Blood stage pilot challenge study to assess the safety and the infectivity of Plasmodium malariae isolate (HMPBS-Pm) in healthy volunteers
An Experimental Study To Characterise The In Vivo Safety And Infectivity Of The Plasmodium Malariae Isolate Hmpbs-Pm In Humans
QIMR Berghofer Medical Research Institute
2 participants
Feb 9, 2017
Interventional
Conditions
Summary
This pilot clinical trial will characterize the wild type Plasmodium malariae isolate HMPBS-Pm as an agent for use in CHMI for the future assessment of antimalarial treatments. The study has been designed based on previous experience with similar Plasmodium spp. master cell banks. Inoculum preparation, administration and clinical score criteria are unchanged. Participant follow up intervals have been adjusted to account for differences in Plasmodium spp. lifecycles. The study population will consist of healthy participants who meet the inclusion and exclusion criteria for similar trials, including appropriate ABO and Rh (female participants) blood group matching. It is hypothesized that the inoculum HMPBS-Pm will demonstrate infectivity in healthy participants. Parasite growth rates are expected to be slower compared to P. falciparum and P. vivax cell banks.
Eligibility
Inclusion Criteria9
- Adult males or non-lactating and non-pregnant females, between 18 and 55 years of age inclusive who do not live alone (from Day 0 until at least the end of the anti-malarial drug treatment) and are contactable and available for the duration of the trial.
- Body weight, minimum 50.0 kg, body mass index between 18.0 and 32.0 kg/m2, inclusive.
- Confirmed as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination).
- Blood group A or AB
- Normal standard 12-lead electrocardiogram (ECG) after 5 minutes resting in supine position;
- Laboratory parameters within the normal range, unless the Investigator considers an abnormality to be clinically irrelevant for healthy participants enrolled in this clinical investigation.
- As there is the risk of adverse effects of the study treatment, it is important that any participants involved in this study do not get pregnant
- All participants must be Duffy Blood group positive. Female participants of childbearing potential should be blood group Rh positive.
- Female participants of childbearing potential must also have adequate contraception in place for the duration of the study
Exclusion Criteria14
- Any history of malaria or participation in a previous malaria challenge study.
- Must not have travelled to or lived (greater than 2 weeks) in a malaria-endemic area/region during the past 12 months or planned travel during the study to a malaria-endemic region during the course of the study
- Has evidence of increased cardiovascular disease risk
- History of splenectomy.
- 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 inoculation with malaria parasites.
- Evidence of acute illness within the four weeks before trial prior to screening that the Investigator deems may compromise participant safety.
- Participation and receipt of any investigational product within the 12 weeks preceding the study.
- Blood donation, any volume, within 1 month before inclusion.
- Participant who has ever received a blood transfusion.
- Any vaccination within the last 28 days.
- Any recent (less than 6 weeks) or current systemic therapy with an antibiotic or drug with potential anti-malarial activity (chloroquine, piperaquine, benzodiazepine, flunarizine, fluoxetine, tetracycline, azithromycin, clindamycin, hydroxychloroquine, etc.).
- Cardiac/QT risk:
- Known hypersensitivity to Riamet or any 4-aminoquinolines, artemether or other artemether derivatives, lumefantrine, or other arylaminoalcohols.
- Known severe reaction to mosquito bites other than local itching and redness.
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Interventions
Each participant will be inoculated on Day 0 with an estimated ~1000 viable parasites in 1.5 x 10^9 erythrocytes administered intravenously. On an outpatient basis, the participants will be monitored initially by phone then daily from Day 6 until the detection of parasites by qPCR. During this time, participants will also be monitored for the unexpected early onset of malaria symptoms, signs or parasitological evidence of malaria. On the day of commencement of treatment, participants will attend the outpatient unit for a visit encompassing first two doses of the anti-malarial treatment with the anti-malarial drug Riamet(Registered Trademark) (Artemether20mg / Lumefantrine 120 mg), transmission experiments and safety monitoring. The anti-malarial treatment will be administered as an oral tablet; 6 doses of 4 tablets (total course 24 tablets) given over a period of 60 hours following food. It is expected some of the doses to be taken by the participants at home. Participants will have a phone call from a study staff member to check on symptoms and ensure compliance/completion with treatment following the dose taken at home. A maximum of two mosquito transmission studies by each of direct (DFA) and membrane feeding assays (MFA) may be performed approximately two days prior to treatment and on the day of treatment (four feeding assays in total). A further MFA may be performed following treatment if there is evidence of gametocytemia or at the Investigator’s discretion. Further follow up visits for safety assessments will be performed on Day 28+/-3, Day 56+/-7 (as required) and Day 84+/-7 (End of Study). Each follow up visit beyond Day 28 should take place as scheduled+/-7 days. The overall period of participation will therefore be around 14 weeks from the time malaria infection. A further follow up period roughly 6 months post completion Riamet(Registered Trademark) treatment may also be requested at the Investigator’s discretion.
Locations(1)
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ACTRN12617000048381