Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
RTS, S/AS02D and RTS, S/AS02A · 8 trials · 2 indications
Occurrence of P. falciparum parasitemia (defined by a positive blood slide) following sporozoite challenge. Post-challenge, parasitemia was determined by microscopy of Giemsa-stained thick blood films (smear). Microscopy was performed on thick smears using a validated standard operation procedure. P. falciparum infection was defined as asexual blood stage P. falciparum parasite density greater than (\>) 0 detected by blood slide reading. For the analysis of proportion affected (relative risk), all subjects included in the analysis were considered at risk of infection and no censoring or elimination was applied for subjects not completing the entire protocol-defined post-challenge follow-up (Day 50 - 28 days post challenge).
The primary case definition is: Plasmodium (P.) falciparum asexual parasitemia greater than (\>)5000 parasites/microliters (μl) and presence of fever (axillary temperature greater than or equal to \[≥\]37.5°C) at the time of presentation and occurring in a child who is unwell and brought for treatment to a healthcare facility. The incidence is expressed as a person year rate for each group (n/T), representing the number of events (n) reported over the risk period, which was counted in days and expressed as person years at risk (T). The objective of this endpoint was to demonstrate the superiority of a Fx012-14-mFxD Group compared to a standard schedule of RTS,S/AS01E with three full doses (R012-20+R012-14 Group) in terms of vaccine efficacy. This analysis was reported for the R012-20+R012-14 Group (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 group until Month 14.
Occurrence of P. falciparum parasitemia (defined by a positive blood slide) following sporozoite challenge. Post-challenge, parasitemia was determined by microscopy of Giemsa-stained thick blood films (smear). Microscopy was performed on thick smears using a validated standard operation procedure. For the analysis of proportion affected (relative risk), all subjects included in the analysis were considered at risk of infection and no censoring or elimination was applied for subjects not completing the entire protocol defined post challenge follow-up (Day 315 - 28 days post challenge).
Concentrations were expressed as geometric mean concentrations (GMCs) in milli-international unit per milliliter (mIU/mL). The cut-off of the assay was the seroprotection cut-off of 10 mIU/mL. Month 3 results are the specific results for this primary outcome measure.
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in international unit per milliliter (IU/mL). The cut-off of the assay was the seroprotection cut-off of 0.1 IU/mL. Month 3 results are the specific results for this primary outcome measure.
Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in international unit per milliliter (IU/mL). The cut-off of the assay was the seroprotection cut-off of 0.1 IU/mL. Month 3 results are the specific results for this primary outcome measure.
Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per milliliter (µg/mL). The cut-off of the assay is the seroprotection cut-off value of 0.15 µg/mL. Month 3 results are the specific results for this primary outcome measure.
Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA unit per milliliter (EL.U/mL). The cut-off of the assay was the seropositivity cut-off of 15 EL.U/mL. Month 3 results are the specific results for this primary outcome measure.
The seroprotection cut-off value was 10 milli-international units per milliliter (mIU/mL). Blood samples were collected prior to vaccination at Week 0 (PRE), at Month 2 and at Month 3. Month 3 results are the specific results for this primary outcome measure.
Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). The seroprotection cut-off value was 0.1 international unit per milliliter (IU/mL). Blood samples were collected prior to vaccination at Week 0 (PRE), and at Month 3. Month 3 results are the specific results for this primary outcome measure.
Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). The seroprotection cut-off value was 0.1 international unit per milliliter (IU/mL). Blood samples were collected prior to vaccination at Week 0 (PRE), and at Month 3. Month 3 results are the specific results for this primary outcome measure.
Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). The seroprotection cut-off value was 0.15 microgram per milliliter (µg/mL). Blood samples were collected prior to vaccination at Week 0 (PRE), and at Month 3. Month 3 results are the specific results for this primary outcome measure.
Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). The seropositivity cut-off value was 15 ELISA units per milliliter (EL.U/mL). Blood samples were collected prior to vaccination at Week 0 (PRE), and at Month 3. Month 3 results are the specific results for this primary outcome measure.
SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.
| Arm | Type | Description |
|---|---|---|
| Groups 1 to 3 | EXPERIMENTAL | Participants receive 3 doses of RTS,S/AS01E vaccine on Day 1, Month 1, and Month 2. |
| Groups 4 and 5 | EXPERIMENTAL | Participants receive 3 doses of RTS,S/AS01E vaccine on Day 1, Month 1, and Month 7. |
| Groups 6 and 7 | EXPERIMENTAL | Participants receive 3 doses of RTS,S/AS01E vaccine on Day 1, Month 2, and Month 7. |
| P-Fx group | EXPERIMENTAL | Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge. |
| NP-Fx group | EXPERIMENTAL | Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and not protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge. |
| InfectivityCtrl group | NO_INTERVENTION | Healthy subjects, between and including 18 and 55 years of age, who did not receive, in the current study, any immunization but underwent sporozoite challenge. |
| R012-20 Group | EXPERIMENTAL | Participants will receive a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2 and at Month 20. |
| R012-14-mD Group | EXPERIMENTAL | Participants will receive a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2 and yearly full doses at Month 14, Month 26 and Month 38. |
| Fx012-14-mFxD Group | EXPERIMENTAL | Participants will receive a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 2 and yearly fractional doses at Month 14, Month 26 and Month 38. |
| Fx017-mFxD Group | EXPERIMENTAL | Participants will receive a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 7 and yearly fractional doses at Month 20 and Month 32. |
| Control Group | EXPERIMENTAL | Participants will receive rabies vaccine at Month 0, Month 1 and Month 2. |
| AduFx Group | ACTIVE_COMPARATOR | Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01B full dose at Month 0 and Month 1 and 1/5th of RTS,S/AS01B full dose at Month 7, and underwent sporozoite challenge. |
| 2PedFx Group | EXPERIMENTAL | Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01E double dose at Month 0 and Month 1, and 1/5th of double dose RTS,S/AS01E at Month 7, and underwent sporozoite challenge. |
| PedFx Group | EXPERIMENTAL | Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01E full dose at Month 0 and Month 1, and 1/5th of RTS,S/AS01E full dose at Month 7, and underwent sporozoite challenge. |
| Adu2Fx Group | EXPERIMENTAL | Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01B full dose at Month 0 and 1/5th of RTS,S/AS01B full dose at Month 1 and Month 7, and underwent sporozoite challenge. |
| Adu1Fx Group | ACTIVE_COMPARATOR | Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01B full dose at Month 0 and 1/5th of RTS,S/AS01B full dose administered at Month 7, and underwent sporozoite challenge. |
| RTS,S/AS02D Group | EXPERIMENTAL | Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh. |
| Engerix-B Group | ACTIVE_COMPARATOR | Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.. |
| Name | Type | Description |
|---|---|---|
| RTS,S/AS01E vaccine | BIOLOGICAL | RTS,S/AS01E vaccine will be administered intramuscularly. |
| RTS,S/AS01E (SB257049) | BIOLOGICAL | Subjects from the P-Fx and NP-Fx groups will receive one Fx booster dose of RTS,S/AS01E at Day 1. |
| RTS,S/AS01E (Full dose) | BIOLOGICAL | Participants will receive intramuscular injection of RTS,S/AS01E (full dose: 0.5 ml). |
| RTS,S/AS01E (1/5th dose) | BIOLOGICAL | Participants will receive intramuscular injection of RTS,S/AS01E (1/5th dose: 0.1 ml). |
| Rabies vaccine | BIOLOGICAL | Participants will receive intramuscular injection of rabies vaccine (0.1 ml). |
| RTS,S/AS01E | BIOLOGICAL | Subjects will receive intramuscular injection of RTS,S/AS01E. |
| RTS,S/AS01B | BIOLOGICAL | Subjects will receive intramuscular injection of RTS,S/AS01B. |
| Sporozoite-infected mosquitoes challenge. | PROCEDURE | Mosquitoes infected approximately 2-3 weeks earlier that are likely to contain sporozoites in their salivary glands will be allowed to feed on the subjects. For each subject, five mosquitoes will be allowed to feed over five minutes, after which they will be dissected to confirm how many were infected, and the salivary glands scored. If required additional mosquitoes will be allowed to feed until a total of five infected mosquitoes with a minimum of 2+ salivary gland scores have fed. The challenge occurs approximately 90 days (three months) after the last vaccination. Subjects will be monitored during 28 days after having bitten by mosquitoes and when parasites are found in their blood, they will be treated with appropriate anti-malarial drugs. |
| RTS,S/AS02D | BIOLOGICAL | 3-dose intramuscular injection in the thigh |
| Engerix-B® | BIOLOGICAL | 3-dose intramuscular injection in the thigh. |
| TETRActHib™ | BIOLOGICAL | 3-dose intramuscular injection in the thigh. |
| RTS,S/AS02A | BIOLOGICAL | - |
| RTS,S/AS02D and RTS,S/AS02A | BIOLOGICAL | - |
Inclusion Criteria: 1. Healthy male or female participants aged 5 to 60 months at the time of the first vaccination, who have previously completed the World Health Organization (WHO) Expanded Programme on Immunization (EPI) vaccinations or for younger infants have received all required vaccinations...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| GSK plc Sponsored ADR | GSK | 3 | PHASE3 | Tafenoquine, Primaquine, Chloroquine |
| Novartis AG Sponsored ADR | NVS | 1 | PHASE2 | INE963, KAE609, KLU156 |
| 60 Degrees Pharmaceuticals, Inc. | SXTP | 1 | PHASE2 | Tafenoquine |
RTS,S/AS02D and RTS,S/AS02A are investigational vaccines being studied for the prevention of malaria. They are being evaluated in children and infants living in malaria-endemic regions of Africa, including Mozambique, Ghana, and Kenya. The vaccines are administered by intramuscular injection according to a 0, 1, 2 month schedule.
RTS,S/AS02D and RTS,S/AS02A are candidate malaria vaccines. They are designed to induce an immune response against the malaria parasite. The vaccines are being studied for their ability to provide protection against malaria infection in young children and infants.
RTS,S/AS02D and RTS,S/AS02A are being developed by GSK plc, a biopharmaceutical company listed on the stock exchange under the ticker GSK. The vaccines are part of GSK's malaria vaccine research program and are being tested in clinical trials in multiple African countries.
RTS,S/AS02D and RTS,S/AS02A are in Phase 2 clinical development. They are investigational vaccines and have not been approved for public use. The vaccines are being studied for their safety, immunogenicity, and efficacy in preventing malaria in children and infants.
RTS,S/AS02D and RTS,S/AS02A have been studied in several clinical trials. Key trials include NCT00197028, which examined safety and immune responses in infants in Mozambique, and NCT00197041, which evaluated safety, immunogenicity, and efficacy in children aged 1 to 4 years. Another trial, NCT03276962, studied different dosing schedules in children 5-17 months of age in Ghana and Kenya.
RTS,S/AS02D and RTS,S/AS02A are also known as the RTS,S/AS01E vaccine. These names refer to the same candidate malaria vaccine developed by GSK plc. The vaccine is being evaluated in clinical trials for its ability to protect against malaria in children and infants living in endemic regions.