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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Plasmodium Falciparum Malaria

Intervention / Treatment
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* Biological: PfAMA-1-FVO[25-545]


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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