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

GlaxoSmithKline110 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Enrollment

110

Conditions

Tuberculosis

Interventions

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * 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. * 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. Exclusion Criteria: * 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. * 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.

Locations (1)

GSK Investigational Site

Ghent, Belgium

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: During the Active Vaccination Phase (from Day 0 up to Month 2)

Data from ClinicalTrials.gov

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Secondary Outcomes

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

Time frame: Prior to (Day 0 and Day 30) and one day (Day 1 and Day 31) after each vaccination