Phase I and IIa Trial for Assessment of Safety, Immunogenicity (Phase Ia) and Efficacy (Phase IIa) Against Sporozoite Challenge of P. Falciparum Pre-Erythrocytic and Blood Stage (PfPEBS-LSP) Malaria Vaccine Candidate

Withdrawn

Conditions: 10037072
Malaria
Plasmodium falciparum

Registration Number: NL-OMON37083

Lead Sponsor: Vac4All

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 36

Inclusion Criteria

•Male and female age > 18 and < 45 years
•Good general health based on history, physical en laboratory examination
•Available for and willingness to undergo a P. falciparum sporozoite infected mosquito challenge following the immunization course
•Resident in or near Lausanne for the duration of the study having 24h access to a mobile telephone
•Willingness to stay in special accommodation (hotel or equivalent) from day 5 up to one day after parasite positivity , or up to day 15 post EHMI
•Agreement to refrain from blood donation during the course of the study and afterwards
•Negative pregnancy test and the use of effective contraception during the whole study period if deemed appropriate
•Willingness to undergo an HIV test and other serologies
•Willingness to allow investigators to notify their general practitioner, if any, of participation in this trial
•Willingness to allow investigators to request medical information, relevant for participation in this trial, from their general practitioner, if any
•Written informed consent following proper understanding of the meaning and procedures of the Phase I and IIa parts of the trial
•Agreement to inform study doctor and to release medical information concerning contra-indications for participation in the study
•Willingness to undergo screening for drugs such as amphetamines, opiates and cocaine

Exclusion Criteria

•Any history of malaria
•Known exposure to malaria in the previous 6 months, defined as a visit to a malaria endemic region. For practical purposes, all regions for which malaria chemoprophylaxis is advised by travel clinic are considered malaria endemic
•Planned to travel to endemic malaria areas during the study period
•Prior administration of an investigational malaria vaccine
•Administration of a vaccine or gammaglobulin not foreseen by the clinical trial protocol within 30 days prior to the first immunization and up to six months after the last immunization.
•Participation in any other clinical trial within 90 days prior to the onset of the trial or more than four clinical trials in the past year
•The use of chronic medication (defined as more than 14 days), especially immunosuppressive agents or antibiotics during the study period
•The use of chronic immunosuppressive drugs or other immune modifying drugs within three months of vaccination (inhaled and topical corticosteroids are allowed)
•Positive serological tests for P. falciparum (PEBS) ELISA and/or a positive P. falciparum whole parasite ELISA
•Known hypersensitivity to vaccine components
•History of severe reactions or allergy to mosquito bites
•Contra indications to Malarone® including treatment taken by the volunteers that interfere with Malarone® (e.g. concurrent use of medicines that prolong QT interval)
•History of allergic disease to or reactions likely to be exacerbated by any component of the vaccine
•Any confirmed or suspected immunosuppressive or immunodeficiency condition, including asplenia.
•History of diabetes mellitus or cancer (except basal cell carcinoma of the skin)
•History of >2 hospitalisations for invasive bacterial infections
•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
•An estimated, ten year risk of fatal cardiovascular disease of >=5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system.
•History of arrhythmia or prolonged QT interval or other cardiac disease
•Positive history for cardiac disease in the 1st and 2nd degree relative < 50 years old
•Clinically significant abnormalities in electrocardiogram (ECG) at screening
•Body Mass Index < 18 kg/m2 or > 32 kg/m2
•Blood pressure > 150/90 in two measurements
•Seropositive for HIV, HBV or HCV
•Any clinically significant deviation from the normal range in biochemistry or haematology blood tests or in urine analysis.
•Volunteers unable to be closely followed for social, geographic or psychological reasons
•Previous history of drug or addiction to alcohol abuse interfering with normal social function during a period of one year prior to enrolment in the study
•Having not reached 10 correct responses to the knowledge questionnaire

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Phase I: The proportion and severity of adverse events in both intervention<br /><br>groups.<br /><br><br /><br>Phase IIa: Efficacy against Liver stages: The proportion of volunteers reaching<br /><br>day 21 post infection without or with a delayed onset of parasitemia compared<br /><br>to control group </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Phase I and lla: Immunogenicity evaluation: Functional activity of antibody and<br /><br>cellular responses elicited by PfPEBS-LSP vaccine formulation.<br /><br>Phase IIa: The length of time (in hours) between parasite inoculation and<br /><br>detection of parasitemia, if any, up to 21 days.</p><br>