Study of AERAS-402 in Healthy Infants
AERAS-402 will be given to infants of at least 16 weeks of age who have already been vaccinated with BCG to determine if AERAS-402 will increase protection of infants to tuberculosis.
Biological: AERAS-402 1.5 x 10^10 vp
Biological: AERAS-402 3.0 x 10^10 vp
Biological: AERAS-402 1.0 x 10^11 vp
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||A Phase II, Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Safety and Immunogenicity of AERAS-402 in BCG-vaccinated, HIV-uninfected Infants Without Evidence of Tuberculosis|
- Adverse Events Collected Per Subject [ Time Frame: Up to 24 months post vaccination ] [ Designated as safety issue: Yes ]Adverse Events (AEs) are recorded for 28 days post vaccination Serious Adverse Events (SAEs) are recorded for the entire study period to assess the safety profile
- Percentage of Cells Expressing Various Cytokines Will be Measured by Intracellular Cytokine Staining (ICS) in All Subjects [ Time Frame: 28 days post last vaccination ] [ Designated as safety issue: No ]To evaluate the immunogenicity of AERAS-402 compared to controls, flow cytometric ICS of CD4 and CD8 T cells producing any of three cytokines (IFN-γ, TNF-α, and/or IL-2) alone or in combination after stimulation with a peptide pool of mycobacterial peptides. Dimethylsulfoxide (DMSO) subtracted responses are presented.
- Interferon-gamma (IFN-gamma) Enzyme-linked Immunospot (ELISpot) Response: Spot Forming Units/10^6 PBMC According to ELISpot Assay [ Time Frame: 28 days post last vaccination ] [ Designated as safety issue: No ]To evaluate the immunogenicity of AERAS-402 compared to controls. ELISpot assay of specific T cell responses after stimulation with a peptide pool of mycobacterial peptides. Values presented have been corrected for background readings.
- Antigen-specific Antibody Response - Mean Optical Density (Mean OD) [ Time Frame: 28 day post last vaccination ] [ Designated as safety issue: No ]To evaluate the immunogenicity of AERAS-402 compared to controls by ELISA Assay for Antigen-specific Antibody Response. Median responses of individual Mean OD (absorbance at 450nm) by study group is presented. Higher OD values suggests the presence of antibody to each of the Mtb antigens (Ag85A, Ag85B and TB10.4).
- Percentage of Subjects Converting From a Negative QuantiFERON Test (QFT) to Positive QFT After Vaccination [ Time Frame: up to 24 months post vaccination ] [ Designated as safety issue: No ]To evaluate the proportion of on-study QuantiFERON conversions from negative to positive in infants that received AERAS-402 compared to controls. A QFT value of on >= 0.35IU/mL was considered positive for this study.
|Study Start Date:||September 2010|
|Study Completion Date:||April 2014|
|Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
Placebo Comparator: Dose Finding Gr 1 placebo x 2
Subjects received two doses (x2) of placebo (sterile buffer) on study days 0 and 28.
Experimental: Dose Finding Gr 2 AERAS-402 (1.5 x 10^10 vp) x2
Subjects received two doses (x2) of AERAS-402 (1.5 x 10^10 vp) on study days 0 and 28.
|Biological: AERAS-402 1.5 x 10^10 vp|
Experimental: Dose Finding Gr 3 AERAS-402 (3.0 x 10^10 vp) x 2
Subjects received two doses (x2) of AERAS-402 (3.0 x 10^10 vp) on study days 0 and 28.
|Biological: AERAS-402 3.0 x 10^10 vp|
Experimental: Dose Finding Gr 4 AERAS-402 (1.0 x 10^11 vp) x 2
Subjects received two doses (x2) of AERAS-402 (1.0 x 10^11 vp) on study days 0 and 28.
|Biological: AERAS-402 1.0 x 10^11 vp|
Experimental: Expanded Safety Phase Gr 5 AERAS-402 (1.0 X 10^11 vp) x 3
Subjects received 3 doses (x3) of AERAS-402 (1.0 X 10^11 vp) on days 0, 28 and 280.
|Biological: AERAS-402 1.5 x 10^10 vp|
Placebo Comparator: Expanded Safety Phase Gr 5 Placebo x3
Subjects received 3 doses (x3) of placebo (sterile buffer) on days 0, 28 and 280.
The only currently available tuberculosis vaccine, bacillus Calmette-Guérin (BCG), is estimated to reduce the risk of tuberculosis (TB) in children by up to 70-80%, but protection is incomplete. Efforts to increase TB protection in children include new vaccines for primary immunizations as well as combinations of vaccines given as primary and boosting vaccinations.
AERAS 402 is a live recombinant serotype 35 replication deficient adenovirus vector expressing a fusion protein of three Mycobacterium tuberculosis (Mtb) antigens (Ag85A, Ag85B and TB10.4). It presents Mtb antigens in the setting of a new, live, replication-deficient adenovirus vaccine that may increase T cell-mediated immunity and thus protection from tuberculosis. AERAS-402 appears safe and immunogenic in adults. Since BCG-vaccinated infants are the population for which AERAS-402 might be indicated, AERAS-402 will be administered to infants of at least 16 weeks of age who have already been vaccinated with BCG. This is the first Phase II study of AERAS-402 in infants.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01198366
|Boro Heath Center|
|KEMRI/CDC Research and Public Heath Collaboration|
|Kisumu, Kenya, 40100|
|Siaya District Hospital|
|CISM: Centro de Investigacao em Saude de Manhica|
|Manhica, Mozambique, 1929|
|Univeristy of Cape Town|
|Cape Town, South Africa, 7925|
|Perinatal HIV Research Unit (PHRU) Chris Hani Baragwanath Hospital|
|Soweto, South Africa, 1864|
|Worcester, South Africa, 6850|
|Study Director:||Robert Walker||Aeras|