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

NCT01080716 | Completed Phase 1 Results DMC

• 3 other identifiers: A-1564709-00211609
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Dysentery; Shigella; Diarrhea

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Count of Subjects With Normal and Abnormal Clinical Laboratory Values During Parts 1 and 2 of Study

  Days 1, 7, 14, and 28

Study Arms (4)

Part 1/Arm 1 of Study: WRSS1 vaccine

EXPERIMENTAL

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

Part 1/Arm 2 of Study: Placebo vaccine

PLACEBO COMPARATOR

Placebo

Biological: Part 1/Arm 2 of Study: Placebo vaccine

Part 2/Arm 1 of Study: S. sonnei 53G

EXPERIMENTAL

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

Part 2/Arm 2 of Study: S sonnei 53G

ACTIVE COMPARATOR

10 subjects (naïve controls) plus 4 alternates are give 53G S sonnei

Biological: Part 2/Arm 2 of Study: S. sonnei 53G

Interventions

Part 1/Arm 1 of Study: WRSS1 vaccine BIOLOGICAL

Single, oral dose of WRSS1

Part 1/Arm 1 of Study: WRSS1 vaccine

Part 1/Arm 2 of Study: Placebo vaccine BIOLOGICAL

Placebo vaccine

Part 1/Arm 2 of Study: Placebo vaccine

Part 2/Arm 1 of Study: S. sonnei 53G BIOLOGICAL

Subject from Part 1/Arm 1 of Study are given 53G S. sonnei

Part 2/Arm 1 of Study: S. sonnei 53G

Part 2/Arm 2 of Study: S. sonnei 53G BIOLOGICAL

10 naïve controls are given S. sonnei 53G

Part 2/Arm 2 of Study: S sonnei 53G

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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);

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead
• Mahidol University: collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University

Bangkok, 10400, Thailand

Location

Related Publications (1)

• 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.

  PMID: 27146000 DERIVED

MeSH Terms

Conditions

Dysentery; Dysentery, Bacillary; Diarrhea

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Punnee Pitisutithum, MBBS, DTM&H, FRCPT
• Organization: Vaccine Trial Treatment Center, Mahidol University

tmppt@mahidol.ac.th

66-2-643-5599

Study Officials

• Ladaporn Bodhidatta, MD

  Department of Enteric Diseases, Armed Forces Research Institute of Medical Sciences

  STUDY DIRECTOR

• Punnee Pitisuttithum, MBBS

  Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University

  PRINCIPAL INVESTIGATOR

• Carl Mason, MD

  Department of Enteric Diseases, Armed Forces Research Institute of Medical Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2009
• First Posted: March 4, 2010
• Study Start: May 1, 2010
• Primary Completion: September 1, 2010
• Study Completion: December 1, 2011
• Last Updated: November 13, 2018
• Results First Posted: November 13, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share

Locations

TH (1)