Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Malaria Vaccine RTS,S/AS01E · 1 trial · 1 indication
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.
| Arm | Type | Description |
|---|---|---|
| Group 1: Positive Parasitemia; Anti-malarial treatment + RTS,S/AS01E Vaccine | EXPERIMENTAL | Participants with detectable P. falciparum parasitemia at baseline received anti-malarial treatment with dihydroartemisinin-piperaquine (DHA/Pip) plus low dose primaquine (LD PQ) 4 weeks prior to the first vaccination and another course of DHA/Pip plus LD PQ two weeks before the second vaccination. One week before the third vaccination, a course of artemether/lumefantrine (A/L) plus LD PQ was administered. Participants received 3 vaccinations with malarial vaccine RTS,S/AS01E by intramuscular injection given on a 0, 1, and 7 month schedule with the final dose being 1/5 of the dose of the first two immunizations. |
| Group 2: No Parasitemia; Anti-malarial Prophylaxis + RTS,S/AS01E Vaccine | EXPERIMENTAL | Participants with no detectable P. falciparum parasitemia at baseline received anti-malarial prophylaxis with DHA/Pip plus LD PQ 4 weeks prior to the first vaccination and a 2nd course of DHA/Pip plus LD PQ 2 weeks before the second vaccination. One week before the third vaccination, a course of A/L plus LD PQ was administered. Participants received 3 vaccinations with malarial vaccine RTS,S/AS01E by intramuscular injection given on a 0, 1, and 7 month schedule with the final dose being 1/5 of the dose of the first two immunizations. |
| Group 3: Positive Parasitemia; RTS,S/AS01E Vaccine | EXPERIMENTAL | Participants with detectable P. falciparum parasitemia at baseline did not receive any anti-malarial medications to clear parasites. Participants received 3 vaccinations with malarial vaccine RTS,S/AS01E by intramuscular injection given on a 0, 1, and 7 month schedule with the final dose being 1/5 of the dose of the first two immunizations. This group is included only for immunological assessment and not for vaccine efficacy. |
| Group 4: Positive Parasitemia; Anti-malarial Treatment + Rabies Vaccine | PLACEBO_COMPARATOR | Participants with detectable P. falciparum parasitemia at baseline received anti-malarial treatment with dihydroartemisinin-piperaquine (DHA/Pip) plus low dose primaquine (LD PQ) 4 weeks prior to the first vaccination and another course of DHA/Pip plus LD PQ two weeks before the second vaccination. One week before the third vaccination, a three-day course of artemether/lumefantrine (A/L) plus LD PQ was administered. Participants received 3 vaccinations of Abhayrab rabies vaccine on a 0, 1, 7 month schedule. |
| Group 5: No Parasitemia, Anti-malarial Prophylaxis + Rabies Vaccine | PLACEBO_COMPARATOR | Participants with no detectable P. falciparum parasitemia at baseline received anti-malarial prophylaxis with DHA/Pip plus LD PQ 4 weeks prior to the first vaccination and a 2nd course of DHA/Pip plus LD PQ 2 weeks before the second vaccination. One week before the third vaccination, a course of A/L plus LD PQ was administered. Participants received 3 vaccinations of Abhayrab rabies vaccine on a 0, 1, 7 month schedule. |
| Name | Type | Description |
|---|---|---|
| Malaria Vaccine RTS,S/AS01E | BIOLOGICAL | RTS,S/AS01E vaccine 0.5 mL, containing 25 μg protein comprising circumsporozoite protein (CS) and hepatitis B surface antigen (RTS,S), 25 μg monophosphoryl lipid (AMPL), 25 μg Quillaja saponaria 21 (QS21) in a liposomal formulation) for the first two immunizations. One-fifth dose RTS,S/AS01E vaccine was used for the third immunization. |
| Abhayrab rabies vaccine | BIOLOGICAL | Abhayrab rabies vaccine, 0.5 mL, contains 2.5 IU rabies antigen. |
| Dihydroartemisinin-piperaquine (DHA/Pip) | DRUG | Dihydroartemisinin (120 mg or 160 mg based on weight) and piperaquine tetraphosphate (960 mg or 1280 mg based on weight) mg) administered once a day for 3 days. DHA/Pip is a long acting anti-malarial used to clear asexual stage and young gametocyte parasites. |
| Artemether / Lumefantrine | DRUG | Artemether (80 mg) and lumefantrine (480 mg) administered twice a day for 3 days. Coartem is a short-acting artemisinin combination therapy used to provide clearance of blood stage parasites in order to establish a clean baseline for determination of vaccine efficacy. |
| Primaquine | DRUG | One dose of 15 mg primaquine. Low dose primaquine (LD PQ) is used to clear mature gametocytes of P. falciparum. |
Inclusion Criteria: * Provision of signed or thumb printed and dated informed consent form * Stated willingness to comply with all study procedures and availability for the duration of the study * Male or female between 18 and 55 years of age, inclusive * In good general health as evidenced by medi...