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

Primary Purpose

Healthy

Status
Completed
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
arm I: PfLSA-3-rec with aluminium hydroxide as adjuvant
arm 2: PfLSA-3-rec with Montanide Isa 720 as adjuvant
Sponsored by
Radboud University Medical Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional prevention trial for Healthy focused on measuring safety, immunogenicity, efficacy

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

(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.

Sites / Locations

  • Radboud University Nijmegen Medical Centre

Outcomes

Primary Outcome Measures

Phase I: proportion and severity of adverse events in both intervention groups.
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).

Secondary Outcome Measures

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.

Full Information

First Posted
July 30, 2007
Last Updated
February 22, 2010
Sponsor
Radboud University Medical Center
Collaborators
Institut Pasteur
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1. Study Identification

Unique Protocol Identification Number
NCT00509158
Brief Title
Safety and Efficacy Study of Plasmodium Falciparum LSA-3 Malaria Vaccine
Acronym
LSA-3-rec
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 Type
Interventional

2. Study Status

Record Verification Date
November 2008
Overall Recruitment Status
Completed
Study Start Date
October 2007 (undefined)
Primary Completion Date
October 2008 (Actual)
Study Completion Date
October 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Radboud University Medical Center
Collaborators
Institut Pasteur

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy
Keywords
safety, immunogenicity, efficacy

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
arm I: PfLSA-3-rec with aluminium hydroxide as adjuvant
Intervention Type
Biological
Intervention Name(s)
arm 2: PfLSA-3-rec with Montanide Isa 720 as adjuvant
Primary Outcome Measure Information:
Title
Phase I: proportion and severity of adverse events in both intervention groups.
Time Frame
1 year from first immunization
Title
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 Measure Information:
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Sauerwein, Prof MD
Organizational Affiliation
Radboud University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Radboud University Nijmegen Medical Centre
City
Nijmegen
ZIP/Postal Code
6500 HB
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
28081133
Citation
Coffeng LE, Hermsen CC, Sauerwein RW, de Vlas SJ. The Power of Malaria Vaccine Trials Using Controlled Human Malaria Infection. PLoS Comput Biol. 2017 Jan 12;13(1):e1005255. doi: 10.1371/journal.pcbi.1005255. eCollection 2017 Jan.
Results Reference
derived

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

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