PATH announces early closure of pivotal Phase 3 study of an injectable rotavirus vaccine candidate

Trivalent P2-VP8 is an injectable non-replicating rotavirus vaccine candidate that PATH and partners have been evaluating in a Phase 3 safety, immunogenicity, and efficacy study in infants 6 to 8 weeks of age in Ghana, Malawi, and Zambia. The trial aimed to determine how well trivalent P2-VP8 prevents rotavirus diarrhea in infants compared to a licensed oral rotavirus vaccine.

The trial’s independent Data Safety Monitoring Board (DSMB) conducted an interim analysis of the data collected and based upon a predetermined number of severe rotavirus gastroenteritis cases identified among enrolled and vaccinated infants, they determined that the study should not continue as planned. At this time there is insufficient evidence that trivalent P2-VP8 provides superior protection against severe rotavirus diarrhea compared to currently licensed oral vaccine options.

This efficacy study, which began in March 2021, enrolled approximately 3,730 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.

“Oral rotavirus vaccines are currently available and work to prevent rotavirus in all populations, however they don’t perform as well in countries with the highest burden. Our goal with this vaccine candidate was to increase protection for these populations that are at highest risk. Unfortunately, the data we have so far suggests that this candidate is not better at preventing rotavirus than existing vaccines,” says Dr. Fred Cassels, PATH’s Global Head of Enteric and Diarrheal Diseases.

Following the recommendation from the DSMB, PATH will continue to follow participants for an additional 6 months or until the child is 12 months old, whichever is longer. Participating infants who received the study vaccine will be offered a licensed oral rotavirus vaccine if they are age-eligible based upon guidelines in each study country. Work is also underway to identify possible causes for why the vaccine candidate did not perform as expected. After the follow-up period is complete, the study will close.

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, and more than 90 percent of these deaths occur in low- and middle-income countries. 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.

PATH has been developing this vaccine candidate since 2011. Data from this study and previous Phase 1 and 2 studies show that the candidate is safe. This was the most advanced injectable rotavirus vaccine candidate in the development pipeline and the first to reach Phase 3 trials. Researchers hoped that as an injectable vaccine, it would provide better protection compared to oral options by bypassing the gut, which scientists think might be responsible for the lower efficacy of live oral rotavirus vaccines observed in high burden settings.

The DSMB for this study was made up of five individuals with pediatric, biostatistics, and vaccine expertise that collectively have experience in the management of pediatric patients and in the conduct and monitoring of randomized clinical trials. There is at least one member from each of the three participating countries.

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