To screen two different formulations of the recombinant malaria vaccine PfLSA-3-rec, one adjuvated with aluminium hydroxide and one with Montanide Isa 720, by assessing the safety and immunogenicity (phase I) profile of each formulation in humans,…
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Brief title
Condition
- Hepatobiliary neoplasms malignant and unspecified
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: The proportion of volunteers reaching day 21 post-infection without
or with a delayed onset of parasitemiae compared to control group (parasitemiae
defined as >=2 parasites per 200 fields in a thick blood film).
Secondary outcome
Phase I and IIa: Immunogenicity evaluation: antibody and cellular responses to
vaccination with PfLSA-3-rec vaccine formulations.
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 2 million deaths each year. The development of
an efficient vaccine would present by far the best solution for solving this
disastrous situation. Liver-Stage-Antigen-3 (LSA-3) is an antigen that is
mainly exhibited by Plasmodium falciparum sporozoites and liver-stage
parasites. It is 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 sporozoite
challenge in animal models. Therefore, PfLSA-3-rec is a promising candidate
vaccine against P. falciparum in humans.
Study objective
To screen two different formulations of the recombinant malaria vaccine
PfLSA-3-rec, one adjuvated with aluminium hydroxide and one with Montanide Isa
720, by assessing the safety and immunogenicity (phase I) profile of each
formulation in humans, as well as its protective efficacy following a
sporozoite challenge (phase IIa).
.
Study design
The phase I of the study is designed as a randomized, double-blind,
uncontrolled, unicentre, parallel intervention trial with two intervention arms
(aluminium hydroxide vs. Montanide Isa720 as adjuvants).
The phase IIa is a controlled, open-label, unicentre trial assessing the
efficacy of the candidate vaccine in a sporozoite challenge (experimental human
malaria infection) by comparison of immunised with non-immunised volunteers
Intervention
Subcutaneous administration of the recombinant malaria vaccine PfLSA-3-rec,
three times to all volunteers.
Intervention arm 1: PfLSA-3-rec with aluminium hydroxide as adjuvant
Intervention arm 2: PfLSA-3-rec with Montanide Isa 720 as adjuvant
Study burden and risks
Benefits: As for any phase I and phase IIa vaccine trial, the benefits for the
immunized subjects are minimal in absence of any data on efficacy of the
PfLSA-3-rec vaccine in the prevention of malaria: the only advantage for these
subjects might be a possible protection from malaria infection after
vaccination. However, as for the phase IIa control group volunteers, no direct
benefit can be claimed.
Risks: In animal experiments (chimpanzees, Aotus monkeys and mice) no severe
adverse events were observed after vaccination with the LSA-3 vaccine. In
addition, as LSA-3 is an unregistered immunological medicinal product,
assessment and approval will be obtained from the National Institute for Public
Health and the Environment (RIVM.) The adjuvants aluminium hydroxide and
Montanide Isa 720 are both registered for use in humans and are considered safe.
Burden: The phase I is associated with 19 visits to the examination site, with
periodical physical examination and completion of a diary after each
vaccination. In addition, blood will be drawn 13 times with a total amount in
the phase I of around 422mL. The phase IIa is associated with a short period
(around one to two weeks) of intense clinical monitoring with frequent site
visits (up to three times a day) and blood examinations. As it is unpredictable
if and/or when subjects will develop a positive thick blood smear for malaria,
it is impossible to state the exact number of site visits and blood
examinations. However, the maximum number (in case a subject does not develop a
positive blood smear) of site visits and blood examinations will be 49 with a
maximum amount of collected blood of 541mL.
25-28 Rue du Dr. Roux
75015, Paris
France
25-28 Rue du Dr. Roux
75015, Paris
France
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 challenge following the immunization course
-Resident near the Radboud University Medical Center Nijmegen, having 24h access to a telephone
-Living with a third party that could contact the clinicians in case of alteration of conscience
-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
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 The Dutch National Coordination Centre for Travellers Health (LCR) 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 immunisation and up to six months after the last immunisation.
-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 immunosuppressive drugs or other immune modifying drugs within three months of vaccination (inhaled and topical corticosteroids are allowed)
-Positive serological tests for P falciparum (LSA-3) ELISA and/or a positive P. falciparum PCR
-Known hypersensitivity to vaccine components
-Contra-indications to Riamet® including treatment taken by the volunteers that interfere with Riamet® (e.g. concurrent use of medicines that prolong QT-interval)
- 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.
Design
Recruitment
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 | EUCTR2006-001743-66-NL |
| CCMO | NL14715.000.06 |