Trial · NCT04661579
Study of Malaria Vaccine RTS,S/AS01E in Plasmodium Falciparum-infected and Uninfected Adults Pre-treated With Anti-malarial Therapy
NCT04661579, Phase 2, Completed, PATH; results first posted 2024-07-19
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ConductScience Library. Study of Malaria Vaccine RTS,S/AS01E in Plasmodium Falciparum-infected and Uninfected Adults Pre-treated With Anti-malarial Therapy. Trials, record NCT04661579. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04661579
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Study of Malaria Vaccine RTS,S/AS01E in Plasmodium Falciparum-infected and Uninfected Adults Pre-treated With Anti-malarial Therapy
- NCT number
- NCT04661579
- Status
- Completed
- Phases
- Phase 2
- Enrollment
- 620 participants, actual
- Lead sponsor
- PATH
- Conditions
- Plasmodium Falciparum
- Interventions
- Malaria Vaccine RTS,S/AS01E, Abhayrab rabies vaccine, Dihydroartemisinin-piperaquine (DHA/Pip), Artemether / Lumefantrine, Primaquine
- First posted
- 2020-12-10
- Last updated
- 2024-07-19
- Results first posted
- 2024-07-19
Source ClinicalTrials.gov
Registered outcomes8
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Time to First PCR-detectable Malaria Infection During the Active Detection of Infection (ADI) Phase in Groups 1 and 4 | The active detection of infection phase began 2 weeks after the third vaccination (approximately week 30) for up to 35 weeks. Participants provided blood samples every 21 days during the ADI phase for PCR assays. | Participants were actively monitored for malarial infection starting 2 weeks after the third vaccination. Blood samples were assayed using a highly sensitive polymerase chain reaction (PCR) (Plasmodium falciparum/ Pan-Plasmodium 18S ribosomal ribonucleic acid (rRNA) laboratory developed test \[LDT\]) that can detect sub-clinical parasitemia at the US Army Medical Research Directorate-Africa (USAMRD-A) / Kenya Medical Research Institute (KEMRI) laboratories in Kisumu, Kenya. A positive PCR result from blood samples collected during the ADI was recorded as a positive event for the presence of P. falciparum blood stage infection. The time to first malaria infection is expressed in terms of rate of first malaria infection, that is, the number of malaria infection events reported over the time period elapsed until the event occurred (i.e. events per Persons Year at Risk \[PYAR\]) for each group. |
| Secondary | Time to First PCR-detectable Malaria Infection During the Active Detection of Infection Phase in Groups 2 and 5 | The active detection of infection phase began 2 weeks after the third vaccination (approximately week 30) for up to 35 weeks. Participants provided blood samples every 21 days during the ADI phase for PCR assays. | Participants were actively monitored for malarial infection starting 2 weeks after the third vaccination. Blood samples were assayed using a highly sensitive PCR (Plasmodium falciparum/ Pan-Plasmodium 18S rRNA LDT) that can detect sub-clinical parasitemia. A positive PCR result from blood samples collected during the ADI phase was recorded as a positive event for the presence of P. falciparum blood stage infection. The time to first malaria infection is expressed in terms of rate of first malaria infection, that is, the number of malaria infection events reported over the time period elapsed until the event occurred (i.e. events per Persons Year at Risk \[PYAR\]) for each group. |
| Secondary | Number of Participants With Serious Adverse Events (SAEs) | From first dose to end of study, up to 65 weeks. | An adverse event is any untoward medical occurrence in a study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product, or temporally associated with a study procedure. A serious adverse event is any adverse event that: * Resulted in death, * Was life-threatening, * Resulted in disability/incapacity, * Required hospitalization or prolongation of existing hospitalization, * Resulted in disability/incapacity. * Resulted in a congenital anomaly and / or birth defect. |
| Secondary | Number of Participants With Solicited Local and Systemic Adverse Events (AEs) | Within 7 days after each vaccination. | Solicited AEs are pre-specified local and systemic AEs that occur relatively more frequently or are known to be associated with immunization, which are monitored actively as potential indicators of vaccine reactogenicity. Solicited local and general AEs were collected among RTS,S vaccinated groups in the first 50 participants enrolled in Groups 1 and 2 and all participants enrolled in Group 3 (Reactogenicity Cohort) for seven days (day of vaccination and six subsequent days) after each dose of vaccine. Local (injection site) adverse events are defined as: * Pain at injection site * Swelling at injection site Systemic adverse events are defined as: * Fever (temperature ≥ 37.5°C) * Headache * Gastrointestinal problems * Fatigue * Muscle ache |
| Secondary | Number of Participants With Unsolicited Adverse Events | Within 28 days after each vaccination. | An adverse event is defined as any untoward medical occurrence in a study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product, or temporally associated with a study procedure. Unsolicited AEs are any AEs reported spontaneously by the participant, observed by the study staff during study visits or those identified during review of medical records or source documents. Solicited AEs with an onset after the seven-day solicitation period were also considered unsolicited AEs. |
| Secondary | Geometric Mean Titer of Anti-Plasmodium Falciparum Circumsporozoite (CS) Antibodies in Groups 1, 2, and 3 | Baseline, Day 29 (28 days after first vaccination), Day 57 (28 days after second vaccination), Day 197 (24 weeks after second vaccination), and Day 225 (28 days after third vaccination) | The RTS,S antigen consists of sequences of both the P. falciparum circumsporozoite protein and hepatitis B surface antigen. Antibody levels against P. falciparum circumsporozoite (CS) protein central repeat region (NANP) were measured from blood samples of participants in Groups 1, 2 and 3 using standard enzyme-linked immunosorbent assays (ELISA) at Walter Reed Army Institute of Research (WRAIR), in Silver Spring, MD, United States. |
| Secondary | Anti-Plasmodium Falciparum Circumsporozoite (CS) Antibody Avidity Index in Groups 1, 2, and 3 | Baseline, Day 29 (28 days after first vaccination), Day 57 (28 days after second vaccination), Day 197 (24 weeks after second vaccination), and Day 225 (28 days after third vaccination) | Antibody levels against P. falciparum circumsporozoite (CS) protein central repeat region (NANP) measured by standard enzyme-linked immunosorbent assays (ELISA) for participants in Groups 1, 2 and 3. To measure antibody-antigen avidity (strength of binding) ELISA was performed with and without urea (to dissociate the antigen-antibody complex). The avidity index is calculated by dividing the serum titer obtained in the presence of the urea by the serum titer without urea. |
| Secondary | Geometric Mean Titer (GMT) of Anti-Hepatitis B Surface Antigen (HBsAg) Antibodies in Groups 1, 2, and 3 | Baseline, Day 29 (28 days after first vaccination) and Day 225 (28 days after third vaccination) | The RTS,S vaccine antigen consists of sequences of both the P. falciparum circumsporozoite protein and hepatitis B surface antigen, hence anti-HBsAg antibodies were also measured. Anti-hepatitis B surface antigen antibodies were assessed at the International AIDS Vaccine Initiative Human Immunology Laboratory (IAVI-HIL) at Imperial College, London, UK, using a commercially available ELISA kit. |
Source ClinicalTrials.gov
Outcomes8
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Time to First PCR-detectable Malaria Infection During the Active Detection of Infection (ADI) Phase in Groups 1 and 4 | The active detection of infection phase began 2 weeks after the third vaccination (approximately week 30) for up to 35 weeks. Participants provided blood samples every 21 days during the ADI phase for PCR assays. | The primary endpoint was pre-specified to be analyzed in Groups 1 and 4 only. The According to Protocol (ATP) cohort for efficacy includes all participants in the TVC with no major protocol deviations that could potentially interfere with the efficacy assessment of the study vaccine and who contributed to the time at risk starting 14 days after the third dose. | Events per person year at risk | NUMBER |
| SECONDARY | Time to First PCR-detectable Malaria Infection During the Active Detection of Infection Phase in Groups 2 and 5 | The active detection of infection phase began 2 weeks after the third vaccination (approximately week 30) for up to 35 weeks. Participants provided blood samples every 21 days during the ADI phase for PCR assays. | This endpoint was pre-specified to be analyzed in Groups 2 and 5 only. The ATP cohort for efficacy includes all participants in the TVC with no major protocol deviations that could potentially interfere with the efficacy assessment of the study vaccine and who contributed to the time at risk starting 14 days after the third dose. | Events per person year at risk | NUMBER |
| SECONDARY | Number of Participants With Serious Adverse Events (SAEs) | From first dose to end of study, up to 65 weeks. | The Safety analysis population includes all enrolled participants who received at least one vaccination and for whom any safety data were available. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Number of Participants With Solicited Local and Systemic Adverse Events (AEs) | Within 7 days after each vaccination. | The Reactogenicity Cohort (the first 50 participants in Groups 1 and 2 and all participants in Group 3) with available reactogenicity data.~Participants in Groups 4 and 5 did not have solicited AEs collected. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Number of Participants With Unsolicited Adverse Events | Within 28 days after each vaccination. | All enrolled participants who received at least one vaccination and for whom any safety data were available. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Geometric Mean Titer of Anti-Plasmodium Falciparum Circumsporozoite (CS) Antibodies in Groups 1, 2, and 3 | Baseline, Day 29 (28 days after first vaccination), Day 57 (28 days after second vaccination), Day 197 (24 weeks after second vaccination), and Day 225 (28 days after third vaccination) | The ATP cohort for immunogenicity included all participants in the TVC who received all vaccinations according to protocol procedures and within the protocol specified intervals, performed blood samplings for immunogenicity according to protocol intervals, and did not use any medication or blood products forbidden by the protocol and did not have any reported underlying medical condition influencing immune responses. Participants with available data at each time point. | titer | GEOMETRIC_MEAN |
| SECONDARY | Anti-Plasmodium Falciparum Circumsporozoite (CS) Antibody Avidity Index in Groups 1, 2, and 3 | Baseline, Day 29 (28 days after first vaccination), Day 57 (28 days after second vaccination), Day 197 (24 weeks after second vaccination), and Day 225 (28 days after third vaccination) | The according to protocol (ATP) cohort for immunogenicity; participants with available data at each time point. | ratio | MEAN |
| SECONDARY | Geometric Mean Titer (GMT) of Anti-Hepatitis B Surface Antigen (HBsAg) Antibodies in Groups 1, 2, and 3 | Baseline, Day 29 (28 days after first vaccination) and Day 225 (28 days after third vaccination) | ATP Cohort for Immunogenicity with available data at each time point. | titer | GEOMETRIC_MEAN |
Source ClinicalTrials.gov
Results by group59
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Time to First PCR-detectable Malaria Infection During the Active Detection of Infection (ADI) Phase in Groups 1 and 4 | Group 1: Positive Parasitemia; Anti-malarial Treatment + RTS,S/AS01E Vaccine | 1.01 | Events per person year at risk | ||
| Time to First PCR-detectable Malaria Infection During the Active Detection of Infection (ADI) Phase in Groups 1 and 4 | Group 4: Positive Parasitemia; Anti-malarial Treatment + Rabies Vaccine | 1.49 | Events per person year at risk | ||
| Time to First PCR-detectable Malaria Infection During the Active Detection of Infection Phase in Groups 2 and 5 | Group 2: No Parasitemia; Anti-malarial Prophylaxis + RTS,S/AS01E Vaccine | 0.77 | Events per person year at risk | ||
| Time to First PCR-detectable Malaria Infection During the Active Detection of Infection Phase in Groups 2 and 5 | Group 5: No Parasitemia, Anti-malarial Prophylaxis + Rabies Vaccine | 0.62 | Events per person year at risk | ||
| Number of Participants With Serious Adverse Events (SAEs) | Group 1: Positive Parasitemia; Anti-malarial Treatment + RTS,S/AS01E Vaccine | 3 | Participants | ||
| Number of Participants With Serious Adverse Events (SAEs) | Group 2: No Parasitemia; Anti-malarial Prophylaxis + RTS,S/AS01E Vaccine | 2 | Participants | ||
| Number of Participants With Serious Adverse Events (SAEs) | Group 3: Positive Parasitemia; RTS,S/AS01E Vaccine | 1 | Participants | ||
| Number of Participants With Serious Adverse Events (SAEs) | Group 4: Positive Parasitemia; Anti-malarial Treatment + Rabies Vaccine | 1 | Participants | ||
| Number of Participants With Serious Adverse Events (SAEs) | Group 5: No Parasitemia, Anti-malarial Prophylaxis + Rabies Vaccine | 3 | Participants | ||
| Number of Participants With Solicited Local and Systemic Adverse Events (AEs) | Group 1: Positive Parasitemia; Anti-malarial Treatment + RTS,S/AS01E Vaccine | Local Solicited AEs | 24 | Participants |
1 to 10 of 59Source ClinicalTrials.gov
See all 59 results by groupParticipant flow20
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Group 1: Positive Parasitemia; Anti-malarial Treatment + RTS,S/AS01E Vaccine | 164 | |
| Overall Study | STARTED | Group 2: No Parasitemia; Anti-malarial Prophylaxis + RTS,S/AS01E Vaccine | 128 | |
| Overall Study | STARTED | Group 3: Positive Parasitemia; RTS,S/AS01E Vaccine | 36 | |
| Overall Study | STARTED | Group 4: Positive Parasitemia; Anti-malarial Treatment + Rabies Vaccine | 164 | |
| Overall Study | STARTED | Group 5: No Parasitemia, Anti-malarial Prophylaxis + Rabies Vaccine | 128 | |
| Overall Study | Received Study Vaccination | Group 1: Positive Parasitemia; Anti-malarial Treatment + RTS,S/AS01E Vaccine | 160 | |
| Overall Study | Received Study Vaccination | Group 2: No Parasitemia; Anti-malarial Prophylaxis + RTS,S/AS01E Vaccine | 124 | |
| Overall Study | Received Study Vaccination | Group 3: Positive Parasitemia; RTS,S/AS01E Vaccine | 35 | |
| Overall Study | Received Study Vaccination | Group 4: Positive Parasitemia; Anti-malarial Treatment + Rabies Vaccine | 159 | |
| Overall Study | Received Study Vaccination | Group 5: No Parasitemia, Anti-malarial Prophylaxis + Rabies Vaccine | 127 |
1 to 10 of 20Source ClinicalTrials.gov
See all 20 participant flowAdverse events630
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Anaemia | Blood and lymphatic system disorders | Group 1: Positive Parasitemia; Anti-malarial Treatment + RTS,S/AS01E Vaccine | 3 | 160 | |
| other | Anaemia | Blood and lymphatic system disorders | Group 2: No Parasitemia; Anti-malarial Prophylaxis + RTS,S/AS01E Vaccine | 1 | 124 | |
| other | Anaemia | Blood and lymphatic system disorders | Group 3: Positive Parasitemia; RTS,S/AS01E Vaccine | 0 | 35 | |
| other | Anaemia | Blood and lymphatic system disorders | Group 4: Positive Parasitemia; Anti-malarial Treatment + Rabies Vaccine | 1 | 159 | |
| other | Anaemia | Blood and lymphatic system disorders | Group 5: No Parasitemia, Anti-malarial Prophylaxis + Rabies Vaccine | 0 | 127 | |
| other | Eosinophilia | Blood and lymphatic system disorders | Group 1: Positive Parasitemia; Anti-malarial Treatment + RTS,S/AS01E Vaccine | 0 | 160 | |
| other | Eosinophilia | Blood and lymphatic system disorders | Group 2: No Parasitemia; Anti-malarial Prophylaxis + RTS,S/AS01E Vaccine | 0 | 124 | |
| other | Eosinophilia | Blood and lymphatic system disorders | Group 3: Positive Parasitemia; RTS,S/AS01E Vaccine | 0 | 35 | |
| other | Eosinophilia | Blood and lymphatic system disorders | Group 4: Positive Parasitemia; Anti-malarial Treatment + Rabies Vaccine | 0 | 159 | |
| other | Eosinophilia | Blood and lymphatic system disorders | Group 5: No Parasitemia, Anti-malarial Prophylaxis + Rabies Vaccine | 1 | 127 |
1 to 10 of 630Source ClinicalTrials.gov
See all 630 adverse eventsAdverse event totals15
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Group 1: Positive Parasitemia; Anti-malarial Treatment + RTS,S/AS01E Vaccine | 1 | 164 |
| Total, all-cause mortality | Group 2: No Parasitemia; Anti-malarial Prophylaxis + RTS,S/AS01E Vaccine | 0 | 128 |
| Total, all-cause mortality | Group 3: Positive Parasitemia; RTS,S/AS01E Vaccine | 0 | 36 |
| Total, all-cause mortality | Group 4: Positive Parasitemia; Anti-malarial Treatment + Rabies Vaccine | 0 | 164 |
| Total, all-cause mortality | Group 5: No Parasitemia, Anti-malarial Prophylaxis + Rabies Vaccine | 0 | 128 |
| Total, other adverse events | Group 1: Positive Parasitemia; Anti-malarial Treatment + RTS,S/AS01E Vaccine | 111 | 160 |
| Total, other adverse events | Group 2: No Parasitemia; Anti-malarial Prophylaxis + RTS,S/AS01E Vaccine | 96 | 124 |
| Total, other adverse events | Group 3: Positive Parasitemia; RTS,S/AS01E Vaccine | 25 | 35 |
| Total, other adverse events | Group 4: Positive Parasitemia; Anti-malarial Treatment + Rabies Vaccine | 110 | 159 |
| Total, other adverse events | Group 5: No Parasitemia, Anti-malarial Prophylaxis + Rabies Vaccine | 92 | 127 |
1 to 10 of 15Source ClinicalTrials.gov
See all 15 adverse event totalsPapers17
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
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