A Study of MVA85A in Healthy Infants
|Tuberculosis||Biological: MVA85A/AERAS-485 Biological: Candida Skin Test Antigen||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||Phase II Double-blinded Randomized Controlled Evaluation of MVA85A/AERAS-485 for Safety, Immunogenicity and Prevention of Tuberculosis in BCG-vaccinated, HIV-negative Infants|
- To Evaluate the Safety Profile of MVA85A/AERAS-485 in Bacillus Calmette-Guerin (BCG) -Vaccinated, HIV-negative Infants. [ Time Frame: AEs recorded 28 days post-vaccination; SAEs recorded for entire study period. ]Adverse events (AE) were collected for 28 days after vaccination. The subject's parent or guardian recorded information regarding occurrences of solicited adverse events in diary cards through 7 days after vaccination. Serious adverse events (SAE) were collected from the time of study vaccine dosing throughout the entire study. A safety cohort (the first 330 infants enrolled) also had serum chemistry and hematology testing up to 28 days post-vaccination.
- To Evaluate the Efficacy of the MVA85A/AERAS-485 Vaccine Compared to Controls in Prevention of Tuberculosis Using an Endpoint Derived From Epidemiological Cohort Surveys in BCG Vaccinated Infants. [ Time Frame: 15 to 36 months post-vaccination ]The number (percentage) of subjects with a diagnosis of tuberculosis based on clinically-derived tuberculosis (TB) diagnostic criteria were summarized by treatment group for all subjects.
- To Evaluate the Immunogenicity of the MVA85A/AERAS-485 Vaccine Compared to Controls as Described by Flow Cytometric Intracellular Cytokine Staining of CD4 and CD8 T Cells. [ Time Frame: 28 days post-vaccination ]Intracellular cytokine staining (ICS) assay immune response was expressed as the percentage of cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8) T cells producing any one of three cytokines (IFN-γ, TNF-α, or IL-2) or any combination of the three cytokines simultaneously after stimulation with an Ag85A peptide pool on a subset of infants.
- To Evaluate the Immunogenicity of the MVA85A/AERAS-485 Vaccine Compared to Controls as Described by the ex Vivo Enzyme Linked Immunospot (ELISPOT) Test Used in Previous MVA85A/AERAS-485 Human Trials. [ Time Frame: 7 days post-vaccination ]An ex vivo IFN-γ ELISPOT assay was used to assess specific T cell responses to an Ag85A peptide pool for a subset of infants.
- To Evaluate the Immunogenicity of the MVA85A/AERAS-485 Vaccine Compared to Controls as Described by the University of Capetown (UCT) Whole Blood Intracellular Cytokine Assay. [ Time Frame: 28 days post-vaccination ]Frequencies of CD4 and CD8 T cells expressing cytokines (IFN-γ, IL-2 and TNF-α) following stimulation of whole blood with an Ag85A peptide pool were also measured by flow cytometry for a subset of infants.
- To Discover Correlates of Protection From Tuberculosis in Infants Vaccinated With MVA85A/AERAS-485. [ Time Frame: 15 to 36 months post-vaccination ]Investigations for determining correlates of immune protection to TB will not be completed as planned because the study did not show TB protection in MVA85A/AERAS-485 recipients.
- To Evaluate the QuantiFERON Conversion Rate at Final Study Assessment in MVA85A/AERAS-485 Recipients Compared to Controls in Infants Without a Diagnosis of Tuberculosis During the Trial. [ Time Frame: 15 to 36 months post-vaccination ]The number (percentage) of infants with QuantiFERON conversions at any time on the study were summarized by treatment group.
|Study Start Date:||July 2009|
|Primary Completion Date:||October 2012 (Final data collection date for primary outcome measure)|
Experimental: Investigational Vaccine
MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests.
Attenuated virus MVA vector with insertion. Single dose vaccine, 1 x 10^8 pfu.
Other Name: Manufactured by IDT of Germany.
Placebo Comparator: Control Group
Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.
Biological: Candida Skin Test Antigen
1 test, administered once as a placebo control.
This was a Phase II double-blinded randomized controlled evaluation of safety, immunogenicity and efficacy of MVA85A/AERAS-485 in BCG vaccinated infants without tuberculosis or HIV infection. Infants (126 to 182 days) received intradermal (ID) study vaccine (MVA85A/AERAS-485 or Candida skin test antigen control). All infants were to be followed for at least 15 months after the last infant was enrolled into the study. Given completion of enrollment in 21 months, the total duration of follow-up for each infant was scheduled to be at least 15 months and up to 36 months. Infants were to be followed for the entire duration of the study both for the development of tuberculosis and serious adverse events.
On enrollment to the study, eligible infants were assigned to a study group starting with Study Group 1 and were randomized in a 1:1 ratio within a study group to receive either MVA85A/AERAS-485 or Candida skin test antigen control. Infants were assigned to a safety cohort (Study Group 1), then into 1 of 3 immunological assay evaluation groups (Study Groups 2-4), and finally the remainder of infants were assigned into the correlate of protection cohort (Study Group 5). At least 330 infants were to be randomized in Study Group 1, up to 50-60 infants each in Study Groups 2-4, and the remaining infants were randomized in Study Group 5.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00953927
|South African Tuberculosis Vaccine Initiative (Satellite)|
|Ceres, South Africa, 6835|
|South African Tuberculosis Vaccine Initiative (Satellite)|
|Robertson, South Africa, 6705|
|South African Tuberculosis Vaccine Initiative (Headquarters)|
|Worcester, South Africa, 6850|
|Principal Investigator:||Michele Tameris, MD||South African Tuberculosis Vaccine Initiative|
|Study Director:||Bernard Landry, MPH||Aeras|
|Study Chair:||Helen McShane, MD||University of Oxford; Centre for Vaccinology & Tropical Medicine|