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

Phase 2
Active, not recruiting
Conditions
Tuberculosis
Interventions
Biological: BCG vaccine SSI
Biological: Placebo
Registration Number
NCT04152161
Lead Sponsor
Bill & Melinda Gates Medical Research Institute
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
1836
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Bacille Calmette Guerin (BCG) groupBCG vaccine SSI-
Placebo groupPlacebo-
Primary Outcome Measures
NameTimeMethod
Number of Participants With Sustained QuantiFERON®-TB Gold Plus Assay (QFT) Conversion From a Negative to Positive Test Based on positive QFT test resultsUp to 48 months

Sustained Conversion means initial conversion and QFT Positive 3 and 6 months later.

Secondary Outcome Measures
NameTimeMethod
Number of Participants With Serious Adverse Drug ReactionsDay 1 through end of study participation i.e. approximately 48 months
Number of Participants With Unsolicited AEsDay 1 through 28 days post vaccination
Number of Participants with Sustained QFT Conversion From a Negative to Positive Test Based on positive QFT test resultsInitial 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 Serious Adverse EventsDay 1 through Month 6
Number of Participants With AEs of Special InterestDay 1 through Month 6

Trial Locations

Locations (1)

Investigational Site

🇿🇦

Worcester, Western Cape, South Africa

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