NCT02992119

Malaria Vaccine Safety and Immunogenicity Study in Healthy Adults

Safety and Immunogenicity Evaluation of the Malaria Vaccine, RTS,S/AS01, in Healthy Thai Adults

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 193 (actual)
• Sponsor: University of Oxford · Academic / Other
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

Targeted malaria elimination (TME), which comprises appropriate case management by village health workers, vector control and mass drug administration, is currently being implemented through pilot projects in selected villages in the Greater Mekong Subregion (GMS) and the scale-up of the intervention to the regional level are underway. Based on mathematical modelling, extending the post-TME parasitaemia-free period in the majority of villagers for as short as 200 days will substantially increase the chances of achieving the interruption of malaria transmission. Immunogenicity of RTS,S is greater in older children, and the short term malaria protective effect is stronger than the overall effect assessed over 1-2 years. Addition of mass RTS,S/AS01E vaccination to the TME arsenal could provide this much needed additional protection. Currently there are no safety and immunogenicity data for the use of RTS,S/AS01 in Asian populations. This trial will generate the required data for the use of this vaccine in Asian populations. For integration with the current TME activities, which provide mass drug administrations at months M0, M1, and M2, it would be most efficient and practical to provide the vaccine at the same intervals. To address a two round intervention (M0, M2) where a three round intervention is not feasible, one study arm will look at the immune response generated by only two doses of vaccine and antimalarial medications. Recent evidence suggests that a vaccination schedule which includes a fractional dose of RTS,S/AS01 (1/5th of the standard dose) could be similarly or more protective than a schedule with three standard full doses, while requiring less vaccine and resources. The trial therefore includes study arms which will assess the safety and immunogenicity of fractional dose schedules. Each participant will be randomized into one of the following study arms in a ratio of 20:20:30:30:30:30:30, as follows: * RTS,S/AS01B Fractional dose group (Group 1) * Double RTS,S /AS01E Fractional dose group (Group 2) * RTS,S/AS01E Standard dose group (Group 3) * RTS,S/AS01E + DHA-PIP+PQ Standard dose group (Group 4) * RTS,S/AS01E Fractional dose group (Group 5) * RTS,S/AS01E + DHA-PIP+PQ Fractional dose group (Group 6) * RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose group (Group 7)

Detailed description

This is a randomized, open-label, single centre, Phase 2 trial of RTS,S/AS01 in healthy Thai adults. Screening and eligibility assessment (Screening visit) All potential volunteers will have a screening visit, which may take place up to 30 days prior to enrolment. Once informed consent is given, a screening number will be assigned in sequential order. Screening numbers will be issued consecutively (e.g. A-01, A-02, A-03…). Enrolment, baseline assessment, regimen allocation, and first vaccination (Month 0 / Day 0 visit; Baseline visit) All inclusion and exclusion criteria will be checked before enrolment in the study. Physical examination will be performed. Any new medical issues or symptoms that have arisen will be assessed. Blood will be collected for baseline parasite microscopy, haemoglobin and biochemistry. Participants with parasitaemia or anaemia will be treated according to national guidelines. Blood will be collected and stored for measurement of antibodies against P. falciparum circumsporozoite (anti-CS antibody) until shipment to the reference laboratory. Urine will be collected from women of child-bearing age for immediate pregnancy test. If all inclusion criteria are fulfilled and none of the exclusion criteria apply, the patient will be enrolled into the study and a CRF specific to each participant completed. Regimen allocation and administration of the vaccine(s) will be on Day 0. The randomization lists will be prepared by MORU. Randomization numbers will be generated in blocks, for the 7 intervention arms in a ratio of 20:20:30:30:30:30:30, as follows: Each participant will be randomized into one of the following study arms Group 1: RTS,S/AS01B Fractional dose group Month 0 and Month 1 will receive RTS,S/AS01B full dose Month 2 will receive RTS,S/AS01B fractional dose (1/5th dose) Group 2: RTS,S/AS01E Fractional dose group Month 0 and Month 1will receive a double dose of RTS,S/AS01E full dose Month 2 will receive a double dose of RTS,S/AS01E fractional dose (1/5th dose) Group 3: RTS,S/AS01E Full dose group Month 0, Month 1 and Month 2 will receive RTS,S/AS01E full dose Group 4: RTS,S/AS01E + DHA-PIP+PQ Full dose group Month 0, Month 1 and Month 2 will receive RTS,S/AS01E full dose + DHA-PIP+PQ Group 5: RTS,S/AS01E Fractional dose group Month 0 and Month 1 will receive RTS,S/AS01E full dose Month 2 will receive RTS,S/AS01E fractional dose (1/5th dose) Group 6: RTS,S/AS01E + DHA-PIP+PQ Fractional dose group Month 0 and Month 1 will receive RTS,S/AS01E full dose + DHA-PIP+PQ Month 2 will receive RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ Group 7: RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose group Month 0 will receive RTS,S/AS01E full dose + DHA-PIP+PQ Month 2 will receive RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ RTS,S/AS01B = Standard dose RTS,S/AS01B: 50µg RTS,S + standard dose AS01B RTS,S/AS01E = Standard dose RTS,S/AS01E: 25µg RTS,S + standard dose AS01E DHA-PIP = Dihydroartemisinin/piperaquine PQ = Primaquine Study participants will be assigned the next available randomization number on the list, and thus will be randomly allocated to Group 1, 2, 3, 4, 5, 6 or 7. Subsequent vaccination visits (Month 1 / Day 0 and Month 2 / Day 0 visits) Subsequent vaccination visits will be done according to the schedule of procedures. Physical examination will be performed. Any new medical issues or symptoms that have arisen will be assessed. Blood will be collected for parasite microscopy, haemoglobin and biochemistry. Participants with parasitaemia or anaemia will be treated according to national guidelines. Blood will be collected and stored for measurement of antibodies against P. falciparum circumsporozoite (anti-CS antibody) until shipment to the reference laboratory. Urine will be collected from women of child-bearing age for immediate pregnancy test. Before vaccination, the on-going eligibility of the volunteer will be reviewed. All participants will attend the clinic for vaccination visits, will be observed closely for at least 30 minutes following the administration of each study vaccine, and will receive a paper diary card for recording solicited AEs, as described above. Information will be recorded in the CRF for subsequent vaccination visits.

Conditions

• Malaria Vaccine

Interventions

Type	Name	Description
BIOLOGICAL	RTS,S/AS01B Fractional dose	RTS,S/AS01B standard dose at Month 0 and Month 1 + RTS,S/AS01B fractional dose (1/5th dose) at Month 2.
BIOLOGICAL	Double RTS,S/AS01E Fractional dose	A double dose of RTS,S/AS01E standard dose at Month 0 and Month 1 + a double dose of RTS,S/AS01E fractional dose (1/5th dose) at Month 2.
BIOLOGICAL	RTS,S/AS01E Standard dose	RTS,S/AS01E standard dose at Month 0, Month 1 and Month 2.
BIOLOGICAL	RTS,S/AS01E + DHA-PIP+PQ Standard dose	RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0, Month 1 and Month 2
BIOLOGICAL	RTS,S/AS01E Fractional dose	RTS,S/AS01E standard dose at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) at Month 2.
BIOLOGICAL	RTS,S/AS01E + DHA-PIP+PQ Fractional dose	RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2.
BIOLOGICAL	RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose	RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2

Timeline

• Start date: 2017-06-04
• Primary completion: 2018-02-20
• Completion: 2018-02-20
• First posted: 2016-12-14
• Last updated: 2022-03-31
• Results posted: 2019-07-29

Locations

1 site across 1 country: Thailand