Phase I Open Label BCG Clinical Trial Assessing TB Drugs and Vaccines

NCT05592223 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 10903RG1122457
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Tuberculosis

Outcome Measures

Primary Outcomes (1)

• 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.

  15 days after BCG dosing

Secondary Outcomes (3)

• The Rate of AE's/SAE's

  Through study completion, an average of 16 weeks.

• Assess Quantitative Bacterial 16S Ribosomal DNA PCR

  Day 15 post BCG dosing

• Quantification by AUC of IgG in the Blood After BCG Immunization and INH or RIF Dosing.

  Day 144

Study Arms (3)

BCG Challenged-Isoniazid Treated

ACTIVE COMPARATOR

Will receive INH in the dose of 300 mg for three days post BCG injection.

Drug: BCG Vaccine USP; Drug: Isoniazid

BCG Challenged-Isoniazid Untreated

PLACEBO COMPARATOR

Will not receive any INH or RIF dose.

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.

Drug: BCG Vaccine USP; Drug: Rifampin

Interventions

BCG Vaccine USP DRUG

2x10\^6 cfu Tice® BCG (ID)

Also known as: BCG

BCG Challenged-Isoniazid Treated; BCG Challenged-Isoniazid Untreated; BCG Challenged-RIF Treated

Isoniazid DRUG

INH in the dose of 300 mg for three days post BCG injection.

Also known as: INH

BCG Challenged-Isoniazid Treated

Rifampin DRUG

RIF in the dose of 600 mg for seven days post BCG injection.

Also known as: RIF

BCG Challenged-RIF Treated

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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,
• 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.

You may not qualify if:

• 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),
• 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.

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Tuberculosis

Interventions

Isoniazid; Rifampin

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Elizabeth Chandler Church
• Organization: Fred Hutchinson Cancer Center

cchurch2@fredhutch.org

2066676982

Study Officials

• James Kublin, MD, MPH

  Fred Hutchinson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Staff, Scientist Vaccine and Infectious Disease Division, Fred Hutch

Study Record Dates

• First Submitted: October 13, 2022
• First Posted: October 24, 2022
• Study Start: December 6, 2022
• Primary Completion: August 23, 2023
• Study Completion: December 1, 2023
• Last Updated: December 16, 2025
• Results First Posted: March 25, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: During the participants active study period.

Locations

US (1)