Clinical trial NCT00397943: Safety and Immunogenicity of 2 Formulations of Tuberculosis Vaccine GSK692342 Given at 0,1 Months to Healthy Adults
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tuberculosis
Keywords: Tuberculosis
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-11-10
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 7-day (Days 0-6) follow-up period after each vaccine dose and across doses
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 7-day (Days 0-6) follow-up period after each vaccine dose and across doses
measure: Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
timeFrame: During the 30-day (Days 0-29) follow-up period after each vaccine dose
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: During the Active Vaccination Phase (from Day 0 up to Month 2)
measure: Number of Subjects With SAEs
timeFrame: From Month 2 up to Month 12
measure: Number of Subjects With SAEs
timeFrame: From Month 12 up to Month 24
measure: Number of Subjects With SAEs
timeFrame: From Month 24 up to Month 36
measure: Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
timeFrame: At Day 0
measure: Number of Subjects With Normal and Abnormal Haematological and Biochemical Levels
timeFrame: At Day 7
measure: Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
timeFrame: At Day 30
measure: Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
timeFrame: At Day 37
measure: Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
timeFrame: At Day 60
measure: Levels of C-reactive Protein
timeFrame: At Day 0
measure: Levels of C-reactive Protein
timeFrame: At Day 1
measure: Levels of C-reactive Protein
timeFrame: At Day 7
measure: Levels of C-reactive Protein
timeFrame: At Day 30
measure: Levels of C-reactive Protein
timeFrame: At Day 31
measure: Levels of C-reactive Protein
timeFrame: At Day 37
measure: Levels of Immunoglobulin E
timeFrame: At Day 0
measure: Levels of Immunoglobulin E
timeFrame: At Day 1
measure: Levels of Immunoglobulin E
timeFrame: At Day 7
measure: Levels of Immunoglobulin E
timeFrame: At Day 30
measure: Levels of Immunoglobulin E
timeFrame: At Day 31
measure: Levels of Immunoglobulin E
timeFrame: At Day 37
Secondary outcomes:
measure: Antibody Concentrations Against Mycobacterium Tuberculosis (M. Tuberculosis) Fusion Proteins M72 and Mtb72F
timeFrame: At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
measure: Antibody Concentrations Against M. Tuberculosis Fusion Protein M72
timeFrame: At Year 2 (Month 24) and Year 3 (Month 36)
measure: Frequency of Mycobacterium Tuberculosis Fusion Protein (M72) Specific Cluster of Differentiation 4/8 (CD4/CD8+) T-cells Expressing at Least Two Different Cytokines
timeFrame: At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
measure: Frequency of Mycobacterium Tuberculosis Fusion Protein (M72) Specific Cluster of Differentiation 4 (CD4+) T-cells Expressing at Least Two Different Cytokines
timeFrame: At Year 2 (Month 24) and Year 3 (Month 36)
measure: Frequency of M72 Specific CD4+ T-cells Expressing at Least One Cytokine and Another Signal Molecule
timeFrame: At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
measure: Frequency of M72 Specific CD4+ T-cells Expressing at Least One Cytokine and Another Signal Molecule
timeFrame: At Year 2 (Month 24) and Year 3 (Month 36)
measure: Number of Subjects With Response to M72-specific CD4+ T-cells Secreting at Least Two Different Cytokines/Activation Markers
timeFrame: At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
measure: Number of Subjects With Response to M72-specific CD4+ T-cells Secreting at Least Two Different Cytokines/Activation Markers
timeFrame: At Year 2 (Month 24) and Year 3 (Month 36)
measure: Concentrations of IFN-γ Produced in Serum Samples
timeFrame: Prior to (Day 0 and Day 30) and one day (Day 1 and Day 31) after each vaccination
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.