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

Primary Purpose

Tuberculosis

Status

Completed

Phase

Phase 2

Locations

South Africa

Study Type

Interventional

Intervention

GSK's investigational vaccine 692342

Placebo

About this trial

This is an interventional prevention trial for Tuberculosis focused on measuring Tuberculosis vaccine

Eligibility Criteria

13 Years - 17 Years (Child)All SexesAccepts Healthy Volunteers

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

Sites / Locations

GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Group A

Group B

Arm Description

Outcomes

Primary Outcome Measures

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.

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.

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.

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 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.

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.

Number of Subjects With Biochemical and Haematological Above Normal Levels

Number of Subjects With Haematological Levels Above Normal

Number of Subjects With Biochemical and Haematological Below Normal Levels

Number of Subjects With Haematological Levels Below Normal

Secondary Outcome Measures

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).

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).

Frequency of M72 Specific CD8+ T Cells Expressing Any Combination of Cytokines

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).

Full Information

NCT ID

NCT00950612

First Posted

July 23, 2009

Last Updated

June 25, 2018

Sponsor

GlaxoSmithKline

Collaborators

Aeras

1. Study Identification

Unique Protocol Identification Number

NCT00950612

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2016

Overall Recruitment Status

Completed

Study Start Date

December 8, 2009 (undefined)

Primary Completion Date

September 30, 2010 (Actual)

Study Completion Date

September 30, 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

Collaborators

Aeras

4. Oversight

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Tuberculosis

Keywords

Tuberculosis vaccine

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

60 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group A

Arm Type

Experimental

Arm Title

Group B

Arm Type

Placebo Comparator

Intervention Type

Biological

Intervention Name(s)

GSK's investigational vaccine 692342

Intervention Description

Intramuscular injection, 2 doses

Intervention Type

Biological

Intervention Name(s)

Placebo

Intervention Description

Intramuscular injection, 2 doses

Primary Outcome Measure Information:

Title

Number of Subjects With Solicited Local Symptoms

Description

Time Frame

During the 7-day (Days 0-6) post-vaccination period following each dose and across doses

Title

Number of Subjects With Solicited General Symptoms

Description

Time Frame

During the 7-day (Days 0-6) post-vaccination period following each dose and across doses

Title

Number of Subjects With Unsolicited Adverse Events (AEs)

Description

Time Frame

During the 30-day (Days 0-29) post-vaccination period

Title

Number of Subjects With Serious Adverse Events (SAEs)

Description

Time Frame

During the entire study period (from Day 0 up to Day 210)

Title

Number of Subjects With Normal Biochemical and Haematological Levels

Description

Time Frame

At Day 0, 7, 30, 37 and 60

Title

Number of Subjects With Normal Haematological Levels

Description

Time Frame

At Day 0, 7, 30, 37 and 60

Title

Number of Subjects With Biochemical and Haematological Above Normal Levels

Description

Time Frame

At Day 0, 7, 30, 37 and 60

Title

Number of Subjects With Haematological Levels Above Normal

Description

Time Frame

At Day 0, 7, 30, 37 and 60

Title

Number of Subjects With Biochemical and Haematological Below Normal Levels

Description

Time Frame

At Day 0, 7, 30, 37 and 60

Title

Number of Subjects With Haematological Levels Below Normal

Description

Time Frame

At Day 0, 7, 30, 37 and 60

Secondary Outcome Measure Information:

Title

Frequency of Mycobacterium Tuberculosis Fusion Protein (M72) Specific Cluster of Differentiation 4/8 (CD4/8+) T Cells Expressing at Least Two Different Cytokines

Description

Time Frame

At Day 0, 7, 30, 37, 60 and 210

Title

Frequency of M72 Specific CD4+ T Cells Expressing Any Combination of Cytokines

Description

Time Frame

At Day 0, 7, 30, 37, 60 and 210

Title

Frequency of M72 Specific CD8+ T Cells Expressing Any Combination of Cytokines

Description

Time Frame

At Day 0, 7, 30, 37, 60 and 210

Title

Anti-M72 Specific Antibody Concentrations

Description

Antibody concentrations given in Enzyme-Linked Immunosorbent Assay (ELISA) units per millilitre (EL.U/mL) were expressed as Geometric Mean Concentrations (GMCs).

Time Frame

At Day 0, 30, 60 and 210

10. Eligibility

Sex

All

Minimum Age & Unit of Time

13 Years

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

GlaxoSmithKline

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

Worcester

State/Province

Western Province

ZIP/Postal Code

6850

Country

South Africa

12. IPD Sharing Statement

Citations:

PubMed Identifier

26072017

Citation

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.

Results Reference

derived

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

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