Safety and Immunogenicity Study of BCG, H4:IC31, and H56:IC31 Revaccination in Healthy Adolescents
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|ClinicalTrials.gov Identifier: NCT02378207|
Recruitment Status : Completed
First Posted : March 4, 2015
Results First Posted : November 18, 2019
Last Update Posted : November 18, 2019
|Condition or disease||Intervention/treatment||Phase|
|Tuberculosis||Biological: H4:IC31 Biological: H56:IC31 Biological: BCG Biological: Control Sodium Chloride 0.9%||Phase 1|
This study proposes to further evaluate the safety and immunogenicity of H4:IC31, H56:IC31, and BCG revaccination. The study will be conducted in previously BCG vaccinated healthy adolescents, and will entail a thorough immunogenicity evaluation of these regimens incorporating unbiased systems vaccinology approaches and novel assessments of baseline and elicited responses that may impact vaccine responses. A major goal for this study is to generate immunological data on a wide range of immune responses using a variety of approaches including validated assessments, unbiased strategies, and novel exploratory assays to increase the likelihood of detecting responses correlating with risk or protection in the prevention of infection study. Investigators contributing to the proposed study have participated in a correlates analysis for an HIV vaccine exhibiting modest efficacy in which 2 correlates of risk were identified.
An additional aim of this study is to explore factors affecting vaccine induced responses that may also impact efficacy. For example, it is hypothesized that exposure to environmental mycobacteria may alter protection provided by BCG vaccination. Reagents for evaluating levels of exposure to environmental mycobacteria are in development as part of a concurrent collaborative study. An exploratory objective for this trial is to apply these reagents to examine whether such exposures influence immune responses elicited by the study vaccine and regimens.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||84 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomized, Placebo-controlled, Partially Blinded Phase 1b Clinical Trial to Evaluate the Safety and Immunogenicity of BCG Revaccination, H4:IC31, and H56:IC31 in Healthy, HIV-1-Uninfected Adolescent Participants|
|Study Start Date :||May 2015|
|Actual Primary Completion Date :||October 31, 2016|
|Actual Study Completion Date :||December 9, 2016|
Experimental: Group 1 H4:IC31
15 mcg H4/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.
H4 contains Mtb antigens Ag85B and TB10.4
Experimental: Group 2 H56:IC31
5 mcg H56/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.
H56 contains Mtb antigens ESAT-6, and Rv2660c
Active Comparator: Group 3 BCG (2-8 x 105 CFU)
Administered IM as 0.1 mL in either deltoid muscle at Day 0.
Placebo Comparator: Group 4 Control Sodium Chloride 0.9%
Administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.
Biological: Control Sodium Chloride 0.9%
- Number of Participants With Adverse Events [ Time Frame: Up to 8 months ]The number of solicited and unsolicited adverse events (AEs), including serious adverse events (SAEs), recorded post-vaccination for all participants.
- Percentage of Participants With Response Rates to TB Antigens as Compared to Baseline [ Time Frame: Days 70 and 168 ]Flow cytometry was used to examine TB Mb-specific CD4+ and CD8+ T-cell responses using the ICS assay. The antigens used to stimulate cells in this assay included peptide pools for the vaccine-matched proteins (Ag85B, ESAT-6, Rv2660c, and TB 10.4) as well as complex TB antigens (TB whole cell lysate [TB WCL], and BCG Pasteur strain.
- Evaluate Humoral Responses Elicited by the Different Vaccine Regimens. [ Time Frame: Up to day 168. ]Vaccine-specific binding antibodies elicited by the vaccine regimens as determined by multiplex antibody assay and/or enzyme-linked immunosorbent assay (ELISA).
- * Evaluate Immune Response From Vaccine Regimens by Measuring Early (Innate) Vaccine-induced Peripheral Blood Transcription Profiles; Determine Which Responses Are Associated With Antigen-specific Adaptive Responses * Evaluate Adaptive Immune Response. [ Time Frame: Up to day 168 ]
- Changes in gene expression measured in longitudinally-collected blood samples relative to samples collected at baseline. The transcriptional profiles will be correlated with antigen-specific adaptive responses measured in Primary objective 2.
- Transcriptional analysis of antigen-stimulated peripheral blood mononuclear cells (PBMC) at 2 weeks post vaccination will be performed..
- Evaluate Changes in Innate Cells in Response to the Vaccine Regimens [ Time Frame: Up to day 168 ]Blood concentrations of innate immune cell populations including lymphocyte populations, dendritic cells, monocytes, and granulocytes before and after vaccination
- Measure Non-classical Major Histocompatibility Complex (MHC)-Restricted T-cell Vaccine-induced Responses, Such as to Mycobacterial Lipids (CD1-restricted) and Metabolites (MR1-restricted). [ Time Frame: Up to day 168 ]
- Frequency of CD4+, CD8+, and CD4/CD8 double-negative T-cell responses restricted by CD1 (recognizing specific Mtb lipids) before and after BCG revaccination in Group 3 participants.
- Frequency of mucosal-associated invariant T-cells (MAIT) restricted by MR1 (recognizing vitamin B metabolites) before and after BCG revaccination in Group 3 participants
- Evaluate QFT-GIT and ESAT-6 Free IGRA Discordance and Conversion/Reversion Rate During the Course of the Trial. [ Time Frame: Up to day 168 ]
- Magnitude and positivity of interferon (IFN)-γ release using QFT-GIT ELISA in QFT-GIT tests.
- Magnitude and positivity of IFN-γ release using QFT-GIT ELISA in ESAT-6 free IGRAs.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02378207
|Desmond Tutu HIV Foundation|
|Cape Town, South Africa|
|Study Chair:||Linda-Gail Bekker, MD||Desmond Tutu HIV Centre|
|Study Chair:||Jim Kublin, MD||HVTN Core, FHCRC|