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A Phase I/IIa AERAS-456 in HIV-Negative Adults With & Without Latent Tuberculosis Infection (C-035-456)

Sponsor
Aeras (Other)
Overall Status
Completed
CT.gov ID
NCT01865487
Collaborator
Statens Serum Institut (Other)
98
Enrollment
2
Locations
6
Arms
27
Duration (Months)
49
Patients Per Site
1.8
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase I/IIa, double-blind, randomized, placebo-controlled, dose- and regimen-finding study in healthy adults with and without LTBI, who are BCG-vaccinated, HIV negative, and have no history or evidence of TB disease. The investigational product is AERAS-456 at 3 dose levels: 5, 15, and 50ug of H56 antigen with 500 nmol IC31. The vaccine is administered by IM injection.

Condition or Disease Intervention/Treatment Phase
  • Biological: H56ug/IC31nmol
  • Biological: Placebo
 Phase 1/Phase 2

Detailed Description

This is a Phase I/IIa, double-blind, randomized, placebo-controlled, dose- and regimen-finding study in healthy adults with and without latent Tuberculosis (TB) Infection, who are Bacille Calmette Guerin (BCG)-vaccinated, HIV negative, and have no history or evidence of TB disease. The investigational product is AERAS-456 at 3 dose levels: 5, 15, and 50ug of H56 antigen with 500 nmol IC31. The vaccine is administered by intramuscular (IM) injection. The study will be conducted at two sites in South Africa.

A total of 98 subjects will be enrolled in 2 phases into 4 groups based on Latent TB Infection (LTBI) status. The initial phase will be a dose ranging study of a 2-dose regimen at 3 dosage levels in LTBI(-) subjects, to select a dosage for the second phase. In the second phase, the study will be expanded to evaluate both 2-dose and 3-dose regimens and to include LTBI(+) subjects. In the first phase, 50 LTBI(-) subjects will be enrolled in Group 1 and randomized at a ratio of 3:3:3:1 to receive 2 doses of 5/500, 15/500, or 50/500 of AERAS-456, or placebo given at Study Days 0 and 56 (Table 0 1).

One dose level of AERAS-456 will be selected by the sponsor and SSI for the second phase of the study, based on analysis of unblinded safety and immunogenicity data through 28 days after the second dose in the first phase, in conjunction with safety and immunogenicity data from study C-032-456. The criteria for dose-selection will be specified in a statistical analysis plan to be finalized prior to the unblinded review. The selected dose, in conjunction with the unblinded safety and immunogenicity data, will be submitted to the SMC for review. In the second phase, 48 subjects will be enrolled concurrently into Group 2 (LTBI[-]) and into Groups 3 and 4 (LTBI[+], Table 0 2). In each of Groups 2 and 4, 16 subjects will be randomized at a ratio of 3:1 to receive 3 doses of AERAS-456 or placebo given at Study Days 0, 56, and 112. In Group 3, 16 subjects will be randomized at a ratio of 3:1 to receive 2 doses of AERAS-456 or placebo given at Study Days 0 and 56.

All subjects will stay on the study for 292 days after receiving the first vaccination. The subjects in Groups 1 and 3 will be followed up for 236 days after the second vaccination and subjects in Groups 2 and 4 will be followed up for 180 days after the third vaccination. The sample size for each study cohort was selected because it was judged to be adequate for preliminary safety and immunogenicity evaluations for a Phase I/IIa study rather than for statistical reasons. Given 12 and 15 subjects in individual AERAS-456 dosing groups, the study will have an 80% probability of detecting at least 1 specified event which occurs at a rate of 12.5% and 10.0%, respectively. If no such events are observed among 12 and 15 subjects receiving active study vaccine, an approximation to the upper one-sided 95% confidence bound on the rate of occurrence for that event would be 22% and 18%, respectively.

Study Design

Study Type:
Interventional
Actual Enrollment :
98 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
A 2 phase study based on LTBI status. Phase 1 is a dose ranging study of a 2 dose regimen at 3 dosage levels and placebo in LTBI negative participants. The second phase evaluated 2 and 3 dose regimens and included + and - LTBI participants.A 2 phase study based on LTBI status. Phase 1 is a dose ranging study of a 2 dose regimen at 3 dosage levels and placebo in LTBI negative participants. The second phase evaluated 2 and 3 dose regimens and included + and - LTBI participants.
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
A Phase I/IIa Double-Blind, Randomized, Placebo-controlled Dose-Finding Study to Evaluate the Safety and Immunogenicity of AERAS-456 in HIV-Negative Adults With and Without Latent Tuberculosis Infection
Study Start Date :
Aug 1, 2013
Actual Primary Completion Date :
Aug 1, 2015
Actual Study Completion Date :
Nov 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: 2-Dose Placebo

Placebo QFT Neg and Pos, 2 Doses, days 0,56

Biological: Placebo
Sterile buffer consisting of 10mM Tris and 169mM NaCl at pH 7.4
Experimental: 2-Dose 5/500 H56ug/IC31nmol

5/500 H56ug/IC31nmol QFT Neg and Pos, 2 Doses, days 0,56

Biological: H56ug/IC31nmol
H56:IC31 (designated as AERAS-456 for Aeras-sponsored clinical development) contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.
Other Names:
  • AERAS-456

    		•
    Experimental: 2-Dose 15/500 H56ug/IC31nmol

    15/500 H56ug/IC31nmol QFT Negative 2 Doses, days 0,56

    Biological: H56ug/IC31nmol
    H56:IC31 (designated as AERAS-456 for Aeras-sponsored clinical development) contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.
    Other Names:
  • AERAS-456

    		•
    Experimental: 2-Dose 50/500 H56ug/IC31nmol

    50/500 H56ug/IC31nmol QFT Negative 2 Doses, days 0,56

    Biological: H56ug/IC31nmol
    H56:IC31 (designated as AERAS-456 for Aeras-sponsored clinical development) contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.
    Other Names:
  • AERAS-456

    		•
    Placebo Comparator: 3-Dose, Placebo

    Placebo QFT Neg and Pos, 3 doses, days 0, 56, 112

    Biological: Placebo
    Sterile buffer consisting of 10mM Tris and 169mM NaCl at pH 7.4
    Experimental: 3-Dose, 5/500 H56ug/IC31nmol

    5/500 H56ug/IC31nmol QFT Neg and Pos, 3 Doses, days 0, 56, 112

    Biological: H56ug/IC31nmol
    H56:IC31 (designated as AERAS-456 for Aeras-sponsored clinical development) contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.
    Other Names:
  • AERAS-456

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number and Percentage of Unsolicited and Solicited Adverse Events Recorded Post Day 0 Vaccination. [Up to 10 months]

      Evaluation of unsolicited and solicited AEs was performed through 28 days after each study vaccination. Serious AEs were collected throughout the entire study period (i.e., 292 days). Evaluation of the safety profile of AERAS-456 was performed using data from all subjects who received at least one dose.

    Secondary Outcome Measures

    1. Evaluate Immunogenicity of Multiple Dosage Levels and Dosing Regimens of H56:IC31 - CD4+ ICS (LTBI-negative) [Day 292]

      LTBI: Latent TB Infection QFT: QuantiFERON-TB Gold Plus (QFT-Plus) is an in vitro diagnostic aid for detection of Mycobacterium tuberculosis infection Percent Antigen-specific T Cell DMSO-subtracted Cytokine Response Change from Baseline 13-color ICS assay using PBMCs T Cell: CD4+ Stimulation Antigen: Total Cytokine: Any

    2. Evaluate Immunogenicity of Multiple Dosage Levels and Dosing Regimens of H56:IC31 - CD4+ ICS (LTBI-positive) [Day 292]

      Percent Antigen-specific T Cell DMSO-subtracted Cytokine Response Change from Baseline. 13-color ICS assay using PBMCs. T Cell: CD4+ Stimulation Antigen: Total Cytokine: Any

    3. Evaluate Immunogenicity of Multiple Dosage Levels and Dosing Regimens of H56:IC31 - IFN-gamma ELISpot [Day 292]

      DMSO-subtracted Antigen-specific IFN-gamma ELISpot Response (SFU - Background/10^6 PBMC) Change from Baseline LTBI Status at Baseline: Total Stimulation Antigen: Total

    4. Evaluate Kinetics of QuantiFERON®-TB Gold Test (QFT) Responses in LTBI-negative Participants [Up to Study Day 292]

      QFT results were summarized using subject count (percentage) for qualitative results. Number of participants QFT-positive at any time point.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 50 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    Subjects must meet all of the following criteria prior to Study Day 0 vaccination:

    1. Has completed the written informed consent process prior to the start of screening evaluations.

    2. Is male or female.

    3. Is age 18 through 50 years at the time of randomization.

    4. Received BCG vaccination at least 5 years prior to randomization.

    5. Females: Ability to avoid pregnancy during the trial: 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 avoid pregnancy with an acceptable method of avoiding pregnancy from 28 days prior to administration of the study vaccine through the end of the study.

    6. Has general good health, confirmed by medical history and physical examination at screening.

    7. Is able and willing to complete the full follow-up period of 292 days as required by the protocol.

    8. Agrees to avoid elective surgery for the full duration of the study.

    9. [Groups 1 and 2] Does not have LTBI, determined by a negative QFT at screening or[Groups 3 and 4] Has LTBI, determined by a positive QFT at screening.

    Exclusion Criteria:
    Subjects must meet none of the following criteria prior to Study Day 0 vaccination:

    1. Acute illness at the time of randomization.

    2. Oral temperature 37.5 degrees C at the time of randomization.

    3. Abnormal laboratory values from blood collected within 21 days prior to Study Day 0 vaccination.

    4. Abnormal urinalysis that, in the opinion of the investigator, indicates systemic or local disease.

    5. History or evidence of tuberculosis disease, including but not limited to pulmonary tuberculosis, pleural tuberculosis, lymph node tuberculosis or tuberculosis meningitis.

    6. Received a TST within 21 days prior to a scheduled study vaccination.

    7. Received investigational Mtb vaccine at any time prior to Study Day 0.

    8. History or evidence of autoimmune disease.

    9. History or laboratory evidence of HIV-1 infection at screening.

    10. Positive test for hepatitis B surface antigen or hepatitis C antibody at screening.

    11. Used immunosuppressive medication (other than inhaled or topical immunosuppressants) within 21 days prior to Study Day 0.

    12. Received immunoglobulin or blood products within 21 days prior to Study Day 0.

    13. Received any investigational product within 21 days prior to Study Day 0, or plans to participate in any other study involving administration of investigational product during the study period.

    14. Inability to discontinue current chronic prescription medications, except contraceptives, inhaled or topical immunosuppressants, or nutritional supplements, during the study period.

    15. Documented history of allergic reaction or hypersensitivity to any component of the study vaccine.

    16. All female subjects: currently pregnant or lactating/nursing; or positive serum pregnancy test during screening; or positive urine pregnancy test on the day of any study vaccination.

    17. History or evidence of any systemic disease or any acute or chronic illness that, in the opinion of the investigator, may compromise the safety of the subject in the study or interfere with the evaluation of the safety or immunogenicity of the vaccine.

    18. History of dermatologic disease or skin features that, in the opinion of the investigator, may interfere with the assessment of injection site reactions.

    19. History or evidence of any medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the investigator, will make it unlikely that the subject will comply with the protocol.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 eKhayavac TB Vaccine Trial Khayelitsha Cape Town South Africa 7784
    2 SATVI Project Office, Brewelskloof Hospital Worcester South Africa 6850

    Sponsors and Collaborators

    • Aeras
    • Statens Serum Institut

    Investigators

    • Study Director: Dereck Tait, MD, Aeras
    • Principal Investigator: Angelique Luabeya, MD, University of Cape Town South African Tuberculosis Vaccine Initiative

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Aeras
    ClinicalTrials.gov Identifier:
    NCT01865487
    Other Study ID Numbers:
    • C-035-456
    First Posted:
    May 31, 2013
    Last Update Posted:
    Dec 19, 2019
    Last Verified:
    Dec 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Aeras
    BCG Vaccinated
    HIV Negative
    Additional relevant MeSH terms:
    Tuberculosis
    Latent Tuberculosis

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Group 1: 2-dose 5/500 Group 1: 2-dose 15/500 Group 1: 2-dose 50/500 Group 1: 2-dose Placebo Group 2: 3-dose 5/500 Group 2: 3-dose Placebo Group 3: 2-dose 5/500 Group 3: 2-dose Placebo Group 4: 3-dose 5/500 Group 4: 3-dose Placebo
    Arm/Group Description 5/500 H56ug/IC31nmol, QFT Negative, 2 doses, days 0 and 56 15/500 H56ug/IC31nmol, QFT Negative, 2 doses, days 0 and 56 50/500 H56ug/IC31nmol, QFT Negative, 2 doses, days 0 and 56 Placebo, QFT Negative, 2 doses, days 0 and 56 5/500 H56ug/IC31nmol, QFT Negative, 3 doses, days 0, 56, 112 Placebo, QFT Negative, 3 doses, days 0, 56, 112 5/500 H56ug/IC31nmol, QFT Positive, 2 doses, Days 0 and 56 Placebo, QFT Positive, 2 doses, Days 0 and 56 5/500 H56ug/IC31nmol, QFT Positive, 3 doses, days 0, 56, 112 Placebo, QFT positive, 3 doses, Days 0, 56, 112
    Period Title: Overall Study
    STARTED 15 15 15 5 12 4 12 4 12 4
    COMPLETED 15 15 15 4 11 4 11 4 12 4
    NOT COMPLETED 0 0 0 1 1 0 1 0 0 0

    Baseline Characteristics

    Arm/Group Title 2-Dose Placebo 2-Dose 5/500 H56/IC31nmol 2-Dose 15/500 H56/IC31nmol 2-Dose 50/500 H56/IC31nmol 3-Dose Placebo 3-Dose 5/500 H56/IC31nmol Total
    Arm/Group Description Placebo, QFT Neg and Pos, 2 doses day 0 and 56 5/500 H56ug/IC31nmol, QFT Neg and Pos, 2 Doses, days 0 and 56 15/500 H56ug/IC31nmol, QFT Negative, 2 Doses, days 0 and 56 50/500 H56ug/IC31nmol, QFT Negative, 2 Doses, days 0 and 56 Placebo QFT Neg and Pos, 3 Doses, days 0, 56, 112 5/500 H56ug/IC31nmol, QFT Neg and Pos, 3 Doses, days 0, 56, 112 Total of all reporting groups
    Overall Participants 9 27 15 15 8 24 98
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    27.9
    (9.51)
    27.2
    (8.71)
    24.3
    (4.08)
    25.3
    (8.76)
    24.9
    (8.25)
    28.4
    (8.34)
    26.6
    (8.06)
    Sex: Female, Male (Count of Participants)
    Female
    7
    77.8%
    19
    70.4%
    6
    40%
    11
    73.3%
    6
    75%
    17
    70.8%
    66
    67.3%
    Male
    2
    22.2%
    8
    29.6%
    9
    60%
    4
    26.7%
    2
    25%
    7
    29.2%
    32
    32.7%
    Race/Ethnicity, Customized (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    5
    55.6%
    9
    33.3%
    6
    40%
    7
    46.7%
    3
    37.5%
    8
    33.3%
    38
    38.8%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Coloured
    4
    44.4%
    18
    66.7%
    9
    60%
    8
    53.3%
    5
    62.5%
    16
    66.7%
    60
    61.2%
    Other
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Baseline BMI (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    26.83
    (8.385)
    27.11
    (6.655)
    25.74
    (8.122)
    31.14
    (10.922)
    27.75
    (12.612)
    25.56
    (5.726)
    27.17
    (8.191)
    LTBI Status at Baseline (Count of Participants)
    LTBI Negative
    5
    55.6%
    15
    55.6%
    15
    100%
    15
    100%
    4
    50%
    12
    50%
    66
    67.3%
    LTBI Positivie
    4
    44.4%
    12
    44.4%
    0
    0%
    0
    0%
    4
    50%
    12
    50%
    32
    32.7%

    Outcome Measures

    1. Primary Outcome
    Title Number and Percentage of Unsolicited and Solicited Adverse Events Recorded Post Day 0 Vaccination.
    Description Evaluation of unsolicited and solicited AEs was performed through 28 days after each study vaccination. Serious AEs were collected throughout the entire study period (i.e., 292 days). Evaluation of the safety profile of AERAS-456 was performed using data from all subjects who received at least one dose.
    Time Frame Up to 10 months

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set
    Arm/Group Title Placebo QFT Neg Placebo QFT Pos 2-Doses 5/500 QFT Neg 2-Doses 15/500 2-Doses 50/500 3-Doses 5/500 QFT Neg 2-Doses 5/500 QFT Pos 3-Doses 5/500 QFT Pos
    Arm/Group Description 2-doses and 3-doses (Groups 1 and 2) 2-doses and 3-doses (Groups 3 and 4) QFT Negative (Group 1) QFT Negative (Group 1) QFT Negative (Group 1) QFT Negative (Group 2) QFT Positive (Group 3) QFT Positive (Group 4)
    Measure Participants 9 8 15 15 15 12 12 12
    Participants with AEs
    7
    77.8%
    8
    29.6%
    15
    100%
    15
    100%
    15
    187.5%
    10
    41.7%
    10
    10.2%
    10
    NaN
    Participants with related AEs
    5
    55.6%
    4
    14.8%
    12
    80%
    11
    73.3%
    12
    150%
    6
    25%
    8
    8.2%
    8
    NaN
    Participants with SAEs
    0
    0%
    0
    0%
    2
    13.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    2. Secondary Outcome
    Title Evaluate Immunogenicity of Multiple Dosage Levels and Dosing Regimens of H56:IC31 - CD4+ ICS (LTBI-negative)
    Description LTBI: Latent TB Infection QFT: QuantiFERON-TB Gold Plus (QFT-Plus) is an in vitro diagnostic aid for detection of Mycobacterium tuberculosis infection Percent Antigen-specific T Cell DMSO-subtracted Cytokine Response Change from Baseline 13-color ICS assay using PBMCs T Cell: CD4+ Stimulation Antigen: Total Cytokine: Any
    Time Frame Day 292

    Outcome Measure Data

    Analysis Population Description
    Immunogenicity analysis set: LTBI-negative at baseline
    Arm/Group Title 2-Dose Placebo 2-Dose 5/500 H56/IC31nmol 2-Dose 15/500 H56/IC31nmol 2-Dose 50/500 H56/IC31nmol 3-Dose Placebo 3-Dose 5/500 H56/IC31nmol
    Arm/Group Description Placebo, QFT Neg and Pos, 2 doses day 0 and 56 5/500 H56ug/IC31nmol, QFT Neg and Pos, 2 Doses, days 0 and 56 15/500 H56ug/IC31nmol, QFT Negative, 2 Doses, days 0 and 56 50/500 H56ug/IC31nmol, QFT Negative, 2 Doses, days 0 and 56 Placebo QFT Neg and Pos, 3 Doses, days 0, 56, 112 5/500 H56ug/IC31nmol, QFT Neg and Pos, 3 Doses, days 0, 56, 112
    Measure Participants 4 13 14 14 3 6
    Mean (Standard Deviation) [Percentage of change from baseline]
    0.002
    (0.018)
    0.088
    (0.104)
    0.027
    (0.031)
    0.031
    (0.047)
    0.012
    (0.014)
    0.045
    (0.056)
    3. Secondary Outcome
    Title Evaluate Immunogenicity of Multiple Dosage Levels and Dosing Regimens of H56:IC31 - CD4+ ICS (LTBI-positive)
    Description Percent Antigen-specific T Cell DMSO-subtracted Cytokine Response Change from Baseline. 13-color ICS assay using PBMCs. T Cell: CD4+ Stimulation Antigen: Total Cytokine: Any
    Time Frame Day 292

    Outcome Measure Data

    Analysis Population Description
    Immunogenicity analysis set: LTBI-positive at baseline
    Arm/Group Title 2-Dose Placebo 2-Dose 5/500 H56/IC31nmol 3-Dose Placebo 3-Dose 5/500 H56/IC31nmol
    Arm/Group Description Placebo, QFT Neg and Pos, 2 doses day 0 and 56 5/500 H56ug/IC31nmol, QFT Neg and Pos, 2 Doses, days 0 and 56 Placebo QFT Neg and Pos, 3 Doses, days 0, 56, 112 5/500 H56ug/IC31nmol, QFT Neg and Pos, 3 Doses, days 0, 56, 112
    Measure Participants 4 10 4 8
    Mean (Standard Deviation) [Percentage of change from baseline]
    0.005
    (0.020)
    0.068
    (0.052)
    0.027
    (0.022)
    0.097
    (0.170)
    4. Secondary Outcome
    Title Evaluate Immunogenicity of Multiple Dosage Levels and Dosing Regimens of H56:IC31 - IFN-gamma ELISpot
    Description DMSO-subtracted Antigen-specific IFN-gamma ELISpot Response (SFU - Background/10^6 PBMC) Change from Baseline LTBI Status at Baseline: Total Stimulation Antigen: Total
    Time Frame Day 292

    Outcome Measure Data

    Analysis Population Description
    Immunogenicity analysis set
    Arm/Group Title 2-Dose Placebo 2-Dose 5/500 H56/IC31nmol 2-Dose 15/500 H56/IC31nmol 2-Dose 50/500 H56/IC31nmol 3-Dose Placebo 3-Dose 5/500 H56/IC31nmol
    Arm/Group Description Placebo, QFT Neg and Pos, 2 doses day 0 and 56 5/500 H56ug/IC31nmol, QFT Neg and Pos, 2 Doses, days 0 and 56 15/500 H56ug/IC31nmol, QFT Negative, 2 Doses, days 0 and 56 50/500 H56ug/IC31nmol, QFT Negative, 2 Doses, days 0 and 56 Placebo QFT Neg and Pos, 3 Doses, days 0, 56, 112 5/500 H56ug/IC31nmol, QFT Neg and Pos, 3 Doses, days 0, 56, 112
    Measure Participants 8 21 13 12 7 13
    Mean (Standard Deviation) [Number of spots per well]
    82.7
    (223.6)
    209.0
    (221.8)
    57.9
    (162.2)
    110.0
    (92.0)
    -53.1
    (79.8)
    167.4
    (364.8)
    5. Secondary Outcome
    Title Evaluate Kinetics of QuantiFERON®-TB Gold Test (QFT) Responses in LTBI-negative Participants
    Description QFT results were summarized using subject count (percentage) for qualitative results. Number of participants QFT-positive at any time point.
    Time Frame Up to Study Day 292

    Outcome Measure Data

    Analysis Population Description
    Conversion of LTBI-negative at baseline to LTBI-positive due to H56:IC31 expression of ESAT-6 (antigen in QFT assay).
    Arm/Group Title Placebo QFT Neg 2-Doses 5/500 QFT Neg 2-Doses 15/500 2-Doses 50/500 3-Doses 5/500 QFT Neg
    Arm/Group Description 2-doses and 3-doses (Groups 1 and 2) QFT Negative (Group 1) QFT Negative (Group 1) QFT Negative (Group 1) QFT Negative (Group 2)
    Measure Participants 9 15 15 15 12
    Count of Participants [Participants]
    2
    22.2%
    7
    25.9%
    6
    40%
    6
    40%
    7
    87.5%

    Adverse Events

    Time Frame 10 months
    Adverse Event Reporting Description Systematic Assessment - includes diary cards, scheduled visits and lab tests Non-systematic Assessment also collected through self reporting
    Arm/Group Title 2-Dose Placebo 2-Dose 5/500 H56ug/IC31nmol 2-Dose 15/500 H56ug/IC31nmol 2-Dose 50/500 H56ug/IC31nmol 3-Dose Placebo 3-Dose 5/500 H56ug/IC31nmol
    Arm/Group Description Placebo QFT neg and pos 2-Dose 5/500 H56ug/IC31nmol, QFT neg and pos 2-Dose 15/500 H56ug/IC31nmol, QFT negative 2-Dose 50/500 H56ug/IC31nmol, QFT negative 3-Dose Placebo QFT neg and pos 3-Dose 5/500 H56ug/IC31nmol, QFT neg and pos
    All Cause Mortality
    2-Dose Placebo 2-Dose 5/500 H56ug/IC31nmol 2-Dose 15/500 H56ug/IC31nmol 2-Dose 50/500 H56ug/IC31nmol 3-Dose Placebo 3-Dose 5/500 H56ug/IC31nmol
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/9 (0%) 0/27 (0%) 0/15 (0%) 0/15 (0%) 0/8 (0%) 0/24 (0%)
    Serious Adverse Events
    2-Dose Placebo 2-Dose 5/500 H56ug/IC31nmol 2-Dose 15/500 H56ug/IC31nmol 2-Dose 50/500 H56ug/IC31nmol 3-Dose Placebo 3-Dose 5/500 H56ug/IC31nmol
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/9 (0%) 2/27 (7.4%) 0/15 (0%) 0/15 (0%) 0/8 (0%) 0/24 (0%)
    Injury, poisoning and procedural complications
    Pneumothorax traumatic 0/9 (0%) 0 1/27 (3.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/8 (0%) 0 0/24 (0%) 0
    Nervous system disorders
    Lumbar radiculopathy 0/9 (0%) 0 1/27 (3.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/8 (0%) 0 0/24 (0%) 0
    Other (Not Including Serious) Adverse Events
    2-Dose Placebo 2-Dose 5/500 H56ug/IC31nmol 2-Dose 15/500 H56ug/IC31nmol 2-Dose 50/500 H56ug/IC31nmol 3-Dose Placebo 3-Dose 5/500 H56ug/IC31nmol
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/9 (100%) 25/27 (92.6%) 15/15 (100%) 15/15 (100%) 6/8 (75%) 20/24 (83.3%)
    Cardiac disorders
    Bradycardia 0/9 (0%) 0 0/27 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/8 (12.5%) 1 0/24 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 0/9 (0%) 0 1/27 (3.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/8 (0%) 0 0/24 (0%) 0
    Diarrhoea 0/9 (0%) 0 0/27 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/8 (0%) 0 0/24 (0%) 0
    Nausea 1/9 (11.1%) 1 1/27 (3.7%) 1 2/15 (13.3%) 2 3/15 (20%) 4 0/8 (0%) 0 2/24 (8.3%) 2
    Toothache 0/9 (0%) 0 0/27 (0%) 0 1/15 (6.7%) 1 1/15 (6.7%) 1 1/8 (12.5%) 1 0/24 (0%) 0
    Vomiting 0/9 (0%) 0 0/27 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/8 (0%) 0 0/24 (0%) 0
    General disorders
    Chills 0/9 (0%) 0 0/27 (0%) 0 1/15 (6.7%) 1 4/15 (26.7%) 4 1/8 (12.5%) 1 1/24 (4.2%) 1
    Fatigue 3/9 (33.3%) 3 5/27 (18.5%) 5 3/15 (20%) 6 5/15 (33.3%) 7 2/8 (25%) 3 1/24 (4.2%) 1
    Injection site erythema 0/9 (0%) 0 2/27 (7.4%) 2 0/15 (0%) 0 0/15 (0%) 0 0/8 (0%) 0 1/24 (4.2%) 1
    Injection site pain 2/9 (22.2%) 2 14/27 (51.9%) 19 5/15 (33.3%) 10 8/15 (53.3%) 11 1/8 (12.5%) 1 7/24 (29.2%) 12
    Injection site swelling 0/9 (0%) 0 2/27 (7.4%) 2 0/15 (0%) 0 0/15 (0%) 0 0/8 (0%) 0 1/24 (4.2%) 1
    Injection site warmth 0/9 (0%) 0 1/27 (3.7%) 1 0/15 (0%) 0 1/15 (6.7%) 1 0/8 (0%) 0 0/24 (0%) 0
    Malaise 0/9 (0%) 0 1/27 (3.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/8 (0%) 0 1/24 (4.2%) 1
    Pyrexia 0/9 (0%) 0 1/27 (3.7%) 1 1/15 (6.7%) 1 1/15 (6.7%) 1 1/8 (12.5%) 1 1/24 (4.2%) 1
    Immune system disorders
    Seasonal allergy 0/9 (0%) 0 0/27 (0%) 0 1/15 (6.7%) 3 1/15 (6.7%) 1 0/8 (0%) 0 1/24 (4.2%) 1
    Infections and infestations
    Gastroenteritis 0/9 (0%) 0 1/27 (3.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/8 (0%) 0 0/24 (0%) 0
    Influenza 0/9 (0%) 0 1/27 (3.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/8 (12.5%) 2 1/24 (4.2%) 1
    Pharyngitis 0/9 (0%) 0 2/27 (7.4%) 2 0/15 (0%) 0 1/15 (6.7%) 1 0/8 (0%) 0 1/24 (4.2%) 1
    Sinusitis 0/9 (0%) 0 2/27 (7.4%) 2 0/15 (0%) 0 2/15 (13.3%) 3 0/8 (0%) 0 1/24 (4.2%) 1
    Upper respiratory tract infection 1/9 (11.1%) 1 1/27 (3.7%) 1 0/15 (0%) 0 2/15 (13.3%) 2 0/8 (0%) 0 1/24 (4.2%) 1
    Urinary tract infection 2/9 (22.2%) 2 0/27 (0%) 0 2/15 (13.3%) 2 2/15 (13.3%) 2 1/8 (12.5%) 1 2/24 (8.3%) 3
    Wound infection 0/9 (0%) 0 1/27 (3.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/8 (0%) 0 0/24 (0%) 0
    Injury, poisoning and procedural complications
    Contusion 0/9 (0%) 0 0/27 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/8 (12.5%) 1 0/24 (0%) 0
    Stab wound 0/9 (0%) 0 0/27 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/8 (0%) 0 0/24 (0%) 0
    Investigations
    Alanine aminotransferase increased 2/9 (22.2%) 2 1/27 (3.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/8 (0%) 0 3/24 (12.5%) 3
    Aspartate aminotransferase increased 0/9 (0%) 0 1/27 (3.7%) 1 1/15 (6.7%) 1 0/15 (0%) 0 0/8 (0%) 0 2/24 (8.3%) 2
    Blood alkaline phosphatase increased 0/9 (0%) 0 0/27 (0%) 0 0/15 (0%) 0 2/15 (13.3%) 2 0/8 (0%) 0 0/24 (0%) 0
    Blood bilirubin increased 0/9 (0%) 0 0/27 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/8 (12.5%) 1 0/24 (0%) 0
    Blood pressure diastolic increased 0/9 (0%) 0 0/27 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/8 (0%) 0 0/24 (0%) 0
    Blood pressure increased 0/9 (0%) 0 1/27 (3.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/8 (12.5%) 1 2/24 (8.3%) 3
    Blood pressure systolic decreased 0/9 (0%) 0 0/27 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/8 (0%) 0 1/24 (4.2%) 1
    Blood pressure systolic increased 0/9 (0%) 0 3/27 (11.1%) 4 2/15 (13.3%) 2 2/15 (13.3%) 2 2/8 (25%) 3 3/24 (12.5%) 4
    Blood urine present 0/9 (0%) 0 0/27 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/8 (12.5%) 1 1/24 (4.2%) 1
    Haemoglobin decreased 0/9 (0%) 0 3/27 (11.1%) 4 1/15 (6.7%) 1 0/15 (0%) 0 0/8 (0%) 0 1/24 (4.2%) 1
    Heart rate decreased 0/9 (0%) 0 0/27 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/8 (0%) 0 0/24 (0%) 0
    Lymphocyte count decreased 0/9 (0%) 0 0/27 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/8 (0%) 0 1/24 (4.2%) 1
    Neutrophil count decreased 1/9 (11.1%) 1 1/27 (3.7%) 1 0/15 (0%) 0 3/15 (20%) 3 1/8 (12.5%) 1 1/24 (4.2%) 1
    Platelet count decreased 0/9 (0%) 0 0/27 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/8 (0%) 0 1/24 (4.2%) 1
    Respiratory rate increased 3/9 (33.3%) 5 13/27 (48.1%) 25 13/15 (86.7%) 21 11/15 (73.3%) 19 0/8 (0%) 0 1/24 (4.2%) 1
    White blood cell count decreased 0/9 (0%) 0 0/27 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/8 (0%) 0 1/24 (4.2%) 1
    White blood cell count increased 0/9 (0%) 0 1/27 (3.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/8 (0%) 0 1/24 (4.2%) 1
    White blood cells urine positive 1/9 (11.1%) 1 0/27 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/8 (0%) 0 0/24 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/9 (22.2%) 2 1/27 (3.7%) 1 1/15 (6.7%) 1 2/15 (13.3%) 3 0/8 (0%) 0 0/24 (0%) 0
    Back pain 1/9 (11.1%) 1 1/27 (3.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/8 (0%) 0 0/24 (0%) 0
    Musculoskeletal chest pain 0/9 (0%) 0 0/27 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/8 (0%) 0 0/24 (0%) 0
    Myalgia 0/9 (0%) 0 4/27 (14.8%) 4 5/15 (33.3%) 6 2/15 (13.3%) 2 2/8 (25%) 2 2/24 (8.3%) 3
    Neck pain 0/9 (0%) 0 0/27 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/8 (0%) 0 0/24 (0%) 0
    Pain in extremity 0/9 (0%) 0 0/27 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/8 (0%) 0 1/24 (4.2%) 1
    Nervous system disorders
    Dizziness 1/9 (11.1%) 1 0/27 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/8 (0%) 0 1/24 (4.2%) 1
    Headache 1/9 (11.1%) 1 4/27 (14.8%) 7 2/15 (13.3%) 2 4/15 (26.7%) 4 1/8 (12.5%) 1 4/24 (16.7%) 4
    Renal and urinary disorders
    Glycosuria 0/9 (0%) 0 0/27 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/8 (0%) 0 0/24 (0%) 0
    Haematuria 1/9 (11.1%) 1 1/27 (3.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/8 (0%) 0 0/24 (0%) 0
    Proteinuria 0/9 (0%) 0 2/27 (7.4%) 3 0/15 (0%) 0 1/15 (6.7%) 1 0/8 (0%) 0 2/24 (8.3%) 2
    Skin and subcutaneous tissue disorders
    Papule 0/9 (0%) 0 0/27 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/8 (0%) 0 1/24 (4.2%) 1
    Vascular disorders
    Systolic hypertension 0/9 (0%) 0 0/27 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/8 (0%) 0 1/24 (4.2%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Dereck Tait
    Organization Aeras
    Phone 27214424991
    Email dtait@aeras.org
    Responsible Party:
    Aeras
    ClinicalTrials.gov Identifier:
    NCT01865487
    Other Study ID Numbers:
    • C-035-456
    First Posted:
    May 31, 2013
    Last Update Posted:
    Dec 19, 2019
    Last Verified:
    Dec 1, 2019