Multicentre Phase IIB Trial Design of the GMZ2 Malaria Vaccine

Background: GMZ2 is a blood stage candidate malaria vaccine which comprises a recombinant fusion protein based on conserved fragments of two P. falciparum asexual blood-stage antigens, the glutamate-rich protein (GLURP) and merozoite surface protein 3 (MSP3), adjuvanted with Alhydrogel (alum). Phase IA and IB trials have shown good safety and immunogenicity of GMZ2 in malaria-naïve adults as well in African adults and children. The aim of the trial is to assess the efficacy of GMZ2 in African children. Methods: GMZ2 phase IIB vaccine trial recruited participants in four African countries with various malaria transmission intensities. The trial was not powered to compare efficacy by site but a multicentre approach was chosen to ensure adequate sample size interms of the number of malaria cases and to evaluate safety and immunogenicity in range of settings. Baseline studies were conducted in each trial sites prior to commencement of the trial to pilot surveillance methods and obtain estimates of incidence rates. The study population was children 1-5 yrs of age, to be randomized to receive three doses of GMZ2 or rabies vaccine one month apart. The primary endpoint of the trial is malaria which was defined as tympanic temperature of >380C or history of fever in the previous 48 hrs and parasite density of ≥ 5000 /µL, ascertained by Passive Case Detection (PCD) at clinics, over a period up to 6 months after the third dose for the primary analysis, with further follow-up for a total of 22 months. Conclusion: This is the first multi-country trial of a blood stage malaria vaccine. The trial included substantial capacity development component to establish a multicentre vaccine trial network. The results will guide the further clinical development of GMZ2.