A pilot study to characterize the safety and infectivity of a Plasmodium knowlesi parasite bank in healthy volunteers
- Conditions
- MalariaInfection - Other infectious diseases
- Registration Number
- ACTRN12623001326684
- Lead Sponsor
- QIMR Berghofer Medical Research Institute
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 4
1. Male or female (non-pregnant, non-lactating) aged 18 to 55 years inclusive who will be contactable and available for the duration of the trial and up to two weeks following the EOS visit.
2. Total body weight greater than or equal to 50 kg, and a body mass index (BMI) within the range of 18 to 32 kg/m2 (inclusive).
3. Certified as healthy by a comprehensive clinical assessment (detailed medical history and full physical examination).
4. Vital signs at screening (measured after 5 min in the supine position):
•Systolic blood pressure (SBP) - 90–140 mmHg,
•Diastolic blood pressure (DBP) - 40–90 mmHg,
•Heart rate (HR) 40–100 bpm.
5.At screening, and pre-inoculation: QTcF less than or equal to 450 msec (male volunteers); QTcF less than or equal to 470 msec (female volunteers); PR interval less than or equal to 210 msec for both males and females.
6. Women of childbearing potential (WOCBP) who anticipate being sexually active with a male during the trial must agree to use a highly effective method of birth control combined with a barrier contraceptive from the screening visit until 30 days after the end of study (covering a full menstrual cycle) and have a negative urine pregnancy test result prior to inoculation with the malaria challenge agent on Day 0.
1.Known hypersensitivity to artesunate or other artemisinin derivatives, lumefantrine, proguanil/atovaquone, primaquine, or 4-aminoquinolines.
2.Any history of anaphylaxis or other severe allergic reactions, or other food or drug allergy that the Investigator considers may impact on participant safety.
3.History of convulsion (including drug or vaccine-induced episodes). A medical history of febrile convulsion during childhood (less than 5 years) is not an exclusion criterion.
4.Presence of current or suspected uncontrolled chronic diseases that may impact participant safety or interpretation of clinical trial results, such as (but not limited to) cardiac or autoimmune disease, diabetes, progressive neurological disease, severe malnutrition, hepatic or renal disease, epilepsy, or asthma.
5.History of malignancy of any organ system (other than localised basal or squamous cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within five years of screening, regardless of whether there is no evidence of local recurrence or metastases.
6.Individuals with history of schizophrenia, bipolar disorder psychoses, attempted or planned suicide, or any other severe (disabling) chronic psychiatric diagnosis including generalised anxiety disorder.
7.History of an episode of depression lasting more than 6 months that required pharmacological therapy and/or psychotherapy within the last 2 years.
8.A score of 20 or more on the Beck Depression Inventory-II (BDI-II) and/or a response of 1, 2 or 3 for item 9 of this inventory (related to suicidal ideation).
•The BDI-II will be used as a validated tool for the assessment of depression at screening. Participants that meet criterion 8 will be referred to a general practitioner or medical specialist as appropriate. Participants with a BDI-II score of 17 to 19 may be enrolled at the discretion of the Investigator if they do not have a history of the psychiatric conditions mentioned in criterion 6 and their mental state is not considered to pose additional risk to the health of the participant during the trial or to the execution of the trial and interpretation of the data gathered.
9.History of splenectomy.
10.Symptomatic postural hypotension at screening (confirmed on two consecutive readings), irrespective of the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease of SBP of greater than or equal to 20 mmHg after 3 min standing and/or a decrease of DBP of greater than or equal to 10 mmHg after 3 min standing. This 3 min standing period will commence after the volunteer has rested for 5 min in the supine position.
11.Cardiac/QT risk:
•Family history of sudden death or of congenital prolongation of the QTc interval or known congenital prolongation of the QTc interval or any clinical condition known to prolong the QTc interval.
•History of symptomatic cardiac arrhythmias or of clinically relevant bradycardia.
12.Evidence of increased cardiovascular disease risk (defined as greater than 10%, 5 year risk for those greater than 35 years of age, as determined by the Australian Absolute Cardiovascular Disease Risk Calculator [http://www.cvdcheck.org.au/]). Risk factors include sex, age, systolic blood pressure (mm/Hg), smoking status, total and HDL cholesterol (mmol/L), and reported diabetes status.
13.Presence of clinically significant infectious disease or fever (e.g., sublingual temperature greater than or equal to 38°C) wit
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To evaluate the safety of the P. knowlesi YH1-HS malaria challenge agent.[The incidence, severity and relationship to the P. knowlesi YH1-HS malaria challenge agent of adverse events determined by self-reported symptoms, clinical laboratory analysis, vital signs, physical examinations and ECG assessments. Additionally, the severity of the induced malaria infection in each participant graded by the malaria clinical score. Adverse event recording: at all clinic visits from parasite inoculation (Day 0) until the end of study (day 24 +/- 3). Adverse events will be recorded at all clinic visits from parasite inoculation (Day 0) until the end of study (day 24 +/- 3). Adverse events will also be measured 4, 8 and 12 hours post administration of antimalarial treatment.]
- Secondary Outcome Measures
Name Time Method