Assessment of Three Formulations of the Candidate Vaccine AMA 1 in Healthy Dutch Adult Volunteers

Assessment of the Safety and Immunogenicity of Three Formulations of the Recombinant Pichia Pastoris Apical Membrane Antigen 1 (PfAMA-1-FVO[25-545]), Blood-Stage Malaria Vaccine in Healthy Dutch Adult Volunteers : a Phase 1, Single- Blind, Randomised, Dose-Escalating, Unicentre Trial

The objective of this study was to evaluate the safety of a candidate malaria vaccine (PfAMA-1) at 3 doses given at monthly intervals of 2 different dosages of AMA-1 (10 μg or 50 μg ) adjuvanted either with alum hydroxide or AS02A or Montanide ISA 720 in healthy adults not previously exposed to the parasite Plasmodium falciparum.

Study Overview

• Status: Completed
• Conditions: Plasmodium Falciparum Malaria
• Intervention / Treatment: Biological: PfAMA-1-FVO[25-545]

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands
    • Radboud University Nijmegen Medical Centre
  • Rijswijk, Netherlands
    • Biomedical Primate Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Age > 18 and < 45 years healthy volunteers.
• General good health based on history and clinical examination.
• All volunteers have to sign the informed consent form.
• Negative pregnancy test.
• Use of adequate contraception for females up to three months after the third injection (D140).
• Reachable by phone during the whole study period (18 months).

Exclusion Criteria:

• History of malaria or residence in malaria endemic areas within the past six months.
• Positive serology for malaria antigen PfAMA-1
• Previously participated in any malaria vaccine study
• 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.
• Any laboratory abnormalities on screened blood samples beyond the normal range, as defined at UMC St Radboud. Positive HIV, HBV or HCV tests.
• Volunteers should not be enrolled in any other clinical trial during the whole trial period.
• Volunteers should not receive chronic medication, especially immunosuppressive agents (steroids, immunomodulating or immunosuppressive drugs) during the three months preceding the screening visit or during the study period.
• Pregnant or lactating women.
• Volunteers unable to give written informed consent.
• Volunteers unable to be closely followed for social, geographic or psychological reasons.
• Previous history of drug or alcohol abuse interfering with normal social function during a period of one year prior to enrollment in the study.
• Volunteers should not perform exercise four hours before blood draw and should not donate blood for non study-related purposes during the entire duration of the study.
• Known hypersensitivity to any of the vaccine components (adjuvant or peptide).
• Volunteers are not allowed to receive any vaccination or gammaglobulin during a period three months prior to the first immunization and up to six months after the 3rd immunization. If a vaccination is necessary during this period, the volunteer will be withdrawn from the study.
• Volunteers are not allowed to travel to malaria endemic countries during the study period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; The experimental vaccine PfAMA1 formulated in Alhydrogel	Biological: PfAMA-1-FVO[25-545]; Subcutaneous vaccination of 0.5ml of two dosage 10 and 50ug PfAMA1
Active Comparator: 2; The experimental vaccine PfAMA1 formulated in Montanide ISA720	Biological: PfAMA-1-FVO[25-545]; Subcutaneous vaccination of 0.5ml of two dosage 10 and 50ug PfAMA1
Active Comparator: 3; The experimental vaccine PfAMA1 formulated in ASO2A	Biological: PfAMA-1-FVO[25-545]; Subcutaneous vaccination of 0.5ml of two dosage 10 and 50ug PfAMA1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Local and systemic reactogenicity	Day 0-14 after each vaccination

Secondary Outcome Measures

Outcome Measure	Time Frame
Biological Safety	28 days after each vaccination
Humoral and Cellular immunogenicity	until 365 days after the first immunisation

Collaborators and Investigators

• Sponsor: European Malaria Vaccine Initiative
• Collaborators: Radboud University Medical Center; GlaxoSmithKline; Biomedical Primate Research Centre; Seppic
• Investigators: Principal Investigator: Robert Sauerwein, Prof. MD, Radboud University Medical Center

Publications and helpful links

General Publications

• Remarque EJ, Roestenberg M, Younis S, Walraven V, van der Werff N, Faber BW, Leroy O, Sauerwein R, Kocken CH, Thomas AW. Humoral immune responses to a single allele PfAMA1 vaccine in healthy malaria-naive adults. PLoS One. 2012;7(6):e38898. doi: 10.1371/journal.pone.0038898. Epub 2012 Jun 29.
• Roestenberg M, Remarque E, de Jonge E, Hermsen R, Blythman H, Leroy O, Imoukhuede E, Jepsen S, Ofori-Anyinam O, Faber B, Kocken CH, Arnold M, Walraven V, Teelen K, Roeffen W, de Mast Q, Ballou WR, Cohen J, Dubois MC, Ascarateil S, van der Ven A, Thomas A, Sauerwein R. Safety and immunogenicity of a recombinant Plasmodium falciparum AMA1 malaria vaccine adjuvanted with Alhydrogel, Montanide ISA 720 or AS02. PLoS One. 2008;3(12):e3960. doi: 10.1371/journal.pone.0003960. Epub 2008 Dec 18.

Helpful Links

• Information on current recruitment at Radboud University Nijmegen Medical Centre

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): September 1, 2007
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: August 6, 2008
• First Submitted That Met QC Criteria: August 7, 2008
• First Posted (Estimate): August 8, 2008

Study Record Updates

• Last Update Posted (Estimate): August 8, 2008
• Last Update Submitted That Met QC Criteria: August 7, 2008
• Last Verified: August 1, 2008

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Falciparum
• Other Study ID Numbers: AMA-1_1_03; EUDRACT No 2005-00232-24