NCT04242264

Phase 2 Shigella Vaccine and Challenge

A Double-Blind Placebo Controlled Randomized Phase 2 Trial to Evaluate the Safety, Reactogenicity and Immunogenicity of a Live-Attenuated Shigella Sonnei Vaccine, WRSs2 and Determine Its Efficacy in a Challenge Model of S. Sonnei 53G in Healthy Adults

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 69 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 49 Years
• Healthy volunteers: Accepted

Summary

This is a trial to evaluate the safety, reactogenicity, immunogenicity and efficacy of a 10\^6 cfu dose of an oral live-attenuated S. sonnei vaccine candidate, WRSs2, in up to 120 healthy males and non-pregnant females aged 18-49, inclusive. This is a two-phase study, an outpatient WRSs2 vaccination phase and an inpatient S. sonnei 53G challenge phase. After the initiation of the study, two participants had Grade 3 diarrhea and/or vomiting in the days following vaccination. The vaccination dose was reduced to 5X10\^5, enrollment was changed to 2 arms and randomized 2:1 (vaccine: placebo). Participants with morbid obesity were excluded and weight loss medications prohibited. The Primary Objective of this study is to estimate combined vaccine efficacy of 2 doses of WRSs2 (10\^6 cfu or 5X10\^5 cfu) in preventing shigellosis, following challenge with S. sonnei strain 53G.

Detailed description

This is a double-blind, placebo controlled, randomized study to test the safety, reactogenicity, immunogenicity and efficacy of up to a 10\^6 cfu dose of an oral live-attenuated S. sonnei vaccine (WRSs2) to protect against shigellosis after a targeted oral challenge with S. sonnei 53G, a virulent strain of S. sonnei. Up to 120 subjects, healthy males and non-pregnant females aged 18-49, will be enrolled and randomized in this study. Using the 10\^6 CFU dose, subjects were randomized 1:1:1 into one of three vaccination arms to receive 2 doses of study agent 28 days apart. Arm 1 received 2 doses of WRSs2, Arm 2 received placebo followed by WRSs2 and Arm 3 received 2 doses of placebo. Twenty-eight (+2) days after the second dose of study agent, subjects were admitted to the inpatient unit and given an oral challenge of approximately 1500 cfu of 53G. The goal was to have 90 subjects (30 per arm) receive a challenge dose of 53G. The study duration is approximately 24 months with subject participation duration approximately 8 months. After the initiation of the study, two participants had Grade 3 diarrhea and/or vomiting in the days following vaccination. The vaccination dose was reduced to 5X10\^5, enrollment was changed to 2 arms and randomized 2:1 (vaccine: placebo). Participants with morbid obesity were excluded and weight loss medications prohibited. The Primary Objective of this study is to estimate combined vaccine efficacy of 2 doses of WRSs2 (10\^6 cfu or 5X10\^5 cfu) in preventing shigellosis, following challenge with S. sonnei strain 53G. The Secondary Objectives are to:1) Estimate vaccine efficacy of 1 dose of 10\^6 cfu, 2 doses of 10\^6 cfu, and 2 doses of 5x10\^5 cfu of WRSs2 in preventing shigellosis following challenge with S. sonnei strain 53G. 2) Evaluate the safety of WRSs2; 3) Evaluate immune responses following vaccination (immunogenicity) with WRSs2 and after challenge with S. sonnei strain 53G by serum anti-LPS and anti-Invaplex IgG and IgA by ELISA; 4) Determine fecal shedding of S. sonnei after WRSs2 vaccination and 53G challenge by qualitative stool culture.

Conditions

• Immunisation
• Shigella Infection

Interventions

Type	Name	Description
OTHER	Placebo	0.9% Sterile Normal Saline, USP
BIOLOGICAL	Shigella sonnei strain 53G	1.5 x 10\^3 Colony Forming Units (cfu) Shigella sonnei 53G, a virulent strain of wildtype Shigella sonnei
BIOLOGICAL	WRSs2	10\^6 Colony Forming Units (cfu) dose of an oral live-attenuated Shigella sonnei vaccine candidate derived from a virulent S. sonnei strain Moseley (WRSs2)-a live, attenuated vaccine that has been manufactured under cGMP conditions at the WRAIR PBF

Timeline

• Start date: 2022-10-12
• Primary completion: 2024-03-11
• Completion: 2024-07-08
• First posted: 2020-01-27
• Last updated: 2025-04-24
• Results posted: 2025-04-24

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study