Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02933281
Recruitment Status : Unknown
Verified March 2019 by International AIDS Vaccine Initiative.
Recruitment status was:  Recruiting
First Posted : October 14, 2016
Last Update Posted : March 26, 2019
Sponsor:
Collaborators:
Biofabri, S.L
Universidad de Zaragoza
South African Tuberculosis Vaccine Initiative
TuBerculosis Vaccine Initiative
Information provided by (Responsible Party):
International AIDS Vaccine Initiative

Tracking Information
First Submitted Date  ICMJE October 10, 2016
First Posted Date  ICMJE October 14, 2016
Last Update Posted Date March 26, 2019
Actual Study Start Date  ICMJE January 24, 2019
Estimated Primary Completion Date February 15, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 1, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 12, 2016)
  • 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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 1, 2018)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: October 12, 2016)
  • 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) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE MTBVAC Study in Adults With and Without Latent Tuberculosis Infection in South Africa
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description

This is a Phase 1b/2a, double-blind, randomized, BCG-controlled, dose-escalation safety and immunogenicity study in 144 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 72 QFT-negative (Cohorts 1-4) and 72 QFT-positive (Cohorts 5-8) participants. Participants will be randomized within each cohort, to receive either MTBVAC (N=96) or BCG (N=48). The cohorts will be enrolled as described in the protocol, as long as no pausing/stopping rules are triggered

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Tuberculosis
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
Publications * Not Provided

*   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 Unknown status
Estimated Enrollment  ICMJE
 (submitted: October 12, 2016)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 15, 2021
Estimated Primary Completion Date February 15, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE South Africa
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02933281
Other Study ID Numbers  ICMJE A-050
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party International AIDS Vaccine Initiative
Study Sponsor  ICMJE International AIDS Vaccine Initiative
Collaborators  ICMJE
  • Biofabri, S.L
  • Universidad de Zaragoza
  • South African Tuberculosis Vaccine Initiative
  • TuBerculosis Vaccine Initiative
Investigators  ICMJE
Principal Investigator: Angelique Luabeya, MD SATVI
PRS Account International AIDS Vaccine Initiative
Verification Date March 2019

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