PATH shares topline results from a Phase 3 study of an injectable rotavirus vaccine candidate

Trivalent P2-VP8 is an injectable non-replicating rotavirus vaccine (NRRV) candidate that PATH and partners have been evaluating in a Phase 3 safety, immunogenicity, and efficacy study in infants six to eight weeks of age in Ghana, Malawi, and Zambia.

The trial aimed to determine how well trivalent P2-VP8 prevents severe rotavirus gastroenteritis (SRVGE) diarrhea in infants compared to a licensed oral rotavirus vaccine. The primary endpoint for the study was protection against SRVGE.

Results from the Phase 3 study indicate that the vaccine candidate is safe and well tolerated by infants. Unfortunately, trivalent P2-VP8 provided inferior protection against SRVGE compared to the licensed oral rotavirus vaccine used in the study, ROTARIX®.

These results align with the interim analysis held in August 2022, and the decision by the trial’s independent Data Safety and Monitoring Board to end the study early.

“It is always a possibility that an experimental vaccine may not work as expected in a clinical trial. While we’re disappointed with these findings, they do not rule out the potential for developing an effective injectable rotavirus vaccine in the future,” says Dr. John Konz, Global Head of Viral Diseases within PATH’s Center for Vaccine Innovation and Access.

Final results from the study will be published in a peer-reviewed journal, expected to appear in late 2025. PATH is conducting additional immunological analysis of serum samples obtained from participants in this trial as well as a follow-on observational study to assess the incidence of moderate-to-severe rotavirus gastroenteritis in the second year of life among eligible participants followed through to their second birthday. The goal of these efforts is to identify a serological correlate of risk reduction against SRVGE.

“We hope that these further analyses will provide important evidence to better understand what type of an immune response is associated with protection against rotavirus disease to aid future rotavirus vaccine development efforts”, says Dr. Stanley Cryz, Director of PATH’s NRRV project.

Oral rotavirus vaccines have decreased severe diarrhea cases and deaths in the communities that have introduced them into their routine vaccination programs. However, rotavirus remains the most common cause of severe diarrheal disease in children worldwide.

The deadly dehydration that it causes kills about 200,000 young children each year, with the vast majority of these deaths occurring in sub-Saharan Africa and Asia. Increased access to rotavirus vaccines and the development of novel rotavirus vaccines with increased efficacy remain a priority to reduce the burden of diarrheal disease and associated deaths.

This efficacy study enrolled approximately 4,069 healthy infants. Researchers randomly assigned half of the participants to receive the study vaccine (trivalent P2-VP8) plus oral placebo and half to receive ROTARIX, a licensed oral rotavirus vaccine, plus injectable placebo.

The study partners include the Center for Infectious Disease Research in Zambia, Malawi Liverpool Wellcome Program, Noguchi Memorial Institute for Medical Research (Ghana), Dodowa Health Research Centre (Ghana), University of Liverpool, and DiagnoSearch Life Sciences Pvt. Ltd, India. The vaccine candidate was manufactured by SK bioscience Co., Ltd., South Korea.