GlaxoSmithKline (GSK) and its partner the PATH Malaria Vaccine Initiative have launched a Phase III trial in seven African countries of RTS,S, billed as “the world’s most clinically advanced malaria vaccine candidate”.

More than 5,000 children have already enrolled in the study, which is expected to recruit up to 16,000 children in total in Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique and Tanzania, researchers announced at the 5th Multilateral Initiative on Malaria Pan-African Malaria Conference in Nairobi, Kenya this week.

The Phase III trial will look at the efficacy of RTS,S in two groups of children. One group will be vaccinated as part of their regular schedule of infant immunisations while the other includes children aged five to 17 months. The vaccine is intended mainly for infants, as these and children under the age of five are the population most vulnerable to malaria.

RTS,S is the first vaccine designed primarily for use in Africa, where malaria kills more than 800,000 people a year, the majority of them children under five years old, GSK pointed out.

By conducting the trial in seven different countries across sub-Saharan Africa, researchers can assess the efficacy of RTS,S in a variety of settings, with diverse patterns of malaria transmission, it noted. For example, some trial sites are located in areas where there is a year-round threat of malaria, while others are in areas subject only to seasonal transmission.

If the Phase III programme progresses as expected, RTS,S could be filed for approval as early as 2012, GSK believes. This could be done under Article 58, a special review procedure that allows the European Medicines Agency (EMEA), in close collaboration with the World Health Organization, to issue a scientific opinion on the quality, safety and efficacy of a medicinal product intended for use exclusively outside the European Union, the company explained.

Under current plans, RTS,S would be submitted to regulatory authorities in 2012 based on efficacy data in children aged five to 17 months. Additional safety and immunogenicity data from the infant population would be filed soon afterwards, followed by efficacy data from infants once those were available.

“Depending on the final clinical profile of the vaccine and the timetable of the regulatory review process, the first vaccine introduction could take place over the next three to five years,” GSK said.

In a Phase II trial published last December in the New England Journal of Medicine, RTS,S was shown to reduce malaria episodes by 53% over an eight-month period compared with a rabies vaccine in children aged five to 17 months.

In another Phase II study, infants were administered either the RTS,S/AS02 formulation of the vaccine or a hepatitis B vaccine at 8, 12 and 16 weeks of age, along with a routine inoculation against diphtheria, tetanus, pertussis and influenza B. The researchers found that vaccination with RTS,S/AS02 led to a 65% reduction in first infection from malaria among children who received three doses and were followed up for a six-month period.

GSK and the PATH Malaria Vaccine Initiative signed a public-private partnership agreement in 2001 to pursue the paediatric development of RTS,S in Africa. The vaccine was invented, developed and manufactured at GSK Biologicals’ headquarters in Belgium in the late 1980s and was initially tested in US volunteers.