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

This study has been completed.
Sponsor:
Collaborator:
Institut Pasteur
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00509158
First received: July 30, 2007
Last updated: February 22, 2010
Last verified: November 2008
  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 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


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
Study Completion Date: October 2008
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

No publications provided

Responsible Party: Prof. dr. R.W. Sauerwein, principle investigator, Radboud University Nijmegen Medical Centre
ClinicalTrials.gov Identifier: NCT00509158     History of Changes
Other Study ID Numbers: LSA3_01_06
Study First Received: July 30, 2007
Last Updated: February 22, 2010
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

Additional relevant MeSH terms:
Aluminum Hydroxide
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antacids
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014