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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 2

Conditions: Tuberculosis

Treatments: Biological: Tritanrix™ HB+Hib; Biological: GSK's investigational vaccine 692342; Biological: Menjugate™; Biological: Polio Sabin™; Biological: Prevnar™

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01098474

2012-004380-44 (EudraCT Number)

112899

Details and patient eligibility

About

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.

Enrollment: 301 patients

Sex: All

Ages: 2 to 7 months old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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301 participants in 6 patient groups

SB692342 2 dose Group

Experimental group

Description:

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.

Treatment:

Biological: GSK's investigational vaccine 692342

SB692342 1 dose Group

Experimental group

Description:

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.

Treatment:

Biological: GSK's investigational vaccine 692342

Control Menjugate Group

Active Comparator group

Description:

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.

Treatment:

Biological: Menjugate™

SB692392 2 dose + Tritanrix + Prevnar + Polio Sabin Group

Experimental group

Description:

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.

Treatment:

Biological: GSK's investigational vaccine 692342

Biological: Prevnar™

Biological: Tritanrix™ HB+Hib

Biological: Polio Sabin™

SB692392 1 dose + Tritanrix + Prevnar + Polio Sabin Group

Experimental group

Description:

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.

Treatment:

Biological: GSK's investigational vaccine 692342

Biological: Prevnar™

Biological: Tritanrix™ HB+Hib

Biological: Polio Sabin™

Control Tritanrix + Prevnar + Polio Sabin Group

Active Comparator group

Description:

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.

Treatment:

Biological: Prevnar™

Biological: Tritanrix™ HB+Hib

Biological: Polio Sabin™