Safety and Immunogenicity Study of a Candidate Tuberculosis Vaccine in Healthy Infants

Safety and Immunogenicity Study of GSK Biologicals' Candidate Tuberculosis Vaccine (692342) When Administered to Healthy Infants

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.

Study Overview

• Status: Completed
• Conditions: Tuberculosis
• Intervention / Treatment: Biological: GSK's investigational vaccine 692342; Biological: Menjugate™; Biological: Tritanrix™ HB+Hib; Biological: Prevnar™; Biological: Polio Sabin™

• Study Type: Interventional
• Enrollment (Actual): 301
• Phase: Phase 2

Contacts and Locations

Study Locations

• Gambia
  • Banjul, Gambia
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 7 months (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SB692342 2 dose Group; Subjects received two doses of SB692342 vaccine (0,5 mL), administered intramuscularly in the anterolateral region of the right thigh, 1 month apart, on a 0, 1 month schedule after having completed their primary EPI regimen.	Biological: GSK's investigational vaccine 692342; Intramuscular, 1 or 2 doses
EXPERIMENTAL: SB692342 1 dose Group; Subjects received one dose of SB692342 vaccine (0,5 mL), administered intramuscularly in the anterolateral region of the right thigh, at Month 0, after having completed their primary EPI regimen.	Biological: GSK's investigational vaccine 692342; Intramuscular, 1 or 2 doses
ACTIVE_COMPARATOR: Control Menjugate Group; Subjects received three doses of the control Menjugate™ vaccine (0,5 mL), administered intramuscularly in the anterolateral region of the right thigh, on a 0, 1, 7 months schedule. The first two doses were administered 1 month apart during the primary vaccination phase and the third dose was administered 6 months after the last primary vaccination dose.	Biological: Menjugate™; Intramuscular, 3 doses
EXPERIMENTAL: SB692392 2 dose + Tritanrix + Prevnar + Polio Sabin Group; Subjects received two doses of SB692342 vaccine (0,5 mL), administered intramuscularly in the anterolateral region of the right thigh, 1 month apart, concomintantly with the last two doses of the primary EPI regimen containing Tritanrix™ HepB+Hiberix™ vaccine, administered intramuscularly in the anterolateral region of the left thigh, Polio Sabin™ vaccine, administered orally, and Prevnar® vaccine, administered instramuscularly in the right arm, on a 0, 1, 2 months schedule. All subjects received a booster dose of the Tritanrix™ HepB+Hiberix™, Polio Sabin™ and Prevnar® vaccines approximately 1 year after their last dose.	Biological: GSK's investigational vaccine 692342; Intramuscular, 1 or 2 doses; Biological: Tritanrix™ HB+Hib; Intramuscular, 3 doses; Biological: Prevnar™; Intramuscular, 3 doses; Biological: Polio Sabin™; Oral, 3 doses
EXPERIMENTAL: SB692392 1 dose + Tritanrix + Prevnar + Polio Sabin Group; Subjects received one dose of SB692342 vaccine (0,5 mL), administered intramuscularly in the anterolateral region of the right thigh, concomitantly with the last dose of the primary EPI regimen containing Tritanrix™ HepB+Hiberix™ vaccine, administered intramuscularly in the anterolateral region of the left thigh, Polio Sabin™ vaccine, administered orally, and Prevnar® vaccine, administered intramuscularly in the right arm, on a 0, 1, 2 months schedule. All subjects received a booster dose of the Tritanrix™ HepB+Hiberix™, Polio Sabin™ and Prevnar® vaccines approximately 1 year after their last dose.	Biological: GSK's investigational vaccine 692342; Intramuscular, 1 or 2 doses; Biological: Tritanrix™ HB+Hib; Intramuscular, 3 doses; Biological: Prevnar™; Intramuscular, 3 doses; Biological: Polio Sabin™; Oral, 3 doses
ACTIVE_COMPARATOR: Control Tritanrix + Prevnar + Polio Sabin Group; Subjects received three doses of the primary EPI regimen containing Tritanrix™ HepB+Hiberix™ vaccine, administered in the anterolateral region of the left thigh, Polio Sabin™ vaccine, administered orally, and Prevnar® vaccine administered intramuscularly in the right arm, on a 0, 1, 2 months schedule. All subjects received a booster dose of the Tritanrix™ HepB+Hiberix™, Polio Sabin™ and Prevnar® vaccines approximately 1 year after their last dose.	Biological: Tritanrix™ HB+Hib; Intramuscular, 3 doses; Biological: Prevnar™; Intramuscular, 3 doses; Biological: Polio Sabin™; Oral, 3 doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Grade 3 Solicited Local Symptoms After Dose 1, Dose 2 and Across Doses	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.	From Day 0 to Day 6
Number of Subjects With Grade 3 Solicited Local Symptoms After Dose 2, Dose 3 and Across Doses.	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.	From Day 0 to Day 6
Number of Subjects With Grade 3 Solicited General Symptoms After Dose 1, Dose 2 and Across Doses.	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.	From Day 0 to Day 6
Number of Subjects With Grade 3 Solicited General Symptoms After Dose 2, Dose 3 and Across Doses.	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.	From Day 0 to Day 6
Number of Subjects With Grade 3 Unsolicited Adverse Events (AEs)	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.	From Day 0 to Day 29
Number of Subjects With Serious Adverse Events (SAEs)	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.	From Month 0 to Month 17
Number of Subjects With Grade 3 Haematological and Biochemical Levels	Haematological/Biochemical parameters assessed were: Haemoglobin (Haem), White Blood Cells (WBC), Platelets (PLA), Alanine Aminotransferase (ALA) and Creatinine (CREA). Grade 3 = Haem.: < 5.0 grams per deciliter (g/dL); WBC.: 1.0 to 1.4 x 10³/micro liter (µL); PLA.: < 25x10³/µL; ALA.: 5.1 to 10.0 x upper limit of normal (ULN) and CREA: 3.1 to 6.0 x ULN.	At Day 0
Number of Subjects With Grade 3 Haematological and Biochemical Levels	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.	At Day 7
Number of Subjects With Grade 3 Haematological and Biochemical Levels	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.	At Day 37
Number of Subjects With Grade 3 Haematological and Biochemical Levels	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.	At Day 67
Number of Subjects With Grade 3 Haematological and Biochemical Levels	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.	At Month 1
Number of Subjects With Grade 3 Haematological and Biochemical Levels	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.	At Month 2
Number of Subjects With Grade 3 Haematological and Biochemical Levels	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.	At Month 3
Number of Subjects With Grade 3 Haematological and Biochemical Levels	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.	At Month 6
Number of Subjects With Grade 3 Haematological and Biochemical Levels	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.	At Month 7
Number of Subjects With Grade 3 Haematological and Biochemical Levels	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.	Six Months post Dose 3 [At Month 13]
Number of Subjects With Grade 3 Haematological and Biochemical Levels	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.	At Month 12
Number of Subjects With Grade 3 Haematological and Biochemical Levels	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.	Twelve Months post Dose 2 [At Month 13]
Number of Subjects With Grade 3 Haematological and Biochemical Levels	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.	At Month 14
Number of Subjects With Grade 3 Haematological and Biochemical Levels	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.	At Month 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Immune markers expressed were among Interleukin-2 (IL-2),Interferon-gamma (INF-γ),Tumour necrosis factor-alpha (TNF-α) and CD40-ligand (CD40-L).	Before vaccination (PRE)
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	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).	Seven Days post each dose (D7)
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	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).	One Month post each dose (M1)
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	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).	Six Months post each dose (M6)
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	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).	Twelve Months post each dose (M12)
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	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).	Before vaccination (PRE)
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	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).	Seven Days after each dose (D7)
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	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).	One Month after each dose (M1)
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	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).	Six Months after each dose (M6)
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	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).	Twelve Months after each dose (M12)
Number of Seropositive Subjects Against M72 Antigen	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).	Before vaccination (PRE) and after each dose [at 1, 6 and 12 months post-vaccination (M1, M6 and M12)]
Concentration of Antibodies Against M72 Antigen	Concentrations given in EL.U/mL were expressed as Geometric Mean Concentrations (GMCs).	Before vaccination (PRE) and after each dose [at 1, 6 and 12 months post-vaccination (M1, M6 and M12)]
Number of Seroprotected Subjects Against Diphtheria Toxoid (Anti-D) and Tetanus Toxoid (Anti-T)	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).	Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
Anti-D, Anti-T Antibody Concentrations	Concentrations given in IU/mL, were expressed as Geometric Mean Concentrations (GMCs).	Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
Number of Seroprotected Subjects Against Haemophilus Influenzae Type B (Anti-PRP)	A seroprotected subject was a subject whose anti-PRP antibody concentration was ≥ 0.15 micrograms per millilitre (µg/mL).	Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
Anti-PRP Antibody Concentrations	Concentrations given in µg/mL were expressed as Geometric Mean Concentrations (GMCs).	Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
Number of Seropositive Subjects Against Bordetella Pertussis (Anti-BPT)	A seropositive subject was a subject whose anti-BPT antibody concentration was ≥ 15 EL.U/mL.	Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
Anti-BPT Antibody Concentrations	Concentrations given in EL.U/mL were expressed as Geometric Mean Concentrations (GMCs).	Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
Number of Seropositive Subjects Against Hepatitis B (Anti-HB)	A seropositive subject was a subject whose anti-HB antibody concentration was ≥ 10 milli-international units per millilitre (mIU/mL).	Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
Number of Seropositive Subjects Against Hepatitis B (Anti-HB) With Antibody Concentrations ≥100mIU/mL	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.	Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
Anti-HB Antibody Concentrations	Concentrations given in mIU/mL were expressed as Geometric Mean Concentrations (GMCs).	Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
Number of Seropositive Subjects Against Polio (Anti-Polio1, Anti-Polio2, Anti-Polio3)	A seropositive subject was a subject whose anti-polio antibody titer was ≥ 1:8.	Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
Anti-Polio1, Anti-Polio2, Anti-Polio3 Antibody Titers	Concentrations given in titers were expressed as Geometric Mean Titers (GMTs).	Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
Number of Seropositive Subjects Against Streptococcus Pneumoniae (Anti-4, Anti-6B, Anti-9V, Anti-14, Anti-18C, Anti-19F, Anti-23F)	A seropositive subject was a subject whose anti-S pneumoniae antibody concentration was ≥ 0.05 µg/mL.	Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
Number of Subjects With S. Pneumoniae Antibody Concentrations ≥ 0.2 Microgram/Milliliter	A seroconverted subject is a vaccinated subject with at least a four fold increased antibody titer post vaccination.	Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
Anti-4, Anti-6B, Anti-9V, Anti-14, Anti-18C, Anti-19F, Anti-23F Antibody Concentrations	Concentrations, given in µg/mL, were expressed as Geometric Mean Concentrations (GMCs).	Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
Number of Subjects With Serious Adverse Events (SAEs)	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.	From Day 0 up to 12 months post last vaccination
Number of Subjects With Normal, Grade 1 (G1), Grade 2 (G2) or Grade 4 (G4) Haematological and Biochemical Markers	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.	Before vaccination (PRE)
Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers	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.	Seven days post Dose 1 [PI(D7)]
Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers	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.	Seven days post Dose 2 [PII(D37)]
Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers	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.	Seven days post Dose 3 [PIII(D67)]
Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers	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.	One Month post Dose 1 [PI(M1)]
Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers	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.	One Month post Dose 2 [PII(M2)]
Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers	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.	One Month post Dose 3 [PIII(M3)]
Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers	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.	Six Months post Dose 1 [PI(M6)]
Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers	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.	Six Months post Dose 2 [PII(M7)]
Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers	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.	Six Months post Dose 3 [PIII(M8)]
Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers	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.	Six Months post Dose 3 [PIII(M13)]
Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers	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.	Twelve Months post Dose 1 [PI(M12)]
Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers	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.	Twelve Months post Dose 2 [PII(M13)]
Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers	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.	Twelve Months post Dose 3 [PIII(M14)]

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: Aeras

Publications and helpful links

General Publications

• Idoko OT, Owolabi OA, Owiafe PK, Moris P, Odutola A, Bollaerts A, Ogundare E, Jongert E, Demoitie MA, Ofori-Anyinam O, Ota MO. Safety and immunogenicity of the M72/AS01 candidate tuberculosis vaccine when given as a booster to BCG in Gambian infants: an open-label randomized controlled trial. Tuberculosis (Edinb). 2014 Dec;94(6):564-78. doi: 10.1016/j.tube.2014.07.001. Epub 2014 Aug 9.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 7, 2010
• Primary Completion (ACTUAL): April 30, 2011
• Study Completion (ACTUAL): March 16, 2012

Study Registration Dates

• First Submitted: March 18, 2010
• First Submitted That Met QC Criteria: April 1, 2010
• First Posted (ESTIMATE): April 2, 2010

Study Record Updates

• Last Update Posted (ACTUAL): June 27, 2019
• Last Update Submitted That Met QC Criteria: June 11, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Tuberculosis vaccine
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 112899; 2012-004380-44 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No