Clinical trial NCT01098474: Safety and Immunogenicity Study of a Candidate Tuberculosis Vaccine in Healthy Infants
Official title: Safety and Immunogenicity Study of GSK Biologicals' Candidate Tuberculosis Vaccine (692342) When Administered to Healthy Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tuberculosis
Keywords: Tuberculosis vaccine
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Aeras
First posted: 2010-04-02
Enrollment: 301
Sex: ALL
Minimum age (years): 2
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Subjects With Grade 3 Solicited Local Symptoms After Dose 1, Dose 2 and Across Doses
timeFrame: From Day 0 to Day 6
measure: Number of Subjects With Grade 3 Solicited Local Symptoms After Dose 2, Dose 3 and Across Doses.
timeFrame: From Day 0 to Day 6
measure: Number of Subjects With Grade 3 Solicited General Symptoms After Dose 1, Dose 2 and Across Doses.
timeFrame: From Day 0 to Day 6
measure: Number of Subjects With Grade 3 Solicited General Symptoms After Dose 2, Dose 3 and Across Doses.
timeFrame: From Day 0 to Day 6
measure: Number of Subjects With Grade 3 Unsolicited Adverse Events (AEs)
timeFrame: From Day 0 to Day 29
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: From Month 0 to Month 17
measure: Number of Subjects With Grade 3 Haematological and Biochemical Levels
timeFrame: At Day 0
measure: Number of Subjects With Grade 3 Haematological and Biochemical Levels
timeFrame: At Day 7
measure: Number of Subjects With Grade 3 Haematological and Biochemical Levels
timeFrame: At Day 37
measure: Number of Subjects With Grade 3 Haematological and Biochemical Levels
timeFrame: At Day 67
measure: Number of Subjects With Grade 3 Haematological and Biochemical Levels
timeFrame: At Month 1
measure: Number of Subjects With Grade 3 Haematological and Biochemical Levels
timeFrame: At Month 2
measure: Number of Subjects With Grade 3 Haematological and Biochemical Levels
timeFrame: At Month 3
measure: Number of Subjects With Grade 3 Haematological and Biochemical Levels
timeFrame: At Month 6
measure: Number of Subjects With Grade 3 Haematological and Biochemical Levels
timeFrame: At Month 7
measure: Number of Subjects With Grade 3 Haematological and Biochemical Levels
timeFrame: Six Months post Dose 3 [At Month 13]
measure: Number of Subjects With Grade 3 Haematological and Biochemical Levels
timeFrame: At Month 12
measure: Number of Subjects With Grade 3 Haematological and Biochemical Levels
timeFrame: Twelve Months post Dose 2 [At Month 13]
measure: Number of Subjects With Grade 3 Haematological and Biochemical Levels
timeFrame: At Month 14
measure: Number of Subjects With Grade 3 Haematological and Biochemical Levels
timeFrame: At Month 8
Secondary outcomes:
measure: 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
timeFrame: Before vaccination (PRE)
measure: 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
timeFrame: Seven Days post each dose (D7)
measure: 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
timeFrame: One Month post each dose (M1)
measure: 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
timeFrame: Six Months post each dose (M6)
measure: 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
timeFrame: Twelve Months post each dose (M12)
measure: 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
timeFrame: Before vaccination (PRE)
measure: 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
timeFrame: Seven Days after each dose (D7)
measure: 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
timeFrame: One Month after each dose (M1)
measure: 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
timeFrame: Six Months after each dose (M6)
measure: 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
timeFrame: Twelve Months after each dose (M12)
measure: Number of Seropositive Subjects Against M72 Antigen
timeFrame: Before vaccination (PRE) and after each dose [at 1, 6 and 12 months post-vaccination (M1, M6 and M12)]
measure: Concentration of Antibodies Against M72 Antigen
timeFrame: Before vaccination (PRE) and after each dose [at 1, 6 and 12 months post-vaccination (M1, M6 and M12)]
measure: Number of Seroprotected Subjects Against Diphtheria Toxoid (Anti-D) and Tetanus Toxoid (Anti-T)
timeFrame: Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
measure: Anti-D, Anti-T Antibody Concentrations
timeFrame: Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
measure: Number of Seroprotected Subjects Against Haemophilus Influenzae Type B (Anti-PRP)
timeFrame: Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
measure: Anti-PRP Antibody Concentrations
timeFrame: Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
measure: Number of Seropositive Subjects Against Bordetella Pertussis (Anti-BPT)
timeFrame: Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
measure: Anti-BPT Antibody Concentrations
timeFrame: Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
measure: Number of Seropositive Subjects Against Hepatitis B (Anti-HB)
timeFrame: Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
measure: Number of Seropositive Subjects Against Hepatitis B (Anti-HB) With Antibody Concentrations ≥100mIU/mL
timeFrame: Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
measure: Anti-HB Antibody Concentrations
timeFrame: Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
measure: Number of Seropositive Subjects Against Polio (Anti-Polio1, Anti-Polio2, Anti-Polio3)
timeFrame: Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
measure: Anti-Polio1, Anti-Polio2, Anti-Polio3 Antibody Titers
timeFrame: Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
measure: Number of Seropositive Subjects Against Streptococcus Pneumoniae (Anti-4, Anti-6B, Anti-9V, Anti-14, Anti-18C, Anti-19F, Anti-23F)
timeFrame: Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
measure: Number of Subjects With S. Pneumoniae Antibody Concentrations ≥ 0.2 Microgram/Milliliter
timeFrame: Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
measure: Anti-4, Anti-6B, Anti-9V, Anti-14, Anti-18C, Anti-19F, Anti-23F Antibody Concentrations
timeFrame: Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)]
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: From Day 0 up to 12 months post last vaccination
measure: Number of Subjects With Normal, Grade 1 (G1), Grade 2 (G2) or Grade 4 (G4) Haematological and Biochemical Markers
timeFrame: Before vaccination (PRE)
measure: Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers
timeFrame: Seven days post Dose 1 [PI(D7)]
measure: Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers
timeFrame: Seven days post Dose 2 [PII(D37)]
measure: Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers
timeFrame: Seven days post Dose 3 [PIII(D67)]
measure: Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers
timeFrame: One Month post Dose 1 [PI(M1)]
measure: Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers
timeFrame: One Month post Dose 2 [PII(M2)]
measure: Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers
timeFrame: One Month post Dose 3 [PIII(M3)]
measure: Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers
timeFrame: Six Months post Dose 1 [PI(M6)]
measure: Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers
timeFrame: Six Months post Dose 2 [PII(M7)]
measure: Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers
timeFrame: Six Months post Dose 3 [PIII(M8)]
measure: Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers
timeFrame: Six Months post Dose 3 [PIII(M13)]
measure: Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers
timeFrame: Twelve Months post Dose 1 [PI(M12)]
measure: Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers
timeFrame: Twelve Months post Dose 2 [PII(M13)]
measure: Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers
timeFrame: Twelve Months post Dose 3 [PIII(M14)]
Other outcomes:
Locations:
city: Banjul
country: Gambia
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.