BCG Revaccination of Healthy Adolescents for the Prevention of Mycobacterium Tuberculosis Sustained Infection
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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.
|
| Placebo Comparator: Placebo group
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Biological: Placebo
Participants will receive a single 0.1 mL volume of normal saline, administered intradermally in deltoid region of the upper arm.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Sustained QuantiFERON®-TB Gold Plus Assay (QFT) Conversion From a Negative to Positive Test Based on an Interferon Gamma (IFN-γ) Concentration cut-off Value of 0.35 International Units per Milliliter (IU/mL) [Up to 48 months]
Sustained Conversion means initial conversion and QFT Positive 3 and 6 months later.
Secondary Outcome Measures
- Number of Participants with Sustained QFT Conversion From a Negative to Positive Test Based on an IFN-γ Concentration cut-off Level of 0.35 IU/mL [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]
- Primary QFT Conversion From a Negative to Positive Test Based on a QFT IFN-γ Concentration cut-off Value of 4 IU/mL (Initial Conversion Only) [At the time of primary endpoint analysis, anticipated to occur within 3.5 years of study start, and after a minimum follow-up of 36- and 48-months post vaccination]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Participant between ≥ 10 years and ≤ 18 years on Study Day 1
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General good health, confirmed by medical history and physical examination
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Vaccinated with Bacille Calmette Guerin (BCG) at least 5 years ago, documented through medical history or by presence of healed BCG scar
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Tests QuantiFERON®-TB Gold Plus Assay (QFT) negative at screening, using the manufacturer's recommended threshold of 0.35 international units per milliliter
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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).
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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
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Capable of giving signed informed consent/assent and completes the written informed consent/assent process.
Exclusion Criteria:
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Acute illness on Study Day 1 . NOTE: This is a temporary exclusion for which the participant may be re-evaluated
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Body temperature ≥37.5 degree Celsius on Study Day 1. NOTE: This is a temporary exclusion for which the participant may be re-evaluated
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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
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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
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History of autoimmune disease
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History or evidence of active tuberculosis (TB) disease
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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
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History of allergic disease that is likely to be exacerbated by any component of the study vaccine
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History of treatment for active TB disease or history of latent Mycobacterium tuberculosis infection
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Received a tuberculin skin test within 6 months prior to Study Day 1
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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.
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Received immunoglobulin or blood products within 42 days before Study Day 1
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Planned administration/administration of a licensed vaccine in the period starting 28 days before and ending 28 days after Study Day 1
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Received investigational TB vaccine at any time prior to Study Day 1
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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
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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
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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
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Shared residence with an individual who is receiving TB treatment or with someone who is known to have incompletely treated TB. e.g., polymerase chain reaction-positive, culture-positive, smear-positive TB, or clinically diagnosed unconfirmed TB
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Child in Care
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Investigational Site | Klipfontein | Cape Town | South Africa | 7750 |
| 2 | Investigational Site | Berea | Durban | South Africa | 4001 |
| 3 | Investigational Site | Hillbrow | Johannesburg | South Africa | 2001 |
| 4 | Investigational Site | Paarl | Western Cape | South Africa | 7626 |
| 5 | Investigational Site | Worcester | Western Cape | South Africa | 6850 |
Sponsors and Collaborators
- Bill & Melinda Gates Medical Research Institute
Investigators
- Study Director: Gates MRI, Bill & Melinda Gates Medical Research Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Gates MRI-TBV01-201