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

Study Overview
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Brief Summary
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This study is an inpatient trial to determine the safety, immunogenicity and efficacy of the WRSS1 candidate vaccine in healthy Thai adult volunteers.

Detailed Description
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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.

Official Title
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Safety, Immunogenicity, and Efficacy Studies of WRSS1, a Live Attenuated Shigella Sonnei Vaccine Candidate, in Healthy Thai Adults

Conditions
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Dysentery, Shigella, Diarrhea

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 20-40 years old; male or female; General good health as determined by a screening evaluation no greater than 30 days before admission; Normal bowel habits (grade 1-2 stools - no more than one to two stools per day with at least one stool per 2 days; 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); Will be available and willing to continue participation in the second part of the study if he/she has been randomly selected; Pass the Assessment of Understanding of the consent form. Exclusion Criteria: 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; Current use of iron or zinc supplements within the past 7 days; current use of antacids (H2 blockers, omeprazole, OTC agents) or immunosuppressive drug; Unwillingness to follow the study procedures Currently breastfeeding, pregnant (βHCG +) or planning to become pregnant within 3 months after the completion of the study; Allergy to quinolone, sulfa, and penicillin classes of antibiotics; 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); Lifetime previous history of known/suspected Shigella diarrhea (except for volunteers who receive vaccines from Part 1) ; Lifetime history of, or active gallbladder disease; 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); Lifetime history of participation in Shigella study (except for volunteers who receive vaccines from Part 1); Concurrent participation in another experimental vaccine or drug study within the past 30 days(except for volunteers who receive vaccines from part1); Serological positive for Shigella sonnei: anti-Shigella sonnei LPS IgG antibody titer in serum >800 (except for volunteers who receive vaccines from Part 1); Receipt of antimicrobial drugs for any reason or acute illness or fever >=38 oC within 7 days before vaccination or challenge; Individuals with household contacts that are immunocompromised; History of major abdominal surgery or laparotomy for any reason in the past 3 years, or abdominal scar of unclear origin; Presence of significant ova or parasite or Shigella bacteria in the stool; 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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1/Arm 1 of Study: WRSS1 vaccine<br>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<br>* Single, oral dose of WRSS1<br>|
| Placebo Comparator: Part 1/Arm 2 of Study: Placebo vaccine<br>Placebo | Biological: Part 1/Arm 2 of Study: Placebo vaccine<br>* Placebo vaccine<br>|
| Experimental: Part 2/Arm 1 of Study: S. sonnei 53G<br>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<br>* Subject from Part 1/Arm 1 of Study are given 53G S. sonnei<br>|
| Active Comparator: Part 2/Arm 2 of Study: S sonnei 53G<br>10 subjects (naïve controls) plus 4 alternates are give 53G S sonnei | Biological: Part 2/Arm 2 of Study: S. sonnei 53G<br>* 10 naïve controls are given S. sonnei 53G<br>|

What is the study measuring?
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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 |