Clinical trial NCT01669096: Study in Healthy Adults to Evaluate Gene Activation After Vaccination With GlaxoSmithKline (GSK) Biologicals' Candidate Tuberculosis (TB) Vaccine GSK 692342
Official title: Evaluation of the Kinetics of mRNA Expression After Two Doses of GSK Biologicals' Candidate Tuberculosis (Tuberculosis) Vaccine GSK 692342 in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tuberculosis
Keywords: adults
Tuberculosis vaccine
HIV negative
healthy
mRNA expression
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Aeras
First posted: 2012-08-20
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The purpose of this study is to assess the safety and immunogenicity of two doses of the TB vaccine administered according to a 0, 1 month schedule. In, addition, blood samples collected at different time points after vaccination will be analysed to see when exactly genes are activated by the vaccine using an assay called mRNA expression profiling. The different methods for mRNA expression profiling using whole blood samples versus Peripheral Blood Mononuclear cell(s) (PBMCs), will also be compared.


Eligibility criteria: Inclusion Criteria:

* Subjects who, in the opinion of the investigator, 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 obtaining informed consent.
* Written informed consent obtained from the subject.
* Healthy subjects as established by medical history and clinical examination before entering into the study.
* Known BCG vaccination or presence of a BCG scar.
* Seronegative for human immunodeficiency virus-1.
* Female 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, and
  * has a negative pregnancy test on the day of screening and the day of first vaccination, and
  * has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.

Exclusion Criteria:

* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
* Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose (for corticosteroids, this will mean prednisone ≥ 20 mg/day or equivalent). Inhaled and topical steroids are allowed.
* Administration of long-acting immune-modifying drugs starting 2 years before the first dose and planned administration during the study.
* Planned administration/administration of a vaccine/product not foreseen by the study protocol within the period starting 30 days before the first dose of study vaccine and ending at the last study visit.
* Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product (pharmaceutical product or device).
* History of TB disease.
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* QuantiFERON® TB Gold positive test result.
* History of medically confirmed autoimmune disease.
* Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
* History of any reaction of hypersensitivity likely to be exacerbated by any component of the vaccine.
* Pregnant or lactating female.
* Female planning to become pregnant or planning to discontinue contraceptive precautions.

Primary outcomes:
measure: Concentration of Specific Interferon Gamma (IFN-γ) Antibodies Secreted in Serum Samples
timeFrame: At Day 0 prior to Dose 1
measure: Concentration of Specific Interferon Gamma (IFN-γ) Antibodies Secreted in Serum Samples
timeFrame: At Day 30 post-Dose 1
measure: Concentration of Specific Interferon Gamma (IFN-γ) Antibodies Secreted in Serum Samples
timeFrame: At Day 31 post-Dose 2
measure: Concentration of Specific Interferon Gamma (IFN-γ) Antibodies Secreted in Serum Samples
timeFrame: At Day 37 post-Dose 2
measure: Concentration of Specific Interferon Gamma (IFN-γ) Antibodies Secreted in Serum Samples
timeFrame: At Day 40 post-Dose 2
measure: Concentration of Specific Interferon Gamma (IFN-γ) Antibodies Secreted in Serum Samples
timeFrame: At Day 44 post-Dose 2
measure: Concentration of Specific Interferon Gamma (IFN-γ) Antibodies Secreted in Serum Samples
timeFrame: At Day 47 post-Dose 2
measure: Frequency of Mycobacterium Tuberculosis Fusion Protein (M72) Specific Cluster of Differentiation CD4+/CD8+ T Cells Expressing at Least Two Different Immune Markers
timeFrame: At Day 0 prior to Dose 1
measure: Frequency of M72 Fusion Protein Specific Cluster of Differentiation CD4+/CD8+ T Cells Expressing at Least Two Different Immune Markers
timeFrame: At Day 60 post-Dose 2
measure: Frequency of M72 Specific Cluster of Differentiation CD4+ T Cells Expressing Any Combination of Immune Markers (M1 to M 14)
timeFrame: At Day 0 prior -Dose 1
measure: Frequency of M72 Specific Cluster of Differentiation CD4+ T Cells Expressing Any Combination of Immune Markers (M15 to M28)
timeFrame: At Day 0 prior-Dose 1
measure: Frequency of M72 Specific Cluster of Differentiation CD4+ T Cells Expressing Any Combination of Immune Markers (M29 to M42)
timeFrame: At Day 0 prior - Dose 1
measure: Frequency of M72 Specific Cluster of Differentiation CD4+ T Cells Expressing Any Combination of Immune Markers (M43 to M56)
timeFrame: At Day 0 (prior- Dose 1)
measure: Frequency of M72 Specific Cluster of Differentiation CD4+ T Cells Expressing Any Combination of Immune Markers (M57 to M63)
timeFrame: At Day 0 (prior to Dose 1)
measure: Frequency of M72 Specific Cluster of Differentiation CD4+ T Cells Expressing Any Combination of Immune Markers, Post Dose 2 (M1 to M14)
timeFrame: At Day 60 post-Dose 2
measure: Frequency of M72 Specific Cluster of Differentiation CD4+ T Cells Expressing Any Combination of Immune Markers, Post Dose 2 (M15 to M28)
timeFrame: At Day 60 post - Dose 2
measure: Frequency of M72 Specific Cluster of Differentiation CD4+ T Cells Expressing Any Combination of Immune Markers, Post Dose 2 (M29 to M42)
timeFrame: At Day 60 post Dose 2
measure: Frequency of M72 Specific Cluster of Differentiation CD4+ T Cells Expressing Any Combination of Immune Markers,Post Dose 2 (M43 to M56)
timeFrame: At Day 60 (post-Dose 2)
measure: Frequency of M72 Specific Cluster of Differentiation CD4+ T Cells Expressing Any Combination of Immune Markers, Post Dose 2 (M57 to M63)
timeFrame: At Day 60 post- Dose 2
measure: Frequency of M72 Specific Cluster of Differentiation CD8+ T Cells Expressing Any Combination of Immune Markers (M1 to M14)
timeFrame: At Day 0 prior-Dose 1
measure: Frequency of M72 Specific Cluster of Differentiation CD8+ T Cells Expressing Any Combination of Immune Markers (M15 to M28)
timeFrame: At Day 0 prior -Dose 1
measure: Frequency of M72 Specific Cluster of Differentiation CD8+ T Cells Expressing Any Combination of Immune Markers (M29 to M42)
timeFrame: At Day 0 prior- Dose 1
measure: Frequency of M72 Specific Cluster of Differentiation CD8+ T Cells Expressing Any Combination of Immune Markers (M43 to M56)
timeFrame: At Day 0 prior to Dose 1
measure: Frequency of M72 Specific Cluster of Differentiation CD8+ T Cells Expressing Any Combination of Immune Markers (M57 to M63)
timeFrame: At Day 0 (prior to Dose 1)
measure: Frequency of M72 Specific Cluster of Differentiation CD8+ T Cells Expressing Any Combination of Immune Markers, Post Dose 2 (M1 to M14)
timeFrame: At Day 60 post-Dose 2
measure: Frequency of M72 Specific Cluster of Differentiation CD8+ T Cells Expressing Any Combination of Immune Markers, Post Dose 2 (M15 to M28)
timeFrame: At Day 60 post -Dose 2
measure: Frequency of M72 Specific Cluster of Differentiation CD8+ T Cells Expressing Any Combination of Immune Markers, Post Dose 2 (M29 to M42)
timeFrame: At Day 60 post- Dose 2
measure: Frequency of M72 Specific Cluster of Differentiation CD8+ T Cells Expressing Any Combination of Immune Markers, Post Dose 2 (M43 to M56)
timeFrame: At Day 60 post-Dose 2
measure: Frequency of M72 Specific Cluster of Differentiation CD8+ T Cells Expressing Any Combination of Immune Markers, Post Dose 2 (M57 to M63)
timeFrame: At Day 60 post Dose 2
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: During the entire study period (from Day 0 to Month 7)
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 7-day (Days 0-6) post-vaccination period following each 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) post-vaccination period following each dose and across doses
measure: Number of Subjects With Unsolicited Adverse Events (AEs)
timeFrame: During the 30-day (Days 0-29) post-vaccination period
measure: Number of Subjects With Potential Immune-Mediated Disease(s) (pIMDs)
timeFrame: During the entire study period (From Day 0 to Month 7)
Secondary outcomes:
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: van den Berg RA, De Mot L, Leroux-Roels G, Bechtold V, Clement F, Coccia M, Jongert E, Evans TG, Gillard P, van der Most RG. Adjuvant-Associated Peripheral Blood mRNA Profiles and Kinetics Induced by the Adjuvanted Recombinant Protein Candidate Tuberculosis Vaccine M72/AS01 in Bacillus Calmette-Guerin-Vaccinated Adults. Front Immunol. 2018 Mar 26;9:564. doi: 10.3389/fimmu.2018.00564. eCollection 2018.