Study of Controlled Human Plasmodium Vivax Infection (VAC068)
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|ClinicalTrials.gov Identifier: NCT03377296|
Recruitment Status : Active, not recruiting
First Posted : December 19, 2017
Last Update Posted : November 30, 2018
|Condition or disease||Intervention/treatment||Phase|
|Malaria, Vivax||Other: Plasmodium vivax infection Procedure: Collection of 250mL blood from each volunteer (N=2)||Not Applicable|
This is a sporozoite-challenge clinical study with the primary aim of assessing the safety and feasibility of controlled human P. vivax malaria infection in two healthy volunteers. The investigators will also assess the growth of and the immune response to P. vivax infection, and assess the induction of sexual gametocytaemia post-CHMI via the natural route of malaria infection (mosquito bite). A secondary objective is to develop a blood inoculum of P. vivax-infected blood for future testing of candidate vaccines.
Two healthy, malaria-naïve adults aged between 18 and 50 years will be recruited at the CCVTM, Oxford. CHMI by sporozoites will be delivered by mosquito bite at Imperial College, London, and follow-up during the post-challenge period will be at the CCVTM in Oxford.
The two volunteers will have blood taken at regular intervals post-CHMI to assess the immune response to primary P. vivax infection, and also the gametocytaemia following P. vivax infection, and the volunteers will be monitored closely until the volunteers meet the criteria for treatment. Up to 250 mL (half a unit) of blood will be taken just prior to treatment from the two successfully infected volunteers (as determined by measurement of the parasitaemia) and frozen down for future use in blood-stage CHMI trials. The volunteers will be treated with a standard 60-hour course of oral artemether-lumefantrine (Riamet) followed by a 2-week course of partially-observed oral Primaquine for radical cure of P. vivax hypnozoites. The volunteers will be followed up for 3 months in the clinic and email follow-up will continue out to 5 years to monitor for clinical relapse.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||2 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Clinical Study to Assess the Safety of Controlled Human Plasmodium Vivax Malaria Infection Through Experimental Sporozoite Infection of Healthy Malaria-naïve UK Adults, and to Characterise Parasite Growth and Immune Responses to P.Vivax|
|Actual Study Start Date :||March 3, 2018|
|Estimated Primary Completion Date :||April 13, 2023|
|Estimated Study Completion Date :||April 13, 2023|
Experimental: Plasmodium Vivax infection
Both volunteers will be infected with Plasmodium Vivax (as described below in full in "Interventions"). i.e., there is only one arm to this study.
Other: Plasmodium vivax infection
Two healthy human volunteers are exposed to the bites of five infectious mosquitoes per participant (by placing their forearms over the pot containing mosquitoes) for 5-10 minutes. Fed mosquitoes (as indicated by the presence of a blood meal in the abdomen) are individually dissected and assessed for sporozoite load (graded 0 to +4; a gland rating of +2 or more, representing 10 or more observed sporozoites, qualifies as being infectious). If, by this method the volunteer is found to have been inoculated by less than five infected mosquitoes, further mosquitoes are allowed to feed on the volunteer until a total of 5 appropriately infected mosquitoes have fed. The bite-challenge procedure continues until the subject has been bitten by 5 infectious mosquitoes.
Procedure: Collection of 250mL blood from each volunteer (N=2)
Collection of 250mL of P. vivax-infected blood from each volunteer when a threshold parasitaemia/ symptoms are met
- Incidence of (Serious) Adverse Events following P. vivax CHMI [ Time Frame: Up to 21 days post challenge ]Safety of P. vivax CHMI, as measured by incidence of (Serious) Adverse Events (Safety and Tolerability)
- Clinical symptoms of malaria infection post CHMI [ Time Frame: Up to 21 days post challenge ]Measure of successful infection (development of clinical symptoms of malaria)
- Parasitaemia post CHMI [ Time Frame: Up to 90 days post challenge ]Measure of successful infection (development of detectable persistent parasitaemia) symptoms).
- Immune response to P. vivax [ Time Frame: Up to 90 days post challlenge ]Immune response to P. vivax, as measured by antibody, B cell and T cell responses.
- Gametocytaemia [ Time Frame: Up to 90 days post challenge ]Gametocytaemia, as measured by qPCR
- Collection and freezing down of P. vivax-infected blood. [ Time Frame: Collected between day 8 and day 14 post challenge, determined by symptoms and parasitaemia ]Collection and freezing down of up to 250 mL P. vivax-infected blood from 2 volunteers.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03377296
|Centre for Clinical Vaccinology & Tropical Medicine|
|Oxford, Oxfordshire, United Kingdom, OX3 7LE|
|John Warin Ward, Oxford University NHS Foundation Trust|
|Oxford, Oxfordshire, United Kingdom, OX3 7LE|
|Principal Investigator:||Angela M Minassian||Jenner Institute, University of Oxford|