Clinical Trial: Effect of Plasmodium Falciparum Exposure and Sickle Cell Trait on Infection Rates and Kinetics After IV Administration of PfSPZ Challenge

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Effect of Plasmodium Falciparum Exposure and Sickle Cell Trait on Infection Rates and Kinetics After IV Administration of PfSPZ Challenge

Brief Summary:

The study is designed to establish infectivity of Plasmodium falciparum sporozoites (PfSPZ) via intravenous (IV) administration in three groups with different malaria immunity-status:

1. Adults with a history of lifelong malaria exposure without sickle cell trait (HbAA)
2. Adults with a history of lifelong malaria exposure with sickle cell trait (HbAS)
3. Adults without previous malaria episodes without sickle cell trait (HbAA)

Initially a dose of 3,200 PfSPZ will be given and the time until thick blood smear positivity after challenge will be assessed. If in any of the groups with a history of lifelong malaria exposure, 50% or less of individuals become thick blood smear positive during the 28 days post injection of PfSPZ Challenge, the dose will be increased 4-fold to 12,800 PfSPZ in this group.

Detailed Summary:

LACHMI-001 is a partially-blinded, human pilot trial to study immunity against P. falciparum malaria in a controlled infection setting. The main objective is to characterise the role of sickle cell trait and naturally acquired immunity in development of malaria, defined by positive smear for P. falciparum and signs or symptoms associated with malaria. Three groups of volunteers will receive radical cure treatment and subsequently PfSPZ Challenge by IV administration. The groups are:

1. Adults with naturally acquired immunity and HbAA (Group IA, n=10-20)
2. Adults with naturally acquired immunity and HbAS (Group IS, n=10-20)
3. Adults without previous exposure to malaria and HbAA (Group NI, n=5)

The initial challenge dose of 3,200 PfSPZ administered once intravenously leads to consistent infection in naïve adults (15/15 in prior studies) and thus should infect all volunteers in Group 3. However, volunteers with naturally acquired immunity or sickle cell trait might require a higher dose. Thus if 50% or less of volunteers become parasitemic in Groups IA or IS, 10 additional volunteers will be enrolled and challenged with 12,800 PfSPZ. All volunteers will be healthy adults aged 18 to 30 years. Safety and infectivity data will be collected for each of the regimens and dose-levels. Effective treatment is initiated immediately upon development of parasitemia together with the presence of symptoms associated with malaria.

Laboratory staff reading blood films and processing samples will be blinded to group allocation. Volunteers and clinical investigators will be blinded to group allocation among the IA and IS groups.

Sponsor: Sanaria Inc.

Current Primary Outcome:

• Days from inoculation to start of malaria episode [ Time Frame: From day of injection until day 28 ]
  The time from parasite inoculation to first detection of malaria will be assessed by thick blood film microscopy and a clinical questionnaire. Malaria is defined as both parasitemia and clinical symptoms suggestive of malaria.
• Frequency, incidence and nature of adverse events [ Time Frame: From day of injection until day 28 ]
  The safety of PfSPZ Challenge administered IV and the resultant P. falciparum infection will be assessed by analysing actively and passively collected data from clinical review of volunteers and laboratory measurements.

Original Primary Outcome:

• Days from inoculation to start of malaria episode [ Time Frame: From day of injection until day 28 ]
  The time from parasite inoculation to first detection of malaria will be assessed by thick blood film microscopy and a clinical questionnaire. Malaria is defined as both parasitemia and clinical symptoms suggestive of malaria.
• Frequency, incidence and nature of adverse events [ Time Frame: From day of injection until day 5 ]
  The safety of PfSPZ Challenge administered IV and the resultant P. falciparum infection will be assessed by analysing actively and passively collected data from clinical review of volunteers and laboratory measurements.

Current Secondary Outcome: Dynamics of P. falciparum parasite growth [ Time Frame: From day 6 after injection until approximately day 28 ]

Original Secondary Outcome: Same as current

Information By: Sanaria Inc.

Dates:
Date Received: August 27, 2014
Date Started: July 2014
Date Completion:
Last Updated: April 21, 2015
Last Verified: April 2015