. Clinical Trial of an Oral Live Shigella sonnei Vaccine Candidate, WRSS1, in Thai Adults. Clin Vaccine Immunol. 2016 Jul 5;23(7):564-75. doi: 10.1128/CVI.00665-15. Print 2016 Jul.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: December 23, 2009
• First Submitted That Met QC Criteria: March 2, 2010
• First Posted (Estimate): March 4, 2010

Study Record Updates

• Last Update Posted (Actual): November 13, 2018
• Last Update Submitted That Met QC Criteria: October 10, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections; Diarrhea; Dysentery, Bacillary; Dysentery; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Vaccines; Complement Factor H
• Other Study ID Numbers: A-15647; 09-0021 (Other Identifier: NIH/DMID); 1609 (Other Identifier: WRAIR IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Mahidol University and National Institutes of Health will have access to study data.