Using a single formulation of PfPEBS LSP administered at two different doses, one of 5*g and the other one of 30*g, both adjuvanted with aluminium hydroxide, in two immunizations at 28 days interval, to evaluate a) the safety and immunogenicity (…
ID
Source
Brief title
Condition
- Protozoal infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Phase I: The proportion and severity of adverse events in both intervention
groups.
Phase IIa: Efficacy against Liver stages: The proportion of volunteers reaching
day 21 post infection without or with a delayed onset of parasitemia compared
to control group
Secondary outcome
Phase I and lla: Immunogenicity evaluation: Functional activity of antibody and
cellular responses elicited by PfPEBS-LSP vaccine formulation.
Phase IIa: The length of time (in hours) between parasite inoculation and
detection of parasitemia, if any, up to 21 days.
Background summary
Malaria is responsible for over 1 million deaths each year. The development of
an efficient vaccine would present an essential complementary tool for
controlling, if not eliminating this Plasmodium infection.
PfPEBS is an antigen characterized by its remarkable antigenicity in humans
with a wide range and a variety of B and T lymphocyte epitopes, by its
extremely high immunogenicity and by an excellent protective efficacy against
both, Pre-erythrocytic and erythrocytic stages of the parasite. The PEBS
candidate presents the unique feature to associate the characteristics of LSA3
and MSP3, two major vaccine candidates against the pre-erythrocytic and the
asexual blood stages of the parasite, respectively. Therefore, PfPEBS peptide
is a promising candidate vaccine against P.falciparum in humans.
Study objective
Using a single formulation of PfPEBS LSP administered at two different doses,
one of 5*g and the other one of 30*g, both adjuvanted with aluminium hydroxide,
in two immunizations at 28 days interval, to evaluate a) the safety and
immunogenicity (phase I) profile of each dose in humans, b) the induction of an
ADCI parasite-killing-effect against erythrocytic stages, and c) to evaluate
protective efficacy following a sporozoite challenge (phase IIa).
Study design
The phase I of the study is designed as a randomized, double-blind, controlled,
against aluminium hydroxide alone, unicentre, parallel intervention trial of
PfPEBS with aluminium hydroxide as adjuvant. The phase IIa is a controlled,
double-blind, bi-centre trial assessing the efficacy of the candidate vaccine
against a sporozoite challenge (experimental human malaria infection) by
comparison of immunised with control volunteers.
Intervention
Intramuscular administration of the malaria vaccine PfPEBS-LSP, two times at 28
days interval to all volunteers.
Study burden and risks
1. side effects: fever, nausea, flu-symptoms, headache
2. strict medical control visits during 10 days starting on day 5 after
inoculation
Rue Lecourbe 26
Parijs F-75015
FR
Rue Lecourbe 26
Parijs F-75015
FR
Listed location countries
Age
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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-002294-54-NL |
| ClinicalTrials.gov | NCT01605786 |
| CCMO | NL41025.000.12 |