TuberculosisPhase 2NCT04152161
Bacille Calmette Guerin (BCG) Revaccination of Healthy Adolescents for the Prevention of Mycobacterium Tuberculosis Sustained Infection
A Phase 2 study testing BCG vaccine SSI in people with Tuberculosis, run by Gates Medical Research Institute at 5 sites in South Africa.
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. Read more about this study
- Who is it for?
- Ages 10 to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- BCG vaccine SSI
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,836 participants
- Where
- 5 sitesSouth Africa
- Study dates
- 16 Oct 2019to 14 May 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 to 18 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 20Show fewer
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
South Africa5 sites
Investigational Site
Berea, Durban, 4001
Investigational Site
Hillbrow, Johannesburg, 2001
Investigational Site
Klipfontein, Cape Town, 7750
Investigational Site
Paarl, Western Cape, 7626
Investigational Site
Worcester, Western Cape, 6850
About this study
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
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.
- Conditions
- Tuberculosis
- Being tested
- BCG vaccine SSI, Placebo
- Keywords
- Mycobacterium tuberculosis infection, Healthy adolescents, Healthy participants, BCG vaccine
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCG vaccine SSIBiological
Participants will receive a single 0.1 milliliter (mL) volume of BCG vaccine SSI, administered intradermally in deltoid region of the upper arm.
PlaceboBiological
Participants will receive a single 0.1 mL volume of normal saline, administered intradermally in deltoid region of the upper arm.
| Study group | Role | What they receive |
|---|---|---|
| Bacille Calmette Guerin (BCG) group | Experimental | Not described Receives: Biological: BCG vaccine SSI |
| Placebo group | Placebo comparator | Not described Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 was defined as sustained QFT conversion from a negative to positive test, with initial conversion at any time after a first negative QFT result post randomization (Day 71 or subsequent visit if Day 71 result was not available), and remaining QFT positive at 3- and 6-months post-conversion.
Measured: Up to 48 months
Secondary outcomes (7)
Number of Participants With Sustained QFT Conversion From a Negative to Positive Test Based on Positive QFT Test Results at 36-Months Follow-up or Discontinued Early
Sustained conversion was defined as sustained QFT conversion from a negative to positive test, with initial conversion at any time after a first negative QFT result post randomization (Day 71 or subsequent visit if Day 71 result was not available), and remaining QFT positive at 3- and 6-months post-conversion.
Measured: 36 Months Follow-up
Number of Participants With Sustained QFT Conversion From a Negative to Positive Test Based on Positive QFT Test Results at 48-Months Follow-up or Discontinued Early
Sustained conversion was defined as sustained QFT conversion from a negative to positive test, with initial conversion at any time after a first negative QFT result post randomization (Day 71 or subsequent visit if Day 71 result was not available), and remaining QFT positive at 3- and 6-months post-conversion.
Measured: 48 Months Follow-up
Number of Participants With Serious and Non-serious Solicited Adverse Events (AEs) Through 7 Days Post Vaccination
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE does not necessarily have a causal relationship with the intervention. Solicited AEs were defined as events that participants were specifically asked about and which were noted by participants in the diary card. Solicited AEs included injection site symptoms of injections site pain, redness and swelling and general body symptoms such as headache, fatigue, gastrointestinal symptoms, and fever.
Measured: Day 1 through Day 7
Number of Participants With Unsolicited AEs Through Day 28, as Well as Solicited AEs That Were Ongoing at Day 7 After Vaccination
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE does not necessarily have a causal relationship with the intervention. Unsolicited AEs were all AEs for which the participants were not specifically questioned in the participant diary card, as well as solicited AEs that were ongoing at Day 7 after vaccination. Number of Participants With Unsolicited AEs Through 28 Days after vaccination has been presented.
Measured: Day 1 through Day 28
Number of Participants With Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Number of Participants reporting SAEs has been presented.
Measured: Up to 6 months
Number of Participants With AEs of Special Interest
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AE of special interest are AEs that the sponsor closely monitors. The AEs of special interest to be collected and reported include immune system disorders (anaphylactic reaction), general disorders (disseminated BCG disease), infections and infestations (osteomyelitis, suppurative lymphadenitis, injection site abscess), skin and subcutaneous tissue disorders (injection site lupus vulgaris, injection site keloid formation), and bone disorders (osteitis).
Measured: Up to 6 months
Number of Participants With Serious Adverse Drug Reactions (ADRs)
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. When an AE is judged to be serious and related to an investigational product, it is a Serious ADR.
Measured: Up to 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2019
- Study start16 Oct 2019
- Primary completion14 May 2024
- Study completion14 May 2024
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 1,836 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gates Medical Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gates MRI, Study director, Gates Medical Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04152161
- Sponsor's protocol ID
- Gates MRI-TBV01-201
- Status last verified
- Jun 2025
- First submitted
- 22 Oct 2019
- Last updated
- 19 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Schmidt AC, Fairlie L, Hellstrom E, Luabeya Kany Kany A, Middelkoop K, Naidoo K, Nair G, Gela A, Nemes E, Scriba TJ, Cinar A, Frahm N, Mogg R, Kaufman D, Dunne MW, Hatherill M; BCG REVAX Study Team. BCG Revaccination for the Prevention of Mycobacterium tuberculosis Infection. N Engl J Med. 2025 May 8;392(18):1789-1800. doi: 10.1056/NEJMoa2412381.
PubMed 40334156
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04152161
- Acronym / sponsor ID
- Gates MRI-TBV01-201
- Conditions
- Tuberculosis
- Keywords
- Mycobacterium tuberculosis infection, Healthy adolescents, Healthy participants, BCG vaccine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision
- Enrolment
- 1,836 participants (actual)
- Lead sponsor
- Gates Medical Research InstituteUniversity, hospital or other
- Study start
- 16 Oct 2019 (actual)
- Primary completion
- 14 May 2024 (actual)
- Study completion
- 14 May 2024 (actual)
- First posted
- 5 Nov 2019 (actual)
- Results
- Posted 19 Jun 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bacille Calmette Guerin (BCG) group | Experimental | Biological: BCG vaccine SSI |
| Placebo group | Placebo comparator | Biological: Placebo |
Who may qualify
- Ages
- 10 to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- 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).
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BCG vaccine SSIParticipants will receive a single 0.1 milliliter (mL) volume of BCG vaccine SSI, administered intradermally in deltoid region of the upper arm. | Biological | Bacille Calmette Guerin (BCG) group |
| PlaceboParticipants will receive a single 0.1 mL volume of normal saline, administered intradermally in deltoid region of the upper arm. | Biological | Placebo group |
Primary outcome
Number of Participants With Sustained QuantiFERON®-TB Gold Plus Assay (QFT) Conversion From a Negative to Positive Test Based on Positive QFT Test Results
Time frame: Up to 48 months
Sustained conversion was defined as sustained QFT conversion from a negative to positive test, with initial conversion at any time after a first negative QFT result post randomization (Day 71 or subsequent visit if Day 71 result was not available), and remaining QFT positive at 3- and 6-months post-conversion.
7 secondary outcomes
Number of Participants With Sustained QFT Conversion From a Negative to Positive Test Based on Positive QFT Test Results at 36-Months Follow-up or Discontinued Early
Time frame: 36 Months Follow-up
Number of Participants With Sustained QFT Conversion From a Negative to Positive Test Based on Positive QFT Test Results at 48-Months Follow-up or Discontinued Early
Time frame: 48 Months Follow-up
Number of Participants With Serious and Non-serious Solicited Adverse Events (AEs) Through 7 Days Post Vaccination
Time frame: Day 1 through Day 7
Number of Participants With Unsolicited AEs Through Day 28, as Well as Solicited AEs That Were Ongoing at Day 7 After Vaccination
Time frame: Day 1 through Day 28
Number of Participants With Serious Adverse Events (SAEs)
Time frame: Up to 6 months
Number of Participants With AEs of Special Interest
Time frame: Up to 6 months
Number of Participants With Serious Adverse Drug Reactions (ADRs)
Time frame: Up to 48 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40334156Schmidt AC, Fairlie L, Hellstrom E, Luabeya Kany Kany A, Middelkoop K, Naidoo K, Nair G, Gela A, Nemes E, Scriba TJ, Cinar A, Frahm N, Mogg R, Kaufman D, Dunne MW, Hatherill M; BCG REVAX Study Team. BCG Revaccination for the Prevention of Mycobacterium tuberculosis Infection. N Engl J Med. 2025 May 8;392(18):1789-1800. doi: 10.1056/NEJMoa2412381.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gates MRI study director
Gates Medical Research Institute
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BCG vaccine SSI in people with Tuberculosis, run by Gates Medical Research Institute at 5 sites in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Sustained QuantiFERON®-TB Gold Plus Assay (QFT) Conversion From a Negative to Positive Test Based on Positive QFT Test Results (time frame: Up to 48 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04152161, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jun 2025.