Phase 1 study

Reproduced exactly, unedited. Written for researchers rather than for patients.

INCLUSION CRITERIA:

• Able and willing to complete the informed consent process
• Available for the entire planned study duration
• Male or Female
• Aged 18 to 55 years
• Willing to have blood samples collected, stored indefinitely and used for research purposes
• Willing to defer blood donations for at least six months after the EoS visit (D180)
• Agreement to adhere to specific Lifestyle Considerations throughout study duration

Clinical Criteria:

• Total body weight ≥ 50 kg, and a body mass index (BMI) within the range of 18 to 32 kg/m2 (inclusive)
• In good general physical and mental health as evaluated through a comprehensive clinical assessment
• Vital signs at screening and pre-inoculation within normal clinical range
• Electrocardiograph (ECG) without significant abnormalities, including: QTcF ≤450 ms for males, QTcF ≤470 ms for females, PR interval ≤210 ms

Laboratory Criteria:

• O negative blood type
• Haemoglobin, white cell count and platelet levels within normal laboratory ranges
• Ferritin, creatinine and alanine aminotransferase (ALT) within normal laboratory ranges
• No clinically significant abnormality in coagulation or clotting
• Normal G6PD enzyme activity levels as defined by the parameters of the specific quantitative G6PD test performed at screening
• Negative for blood borne viruses, including Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV), Hepatitis C virus (HCV), Human T-lymphotropic virus type 1 (HTLV); and other blood borne pathogens including West Nile Virus (WNV), Babesia species, Treponema pallidum, and Trypanosoma cruzi

Criteria specific to female participants:

• Post-menopausal for at least 1 one year, post-hysterectomy, or bilateral oophorectomy with a correlating follicle stimulating hormone (FSH) level.

OR

• Females of childbearing age have a negative beta-human chorionic gonadotrophin (b-HCG) pregnancy test (urine or serum) on day of enrolment and prior to CHMI inoculation and agreement to use effective birth control through the duration of the study.

EXCLUSION CRITERIA:

• Participant lives alone and is unable provide contact details of a support person who is aware of the individual's participation in the study and is available to provide assistance if required
• Participation in any investigational product study within the 12 weeks preceding inoculation
• Positive urine drug test at screening or on the day of malaria inoculation unless there is an explanation acceptable to the Investigator (e.g. the volunteer has stated in advance that they consumed a prescription or over-the-counter product which contained the detected drug) and/or the volunteer has a negative urine drug screen on retest by the pathology laboratory
• Positive alcohol breath test at screening or on the day of malaria inoculation

Malaria History:

• Any previous history of malaria infection, including participation in a malaria research study
• Receipt of a malaria vaccination at any time, including as part of a research study
• Travelled to or lived (more than two weeks) in a malaria-endemic region during the past 12 months or planned travel to a malaria-endemic region over the course of the study
• Lived for more than one year in a malaria-endemic region in the past 10 years
• Lived in a malaria-endemic region for more than 10 years inclusive

Clinical History:

• Anyone who is pregnant, breastfeeding or planning pregnancy during the study period
• History of severe allergic reaction, including angioedema or anaphylaxis
• Receipt of any live attenuated vaccines within 21 days prior to enrolment
• Has ever received a blood transfusion
• Use of blood products or immunoglobulins within the previous 6 months
• Without good peripheral venous access
• Clinical history of: Sickle cell disease, sickle cell trait or other haemoglobinopathies; Splenectomy or fuctional asplenia; Skeeter syndrome or anaphylactic response to mosquito bites
• Known intolerance, hypersensitivity or other contraindication to artemether or other artemisinin derivatives, lumefantrine, atovaquone, proguanil, primaquine, or artesunate or any of its excipients
• Use or planned use of any drug, including antibiotics, with antimalarial activity four weeks prior to inoculation
• Use of any of the following drugs: Anticoagulants (within 14 days of enrolment); Systemic corticosteroids (within 3 months of enrolment); Any prescription or non-prescription drugs, and or supplements that in the opinion of the investigator would jeopardise the safety of the volunteer
• Any other chronic or clinically significant medical condition that in the opinion of the investigator would jeopardize the safety or rights of the volunteer, including but not limited to: diabetes mellitus type I, chronic hepatitis; OR clinically significant forms of: drug or alcohol abuse, asthma, autoimmune disease, infectious diseases, psychiatric disorders, heart disease, or cancer

Clinical Risk:

• Evidence at screening of increased cardiovascular disease risk (defined as >10%, 5-year risk for those greater than 35 years of age), as determined by the Australian Absolute Cardiovascular Disease Risk Calculator