- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01868464
Challenge Model for Assessment of Human TB Immunity
Phase I Open-Label Dose Escalation Trial for the Development of a Human BCG Challenge Model for Assessment of TB Immunity
Study Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Georgia
-
Decatur, Georgia, United States, 30030-1705
- Emory Vaccine Center - The Hope Clinic
-
-
Missouri
-
Saint Louis, Missouri, United States, 63104-1015
- Saint Louis University - Center for Vaccine Development
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
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.
Exclusion Criteria:
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.
- 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 4.0x10^3/UL or greater than 10.5x10^3/UL.
- Have hemoglobin less than 11.5x10^3/UL (female) or less than 12.5x10^3/UL (male).
- Have a platelet count less than 140x10^3/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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: BCG 16x10^6 CFU
30 subjects, one dose of Tice BCG intradermally, 16x10^6 cfu
|
All doses: Tice Bacillus Calmette-Guerin (BCG) will be administered as a single 0.1 ml ID injection over the deltoid muscle of the preferred arm.
Groups 1 - 4 will receive one dose of Tice BCG intradermally at 2x10^6 cfu, 4x10^6 cfu, 8x10^6 cfu and 16x10^6 cfu, respectively.
|
Experimental: BCG 2x10^6 CFU
30 subjects, one dose of Tice Bacillus Calmette-Guerin vaccine (BCG) intradermally, 2x10^6 colony forming units (cfu)
|
All doses: Tice Bacillus Calmette-Guerin (BCG) will be administered as a single 0.1 ml ID injection over the deltoid muscle of the preferred arm.
Groups 1 - 4 will receive one dose of Tice BCG intradermally at 2x10^6 cfu, 4x10^6 cfu, 8x10^6 cfu and 16x10^6 cfu, respectively.
|
Experimental: BCG 4x10^6 CFU
30 subjects, one dose of Tice BCG intradermally, 4x10^6 cfu
|
All doses: Tice Bacillus Calmette-Guerin (BCG) will be administered as a single 0.1 ml ID injection over the deltoid muscle of the preferred arm.
Groups 1 - 4 will receive one dose of Tice BCG intradermally at 2x10^6 cfu, 4x10^6 cfu, 8x10^6 cfu and 16x10^6 cfu, respectively.
|
Experimental: BCG 8x10^6 CFU
30 subjects, one dose of Tice BCG intradermally, 8x10^6 cfu
|
All doses: Tice Bacillus Calmette-Guerin (BCG) will be administered as a single 0.1 ml ID injection over the deltoid muscle of the preferred arm.
Groups 1 - 4 will receive one dose of Tice BCG intradermally at 2x10^6 cfu, 4x10^6 cfu, 8x10^6 cfu and 16x10^6 cfu, respectively.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Serious adverse events related to Tice® BCG administration
Time Frame: Day 1 to Day 181
|
Day 1 to Day 181
|
Summary of distribution, in terms of its precision, of BCG shedding from intradermal challenge sites using subjects' peak shedding, as detected by each of 3 assays (quantitative PCR, quantitative CFU plating and quantitative MGIT BACTEC culture).
Time Frame: Following Tice® BCG administration biweekly to Week 6
|
Following Tice® BCG administration biweekly to Week 6
|
Summary of distribution, terms of its central tendency (mean or GM), of BCG shedding from intradermal challenge sites at 3 time points, as detected by each of 3 assays (quantitative PCR, quantitative CFU plating and quantitative MGIT BACTEC culture).
Time Frame: Following Tice® BCG administration biweekly to Week 6
|
Following Tice® BCG administration biweekly to Week 6
|
The number of subjects experiencing Grade 3 (severe) clinical safety laboratory adverse events
Time Frame: Day 1 to Day 181
|
Day 1 to Day 181
|
The number of subjects experiencing Grade 3 (severe) injection site reactions following Tice® BCG administration.
Time Frame: Day 1 to Day 15
|
Day 1 to Day 15
|
The number of subjects experiencing Grade 3 (severe) solicited systemic reactions following Tice® BCG administration
Time Frame: Day 1 to Day 15
|
Day 1 to Day 15
|
The number of subjects in groups 3 and 4 experiencing Grade 3 (severe) injection site reactions.
Time Frame: Between Days 16 and 99 following Tice® BCG administration
|
Between Days 16 and 99 following Tice® BCG administration
|
The number of subjects spontaneously reporting Grade 3 (severe) adverse events related to Tice® BCG administration following Tice® BCG administration.
Time Frame: Day 1 to Day 56
|
Day 1 to Day 56
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Summary of distribution of the area under the curve for repeated measures of shedding over time from 3 assays (quantitative PCR, quantitative CFU plating and quantitative MGIT BACTEC culture). Summarized in terms of its central tendency (mean or GM)
Time Frame: 8 weeks (56 days) following Tice® BCG administration
|
8 weeks (56 days) following Tice® BCG administration
|
Summary of distribution of the area under the curve, in terms of its precision, for repeated measures of shedding over time from 3 assays (quantitative PCR, quantitative CFU plating and quantitative MGIT BACTEC culture).
Time Frame: 8 weeks (56 days) following Tice® BCG administration
|
8 weeks (56 days) following Tice® BCG administration
|
Summary of distribution, in terms of its precision, of BCG shedding from intradermal challenge sites using subjects' peak shedding, as detected by each of 3 assays (quantitative PCR, quantitative CFU plating and quantitative MGIT BACTEC culture).
Time Frame: 8 weeks (56 days) following Tice® BCG administration
|
8 weeks (56 days) following Tice® BCG administration
|
Summary of distribution, terms of its central tendency (mean or GM), of BCG shedding from intradermal challenge sites at 3 time points, as detected by each of 3 assays (quantitative PCR, quantitative CFU plating and quantitative MGIT BACTEC culture).
Time Frame: 8 weeks (56 days) following Tice® BCG administration
|
8 weeks (56 days) following Tice® BCG administration
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 11-0033
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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