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

NCT02933281 | Completed Phase 1 FDA Drug

• 1 other identifier: A-050
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

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.

Conditions

Tuberculosis

Outcome Measures

Primary Outcomes (1)

• Safety and reactogenicity of MTBVAC at escalating dose levels compared to BCG vaccine by assessing number of participants with AEs and SAEs

  Collection of systemic solicited and unsolicited adverse events; solicited and unsolicited injection site reactions; and serious adverse reactions.

  Study Days 0 to Day 365

Secondary Outcomes (3)

• 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

  Study Days 0, 28, 56, 182, and 365

• 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

  Screening and Study Day 365 (all cohorts); and Study Days 28, 56, 84, and 182 (Cohorts 1-4)

• 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

  Screening and Study Day 365 (all cohorts); and Study Days 28, 56, 84, and 182 (Cohorts 1-4)

Study Arms (9)

Cohort 1: MTBVAC 5 x 10^3 CFU

EXPERIMENTAL

Quantiferon (QFT) negative, 1 dose on Day 0

Biological: MTBVAC

Cohort 2: MTBVAC 5 x 10^4 CFU

EXPERIMENTAL

QFT Negative, 1 dose on Day 0

Biological: MTBVAC

Cohort 3: MTBVAC 5 x 10^5 CFU

EXPERIMENTAL

QFT Negative, 1 dose on Day 0

Biological: MTBVAC

Cohort 4: MTBVAC 5 x 10^6 CFU

EXPERIMENTAL

QFT Negative, 1 dose on Day 0

Biological: MTBVAC

Cohort 5: MTBVAC 5 x 10^3 CFU

EXPERIMENTAL

QFT Positive, 1 dose on Day 0

Biological: MTBVAC

Cohort 6: MTBVAC 5 x 10^4 CFU

EXPERIMENTAL

QFT Positive, 1 dose on Day 0

Biological: MTBVAC

Cohort 7: MTBVAC 5 x 10^5 CFU

EXPERIMENTAL

QFT Positive, 1 dose on Day 0

Biological: MTBVAC

Cohort 8: MTBVAC 5 x 10^6 CFU

EXPERIMENTAL

QFT Positive, 1 dose on Day 0

Biological: MTBVAC

BCG 5 x 10^5 CFU

ACTIVE COMPARATOR

Both QFT positive and negative, 1 dose on Day 0

Biological: BCG

Interventions

MTBVAC 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 1: MTBVAC 5 x 10^3 CFU; Cohort 2: MTBVAC 5 x 10^4 CFU; Cohort 3: MTBVAC 5 x 10^5 CFU; Cohort 4: MTBVAC 5 x 10^6 CFU; Cohort 5: MTBVAC 5 x 10^3 CFU; Cohort 6: MTBVAC 5 x 10^4 CFU; Cohort 7: MTBVAC 5 x 10^5 CFU; Cohort 8: MTBVAC 5 x 10^6 CFU

BCG BIOLOGICAL

BCG 5 x 10\^5 CFU

Also known as: BCG 5 x 10^5 CFU

BCG 5 x 10^5 CFU

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Has completed the written informed consent process.
• Is male or female aged 18 through 50 years on Study Day 0.
• 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.
• 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).
• For male participants: agrees to use barrier contraception with his partner for at least 2 weeks after dosing with MTBVAC or BCG.
• Has general good health, confirmed by medical history and physical examination.
• Had BCG vaccination, documented through medical history or presence of scar.
• Has not shared enclosed living or work space with someone diagnosed with TB during the 3 months prior to Study Day 0.
• \[Cohorts 1-4\] 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.

You may not qualify if:

• Acute illness on Study Day 0.
• Axillary temperature \>or= 37.5C on Study Day 0.
• 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.
• Severe anemia, defined as \<10 g/dL hemoglobin or hematocrit \<30%.
• Screening thyroid stimulating hormone (TSH) \>upper limit of normal per local laboratory range.
• 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.
• History of treatment for TB disease.
• History of autoimmune disease or immunosuppression.
• Used immunosuppressive medication within 42 days before Study Day 0 (inhaled and topical corticosteroids are permitted).
• Received immunoglobulin or blood products within 42 days before Study Day 0.
• 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.
• Received investigational vaccine against TB at any time prior to Study Day 0.
• Planned administration/administration of a licensed vaccine in the period starting 28 days before and ending 28 days after dosing with investigational product.
• 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.
• History of allergic disease or reactions, including eczema, likely to be exacerbated by any component of the investigational product.

Sponsors & Collaborators

• International AIDS Vaccine Initiative: lead
• Biofabri, S.L: collaborator
• Universidad de Zaragoza: collaborator
• South African Tuberculosis Vaccine Initiative: collaborator

Study Sites (1)

SATVI: Worcester

Worcester, 6850, South Africa

Location

MeSH Terms

Conditions

Tuberculosis

Interventions

MTBVAC vaccine

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Angelique Luabeya, MD

  SATVI

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2016
• First Posted: October 14, 2016
• Study Start: May 14, 2018
• Primary Completion: September 5, 2021
• Study Completion: September 5, 2021
• Last Updated: February 27, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1)