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

Study Overview
=================
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.

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

Conditions
-----------------
Tuberculosis

Intervention / Treatment
-----------------
* Biological: BCG vaccine SSI
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 10 Years
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

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 | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Mycobacterium tuberculosis infection, Healthy adolescents, Healthy participants, BCG vaccine