Experimental Human Malaria Infection by PfSPZ

Sanaria

Status and phase

Completed

Phase 1

Conditions

Malaria

Treatments

Biological: PfSPZ Challenge

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01086917

TIP2

Details and patient eligibility

About

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).

Full 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.

Enrollment

18 patients

Sex

All

Ages

19 to 34 years old

Volunteers

Accepts Healthy Volunteers

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)
Available to attend all study visits
Agreement to refrain from blood donation to Sanquin or for other purposes, during the study period until day 140.
Willingness to undergo HIV, hepatitis B and hepatitis C tests
Negative urine toxicology screening test at screening visit and day before challenge
Willingness to take a curative regimen of Malarone®

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
Body Mass Index (BMI) below 18 or above 30 kg/m2
Any clinically significant deviation from the normal range in biochemistry or hematology blood tests or in urine analysis
Positive HIV, HBV or HCV tests
Participation in any other clinical study within 30 days prior to the onset of the study
Enrollment in any other clinical study during the study period
Pregnant or lactating women
Volunteers unable to give written informed consent
Volunteers unable to be closely followed for social, geographic or psychological reasons
Previous history of drug or alcohol abuse interfering with normal social function during a period of one year prior to enrolment in the study
A history of psychiatric disease
Known hypersensitivity to anti-malaria drugs
The use of chronic immunosuppressive drugs, antibiotics, or other immune modifying drugs within three months of study onset (inhaled and topical corticosteroids are allowed) and during the study period
Contra-indications to Malarone® including treatment taken by the volunteer that interferes with Malarone®
Any confirmed or suspected immunosuppressive or immunodeficient condition, including asplenia
Co-workers of the departments of Medical Microbiology or Internal Medicine of the Radboud University Nijmegen Medical Centre or Sanaria Inc.
A history of sickle cell anemia, sickle cell trait, thalassemia , thalassemia trait or G6PD deficiency