Healthy volunteers (evaluation of safety and reactogenicity of TB vaccine when administered in healthy infants)
Conditions
Interventions
Product Name: TB vaccine M72 AS01E
Pharmaceutical Form: Powder and solvent for suspension for injection
INN or Proposed INN: -
Current Sponsor code: M72 protein
Other descriptive name: Recombinant Tub
Sponsors
GlaxoSmithKline Biologicals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Male and female subjects who the investigator believes that their parent(s)/legally acceptable representative(s) [LAR(s)] can and will comply with the requirements of the protocol. •Written or oral, signed or thumb-printed and witnessed informed consent obtained from the subject's parent(s)/LAR(s). •Subjects who received their birth dose of BCG. •Healthy subjects as established by medical history and clinical examination before entering into the study. For the 'Outside EPI' cohort: •Must have documented evidence that he/she has completed the primary EPI regimen at least 1 month prior to planned vaccination with M72/AS01E. •Aged between 5 and 7 months at the time of the first study vaccination. For the 'Within EPI' cohort: •Must have received the birth dose of BCG, OPV and Hepatitis B vaccine but NO further EPI vaccines. •Aged between 2 and 4 months at the time of the first study vaccination with DTPwHepB/Hib + PCV+ OPV. Are the trial subjects under 18? yes Number of subjects for this age range: 301 F.1.2 Adults (18-64 years) no 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: •Child in care •Acute or chronic, clinically significant pulmonary, cardio-vascular, hepatic or renal abnormality, as determined by physical examination and/or laboratory screening tests. •Laboratory screening tests out of range, which in the investigator's opinion affects the ability of the child to take part in the study, specifically: -Alanine aminotransferase (ALT) above acceptable limit -Creatinine above acceptable limit -Haemoglobin below acceptable limit -Platelet count below acceptable limit -Total white cell count below acceptable limit •Any confirmed or suspected immunosuppressive or im-munodeficient condition, based on medical history and physical examination. •A family history of congenital or hereditary immunodefi-ciency. •Major congenital defects. •History of any neurological disorders or seizures. •Any condition or illness or medication, which in the opinion of the investigator might interfere with the evaluation of the safety or immunogenicity of the study vaccine. •Any other findings that the investigator feels would in-crease the risk of having an adverse outcome from par-ticipation in the trial. •Acute disease and/or fever at the time of enrolment: -fever is defined as temperature >= 37.5°C on oral, axillary or tympanic setting, or >= 38.0°C on rectal setting. -Subjects with a minor illness without fever may be enrolled at the discretion of the investigator. •Use of any investigational or non-registered product other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period. •For the 'Within EPI' Cohort only: Previous vaccination with diphtheria, tetanus, pertussis, H. influenzae type b and pneumococcal conjugate vaccine. •History of previous administration of experimental Mycobacterium tuberculosis vaccines. •Administration of immunoglobulins, blood transfusions and/or other blood products since birth to the first dose of study vaccine or planned administration during the study period. •Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. For corticosteroids, this will mean prednisone >= 0.5 mg/kg/day, or equivalent. Inhaled and topical steroids are allowed. •Planned participation or 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. •Any chronic drug therapy to be continued during the study period, with the exception of vitamins and/or dietary supplements •History of allergic reactions or anaphylaxis to any vaccine. •History of any reaction or hypersensitivity likely to be exacerbated by any component of the study vaccines. •Severe malnutrition defined as weight-for-age Z-score < -3 SD* •Children will not be enrolled if any maternal, obstetrical or neonatal event that has occurred might, in the judgment of the investigator, result in increased neonatal/infant morbidity. * World Health Organisation (WHO) Global Database on Child Growth and Malnutrition, Geneva, 1997.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To evaluate the safety and reactogenicity of one or two doses of the TB vaccine candidate (M72/AS01E) when given to healthy infants concomitantly with the Expanded Programme on Immunisation (EPI) regimen containing DTPwHepB/Hib + pneumococcal conjugate vaccine (PCV) + oral polio vaccine (OPV). •To evaluate the safety and reactogenicity of one or two doses of the TB vaccine candidate (M72/AS01E) when given to healthy infants after receiving the EPI vaccines containing DTPwHepB/Hib+PCV+OPV.;Secondary Objective: •To evaluate the cell-mediated immune (CMI) response of the TB vaccine candidate (M72/AS01E) when given as one or two doses to healthy infants concomitantly with, or after completion of the EPI regimen containing DTPwHepB/Hib+PCV+OPV. •To evaluate the humoral immune response of the TB vaccine candidate (M72/AS01E) when given to healthy in-fants as one or two doses concomitantly with, or after completion of the EPI regimen containing DTPwHepB/Hib+PCV +OPV. •To describe the humoral immune response to diphtheria, tetanus, whole-cell pertussis, polio serotypes 1, 2 and 3, Streptococcus pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F, Hepatitis B and Haemophilus influenzae (H. influenzae) (type b following vaccination with the EPI vaccines containing DTPwHepB/Hib+PCV+OPV.;Primary end point(s): 1) Occurrence of grade 3 solicited local and general adverse events (AEs) after each vaccine dose. 2) Occurrence of grade 3 unsolicited AEs after each vaccine dose. 3) Occurrence of serious adverse events (SAEs) 4) Occurrence of grade 3 haematological and biochemical levels at defined timepoints.;Timepoint(s) of evaluation of this end point: 1) During the 7-day follow-up period (day of vaccination and 6 subsequent days) after each dose of M72/AS01E or control. 2) During the 30-day follow-up period (day of vaccination and 29 subsequent days) after each dose of M72/AS01E or control. 3) From study start up till 1 month after the last vaccination with M72/AS | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1) Both cohorts, 1 (2) dose(s) of M72: Day 0, Week 1, Month 1, 6 and Year 1 after dose 1 (2) of M72 Control group: D0, W1, M1, M6 and Y1 after dose 2 of meningitis vaccine (Outside EPI cohort) or after dose 3 of EPI regimen (Within EPI cohort) 2) Both cohorts, 1 (2) dose(s) of M72: D0, M1, M6 and Y1 after dose 1 (2) of M72 Control group: D0, M1, M6 and Y1 after dose 2 of meningitis vaccine (Outside EPI). Before first dose of EPI regimen (Within EPI) 3) Before first vaccination and M1 after dose 3 of EPI regimen 4) During the 7-day follow-up period after each dose of M72 or control 5) During the 30-day FU period after each dose of M72 or control 6) During the study period 7) D0, D7 after each dose of M72 or control, M1, M6 and Y1 after last dose of M72 or control;Secondary end point(s): 1) Cell-mediated immunogenicity with respect to components of the investigational vaccine at defined timepoints. •Frequency of M72-specific CD4+/CD8+ T-cells per 10E6 cells expressing at least two different immune markers (IL-2 and/or IFN-g and/or TNF-a and/or CD40-L) in order to assess the magnitude of immune response by M72-specific CD4+/CD8+ T-cells. •Frequency of M72-specific CD4+/CD8+ T-cells per 10E6 cells expressing all combinations of immune markers among IL-2, IFN-g, TNF-a and CD40-L in order to assess the phenotypic expression profile of M72-specific CD4+/CD8+ T-cells. 2) Humoral immune response to components of the investigational vaccine at defined timepoints. •Antibody titres specific to the M72 antigen. 3) For the 'Within EPI' cohort only: Immune response to components of the EPI vaccines at defined timepoints •Humoral immune response to diphtheria, tetanus, whole-cell pertussis, polio serotypes 1, 2 and 3, Hepatitis B and H. influenzae type b and PCV serotypes. 4) Occurrence of solicited local and general AEs after each vaccine dose. 5) Occurrence of unsolicited AEs after each vaccine dose. 6) Oc | — |
Countries
Gambia
Contacts
Public ContactClinical Disclosure Advisor
GlaxoSmithKline Biologicals
Outcome results
None listed