Controlled Human Malarial Infection by Intravenous Injection of Plasmodium Falciparum Sporozoites in Non-Immune Adults
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Malaria
- Sponsor
- Sanaria Inc.
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- The infectivity of the administration regimens will be assessed by thick film microscopy and PCR for P. falciparum DNA.
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
The study is designed to establish the best dose to safely infect healthy individuals with Plasmodium falciparum sporozoites (PfSPZ) via intravenous (IV) injection.
Detailed Description
TÜCHMI-001 is a single center, open label, randomized and controlled human pilot study to optimize controlled human malaria infection(CHMI) administered by PfSPZ Challenge. Volunteers will be inoculated with PfSPZ Challenge. Controls will receive the PfSPZ Challenge by ID administration. The remaining volunteers will receive the PfSPZ Challenge by IV administration. All volunteers recruited will be healthy adults aged between 18 and 45 years. Safety and infectivity data will be collected for each of the regimens and dose-levels. Volunteers and clinical investigators will not be blinded to group allocation, however laboratory investigators processing blood films and samples for PCR analysis will be blinded to group allocation.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy adults aged 18 to 45 years
- •Able and willing (in the Investigator's opinion) to comply with all study requirements
- •Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner if required
- •Women only: Must agree to practice continuous effective contraception for the duration of the study (a method which results in a low failure rate; i.e. less than 1% per year)
- •Agreement to refrain from blood donation during the course of the study and after the end of their involvement in the study according to the local blood banking eligibility criteria
- •Written informed consent to undergo CHMI
- •Reachable (24/7) by mobile phone during the whole study period
- •Willingness to take a curative anti-malarial regimen
- •Agreement to stay overnight for observation during the period of intensive follow-up post-challenge if required
- •Answer all questions on the informed consent quiz correctly
Exclusion Criteria
- •History of P. falciparum malaria
- •History of long term residence (\>5 years) in area known to have significant transmission of P. falciparum
- •Use of systemic antibiotics with known antimalarial activity within 30 days of study enrolment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones, or azithromycin)
- •Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period
- •Prior receipt of an investigational malaria vaccine
- •HIV infection
- •Any confirmed or suspected immunosuppressive or immunodeficient state, asplenia, recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed)
- •Use of immunoglobulins or blood products within 3 months prior to enrolment
- •Presence of sickle cell anemia, sickle cell trait, thalassemia or thalassemia trait
- •Pregnancy, lactation or intention to become pregnant during the study
Outcomes
Primary Outcomes
The infectivity of the administration regimens will be assessed by thick film microscopy and PCR for P. falciparum DNA.
Time Frame: Day 5 until day 21 or until treatment
Parasitology and parasite molecular biology tests: These tests are used to determine malaria parasites (thick blood smear and PCR). Both tests are performed at screening and then approximately every 12 hours during the period of intense observation from day 5 until day 21 or until treatment. Thereafter, these tests are performed during safety follow-ups at Days 28, 84, and 168. Turn over time for thick blood smear microscopy is \< 2 hours to ensure timely treatment in case of a positive result. PCR results are available only after study completion.
Secondary Outcomes
- The time from parasite inoculation to first detection of blood stage parasitemia will be assessed by thick blood film microscopy.(Day 5 until day 21 or until treatment)
- The safety of PfSPZ Challenge administered ID or 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(Screening to Day 168)