Characterisation of the Immune Responses of 2 Experimental Malaria Vaccines

Study Overview
=================
Brief Summary
-----------------
In this study, two experimental malaria vaccines (with adjuvants) are tested to evaluate and characterise how the vaccine exactly works on the immune system by comparing it to a control (without adjuvant). The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Official Title
-----------------
Adjuvant Justification Study of Candidate Malaria Vaccines (257049), Administered According to a 0, 1, 2 Months Schedule .

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

Intervention / Treatment
-----------------
* Biological: GSK Malaria vaccine 257049


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects who the investigator believes can and will comply with the requirements of the protocol. A male or female between, and including, 18 and 45 years of age at the time of the first vaccination. Written informed consent obtained from the subject. Free of obvious health problems as established by medical history and clinical examination before entering into the study. Have clinically normal laboratory values for creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), complete blood count (CBC) and differential at screening. Be seronegative for human immunodeficiency virus-1 and 2 (HIV 1/2) antibodies, HBsAg and hepatitis C virus (HCV) antibodies. Have anti HBs titre ≥ 10mIU/ml at screening. If the subject is female, she must be of non-childbearing potential or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the vaccination series. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the first vaccine dose. Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccine. Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device). Any history of clinical malaria. Known exposure to malaria parasites within the previous 12 months. Planned travel to a malaria endemic region during the study period. History of allergic reactions or anaphylaxis to previous immunizations. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. Personal history of autoimmune disease or subjects who describe a first-degree relative with clearly documented autoimmune disease. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s). Major congenital defects or serious chronic illness(es). Acute disease at the time of enrolment. History of any neurologic disorders or seizures. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests. Hepatomegaly, right upper quadrant abdominal pain or tenderness. Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period. History of previous exposure to experimental products containing any component of the vaccines used in this study. Pregnant or lactating female. History of chronic alcohol consumption and/or drug abuse. Female planning to become pregnant or planning to discontinue contraceptive precautions.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br> | Biological: GSK Malaria vaccine 257049<br>* Three-dose vaccination by slow intramuscular injection. Three different formulations of this vaccine are tested (without adjuvant, with adjuvant AS01B, with adjuvant AS02A).<br>|
| Experimental: Group B<br> | Biological: GSK Malaria vaccine 257049<br>* Three-dose vaccination by slow intramuscular injection. Three different formulations of this vaccine are tested (without adjuvant, with adjuvant AS01B, with adjuvant AS02A).<br>|
| Experimental: Group C<br> | Biological: GSK Malaria vaccine 257049<br>* Three-dose vaccination by slow intramuscular injection. Three different formulations of this vaccine are tested (without adjuvant, with adjuvant AS01B, with adjuvant AS02A).<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-CS antibody titers. |  | One month post Dose 3. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence, intensity and relationship to vaccination of solicited local and general symptoms. |  | During the 7-day follow-up period following vaccination after each vaccine dose. | 
| Occurrence, intensity and relationship to vaccination of unsolicited symptoms. |  | During the 30-day follow-up period following vaccination after each vaccine dose. | 
| Occurrence of serious adverse events. |  | Up until 1 month post dose 3. | 
| Antibody responses to the P. falciparum circumsporozoite (CS) antigen. |  | At Day 0, prior to dose 2, prior to dose 3 and 1 month post-dose 3. | 
| Antibody responses to HBs antigen. |  | At Day 0, prior to dose 2, prior to dose 3 and 1 month post-dose 3 | 
| Frequency of CS and Hepatitis B surface agent (HBs)-specific CD4+ and CD8+ T cells expressing Th1 specific activation markers and cytokines. |  | At Day 0, prior to dose 2, prior to dose 3 and 1 month post-dose 3 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Adjuvant, Malaria, Safety, Immunogenicity