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

Tuberculosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04152161
• Other study ID #: Gates MRI-TBV01-201
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 16, 2019
• Est. completion date: September 1, 2025

Study information

• Verified date: October 2023
• Source: Bill & Melinda Gates Medical Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1836
• Est. completion date: September 1, 2025
• Est. primary completion date: September 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 10 Years to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Infections
• Mycobacterium Infections
• Tuberculosis

Intervention

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

Locations

Country	Name	City	State
South Africa	Investigational Site	Berea	Durban
South Africa	Investigational Site	Hillbrow	Johannesburg
South Africa	Investigational Site	Klipfontein	Cape Town
South Africa	Investigational Site	Paarl	Western Cape
South Africa	Investigational Site	Worcester	Western Cape

Sponsors (1)

Lead Sponsor	Collaborator
Bill & Melinda Gates Medical Research Institute

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Number of Participants With Solicited Adverse Events (AEs)		Day 1 through 7 days post vaccination
Secondary	Number of Participants With Unsolicited AEs		Day 1 through 28 days post vaccination
Secondary	Number of Participants With Serious Adverse Events		Day 1 through Month 6
Secondary	Number of Participants With AEs of Special Interest		Day 1 through Month 6
Secondary	Number of Participants With Serious Adverse Drug Reactions		Day 1 through end of study participation i.e. approximately 48 months