E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Vaccination against tuberculosis |
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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 |
To evaluate the safety and reactogenicity of GSK Biologicals’ candidate M72/AS02A and M72/AS01B tuberculosis vaccines and the comparator vaccines (Mtb72F/AS02A, M72/Saline and AS01B) when given according to a 0, 1 month schedule in healthy PPD-negative adults aged 18 to 50 years. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the humoral immunogenicity as measured by ELISA for the candidate tuberculosis vaccines (M72/AS02A and M72/AS01B) and the comparator vaccines (Mtb72F/AS02A, M72/Saline and AS01B). • To evaluate cellular mediated immune response for the candidate tuberculosis vaccines (M72/AS02A and M72/AS01B) and the comparator vaccines (Mtb72F/AS02A, M72/Saline and AS01B) in terms of Th1 cytokine expression of antigen-specific CD4/CD8 T cells, as determined by flow cytometry after in-vitro stimulation of frozen PBMCs. in terms of Th1 cytokine production in serum as determined by ELISA.
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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 50 years of age at the time of the first vaccination. • Written informed consent obtained from the subject prior to any study procedure. • Free of obvious health problems as established by medical history and clinical examination before entering into the study. • Subjects must have PPD negative skin reactivity (0 mm induration 48 to72 hours after PPD skin test administration). • Clinically normal laboratory values for creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), complete blood count (CBC) and differential, haemoglobin, platelet count and urinalysis. • Seronegative for human immunodeficiency virus 1 and 2 (HIV 1/2) antibodies, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibodies. • If the subject is female, she must be of non-childbearing potential, i.e. either surgically sterilized or one year post-menopausal; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series. • No evidence of pulmonary pathology (i.e. acute or chronic pulmonary disease; past TB infection/disease) as confirmed by chest X-ray. |
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E.4 | Principal exclusion criteria |
• History of previous exposure to experimental products containing AS02A, AS01B or related products containing MPL and QS21. • Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine 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). • Any chronic drug therapy to be continued during the study period, with the exception of vitamins and/or dietary supplements, herbal medications, birth control pills, anti-histamines for seasonal allergies, SSRIs (e.g. Prozac, Zoloft, Paxil), NSAIDs (nonsteroidal anti-inflammatory drugs e.g. aspirin, ibuprofen), and acetaminophen. • History of previous administration of experimental Mycobacterium tuberculosis vaccines • History of documented work related or close personal contact (same household) exposure to persons infected with Mycobacterium tuberculosis • Administration of any immunoglobulins, any immunotherapy and/or any blood products within the 3 months preceding the first dose of study vaccination, or planned administrations during the study period. • Participation in another experimental protocol during the study period. • Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination (no laboratory testing is required). • History of any acute or chronic illness or medication that, in the opinion of the investigator, may interfere with the evaluation of the safety or immunogenicity of the vaccine. • Volunteers with a personal history of autoimmune disease or who describe a first-degree relative with clearly documented autoimmune disease • History of any neurologic disorders or seizures. • History of chronic alcohol consumption and/or drug abuse. • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. • Major congenital defects. • Pregnant or lactating female. • 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) |
Safety and reactogenicity as determined by • Occurrence, intensity and relationship to vaccination of solicited local and general symptoms during the 7-day follow-up period following vaccination (day of vaccination and 6 subsequent days) after each vaccine dose in each group. • Occurrence, intensity and relationship to vaccination of unsolicited symptoms during the 30-day follow-up period following vaccination (day of vaccination and 29 subsequent days) after each vaccine dose in each group. • Occurrence and relationship to vaccination of serious adverse events during the entire study period in each group. • Haematological and biochemical levels, at Days 0, 1, 7, 30, 31, 37 and 60 in each group.
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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 | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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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Active phase consists of a 2-dose vaccination schedule with a 1 month follow-up period. Follow-up for safety and immunogenicity will continue for 3 years after administration of vaccination with a retrospective follow-up for serious adverse events and a blood sample collected each year. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |