Malaria disease
Conditions
Interventions
Product Name: Active control
Product Code: RTS,S/saline diluent
Pharmaceutical Form: Powder and solvent for suspension for injection
Current Sponsor code: RTS,S
Concentration unit: µg/ml microgram(s)/
Sponsors
GlaxoSmithKline Biologicals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • 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, hepatitis B surface antigen (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, i.e. have a current tubal ligation, hysterectomy, ovariectomy or be post-menopausal, 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 six months prior to the first vaccine dose. (For corticosteroids, this will mean prednisone, or equivalent, >= 0.5 mg/kg/day. Inhaled and topical steroids are allowed.) • 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 (significant Immunoglobulin [IgE]-mediated events) or anaphylaxis to previous immunizations. • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). • Personal history of autoimmune disease or subjects who describe a first-degree relative with clearly documented autoimmune disease. Exclusionary medical histories will include the following diagnoses: systemic lupus erythmatosus, rheumatoid arthritis, mixed connective tissue disease, scleroderma, vasculitis, and multiple sclerosis. • 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). • History of any neurologic disorders or seizures. • Acute disease at the time of enrolment. (Acute disease is defined as the presence of a moderate or severe illness with or without fever. All vaccines can be administered to persons with a minor illness such as diarrhoea, mild upper respiratory infection with or without low-grade febrile illness, i.e. Oral temperature <37.5°C (99.5°F) / axillary temperature <37.5°C (99.5°F). • 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 AS02A, AS01B or related products containing MPL and QS21. • Pregnant or lactating female. • History of chronic alcohol consumption and/or drug abuse. • Female planning to become pregnant or planning to discontinue contraceptive precautions.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Immunogenicity • To demonstrate the superiority of anti-CS antibody response at 1 month post Dose 3 induced by RTS,S vaccine antigen formulated with AS01B adjuvant compared to RTS,S vaccine antigen reconstituted with saline. • To demonstrate the superiority of the anti-CS antibody response at 1 month post Dose 3 induced by RTS,S vaccine antigen formulated with AS02A adjuvant compared to RTS,S vaccine antigen reconstituted with saline. The primary objective of the trial is considered reached if 1 of the 2 co-primary objectives is met.;Secondary Objective: Safety • To assess the safety and reactogenicity of RTS,S/AS01B and RTS,S/AS02A vaccine formulations as well as that of RTS,S reconstituted with saline diluent, following a three-dose vaccination regimen according to a 0, 1, 2-month schedule to malaria-naïve adults aged 18 to 45 years. Immunogenicity • To describe the humoral and cellular immunogenicity of RTS,S/AS01B and RTS,S/AS02A vaccine formulations as well as that of RTS,S vaccine antigen reconstituted with saline diluent when administered according to a 0, 1, 2-month schedule to malaria-naïve adults aged 18 to 45 years by: ? assessing the antibody responses to CS and HBs antigens. ? assessing the cellular immune responses to the CS and HBs antigens by flow cytometry using intracellular cytokine staining (ICS) analyses on frozen peripheral blood mononuclear cells (PBMCs). ;Primary end point(s): Immunogenicity Anti-CS antibody titers one month post Dose 3 for RTS,S/AS01B, RTS,S/AS02A and RTS,S/Saline Groups. | — |
Countries
Belgium
Outcome results
None listed