Just as GlaxoSmithKline's Mosquirix is set to undergo a pilot study among infants in three African countries, PATH and U.S. Army researchers are trying to determine if modifications to the regimen could provide better protection.
For the World Health Organization-required pilot study, the GSK shot is administered in four doses, with the first three administered one month apart and the fourth 15 to 18 months later. But a previous small-size phase 2a conducted at the Walter Reed Army Institute of Research found that delaying the third dose until month 7 and reducing it to only 1/5 of the full dose actually improved protection against malaria infection.
Hoping to verify the results of that study, GSK, PATH and Walter Reed have partnered in a 160-participant trial.
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Apart from those on placebo, the volunteers, all healthy U.S. adults, will be divided into five arms to receive different doses of the vaccine mostly at month 0, 1 and 7, except for one group that will skip month 1 dosage. After that, they will be exposed to malaria-causing parasites through mosquito bites under controlled laboratory conditions so that researchers can evaluate the vaccine’s safety and efficacy. According to the groups, the new study is the largest controlled malaria infection trial to date.
Researchers are also comparing the pediatric formulation of the vaccine currently applied in the pilot program with an adult formulation—which has higher dosage of vaccine and adjuvant—with the hope that the same vaccine formulation could be used in both adults and children.
“This study represents an important step in determining whether the RTS,S vaccine, originally developed to prevent clinical malaria in young African children, can be effectively adapted to prevent infection in all at-risk populations in endemic countries to accelerate parasite elimination,” Ashley Birkett, Ph.D., director of the Malaria Vaccine Intiative at PATH, said in a statement.
In an emailed response sent to FiercePharma, Birkett pointed out that since the delayed fractional dose regimen has not yet been tested in endemic countries, “it is critical for the pilot implementation to proceed with the standard dose and regimen that has been studied through large-scale trials across sub-Saharan Africa ... to avert cases of malaria and save lives while scientists continue work to develop the next-generation of vaccines.”
Walter Reed will carry out the research at its Silver Spring, Maryland, facility, while PATH’s Malaria Vaccine Initiative will offer financial support, as well as input into trial design and oversight. GSK is the trial sponsor and will support the study where needed. The partnership will provide readouts for the study next September, according to PATH.
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The first approved malaria shot, GSK's Mosquirix aroused some skepticism when previous studies suggested that its efficacy could dwindle significantly at the fourth year after vaccination. That concern actually led officials at WHO to require a pilot test program that involves at least 360,000 children starting from next year before full implementation.
In malaria, PATH is not betting all its chips on one single project. The nonprofit partnered in June with Radboud University Medical Center in the Netherlands and Instituto de Medicina Molecular in Portugal to test a vaccine that contains a genetically modified and tamed malaria parasite. Other than that, Maryland-based Sanaria is also trying to determine the optimal formulation of its candidate, PfSPZ, in early stage clinical trials.
Editor's Note: The story has been updated with a response from Ashley Birkett, Ph.D., at PATH.