Safety and Immunogenicity of Apical Membrane Antigen 1 (PfAMA-1-FVO[25-545])

Study Overview
=================
Brief Summary
-----------------
This study will be the first time that the candidate malaria vaccine Apical Membrane Antigen 1 (PfAMA-1-FVO[25-545]) will be tested in malaria endemic populations. The phase Ib study will include adults who will be randomly allocated to either receive the malaria vaccine or the vaccine against Tetanus. Each participant will receive 3 immunizations, without the clinical investigators or the participants themselves knowing what has been given. They will then be follow-up up for immediate reactions to vaccination, and also over a longer term of one year. Blood will be taken to evaluate the biological safety parameters and also immune responses.

Detailed Description
-----------------
This will be a randomized controlled trial to evaluate the Safety and Immunogenicity of recombinant pichia pastoris blood stage malaria vaccine Apical Membrane Antigen 1 (PfAMA-1-FVO[25-545]) versus tetanus toxoid, in healthy Malian adults in Bandiagara. A phase Ia trial is currently ongoing and its interim results will be used to select the best dose/adjuvant combination to be brought to Africa. The trial is evaluating safety and immunogenicity of AMA-1 (10 µg or 50 µg) adjuvanted with aluminum hydroxide or Montanide ISA 720, or ASO2. Primary objective: - To evaluate the safety of one dose of AMA-1 (10 µg or 50 µg) adjuvanted with aluminum hydroxide or Montanide ISA 720, or ASO2, given at D0, D28 and D56 in healthy Malian adults. Secondary Objectives: To assess the humoral response to the vaccine antigen by measuring the variation in the level of IgG and its ability to recognize the native protein on merozoites. To assess the cellular immune response by measuring the T cell proliferation and cytokine production following in vitro stimulation with the vaccine antigen. The primary immunizations will be administered on days 0, 28 and a boost given at day 56. The participants will be followed up actively during the vaccination phase, and passively for one another 9 months. The will be 19 scheduled clinic visits and following will the the schedule for obtaining serology data D-28, D0, D28, D56, D84, D140 and D365 The primary evaluation will include the following: Solicited adverse events measured from day 0 to day 7 after each dose; Unsolicited adverse events measured up to one month after each dose; Serious Adverse Event (SAE) measured during the 12 months of study duration. Biological safety: two and four weeks after each vaccination, and thereafter every 12 weeks, in reference with the baseline before the first dose, by measuring the following RBC, hemoglobin, hematocrit, MCV, MCH, MCHC, platelets, WBC with differential counts, potassium, sodium, ASAT, ALAT, total bilirubin, alkaline phosphatase, γGT, creatinin. Secondary evaluation criteria: The humoral response to the vaccine antigen: assessed by measuring the level of IgG by ELISA. An IFA for at least two parasite strains will be used to verify that the antibodies elicited by the vaccine recognize the native protein on merozoites Statistical methods: Descriptive methods shall be employed to evaluate the above criteria.

Official Title
-----------------
Randomized Controlled Trial to Evaluate the Safety and Immunogenicity of Recombinant Pichia Pastoris-Expressed P. Falciparum Apical Membrane Antigen 1 (PfAMA-1-FVO[25-545]) Versus Tetanus Toxoid, in Healthy Malian Adult in Bandiagara

Conditions
-----------------
Malaria

Intervention / Treatment
-----------------
* Biological: Malaria vaccine AMA1 (PfAMA-1-FVO[25-545]
* Biological: AMA1


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18-55 years inclusive at the time of screening Residing in Bandiagara for the duration of the study Separate written informed consent obtained before screening and study start, respectively Available to participate in follow-up for the duration of study (14 months) General good health based on history and clinical examination Willingness not to become pregnant during the first five months of the study for female participants Exclusion Criteria: Previous vaccination with a investigational vaccine or a rabies vaccine Use of a investigational or non-registered drug or vaccine other than the study vaccine(s) within 30 days preceding the first study immunization, or planned use up to 30 days after the third immunization Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first immunization. This includes any dose level of oral steroids or inhaled steroids, but not topical steroids Confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection Confirmed or suspected autoimmune disease History of allergic reactions or anaphylaxis to immunizations or to any vaccine component History of serious allergic reactions to any substance, requiring hospitalization or emergent medical care History of allergy to vaccines components History of splenectomy Laboratory evidence of liver disease (alanine aminotransferase [ALT] greater than 1.25 times the upper limit of normal of the testing laboratory). Laboratory evidence of renal disease (serum creatinine greater than the upper limit of normal of the testing laboratory, or more than trace protein or blood on urine dipstick testing). Laboratory evidence of hematologic disease (absolute leukocyte count <4000/mm3 or >14,500/mm3, absolute lymphocyte count <1500/mm3, platelet count <120,000/mm3, or hemoglobin <10.0 g/dL). Administration of immunoglobulins and/or any blood products within the three months preceding the first study immunization or planned administration during the study period. Simultaneous participation in any other interventional clinical trial Acute or chronic pulmonary, cardiovascular, hepatic, renal or neurological condition, malnutrition, or any other clinical findings that in the opinion of the PI may increase the risk of participating in the study Other condition that in the opinion of the PI would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: I, AMA1 vaccine<br>20 volunteers will receive 3 doses of the vaccine | Biological: Malaria vaccine AMA1 (PfAMA-1-FVO[25-545]<br>* 3 doses of AMA 1 vaccine<br>Biological: AMA1<br>* 50 micrograms of AMA1<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| *Safety evaluation through: |  | 1 year | 
| Solicited adverse events measured from day 0 to day 7 after each dose; |  | 7 days | 
| Unsolicited adverse events measured up to one month after each dose; |  | 84 days | 
| Serious Adverse Events measured during the 12 months of study duration. |  | 1 year | 
| Biological safety: two and four weeks after each vaccination, and thereafter every 12 weeks, in reference with the baseline before the first dose, by measuring the following : |  | 1 year | 
| RBC, hemoglobin, hematocrit, MCV, MCH, MCHC, platelets, WBC with differential counts, potassium, sodium, ASAT, ALAT, total bilirubin, alkaline phosphatase, γGT, creatinin |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| *Immunogenicity evaluation through: |  | 84 days | 
| The humoral response to the vaccine antigen: assessed by measuring the level of IgG by ELISA. |  | 84 days | 
| An IFA for at least two parasite strains will be used to verify that the antibodies elicited by the vaccine recognize the native protein on merozoites. |  | 84 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Malaria, vaccine, Apical Membrane Antigene, Mali, Adults