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| Sponsor: | National Institute of Allergy and Infectious Diseases (NIAID) |
|---|---|
| Information provided by: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT00396370 |
Purpose
This study will assess the safety of a Bacillus Calmette-Guérin (BCG) vaccine against tuberculosis (TB) and will evaluate if giving the vaccine by mouth, injection, or by both methods produces greater results. BCG vaccine and/or placebo (substance containing no medication) will be given by mouth and/or by injection into the skin. This study, conducted at Saint Louis University, will enroll 60 (up to 80) healthy volunteers, 18-40 years old, who are negative for a TB test (QuantiFERON®-Gold) and human immunodeficiency virus (HIV). Study procedures will include a physical exam; review of TB exposure history and medical history; collection of multiple samples of blood, urine, stool, tears, and nose fluid; and skin and blood tests for TB. Volunteers may participate for about 24 months.
| Condition | Intervention | Phase |
|---|---|---|
|
Tuberculosis |
Drug: Placebo (ID) Drug: Placebo (PO) Biological: BCG (ID) Biological: Connaught strain BCG Biological: BCG (PO) |
Phase I |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Prevention |
| Official Title: | Phase I Studies of the Safety and Immunogenicity of Primary and Secondary BCG Vaccination Delivered Intradermally, Orally and by Combined Routes of Administration in Healthy and Previously Immunologically Naïve Volunteers |
| Estimated Enrollment: | 80 |
| Study Start Date: | December 2008 |
| Estimated Study Completion Date: | June 2012 |
| Estimated Primary Completion Date: | June 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Group A: BCG ID/Placebo PO; Placebo ID/Placebo PO
Primary vaccination: BCG ID (Danish)/Placebo PO; secondary vaccination (1 year later): Placebo ID/Placebo PO.
|
Drug: Placebo (ID)
0.1 mL of sterile Sauton medium for intradermal administration.
Drug: Placebo (PO)
60 mL of sterile phosphate buffered saline (PBS) for oral administration.
Biological: BCG (ID)
Bacillus Calmette-Guerin (BCG) strain Danish from the Statens Serum Institute (SSI BCG). 2-8 X 10^5 colony-forming units (CFU) intradermal in 100 microliters diluent.
|
|
Experimental: Group B: BCG ID/Placebo PO; BCG ID/Placebo PO
Primary vaccination: BCG ID (Danish)/Placebo PO; secondary vaccination (1 year later): BCG ID (Danish)/Placebo PO.
|
Drug: Placebo (PO)
60 mL of sterile phosphate buffered saline (PBS) for oral administration.
Biological: BCG (ID)
Bacillus Calmette-Guerin (BCG) strain Danish from the Statens Serum Institute (SSI BCG). 2-8 X 10^5 colony-forming units (CFU) intradermal in 100 microliters diluent.
|
|
Experimental: Group D: Placebo ID/BCG PO; Placebo ID/BCG PO
Primary vaccination: Placebo ID/BCG PO (Danish); secondary vaccination (1 year later): Placebo ID/BCG PO (Danish).
|
Drug: Placebo (ID)
0.1 mL of sterile Sauton medium for intradermal administration.
Biological: BCG (PO)
Bacillus Calmette-Guerin (BCG) strain Danish from the Statens Serum Institute (SSI BCG). 1.2 X 10^8 colony-forming units (CFU) oral (PO) in 60 mililiters phosphate buffered saline (PBS).
|
|
Experimental: Group C: Placebo ID/BCG PO; Placebo ID/Placebo PO
Primary vaccination: Placebo ID/BCG PO (Danish); secondary vaccination (1 year later): Placebo ID/Placebo PO.
|
Drug: Placebo (ID)
0.1 mL of sterile Sauton medium for intradermal administration.
Drug: Placebo (PO)
60 mL of sterile phosphate buffered saline (PBS) for oral administration.
Biological: BCG (PO)
Bacillus Calmette-Guerin (BCG) strain Danish from the Statens Serum Institute (SSI BCG). 1.2 X 10^8 colony-forming units (CFU) oral (PO) in 60 mililiters phosphate buffered saline (PBS).
|
|
Experimental: Group F: BCG ID/BCG PO; BCG ID/BCG PO
Primary vaccination: BCG ID (Danish)/BCG PO (Danish); secondary vaccination (1 year later): BCG ID (Danish)/BCG PO (Danish).
|
Biological: BCG (ID)
Bacillus Calmette-Guerin (BCG) strain Danish from the Statens Serum Institute (SSI BCG). 2-8 X 10^5 colony-forming units (CFU) intradermal in 100 microliters diluent.
Biological: BCG (PO)
Bacillus Calmette-Guerin (BCG) strain Danish from the Statens Serum Institute (SSI BCG). 1.2 X 10^8 colony-forming units (CFU) oral (PO) in 60 mililiters phosphate buffered saline (PBS).
|
|
Experimental: Group G: Connaught strain BCG ID
Primary vaccination: Connaught strain BCG ID; secondary vaccination (1 year later): none.
|
Biological: Connaught strain BCG
Connaught strain Bacillus Calmette-Guerin (BCG), 8-32 x 10^5 CFU vaccine for intradermal administration.
|
|
Experimental: Group E: BCG ID/BCG PO; Placebo ID/Placebo PO
Primary vaccination: BCG ID (Danish)/BCG PO (Danish); secondary vaccination (1 year later): Placebo ID/Placebo PO.
|
Drug: Placebo (ID)
0.1 mL of sterile Sauton medium for intradermal administration.
Drug: Placebo (PO)
60 mL of sterile phosphate buffered saline (PBS) for oral administration.
Biological: BCG (ID)
Bacillus Calmette-Guerin (BCG) strain Danish from the Statens Serum Institute (SSI BCG). 2-8 X 10^5 colony-forming units (CFU) intradermal in 100 microliters diluent.
Biological: BCG (PO)
Bacillus Calmette-Guerin (BCG) strain Danish from the Statens Serum Institute (SSI BCG). 1.2 X 10^8 colony-forming units (CFU) oral (PO) in 60 mililiters phosphate buffered saline (PBS).
|
Vaccination with Bacillus Calmette-Guérin (BCG) is used as part of tuberculosis (TB) control strategies in most of the world outside of the United States and constitutes the most widely implemented vaccination strategy worldwide. However, despite widespread use of BCG, TB remains a leading infectious cause of death worldwide and it is estimated that one-third of the world's population is chronically and asymptomatically (latently) infected with Mycobacterium tuberculosis (Mtb), the causative agent of TB. This is a phase I, single-center, randomized, vaccine trial including six double-blind, placebo-controlled groups and one open-label group. Approximately 68 (up to 80) healthy male and female subjects 18-40 years old, inclusive, who are negative for QuantiFERON®-TB Gold and human immunodeficiency virus will be enrolled. The expected total duration of the volunteer enrollment, vaccination, and follow-up (volunteer participation) for this study is 30 months. All volunteers are expected to be enrolled over a period of 9 months and on study for 24 months. Detailed immune studies with frozen samples will be expected to continue after collection of all samples and after the protocol has been completed. Eligibility will be determined by volunteer's health at prescreening and eligible subjects will give study specific main study informed consent for enrollment in the study. Subjects randomized to Groups A-F will receive, at Day 0 and 1 year later, BCG intradermally, orally, or by both routes. PBS (PO) and Sauton medium (injectable) placebo will be used to blind the study. Subjects randomized to Group G will receive BCG intradermally at Day 0 only. The primary study objectives are the assessment of the safety of combined and individual intradermal (ID) and oral (PO) vaccination with Statens Serum Institut (SSI) BCG in healthy, immunologically naïve volunteers; comparisons of mycobacteria-specific interferon-gamma responses and mucosal immunoglobulin-A induced by SSI BCG vaccination given intradermally, orally and by both routes combined; and comparison of safety and immunogenicity of Danish and Connaught BCG given intradermally. The secondary study objectives are the assessment of purified protein derivative skin test responses as an indication of cutaneous T cell trafficking after vaccination with SSI BCG; and quantitation of BCG replication in Sanofi Pasteur ID BCG ulcerative lesions after ID BCG vaccination. The exploratory study objectives are comparisons of intracellular killing activity induced by SSI BCG vaccination given intradermally, orally, and by both routes combined; and characterization of mycobacteria-specific T cells induced intradermally, orally, or both routes by vaccination with SSI BCG using dendritic cells as antigen-presenting cells and stored peripheral blood mononuclear cells as a source for matched T cells collected before and after vaccination.
Eligibility| Ages Eligible for Study: | 18 Years to 40 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Exclusion Criteria:
Contacts and Locations
More Information
| Responsible Party: | Director ORA, HHS/NIAID/DMID |
| ClinicalTrials.gov Identifier: | NCT00396370 History of Changes |
| Other Study ID Numbers: | 01-351, Concept 904-004, N01AI80003C |
| Study First Received: | November 3, 2006 |
| Last Updated: | February 2, 2012 |
| Health Authority: | United States: Federal Government; United States: Food and Drug Administration; United States: Institutional Review Board |
|
tuberculosis, Bacillus Calmette-Guérin |
|
Tuberculosis Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections Bacterial Infections |
BCG Vaccine Adjuvants, Immunologic Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions |