Safety and Efficacy Study of Plasmodium Falciparum LSA-3 Malaria Vaccine - Full Text View

Sponsors and Collaborators:	Radboud University Institut Pasteur
Information provided by:	Radboud University
ClinicalTrials.gov Identifier:	NCT00509158

Purpose

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 The aim is 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).

Condition	Intervention	Phase
Healthy	Biological: arm I: PfLSA-3-rec with aluminium hydroxide as adjuvant Biological: arm 2: PfLSA-3-rec with Montanide Isa 720 as adjuvant	Phase I Phase II

MedlinePlus related topics: Malaria

Drug Information available for: Malaria Vaccines Aluminum hydroxide Algeldrate Aluminum

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Uncontrolled, Parallel Assignment, Safety/Efficacy Study
Official Title:	Phase I and IIa Trial for Assessment of Safety, Immunogenicity and Efficacy Against Sporozoite Challenge of the Candidate Malaria Vaccine PfLSA-3-Rec

Further study details as provided by Radboud University:

Primary Outcome Measures:

Phase I: proportion and severity of adverse events in both intervention groups. [ Time Frame: 1 year from first immunization ] [ Designated as safety issue: Yes ]
Phase IIa: proportion of volunteers reaching day 21 post-infection without or with a delayed onset of parasitemiae compared to control group (parasetimiae defined as ≥2 parasites per 200 fields in a thick blood film). [ Time Frame: 6 weeks from sporozoite challenge ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Phase I and IIa: Immunogenicity evaluation: antibody and cellular responses to vaccination with PfLSA-3-rec vaccine formulations. [ Time Frame: 1 year from first immunization ] [ Designated as safety issue: No ]
Phase IIa: The length of time (in hours) between parasite inoculation and detection of parasitemia, if any, up to 21 days. [ Time Frame: 6 weeks from sporozoite challenge ] [ Designated as safety issue: No ]

Estimated Enrollment:	36
Study Start Date:	October 2007
Estimated Study Completion Date:	October 2008
Estimated Primary Completion Date:	October 2008 (Final data collection date for primary outcome measure)

Eligibility

Ages Eligible for Study:	18 Years to 45 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

(Main) 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

(Main) Exclusion Criteria:

Any history of malaria
Known exposure to malaria in the previous 6 months, defined as a visit to a malaria-endemic region.
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 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00509158

Locations

Netherlands
Radboud University Nijmegen Medical Centre
Nijmegen, Netherlands, 6500 HB

Sponsors and Collaborators

Radboud University

Institut Pasteur

Investigators

Principal Investigator:

Robert Sauerwein, Prof MD

Radboud University

More Information

Responsible Party:	Radboud University Nijmegen Medical Centre ( Prof. dr. R.W. Sauerwein, principle investigator )
Study ID Numbers:	LSA3_01_06
Study First Received:	July 30, 2007
Last Updated:	November 5, 2008
ClinicalTrials.gov Identifier:	NCT00509158
Health Authority:	The Netherlands: Central Committee on Research involving Human Subjects; The Netherlands: National Institute for Public Health and Environment

Keywords provided by Radboud University:

safety
immunogenicity
efficacy

Study placed in the following topic categories:

Malaria
Healthy
Aluminum Hydroxide

Additional relevant MeSH terms:

Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

Adjuvants, Immunologic
Antacids
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009