TuberculosisPhase 1NCT05592223
Phase I Open Label BCG Clinical Trial Assessing TB Drugs and Vaccines
A Phase 1 study testing BCG Vaccine USP, Isoniazid and Rifampin in people with Tuberculosis, run by Fred Hutchinson Cancer Center at 1 site in United States.
Trial summary
The purpose of the study is to develop a BCG challenge model for use in short term Phase I human trials capable of assessing the ability of TB drugs and/or vaccine-induced immune responses to impact in vivo mycobacterial replication as a method of assessing antimycobacterial agents and/or protective immunity elicited… Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- BCG Vaccine USP, Isoniazid and Rifampin
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Dec 2022to 1 Dec 2023
- Phase
- Phase 1
- 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 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Provide written informed consent prior to initiation of any study procedures,
- Are males or non-pregnant females between the ages of 18 and 45 years, inclusive,
- Women of childbearing potential in sexual relationships with men must use an acceptable method of preventing conception from 30 days prior to 3 months after Tice® BCG administration. Not sterilized via tubal ligation, bilateral oophorectomy, hysterectomy or successful device placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or < 1 year of the last menses if menopausal). Includes but is not limited to, sexual abstinence, monogamous relationship with vasectomized partner who has been vasectomized for 6 months or more prior to the subject receiving Tice® BCG, barrier methods such as condoms or diaphragms with spermicide or foam, effective intrauterine devices, NuvaRing ®, and licensed hormonal methods such as implants, injectables or oral contraceptives ("the pill").
- For women of childbearing potential, negative serum pregnancy test at screening and negative urine pregnancy test within 24 hours prior to enrollment and Tice® BCG administration,
- Are in good health, as judged by the investigator and determined by vital signs (oral temperature, pulse, and blood pressure), medical history and physical examination,
- Have a negative HIV-1 ELISA test,
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- Have negative serology tests for hepatitis B surface antigen and hepatitis C virus antibody,
- Have a negative QuantiFERON-TB Gold test,
- Negative is defined as Nil response < 0.8 IU/ml and TB Antigen response minus Nil response <0.35 IU/mL or TB Antigen response minus Nil response > 0.35 IU/mL and < 25% of Nil response and Mitogen response minus Nil response > 0.5 IU/ml,
- Have a urine dipstick for protein less than 1,
- Have a urine dipstick negative for glucose,
- Ability to understand and complete all study visits as required per protocol and be reachable by telephone.
Who cannot join
- Have a history of suspected, confirmed, treated or have other evidence of active tuberculosis,
- Symptoms may include recurrent fever, fatigue, night sweats, weight loss, oral ulcers, diarrhea, nausea, vomiting, or bleeding,
- Have any systemic symptoms* within 72 hours before Tice® BCG administration or signs of lymphadenopathy, hepatosplenomegaly, or pulmonary disease by physical examination on day of Tice® BCG administration. Includes fever, chills, malaise, fatigue, headache, night sweats, weight loss, nausea, vomiting, bleeding, diarrhea, abdominal pain, rhinorrhea, cough, wheezing, or shortness of breath.
- Have history of any significant acute or chronic medical conditions* or need for chronic medications that, in the opinion of the investigator, will interfere with immunity or affect safety. Includes, but is not limited to, disorders of the liver, kidney, lung, heart, or nervous system, or other metabolic or autoimmune/inflammatory conditions. Have any history of excessive scarring or keloid formation.
- Have household contact or occupation involving significant contact with someone who is immunocompromised. Includes persons with HIV, AIDs, or active cancer; infants (children < 1 year); pregnant women; or persons who are immunosuppressed for approximately 6 weeks (during the time of active ID lesion drainage).
- Have a history of epilepsy (does not include febrile seizures as a child),
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- Have a pacemaker, prosthetic valve, or implantable cardiac devices,
- Have a history of bleeding disorder,
- Have a known allergy to any Tice® BCG components (glycerin, asparagine, citric acid, potassium phosphate, magnesium sulfate, iron ammonium citrate, and lactose),
- Received blood products or immunoglobulin within 6 months prior to Tice® BCG administration,
- Received immunotherapy within one year prior to Tice® BCG administration,
- Received or plan to receive live attenuated vaccines 4 weeks before or after Tice® BCG administration,
- Received or plan to receive inactivated or killed vaccines 2 weeks before or after Tice® BCG administration,
- Plans to enroll in another clinical trial* that could interfere with safety assessment of the investigational product at any time during the study period. Includes trials that have a study intervention such as a drug, biologic, or device.
- Received an experimental agent* within 30 days prior to Tice® BCG administration or planned receipt of an experimental agent within 90 days after Tice® BCG administration, Includes vaccine, drug, biologic, device, blood product, or medication.
- Have a history of use of a systemic antibiotic within 14 days prior to Tice® BCG administration or planned use of a systemic antibiotic for 3 months after Tice® BCG administration,
- Have any medical, psychiatric, occupational, or behavioral problems that make it unlikely for the subject to comply with the protocol as determined by the investigator,
- Are health care providers at the highest risk of acquiring MTB infection, such as pulmonologists performing bronchoscopies on TB patients,
- Are breastfeeding or plan to breastfeed at any given time throughout the study,
- Have long term use of high dose oral or parenteral glucocorticoids, or high-dose inhaled steroids. Defined as taken for 2 weeks or more in total at any time during the past 2 months. High dose defined as prednisone ≥ 20 mg total daily dose, or equivalent dose of other glucocorticoids. High dose defined as > 800 mcg/day of beclomethasone dipropionate or equivalent. If short term corticosteroids are given, then the subject should not receive Tice® BCG or have blood collected for immunogenicity studies within 1 week of steroid administration.
- Have immunosuppression or are taking systemic immunosuppressants as a result of an underlying illness or treatment,
- Use of anticancer chemotherapy or radiation therapy (cytotoxic) within 36 months prior to Tice® BCG administration,
- Any active neoplastic disease,
- Have a pulse rate less than 50 bpm or greater than 100 bpm,
- Have a systolic blood pressure less than 90 mm Hg or greater than 140 mm Hg,
- Have a diastolic blood pressure less than 50 mm Hg or greater than 90 mmHg,
- Have a WBC less than 4.0x103/uL or greater than 10.5x103/uL,
- Have hemoglobin less than 11.5x103/uL (female) or less than 12.5x103/uL (male),
- Have a platelet count less than 140x103/UL,
- Have a creatinine greater than 1.30 mg/dL,
- Have an ALT (SGPT) greater than 40 IU/L (female) or greater than 55 IU/L (male),
- Have known HIV, Hepatitis B, or Hepatitis C infection,
- Have a history of alcohol or drug abuse in the last 5 years,
- Have had a positive PPD skin test in the past or received BCG vaccine (BCG vaccination history will be determined by self-report, country of birth, and/or evidence of BCG scar),
- Have a BMI >35,
- PPD skin test within 2 months prior to Tice® BCG administration or planned receipt during the study other than from participation in this study,
- Oral temperature ≥ 100.4°F (≥ 38.0°C) or other symptoms of an acute illness within 3 days before Tice® BCG administration. (Subject may be rescheduled),
- Any medical disease or condition that, in the opinion of the investigator, is a contraindication to study participation. Includes medical disease or condition that would place the subject at an unacceptable risk of injury, render them unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or their successful completion of the study.
- Have any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol or compromise the interpretation of data or the scientific integrity of the protocol.
Trial locations and contacts
1 site in 1 country.
United States1 site
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
About this study
Official title: A Phase I Single Site Open Label Clinical Trial for the Development of a Human BCG Challenge Model to Assess TB Drugs and Vaccines.
The purpose of the study is to develop a BCG challenge model for use in short term Phase I human trials capable of assessing the ability of TB drugs and/or vaccine-induced immune responses to impact in vivo mycobacterial replication as a method of assessing antimycobacterial agents and/or protective immunity elicited by vaccines or host-directed therapy. The trial will illuminate the nature of local and systemic immune responses to BCG and treatment response, as well as demonstrate our local capacity for newer, more innovative study designs.
Read the detailed description
This is phase 1, open-label, randomized clinical protocol to develop a human challenge model using the licensed and available BCG VACCINE USP (TICE® strain) with and without INH or Rifampin (RIF). Part 1 will involve 10 participants who will be screened and consented, given an intradermal injection of BCG; five of these participants will receive oral INH for 3 days. Part 2 will involve 10 participants who will be screened and consented, given an intradermal injection of BCG; five of these participants will receive oral RIF for 7 days. All participants will undergo physical exams, clinical evaluations, blood draws, urine collections, skin biopsies, and pregnancy tests. This study will measure the rate of replication by utilizing qPCR and in vitro culture, systemic innate and adaptive immune responses, including humoral and cellular assay analyses and the evaluation and PPD/IGRA status.
- Conditions
- Tuberculosis
- Being tested
- BCG Vaccine USP, Isoniazid, Rifampin
- 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 USPDrug
Also called BCG
2x10^6 cfu Tice® BCG (ID)
IsoniazidDrug
Also called INH
INH in the dose of 300 mg for three days post BCG injection.
RifampinDrug
Also called RIF
RIF in the dose of 600 mg for seven days post BCG injection.
| Study group | Role | What they receive |
|---|---|---|
| BCG Challenged-Isoniazid Treated | Active comparator | Will receive INH in the dose of 300 mg for three days post BCG injection. Receives: Drug: BCG Vaccine USP; Drug: Isoniazid |
| BCG Challenged-Isoniazid Untreated | Placebo comparator | Will not receive any INH or RIF dose. Receives: Drug: BCG Vaccine USP |
| BCG Challenged-RIF Treated | Active comparator | Will receive RIF in the dose of 600 mg for seven days post BCG injection. Receives: Drug: BCG Vaccine USP; Drug: Rifampin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess Viable BCG Bacteria From Intradermal Challenge Site From Culture.
Through microbial culture, quantify in colony forming units (CFU) BCG bacterial burden in skin biopsies from challenge sites. Outcome measure if the mean cfu from day 15 biopsy specimens.
Measured: 15 days after BCG dosing
Secondary outcomes (3)
The Rate of AE's/SAE's
Mild (grade 1): events do not require treatment and do not interfere with the patient's daily activities
Moderate (grade 2): events result in a low level of inconvenience or concern with the therapeutic measures. Moderate events may cause some interference with functioning and daily activities
Severe (grade 3): events interrupt a patient's usual daily activity and may require systemic drug therapy or other treatment. Severe events are usually incapacitating.
Measured: Through study completion, an average of 16 weeks.
Assess Quantitative Bacterial 16S Ribosomal DNA PCR
Assessing the number of real time BCG genomes present in skin biopsies from challenge sites.
Measured: Day 15 post BCG dosing
Quantification by AUC of IgG in the Blood After BCG Immunization and INH or RIF Dosing.
To assess the IgG immune response after INH or RIF dosing. The AUC we report is not a integration of concentration over time. Instead, AUC reported here quantifies the overall antibody binding signal across a titration series from a single time point (Day 144). In this assay, each sample from a single visit is measured at multiple dilutions, and the signal is expressed AUC in unit MFI × log₁₀(dilution). Plotting MFI as a function of dilution generates a curve that reflects how strongly and consistently the antibodies bind over the dilution range. The AUC therefore summarizes the entire binding titration curve - capturing both signal intensity and how long the signal is maintained across dilutions.
Measured: Day 144
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2022
- Study start6 Dec 2022
- Primary completion23 Aug 2023
- Study completion1 Dec 2023
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.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by Fred Hutchinson Cancer CenterThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, James Kublin, Fred Hutchinson Cancer Center
- Investigators
- James Kublin, MD, MPH, Principal investigator, Fred Hutchinson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05592223
- Sponsor's protocol ID
- 10903
- Other IDs
- RG1122457
- Status last verified
- Dec 2025
- First submitted
- 13 Oct 2022
- Last updated
- 16 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Sharing de-identified AE's/SAE's from all individual participants with Merck \& Co during the trial.
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Single Site Open Label Clinical Trial for the Development of a Human BCG Challenge Model to Assess TB Drugs and Vaccines.
- ClinicalTrials.gov ID
- NCT05592223
- Acronym / sponsor ID
- 10903
- Conditions
- Tuberculosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Fred Hutchinson Cancer CenterUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 6 Dec 2022 (actual)
- Primary completion
- 23 Aug 2023 (actual)
- Study completion
- 1 Dec 2023 (actual)
- First posted
- 24 Oct 2022 (actual)
- Results
- Posted 25 Mar 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 the study is to develop a BCG challenge model for use in short term Phase I human trials capable of assessing the ability of TB drugs and/or vaccine-induced immune responses to impact in vivo mycobacterial replication as a method of assessing antimycobacterial agents and/or protective immunity elicited by vaccines or host-directed therapy. The trial will illuminate the nature of local and systemic immune responses to BCG and treatment response, as well as demonstrate our local capacity for newer, more innovative study designs.
Detailed description
This is phase 1, open-label, randomized clinical protocol to develop a human challenge model using the licensed and available BCG VACCINE USP (TICE® strain) with and without INH or Rifampin (RIF). Part 1 will involve 10 participants who will be screened and consented, given an intradermal injection of BCG; five of these participants will receive oral INH for 3 days. Part 2 will involve 10 participants who will be screened and consented, given an intradermal injection of BCG; five of these participants will receive oral RIF for 7 days. All participants will undergo physical exams, clinical evaluations, blood draws, urine collections, skin biopsies, and pregnancy tests. This study will measure the rate of replication by utilizing qPCR and in vitro culture, systemic innate and adaptive immune responses, including humoral and cellular assay analyses and the evaluation and PPD/IGRA status.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| BCG Challenged-Isoniazid Treated | Active comparator | Drug: BCG Vaccine USP, Drug: IsoniazidWill receive INH in the dose of 300 mg for three days post BCG injection. |
| BCG Challenged-Isoniazid Untreated | Placebo comparator | Drug: BCG Vaccine USPWill not receive any INH or RIF dose. |
| BCG Challenged-RIF Treated | Active comparator | Drug: BCG Vaccine USP, Drug: RifampinWill receive RIF in the dose of 600 mg for seven days post BCG injection. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Provide written informed consent prior to initiation of any study procedures,
- Are males or non-pregnant females between the ages of 18 and 45 years, inclusive,
- Women of childbearing potential in sexual relationships with men must use an acceptable method of preventing conception from 30 days prior to 3 months after Tice® BCG administration. Not sterilized via tubal ligation, bilateral oophorectomy, hysterectomy or successful device placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or < 1 year of the last menses if menopausal). Includes but is not limited to, sexual abstinence, monogamous relationship with vasectomized partner who has been vasectomized for 6 months or more prior to the subject receiving Tice® BCG, barrier methods such as condoms or diaphragms with spermicide or foam, effective intrauterine devices, NuvaRing ®, and licensed hormonal methods such as implants, injectables or oral contraceptives ("the pill").
- For women of childbearing potential, negative serum pregnancy test at screening and negative urine pregnancy test within 24 hours prior to enrollment and Tice® BCG administration,
- Are in good health, as judged by the investigator and determined by vital signs (oral temperature, pulse, and blood pressure), medical history and physical examination,
Key exclusion criteria (39 listed)
- Have a history of suspected, confirmed, treated or have other evidence of active tuberculosis,
- Symptoms may include recurrent fever, fatigue, night sweats, weight loss, oral ulcers, diarrhea, nausea, vomiting, or bleeding,
- Have any systemic symptoms* within 72 hours before Tice® BCG administration or signs of lymphadenopathy, hepatosplenomegaly, or pulmonary disease by physical examination on day of Tice® BCG administration. Includes fever, chills, malaise, fatigue, headache, night sweats, weight loss, nausea, vomiting, bleeding, diarrhea, abdominal pain, rhinorrhea, cough, wheezing, or shortness of breath.
- Have history of any significant acute or chronic medical conditions* or need for chronic medications that, in the opinion of the investigator, will interfere with immunity or affect safety. Includes, but is not limited to, disorders of the liver, kidney, lung, heart, or nervous system, or other metabolic or autoimmune/inflammatory conditions. Have any history of excessive scarring or keloid formation.
- Have household contact or occupation involving significant contact with someone who is immunocompromised. Includes persons with HIV, AIDs, or active cancer; infants (children < 1 year); pregnant women; or persons who are immunosuppressed for approximately 6 weeks (during the time of active ID lesion drainage).
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 USPAlso: BCG2x10^6 cfu Tice® BCG (ID) | Drug | BCG Challenged-Isoniazid Treated, BCG Challenged-Isoniazid Untreated, BCG Challenged-RIF Treated |
| IsoniazidAlso: INHINH in the dose of 300 mg for three days post BCG injection. | Drug | BCG Challenged-Isoniazid Treated |
| RifampinAlso: RIFRIF in the dose of 600 mg for seven days post BCG injection. | Drug | BCG Challenged-RIF Treated |
Primary outcome
Assess Viable BCG Bacteria From Intradermal Challenge Site From Culture.
Time frame: 15 days after BCG dosing
Through microbial culture, quantify in colony forming units (CFU) BCG bacterial burden in skin biopsies from challenge sites. Outcome measure if the mean cfu from day 15 biopsy specimens.
3 secondary outcomes
The Rate of AE's/SAE's
Time frame: Through study completion, an average of 16 weeks.
Assess Quantitative Bacterial 16S Ribosomal DNA PCR
Time frame: Day 15 post BCG dosing
Quantification by AUC of IgG in the Blood After BCG Immunization and INH or RIF Dosing.
Time frame: Day 144
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Sharing de-identified AE's/SAE's from all individual participants with Merck \& Co during the trial.
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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.
James Kublin, MD, MPH principal investigator
Fred Hutchinson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BCG Vaccine USP, Isoniazid and Rifampin in people with Tuberculosis, run by Fred Hutchinson Cancer Center at 1 site in United States.
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 12 inclusion and 39 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: finished, as of the sponsor's last update on 16 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 25 Mar 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?
Assess Viable BCG Bacteria From Intradermal Challenge Site From Culture. (time frame: 15 days after BCG dosing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Dec 2025.