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Dose-Escalation Study to Evaluate the Safety and Immunogenicity of MTBVAC Vaccine in Comparison With BCG Vaccine. (MTBVAC)

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ClinicalTrials.gov Identifier: NCT02013245
Recruitment Status : Completed
First Posted : December 17, 2013
Results First Posted : March 24, 2017
Last Update Posted : March 24, 2017
Sponsor:
Collaborators:
Universidad de Zaragoza
Centre Hospitalier Universitaire Vaudois
TuBerculosis Vaccine Initiative
Information provided by (Responsible Party):
Biofabri, S.L

Tracking Information
First Submitted Date  ICMJE December 3, 2013
First Posted Date  ICMJE December 17, 2013
Results First Submitted Date  ICMJE March 15, 2016
Results First Posted Date  ICMJE March 24, 2017
Last Update Posted Date March 24, 2017
Study Start Date  ICMJE January 2013
Actual Primary Completion Date June 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 6, 2017)
Number of Participants With Adverse Events up to 210 Days After Vaccination [ Time Frame: 7 months follow up ]
Safety and reactogenicity for all subjects as determined by:
  • Occurrence of solicited symptoms during the 7-day follow-up period following vaccination and occurrence of unsolicited symptoms during the 210-day follow-up period following vaccination.
  • Occurrence of grade 3 vaccine related local and general symptoms during the 210-day follow-up period following vaccination and occurrence of serious adverse events throughout the entire study period.
  • Haematological and biochemical safety test levels prior and after vaccination
Original Primary Outcome Measures  ICMJE
 (submitted: December 11, 2013)
Safety and reactogenicity for all subjects. [ Time Frame: 7 months follow up ]
Safety and reactogenicity for all subjects as determined by:
  • Occurrence of solicited symptoms during the 7-day follow-up period following vaccination and occurrence of unsolicited symptoms during the 210-day follow-up period following vaccination.
  • Occurrence of grade 3 vaccine related local and general symptoms during the 210-day follow-up period following vaccination and occurrence of serious adverse events throughout the entire study period.
  • Haematological and biochemical safety test levels prior and after vaccination
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 6, 2017)
Number of Participants With Three-cytokine-positive CD4+ T-cell Response [ Time Frame: Day 28 ]
Measure of the kinetics of CD4+ T-cell responses to MTBVAC or BCG vaccination by tracking the expression of IFNγ, TNFα and IL-2 upon stimulation with live MTBVAC or BCG
Original Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2013)
Cell mediated immune response assessment [ Time Frame: 7 months follow up ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose-Escalation Study to Evaluate the Safety and Immunogenicity of MTBVAC Vaccine in Comparison With BCG Vaccine.
Official Title  ICMJE Phase I Double Blind, Randomized, Controlled, Dose-Escalation Study to Evaluate the Safety and Immunogenicity of MTBVAC in Comparison With BCG in Elispot TB(ESAT-6, CFP10, PPD)- and HIV- Negative Volunteers
Brief Summary The purpose of this study is to test the safety and immunogenicity of MTBVAC as a potential substitute for BCG vaccination. BCG vaccination has indeed demonstrated its major limitation in inducing protection against tuberculosis (TB). Novel vaccines are essential to fight against the current world epidemics in tuberculosis and resistance to anti-TB drugs.
Detailed Description A randomized, double-blind, controlled Phase I study conducted at CHUV, Lausanne, Switzerland, to compare MTBVAC to licensed BCG in healthy, PPD-negative adult male and female volunteers. The study involves random allocation of up to 36 subjects (4 vaccine groups of 9 volunteers fulfilling the inclusion criteria) to MTBVAC (tested at three separate doses) or standard dose BCG (on a 3 verum : 1control basis) in a dose-escalation manner to one of three cohorts. Each cohort includes 9 subjects set to receive MTBVAC lowest dose 5x10E03, or MTBVAC intermediate dose 5x10E04, or high dose 5x10E05 colony forming units (CFU) in 0.1 mL and 3 subjects set to receive standard dose BCG (5x10E05 CFU in 0.1 mL). A single intradermal injection is given in the non-dominant arm of each volunteer starting with the lowest MTBVAC dose. Each MTBVAC vaccine dose is administered staggered by cohort, starting with the cohort with the lowest MTBVAC dose level. After at least 35 days of follow-up within each cohort a safety review and evaluation by Independent Data Safety Monitoring Board provides go/no-go for vaccination of the subsequent cohorts if no safety issues as defined by preset stopping rules.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Tuberculosis
  • Healthy
Intervention  ICMJE
  • Biological: MTBVAC live vaccine
    Live-attenuated Mycobacterium tuberculosis vaccine
  • Biological: Commercially available BCG live vaccine
    Live-attenuated Mycobacterium bovis vaccine
Study Arms  ICMJE
  • Experimental: MTBVAC group 1
    Intervention: MTBVAC live vaccine (low dose 5 x 10E03 CFU/0.1mL)
    Intervention: Biological: MTBVAC live vaccine
  • Experimental: MTBVAC Group 2
    Intervention: MTBVAC live vaccine (middle dose 5 x 10E04 CFU/0.1mL)
    Intervention: Biological: MTBVAC live vaccine
  • Experimental: MTBVAC Group 3
    Intervention: MTBVAC live vaccine (high dose 5 x 10E05 CFU/0.1mL)
    Intervention: Biological: MTBVAC live vaccine
  • Active Comparator: BCG Control Group
    Intervention: Commercially available BCG live vaccine (dose 5 x 10E05 CFU/0.1mL)
    Intervention: Biological: Commercially available BCG live vaccine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 11, 2013)
36
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 2014
Actual Primary Completion Date June 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects who the Investigator believes that they can and will comply with the requirements of the protocol
  • Subjects who have no evidence of exposition to BCG as demonstrated by a ELISPOT PPD assay along with no history of BCG vaccination and no BCG scar
  • A male or female between, and including, 18 and 45 years of age at the time of the vaccination.
  • Written informed consent obtained from the subject prior to any study procedure.
  • If the subject is female, she must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception
  • Clinically acceptable laboratory values for blood tests.
  • Seronegative for human immunodeficiency virus 1 and -2 (HIV-1/2) antibodies, p24 antigen, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibodies.
  • No evidence of pulmonary pathology as confirmed by chest X-ray.
  • No history of extrapulmonary TB.
  • No history of previous contact with M. tuberculosis (latent tuberculosis) as demonstrated by a negative ELISPOT Tb (ESAT-6, CFP10) assay.

Exclusion Criteria:

  • History of allergic reactions (significant IgE-mediated events) or anaphylaxis to previous immunisations (any vaccine).
  • History of allergic disease or reactions
  • History of previous administration of experimental Mycobacterium tuberculosis vaccines.
  • Use of any investigational or non-registered product (drug or vaccine) in another experimental protocol other than the study vaccines within 30 days preceding the vaccination, or planned use during the study period.
  • Any chronic drug therapy to be continued during the study period.
  • Chronic administration of immunosuppressors or other immune-modifying drugs.
  • Administration of any immunoglobulins, any immunotherapy and/or any blood products within the three months preceding the vaccination, or planned administrations during the study period.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition (including HIV) based on medical history and physical examination.
  • Any condition or history of any acute or chronic illness or medication which, in the opinion of the Investigator, may interfere with the evaluation of the study objectives.
  • A family history of congenital or hereditary immunodeficiency.
  • A stay of more than 2 months in a highly endemic area (e.g. Eastern Europe (Romania, Bulgaria) and low-income countries) within 6 months prior to the screening visit or travel of more than 2 months foreseen in an area of high endemicity after the enrolment into the study.
  • History of any neurologic disorders or seizures.
  • History of chronic alcohol consumption and/or drug abuse.
  • Major congenital defects.
  • Pregnant or lactating female.
  • Female planning to become pregnant or planning to discontinue contraceptive precautions.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02013245
Other Study ID Numbers  ICMJE MTBVAC-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Biofabri, S.L
Study Sponsor  ICMJE Biofabri, S.L
Collaborators  ICMJE
  • Universidad de Zaragoza
  • Centre Hospitalier Universitaire Vaudois
  • TuBerculosis Vaccine Initiative
Investigators  ICMJE
Principal Investigator: François Spertini, MD Centre Hospitalier Universitaire Vaudois
PRS Account Biofabri, S.L
Verification Date February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP