Clinical trial NCT00730795: Safety and Immunogenicity of a Candidate Tuberculosis (TB) Vaccine Given to PPD-Negative Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Tuberculosis (TB)
Keywords: Tuberculosis vaccine
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Corixa Corporation
First posted: 2008-08-08
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Occurrence of dose limiting toxicity
timeFrame: From study start up to Day 56.
measure: Occurrence of serious adverse events
timeFrame: During the entire study period.
measure: Occurrence of adverse events
timeFrame: At each visit
measure: Laboratory measurements of serum chemistry and hematology
timeFrame: At study start, prior to each vaccination and 1 and 6 months after dose 3
measure: Resting vital signs (blood pressure, pulse, temperature)
timeFrame: At study start, prior to each vaccination and 1 and 6 months after dose 3
measure: Chest X-ray findings
timeFrame: At study start and study end
Secondary outcomes:
measure: Evaluation of T cell and antibody responses to the fusion protein and to each of the three Mycobacterium tuberculosis antigen domains.
timeFrame: Prior to each vaccination and 1 and 6 months after dose 3
measure: Evaluation of PPD skin reactivity
timeFrame: At study start and study end
Other outcomes:
Locations:
city: Tacoma
country: United States
facility: GSK Clinical Trials Call Center
state: Washington
Study officials:
affiliation: GlaxoSmithKline
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Von Eschen K, Morrison R, Braun M, Ofori-Anyinam O, De Kock E, Pavithran P, Koutsoukos M, Moris P, Cain D, Dubois MC, Cohen J, Ballou WR. The candidate tuberculosis vaccine Mtb72F/AS02A: Tolerability and immunogenicity in humans. Hum Vaccin. 2009 Jul;5(7):475-82. doi: 10.4161/hv.8570. Epub 2009 Jul 27.