Safety and Immunogenicity of a Candidate Tuberculosis (TB) Vaccine Given to PPD-Negative Adults

Study Overview
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Brief Summary
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This Phase I study will evaluate the safety and immunogenicity of two doses GSK Biologicals' candidate TB vaccine (692342) according to a 0, 1, 2 months schedule in PPD-negative adults.

Official Title
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A Phase I Open Label, Dose-Escalation Study to Evaluate the Safety and Immunogenicity of the Recombinant Mycobacterium Tuberculosis Vaccine, Mtb72F With AS02A Adjuvant, When Administered Intramuscularly to Healthy PPD-Negative Adults

Conditions
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Tuberculosis (TB)

Intervention / Treatment
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* Biological: GSK's candidate Mycobacterium tuberculosis vaccine 692342


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female between 18 and 40 years of age at the time of screening Negative PPD skin test at screening. Subjects must have chest X-ray showing no evidence of pulmonary pathology. Female subjects of childbearing potential must have a negative serum pregnancy test at screening, must not be breast-feeding and are required to use adequate contraception from enrolment till 1 month after dose 3. Screening laboratory values must be within the laboratory normal ranges. Negative for human immunodeficiency virus-1 and 2 (HIV 1/2) antibody, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibody. Subjects must give written informed consent. Subjects must be willing to make all evaluation visits, be readily reachable by telephone or personal contact by the study site personnel and have a permanent address. Subjects' resting seated vital signs must be within the protocol-defined ranges. Exclusion Criteria: History of prior Bacillus Calmette-Guérin (BCG) vaccinations. History of documented exposure to Mycobacterium tuberculosis. History of previous administration of experimental Mycobacterium tuberculosis vaccines or previous exposure to experimental products containing components of the experimental vaccine. History of employment in a healthcare facility in a capacity that had direct or indirect contact with TB patients. Administration of any immunoglobulins or any immunotherapy within the 3 months preceding the first dose of study vaccination, and/or any blood products within the 4 months preceding HIV screening, or planned administrations during the study period. Use of St. John's Wort within six months of the Day 0 visit or planned administrations during the study period. Participation in another experimental protocol and/or receipt of any investigational products within 30 days prior to Day 0. History of autoimmune disease or causes of immunosuppressive states. 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. History of significant psychiatric illness. Current drug or alcohol abuse History of previous anaphylaxis or severe allergic reaction to vaccines or any other allergen. Subjects who are, in the opinion of the investigator, at significantly increased risk of non-cooperation with requirements of the study protocol. Any chronic drug therapy to be continued during the study period, with the exception of vitamins and/or dietary supplements (including mineral preparations such as calcium carbonate), herbal medications except St. John's Wort, birth control pills, anti-histamines for seasonal allergies, SSRIs (e.g. Prozac, Zoloft, Paxil), NSAIDs (e.g. aspirin, ibuprofen), and acetominophen. Chronic administration (defined as more than 14 days total) of immunosuppressants or other immune modifying drugs within six months prior to the first vaccine dose. History of chronic or intermittently recurring illnesses such as migraine headaches, diabetes, heart disease, and asthma. Current administration of anti-TB prophylaxis or therapy. History of administration of a live attenuated virus vaccine within 30 days of enrollment. History of administration of a subunit or killed vaccine within 14 days of enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Subjects receiving the low-dose antigen candidate TB vaccine | Biological: GSK's candidate Mycobacterium tuberculosis vaccine 692342<br>* Intramuscular injection, 3 doses at 0, 1, 2 months Different antigen doses (low and high)<br>|
| Experimental: Group B<br>Subjects receiving the high-dose antigen candidate TB vaccine | Biological: GSK's candidate Mycobacterium tuberculosis vaccine 692342<br>* Intramuscular injection, 3 doses at 0, 1, 2 months Different antigen doses (low and high)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of dose limiting toxicity |  | From study start up to Day 56. | 
| Occurrence of serious adverse events |  | During the entire study period. | 
| Occurrence of adverse events |  | At each visit | 
| Laboratory measurements of serum chemistry and hematology |  | At study start, prior to each vaccination and 1 and 6 months after dose 3 | 
| Resting vital signs (blood pressure, pulse, temperature) |  | At study start, prior to each vaccination and 1 and 6 months after dose 3 | 
| Chest X-ray findings |  | At study start and study end | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of T cell and antibody responses to the fusion protein and to each of the three Mycobacterium tuberculosis antigen domains. |  | Prior to each vaccination and 1 and 6 months after dose 3 | 
| Evaluation of PPD skin reactivity |  | At study start and study end | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tuberculosis vaccine