Conditions: Plasmodium Falciparum, Malaria
Keywords: Malaria, Plasmodium falciparum sporozoite challenge, DSM265
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 22
Healthy volunteers: yes

Brief summary:
Study to evaluate the efficacy of DSM265 as a causal prophylactic in a standardized and validated Human Challenge model using direct venous inoculation of aseptic, purified, cryopreserved, vialed Plasmodium falciparum sporozoites.

Detailed description:
This study follows the First In Human dose-escalation study of DSM265 (25 - 800 mg of DSM265) and an Induced-Blood Stage Malaria Challenge study (150 mg of DSM265) conducted in healthy adult volunteers in Australia. After identification of efficacious DSM265 plasma concentrations in the Induced-Blood Stage Malaria model, the current study will evaluate the efficacy of DSM265 as a causal prophylactic in a standardized and validated Human Challenge model using direct venous inoculation of aseptic, purified, cryopreserved, vialed Plasmodium falciparum sporozoites (Challenge).

Three sequential cohorts of healthy male and women volunteers, of non-childbearing potential or of childbearing potential with predefined accepted methods of contraception, are planned in order to investigate three preventive conditions with regard to administration of DSM265. Preventive administration of the study drug will occur 1 and 7 days before inoculum of Plasmodium falciparum sporozoite Challenge, with a last cohort administered at a time point to be determined from the 2 previous cohorts but which will not exceed 28 days before the challenge. The study will also include a cohort where subjects will be treated with atovaquone-proguanil (Malarone®) using the approved regimen for chemoprophylaxis.

Arms:
arm 1: DSM265 400mg / placebo Day -1, sporozoite inoculum Day 0 arm 2: Malarone daily for 9 days from Day -1 to Day 7, sporozoite inoculum Day 0 arm 3: DSM265 400mg / placebo Day -7, sporozoite inoculum Day 0 arm 4: DSM265 400mg / placebo Day -X, sporozoite inoculum Day 0

Interventions: intervention 1: DSM265 400mg intervention 2: Placebo to DSM265 400 mg intervention 3: Plasmodium falciparum sporozoite challenge intervention 4: Malarone
Intervention descriptions: intervention 1: DSM265 400mg, single oral administration in a fed state intervention 2: Placebo to DSM265 400mg, single oral administration in a fed state intervention 3: IV Plasmodium falciparum sporozoites (3200) by direct venous inoculation intervention 4: 250 mg atovaquone, 100 mg proguanil hydrochloride

Protocol document: