Table 1 Efficacy endpoints

Primary Efficacy Endpoint

Efficacy against clinical malaria when primary immunization starts at 6-12 weeks, or 5-17 months of age

Occurrence of cases of malaria meeting the primary case definition for clinical malaria over a period starting 14 days post Dose 3 for 12 months in children aged 6-12 weeks

Occurrence of cases of malaria meeting the primary case definition for clinical malaria over a period starting 14 days post Dose 3 for 12 months in children aged 5-17

Secondary Efficacy Endpoints

Efficacy against severe disease

Occurrence of severe malaria meeting the primary and secondary case definitions

Efficacy against incident severe anaemia and malaria hospitalization

Occurrence of incident severe anaemia and malaria hospitalization meeting the primary and secondary case definitions

Duration of efficacy of a primary course

For a primary schedule without a boost, the occurrence of clinical malaria meeting the primary case definition analysed over the time periods starting 14 days post Dose 3 until boost, boost until study end and 14 days post Dose 3 until study end

Potential added benefit of a booster dose

For a primary schedule with and without a boost, the occurrence of clinical malaria meeting the primary case definition analysed over the time period starting at boost until study end

Efficacy under different transmission settings

For each site, occurrence of clinical malaria disease meeting the primary case definitions

Efficacy against secondary case definitions of clinical malaria

Occurrence of clinical malaria disease meeting the secondary case definitions

Efficacy against prevalence of parasitaemia

Presence of parasitaemia at 18 months and 30 months post Dose 3 and 12 months after the booster dose

Efficacy against prevalence of moderate and severe anaemia

Presence of moderate and severe anaemia at 18 months and 30 months post Dose 3 and 12 months after the booster dose

Efficacy against other serious illness

Occurrence of other serious illness meeting the primary and secondary case definitions. Other serious illness is all medical hospitalization, sepsis and pneumonia

Efficacy against fatal malaria and all-cause mortality

Occurrence of fatal malaria (meeting the case definitions) and all-cause mortality

Effect on growth

Compare the height/length, weight and mid-upper arm circumference for age z-score

Gender-specific efficacy

In male and female children, the occurrence of clinical malaria disease meeting the primary case definition