Genetically attenuated sporozoite vaccine PfGAP3KO in healthy adult male volunteers

The proposed clinical study is a two stage open label, Phase I study. The purpose of Stage 1 in this study, is to determine the safety and tolerability of the Genetically Attenuated Plasmodium falciparum 3D7 (GAP) vaccine candidate (3D7-KAHRP-KO GAP parasite vaccine) when delivered intravenously to healthy volunteers. Up to three consecutive cohorts of two volunteers will be inoculated with a single escalating dose of GAP Vaccine aiming to test for safety and course of parasitaemia as determined by qPCR. The first cohort will receive a dose of ~1,800 GMO parasites. If parasitaemia does not eventuate (i.e. parasites are significantly attenuated) in Cohort 1, and no safety-limiting AEs occur, the second cohort will proceed using a dose of parasites 100-fold higher (180,000 parasites) and volunteers followed as cohort 1. If parasitaemia does not occur at this higher dose, a third and final cohort will proceed, using a dose of parasites equivalent to that released from the liver after a 5 mosquito bite Controlled Human Malaria Infection study (~3x10e6 parasites). Following each inoculation, volunteers will be monitored on an outpatient basis by qPCR, a method previously shown to be highly sensitive. The monitoring will initially include qPCR on day 0 prior to inoculation, day 1 and day 4 post inoculation and then daily or twice daily once qPCR is positive. The treatment will be initiated within 24 hours once the treatment threshold is reached or on Day 28 if they don’t reach the treatment threshold. The threshold for commencement of treatment will be when qPCR quantification of the participants in the cohort is greater than or equal to 5,000 parasites/mL and/or clinical symptoms of malaria (a recorded temperature of
above 38 degrees Celcius) are observed. If the participant has a clinical symptom score greater than 6, or if clinical or parasitological evidence of malaria occurs in any participant before all participants have reached the treatment threshold (qPCR quantification of greater than or equal to 5,000). If the participants do not develop parasitaemia, or their qPCR results do not reach the treatment threshold of greater than or equal to 5000p/mL up until Day 14, monitoring by qPCR will continue three times/week until Day 28+/-3 when they will receive empiric treatment with Riamet ‘Registered Trademark’ commencing on study Day 28+/-3 on an outpatient basis.
The dosing with Riamet (20mg Artemether and 120mg Lumefantrine per tablet) will be as per manufacturer instructions. A course of treatment comprises six doses of four tablets (a total course of 24 tablets) given over a period of 60 hours. Each dose should be administered orally followed by food or drinks rich in fat (e.g., milk). The first dose, given at the time of initial diagnosis (or as advised by the PI), should be followed by five further doses given at 12, 24, 36, 48, and 60 hours. The trial will be conducted under the Australian Therapeutic Goods Administration (TGA) Clinical Trial Notification Scheme (CTN).

Study type: Interventional
Enrollment: 6 participant
Primary purpose: Treatment
Allocation: Non-Randomized
Masking: Open label
Trial Number: ACTRN12617000824369
Phase: Phase I

ANZCTR registration

Vaccines

Jun 2017 — May 2018

Australia