Trial Outcomes & Findings for Study to Assess the Vaccine Efficacy Against Malaria Infection, in Children Immunized With the Primary and Yearly Booster of the RTS,S/AS01E Vaccine, as Part of Their Participation in the Malaria-094 (204889/NCT03276962) Study. (NCT NCT03281291)

Results Overview

The number of days from the time origin in each analysis to the visit date associated with the first molecular detection of a new malaria infection. A new molecularly confirmed malaria infection was defined by a detected new infection from genomic analysis of dried blood spot samples originating either from active monthly screening for infection or from unscheduled visits intended for the assessment of clinical malaria.

Recruitment status

COMPLETED

Target enrollment

1500 participants

Primary outcome timeframe

Up to 20 months post Dose 1

Results posted on

2025-01-23

Participant Flow

This is an ancillary study of the Malaria-094 study (204889/NCT03276962). Consequently, the data reported in the Participant Flow and Baseline Characteristics sections were collected from participants from that study.

As pre-specified in the analysis plan, efficacy outcome measures corresponding to vaccine efficacy against first new infection (ATP Cohort) and vaccine efficacy against all new infections (ATP Cohort), presented data for the R012-20 + R012-14-mD Pooled Group because the interventional strategy (1st dose at Month 0, 2nd dose at Month 1, 3rd dose at Month 2) was the same for both the R012-20 Group and the R012-14-mD Group until Month 14.

Participant milestones

Participant milestones
Measure	R012-20 Group Participants received a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2 and Month 20 of study NCT03276962.	R012-14-mD Group Participants received a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2, Month 14, Month 26 and Month 38 of study NCT03276962.	Fx012-14-mFxD Group Participants received a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 2, Month 14, Month 26 and Month 38 of study NCT03276962.	Fx017-mFxD Group Participants received a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 7, Month 20 and Month 32 of study NCT03276962.	Control Group Participants received rabies vaccine at Month 0, Month 1 and Month 2 of study NCT03276962.
Overall Study STARTED	298	294	304	311	293
Overall Study COMPLETED	229	232	242	247	237
Overall Study NOT COMPLETED	69	62	62	64	56

Reasons for withdrawal

Reasons for withdrawal
Measure	R012-20 Group Participants received a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2 and Month 20 of study NCT03276962.	R012-14-mD Group Participants received a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2, Month 14, Month 26 and Month 38 of study NCT03276962.	Fx012-14-mFxD Group Participants received a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 2, Month 14, Month 26 and Month 38 of study NCT03276962.	Fx017-mFxD Group Participants received a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 7, Month 20 and Month 32 of study NCT03276962.	Control Group Participants received rabies vaccine at Month 0, Month 1 and Month 2 of study NCT03276962.
Overall Study Serious Adverse Event And/Or pIMD	2	1	0	4	1
Overall Study Protocol Deviation	2	0	1	2	1
Overall Study Consent Withdrawal, Not Due To An Adverse Event/A Serious Adverse Event	29	21	13	21	16
Overall Study Migrated / Moved From The Study Area	26	28	44	29	27
Overall Study Lost to Follow-up	10	10	4	6	10
Overall Study Other	0	2	0	2	1

Baseline Characteristics

Study to Assess the Vaccine Efficacy Against Malaria Infection, in Children Immunized With the Primary and Yearly Booster of the RTS,S/AS01E Vaccine, as Part of Their Participation in the Malaria-094 (204889/NCT03276962) Study.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	R012-20 Group n=8859 Blood samples collected Participants received a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2 and Month 20 of study NCT03276962.	R012-14-mD Group n=8761 Blood samples collected Participants received a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2, Month 14, Month 26 and Month 38 of study NCT03276962.	Fx012-14-mFxD Group n=9140 Blood samples collected Participants received a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 2, Month 14, Month 26 and Month 38 of study NCT03276962.	Fx017-mFxD Group n=9392 Blood samples collected Participants received a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 7, Month 20 and Month 32 of study NCT03276962.	Control Group n=9207 Blood samples collected Participants received rabies vaccine at Month 0, Month 1 and Month 2 of study NCT03276962.	Total n=45359 Blood samples collected Total of all reporting groups
Age, Continuous	10.2 Months STANDARD_DEVIATION 3.9 • n=5 Participants	10.3 Months STANDARD_DEVIATION 3.8 • n=7 Participants	10.5 Months STANDARD_DEVIATION 4.0 • n=5 Participants	10.2 Months STANDARD_DEVIATION 3.8 • n=4 Participants	10.5 Months STANDARD_DEVIATION 3.9 • n=21 Participants	10.3 Months STANDARD_DEVIATION 3.9 • n=8 Participants
Sex: Female, Male Female	119 Participants n=5 Participants	155 Participants n=7 Participants	172 Participants n=5 Participants	163 Participants n=4 Participants	152 Participants n=21 Participants	761 Participants n=8 Participants
Sex: Female, Male Male	179 Participants n=5 Participants	139 Participants n=7 Participants	132 Participants n=5 Participants	148 Participants n=4 Participants	141 Participants n=21 Participants	739 Participants n=8 Participants
Race/Ethnicity, Customized Black Or African American	298 Participants n=5 Participants	294 Participants n=7 Participants	304 Participants n=5 Participants	311 Participants n=4 Participants	293 Participants n=21 Participants	1500 Participants n=8 Participants

PRIMARY outcome

Timeframe: Up to 20 months post Dose 1

Population: The analysis was performed on the Total Vaccinated Cohort (TVC) which included all the participants who received at least one dose of study vaccine per Malaria-094 protocol.

The number of days from the time origin in each analysis to the visit date associated with the first molecular detection of a new malaria infection. A new molecularly confirmed malaria infection was defined by a detected new infection from genomic analysis of dried blood spot samples originating either from active monthly screening for infection or from unscheduled visits intended for the assessment of clinical malaria.

Outcome measures

Outcome measures
Measure	R012-20 Group n=298 Participants Participants received a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2 and Month 20 of study NCT03276962.	R012-14-mD Group n=294 Participants Participants received a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2, Month 14, Month 26 and Month 38 of study NCT03276962.	Fx012-14-mFxD Group n=304 Participants Participants received a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 2, Month 14, Month 26 and Month 38 of study NCT03276962.	Fx017-mFxD Group n=311 Participants Participants received a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 7, Month 20 and Month 32 of study NCT03276962.	Control Group n=293 Participants Participants received rabies vaccine at Month 0, Month 1 and Month 2 of study NCT03276962.
Time From First Vaccination to the Detection of the First New Malaria Infection Through to the Month 20 Study Visit	43.1 Weeks Interval 15.1 to 85.9	43.9 Weeks Interval 17.4 to 86.4	39 Weeks Interval 19.4 to 79.3	39 Weeks Interval 15.7 to 87.7	31.9 Weeks Interval 10.4 to 64.9

PRIMARY outcome

Timeframe: From Month 2.5 to Month 14 for the R012-20 + R012-14-mD Pooled Group, the Fx012-14-mFxD Group and the Control Group, and from Month 7.5 to Month 19 for the Fx017-mFxD Group

Population: The analysis was performed on the According-To-Protocol (ATP) cohort, including participants who received the first three vaccinations per Malaria-094 protocol and were at risk for a molecularly confirmed infection 14 days after Dose 3. As pre-specified in the analysis plan, this outcome measure was reported for the R012-20 + R012-14-mD Pooled Group because both the R012-20 Group and R012-14-mD Group followed the same interventional strategy until Month 14.

The number of days from the time origin in each analysis to the visit date associated with the first molecular detection of a new malaria infection. A new molecularly confirmed malaria infection was defined by a detected new infection from genomic analysis of dried blood spot samples originating either from active monthly screening for infection or from unscheduled visits intended for the assessment of clinical malaria.

Outcome measures

Outcome measures
Measure	R012-20 Group n=523 Participants Participants received a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2 and Month 20 of study NCT03276962.	R012-14-mD Group n=271 Participants Participants received a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2, Month 14, Month 26 and Month 38 of study NCT03276962.	Fx012-14-mFxD Group n=273 Participants Participants received a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 2, Month 14, Month 26 and Month 38 of study NCT03276962.	Fx017-mFxD Group n=265 Participants Participants received a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 7, Month 20 and Month 32 of study NCT03276962.	Control Group Participants received rabies vaccine at Month 0, Month 1 and Month 2 of study NCT03276962.
Time From First Vaccination to the Detection of the First New Malaria Infection From 14 Days Post-Dose 3 Through to 12 Months Post-Dose 3	40.6 Weeks Interval 20.4 to The upper limit represents the time at which 75% of the population has experienced the event. This was not reached because, by the end of the study, less than 75% of the participants have experienced the event, therefore, this value could not be estimated. Q3 values are missing due to Kaplan Meier estimates accounting for right censoring.	36.7 Weeks Interval 21.9 to The upper limit represents the time at which 75% of the population has experienced the event. This was not reached because, by the end of the study, less than 75% of the participants have experienced the event, therefore, this value could not be estimated. Q3 values are missing due to Kaplan Meier estimates accounting for right censoring.	38.6 Weeks Interval 12.6 to The upper limit represents the time at which 75% of the population has experienced the event. This was not reached because, by the end of the study, less than 75% of the participants have experienced the event, therefore, this value could not be estimated. Q3 values are missing due to Kaplan Meier estimates accounting for right censoring.	28.7 Weeks Interval 10.6 to The upper limit represents the time at which 75% of the population has experienced the event. This was not reached because, by the end of the study, less than 75% of the participants have experienced the event, therefore, this value could not be estimated. Q3 values are missing due to Kaplan Meier estimates accounting for right censoring.	—

PRIMARY outcome

Timeframe: Up to 32 months post Dose 1

Population: The analysis was performed on the TVC which included all the participants who received at least one dose of study vaccine per Malaria-094 protocol.

The number of days from the time origin in each analysis to the visit date associated with the first molecular detection of a new malaria infection. A new molecularly confirmed malaria infection was defined by a detected new infection from genomic analysis of dried blood spot samples originating either from active monthly screening for infection or from unscheduled visits intended for the assessment of clinical malaria.

Outcome measures

Outcome measures
Measure	R012-20 Group n=298 Participants Participants received a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2 and Month 20 of study NCT03276962.	R012-14-mD Group n=294 Participants Participants received a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2, Month 14, Month 26 and Month 38 of study NCT03276962.	Fx012-14-mFxD Group n=304 Participants Participants received a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 2, Month 14, Month 26 and Month 38 of study NCT03276962.	Fx017-mFxD Group n=311 Participants Participants received a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 7, Month 20 and Month 32 of study NCT03276962.	Control Group n=293 Participants Participants received rabies vaccine at Month 0, Month 1 and Month 2 of study NCT03276962.
Time From First Vaccination to the Detection of the First New Malaria Infection Through to the Month 32 Study Visit	42.4 Weeks Interval 12.6 to 97.1	42.7 Weeks Interval 12.7 to 97.7	38.9 Weeks Interval 19.6 to 79.3	37.7 Weeks Interval 14.7 to 94.0	31 Weeks Interval 10.3 to 64.0

PRIMARY outcome

Timeframe: From Month 2.5 to Month 26 for the R012-20 Group, the R012-14-mD Group, the Fx012-14-mFxD Group and the Control Group, and from Month 7.5 to Month 31 for the Fx017-mFxD Group

Population: The analysis was performed on the ATP cohort which included all participants who received the first three vaccinations according to the Malaria-094 protocol procedures and who were observed to be at risk for a molecularly confirmed malaria infection at 14 days post-Dose 3.

The number of days from the time origin in each analysis to the visit date associated with the first molecular detection of a new malaria infection. A new molecularly confirmed malaria infection was defined by a detected new infection from genomic analysis of dried blood spot samples originating either from active monthly screening for infection or from unscheduled visits intended for the assessment of clinical malaria.

Outcome measures

Outcome measures
Measure	R012-20 Group n=259 Participants Participants received a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2 and Month 20 of study NCT03276962.	R012-14-mD Group n=264 Participants Participants received a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2, Month 14, Month 26 and Month 38 of study NCT03276962.	Fx012-14-mFxD Group n=271 Participants Participants received a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 2, Month 14, Month 26 and Month 38 of study NCT03276962.	Fx017-mFxD Group n=273 Participants Participants received a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 7, Month 20 and Month 32 of study NCT03276962.	Control Group n=265 Participants Participants received rabies vaccine at Month 0, Month 1 and Month 2 of study NCT03276962.
Time From First Vaccination to the Detection of the First New Malaria Infection From 14 Days Post-Dose 3 Through to 24 Months Post-Dose 3	40.3 Weeks Interval 20.0 to The upper limit represents the time at which 75% of the population has experienced the event. This was not reached because, by the end of the study, less than 75% of the participants have experienced the event, therefore, this value could not be estimated. Q3 values are missing due to Kaplan Meier estimates accounting for right censoring.	42 Weeks Interval 20.3 to The upper limit represents the time at which 75% of the population has experienced the event. This was not reached because, by the end of the study, less than 75% of the participants have experienced the event, therefore, this value could not be estimated. Q3 values are missing due to Kaplan Meier estimates accounting for right censoring.	36.7 Weeks Interval 21.9 to 83.7	38.4 Weeks Interval 12.6 to The upper limit represents the time at which 75% of the population has experienced the event. This was not reached because, by the end of the study, less than 75% of the participants have experienced the event, therefore, this value could not be estimated. Q3 values are missing due to Kaplan Meier estimates accounting for right censoring.	28.7 Weeks Interval 10.4 to The upper limit represents the time at which 75% of the population has experienced the event. This was not reached because, by the end of the study, less than 75% of the participants have experienced the event, therefore, this value could not be estimated. Q3 values are missing due to Kaplan Meier estimates accounting for right censoring.

PRIMARY outcome

Timeframe: Up to 20 months post Dose 1

Population: The analysis was performed on the TVC which included all the participants who received at least one dose of study vaccine per Malaria-094 protocol.

A new molecularly confirmed malaria infection was defined by a detected new infection from genomic analysis of dried blood spot samples originating either from active monthly screening for infection or from unscheduled visits intended for the assessment of clinical malaria.

Outcome measures

Outcome measures
Measure	R012-20 Group n=298 Participants Participants received a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2 and Month 20 of study NCT03276962.	R012-14-mD Group n=294 Participants Participants received a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2, Month 14, Month 26 and Month 38 of study NCT03276962.	Fx012-14-mFxD Group n=304 Participants Participants received a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 2, Month 14, Month 26 and Month 38 of study NCT03276962.	Fx017-mFxD Group n=311 Participants Participants received a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 7, Month 20 and Month 32 of study NCT03276962.	Control Group n=293 Participants Participants received rabies vaccine at Month 0, Month 1 and Month 2 of study NCT03276962.
Number of Molecularly Confirmed New Malaria Infections Through to the Month 20 Study Visit	758 Infections	558 Infections	605 Infections	673 Infections	996 Infections

PRIMARY outcome

Timeframe: From Month 2.5 to Month 14 for the R012-20 + R012-14-mD Pooled Group, the Fx012-14-mFxD Group and the Control Group, and from Month 7.5 to Month 19 for the Fx017-mFxD Group

Population: The analysis was performed on the ATP cohort which included all participants who received the first 3 vaccinations according to the Malaria-094 protocol and who were observed to be at risk for a molecularly confirmed malaria infection at 14 days post-Dose 3. As pre-specified in the analysis plan, this outcome measure was reported for the R012-20 + R012-14-mD Pooled Group because both the R012-20 Group and R012-14-mD Group followed the same interventional strategy until Month 14.

A new molecularly confirmed malaria infection was defined by a detected new infection from genomic analysis of dried blood spot samples originating either from active monthly screening for infection or from unscheduled visits intended for the assessment of clinical malaria.

Outcome measures

Outcome measures
Measure	R012-20 Group n=523 Participants Participants received a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2 and Month 20 of study NCT03276962.	R012-14-mD Group n=271 Participants Participants received a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2, Month 14, Month 26 and Month 38 of study NCT03276962.	Fx012-14-mFxD Group n=273 Participants Participants received a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 2, Month 14, Month 26 and Month 38 of study NCT03276962.	Fx017-mFxD Group n=265 Participants Participants received a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 7, Month 20 and Month 32 of study NCT03276962.	Control Group Participants received rabies vaccine at Month 0, Month 1 and Month 2 of study NCT03276962.
Number of Molecularly Confirmed New Malaria Infections From 14 Days Post-Dose 3 Through to 12 Months Post-Dose 3	1825 Infections	337 Infections	368 Infections	477 Infections	—

PRIMARY outcome

Timeframe: Up to 32 months post Dose 1

Population: The analysis was performed on the TVC which included all the participants who received at least one dose of study vaccine per Malaria-094 protocol.

A new molecularly confirmed malaria infection was defined by a detected new infection from genomic analysis of dried blood spot samples originating either from active monthly screening for infection or from unscheduled visits intended for the assessment of clinical malaria.

Outcome measures

Outcome measures
Measure	R012-20 Group n=298 Participants Participants received a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2 and Month 20 of study NCT03276962.	R012-14-mD Group n=294 Participants Participants received a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2, Month 14, Month 26 and Month 38 of study NCT03276962.	Fx012-14-mFxD Group n=304 Participants Participants received a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 2, Month 14, Month 26 and Month 38 of study NCT03276962.	Fx017-mFxD Group n=311 Participants Participants received a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 7, Month 20 and Month 32 of study NCT03276962.	Control Group n=293 Participants Participants received rabies vaccine at Month 0, Month 1 and Month 2 of study NCT03276962.
Number of Molecularly Confirmed New Malaria Infections Through to the Month 32 Study Visit	1105 Infections	940 Infections	910 Infections	1029 Infections	1420 Infections

PRIMARY outcome

Timeframe: From Month 2.5 to Month 26 for the R012-20 Group, the R012-14-mD Group, the Fx012-14-mFxD Group and the Control Group, and from Month 7.5 to Month 31 for the Fx017-mFxD Group

Population: The analysis was performed on the ATP cohort which included all participants who received the first three vaccinations according to the Malaria-094 protocol procedures and who are observed to be at risk for a molecularly confirmed malaria infection at 14 days post-Dose 3.

A new molecularly confirmed malaria infection was defined by a detected new infection from genomic analysis of dried blood spot samples originating either from active monthly screening for infection or from unscheduled visits intended for the assessment of clinical malaria.