A Study of MVA85A in Healthy Infants

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
Condition:	Tuberculosis
Interventions:	Biological: MVA85A/AERAS-485; Biological: Candida Skin Test Antigen

  Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Investigational Vaccine	MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests.
Control Group	Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.

Participant Flow:   Overall Study

	Investigational Vaccine	Control Group
STARTED	1399	1398
COMPLETED	1294	1303
NOT COMPLETED	105	95
Lost to Follow-up	61	65
Withdrawal by Subject	36	25
Death	7	4
Other study discontinuation	1	1

  Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent to treat population

Reporting Groups

	Description
Investigational Vaccine	MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests.
Control Group	Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.
Total	Total of all reporting groups

Baseline Measures

	Investigational Vaccine	Control Group	Total
Overall Participants Analyzed; [Units: Participants]	1399	1398	2797
Age; [Units: Participants]
<=18 years	1399	1398	2797
Between 18 and 65 years	0	0	0
>=65 years	0	0	0
Age; [Units: Years]; Mean (Standard Deviation)	.401 (.039)	.399 (.037)	.400 (.038)
Gender; [Units: Participants]
Female	691	682	1373
Male	708	716	1424
Region of Enrollment; [Units: Participants]
South Africa	1399	1398	2797

  Outcome Measures

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1. Primary:

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. ]

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Measure Type	Primary
Measure Title	To Evaluate the Safety Profile of MVA85A/AERAS-485 in Bacillus Calmette-Guerin (BCG) -Vaccinated, HIV-negative Infants.
Measure Description	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.
Time Frame	AEs recorded 28 days post-vaccination; SAEs recorded for entire study period.

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subjects vaccinated.

Reporting Groups

	Description
Investigational Vaccine	MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests.
Control Group	Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.

Measured Values

	Investigational Vaccine	Control Group
Participants Analyzed; [Units: Participants]	1399	1396
To Evaluate the Safety Profile of MVA85A/AERAS-485 in Bacillus Calmette-Guerin (BCG) -Vaccinated, HIV-negative Infants.; [Units: Percentage of all subjects vaccinated]; Number (95% Confidence Interval)	95.9; (94.7 to 96.8)	83.7; (81.7 to 85.6)

No statistical analysis provided for To Evaluate the Safety Profile of MVA85A/AERAS-485 in Bacillus Calmette-Guerin (BCG) -Vaccinated, HIV-negative Infants.

2. Secondary:

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 ]

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3. Secondary:

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 ]

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4. Secondary:

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 ]

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5. Secondary:

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 ]

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Measure Type	Secondary
Measure Title	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.
Measure Description	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.
Time Frame	28 days post-vaccination

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pre-specified population subset

Reporting Groups

	Description
Investigational Vaccine	MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests.
Control Group	Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.

Measured Values

	Investigational Vaccine	Control Group
Participants Analyzed; [Units: Participants]	17	19
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.; [Units: Percentage of cytokine expressing cells]; Median (95% Confidence Interval)
Percent IL2/IFN-gamma/TNF expressing CD4 cells	0.030; (0.022 to 0.079)	0.001; (0.000 to 0.001)
Percent IL2/IFN-gamma/ TNF expressing CD8 cells	0.000; (0.000 to 0.000)	0.000; (0.000 to 0.000)

No statistical analysis provided for 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.

6. Secondary:

To Discover Correlates of Protection From Tuberculosis in Infants Vaccinated With MVA85A/AERAS-485. [ Time Frame: 15 to 36 months post-vaccination ]

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7. Secondary:

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 ]

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  Serious Adverse Events

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  Other Adverse Events

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  Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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