TuberculosisPhase 2NCT00397943

Safety and Immunogenicity of 2 Formulations of Tuberculosis Vaccine GSK692342 Given at 0,1 Months to Healthy Adults

A Phase 2 study testing GSK's candidate Mycobacterium tuberculosis vaccine 692342, Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and adjuvant system and Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and physiological saline in people with Tuberculosis, run by GlaxoSmithKline at 1 site in Belgium.

Completed

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

Official record

Search all trials

Trial summary

This study will assess the safety and immunogenicity of 2 different formulations of tuberculosis vaccine GSK692342 in healthy adults. Read more about this study

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Tuberculosis
What is being tested?: GSK's candidate Mycobacterium tuberculosis vaccine 692342, Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and adjuvant system and Comparator vaccine with recombinant Mycobacterium tuberculosis antigen 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: 110 participants
Where: 1 siteBelgium
Study dates: 15 Nov 2006to 1 Dec 2009
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 50 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 50 years of age at the time of the first vaccination.
Written informed consent obtained from the subject prior to any study procedure.
Free of obvious health problems as established by medical history and clinical examination before entering into the study.
Subjects must have PPD negative skin reactivity (0 mm induration 48 to 72 hours after PPD skin test administration).
Clinically normal laboratory values for creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), complete blood count (CBC) and differential, haemoglobin, platelet count and urinalysis.

Show all 9Show fewer

Seronegative for human immunodeficiency virus-1 and 2 (HIV 1/2) antibodies, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibodies
If the subject is female, she must be of non-childbearing potential, or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series.
No evidence of pulmonary pathology (i.e. acute or chronic pulmonary disease; past TB infection/disease) as confirmed by chest X-ray.

Who cannot join

History of previous exposure to experimental products containing components of the experimental vaccine.
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.
Chronic administration of immunosuppressants or other immune-modifying drugs within 6 months prior to the first vaccine dose.
Any chronic drug therapy to be continued during the study period. Vitamins and/or dietary supplements, herbal medications, birth control pills, anti-histamines for seasonal allergies, SSRIs (e.g. Prozac, Zoloft, Paxil), NSAIDs (nonsteroidal anti-inflammatory drugs e.g. aspirin, ibuprofen), and acetaminophen are allowed.
History of documented exposure to Mycobacterium tuberculosis.
History of prior vaccination with experimental Mycobacterium tuberculosis vaccines.

Show all 17Show fewer

Administration of any immunoglobulins, any immunotherapy and/or any blood products within the 3 months preceding the first dose of study vaccination, or planned administrations during the study period.
Participation in another experimental protocol during the study period.
Any confirmed or suspected immunosuppressive or immunodeficient condition; or family history of congenital or hereditary immunodeficiency.
History of hypersensitivity to vaccines or vaccine components
History of any acute or chronic illness or medication that, in the opinion of the investigator, may interfere with the evaluation of the safety or immunogenicity of the vaccine.
Volunteers with a personal history of autoimmune disease or who describe a first-degree relative with clearly documented autoimmune disease.
History of any neurological disorders or seizures.
History of chronic alcohol consumption and/or drug abuse.
History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
Major congenital defects.
Pregnant female, lactating female or female planning to become pregnant or planning to discontinue contraceptive precautions.

Trial locations and contacts

1 site in 1 country.

Belgium1 site

GSK Investigational Site
Ghent, 9000

Other trials in Belgium

About this study

Official title: Safety, Reactogenicity & Immunogenicity of 2 Formulations of Tuberculosis Vaccine GSK692342 Administered Intramuscularly According to a Schedule of 0, 1 Month, to Healthy Adults Aged 18 to 50 Years

This study will assess the safety and immunogenicity of 2 different formulations of tuberculosis vaccine GSK692342 in healthy adults.

Read the detailed description

The study is designed to have a vaccination phase (includes screening, 2 doses of vaccine 1 month apart and follow-up until 1 month post dose 2), which will be performed in an observer blinded manner. This will be followed by 3 years of follow-up which will continue in an open manner.

No new subjects will be recruited at the follow-up phase. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Conditions: Tuberculosis
Being tested: GSK's candidate Mycobacterium tuberculosis vaccine 692342, Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and adjuvant system, Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and physiological saline, Control vaccine with the adjuvant system.
Keywords: Tuberculosis
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 candidate Mycobacterium tuberculosis vaccine 692342Biological
Intramuscular injection, 2 doses at 0, 1 month
Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and adjuvant systemBiological
Intramuscular injection, 2 doses at 0, 1 month
Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and physiological salineBiological
Intramuscular injection, 2 doses at 0, 1 month
Control vaccine with the adjuvant system.Biological
Intramuscular injection, 2 doses at 0, 1 month

Study groups in NCT00397943
Study group	Role	What they receive
M72/AS01B Group	Experimental	Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of M72/AS01B vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1. Receives: Biological: GSK's candidate Mycobacterium tuberculosis vaccine 692342
M72/AS02A Group	Experimental	Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of M72/AS02A vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1. Receives: Biological: GSK's candidate Mycobacterium tuberculosis vaccine 692342
Mtb72F/AS02A Group	Active comparator	Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of the comparator Mtb72F/AS02A vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1. Receives: Biological: Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and adjuvant system
Non-adjuvanted Group	Active comparator	Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of the comparator GSK Biologicals' candidate recombinant M. tuberculosis vaccine, non-adjuvanted, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1. Receives: Biological: Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and physiological saline
Control Group	Placebo comparator	Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of the adjuvant system alone, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1. Receives: Biological: Control vaccine with the adjuvant system.

What is being measured

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

Number of Subjects With Any and Grade 3 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.
Measured: During the 7-day (Days 0-6) follow-up period after each vaccine dose and across doses
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Assessed solicited general symptoms were fatigue, fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)], gastrointestinal symptoms and headache. 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 causally related to the study vaccination.
Measured: During the 7-day (Days 0-6) follow-up period after each vaccine dose and across doses
Number of Subjects With Any, Grade 3 and Related 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 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. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.
Measured: During the 30-day (Days 0-29) follow-up period after each vaccine dose
Number of Subjects With Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Measured: During the Active Vaccination Phase (from Day 0 up to Month 2)
Number of Subjects With SAEs
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 Month 2 up to Month 12
Number of Subjects With SAEs
SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Note: Follow-up during Year 2 continued only for the M72/AS01B Group and M72/AS02A Group.
Measured: From Month 12 up to Month 24
Number of Subjects With SAEs
SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Note: Follow-up during Year 3 continued only for the M72/AS01B Group and M72/AS02A Group.
Measured: From Month 24 up to Month 36
Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
Measured: At Day 0
Number of Subjects With Normal and Abnormal Haematological and Biochemical Levels
Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
Measured: At Day 7
Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
Measured: At Day 30
Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
Measured: At Day 37
Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
Measured: At Day 60
Levels of C-reactive Protein
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Measured: At Day 0
Levels of C-reactive Protein
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Measured: At Day 1
Levels of C-reactive Protein
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Measured: At Day 7
Levels of C-reactive Protein
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Measured: At Day 30
Levels of C-reactive Protein
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Measured: At Day 31
Levels of C-reactive Protein
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Measured: At Day 37
Levels of Immunoglobulin E
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
Measured: At Day 0
Levels of Immunoglobulin E
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
Measured: At Day 1
Levels of Immunoglobulin E
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
Measured: At Day 7
Levels of Immunoglobulin E
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
Measured: At Day 30
Levels of Immunoglobulin E
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
Measured: At Day 31
Levels of Immunoglobulin E
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
Measured: At Day 37

Secondary outcomes (9)

Antibody Concentrations Against Mycobacterium Tuberculosis (M. Tuberculosis) Fusion Proteins M72 and Mtb72F
Antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in Enzyme-Linked Immunosorbent Assay (ELISA) units per milliliter (EU/mL). The reference seropositivity cut-off values for anti-M72 and anti-Mtb72F antibodies were ≥ 2.8 EU/mL and ≥ 1.0 EU/mL, respectively.
Measured: At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
Antibody Concentrations Against M. Tuberculosis Fusion Protein M72
Antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EU/mL). The reference seropositivity cut-off value for anti-M72 antibodies was ≥ 2.8 EU/mL.
Measured: At Year 2 (Month 24) and Year 3 (Month 36)
Frequency of Mycobacterium Tuberculosis Fusion Protein (M72) Specific Cluster of Differentiation 4/8 (CD4/CD8+) T-cells Expressing at Least Two Different Cytokines
Among cytokines expressed were interleukin-2 [IL-2] and/or interferon-gamma [IFN-γ] and/or tumour necrosis factor-alpha [TNF-α] and/or cluster of differentiation 40-ligand [CD40-L]. The analysis of cytokines expression was performed by flow cytometry using intracellular cytokine staining (ICS) on frozen peripheral blood mononuclear cell (PBMCs). Note: No vaccine induced responses were observed for CD8+ T-cells, so no results are presented throughout the record.
Measured: At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
Frequency of Mycobacterium Tuberculosis Fusion Protein (M72) Specific Cluster of Differentiation 4 (CD4+) T-cells Expressing at Least Two Different Cytokines
Among cytokines expressed were interleukin-2 [IL-2] and/or interferon-gamma [IFN-γ] and/or tumour necrosis factor-alpha [TNF-α] and/or cluster of differentiation 40-ligand [CD40-L]. The analysis of cytokines expression was performed by flow cytometry using intracellular cytokine staining (ICS) on frozen peripheral blood mononuclear cell (PBMCs).
Measured: At Year 2 (Month 24) and Year 3 (Month 36)
Frequency of M72 Specific CD4+ T-cells Expressing at Least One Cytokine and Another Signal Molecule
Expressed cytokine combinations for CD4+ T-cells were CD40-L and interleukin-2 [IL-2] or interferon-gamma [IFN-γ] or tumour necrosis factor-alpha [TNF-α]; IL-2 and CD40-L, or IFN-γ, or TNF-α; IFN-γ and CD40-L, or IL-2, or TNF-α; TNF-α and CD40-L, or IL-2, or IFN-γ.
Measured: At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
Frequency of M72 Specific CD4+ T-cells Expressing at Least One Cytokine and Another Signal Molecule
Expressed cytokine combinations for CD4+ T cells were CD40-L and interleukin-2 [IL-2] or interferon-gamma [IFN-γ] or tumour necrosis factor-alpha [TNF-α]; IL-2 and CD40-L, or IFN-γ, or TNF-α; IFN-γ and CD40-L, or IL-2, or TNF-α; TNF-α and CD40-L, or IL-2, or IFN-γ.
Measured: At Year 2 (Month 24) and Year 3 (Month 36)
Number of Subjects With Response to M72-specific CD4+ T-cells Secreting at Least Two Different Cytokines/Activation Markers
The cut-off value used for analysis of the frequency of cells expressing cytokines/immune markers was the 313 CD4+ T-cells per million CD4+ T-cells, i.e. the 95th percentile of the pre-vaccination level of cells expressing cytokines/immune markers.
Measured: At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
Number of Subjects With Response to M72-specific CD4+ T-cells Secreting at Least Two Different Cytokines/Activation Markers
The cut-off value used for analysis of the frequency of cells expressing cytokines/immune markers was the 313 CD4+ T-cells per million CD4+ T-cells, i.e. the 95th percentile of the pre-vaccination level of cells expressing cytokines/immune markers.
Measured: At Year 2 (Month 24) and Year 3 (Month 36)
Concentrations of IFN-γ Produced in Serum Samples
Concentrations are presented as geometric mean concentrations (GMCs), expressed in picogram per milliliter (pg/mL). The reference seropositivity cut-off value was equal to or above (≥) 1 pg/mL.
Measured: Prior to (Day 0 and Day 30) and one day (Day 1 and Day 31) after each vaccination

Timeline

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

15 Nov 20061 Dec 2009

First posted10 Nov 2006 (estimated)
Study start15 Nov 2006
Primary completion1 Dec 2009
Study completion1 Dec 2009

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 (2)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: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 110 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00397943
Sponsor's protocol ID: 106227
Other IDs: 106228, 108736, 108738, 2005-004497-24, 2005
Status last verified: Jun 2019
First submitted: 9 Nov 2006
Last updated: 19 Jun 2019
Results posted: Yes, on ClinicalTrials.gov
Individual data sharing: Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Publications

Leroux-Roels I, Forgus S, De Boever F, Clement F, Demoitie MA, Mettens P, Moris P, Ledent E, Leroux-Roels G, Ofori-Anyinam O; M72 Study Group. Improved CD4(+) T cell responses to Mycobacterium tuberculosis in PPD-negative adults by M72/AS01 as compared to the M72/AS02 and Mtb72F/AS02 tuberculosis candidate vaccine formulations: a randomized trial. Vaccine. 2013 Apr 19;31(17):2196-206. doi: 10.1016/j.vaccine.2012.05.035. Epub 2012 May 27.
PubMed 22643213
Moris P, Bellanger A, Ofori-Anyinam O, Jongert E, Yarzabal Rodriguez JP, Janssens M. Whole blood can be used as an alternative to isolated peripheral blood mononuclear cells to measure in vitro specific T-cell responses in human samples. J Immunol Methods. 2021 May;492:112940. doi: 10.1016/j.jim.2020.112940. Epub 2021 Jan 23.
PubMed 33493551

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

RecruitingPhase 4
Short-term Antibiotic Therapy in Mycobacterium Avium Complex Pulmonary Disease
Mycobacterium Avium Complex Pulmonary Disease
RecruitingObservational study
Paradoxical Tuberculosis Reactions in Patients Without HIV Infection
Tuberculosis
Not yet recruitingPhase 2
Re-evaluating the Duration in Children of TB Treatment
Tuberculosis
RecruitingPhase 1/2
A Study of Daily Rifapentine Combined With Isoniazid (1HP) for Tuberculosis Prevention in Children Less Than 13 Years of Age With and Without HIV
Tuberculosis
Active, not recruitingPhase 3
Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients
Tuberculosis, MDR

All Tuberculosis trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Safety, Reactogenicity & Immunogenicity of 2 Formulations of Tuberculosis Vaccine GSK692342 Administered Intramuscularly According to a Schedule of 0, 1 Month, to Healthy Adults Aged 18 to 50 Years
ClinicalTrials.gov ID: NCT00397943
Acronym / sponsor ID: 106227
Conditions: Tuberculosis
Keywords: Tuberculosis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 110 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 15 Nov 2006 (actual)
Primary completion: 1 Dec 2009 (actual)
Study completion: 1 Dec 2009 (actual)
First posted: 10 Nov 2006 (estimated)
Results: Posted 13 Aug 2018

Clinical summary

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

This study will assess the safety and immunogenicity of 2 different formulations of tuberculosis vaccine GSK692342 in healthy adults.

Detailed description

No new subjects will be recruited at the follow-up phase. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 5

Arm	Type	Receives
M72/AS01B Group	Experimental	Biological: GSK's candidate Mycobacterium tuberculosis vaccine 692342Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of M72/AS01B vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.
M72/AS02A Group	Experimental	Biological: GSK's candidate Mycobacterium tuberculosis vaccine 692342Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of M72/AS02A vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.
Mtb72F/AS02A Group	Active comparator	Biological: Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and adjuvant systemHealthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of the comparator Mtb72F/AS02A vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.
Non-adjuvanted Group	Active comparator	Biological: Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and physiological salineHealthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of the comparator GSK Biologicals' candidate recombinant M. tuberculosis vaccine, non-adjuvanted, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.
Control Group	Placebo comparator	Biological: Control vaccine with the adjuvant system.Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of the adjuvant system alone, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (9 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 50 years of age at the time of the first vaccination.
Written informed consent obtained from the subject prior to any study procedure.
Free of obvious health problems as established by medical history and clinical examination before entering into the study.
Subjects must have PPD negative skin reactivity (0 mm induration 48 to 72 hours after PPD skin test administration).

Key exclusion criteria (17 listed)

History of previous exposure to experimental products containing components of the experimental vaccine.
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.
Chronic administration of immunosuppressants or other immune-modifying drugs within 6 months prior to the first vaccine dose.
Any chronic drug therapy to be continued during the study period. Vitamins and/or dietary supplements, herbal medications, birth control pills, anti-histamines for seasonal allergies, SSRIs (e.g. Prozac, Zoloft, Paxil), NSAIDs (nonsteroidal anti-inflammatory drugs e.g. aspirin, ibuprofen), and acetaminophen are allowed.
History of documented exposure to Mycobacterium tuberculosis.

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 candidate Mycobacterium tuberculosis vaccine 692342Intramuscular injection, 2 doses at 0, 1 month	Biological	M72/AS01B Group, M72/AS02A Group
Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and adjuvant systemIntramuscular injection, 2 doses at 0, 1 month	Biological	Mtb72F/AS02A Group
Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and physiological salineIntramuscular injection, 2 doses at 0, 1 month	Biological	Non-adjuvanted Group
Control vaccine with the adjuvant system.Intramuscular injection, 2 doses at 0, 1 month	Biological	Control Group

Primary outcome

Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Time frame: During the 7-day (Days 0-6) follow-up period after each vaccine dose and across doses
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.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Time frame: During the 7-day (Days 0-6) follow-up period after each vaccine dose and across doses
Assessed solicited general symptoms were fatigue, fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)], gastrointestinal symptoms and headache. 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 causally related to the study vaccination.
Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
Time frame: During the 30-day (Days 0-29) follow-up period after each vaccine dose
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. 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)
Time frame: During the Active Vaccination Phase (from Day 0 up to Month 2)
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 SAEs
Time frame: From Month 2 up to Month 12
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 SAEs
Time frame: From Month 12 up to Month 24
SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Note: Follow-up during Year 2 continued only for the M72/AS01B Group and M72/AS02A Group.
Number of Subjects With SAEs
Time frame: From Month 24 up to Month 36
SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Note: Follow-up during Year 3 continued only for the M72/AS01B Group and M72/AS02A Group.
Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
Time frame: At Day 0
Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
Number of Subjects With Normal and Abnormal Haematological and Biochemical Levels
Time frame: At Day 7
Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
Time frame: At Day 30
Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
Time frame: At Day 37
Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
Time frame: At Day 60
Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
Levels of C-reactive Protein
Time frame: At Day 0
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Levels of C-reactive Protein
Time frame: At Day 1
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Levels of C-reactive Protein
Time frame: At Day 7
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Levels of C-reactive Protein
Time frame: At Day 30
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Levels of C-reactive Protein
Time frame: At Day 31
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Levels of C-reactive Protein
Time frame: At Day 37
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Levels of Immunoglobulin E
Time frame: At Day 0
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
Levels of Immunoglobulin E
Time frame: At Day 1
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
Levels of Immunoglobulin E
Time frame: At Day 7
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
Levels of Immunoglobulin E
Time frame: At Day 30
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
Levels of Immunoglobulin E
Time frame: At Day 31
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
Levels of Immunoglobulin E
Time frame: At Day 37
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).

9 secondary outcomes

Antibody Concentrations Against Mycobacterium Tuberculosis (M. Tuberculosis) Fusion Proteins M72 and Mtb72F
Time frame: At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
Antibody Concentrations Against M. Tuberculosis Fusion Protein M72
Time frame: At Year 2 (Month 24) and Year 3 (Month 36)
Frequency of Mycobacterium Tuberculosis Fusion Protein (M72) Specific Cluster of Differentiation 4/8 (CD4/CD8+) T-cells Expressing at Least Two Different Cytokines
Time frame: At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
Frequency of Mycobacterium Tuberculosis Fusion Protein (M72) Specific Cluster of Differentiation 4 (CD4+) T-cells Expressing at Least Two Different Cytokines
Time frame: At Year 2 (Month 24) and Year 3 (Month 36)
Frequency of M72 Specific CD4+ T-cells Expressing at Least One Cytokine and Another Signal Molecule
Time frame: At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
Frequency of M72 Specific CD4+ T-cells Expressing at Least One Cytokine and Another Signal Molecule
Time frame: At Year 2 (Month 24) and Year 3 (Month 36)
Number of Subjects With Response to M72-specific CD4+ T-cells Secreting at Least Two Different Cytokines/Activation Markers
Time frame: At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
Number of Subjects With Response to M72-specific CD4+ T-cells Secreting at Least Two Different Cytokines/Activation Markers
Time frame: At Year 2 (Month 24) and Year 3 (Month 36)
Concentrations of IFN-γ Produced in Serum Samples
Time frame: Prior to (Day 0 and Day 30) and one day (Day 1 and Day 31) after each vaccination

Results and safety

Results posted to the registry on 13 Aug 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
M72/AS01B Group	40	28
M72/AS02A Group	40	31
Mtb72F/AS02A Group	10	10
Non-adjuvanted Group	10	10
Control Group	10	10

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

Time frame: During the 7-day (Days 0-6) follow-up period after each vaccine dose and across doses. Count of participants. Unit: Participants

Measure	M72/AS01B Group n = 40	M72/AS02A Group n = 40	Mtb72F/AS02A Group n = 10	Non-adjuvanted Group n = 10	Control Group n = 10
Any Pain, Dose 1	38	40	9	1	10
Grade 3 Pain, Dose 1	7	5	4	0	1
Any Redness, Dose 1	4	2	0	0	1
Grade 3 Redness, Dose 1	2	2	0	0	0
Any Swelling, Dose 1	4	8	2	0	2
Grade 3 Swelling, Dose 1	2	3	0	0	1
Any Pain, Dose 2	39	37	9	2	10
Grade 3 Pain, Dose 2	7	4	2	0	0

Population analysed: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine administration documented.

Primary outcome: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

Time frame: During the 7-day (Days 0-6) follow-up period after each vaccine dose and across doses. Count of participants. Unit: Participants

Measure	M72/AS01B Group n = 40	M72/AS02A Group n = 40	Mtb72F/AS02A Group n = 10	Non-adjuvanted Group n = 10	Control Group n = 10
Any Fatigue, Dose 1	27	21	6	2	3
Grade 3 Fatigue, Dose 1	0	1	0	1	0
Related Fatigue, Dose 1	26	19	5	2	3
Any Fever, Dose 1	5	2	1	0	1
Grade 3 Fever, Dose 1	0	0	0	0	0
Related Fever, Dose 1	3	2	0	0	1
Any Gastrointestinal symptoms, Dose 1	9	7	3	2	1
Grade 3 Gastrointestinal symptoms, Dose 1	1	0	0	0	0

Population analysed: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine administration documented.

Primary outcome: Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)

Time frame: During the 30-day (Days 0-29) follow-up period after each vaccine dose. Count of participants. Unit: Participants

Measure	M72/AS01B Group n = 40	M72/AS02A Group n = 40	Mtb72F/AS02A Group n = 10	Non-adjuvanted Group n = 10	Control Group n = 10
Any AE(s)	37	33	10	7	7
Grade 3 AE(s)	12	7	4	2	1
Related AE(s)	31	21	8	2	4

Population analysed: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine administration documented.

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

Time frame: During the Active Vaccination Phase (from Day 0 up to Month 2). Count of participants. Unit: Participants

Measure	M72/AS01B Group n = 40	M72/AS02A Group n = 40	Mtb72F/AS02A Group n = 10	Non-adjuvanted Group n = 10	Control Group n = 10
Value	0	0	1	0	0

Population analysed: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine administration documented.

9 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 Month 36) for the M72/AS01B Group and M72/AS02A Group, up to Month 12 for the Mtb72F/AS02A Group, Non-adjuvanted Group, and Control Group.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
M72/AS01B Group	2 of 40 (5%)	40 of 40 (100%)	0 of 40
M72/AS02A Group	0 of 40 (0%)	40 of 40 (100%)	0 of 40
Mtb72F/AS02A Group	1 of 10 (10%)	10 of 10 (100%)	0 of 10
Non-adjuvanted Group	0 of 10 (0%)	9 of 10 (90%)	0 of 10
Control Group	1 of 10 (10%)	10 of 10 (100%)	0 of 10

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 22643213Leroux-Roels I, Forgus S, De Boever F, Clement F, Demoitie MA, Mettens P, Moris P, Ledent E, Leroux-Roels G, Ofori-Anyinam O; M72 Study Group. Improved CD4(+) T cell responses to Mycobacterium tuberculosis in PPD-negative adults by M72/AS01 as compared to the M72/AS02 and Mtb72F/AS02 tuberculosis candidate vaccine formulations: a randomized trial. Vaccine. 2013 Apr 19;31(17):2196-206. doi: 10.1016/j.vaccine.2012.05.035. Epub 2012 May 27.
Derived from this study: PubMed 33493551Moris P, Bellanger A, Ofori-Anyinam O, Jongert E, Yarzabal Rodriguez JP, Janssens M. Whole blood can be used as an alternative to isolated peripheral blood mononuclear cells to measure in vitro specific T-cell responses in human samples. J Immunol Methods. 2021 May;492:112940. doi: 10.1016/j.jim.2020.112940. Epub 2021 Jan 23.
Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Related trials for Tuberculosis

RecruitingPhase 4
Short-term Antibiotic Therapy in Mycobacterium Avium Complex Pulmonary Disease
Mycobacterium Avium Complex Pulmonary Disease
RecruitingObservational study
Paradoxical Tuberculosis Reactions in Patients Without HIV Infection
Tuberculosis
Not yet recruitingPhase 2
Re-evaluating the Duration in Children of TB Treatment
Tuberculosis
RecruitingPhase 1/2
A Study of Daily Rifapentine Combined With Isoniazid (1HP) for Tuberculosis Prevention in Children Less Than 13 Years of Age With and Without HIV
Tuberculosis
Active, not recruitingPhase 3
Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients
Tuberculosis, MDR

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?

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 9 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 19 Jun 2019. 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 Belgium. 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 13 Aug 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 Any and Grade 3 Solicited Local Symptoms (time frame: During the 7-day (Days 0-6) follow-up period after each vaccine dose and across doses). The study lists 24 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 NCT00397943, which also lists 2 linked publications.

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 19 Jun 2019.