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MTBVAC Study in Adults With and Without Latent Tuberculosis Infection in South Africa (A-050)

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ClinicalTrials.gov Identifier: NCT02933281
Recruitment Status : Not yet recruiting
First Posted : October 14, 2016
Last Update Posted : October 3, 2018
Sponsor:
Collaborators:
Biofabri, S.L
Universidad de Zaragoza
South African Tuberculosis Vaccine Initiative
TuBerculosis Vaccine Initiative
Information provided by (Responsible Party):
Aeras

October 10, 2016
October 14, 2016
October 3, 2018
October 2018
December 2019   (Final data collection date for primary outcome measure)
Safety and reactogenicity of MTBVAC at escalating dose levels compared to BCG vaccine by assessing number of participants with AEs and SAEs [ Time Frame: Study Days 7 to Day 365 ]
Collection of systemic solicited and unsolicited adverse events; solicited and unsolicited injection site reactions; and serious adverse reactions.
  • Occurrence of systemic solicited adverse events and unsolicited adverse events. [ Time Frame: Up to Day 28 ]
  • Occurrence of solicited and unsolicited injection site reactions. [ Time Frame: Up to Day 84 ]
  • Occurrence of serious adverse events after vaccination. [ Time Frame: Through the end of study follow up - day 182 ]
Complete list of historical versions of study NCT02933281 on ClinicalTrials.gov Archive Site
  • Difference in T cell response between MTBVAC dose levels across all post-immunization time points measured by percentage of MTBVAC-specific CD4 and CD8 T cells that produce any or a combination of relevant cytokines in ICS assay [ Time Frame: Study Days 0, 28, 56, 182, and 365 ]
    12 hour whole blood (WB) intracellular cytokine staining (ICS) assay
  • Qualitative and quantitative results from QuantiFERON® TB (QFT) test summarized using participant count (percentage) summaries conversion and reversion rates in participants receiving escalating dose levels of MTBVAC [ Time Frame: Screening and Study Day 365 (all cohorts); and Study Days 28, 56, 84, and 182 (Cohorts 1-4) ]
    QFT Gold Plus assay
  • Qualitative and quantitative results from QFT test using percentage conversion and reversion rates of participants receiving escalating dose levels of MTBVAC compared to BCG dose levels of MTBVAC in comparison to BCG measured by QFT Gold Plus assay [ Time Frame: Screening and Study Day 365 (all cohorts); and Study Days 28, 56, 84, and 182 (Cohorts 1-4) ]
    QFT Gold Plus assay
  • Immunogenicity of MTBVAC at escalating dose levels measured by 12 hour whole blood (WB) intracellular cytokine staining (ICS) assay [ Time Frame: Days 0, 28, 56, 84, and 182 ]
  • QuantiFERON® TB (QFT) conversion rates in QFT-negative adults, receiving escalating dose levels of MTBVAC measured with QFT Gold Plus assay [ Time Frame: Screening and Study Day 182 (all cohorts); and Study Days 28 and 84 (Cohorts 1-4) ]
  • QFT conversion rates in QFT-negative adults, receiving escalating dose levels of MTBVAC in comparison to BCG measured by QFT Gold Plus assay [ Time Frame: Screening and Study Day 182 (all cohorts) ]
Not Provided
Not Provided
 
MTBVAC Study in Adults With and Without Latent Tuberculosis Infection in South Africa
MTBVAC Phase 1b/2a Randomized, Double-blind, Active-controlled,Safety, Immunogenicity, and Dose-escalation Study in Adults With and Without Latent Tuberculosis Infection in South Africa
MTBVAC at four dose levels: 5 x 10^3 CFU, 5 x 10^4 CFU, 5 x 10^5 CFU, and 5 x 10^6 CFU. The active control is BCG (5 x 10^5 CFU). Participants will receive a single dose of MTBVAC or BCG revaccination administered intradermally on Study Day 0.

This is a Phase 1b/2a, double-blind, randomized, BCG-controlled, dose-escalation safety and immunogenicity study in 120 healthy adults with and without LTBI. All participants will have received previous BCG vaccination in infancy. The investigational product is MTBVAC at four dose levels: 5 x 10^3 CFU, 5 x 10^4 CFU, 5 x 10^5 CFU, and 5 x 10^6 CFU. The active control is BCG (5 x 10^5 CFU).

Participants meeting the inclusion/exclusion criteria will be randomized within a study cohort to receive a single dose of MTBVAC or BCG revaccination administered intradermally on Study Day 0. The study will be conducted at one site in South Africa. Participants will be enrolled into one of eight cohorts and followed for safety and immunogenicity endpoints through Study Day 182. The estimated time to complete enrolment is approximately 9 months.

Cohorts 1-8 will include 60 QFT-negative (Cohorts 1-4) and 60 QFT-positive (Cohorts 5-8) participants. Participants will be randomized within each cohort, to receive either MTBVAC (N=96) or BCG (N=24). The cohorts will be enrolled as described in the protocol, as long as no pausing/stopping rules are triggered

Interventional
Phase 1
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Tuberculosis
  • Biological: MTBVAC
    Escalating dose levels (5 x 10^3 CFU, 5 x 10^4 CFU, 5 x 10^5 CFU, and 5 x 10^6 CFU
  • Biological: BCG
    BCG 5 x 10^5 CFU
    Other Name: BCG 5 x 10^5 CFU
  • Experimental: Cohort 1: MTBVAC 5 x 10^3 CFU
    Quantiferon (QFT) negative, 1 dose on Day 0
    Intervention: Biological: MTBVAC
  • Experimental: Cohort 2: MTBVAC 5 x 10^4 CFU
    QFT Negative, 1 dose on Day 0
    Intervention: Biological: MTBVAC
  • Experimental: Cohort 3: MTBVAC 5 x 10^5 CFU
    QFT Negative, 1 dose on Day 0
    Intervention: Biological: MTBVAC
  • Experimental: Cohort 4: MTBVAC 5 x 10^6 CFU
    QFT Negative, 1 dose on Day 0
    Intervention: Biological: MTBVAC
  • Experimental: Cohort 5: MTBVAC 5 x 10^3 CFU
    QFT Positive, 1 dose on Day 0
    Intervention: Biological: MTBVAC
  • Experimental: Cohort 6: MTBVAC 5 x 10^4 CFU
    QFT Positive, 1 dose on Day 0
    Intervention: Biological: MTBVAC
  • Experimental: Cohort 7: MTBVAC 5 x 10^5 CFU
    QFT Positive, 1 dose on Day 0
    Intervention: Biological: MTBVAC
  • Experimental: Cohort 8: MTBVAC 5 x 10^6 CFU
    QFT Positive, 1 dose on Day 0
    Intervention: Biological: MTBVAC
  • Active Comparator: BCG 5 x 10^5 CFU
    Both QFT positive and negative, 1 dose on Day 0
    Intervention: Biological: BCG
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
120
Same as current
December 2019
December 2019   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Has completed the written informed consent process.
  2. Is male or female aged 18 through 50 years on Study Day 0.
  3. Agrees to stay in contact with the clinical trial site for the duration of the study, provide updated contact information as necessary, and has no current plans to move from the study area for the duration of the study.
  4. For female participants: agrees to avoid pregnancy from 21 days prior to Study Day 0 and for the full duration of the study. Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses if menopausal) in sexual relationships with men must use an acceptable method of avoiding pregnancy during this period. Acceptable methods of avoiding pregnancy include a sterile sexual partner, hormonal contraceptives (oral, injection, transdermal patch, or implant), vaginal ring, or intrauterine device (IUD).
  5. Has general good health, confirmed by medical history and physical examination.
  6. Had BCG vaccination, documented through medical history or presence of scar.
  7. Has not shared enclosed living or work space with someone diagnosed with TB during the 3 months prior to Study Day 0.
  8. [Cohorts 1-4] Does not have LTBI, determined by a negative QFT test at screening.

or [Cohorts 5-8] Has LTBI, determined by a positive QFT test at screening.

Exclusion Criteria:

  1. Acute illness on Study Day 0.
  2. Oral temperature >37.5 degrees C on Study Day 0.
  3. Abnormal laboratory values from most recent blood collection prior to Study Day 0 randomization that are equivalent to Grade 2 or more toxicity, per the protocol toxicity table, or if deemed clinically significant.
  4. Severe anemia, defined as <10 g/dL or hematocrit <30%.
  5. Suspicion or evidence (including but not limited to sputum Xpert MTB/RIF positive) of active TB disease at any site. An attempt must be made to obtain sputum from each participant; persons who are sputum unproductive will be assumed to be Xpert MTB/RIF negative.
  6. History of treatment for TB disease.
  7. History of autoimmune disease or immunosuppression.
  8. Used immunosuppressive medication within 42 days before Study Day 0 (inhaled and topical corticosteroids are permitted).
  9. Received immunoglobulin or blood products within 42 days before Study Day 0.
  10. Received any investigational drug or investigational vaccine within 182 days before Study Day 0, or planned participation in any other investigational study during the study period.
  11. Received investigational Mtb vaccine at any time prior to Study Day 0.
  12. Planned administration/administration of a licensed vaccine in the period starting 28 days before and ending 28 days after dosing with investigational product.
  13. History or laboratory evidence of any past, present, or future possible immunodeficiency state including but not limited to any laboratory indication of HIV-1 infection.
  14. History of allergic disease or reactions, including eczema, likely to be exacerbated by any component of the investigational product.
  15. Previous medical history that may compromise the safety of the participant in the study, including but not limited to: impairment of pulmonary function from TB infection or other pulmonary disease; chronic illness with signs of cardiac or renal failure; suspected progressive neurological disease; uncontrolled epilepsy or infantile spasms; or diabetes mellitus.
  16. History or evidence on physical examination of any systemic disease or any acute or chronic illness that, in the opinion of the investigator, may interfere with the evaluation of the safety or immunogenicity of the vaccine, including axillary lymphadenopathy.
  17. Female participants: currently pregnant or lactating/nursing; or positive urine pregnancy test during screening or pre-vaccination on Study Day 0.
  18. Any current medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the investigator, could endanger the participant or make it unlikely that the participant will comply with the protocol.
Sexes Eligible for Study: All
18 Years to 50 Years   (Adult)
Yes
Contact: Dereck Tait, MD 27214424991 dtait@aeras.org
Not Provided
 
 
NCT02933281
A-050
No
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: Undecided
Aeras
Aeras
  • Biofabri, S.L
  • Universidad de Zaragoza
  • South African Tuberculosis Vaccine Initiative
  • TuBerculosis Vaccine Initiative
Principal Investigator: Michelle Tameris, MD SATVI
Aeras
October 2018

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