# Safety and Immunogenicity Study of a Candidate Tuberculosis Vaccine in Healthy Infants ## 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. ## Eligibility 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. ## Interventions - **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 - **BIOLOGICAL: Menjugate™**: Intramuscular, 3 doses ## Outcomes - **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. - **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. - **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. - **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. - **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. - **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. - **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. - **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. - **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. - **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. - **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. - **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. - **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. - **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. - **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. - **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. - **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. - **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. - **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. - **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.

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

Abstract

MeSH terms

Related papers