TuberculosisPhase 2NCT01262976

Safety and Immunogenicity Study of a Candidate Tuberculosis Vaccine in Human Immunodeficiency Virus (HIV)-Positive Adults

A Phase 2 study testing GSK's investigational vaccine 692342 and Physiological saline in people with Tuberculosis, run by GlaxoSmithKline at 1 site in India.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of the study is to assess the safety and immunogenicity of a GlaxoSmithKline (GSK) Biologicals' candidate tuberculosis vaccine (692342) administered to Human Immunodeficiency Virus (HIV)-positive adults aged 18 to 59 years, living in a tuberculosis endemic region. Subjects will be followed-up for 3 years. Read more about this study

Who is it for?: Ages 18 to 59 yearsHealthy volunteers can take part
Conditions the study is for: Tuberculosis
What is being tested?: GSK's investigational vaccine 692342 and Physiological saline
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 240 participants
Where: 1 siteIndia
Study dates: 17 Jan 2011to 4 Jun 2015
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 59 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Subjects who the investigator believes that they can and will comply with the requirements of the protocol.
A male or female between, and including, 18 and 59 years of age at the time of the first vaccination.
Written informed consent obtained from the subject prior to any study procedure.
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:
has practiced adequate contraception for 30 days prior to vaccination,

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has a negative pregnancy test on the day of vaccination, and
has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.
Clinically acceptable laboratory values at screening as determined by the investigator.
No evidence of tuberculosis disease with no evidence of pulmonary pathology as confirmed by chest X-ray.
No history of extra pulmonary tuberculosis.
Based on their medical history, all subjects must have no history of chemotherapy for tuberculosis.
Additional inclusion criteria for subjects to be enrolled in HIV+ on highly active antiretroviral therapy cohort:
Subjects must be HIV-positive and under care of a physician for at least 6 months.
Subjects must have a CD4+T cell count >= 250 cells/mm3 at screening.
Subjects must be stable on highly active antiretroviral therapy for at least 6 months, with an undetectable HIV viral load level at screening.
Additional inclusion criteria for subjects to be enrolled in HIV+ treatment naïve cohort:
Subjects must be HIV-positive and under care of a physician for at least 6 months
Subjects must be highly active antiretroviral therapy-naïve (never received anti-retroviral therapy after HIV diagnosis)
Subjects must have a CD4 + T cell count above 350 cells/mm3 at screening.
Subjects for whom commencement of highly active antiretroviral therapy is not expected based on current assessment within next year.
Subjects must have a viral load between 5000 - 80000 copies/mL at screening.
Additional inclusion criteria for subjects to be enrolled in HIV-negative cohort
Subjects must be negative for HIV-1.

Who cannot join

Use of any investigational or non-registered product 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 experimental Mtb vaccines.
History of previous exposure to components of the investigational vaccine within 30 days preceding the first dose of study vaccine
Chronic administration of immunosuppressant or other immune-modifying drugs within six months prior to the first vaccine/product dose. For corticosteroids, this will mean prednisone >= 20 mg/kg/day, or equivalent. Inhaled and topical steroids are allowed.
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 vaccine.

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Planned participation or participation in another experimental protocol with an experimental product during the study period.
Administration of any immunoglobulin, any immunotherapy and/or any blood products within the three months preceding the first dose of study vaccination, or planned administrations during the study period.
Subjects taking any of the following medication: chronic administration of systemic steroids, interleukins, systemic interferon or systemic chemotherapy.
History of allergic reactions or anaphylaxis to any drug or vaccine.
History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
History of chronic alcohol consumption and/or drug abuse which in the Investigator's opinion would put the subject at risk.
Pregnant female, lactating female or female planning to become pregnant or stop contraception.
Acute or chronic clinically relevant pulmonary, cardiovascular, hepatic or renal function abnormality as determined by physical examination or laboratory screening tests.
Additional exclusion criteria for subjects to be enrolled in HIV+ on highly active antiretroviral therapy cohort:
Any change in anti-retroviral drug regimen within 12 weeks prior to screening.
Any chronic drug therapy, other than highly active antiretroviral therapy or prophylaxis for opportunistic HIV related infections, birth control pills, anti-histamines for seasonal allergies and SSRIs.

Trial locations and contacts

1 site in 1 country.

India1 site

GSK Investigational Site
Tharamani Chennai, 600113

Other trials in India

About this study

Official title: Safety and Immunogenicity of GSK Biologicals' Candidate Tuberculosis Vaccine (692342) When Administered to HIV-positive Adults Living in a Tuberculosis Endemic Region

Subjects will be followed-up for 3 years.

Subjects will be enrolled in 3 cohorts:

HIV-positive adults on highly active antiretroviral therapy
HIV-positive adults not on highly active antiretroviral therapy
HIV-negative adults

Each cohort will have 2 groups.

Read the detailed description

This Protocol Posting has been updated following Protocol Amendment 1, February 2011, leading to the update of the outcome measures and the inclusion and exclusion criteria.

Conditions: Tuberculosis
Being tested: GSK's investigational vaccine 692342, Physiological saline
Keywords: Tuberculosis vaccine
Medical subject headings: Tuberculosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GSK's investigational vaccine 692342Biological
Intramuscular, 2 doses
Physiological salineBiological
Intramuscular, 2 doses

Study groups in NCT01262976
Study group	Role	What they receive
HIV(+)-HA/GSK692342	Experimental	HIV-infected subjects between and including 18 to 59 years of age, who were on Highly Active Anti-Retroviral Therapy (HAART) at the time of study enrolment, received two doses of GSK692342 vaccine (TB) at Day 0 and Day 30, intramuscularly into the arm's deltoid region. Receives: Biological: GSK's investigational vaccine 692342
HIV(+)-HA/Placebo	Placebo comparator	HIV-infected subjects between and including 18 to 59 years of age, who were on Highly Active Anti-Retroviral Therapy (HAART) at the time of study enrolment, received two doses of saline solution at Day 0 and Day 30, intramuscularly into the arm's deltoid region. Receives: Biological: Physiological saline
HIV(+)-TN/GSK692342	Experimental	HIV-infected subjects between and including 18 to 59 years of age, who were HAART-treatment naive (TN) at the time of study enrolment, received two doses of GSK692342 vaccine (TB) at Day 0 and Day 30, intramuscularly into the arm's deltoid region. Receives: Biological: GSK's investigational vaccine 692342
HIV(+)-TN/Placebo	Placebo comparator	HIV-infected subjects between and including 18 to 59 years of age, who were HAART-treatment naive (TN) at the time of study enrolment, received two doses of saline solution at Day 0 and Day 30, intramuscularly into the arm's deltoid region. Receives: Biological: Physiological saline
HIV(-)/GSK692342	Experimental	Subjects between and including 18 to 59 years of age, who were HIV-negative at the time of study enrolment, received two doses of GSK692342 vaccine (TB) at Day 0 and Day 30, intramuscularly into the arm's deltoid region. Receives: Biological: GSK's investigational vaccine 692342
HIV(-)/Placebo	Placebo comparator	Subjects between and including 18 to 59 years of age, who were HIV-negative at the time of study enrolment, received two doses of saline solution at Day 0 and Day 30, intramuscularly into the arm's deltoid region. Receives: Biological: Physiological saline

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Subjects With Grade 3 Solicited Local Symptoms
Solicited local symptoms assessed were pain and swelling. Grade 3 pain = pain that prevented normal activity. Grade 3 swelling = swelling spreading beyond 50 millimeters (mm) of injection site.
Measured: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Number of Subjects With Grade 3 Solicited General Symptoms
Solicited general symptoms assessed 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. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever ≥ 39.5 °C.
Measured: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Number of Subjects With Grade 3 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. Grade 3 AE = an AE which prevented normal, everyday activities.
Measured: During the 30-day (Days 0-29) post-vaccination period
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.
Measured: From screening up to one month post Dose 2
Number of Subjects With Grade 3 and Grade 4 Haematological and Biochemical Levels
Haematological and biochemical parameters assessed were haemoglobin [Hgb], white blood cells [WBC], platelets [PLA], alanine aminotransferase [ALT], aspartate aminotransferase [AST] and creatinine [CREA]. The haematology and biochemistry toxicity grading scale was based on the Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.
Measured: At Day 0
Number of Subjects With Grade 3 and 4 Haematological and Biochemical Levels
Haematological and biochemical parameters assessed were haemoglobin [Hgb], white blood cells [WBC], platelets [PLA], alanine aminotransferase [ALT], aspartate aminotransferase [AST] and creatinine [CREA]. The haematology and biochemistry toxicity grading scale was based on the Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.
Measured: At Day 7
Number of Subjects With Grade 3 and Grade 4 Haematological/Biochemical Levels
Haematological and biochemical parameters assessed were haemoglobin [Hgb], white blood cells [WBC], platelets [PLA], alanine aminotransferase [ALT], aspartate aminotransferase [AST] and creatinine [CREA]. The haematology and biochemistry toxicity grading scale was based on the Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.
Measured: At Day 30
Number of Subjects With Grade 3-4 Haematological and Biochemical Levels
Haematological and biochemical parameters assessed were haemoglobin [Hgb], white blood cells [WBC], platelets [PLA], alanine aminotransferase [ALT], aspartate aminotransferase [AST] and creatinine [CREA]. The haematology and biochemistry toxicity grading scale was based on the Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.
Measured: At Day 37
Number of Subjects With Grade 3-4 Haematological/Biochemical Levels
Haematological and biochemical parameters assessed were haemoglobin [Hgb], white blood cells [WBC], platelets [PLA], alanine aminotransferase [ALT], aspartate aminotransferase [AST] and creatinine [CREA]. The haematology and biochemistry toxicity grading scale was based on the Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.
Measured: At Day 60

Secondary outcomes (15)

Anti-Mycobacterium Tuberculosis Fusion Protein (M72) Specific Antibody Concentrations
Concentration of M72-specific antibodies, as measured by the enzyme-linked immunosorbent assay (ELISA), were given in ELISA units per milliliter (EU/mL) and expressed as geometric mean concentrations (GMCs).
Measured: At Days 0, 30, 60, 210 and at Years 1, 2 and 3
Number of Seroconverted Subjects for M72-specific Antibodies
A seroconverted subject for M72 antibodies was defined as a seronegative subject at baseline, with the appearance of M72 antibody concentration higher than or equal to (≥) the cut-off value of 2.8 EL.U/mL post vaccination. Antibody concentrations below the cut-off value of the assay were given an arbitrary value of half the cut-off value for the purpose of GMC calculation.
Measured: At Days 0, 30, 60, 210 and at Years 1, 2 and 3
Frequency of M72-cluster of Differentiation 4 (CD4+) T-cells Expressing at Least 2 Immune Markers
Among immune markers expressed after background reduction were interleukin-2 (IL-2), interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and cluster of differentiation 40 - ligand (CD40-L). This endpoint presents results for CD4-all doubles.
Measured: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
Frequency of M72-CD4+ T-cells Expressing Any Combination of Cytokines
Among cytokines expressed after background reduction were cluster of differentiation 40-ligand (CD40-L), interleukin-2 (IL-2), interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α). This endpoint presents results for the following cytokine combinations: CD4.CD40L(+)+IL2(+)+TNFa(+)+IFNg(+), CD4.CD40L(+)+IL2(+)+TNFa(+)+IFNg(-),CD4.CD40L(+)+IL2(+)+TNFa(-)+IFNg(+),CD4.CD40L(+)+IL2(+)+TNFa(-)+IFNg(-),CD4.CD40L(+)+IL2(-)+TNFa(+)+IFNg(+).
Measured: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
M72-cluster of Differentiation 4 (CD4+) T-cells Frequency Expressing Any Combination of Cytokines
Among cytokines expressed after background reduction were cluster of differentiation 40-ligand (CD40-L), interleukin-2 (IL-2), interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α). This endpoint presents results for the following cytokine combination: CD4.CD40L(+)+IL2(-)+TNFa(+)+IFNg(-), CD4.CD40L(+)+IL2(-)+TNFa(-)+IFNg(+),CD4.CD40L(+)+IL2(-)+TNFa(-)+IFNg(-),CD4.CD40L(-)+IL2(+)+TNFa(+)+IFNg(+),CD4.CD40L(-)+IL2(+)+TNFa(+)+IFNg(-)
Measured: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
M72-CD4+ T-cells Frequency Expressing Any Combination of Cytokines
Among cytokines expressed after background reduction were cluster of differentiation 40-ligand (CD40-L), interleukin-2 (IL-2), interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α). This endpoint presents results for the following cytokine combination: CD4.CD40L(-)+IL2(+)+TNFa(-)+IFNg(+), CD4.CD40L(-)+IL2(+)+TNFa(-)+IFNg(-),CD4.CD40L(-)+IL2(-)+TNFa(+)+IFNg(+),CD4.CD40L(-)+IL2(-)+TNFa(+)+IFNg(-), CD4.CD40L(-)+IL2(-)+TNFa(-)+IFNg(+).
Measured: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
Frequency of M72-cluster of Differentiation 8 (CD8+) T-cells Expressing at Least 2 Immune Markers
Among immune markers expressed after background reduction were interleukin-2 (IL-2), interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α). This endpoint presents results for CD8-all doubles.
Measured: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
Frequency of M72-CD8+ T-cells Expressing Any Combination of Cytokines
Among cytokines expressed after background reduction were cluster of differentiation 40-ligand (CD40-L) interleukin-2 (IL-2), interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α). This endpoint presents results for the following cytokine combination: CD8.CD40L(+)+IL2(+)+TNFa(+)+IFNg(+),CD8.CD40L(+)+IL2(+)+TNFa(+)+IFNg(-),CD8.CD40L(+)+IL2(+)+TNFa(-)+IFNg(+),CD8.CD40L(+)+IL2(+)+TNFa(-)+IFNg(-),CD8.CD40L(+)+IL2(-)+TNFa(+)+IFNg(+).
Measured: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
M72-cluster of Differentiation 8 (CD8+) T Frequency Cells Expressing Any Combination of Cytokines
Among cytokines expressed after background reduction were cluster of differentiation 40-ligand (CD40-L) interleukin-2 (IL-2), interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α). This endpoint presents results for the following cytokine combination: CD8.CD40L(+)+IL2(-)+TNFa(+)+IFNg(-),CD8.CD40L(+)+IL2(-)+TNFa(-)+IFNg(+),CD8.CD40L(+)+IL2(-)+TNFa(-)+IFNg(-),CD8.CD40L(-)+IL2(+)+TNFa(+)+IFNg(+),CD8.CD40L(-)+IL2(+)+TNFa(+)+IFNg(-).
Measured: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
M72-CD8+ T-cells Frequency Expressing Any Combination of Cytokines
Among cytokines expressed after background reduction were cluster of differentiation 40-ligand (CD40-L) interleukin-2 (IL-2), interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α). This endpoint presents results for the following cytokine combination: CD8.CD40L(-)+IL2(+)+TNFa(-)+IFNg(+), CD8.CD40L(-)+IL2(+)+TNFa(-)+IFNg(-),CD8.CD40L(-)+IL2(-)+TNFa(+)+IFNg(+), CD8.CD40L(-)+IL2(-)+TNFa(+)+IFNg(-),CD8.CD40L(-)+IL2(-)+TNFa(-)+IFNg(+).
Measured: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
Number of Subjects With Any Solicited Local Symptoms
Solicited local symptoms assessed were pain and swelling. Any = occurrence of the symptom regardless of intensity grade.
Measured: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Number of Subjects With Any Solicited General Symptoms
Solicited general symptoms assessed were fatigue, gastrointestinal symptoms (Gastro), headache, malaise, myalgia and temperature. Any = occurrence of the symptom regardless of intensity grade.
Measured: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Number of Subjects With Any Unsolicited 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 outside 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.
Measured: During the 30-day (Days 0-29) post-vaccination period
Number of Subjects With 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.
Measured: From one month post Dose 2 up to study end (Year 3)
Number of Subjects Presenting Different Grades of Haematological and Biochemical Values
Biochemical and haematological parameters included haemoglobin [Hgb], white blood cells [WBC], platelets [PLA], alanine aminotransferase [ALT], aspartate aminotransferase [AST] and creatinine [CREA]. Levels assessed were - normal, grade 1, grade 2 and missing grade. The haematology and biochemistry toxicity grading scale was based on the Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.
Measured: At Days 0, 7, 30, 37 and 60

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

17 Jan 20114 Jun 2015

First posted20 Dec 2010 (estimated)
Study start17 Jan 2011
Primary completion17 Jul 2012
Study completion4 Jun 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for TuberculosisStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 240 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01262976
Sponsor's protocol ID: 113935
Status last verified: Nov 2017
First submitted: 16 Dec 2010
Last updated: 17 Sep 2018
Results posted: Yes, on ClinicalTrials.gov

Publications

Kumarasamy N, Poongulali S, Beulah FE, Akite EJ, Ayuk LN, Bollaerts A, Demoitie MA, Jongert E, Ofori-Anyinam O, Van Der Meeren O. Long-term safety and immunogenicity of the M72/AS01E candidate tuberculosis vaccine in HIV-positive and -negative Indian adults: Results from a phase II randomized controlled trial. Medicine (Baltimore). 2018 Nov;97(45):e13120. doi: 10.1097/MD.0000000000013120.
PubMed 30407329

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 17 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Safety and Immunogenicity of GSK Biologicals' Candidate Tuberculosis Vaccine (692342) When Administered to HIV-positive Adults Living in a Tuberculosis Endemic Region
ClinicalTrials.gov ID: NCT01262976
Acronym / sponsor ID: 113935
Conditions: Tuberculosis
Keywords: Tuberculosis vaccine
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 240 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 17 Jan 2011 (actual)
Primary completion: 17 Jul 2012 (actual)
Study completion: 4 Jun 2015 (actual)
First posted: 20 Dec 2010 (estimated)
Results: Posted 17 Sep 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Subjects will be followed-up for 3 years.

Subjects will be enrolled in 3 cohorts:

HIV-positive adults on highly active antiretroviral therapy
HIV-positive adults not on highly active antiretroviral therapy
HIV-negative adults

Each cohort will have 2 groups.

Detailed description

This Protocol Posting has been updated following Protocol Amendment 1, February 2011, leading to the update of the outcome measures and the inclusion and exclusion criteria.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 6

Arm	Type	Receives
HIV(+)-HA/GSK692342	Experimental	Biological: GSK's investigational vaccine 692342HIV-infected subjects between and including 18 to 59 years of age, who were on Highly Active Anti-Retroviral Therapy (HAART) at the time of study enrolment, received two doses of GSK692342 vaccine (TB) at Day 0 and Day 30, intramuscularly into the arm's deltoid region.
HIV(+)-HA/Placebo	Placebo comparator	Biological: Physiological salineHIV-infected subjects between and including 18 to 59 years of age, who were on Highly Active Anti-Retroviral Therapy (HAART) at the time of study enrolment, received two doses of saline solution at Day 0 and Day 30, intramuscularly into the arm's deltoid region.
HIV(+)-TN/GSK692342	Experimental	Biological: GSK's investigational vaccine 692342HIV-infected subjects between and including 18 to 59 years of age, who were HAART-treatment naive (TN) at the time of study enrolment, received two doses of GSK692342 vaccine (TB) at Day 0 and Day 30, intramuscularly into the arm's deltoid region.
HIV(+)-TN/Placebo	Placebo comparator	Biological: Physiological salineHIV-infected subjects between and including 18 to 59 years of age, who were HAART-treatment naive (TN) at the time of study enrolment, received two doses of saline solution at Day 0 and Day 30, intramuscularly into the arm's deltoid region.
HIV(-)/GSK692342	Experimental	Biological: GSK's investigational vaccine 692342Subjects between and including 18 to 59 years of age, who were HIV-negative at the time of study enrolment, received two doses of GSK692342 vaccine (TB) at Day 0 and Day 30, intramuscularly into the arm's deltoid region.
HIV(-)/Placebo	Placebo comparator	Biological: Physiological salineSubjects between and including 18 to 59 years of age, who were HIV-negative at the time of study enrolment, received two doses of saline solution at Day 0 and Day 30, intramuscularly into the arm's deltoid region.

Who may qualify

Ages: 18 to 59 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (24 listed)

Subjects who the investigator believes that they can and will comply with the requirements of the protocol.
A male or female between, and including, 18 and 59 years of age at the time of the first vaccination.
Written informed consent obtained from the subject prior to any study procedure.
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:

Key exclusion criteria (17 listed)

Use of any investigational or non-registered product 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 experimental Mtb vaccines.
History of previous exposure to components of the investigational vaccine within 30 days preceding the first dose of study vaccine
Chronic administration of immunosuppressant or other immune-modifying drugs within six months prior to the first vaccine/product dose. For corticosteroids, this will mean prednisone >= 20 mg/kg/day, or equivalent. Inhaled and topical steroids are allowed.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GSK's investigational vaccine 692342Intramuscular, 2 doses	Biological	HIV(+)-HA/GSK692342, HIV(+)-TN/GSK692342, HIV(-)/GSK692342
Physiological salineIntramuscular, 2 doses	Biological	HIV(+)-HA/Placebo, HIV(+)-TN/Placebo, HIV(-)/Placebo

Primary outcome

Number of Subjects With Grade 3 Solicited Local Symptoms
Time frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Solicited local symptoms assessed were pain and swelling. Grade 3 pain = pain that prevented normal activity. Grade 3 swelling = swelling spreading beyond 50 millimeters (mm) of injection site.
Number of Subjects With Grade 3 Solicited General Symptoms
Time frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Solicited general symptoms assessed 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. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever ≥ 39.5 °C.
Number of Subjects With Grade 3 Unsolicited Adverse Events (AEs)
Time frame: During the 30-day (Days 0-29) post-vaccination period
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. Grade 3 AE = an AE which prevented normal, everyday activities.
Number of Subjects With Serious Adverse Events (SAEs)
Time frame: From screening up to one month post Dose 2
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 and Grade 4 Haematological and Biochemical Levels
Time frame: At Day 0
Haematological and biochemical parameters assessed were haemoglobin [Hgb], white blood cells [WBC], platelets [PLA], alanine aminotransferase [ALT], aspartate aminotransferase [AST] and creatinine [CREA]. The haematology and biochemistry toxicity grading scale was based on the Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.
Number of Subjects With Grade 3 and 4 Haematological and Biochemical Levels
Time frame: At Day 7
Haematological and biochemical parameters assessed were haemoglobin [Hgb], white blood cells [WBC], platelets [PLA], alanine aminotransferase [ALT], aspartate aminotransferase [AST] and creatinine [CREA]. The haematology and biochemistry toxicity grading scale was based on the Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.
Number of Subjects With Grade 3 and Grade 4 Haematological/Biochemical Levels
Time frame: At Day 30
Haematological and biochemical parameters assessed were haemoglobin [Hgb], white blood cells [WBC], platelets [PLA], alanine aminotransferase [ALT], aspartate aminotransferase [AST] and creatinine [CREA]. The haematology and biochemistry toxicity grading scale was based on the Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.
Number of Subjects With Grade 3-4 Haematological and Biochemical Levels
Time frame: At Day 37
Haematological and biochemical parameters assessed were haemoglobin [Hgb], white blood cells [WBC], platelets [PLA], alanine aminotransferase [ALT], aspartate aminotransferase [AST] and creatinine [CREA]. The haematology and biochemistry toxicity grading scale was based on the Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.
Number of Subjects With Grade 3-4 Haematological/Biochemical Levels
Time frame: At Day 60
Haematological and biochemical parameters assessed were haemoglobin [Hgb], white blood cells [WBC], platelets [PLA], alanine aminotransferase [ALT], aspartate aminotransferase [AST] and creatinine [CREA]. The haematology and biochemistry toxicity grading scale was based on the Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.

15 secondary outcomes

Anti-Mycobacterium Tuberculosis Fusion Protein (M72) Specific Antibody Concentrations
Time frame: At Days 0, 30, 60, 210 and at Years 1, 2 and 3
Number of Seroconverted Subjects for M72-specific Antibodies
Time frame: At Days 0, 30, 60, 210 and at Years 1, 2 and 3
Frequency of M72-cluster of Differentiation 4 (CD4+) T-cells Expressing at Least 2 Immune Markers
Time frame: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
Frequency of M72-CD4+ T-cells Expressing Any Combination of Cytokines
Time frame: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
M72-cluster of Differentiation 4 (CD4+) T-cells Frequency Expressing Any Combination of Cytokines
Time frame: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
M72-CD4+ T-cells Frequency Expressing Any Combination of Cytokines
Time frame: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
Frequency of M72-cluster of Differentiation 8 (CD8+) T-cells Expressing at Least 2 Immune Markers
Time frame: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
Frequency of M72-CD8+ T-cells Expressing Any Combination of Cytokines
Time frame: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
M72-cluster of Differentiation 8 (CD8+) T Frequency Cells Expressing Any Combination of Cytokines
Time frame: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
M72-CD8+ T-cells Frequency Expressing Any Combination of Cytokines
Time frame: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
Number of Subjects With Any Solicited Local Symptoms
Time frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Number of Subjects With Any Solicited General Symptoms
Time frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Number of Subjects With Any Unsolicited AEs
Time frame: During the 30-day (Days 0-29) post-vaccination period
Number of Subjects With SAEs
Time frame: From one month post Dose 2 up to study end (Year 3)
Number of Subjects Presenting Different Grades of Haematological and Biochemical Values
Time frame: At Days 0, 7, 30, 37 and 60

Results and safety

Results posted to the registry on 17 Sep 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
HIV(+)-HA/GSK692342	40	37
HIV(+)-HA/Placebo	40	39
HIV(+)-TN/GSK692342	40	39
HIV(+)-TN/Placebo	40	38
HIV(-)/GSK692342	40	38
HIV(-)/Placebo	40	36

Primary outcome: Number of Subjects With Grade 3 Solicited Local Symptoms

Time frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses. Count of participants. Unit: Participants

Measure	HIV(+)-HA/GSK692342 n = 40	HIV(+)-TN/ GSK692342 n = 40	HIV(-)/GSK692342 n = 40
Grade 3 Pain, Dose 1	1	1	2
Grade 3 Swelling, Dose 1	0	0	0
Grade 3 Pain, Dose 2	3	2	4
Grade 3 Swelling, Dose 2	0	0	0
Grade 3 Pain, Across doses	3	3	4
Grade 3 Swelling, Across doses	0	0	0

Population analysed: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available and who had filled in the symptom sheet.

Primary outcome: Number of Subjects With Grade 3 Solicited General Symptoms

Time frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses. Count of participants. Unit: Participants

Measure	HIV(+)-HA/GSK692342 n = 40	HIV(+)-HA/Placebo n = 40	HIV(-)/GSK692342 n = 40	HIV(-)/Placebo n = 40
Grade 3 Fatigue, Dose 1	0	0	1	0
Grade 3 Gastro, Dose 1	0	0	0	1
Grade 3 Headache, Dose 1	0	1	3	0
Grade 3 Malaise, Dose 1	0	0	1	0
Grade 3 Myalgia, Dose 1	0	0	1	0
Grade 3 Temperature, Dose 1	0	0	0	0
Grade 3 Fatigue, Dose 2	1	0	1	0
Grade 3 Gastro, Dose 2	0	0	0	0

Population analysed: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available and who had filled in the symptom sheet.

Primary outcome: Number of Subjects With Grade 3 Unsolicited Adverse Events (AEs)

Time frame: During the 30-day (Days 0-29) post-vaccination period. Count of participants. Unit: Participants

Measure	HIV(+)-HA/GSK692342 n = 40	HIV(+)-HA/Placebo n = 40	HIV(+)-TN/ GSK692342 n = 40	HIV(+)-TN/Placebo n = 40	HIV(-)/GSK692342 n = 40	HIV(-)/Placebo n = 40
Value	26	27	35	33	13	13

Population analysed: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Primary outcome: Number of Subjects With Serious Adverse Events (SAEs)

Time frame: From screening up to one month post Dose 2. Count of participants. Unit: Participants

Measure	HIV(+)-HA/GSK692342 n = 40	HIV(+)-HA/Placebo n = 40	HIV(+)-TN/ GSK692342 n = 40	HIV(+)-TN/Placebo n = 40	HIV(-)/GSK692342 n = 40	HIV(-)/Placebo n = 40
Value	1	0	2	0	0	0

Population analysed: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

15 secondary outcomes are reported in the full results.

Adverse events

Time frame: Solicited local and general symptoms: during the 7-day (Days 0-6) post-vaccination period; Unsolicited AEs: during the 30-day (Days 0-29) post-vaccination period; SAEs: during the entire study period (from Day 0 up to Year 3).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
HIV(+)-HA/GSK692342	2 of 40 (5%)	29 of 40 (72.5%)	0 of 40
HIV(+)-HA/Placebo	0 of 40 (0%)	29 of 40 (72.5%)	0 of 40
HIV(+)-TN/GSK692342	3 of 40 (7.5%)	33 of 40 (82.5%)	2 of 40
HIV(+)-TN/Placebo	0 of 40 (0%)	33 of 40 (82.5%)	0 of 40
HIV(-)/GSK692342	0 of 40 (0%)	19 of 40 (47.5%)	0 of 440
HIV(-)/Placebo	0 of 40 (0%)	13 of 40 (32.5%)	0 of 40

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 30407329Kumarasamy N, Poongulali S, Beulah FE, Akite EJ, Ayuk LN, Bollaerts A, Demoitie MA, Jongert E, Ofori-Anyinam O, Van Der Meeren O. Long-term safety and immunogenicity of the M72/AS01E candidate tuberculosis vaccine in HIV-positive and -negative Indian adults: Results from a phase II randomized controlled trial. Medicine (Baltimore). 2018 Nov;97(45):e13120. doi: 10.1097/MD.0000000000013120.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GSK's investigational vaccine 692342 and Physiological saline in people with Tuberculosis, run by GlaxoSmithKline at 1 site in India.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects With Grade 3 Solicited Local Symptoms (time frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01262976, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2018.