Malaria
Conditions
Keywords
malaria vaccine, infants, malaria, RTS,S/AS01, falciparum, genomics, efficacy
Brief summary
The aim of this study was to evaluate the effectiveness of the RTS,S/AS01E malaria vaccine against both clinical and asymptomatic malaria infections by detecting Plasmodium falciparum (P. falciparum) parasites in blood samples collected from children who received the primary and yearly booster doses of the RTS,S/AS01E vaccine, as part of their participation in the Malaria-094 parent clinical study. The genomic analysis was conducted on parasites found in blood spot samples from children aged 5-17 months, who were vaccinated according to different dosage and schedule regimens as part of the Malaria-094 parent clinical study.
Detailed description
This genotyping study of malaria parasites, collected from serial blood samples following RTS,S/AS01E immunization, assessed vaccine efficacy using molecular genetic data. The study aimed to identify the first infections post-vaccination and distinguish new infections from existing ones through an amplicon sequencing-based strategy. This involved deep sequencing of small, highly variable regions of the parasite genome, enabling both: 1. Highly sensitive detection of parasitemia (similar to conventional polymerase chain reaction \[PCR\]-based detection), and 2. Identification of genetically distinct parasite populations within or between affected individuals.
Interventions
None listed
Sponsors
GlaxoSmithKline
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
5 Months to 17 Months
Healthy volunteers
Yes
Inclusion criteria
* Participants' parent(s)/LAR(s) who, in the opinion of the investigator, complied with the requirements of the protocol (e.g. return for follow-up visits). * Signed or thumb-printed and witnessed informed consent obtained from the parent(s)/LAR(s) of the participant prior to performance of any study specific procedure. Where parent(s)/LAR(s) were illiterate, the consent form was countersigned by an independent witness. * A male or female between, and including, five and 17 months of age at the time of the first vaccination. * Healthy participants as established by medical history and clinical examination before entering into the study. * Previously received three documented doses of diphtheria, tetanus, pertussis, hepatitis B vaccine (DTPHepB), and at least three doses of oral polio vaccine.
Exclusion criteria
* Child in care. * Use of a drug or vaccine that is not approved for that indication (by one of the following regulatory authorities: Food and Drug Administration \[FDA; USA\] or European Union member state or WHO \[with respect to prequalification\]) other than the study vaccines during the period starting 30 days before the first dose of study vaccines (Day -29 to Day 0), or planned use during the study period. * Any medical condition that in the judgment of the investigator would have made the intramuscular injection unsafe. Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine dose. For corticosteroids, this meant prednisone (0.5 mg/kg/day (for pediatric participants) or equivalent. Inhaled and topical steroids are allowed. * Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting seven days before each dose and ending seven days after each dose of vaccine administration. * Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or was to be exposed to an investigational or a non-investigational vaccine/product (pharmaceutical product or device). * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). * Family history of congenital or hereditary immunodeficiency. * History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. * History of anaphylaxis post-vaccination. * History of any, or documented, serious adverse reaction to rabies vaccination. * Contraindication to rabies vaccination (Rabipur is contraindicated in participants with a history of a severe hypersensitivity to any of the ingredients in the vaccine. Note that the vaccine contains polygeline and residues of chicken proteins, and may contain traces of neomycin, chlortetracycline and amphotericin B). * Major congenital defects. * Serious chronic illness. * Children with a past history of a neurological disorder or atypical febrile seizure (a febrile seizure is atypical if it meets one of the following criteria: not associated with fever; lasts \> 5 minutes; focal (not generalized); followed by transient or persistent neurological abnormality; occurs in a child \< 6 months of age). * Acute disease and/or fever at the time of enrolment. * Fever is defined as temperature ≥ 37.5°C/99.5°F for oral, axillary or tympanic route, or ≥ 38.0°C/100.4°F for rectal route. * Participants with a minor illness (such as mild diarrhea, mild upper respiratory infection) without fever may have been enrolled at the discretion of the investigator. * Administration of immunoglobulins and/or any blood products during the period starting three months before the first dose of study vaccine or planned administration during the study period. * Moderate or severe malnutrition at screening defined as weight for age or weight for height Z-score \< -2. * Hemoglobin concentration \< 8 g/dl at screening. * Same sex twins (to avoid misidentification). * Maternal death. * Prior receipt of an investigational malaria vaccine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time From First Vaccination to the Detection of the First New Malaria Infection Through to the Month 20 Study Visit | Up to 20 months post Dose 1 | 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. |
| 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 | 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 | 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. |
| Time From First Vaccination to the Detection of the First New Malaria Infection Through to the Month 32 Study Visit | Up to 32 months post Dose 1 | 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. |
| 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 | 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 | 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. |
| Number of Molecularly Confirmed New Malaria Infections Through to the Month 20 Study Visit | Up to 20 months post Dose 1 | 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. |
| Number of Molecularly Confirmed New Malaria Infections From 14 Days Post-Dose 3 Through to 12 Months Post-Dose 3 | 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 | 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. |
| Number of Molecularly Confirmed New Malaria Infections Through to the Month 32 Study Visit | Up to 32 months post Dose 1 | 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. |
| Number of Molecularly Confirmed New Malaria Infections From 14 Days Post-Dose 3 Through to 24 Months Post-Dose 3 | 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 | 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. |
Countries
Ghana, Kenya
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 298 |
| 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. | 8,859 |
| 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. | 294 |
| 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. | 8,761 |
| 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. | 304 |
| 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. | 9,140 |
| 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. | 311 |
| 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. | 9,392 |
| Control Group Participants received rabies vaccine at Month 0, Month 1 and Month 2 of study NCT03276962. | 293 |
| Control Group Participants received rabies vaccine at Month 0, Month 1 and Month 2 of study NCT03276962. | 9,207 |
| Total | 46,859 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Consent Withdrawal, Not Due To An Adverse Event/A Serious Adverse Event | 29 | 21 | 13 | 21 | 16 |
| Overall Study | Lost to Follow-up | 10 | 10 | 4 | 6 | 10 |
| Overall Study | Migrated / Moved From The Study Area | 26 | 28 | 44 | 29 | 27 |
| Overall Study | Other | 0 | 2 | 0 | 2 | 1 |
| Overall Study | Protocol Deviation | 2 | 0 | 1 | 2 | 1 |
| Overall Study | Serious Adverse Event And/Or pIMD | 2 | 1 | 0 | 4 | 1 |
Baseline characteristics
| Characteristic | R012-20 Group | R012-14-mD Group | Fx012-14-mFxD Group | Fx017-mFxD Group | Control Group | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 10.2 Months STANDARD_DEVIATION 3.9 | 10.3 Months STANDARD_DEVIATION 3.8 | 10.5 Months STANDARD_DEVIATION 4 | 10.2 Months STANDARD_DEVIATION 3.8 | 10.5 Months STANDARD_DEVIATION 3.9 | 10.3 Months STANDARD_DEVIATION 3.9 |
| Race/Ethnicity, Customized Black Or African American | 298 Participants | 294 Participants | 304 Participants | 311 Participants | 293 Participants | 1500 Participants |
| Sex: Female, Male Female | 119 Participants | 155 Participants | 172 Participants | 163 Participants | 152 Participants | 761 Participants |
| Sex: Female, Male Male | 179 Participants | 139 Participants | 132 Participants | 148 Participants | 141 Participants | 739 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Number of Molecularly Confirmed New Malaria Infections From 14 Days Post-Dose 3 Through to 12 Months 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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| R012-20 Group | Number of Molecularly Confirmed New Malaria Infections From 14 Days Post-Dose 3 Through to 12 Months Post-Dose 3 | 1825 Infections |
| R012-14-mD Group | Number of Molecularly Confirmed New Malaria Infections From 14 Days Post-Dose 3 Through to 12 Months Post-Dose 3 | 337 Infections |
| Fx012-14-mFxD Group | Number of Molecularly Confirmed New Malaria Infections From 14 Days Post-Dose 3 Through to 12 Months Post-Dose 3 | 368 Infections |
| Fx017-mFxD Group | Number of Molecularly Confirmed New Malaria Infections From 14 Days Post-Dose 3 Through to 12 Months Post-Dose 3 | 477 Infections |
Comparison: To detect a significant difference in the mean number of new molecularly confirmed malaria infections in the ATP cohort between months 2.5 to 14, for R012-20 + R012-14-mD Pooled Group vs Control Group.95% CI: [-1.068, -0.469]Wald test
Comparison: To detect a significant difference in the mean number of new molecularly confirmed malaria infections in the ATP cohort between months 2.5 to 14, for Fx012-14-mFxD groups vs Control Group.95% CI: [-1.133, -0.439]Wald test
Comparison: To detect a significant difference in the mean number of new molecularly confirmed malaria infections in the ATP cohort between months 7.5 to 19, for Fx017-mFxD groups vs Control Group.95% CI: [-1.592, -0.959]Wald test
Primary
Number of Molecularly Confirmed New Malaria Infections From 14 Days Post-Dose 3 Through to 24 Months 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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| R012-20 Group | Number of Molecularly Confirmed New Malaria Infections From 14 Days Post-Dose 3 Through to 24 Months Post-Dose 3 | 804 Infections |
| R012-14-mD Group | Number of Molecularly Confirmed New Malaria Infections From 14 Days Post-Dose 3 Through to 24 Months Post-Dose 3 | 728 Infections |
| Fx012-14-mFxD Group | Number of Molecularly Confirmed New Malaria Infections From 14 Days Post-Dose 3 Through to 24 Months Post-Dose 3 | 704 Infections |
| Fx017-mFxD Group | Number of Molecularly Confirmed New Malaria Infections From 14 Days Post-Dose 3 Through to 24 Months Post-Dose 3 | 836 Infections |
| Control Group | Number of Molecularly Confirmed New Malaria Infections From 14 Days Post-Dose 3 Through to 24 Months Post-Dose 3 | 1071 Infections |
Comparison: To detect a significant difference in the mean number of new molecularly confirmed malaria infections in the ATP cohort between months 2.5 to 26, for R012-20 group vs Control Group.95% CI: [-2.252, -1.015]Wald test
Comparison: To detect a significant difference in the mean number of new molecularly confirmed malaria infections in the ATP cohort between months 2.5 to 26, for R012-14 group vs Control Group.95% CI: [-2.601, -1.393]Wald test
Comparison: To detect a significant difference in the mean number of new molecularly confirmed malaria infections in the ATP cohort between months 2.5 to 26, for Fx012-14-mFxD group vs Control Group.95% CI: [-2.399, -1.153]Wald test
Comparison: To detect a significant difference in the mean number of new molecularly confirmed malaria infections in the ATP cohort between months 7.5 to 31, for Fx017-mFxD group vs Control Group.95% CI: [-2.527, -1.158]Wald test
Primary
Number of Molecularly Confirmed New Malaria Infections Through to the Month 20 Study Visit
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| R012-20 Group | Number of Molecularly Confirmed New Malaria Infections Through to the Month 20 Study Visit | 758 Infections |
| R012-14-mD Group | Number of Molecularly Confirmed New Malaria Infections Through to the Month 20 Study Visit | 558 Infections |
| Fx012-14-mFxD Group | Number of Molecularly Confirmed New Malaria Infections Through to the Month 20 Study Visit | 605 Infections |
| Fx017-mFxD Group | Number of Molecularly Confirmed New Malaria Infections Through to the Month 20 Study Visit | 673 Infections |
| Control Group | Number of Molecularly Confirmed New Malaria Infections Through to the Month 20 Study Visit | 996 Infections |
Comparison: To detect a significant difference in the mean number of new molecularly confirmed malaria infections in the TVC between enrollment and Month 20 visit, for R012-20 Group vs Control Group.95% CI: [-1.979, -1.022]Wald Test
Comparison: To detect a significant difference in the mean number of new molecularly confirmed malaria infections in the TVC between enrollment and Month 20 visit, for R012-14-mD Group vs Control Group.95% CI: [-2.027, -1.061]Wald test
Comparison: To detect a significant difference in the mean number of new molecularly confirmed malaria infections in the TVC between enrollment and Month 20 visit, for Fx012-14-mFxD Group vs Control Group.95% CI: [-2.065, -1.085]Wald test
Comparison: To detect a significant difference in the mean number of new molecularly confirmed malaria infections in the TVC between enrollment and Month 20 visit, for Fx017-mFxD Group vs Control Group.95% CI: [-1.635, -0.586]Wald test
Primary
Number of Molecularly Confirmed New Malaria Infections Through to the Month 32 Study Visit
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| R012-20 Group | Number of Molecularly Confirmed New Malaria Infections Through to the Month 32 Study Visit | 1105 Infections |
| R012-14-mD Group | Number of Molecularly Confirmed New Malaria Infections Through to the Month 32 Study Visit | 940 Infections |
| Fx012-14-mFxD Group | Number of Molecularly Confirmed New Malaria Infections Through to the Month 32 Study Visit | 910 Infections |
| Fx017-mFxD Group | Number of Molecularly Confirmed New Malaria Infections Through to the Month 32 Study Visit | 1029 Infections |
| Control Group | Number of Molecularly Confirmed New Malaria Infections Through to the Month 32 Study Visit | 1420 Infections |
Comparison: To detect a significant difference in the mean number of new molecularly confirmed malaria infections in the TVC between enrollment and Month 32 visit, for R012-20 Group vs Control Group.95% CI: [-3.448, -1.924]Wald test
Comparison: To detect a significant difference in the mean number of new molecularly confirmed malaria infections in the TVC between enrollment and Month 32 visit, for R012-14-mD Group vs Control Group.95% CI: [-3.217, -1.686]Wald test
Comparison: To detect a significant difference in the mean number of new molecularly confirmed malaria infections in the TVC between enrollment and Month 32 visit, for Fx012-14-mFxD Group vs Control Group.95% CI: [-3.345, -1.824]Wald test
Comparison: To detect a significant difference in the mean number of new molecularly confirmed malaria infections in the TVC between enrollment and Month 32 visit, for Fx017-mFxD Group vs Control Group.95% CI: [-2.726, -1.067]Wald test
Primary
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
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| R012-20 Group | 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 |
| R012-14-mD Group | 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 | 36.7 Weeks |
| Fx012-14-mFxD Group | 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 | 38.6 Weeks |
| Fx017-mFxD Group | 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 | 28.7 Weeks |
Comparison: Comparison of vaccine efficacy in the ATP cohort against the first new genotypic infection, between months 2.5 and 14, for R012-20 + R012-14-mD Pooled Group vs Control Group.95% CI: [30.7, 52.8]Regression, Cox
Comparison: Comparison of vaccine efficacy in the ATP cohort against the first new genotypic infection, between months 2.5 and 14, for Fx012-14-mFxD Group vs Control Group.95% CI: [21.2, 49.2]Regression, Cox
Comparison: Comparison of vaccine efficacy in the ATP cohort against the first new genotypic infection, between months 7.5 and 19, for Fx017-mFxD Group vs Control Group.95% CI: [26.7, 53.1]Regression, Cox
Primary
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
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| R012-20 Group | 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 |
| R012-14-mD Group | 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 | 42 Weeks |
| Fx012-14-mFxD Group | 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 | 36.7 Weeks |
| Fx017-mFxD Group | 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 | 38.4 Weeks |
| Control Group | 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 | 28.7 Weeks |
Comparison: Comparison of vaccine efficacy in the ATP cohort against the first new genotypic infection, between months 2.5 and 26, for R012-20 Group vs Control Group.95% CI: [28.6, 52.5]Regression, Cox
Comparison: Comparison of vaccine efficacy in the ATP cohort against the first new genotypic infection, between months 2.5 and 26, for R012-14-mD Group vs Control Group.95% CI: [26.8, 50.6]Regression, Cox
Comparison: Comparison of vaccine efficacy in the ATP cohort against the first new genotypic infection, between months 2.5 and 26, for Fx012-14-mFxD Group vs Control Group.95% CI: [19.3, 45.3]Regression, Cox
Comparison: Comparison of vaccine efficacy in the ATP cohort against the first new genotypic infection, between months 7.5 and 31, for Fx017-mFxD Group vs Control Group.95% CI: [27.2, 51.5]Regression, Cox
Primary
Time From First Vaccination to the Detection of the First New Malaria Infection Through to the Month 20 Study Visit
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| R012-20 Group | Time From First Vaccination to the Detection of the First New Malaria Infection Through to the Month 20 Study Visit | 43.1 Weeks |
| R012-14-mD Group | Time From First Vaccination to the Detection of the First New Malaria Infection Through to the Month 20 Study Visit | 43.9 Weeks |
| Fx012-14-mFxD Group | Time From First Vaccination to the Detection of the First New Malaria Infection Through to the Month 20 Study Visit | 39 Weeks |
| Fx017-mFxD Group | Time From First Vaccination to the Detection of the First New Malaria Infection Through to the Month 20 Study Visit | 39 Weeks |
| Control Group | Time From First Vaccination to the Detection of the First New Malaria Infection Through to the Month 20 Study Visit | 31.9 Weeks |
Comparison: Comparison of vaccine efficacy (VE) in the TVC against the first new genotypic infection, between enrollment and Month 20 visit, for R012-20 Group vs Control Group.95% CI: [14.7, 42.1]Regression, Cox
Comparison: Comparison of vaccine efficacy in the TVC against the first new genotypic infection, between enrollment and Month 20 visit, for R012-14-mD Group vs Control Group.95% CI: [16.4, 43.3]Regression, Cox
Comparison: Comparison of vaccine efficacy in the TVC against the first new genotypic infection, between enrollment and Month 20 visit, for Fx012-14-mFxD Group vs Control Group.95% CI: [9, 37.6]Regression, Cox
Comparison: Comparison of vaccine efficacy in the TVC against the first new genotypic infection, between enrollment and Month 20 visit, for Fx017-mFxD Group vs Control Group.95% CI: [13.9, 41.1]Regression, Cox
Primary
Time From First Vaccination to the Detection of the First New Malaria Infection Through to the Month 32 Study Visit
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| R012-20 Group | Time From First Vaccination to the Detection of the First New Malaria Infection Through to the Month 32 Study Visit | 42.4 Weeks |
| R012-14-mD Group | Time From First Vaccination to the Detection of the First New Malaria Infection Through to the Month 32 Study Visit | 42.7 Weeks |
| Fx012-14-mFxD Group | Time From First Vaccination to the Detection of the First New Malaria Infection Through to the Month 32 Study Visit | 38.9 Weeks |
| Fx017-mFxD Group | Time From First Vaccination to the Detection of the First New Malaria Infection Through to the Month 32 Study Visit | 37.7 Weeks |
| Control Group | Time From First Vaccination to the Detection of the First New Malaria Infection Through to the Month 32 Study Visit | 31 Weeks |
Comparison: Comparison of vaccine efficacy in the TVC against the first new genotypic infection, between enrollment and Month 32 visit, for R012-20 Group vs Control Group.95% CI: [15.4, 41.5]Regression, Cox
Comparison: Comparison of vaccine efficacy in the TVC against the first new genotypic infection, between enrollment and Month 32 visit, for R012-14-mD Group vs Control Group.95% CI: [16.6, 42.2]Regression, Cox
Comparison: Comparison of vaccine efficacy in the TVC against the first new genotypic infection, between enrollment and Month 32 visit, for Fx012-14-mFxD Group vs Control Group.95% CI: [13.1, 39.4]Regression, Cox
Comparison: Comparison of vaccine efficacy in the TVC against the first new genotypic infection, between enrollment and Month 32 visit, for Fx017-mFxD Group vs Control Group.95% CI: [11.9, 38.3]Regression, Cox