E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 4 |