Phase 1b Safety and Immunogenicity Trial of BCG Revaccination, H4:IC31, and H56:IC31 in Healthy, HIV-1-Uninfected Adolescents (A-042)
|Tuberculosis||Biological: H4:IC31 Biological: H56:IC31 Biological: BCG Biological: Control Sodium Chloride 0.9%||Phase 1|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|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|
- Safety and tolerability of the different vaccine regimens in adolescents [ Time Frame: Up to 8 months ]The number and percentage of solicited and unsolicited adverse events (AEs), recorded postvaccination for all participants.
- Cellular immune responses of the different vaccine regimens in adolescents compared to those measured at baseline. [ Time Frame: Up to day 70 ]T-cell responses by flow cytometric intracellular cytokine staining (ICS) of CD4+ T cells after stimulation with a pool of mycobacterial peptides and/or PPD (purified protein derivative) using cryopreserved peripheral blood mononuclear cells (PBMC).
- Cellular immune responses of the different vaccine regimens in adolescents compared to those measured at baseline. [ Time Frame: Up to day 70 ]T-cell responses by flow cytometric intracellular cytokine staining (ICS) of CD8+ T cells after stimulation with a pool of mycobacterial peptides and/or PPD (purified protein derivative) using cryopreserved peripheral blood mononuclear cells (PBMC).
|Study Start Date:||May 2015|
|Study Completion Date:||December 9, 2016|
|Primary Completion Date:||October 31, 2016 (Final data collection date for primary outcome measure)|
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.
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.
Active Comparator: Group 3 BCG (2-8 x 105 CFU)
Administered ID 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%|
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 these regimens.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02378207
|Desmond Tutu HIV Foundation|
|Cape Town, South Africa|
|Study Chair:||Linda-Gail Bekker, MD||Desmond Tutu HIV Foundation|
|Study Chair:||Jim Kublin, MD||HVTN Core, FHCRC|