Clinical Trial for the Development of a Safe Malaria Challenge Model That Can be Reproduced in Humans (Pvivax)
The purpose of this study is to demonstrate that volunteers can be safely and reproducibly infected with Plasmodium vivax (P. vivax) by the bites of experimentally infected Anopheles dirus (An. dirus) mosquitoes carrying P. vivax sporozoites in their salivary glands.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||Development of a Safe and Reproducible Human Sporozoite Challenge Model for Plasmodium Vivax in Healthy Adults in the United States|
- Detection of erythrocytic stage P. vivax parasites by blood smear in volunteers during the 28 day period post challenge via the bites of five P. vivax-infected mosquitoes; Occurrence and intensity of solicited and unsolicited symptoms post challenge [ Time Frame: 28 days post challenge ] [ Designated as safety issue: Yes ]
- Parasitologic and clinical infections in challenge volunteers will be characterized by descriptive analysis of prepatent and patent periods, incubation period and time to resolution of signs and symptoms, and timing and number of relapses. [ Time Frame: Cross-sectional ] [ Designated as safety issue: Yes ]
|Study Start Date:||April 2009|
|Study Completion Date:||September 2011|
|Primary Completion Date:||June 2011 (Final data collection date for primary outcome measure)|
Experimental: Cohort 1
The first cohort will be challenged with 5 bites from P. vivax-infected mosquitoes each carrying at least a grade 2 sporozoite infection (>10 sporozoites in salivary gland).
Biological: Malaria Challenge
Experimental: Cohort 2
If the first cohort has less than 100% infectivity rate, the second cohort will be challenged with up to 10 grade 2 infective bites to ensure 100% infectivity rate.
Biological: Malaria Challenge
The study is a proof-of-concept clinical investigation designed to develop a safe and practical sporozoite challenge model for Plasmodium vivax in humans with a goal of 100% infectivity rate. The development and standardization of such a model will make possible efficacy evaluations of candidate P. vivax vaccines in Phase 2a trials. This trial is conducted in collaboration with Armed Forces Research Institute of Medical Sciences (AFRIMS) investigators in Bangkok, Thailand, who will be recruiting adult blood donors from a pool of patients who present with active P. vivax infections in Thailand. Samples of P. vivax infected blood will be collected and fed via membrane feeding apparatus to colony-reared Anopheles dirus mosquitoes at the AFRIMS Entomology Lab. A portion of the same blood will meanwhile be screened for potential co-infections at the AFRIMS Retrovirology Laboratory. When screening tests have confirmed the presence of only P. vivax in the blood (no co-infections with other malaria species), and selected dissection on days 3-7 has revealed oocyst production in the blood-fed mosquitoes, the mosquitoes will be transported from the AFRIMS insectary in Thailand to the WRAIR insectary in the US by a standard procedure (herein described) including permits and assurance against accidental release of the infected mosquitoes. Transport will be conducted in compliance with Thai exporting and US importing requirements.
Our study will involve two cohorts, each to be challenged once, in the hope of demonstrating reproducibility of the entire challenge procedure. Each cohort comprises up to 6 healthy adult volunteers. The first cohort will be challenged with 5 bites from P. vivax-infected mosquitoes each carrying at least a grade 2 sporozoite infection (>10 sporozoites in salivary gland).
If all six volunteers in the first cohort develop P. vivax infection, the same procedure will be repeated in the second cohort. If the first cohort has less than 100% infectivity rate, the second cohort will be challenged with up to 10 grade 2 infective bites to ensure 100% infectivity rate. Volunteers will be closely monitored post-infection, and will be treated with standard chloroquine and primaquine therapies when the infection becomes patent in the peripheral blood.
|United States, Maryland|
|WRAIR Clinical Trials Center|
|Silver Spring, Maryland, United States, 20910|
|Principal Investigator:||Ilin Chuang, MD, MPH||US Military Malaria Vaccine Program, Naval Medical Research Center|