Bacille Calmette Guerin (BCG) Revaccination of Healthy Adolescents for the Prevention of Mycobacterium Tuberculosis Sustained Infection

NCT04152161 | Terminated Phase 2 Results DMC

• 1 other identifier: Gates MRI-TBV01-201
• Study Type: interventional
• Target: 1,836
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to demonstrate the efficacy of Bacille Calmette Guerin (BCG) revaccination against sustained Mycobacterium tuberculosis infection versus placebo in previously BCG vaccinated QuantiFERON®-TB Gold Plus Assay (QFT) negative, healthy adolescents.

Conditions

Tuberculosis

Keywords

Mycobacterium tuberculosis infection; Healthy adolescents; Healthy participants; BCG vaccine

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Sustained QuantiFERON®-TB Gold Plus Assay (QFT) Conversion From a Negative to Positive Test Based on Positive QFT Test Results

  Sustained conversion was defined as sustained QFT conversion from a negative to positive test, with initial conversion at any time after a first negative QFT result post randomization (Day 71 or subsequent visit if Day 71 result was not available), and remaining QFT positive at 3- and 6-months post-conversion.

  Up to 48 months

Secondary Outcomes (7)

• Number of Participants With Sustained QFT Conversion From a Negative to Positive Test Based on Positive QFT Test Results at 36-Months Follow-up or Discontinued Early

  36 Months Follow-up

• Number of Participants With Sustained QFT Conversion From a Negative to Positive Test Based on Positive QFT Test Results at 48-Months Follow-up or Discontinued Early

  48 Months Follow-up

• Number of Participants With Serious and Non-serious Solicited Adverse Events (AEs) Through 7 Days Post Vaccination

  Day 1 through Day 7

• Number of Participants With Unsolicited AEs Through Day 28, as Well as Solicited AEs That Were Ongoing at Day 7 After Vaccination

  Day 1 through Day 28

• Number of Participants With Serious Adverse Events (SAEs)

  Up to 6 months

Study Arms (2)

Bacille Calmette Guerin (BCG) group

EXPERIMENTAL

Biological: BCG vaccine SSI

Placebo group

PLACEBO COMPARATOR

Biological: Placebo

Interventions

BCG vaccine SSI BIOLOGICAL

Participants will receive a single 0.1 milliliter (mL) volume of BCG vaccine SSI, administered intradermally in deltoid region of the upper arm.

Bacille Calmette Guerin (BCG) group

Placebo BIOLOGICAL

Participants will receive a single 0.1 mL volume of normal saline, administered intradermally in deltoid region of the upper arm.

Placebo group

Eligibility Criteria

• Age: 10 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participant between ≥ 10 years and ≤ 18 years on Study Day 1
• General good health, confirmed by medical history and physical examination
• Vaccinated with Bacille Calmette Guerin (BCG) at least 5 years ago, documented through medical history or by presence of healed BCG scar
• Tests QuantiFERON®-TB Gold Plus Assay (QFT) negative at screening.
• For female participants: not pregnant and agrees to avoid pregnancy throughout the first 12 months of the study. Women physically capable of pregnancy must agree to use an acceptable method of avoiding pregnancy during this period. Acceptable methods of avoiding pregnancy include sexual abstinence (not engaging in sexual intercourse), a confirmed sterile partner, or at least 2 contraception methods from the following list: male or female condom, diaphragm, intrauterine devices (IUDs), hormonal contraceptive (oral, injection, transdermal patch, or implant).
• Agrees to stay in contact with the study 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
• Capable of giving signed informed consent/assent and completes the written informed consent/assent process.

You may not qualify if:

• History or evidence of any clinically significant disease, including severe eczema and severe asthma, or any acute or chronic illness that might affect the safety, immunogenicity, or efficacy of study vaccine in the opinion of the investigator
• Any current medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the investigator, will make it unlikely that the participant will comply with the protocol
• History of autoimmune disease
• History or evidence of active tuberculosis (TB) disease
• History or laboratory evidence of any past or present possible immunodeficiency state including, but not limited to, any laboratory indication of human immunodeficiency virus - 1 (HIV-1) infection
• History of allergic disease that is likely to be exacerbated by any component of the study vaccine
• History of treatment for active TB disease or history of latent Mycobacterium tuberculosis infection
• Received a tuberculin skin test within 6 months prior to Study Day 1
• Received immunosuppressive treatment, e.g., chemotherapy, biologics or radiation therapy, or used immunosuppressive medication (daily steroid equivalent of ≥5 milligrams prednisone) within 42 days before Study Day 1. Inhaled and topical corticosteroids are permitted.
• Received immunoglobulin or blood products within 42 days before Study Day 1
• Planned administration/administration of a licensed vaccine in the period starting 28 days before and ending 28 days after Study Day 1
• Received investigational TB vaccine at any time prior to Study Day 1
• Received any investigational drug therapy or investigational vaccine within 180 days before Study Day 1, or planned participation in any other clinical trial using investigational product during the study period
• Urinalysis abnormality greater than Grade 1 on the Toxicity Scale (with the exception of hematuria in a menstruating female), or urinalysis abnormality judged clinically significant by the investigator
• Shared residence with an individual who is receiving TB treatment or with someone who is known to have incompletely treated TB. e.g., Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) assay-positive, polymerase chain reaction-positive, culture-positive, smear-positive TB, or clinically diagnosed unconfirmed TB

Sponsors & Collaborators

• Gates Medical Research Institute: lead

Study Sites (5)

Investigational Site

Klipfontein, Cape Town, 7750, South Africa

Location

Investigational Site

Berea, Durban, 4001, South Africa

Location

Investigational Site

Hillbrow, Johannesburg, 2001, South Africa

Location

Investigational Site

Paarl, Western Cape, 7626, South Africa

Location

Investigational Site

Worcester, Western Cape, 6850, South Africa

Location

Related Publications (1)

• Schmidt AC, Fairlie L, Hellstrom E, Luabeya Kany Kany A, Middelkoop K, Naidoo K, Nair G, Gela A, Nemes E, Scriba TJ, Cinar A, Frahm N, Mogg R, Kaufman D, Dunne MW, Hatherill M; BCG REVAX Study Team. BCG Revaccination for the Prevention of Mycobacterium tuberculosis Infection. N Engl J Med. 2025 May 8;392(18):1789-1800. doi: 10.1056/NEJMoa2412381.

  PMID: 40334156 DERIVED

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Gates MRI

clinical.trials@gatesmri.org

+1 857 702 2108

Study Officials

• Gates MRI

  Gates Medical Research Institute

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2019
• First Posted: November 5, 2019
• Study Start: October 16, 2019
• Primary Completion: May 14, 2024
• Study Completion: May 14, 2024
• Last Updated: June 19, 2025
• Results First Posted: June 19, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

ZA (5)