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

A Randomized, Placebo Controlled, Observer-Blind, Phase IIb Study to Evaluate the Efficacy, Safety, and Immunogenicity of BCG Revaccination in Healthy Adolescents for the Prevention of Sustained Infection With Mycobacterium Tuberculosis

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Tuberculosis
• Intervention / Treatment: Biological: BCG vaccine SSI; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1836
• Phase: Phase 2

Contacts and Locations

Study Locations

• South Africa
  • Cape Town
    • Klipfontein, Cape Town, South Africa, 7750
      • Investigational Site
  • Durban
    • Berea, Durban, South Africa, 4001
      • Investigational Site
  • Johannesburg
    • Hillbrow, Johannesburg, South Africa, 2001
      • Investigational Site
  • Western Cape
    • Paarl, Western Cape, South Africa, 7626
      • Investigational Site
    • Worcester, Western Cape, South Africa, 6850
      • Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• Acute illness on Study Day 1. NOTE: This is a temporary exclusion for which the participant may be re-evaluated
• Body temperature ≥37.5 degree Celsius on Study Day 1. NOTE: This is a temporary exclusion for which the participant may be re-evaluated
• 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
• Laboratory values from the most recent blood collected prior to randomization outside the normal range that are suggestive of a disease state. Grade 1 abnormalities (as per Division of Acquired Immunodeficiency Syndrome toxicity table version 2.1) do not lead to exclusion if the investigator considers them not clinically significant
• 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
• Child in Care
• Female participants currently pregnant or lactating/nursing; or positive serum pregnancy test during screening or on Day 1, prior to vaccination, or planning a pregnancy within the first 12 months after study intervention

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo group	Biological: Placebo; Participants will receive a single 0.1 mL volume of normal saline, administered intradermally in deltoid region of the upper arm.
Experimental: Bacille Calmette Guerin (BCG) group	Biological: BCG vaccine SSI; Participants will receive a single 0.1 milliliter (mL) volume of BCG vaccine SSI, administered intradermally in deltoid region of the upper arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 means initial conversion and QFT Positive 3 and 6 months later.	Up to 48 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Solicited Adverse Events (AEs)	Day 1 through 7 days post vaccination
Number of Participants With Unsolicited AEs	Day 1 through 28 days post vaccination
Number of Participants With Serious Adverse Events	Day 1 through Month 6
Number of Participants With AEs of Special Interest	Day 1 through Month 6
Number of Participants With Serious Adverse Drug Reactions	Day 1 through end of study participation i.e. approximately 48 months
Number of Participants with Sustained QFT Conversion From a Negative to Positive Test Based on positive QFT test results	Initial conversion and QFT-positive at 3- and 6-months post conversion, with a minimum follow-up of 36- and 48-months post vaccination

Collaborators and Investigators

• Sponsor: Bill & Melinda Gates Medical Research Institute
• Investigators: Study Director: Gates MRI, Bill & Melinda Gates Medical Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2019
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: October 22, 2019
• First Submitted That Met QC Criteria: November 1, 2019
• First Posted (Actual): November 5, 2019

Study Record Updates

• Last Update Posted (Actual): October 5, 2023
• Last Update Submitted That Met QC Criteria: October 4, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: BCG vaccine; Healthy participants; Mycobacterium tuberculosis infection; Healthy adolescents
• Additional Relevant MeSH Terms: Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Infections; Mycobacterium Infections; Tuberculosis; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; BCG Vaccine
• Other Study ID Numbers: Gates MRI-TBV01-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No