MTBVAC Study in Adults With and Without Latent Tuberculosis Infection in South Africa

NCT ID: NCT02933281

Last Updated: 2023-02-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

144 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-05-14

Study Completion Date

2021-09-05

Brief Summary

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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

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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 365. The estimated time to complete enrolment is approximately 12 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

Conditions

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Tuberculosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Cohort 1: MTBVAC 5 x 10^3 CFU

Quantiferon (QFT) negative, 1 dose on Day 0

Group Type EXPERIMENTAL

MTBVAC

Intervention Type BIOLOGICAL

Escalating dose levels (5 x 10\^3 CFU, 5 x 10\^4 CFU, 5 x 10\^5 CFU, and 5 x 10\^6 CFU

Cohort 2: MTBVAC 5 x 10^4 CFU

QFT Negative, 1 dose on Day 0

Group Type EXPERIMENTAL

MTBVAC

Intervention Type BIOLOGICAL

Escalating dose levels (5 x 10\^3 CFU, 5 x 10\^4 CFU, 5 x 10\^5 CFU, and 5 x 10\^6 CFU

Cohort 3: MTBVAC 5 x 10^5 CFU

QFT Negative, 1 dose on Day 0

Group Type EXPERIMENTAL

MTBVAC

Intervention Type BIOLOGICAL

Escalating dose levels (5 x 10\^3 CFU, 5 x 10\^4 CFU, 5 x 10\^5 CFU, and 5 x 10\^6 CFU

Cohort 4: MTBVAC 5 x 10^6 CFU

QFT Negative, 1 dose on Day 0

Group Type EXPERIMENTAL

MTBVAC

Intervention Type BIOLOGICAL

Escalating dose levels (5 x 10\^3 CFU, 5 x 10\^4 CFU, 5 x 10\^5 CFU, and 5 x 10\^6 CFU

Cohort 5: MTBVAC 5 x 10^3 CFU

QFT Positive, 1 dose on Day 0

Group Type EXPERIMENTAL

MTBVAC

Intervention Type BIOLOGICAL

Escalating dose levels (5 x 10\^3 CFU, 5 x 10\^4 CFU, 5 x 10\^5 CFU, and 5 x 10\^6 CFU

Cohort 6: MTBVAC 5 x 10^4 CFU

QFT Positive, 1 dose on Day 0

Group Type EXPERIMENTAL

MTBVAC

Intervention Type BIOLOGICAL

Escalating dose levels (5 x 10\^3 CFU, 5 x 10\^4 CFU, 5 x 10\^5 CFU, and 5 x 10\^6 CFU

Cohort 7: MTBVAC 5 x 10^5 CFU

QFT Positive, 1 dose on Day 0

Group Type EXPERIMENTAL

MTBVAC

Intervention Type BIOLOGICAL

Escalating dose levels (5 x 10\^3 CFU, 5 x 10\^4 CFU, 5 x 10\^5 CFU, and 5 x 10\^6 CFU

Cohort 8: MTBVAC 5 x 10^6 CFU

QFT Positive, 1 dose on Day 0

Group Type EXPERIMENTAL

MTBVAC

Intervention Type BIOLOGICAL

Escalating dose levels (5 x 10\^3 CFU, 5 x 10\^4 CFU, 5 x 10\^5 CFU, and 5 x 10\^6 CFU

BCG 5 x 10^5 CFU

Both QFT positive and negative, 1 dose on Day 0

Group Type ACTIVE_COMPARATOR

BCG

Intervention Type BIOLOGICAL

BCG 5 x 10\^5 CFU

Interventions

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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

Intervention Type BIOLOGICAL

BCG

BCG 5 x 10\^5 CFU

Intervention Type BIOLOGICAL

Other Intervention Names

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BCG 5 x 10^5 CFU

Eligibility Criteria

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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. For male participants: agrees to use barrier contraception with his partner for at least 2 weeks after dosing with MTBVAC or BCG.
6. Has general good health, confirmed by medical history and physical examination.
7. Had BCG vaccination, documented through medical history or presence of scar.
8. Has not shared enclosed living or work space with someone diagnosed with TB during the 3 months prior to Study Day 0.
9. \[Cohorts 1-4\] 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. Axillary temperature \>or= 37.5C 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 hemoglobin or hematocrit \<30%.
5. Screening thyroid stimulating hormone (TSH) \>upper limit of normal per local laboratory range.
6. 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.
7. History of treatment for TB disease.
8. History of autoimmune disease or immunosuppression.
9. Used immunosuppressive medication within 42 days before Study Day 0 (inhaled and topical corticosteroids are permitted).
10. Received immunoglobulin or blood products within 42 days before Study Day 0.
11. 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.
12. Received investigational vaccine against TB at any time prior to Study Day 0.
13. Planned administration/administration of a licensed vaccine in the period starting 28 days before and ending 28 days after dosing with investigational product.
14. 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.
15. History of allergic disease or reactions, including eczema, likely to be exacerbated by any component of the investigational product.
16. 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.
17. 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.
18. Female participants: currently pregnant or lactating/nursing; or positive urine pregnancy test during screening or pre-vaccination on Study Day 0.
19. 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Biofabri, S.L

INDUSTRY

Sponsor Role collaborator

Universidad de Zaragoza

OTHER

Sponsor Role collaborator

South African Tuberculosis Vaccine Initiative

OTHER

Sponsor Role collaborator

International AIDS Vaccine Initiative

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Angelique Luabeya, MD

Role: PRINCIPAL_INVESTIGATOR

SATVI

Locations

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SATVI: Worcester

Worcester, , South Africa

Site Status

Countries

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South Africa

Other Identifiers

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A-050

Identifier Type: -

Identifier Source: org_study_id

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