Challenge Model for Assessment of Human TB Immunity

Completed · Phase 1

Conditions studied: Tuberculosis

In brief

This is a Phase I open-label, dose escalation trial to evaluate the use of Tice® BCG as a challenge for future assessment of in vivo TB immunity. Subjects will be recruited from the target population reflecting the community at 2 VTEU sites. Enrollment will occur over 14 months. Subjects who provide informed consent will be screened, and up to 120 eligible, HIV and TB uninfected subjects, 18-45 years, inclusive, will be enrolled for study interventions and sequentially assigned to 1 of 4 dose groups. Doses of Tice BCG from 2 to 16x10\^6 cfu will be delivered ID in a dose escalation format to 4 groups of 30 subjects per dose group. Primary Objectives: 1) Evaluate the safety of different doses of ID Tice BCG for use as a human challenge model for TB infection. 2) Examine shedding from ID challenge sites after administration of different doses of Tice BCG in TB naive healthy subjects. 3) Evaluate the reproducibility of BCG shedding over time with both quantitative PCR and culture.

Key facts

Study ID

NCT01868464

Run by

National Institute of Allergy and Infectious Diseases (NIAID)

People needed

92

Starts

2014-05-28

Expected to finish

2017-12-18

Last updated by the study team

2020-01-27

Who can join

Age: 18 and older, up to 45. Sex: any. Healthy volunteers: accepted.

You may qualify if…

• Eligibility Criteria for Study Entry:
• 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 Essure 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®, successful Essure® placement (permanent, non-surgical, non-hormonal sterilization) with documented confirmation test at least 3 months after the procedure), 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…

• Exclusion Criteria for Study Entry:
• 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.
• 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.

Where it is running

• Emory Vaccine Center - The Hope Clinic — Decatur, Georgia, United States
• Saint Louis University - Center for Vaccine Development — St Louis, Missouri, United States

Full record on ClinicalTrials.gov

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