This is a randomized, open label, single centre, Phase 2 study.
Screening and eligibility assessment (Screening visit) All potential volunteers will have a screening visit, which may take place up to 7 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. R21-001, R21-002, R21-003, …)
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 P. falciparum testing, 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-circumsporozoite antibody) until shipment to the reference laboratory. Urine will be collected from women of child-bearing age for immediate pregnancy test.
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 P. falciparum testing, haemoglobin and biochemistry. Blood will be collected and stored for measurement of antibodies against P. falciparum circumsporozoite (anti-circumsporozoite 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 case record form (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 Mahidol-Oxford Tropical Medicine Research Unit (MORU).
Randomization numbers will be generated in blocks, for the 3 study arms in a ratio of 5:5:2, as follows:
* R21/MatrixM + DHA-PIP+PQ (Group 1)
* R21/MatrixM alone (Group 2)
* DHA-PIP+PQ alone (Group 3)
Study participants will be assigned the next available randomization number on the list, and thus will be randomly allocated to Group 1, 2, or 3. This is an open-label study. Participants and clinical investigators will not be blinded to group allocation.
Subjects (in group 1 and 2) will then be vaccinated by intramuscular (IM) needle injection into the deltoid region of the arm. Subjects in Groups 1 and 3 will also receive anti-malarial medications.
The study participants will be observed closely for at least 30 minutes following the administration of each study vaccine, with appropriate medical treatment readily available in case of an anaphylactic reaction.
Subsequent vaccination visits (Month 1 / Day 0 and Month 2 / Day 0 visits)
Physical examination will be performed. Any new medical issues or symptoms that have arisen will be assessed. Blood will be collected for P. falciparum testing. 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-circumsporozoite) 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.
Follow up assessments
Follow-up assessments (visits not involving vaccination) will be done at month 3 and month 6 after the first vaccination.
Blood tests
Blood will be drawn at the time points indicated in the schedule of procedures and the following laboratory assays performed:
At screening:
* Haematology: haemoglobin (Hb), leukocytes (white blood cells \[WBC\]) and platelets (PLT).
* Biochemistry: alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine (CREA).
* Diagnostic serology: HBsAg, HCV antibodies, HIV antibodies (Counselling will be given prior to testing blood for these blood-borne viruses)
* P. falciparum testing
At M0, D0: P. falciparum testing, Haematology: Hb, WBC, PLT, Biochemistry: ALT, AST, CREA, anti-circumsporozoite antibody; Pharmacokinetics (piperaquine and primaquine drug levels will be assessed if additional data are required) At M0, D1: Pharmacokinetics (piperaquine and primaquine drug levels) At M0, D2: Pharmacokinetics (piperaquine drug levels) At M0, D7: Haematology: Hb, WBC, PLT; Biochemistry: ALT, AST, CREA; Pharmacokinetics (piperaquine drug levels) At M1, D0: P. falciparum testing, anti-circumsporozoite antibody; Pharmacokinetics (piperaquine drug levels) At M1, D1: Pharmacokinetics (piperaquine and primaquine drug levels) At M1, D2: Pharmacokinetics (piperaquine drug levels) At M1, D7: Haematology: Hb, WBC, PLT; Biochemistry: ALT, AST, CREA; Pharmacokinetics (piperaquine drug levels) At M2, D0: P. falciparum testing, anti-circumsporozoite antibody; Pharmacokinetics (piperaquine drug levels) At M2, D1: Pharmacokinetics (piperaquine and primaquine drug levels) At M2, D2: Pharmacokinetics (piperaquine drug levels) At M2, D7: Haematology: Hb, WBC, PLT; Biochemistry: ALT, AST, CREA; Pharmacokinetics (piperaquine drug levels) At M3: P. falciparum testing, Haematology: Hb, WBC, PLT; Biochemistry: ALT, AST, CREA; anti-circumsporozoite antibody At M6: P. falciparum testing, anti-circumsporozoite antibody
