Experimental Human Malaria Infection by Intradermal Injection of Plasmodium Falciparum Sporozoites (PfSPZ Challenge)
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Malaria
- Sponsor
- Sanaria Inc.
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Number of volunteers with Plasmodium falciparum Infection
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
The study is a single center, varied dose, open label study. A maximum of eighteen volunteers will be exposed to live NF54 P. falciparum sporozoites (PfSPZ Challenge) by intradermal injection. Volunteers will be divided into three groups of 6 volunteers, each group spaced 25 days apart (21 days after the last challenge of the last volunteer from the previous dose group).
Detailed Description
In every group on day 1, two volunteers will be injected. On day 3 the remaining four volunteers of the group will be injected. Injections in subsequent volunteers are always spaced at least one hour apart in any group. Injection of subsequent (groups of) volunteers will only commence if the previous injection was shown to be safe. Three different doses of PfSPZ will be administered: a dose of 2,500 PfSPZ Challenge (Group 1); a dose of 10,000 PfSPZ Challenge (Group 2) if not all volunteers become thick smear positive (TS+) in Group 1; and a dose of 25,000 PfSPZ Challenge (Group 3) if there is not 100% TS+ in Group 2. If all volunteers in Group 1 (2,500 PfSPZ Challenge) become thick smear positive, then Group 2a will receive 1,000 PfSPZ Challenge. If all volunteers in Group 2a become TS+, the volunteers in Group 3a will receive 500 PfSPZ Challenge. If all volunteers in Group 2 (10,000 PfSPZ Challenge) become TS+, Group 3b will receive 5,000 PfSPZ. If less than 100% of volunteers in Group 2a (1,000 PfSPZ Challenge) become TS+ then Group 3c will receive 1,750 PfSPZ Challenge. The clinical, biological, parasitological and immunological data of these groups' volunteers will be compared. Volunteers and the investigator will not be blinded, but the laboratory personnel will be blinded.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age \> 18 and \< 35 years healthy volunteers (males or females)
- •Good health based on history and clinical examination
- •Negative pregnancy test
- •Use of adequate contraception for females
- •All volunteers must sign the informed consent form demonstrating their understanding of the meaning and procedures of the study
- •Volunteer agrees to inform the general practitioner and agrees to sign a request to release medical information concerning contra-indications for participation in the study
- •Willingness to undergo a Pf sporozoite challenge
- •For volunteers not living in Nijmegen: agreement to stay in a hotel room close to the trial center during a part of the study (Day 5 till 3 days after treatment)
- •Reachable (24/7) by mobile phone during the whole study period
- •Living with a third party that could contact the clinicians in case of alteration of consciousness or agreement to stay in a hotel room close to the trial center during a part of the study (Day 5 till 3 days after treatment)
Exclusion Criteria
- •History of malaria
- •Plans to travel to malaria endemic areas during the 140 day study period
- •Plans to travel outside of the Netherlands during day 0-28 of the study
- •Previous participation in any malaria vaccine study and/or positive serology for Pf
- •Symptoms, physical signs and laboratory values suggestive of systemic disorders including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric, and other conditions which could interfere with the interpretation of the study results or compromise the health of the volunteers
- •History of diabetes mellitus or cancer (except basal cell carcinoma of the skin)
- •History of arrhythmias or prolonged QT-interval
- •Positive family history in 1st and 2nd degree relatives for cardiac disease \< 50 years old
- •An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system
- •Clinically significant abnormalities in electrocardiogram (ECG) at screening
Outcomes
Primary Outcomes
Number of volunteers with Plasmodium falciparum Infection
Time Frame: Upto 7 months
To achieve a 100% infection rate of human volunteers by intradermal injection of aseptic, purified, cryopreserved Pf sporozoites (PfSPZ Challenge)as measured by 100% thick smear positivity (thick blood smears) of all volunteers from one group
Secondary Outcomes
- Kinetics of infection(Upto 7 months)