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

NCT00509158 | Completed Phase 1 DMC

• 1 other identifier: LSA3_01_06
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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).

Conditions

Healthy

Keywords

safety; immunogenicity; efficacy

Outcome Measures

Primary Outcomes (2)

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

  1 year from first immunization

• 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).

  6 weeks from sporozoite challenge

Secondary Outcomes (2)

• Phase I and IIa: Immunogenicity evaluation: antibody and cellular responses to vaccination with PfLSA-3-rec vaccine formulations.

  1 year from first immunization

• Phase IIa: The length of time (in hours) between parasite inoculation and detection of parasitemia, if any, up to 21 days.

  6 weeks from sporozoite challenge

Interventions

arm I: PfLSA-3-rec with aluminium hydroxide as adjuvant BIOLOGICAL

arm 2: PfLSA-3-rec with Montanide Isa 720 as adjuvant BIOLOGICAL

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Institut Pasteur: collaborator

Study Sites (1)

Radboud University Nijmegen Medical Centre

Nijmegen, 6500 HB, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 28081133 DERIVED

MeSH Terms

Interventions

Aluminum Hydroxide; Adjuvants, Pharmaceutic; mannide monooleate

Intervention Hierarchy (Ancestors)

Hydroxides; Alkalies; Inorganic Chemicals; Aluminum Compounds; Anions; Ions; Electrolytes; Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses

Study Officials

• Robert Sauerwein, Prof MD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 30, 2007
• First Posted: July 31, 2007
• Study Start: October 1, 2007
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: February 23, 2010

Record last verified: 2008-11

Locations

NL (1)