Dose ranging study to examine the infectivity of the Plasmodium falciparum NF54 cell bank MCB-002 in healthy adult males

Exclusion Criteria28

• History of clinical malaria.
• Travelled to or lived (>2 weeks) in a malaria-endemic country during the past 12 months or planned travel to a malaria-endemic country during the course of the study.
• Has evidence of increased cardiovascular disease risk (defined as >10%, 5 year risk) as determined by the method of Gaziano et al. Risk factors include sex, age, systolic blood pressure (mm Hg), smoking status, body mass index (BMI, kg/mm2), reported diabetes status and blood pressure.
• History of splenectomy.
• History of a severe allergic reaction, anaphylaxis or convulsions following any vaccination, infusion or treatment with the anti-malarial drugs artemether and/or lumefantrine.
• Presence of current or suspected serious chronic diseases such as cardiac or autoimmune disease (HIV or other immunodeficiencies), insulin dependent diabetes, progressive neurological disease, severe malnutrition, acute or progressive hepatic disease, acute or progressive renal disease, psoriasis, rheumatoid arthritis, asthma, epilepsy or obsessive compulsive disorder, skin carcinoma excluding non-spreadable skin cancers such as basal cell and squamous cell carcinoma.
• Known inherited genetic anomaly (known as cytogenetic disorders) e.g., Down’s syndrome.
• Individuals wishing to donate blood to the Australian Red Cross Blood Service during the study or within 6 months of administration of the malaria inoculum.
• The volunteer has a diagnosis of schizophrenia, severe depression, bi-polar disease, or other severe (disabling) chronic psychiatric diagnosis. Participants who are receiving a single antidepressant drug and are stable for at least 3 months prior to enrollment without decompensating may be allowed to enroll in the study at the investigator’s discretion.
• Known pre-existing prolongation of the QTc interval. Family history of congenital prolongation of the QTc interval on electrocardiograms or of sudden death or any other clinical condition known to prolong the QTc interval, e.g. volunteers with a history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease.
• Recent or current therapy with an antibiotic or drug with potential anti-malarial activity (tetracycline, azthromycin, clindamycin, hydroxychloroquine etc).
• Concomitant use of any drug which is metabolised by the cytochrome enzyme CYP2D6 (e.g. flecainide, metoprolol, imipramine, amitriptyline, clomipramine) OR drugs that are known to prolong the QTc interval, e.g. antiarrhythmics of classes IA and III, neuroleptics, antidepressant agents, certain antibiotics (including some agents of the following classes: macrolides, fluoroquinolones, imidazole and triazole antifungal agents), certain nonsedating antihistamines (terfenadine, astemizole), cisapride.
• Use of corticosteroids, anti-inflammatory drugs, any immunomodulators or anticoagulants. Currently receiving or have previously received immunosuppressive therapy, including systemic steroids including ACTH or inhaled steroids in dosages which are associated with hypothalamic-pituitary-adrenal axis suppression such as 1mg/kg/day of prednisone or its equivalent or chronic use of inhaled high potency corticosteroids (budesonide 800 micrograms per day or fluticasone 750 micrograms).
• Presence of acute infectious disease or fever (e.g., sub-lingual temperature greater than or equal to 38.5 degrees celsius) within the five days prior to study product administration).
• Evidence of acute illness within the four weeks before trial prior to screening.
• Significant intercurrent disease of any type, in particular liver, renal, cardiac, pulmonary, neurologic, rheumatologic, or autoimmune disease by history, physical examination, and/or laboratory studies including urinalysis.
• Alcohol consumption greater than community norms (i.e. more than 21 standard drinks per week for males).
• A history of drug habituation, or any prior intravenous usage of an illicit substance.
• Medical requirement for intravenous immunoglobulin or blood transfusions.
• Participation in any research study involving significant blood sampling, or blood donation to Red Cross (or other) blood bank during the 8 weeks preceding administration of the IP in the study.
• Have ever received a blood transfusion.
• Positive test for HIV, Hepatitis B, hepatitis C, Human T-cell Lymphotropic Virus I & II (HTLVI & HTLVII), TB or syphilis.
• Any clinically significant biochemical or haematologic abnormality (Hb must be greater than or equal to 13.5g/dL).
• Ingestion of any poppy seeds within the 48 hours prior to the screening blood test
• (volunteers will be advised by phone not to consume any poppy seed in this time period).
• Detection of any drug in the urine drug screen unless there is an explanation acceptable to the medical investigator (e.g. the subject has stated in advance that they consumed a prescription or OTC product which contained the detected drug) and/or the subject has a negative urine drug screen on retest by the pathology laboratory. These drugs include: Amphetamines, Methamphetamines, Barbituates, Benzodiazepines, Cocaine, Methadone, Opiates, Phencyclidine, Tetrahydrocannabinols and Tricyclic anti-depressants.
• Evidence of any condition that, in the opinion of the clinical investigator, might interfere with the evaluation of the study objectives or pose excessive risks to participants. (this criterion is complete)
• Participation in any investigational product study within the 8 weeks preceding the study.