Safety and Immunogenicity of a Candidate Tuberculosis (TB) Vaccine in Healthy HIV Negative Adolescents

Safety and Immunogenicity Study of GSK Biologicals' Candidate Tuberculosis Vaccine (692342) When Administered to Healthy HIV-negative Adolescents Living in a TB Endemic Region

This observer blind study will assess the safety and immunogenicity of GSK Biologicals' investigational 692342 vaccine administered at 0, 1 month to healthy adolescents living in a TB-endemic region.

Study Overview

• Status: Completed
• Conditions: Tuberculosis
• Intervention / Treatment: Biological: Placebo; Biological: GSK's investigational vaccine 692342

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• South Africa
  • Western Province
    • Worcester, Western Province, South Africa, 6850
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 17 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who the investigator believes that they and their parent(s)/ legal guardian(s) can and will comply with the requirements of the protocol.
• A male or female between, and including, 13 and 17 years of age at the time of the first vaccination.
• Written informed consent obtained from the subject's parent(s) or legal guardian(s).
• Written informed assent obtained from the subject.
• Free of obvious health problems as established by medical history and clinical examination before entering into the study.
• Seronegative for HIV-1.
• No history of TB disease.
• No active pulmonary disease on chest X-ray.
• Availability for the duration of the immunisation and follow-up period, with the family not planning to move away from the study area within the next year.
• Female subjects of non-childbearing potential may be enrolled in the study.
• Female subjects of childbearing potential may be enrolled in the study, if the subject is abstinent, has practiced adequate contraception for 30 days prior to vaccination, and has a negative pregnancy test on the day of vaccination, and has agreed to continue adequate contraception during the entire vaccination period and for 2 months after completion of the vaccination series.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Administration of a registered live vaccine not foreseen by the study within 30 days preceding the first dose of study vaccine and administration of a registered inactivated vaccine within 14 days preceding the first dose of study vaccine.
• History of previous administration of investigational Mycobacterium tuberculosis vaccines.
• History of previous exposure to components of the investigational vaccine.
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
• Any condition or illness (acute, chronic or history) or medication, which in the opinion of the investigator might interfere with the evaluation of the safety or immunogenicity of the study vaccine.
• Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of vaccine, or planned administration during the study.
• Planned participation or participation in another experimental clinical study during the study period.
• A family history of congenital or hereditary immunodeficiency.
• Any chronic drug therapy to be continued during the study period, with the exception of vitamins and/or dietary supplements, birth control pills, anti-histamines for seasonal allergies and Specific Serotonin Reuptake Inhibitors (SSRIs).
• History of allergic reactions (significant IgE-mediated events) or anaphylaxis to any vaccine.
• History of allergic disease or reactions likely to be exacerbated by any component of the study vaccine.
• Pregnant female, lactating female or female planning to become pregnant or discontinue contraceptive precautions.
• Drug and/or alcohol abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A	Biological: GSK's investigational vaccine 692342; Intramuscular injection, 2 doses
Placebo Comparator: Group B	Biological: Placebo; Intramuscular injection, 2 doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	During the entire study period (from Day 0 up to Day 210)
Number of Subjects With Solicited Local Symptoms	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site. Relationship analysis was not performed.	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Number of Subjects With Solicited General Symptoms	Assessed solicited general symptoms were fatigue, temperature [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], gastrointestinal symptoms (gastro) [nausea, vomiting, diarrhoea and/or abdominal pain], headache, malaise and myalgia. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever ≥ 39.5 °C. Related = symptom assessed by the investigator as related to the vaccination.	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Number of Subjects With Unsolicited Adverse Events (AEs)	An unsolicited AE covers 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 and reported in addition to those solicited during the clinical study and any solicited symptom with onset out-side the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.	During the 30-day (Days 0-29) post-vaccination period
Number of Subjects With Normal Biochemical and Haematological Levels	Among biochemical and haematological parameters assessed were alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine [CREA], haemoglobin [Hgb]. Levels of haematological/biochemical parameters assessed in terms of normal laboratory values were - normal, below and above.	At Day 0, 7, 30, 37 and 60
Number of Subjects With Normal Haematological Levels	Among haematological parameters assessed were platelets [PLA], red blood cells [RBC] and white blood cells [WBC]. Levels of haematological parameters assessed in terms of normal laboratory values were - normal, below and above.	At Day 0, 7, 30, 37 and 60
Number of Subjects With Biochemical and Haematological Above Normal Levels	Among biochemical and haematological parameters assessed were alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine [CREA], haemoglobin [Hgb]. Levels of haematological/biochemical parameters assessed in terms of normal laboratory values were - normal, below and above.	At Day 0, 7, 30, 37 and 60
Number of Subjects With Haematological Levels Above Normal	Among haematological parameters assessed were platelets [PLA], red blood cells [RBC] and white blood cells [WBC]. Levels of haematological parameters assessed in terms of normal laboratory values were - normal, below and above.	At Day 0, 7, 30, 37 and 60
Number of Subjects With Biochemical and Haematological Below Normal Levels	Among biochemical and haematological parameters assessed were alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine [CREA], haemoglobin [Hgb]. Levels of haematological/biochemical parameters assessed in terms of normal laboratory values were - normal, below and above.	At Day 0, 7, 30, 37 and 60
Number of Subjects With Haematological Levels Below Normal	Among haematological parameters assessed were platelets [PLA], red blood cells [RBC] and white blood cells [WBC]. Levels of haematological parameters assessed in terms of normal laboratory values were - normal, below and above.	At Day 0, 7, 30, 37 and 60

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Mycobacterium Tuberculosis Fusion Protein (M72) Specific Cluster of Differentiation 4/8 (CD4/8+) T Cells Expressing at Least Two Different Cytokines	Among cytokines expressed were interleukin-2 [IL-2], interferon-gamma [IFN-γ], tumour necrosis factor-alpha [TNF-α] and cluster of differentiation 40-ligand [CD40-L]. Analysis of cytokines expression was done by means of in vitro flow cytometry, using intracellular cytokine staining (ICS).	At Day 0, 7, 30, 37, 60 and 210
Frequency of M72 Specific CD4+ T Cells Expressing Any Combination of Cytokines	Among cytokines expressed were interleukin-2 [IL-2], interferon-gamma [IFN-γ], tumour necrosis factor-alpha [TNF-α] and cluster of differentiation 40-ligand [CD40-L], after background reduction stimulated by M72. Analysis of cytokines expression was done by means of in vitro flow cytometry, using intracellular cytokine staining (ICS).	At Day 0, 7, 30, 37, 60 and 210
Frequency of M72 Specific CD8+ T Cells Expressing Any Combination of Cytokines	Among cytokines expressed were interleukin-2 [IL-2], interferon-gamma [IFN-γ], tumour necrosis factor-alpha [TNF-α] and cluster of differentiation 40-ligand [CD40-L], after background reduction stimulated by M72. Analysis of cytokines expression was done by means of in vitro flow cytometry, using intracellular cytokine staining (ICS).	At Day 0, 7, 30, 37, 60 and 210
Anti-M72 Specific Antibody Concentrations	Antibody concentrations given in Enzyme-Linked Immunosorbent Assay (ELISA) units per millilitre (EL.U/mL) were expressed as Geometric Mean Concentrations (GMCs).	At Day 0, 30, 60 and 210

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: Aeras

Publications and helpful links

General Publications

• Penn-Nicholson A, Geldenhuys H, Burny W, van der Most R, Day CL, Jongert E, Moris P, Hatherill M, Ofori-Anyinam O, Hanekom W; Vaccine Study Team; Bollaerts A, Demoitie MA, Kany Luabeya AK, De Ruymaeker E, Tameris M, Lapierre D, Scriba TJ. Safety and immunogenicity of candidate vaccine M72/AS01E in adolescents in a TB endemic setting. Vaccine. 2015 Jul 31;33(32):4025-34. doi: 10.1016/j.vaccine.2015.05.088. Epub 2015 Jun 10.

Study record dates

Study Major Dates

• Study Start: December 8, 2009
• Primary Completion (Actual): September 30, 2010
• Study Completion (Actual): September 30, 2010

Study Registration Dates

• First Submitted: July 23, 2009
• First Submitted That Met QC Criteria: July 30, 2009
• First Posted (Estimate): August 3, 2009

Study Record Updates

• Last Update Posted (Actual): August 17, 2018
• Last Update Submitted That Met QC Criteria: June 25, 2018
• Last Verified: November 1, 2016

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
• Other Study ID Numbers: 112898