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Pivotal Shigella Vaccine Efficacy Trials-Study Design Considerations from a Shigella Vaccine Trial Design Working
Patricia B Pavlinac1, Elizabeth T Rogawski McQuade2, James A Platts-Mills3
1Departments of Global Health and Epidemiology, University of Washington, Seattle, WA 98105, USA.
Insights
New Shigella vaccine trials are nearing phase 3. Key design choices will ensure regulatory approval for preventing moderate to severe shigellosis in children, guiding licensure and implementation.
Area of Science:
- Vaccinology
- Infectious Diseases
- Pediatrics
Background:
- Shigella infections cause significant childhood morbidity and mortality, particularly in low- and middle-income countries.
- Shigella vaccine candidates are advancing towards Phase 3 clinical trials, necessitating careful trial design for regulatory success.
Purpose of the Study:
- To identify critical study design elements for pivotal Shigella vaccine trials.
- To meet regulatory requirements for preventing moderate or severe shigellosis caused by vaccine-specific strains.
Main Methods:
- Convened an ad hoc working group to deliberate on trial design aspects.
- Proposed a primary endpoint focusing on vaccine efficacy against the first episode of moderate or severe diarrhea.
- Defined moderate or severe shigellosis using a modified Vesikari score, dysentery, and molecular detection of vaccine-preventable strains.
Main Results:
- The proposed primary endpoint is vaccine efficacy against moderate or severe shigellosis.
- A clear definition for moderate or severe shigellosis is crucial for trial consistency.
- Considerations for trial design will evolve with emerging data and regulatory consultations.
Conclusions:
- Strategic trial design is essential for the successful licensure and implementation of Shigella vaccines.
- The proposed endpoint and case definition aim to provide robust evidence of vaccine effectiveness.
- Ongoing dialogue with regulators and policymakers is vital for advancing Shigella vaccine development.
Abstract:
Vaccine candidates for Shigella are approaching phase 3 clinical trials in the target population of young children living in low- and middle-income countries. Key study design decisions will need to be made to maximize the success of such trials and minimize the time to licensure and implementation. We convened an ad hoc working group to identify the key aspects of trial design that would meet the regulatory requirements to achieve the desired indication of prevention of moderate or severe shigellosis due to strains included in the vaccine. The proposed primary endpoint of pivotal Shigella vaccine trials is the efficacy of the vaccine against the first episode of acute moderate or severe diarrhea caused by the Shigella strains contained within the vaccine. Moderate or severe shigellosis could be defined by a modified Vesikari score with dysentery and molecular detection of vaccine-preventable Shigella strains. This report summarizes the rationale and current data behind these considerations, which will evolve as new data become available and after further review and consultation by global regulators and policymakers.
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