Safety and Immunogenicity Study of a Candidate Tuberculosis Vaccine in Healthy Infants
- Conditions
- Tuberculosis
- Registration Number
- NCT01098474
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
This purpose of the study is to assess the safety and immunogenicity of a GSK Biologicals' candidate tuberculosis vaccine (692342) when administered concomitantly with or after the Expanded Programme of Immunisation vaccines regimen to healthy infants aged between and including 2 and 7 months, living in a tuberculosis endemic region.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 301
- Male and female subjects who the investigator believes that their parent(s)/ Legally Acceptable Representative (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 Bacille Calmette Guerrin.
- Healthy subjects as established by medical history and clinical examination before entering into the study.
For the 'Outside Expanded Programme on Immunisation' cohort:
- Must have documented evidence that he/she has completed the primary Expanded Programme on Immunisation regimen at least 1 month prior to planned vaccination with investigational vaccination regimen.
- 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 Bacille Calmette Guerrin, oral polio vaccine and Hepatitis B vaccine but NO further Expanded Programme on Immunisation vaccines.
- Aged between 2 and 4 months at the time of the first study vaccination with diphtheria, tetanus, whole cell pertussis/ Haemophilus influenzae type b vaccine + pneumococcal conjugate vaccine + oral polio vaccine.
- Child in care
- Acute or chronic, clinically significant pulmonary, cardiovascular, 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.
- Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
- A family history of congenital or hereditary immunodeficiency.
- 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 increase the risk of having an adverse outcome from participation in the trial.
- Acute disease and/or fever at the time of enrolment.
- 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 Expanded Programme on Immunisation' Cohort only: Previous vaccination with diphtheria, tetanus, pertussis, Haemophilus 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.
- 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 at screening defined as weight-for-age Z-score < -3 standard deviation.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Number of Subjects With Grade 3 Solicited Local Symptoms After Dose 1, Dose 2 and Across Doses From Day 0 to Day 6 Solicited local symptoms assessed were pain, redness and swelling. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.
Number of Subjects With Grade 3 Solicited Local Symptoms After Dose 2, Dose 3 and Across Doses. From Day 0 to Day 6 Solicited local symptoms were only collected after Dose 2 of EPI vaccination. Solicited local symptoms assessed were pain, redness and swelling. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.
Number of Subjects With Grade 3 Solicited General Symptoms After Dose 1, Dose 2 and Across Doses. From Day 0 to Day 6 Solicited general symptoms assessed were drowsiness, fever \[defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)\], irritability/fussiness and loss of appetite. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever \> 39.0 °C.
Number of Subjects With Serious Adverse Events (SAEs) From Month 0 to Month 17 Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Number of Subjects With Grade 3 Solicited General Symptoms After Dose 2, Dose 3 and Across Doses. From Day 0 to Day 6 Solicited general symptoms were only collected after Dose 2 of EPI vaccination. Solicited general symptoms assessed were drowsiness, fever \[defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)\], irritability/fussiness and loss of appetite. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever \> 39.0 °C.
Number of Subjects With Grade 3 Unsolicited Adverse Events (AEs) From Day 0 to Day 29 An unsolicited adverse event is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Number of Subjects With Grade 3 Haematological and Biochemical Levels At Month 8 Haematological/Biochemical parameters assessed were: Haemoglobin (Haem), White Blood Cells (WBC), Platelets (PLA), Alanine Aminotransferase (ALA) and Creatinine (CREA). Grade 3 = Haem.: \< 5.0 g/dL; WBC.: 1.0 to 1.4 x 10³/µL; PLA.: \< 25x10³/µL; ALA.: 5.1 to 10.0 x ULN and CREA: 3.1 to 6.0 x ULN.
- Secondary Outcome Measures
Name Time Method Number of Seropositive Subjects Against M72 Antigen Before vaccination (PRE) and after each dose [at 1, 6 and 12 months post-vaccination (M1, M6 and M12)] A seropositive subject was a subject whose M72 antibody concentration was greater than or equal to 2.8 ELISA units per millilitre (EL.U/mL).
Number of Seropositive Subjects Against Bordetella Pertussis (Anti-BPT) Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)] A seropositive subject was a subject whose anti-BPT antibody concentration was ≥ 15 EL.U/mL.
Number of Seropositive Subjects Against Polio (Anti-Polio1, Anti-Polio2, Anti-Polio3) Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)] A seropositive subject was a subject whose anti-polio antibody titer was ≥ 1:8.
Concentration of Antibodies Against M72 Antigen Before vaccination (PRE) and after each dose [at 1, 6 and 12 months post-vaccination (M1, M6 and M12)] Concentrations given in EL.U/mL were expressed as Geometric Mean Concentrations (GMCs).
Number of Seroprotected Subjects Against Haemophilus Influenzae Type B (Anti-PRP) Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)] A seroprotected subject was a subject whose anti-PRP antibody concentration was ≥ 0.15 micrograms per millilitre (µg/mL).
Anti-HB Antibody Concentrations Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)] Concentrations given in mIU/mL were expressed as Geometric Mean Concentrations (GMCs).
Anti-Polio1, Anti-Polio2, Anti-Polio3 Antibody Titers Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)] Concentrations given in titers were expressed as Geometric Mean Titers (GMTs).
Frequency of M. Tuberculosis Fusion Protein M72 (M72)-Specific Cluster of Differentiation (CD)4+ T Cells Per Million Cells Expressing at Least Two Different Immune Markers Twelve Months post each dose (M12) Immune markers expressed were among Interleukin-2 (IL-2) and/or Interferon-gamma (INF-γ) and/or Tumour necrosis factor-alpha (TNF-α) and/or CD40-ligand (CD40-L).
Number of Seroprotected Subjects Against Diphtheria Toxoid (Anti-D) and Tetanus Toxoid (Anti-T) Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)] A seroprotected subject was a subject whose anti-diphtheria toxoid (anti-D)/anti-tetanus toxoid (anti-T) antibody concentration was ≥ 0.1 international-units per millilitre (IU/mL).
Anti-BPT Antibody Concentrations Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)] Concentrations given in EL.U/mL were expressed as Geometric Mean Concentrations (GMCs).
Number of Subjects With Serious Adverse Events (SAEs) From Day 0 up to 12 months post last vaccination Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Anti-PRP Antibody Concentrations Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)] Concentrations given in µg/mL were expressed as Geometric Mean Concentrations (GMCs).
Number of Seropositive Subjects Against Streptococcus Pneumoniae (Anti-4, Anti-6B, Anti-9V, Anti-14, Anti-18C, Anti-19F, Anti-23F) Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)] A seropositive subject was a subject whose anti-S pneumoniae antibody concentration was ≥ 0.05 µg/mL.
Number of Subjects With S. Pneumoniae Antibody Concentrations ≥ 0.2 Microgram/Milliliter Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)] A seroconverted subject is a vaccinated subject with at least a four fold increased antibody titer post vaccination.
Number of Subjects With Normal, Grade 1 (G1), Grade 2 (G2) or Grade 4 (G4) Haematological and Biochemical Markers Before vaccination (PRE) Levels assessed for Haemoglobin (Haem), White Blood Cells (WBC), Platelets (PLA), Alanine Aminotransferase (ALA) and Creatinine (CREA) were: normal, G1, G2 and G4 . Values that did not fall under normal levels or assessed grades were missing.
Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers Twelve Months post Dose 3 [PIII(M14)] Levels assessed for Haemoglobin (Haem), White Blood Cells (WBC), Platelets (PLA), Alanine Aminotransferase (ALA) and Creatinine (CREA) were: normal, grade 1 (G1), grade 2 (G2) and grade 4 (G4). Values that did not fall under normal levels or assessed grades were missing.
Frequency of M. Tuberculosis Fusion Protein M72 (M72)-Specific Cluster of Differentiation (CD)8+ T Cells Per Million Cells Expressing at Least Two Different Immune Markers Twelve Months after each dose (M12) Immune markers expressed were among Interleukin-2 (IL-2) and/or Interferon-gamma (INF-γ) and/or Tumour necrosis factor-alpha (TNF-α) and/or CD40-ligand (CD40-L).
Number of Seropositive Subjects Against Hepatitis B (Anti-HB) Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)] A seropositive subject was a subject whose anti-HB antibody concentration was ≥ 10 milli-international units per millilitre (mIU/mL).
Number of Seropositive Subjects Against Hepatitis B (Anti-HB) With Antibody Concentrations ≥100mIU/mL Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)] A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following partial or complete retesting/reanalysis. Following from this, the table shows data with titers ≥ 100 mIU/mL.
Anti-4, Anti-6B, Anti-9V, Anti-14, Anti-18C, Anti-19F, Anti-23F Antibody Concentrations Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)] Concentrations, given in µg/mL, were expressed as Geometric Mean Concentrations (GMCs).
Anti-D, Anti-T Antibody Concentrations Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)] Concentrations given in IU/mL, were expressed as Geometric Mean Concentrations (GMCs).
Trial Locations
- Locations (1)
GSK Investigational Site
🇬🇲Banjul, Gambia
GSK Investigational Site🇬🇲Banjul, Gambia