Safety and Efficacy Study of Plasmodium Falciparum LSA-3 Malaria Vaccine (LSA-3-rec)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00509158
Recruitment Status : Completed
First Posted : July 31, 2007
Last Update Posted : February 23, 2010
Institut Pasteur
Information provided by:
Radboud University

Brief 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 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 or disease Intervention/treatment 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 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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
Study Start Date : October 2007
Actual Primary Completion Date : October 2008
Actual Study Completion Date : October 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria
Drug Information available for: Aluminum

Primary Outcome Measures :
  1. Phase I: proportion and severity of adverse events in both intervention groups. [ Time Frame: 1 year from first immunization ]
  2. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

(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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00509158

Radboud University Nijmegen Medical Centre
Nijmegen, Netherlands, 6500 HB
Sponsors and Collaborators
Radboud University
Institut Pasteur
Principal Investigator: Robert Sauerwein, Prof MD Radboud University

Responsible Party: Prof. dr. R.W. Sauerwein, principle investigator, Radboud University Nijmegen Medical Centre Identifier: NCT00509158     History of Changes
Other Study ID Numbers: LSA3_01_06
First Posted: July 31, 2007    Key Record Dates
Last Update Posted: February 23, 2010
Last Verified: November 2008

Keywords provided by Radboud University:

Additional relevant MeSH terms:
Protozoan Infections
Parasitic Diseases
Aluminum Hydroxide
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Agents