Clinical trial NCT00400101: Phase Ia Malaria Vaccine Trial of Two Virosome-Formulated Peptides
Official title: A Randomized Placebo-Controlled Phase Ia Malaria Vaccine Trial of Two Virosome-Formulated Synthetic Peptides in Healthy Adult Volunteers
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Falciparum Malaria
Keywords: Malaria
Vaccine
Plasmodium
falciparum
Phase I
Peptide
Virosome
safety
immunogenicity
Lead sponsor: Swiss Tropical & Public Health Institute
Sponsor class: OTHER
First posted: 2006-11-16
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Influenza virosomes represent an innovative human-compatible antigen delivery system that has already proven its suitability for subunit vaccine design. The aim of the study was to proof the concept that virosomes can also be used to elicit high titers of antibodies against synthetic peptides derived from the circumsporozoite protein and from the apical-membrane-antigen 1 and that the formulations are safe in humans.

Detailed description: Influenza virosomes represent an innovative human-compatible antigen delivery system that has already proven its suitability for subunit vaccine design. The aim of the study was to proof the concept that virosomes can also be used to elicit high titers of antibodies against synthetic peptides. The specific objective was to demonstrate the safety and immunogenicity of two virosome-formulated P. falciparum protein derived synthetic peptide antigens given in two different doses alone or in combination.

Methodology The design was a single blind, randomized, placebo controlled, dose-escalating study involving 46 healthy Caucasian volunteers aged 18-45 years. Five groups of 8 subjects received virosomal formulations containing 10 ug or 50 ug of AMA 49-CPE, an apical membrane antigen-1 (AMA-1) derived synthetic phospatidylethanolamine (PE)-peptide conjugate or 10 ug or 50 ug of UK39, a circumsporozoite protein (CSP) derived synthetic PE-peptide conjugate or 50 ug of both antigens each. A control group of 6 subjects received unmodified virosomes. Virosomal formulations of the antigens (designated PEV301 and PEV302 for the AMA-1 and the CSP virosomal vaccine, respectively) or unmodified virosomes were injected i. m. on days 0, 60 and 180.

Eligibility criteria: Inclusion Criteria:

* Healthy volunteers of both sexes, aged between 18 and 45 years, with a BMI \> 18.5 and \<30 were included if they gave written informed consent

Exclusion Criteria:

* Chronix or acute illness, immunosuppression, lived in the past in a malaria endemic area, had visited such an area in the last 12 months, or had a history of clinical malaria

Primary outcomes:
measure: Incidence of adverse events
measure: Antibody concentration by Elisa
Secondary outcomes:
measure: Antibody concentration by IFAT and Western blot
measure: Cellular immunity
Other outcomes:
Locations:
Study officials:
affiliation: Swiss Tropical & Public Health Institute
name: Blaise Genton, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Okitsu SL, Silvie O, Westerfeld N, Curcic M, Kammer AR, Mueller MS, Sauerwein RW, Robinson JA, Genton B, Mazier D, Zurbriggen R, Pluschke G. A virosomal malaria peptide vaccine elicits a long-lasting sporozoite-inhibitory antibody response in a phase 1a clinical trial. PLoS One. 2007 Dec 5;2(12):e1278. doi: 10.1371/journal.pone.0001278.
citation: Genton B, Pluschke G, Degen L, Kammer AR, Westerfeld N, Okitsu SL, Schroller S, Vounatsou P, Mueller MM, Tanner M, Zurbriggen R. A randomized placebo-controlled phase Ia malaria vaccine trial of two virosome-formulated synthetic peptides in healthy adult volunteers. PLoS One. 2007 Oct 10;2(10):e1018. doi: 10.1371/journal.pone.0001018.