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A Study of MVA85A in Healthy Infants

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ClinicalTrials.gov Identifier: NCT00953927
Recruitment Status : Completed
First Posted : August 6, 2009
Results First Posted : December 12, 2013
Last Update Posted : May 24, 2016
Sponsor:
Collaborators:
University of Oxford
University of Cape Town
Information provided by (Responsible Party):
Aeras

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
Enrollment 2797

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Investigational Vaccine Control Group
Hide Arm/Group Description MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests. Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.
Period Title: Overall Study
Started 1399 1398
Completed 1294 1303
Not Completed 105 95
Reason Not Completed
Lost to Follow-up             61             65
Withdrawal by Subject             36             25
Death             7             4
Other study discontinuation             1             1
Arm/Group Title Investigational Vaccine Control Group Total
Hide Arm/Group Description MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests. Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests. Total of all reporting groups
Overall Number of Baseline Participants 1399 1398 2797
Hide Baseline Analysis Population Description
Intent to treat population
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1399 participants 1398 participants 2797 participants
<=18 years
1399
 100.0%
1398
 100.0%
2797
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1399 participants 1398 participants 2797 participants
.401  (.039) .399  (.037) .400  (.038)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1399 participants 1398 participants 2797 participants
Female
691
  49.4%
682
  48.8%
1373
  49.1%
Male
708
  50.6%
716
  51.2%
1424
  50.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
South Africa Number Analyzed 1399 participants 1398 participants 2797 participants
1399 1398 2797
1.Primary Outcome
Title To Evaluate the Safety Profile of MVA85A/AERAS-485 in Bacillus Calmette-Guerin (BCG) -Vaccinated, HIV-negative Infants.
Hide 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects vaccinated.
Arm/Group Title Investigational Vaccine Control Group
Hide Arm/Group Description:
MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests.
Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.
Overall Number of Participants Analyzed 1399 1396
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of all subjects vaccinated
95.9
(94.7 to 96.8)
83.7
(81.7 to 85.6)
2.Secondary Outcome
Title 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.
Hide Description 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.
Time Frame 15 to 36 months post-vaccination
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Hide Analysis Population Description
Per protocol population
Arm/Group Title Investigational Vaccine Control Group
Hide Arm/Group Description:
MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests.
Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.
Overall Number of Participants Analyzed 1399 1395
Measure Type: Number
Unit of Measure: participants with a diagnosis of TB
32 39
3.Secondary Outcome
Title 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.
Hide Description 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.
Time Frame 28 days post-vaccination
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Hide Analysis Population Description
Pre-specified population subset
Arm/Group Title Investigational Vaccine Control Group
Hide Arm/Group Description:
MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests.
Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.
Overall Number of Participants Analyzed 27 27
Median (95% Confidence Interval)
Unit of Measure: percentage of cytokine expressing cells
Percent cytokine expressing CD4 cells
0.012
(0.003 to 0.038)
0.003
(0.000 to 0.011)
Percent cytokine expressing CD8 cells
0.007
(0.000 to 0.011)
0.000
(0.000 to 0.010)
4.Secondary Outcome
Title 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.
Hide Description 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.
Time Frame 7 days post-vaccination
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Hide Analysis Population Description
Pre-specified population subset
Arm/Group Title Investigational Vaccine Control Group
Hide Arm/Group Description:
MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests.
Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.
Overall Number of Participants Analyzed 27 27
Median (95% Confidence Interval)
Unit of Measure: SFC per million PBMCs
143.000
(107.000 to 295.350)
1.000
(0.000 to 2.000)
5.Secondary Outcome
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.
Hide 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
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Hide Analysis Population Description
Pre-specified population subset
Arm/Group Title Investigational Vaccine Control Group
Hide Arm/Group Description:
MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests.
Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.
Overall Number of Participants Analyzed 17 19
Median (95% Confidence Interval)
Unit of Measure: percentage of cytokine expressing cells
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)
6.Secondary Outcome
Title To Discover Correlates of Protection From Tuberculosis in Infants Vaccinated With MVA85A/AERAS-485.
Hide Description 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.
Time Frame 15 to 36 months post-vaccination
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Investigational Vaccine Control Group
Hide Arm/Group Description:
MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests.
Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title 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.
Hide Description The number (percentage) of infants with QuantiFERON conversions at any time on the study were summarized by treatment group.
Time Frame 15 to 36 months post-vaccination
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Hide Analysis Population Description
Per protocol population who were quantiferon negative at baseline.
Arm/Group Title Investigational Vaccine Control Group
Hide Arm/Group Description:
MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests.
Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.
Overall Number of Participants Analyzed 1398 1394
Measure Type: Number
Unit of Measure: participants
178 171
Time Frame [Not Specified]
Adverse Event Reporting Description Two subjects within the control group were randomized but did not receive control vaccination.
 
Arm/Group Title Investigational Vaccine Control Group
Hide Arm/Group Description MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests. Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.
All-Cause Mortality
Investigational Vaccine Control Group
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Investigational Vaccine Control Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   257/1399 (18.37%)      258/1396 (18.48%)    
Congenital, familial and genetic disorders     
Cryptorchism  0/1399 (0.00%)  0 1/1396 (0.07%)  1
Phimosis  1/1399 (0.07%)  1 2/1396 (0.14%)  2
Gastrointestinal disorders     
Abnormal faeces  0/1399 (0.00%)  0 1/1396 (0.07%)  1
Aphthous stomatitis  1/1399 (0.07%)  1 0/1396 (0.00%)  0
Constipation  1/1399 (0.07%)  1 1/1396 (0.07%)  1
Diarrhoea  1/1399 (0.07%)  1 0/1396 (0.00%)  0
Enteritis  1/1399 (0.07%)  1 0/1396 (0.00%)  0
Gastrooesophageal reflux disease  0/1399 (0.00%)  0 1/1396 (0.07%)  1
Intestinal functional disorder  0/1399 (0.00%)  0 1/1396 (0.07%)  1
Intussusception  0/1399 (0.00%)  0 2/1396 (0.14%)  2
Stomatitis  1/1399 (0.07%)  1 1/1396 (0.07%)  1
Vomiting  3/1399 (0.21%)  3 0/1396 (0.00%)  0
General disorders     
Pyrexia  1/1399 (0.07%)  1 3/1396 (0.21%)  3
Sudden death  1/1399 (0.07%)  1 0/1396 (0.00%)  0
Hepatobiliary disorders     
Hepatosplenomegaly  0/1399 (0.00%)  0 1/1396 (0.07%)  1
Infections and infestations     
Abscess  1/1399 (0.07%)  1 3/1396 (0.21%)  3
Bronchiolitis  10/1399 (0.71%)  11 8/1396 (0.57%)  8
Bronchitis  0/1399 (0.00%)  0 2/1396 (0.14%)  2
Bronchopneumonia  27/1399 (1.93%)  29 28/1396 (2.01%)  30
Burn infection  0/1399 (0.00%)  0 1/1396 (0.07%)  1
Cellulitis  2/1399 (0.14%)  2 2/1396 (0.14%)  2
Croup infectious  8/1399 (0.57%)  8 11/1396 (0.79%)  12
Dysentery  1/1399 (0.07%)  1 1/1396 (0.07%)  1
Empyema  1/1399 (0.07%)  1 0/1396 (0.00%)  0
Escherichia urinary tract infection  3/1399 (0.21%)  3 0/1396 (0.00%)  0
Gastroenteritis  91/1399 (6.50%)  101 88/1396 (6.30%)  94
Hepatitis A  0/1399 (0.00%)  0 1/1396 (0.07%)  1
Impetigo  2/1399 (0.14%)  2 2/1396 (0.14%)  2
Liver abscess  0/1399 (0.00%)  0 1/1396 (0.07%)  1
Lobar pneumonia  0/1399 (0.00%)  0 2/1396 (0.14%)  2
Lower respiratory tract infection  25/1399 (1.79%)  26 29/1396 (2.08%)  30
Lower respiratory tract infection viral  0/1399 (0.00%)  0 1/1396 (0.07%)  1
Measles  2/1399 (0.14%)  2 0/1396 (0.00%)  0
Meningitis  3/1399 (0.21%)  3 2/1396 (0.14%)  2
Meningitis bacterial  1/1399 (0.07%)  1 0/1396 (0.00%)  0
Meningitis tuberculous  0/1399 (0.00%)  0 1/1396 (0.07%)  1
Meningitis viral  1/1399 (0.07%)  1 0/1396 (0.00%)  0
Oral herpes  3/1399 (0.21%)  3 2/1396 (0.14%)  2
Pneumonia  31/1399 (2.22%)  35 25/1396 (1.79%)  27
Pneumonia measles  2/1399 (0.14%)  2 0/1396 (0.00%)  0
Pneumonia respiratory syncytial viral  0/1399 (0.00%)  0 1/1396 (0.07%)  1
Pneumonia viral  1/1399 (0.07%)  1 2/1396 (0.14%)  2
Pulmonary tuberculosis  6/1399 (0.43%)  6 5/1396 (0.36%)  5
Respiratory tract infection  6/1399 (0.43%)  6 10/1396 (0.72%)  10
Sepsis  3/1399 (0.21%)  3 0/1396 (0.00%)  0
Subcutaneous abscess  1/1399 (0.07%)  1 0/1396 (0.00%)  0
Tonsillitis  2/1399 (0.14%)  2 3/1396 (0.21%)  3
Tuberculosis  5/1399 (0.36%)  5 5/1396 (0.36%)  5
Upper respiratory tract infection  5/1399 (0.36%)  5 3/1396 (0.21%)  3
Urinary tract infection  8/1399 (0.57%)  8 4/1396 (0.29%)  4
Varicella  1/1399 (0.07%)  1 1/1396 (0.07%)  1
Injury, poisoning and procedural complications     
Accidental drug intake by child  1/1399 (0.07%)  1 0/1396 (0.00%)  0
Accidental exposure  0/1399 (0.00%)  0 3/1396 (0.21%)  4
Burns third degree  0/1399 (0.00%)  0 1/1396 (0.07%)  1
Concussion  1/1399 (0.07%)  1 1/1396 (0.07%)  1
Excoriation  0/1399 (0.00%)  0 1/1396 (0.07%)  1
Eye injury  0/1399 (0.00%)  0 1/1396 (0.07%)  1
Femur fracture  2/1399 (0.14%)  2 4/1396 (0.29%)  4
Head injury  0/1399 (0.00%)  0 1/1396 (0.07%)  1
Injury  0/1399 (0.00%)  0 2/1396 (0.14%)  2
Near drowning  1/1399 (0.07%)  1 0/1396 (0.00%)  0
Pneumonitis chemical  1/1399 (0.07%)  1 0/1396 (0.00%)  0
Skin laceration  1/1399 (0.07%)  1 0/1396 (0.00%)  0
Thermal burn  7/1399 (0.50%)  7 10/1396 (0.72%)  10
Tibia fracture  1/1399 (0.07%)  1 0/1396 (0.00%)  0
Investigations     
HIV test positive  0/1399 (0.00%)  0 1/1396 (0.07%)  1
Metabolism and nutrition disorders     
Kwashiorkor  4/1399 (0.29%)  4 1/1396 (0.07%)  1
Malnutrition  2/1399 (0.14%)  2 0/1396 (0.00%)  0
Nervous system disorders     
Altered state of consciousness  1/1399 (0.07%)  1 1/1396 (0.07%)  1
Cerebral infarction  1/1399 (0.07%)  1 0/1396 (0.00%)  0
Convulsion  2/1399 (0.14%)  2 1/1396 (0.07%)  1
Encephalitis  0/1399 (0.00%)  0 1/1396 (0.07%)  1
Febrile convulsion  7/1399 (0.50%)  7 12/1396 (0.86%)  12
Guillain-Barre syndrome  1/1399 (0.07%)  1 0/1396 (0.00%)  0
Reproductive system and breast disorders     
Balanitis  1/1399 (0.07%)  1 0/1396 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  0/1399 (0.00%)  0 1/1396 (0.07%)  1
Apnoeic attack  0/1399 (0.00%)  0 1/1396 (0.07%)  1
Asphyxia  1/1399 (0.07%)  1 0/1396 (0.00%)  0
Asthma  3/1399 (0.21%)  4 3/1396 (0.21%)  3
Bronchospasm  1/1399 (0.07%)  1 2/1396 (0.14%)  2
Obstructive airways disorder  1/1399 (0.07%)  1 0/1396 (0.00%)  0
Pneumonitis  0/1399 (0.00%)  0 1/1396 (0.07%)  1
Sleep apnoea syndrome  1/1399 (0.07%)  1 0/1396 (0.00%)  0
Status asthmaticus  1/1399 (0.07%)  1 0/1396 (0.00%)  0
Skin and subcutaneous tissue disorders     
Dermatitis  0/1399 (0.00%)  0 1/1396 (0.07%)  1
Eczema  1/1399 (0.07%)  1 1/1396 (0.07%)  1
Surgical and medical procedures     
Finger amputation  1/1399 (0.07%)  1 0/1396 (0.00%)  0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Investigational Vaccine Control Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1319/1399 (94.28%)      1064/1396 (76.22%)    
Gastrointestinal disorders     
Diarrhoea  259/1399 (18.51%)  308 216/1396 (15.47%)  245
Vomiting  191/1399 (13.65%)  240 157/1396 (11.25%)  199
General disorders     
Injection site erythema  1121/1399 (80.13%)  1183 446/1396 (31.95%)  459
Injection site exfoliation  143/1399 (10.22%)  143 13/1396 (0.93%)  13
Injection site pain  363/1399 (25.95%)  421 154/1396 (11.03%)  175
Injection site swelling  1050/1399 (75.05%)  1146 267/1396 (19.13%)  273
Injection site warmth  473/1399 (33.81%)  561 222/1396 (15.90%)  279
Irritability  523/1399 (37.38%)  659 431/1396 (30.87%)  553
Pyrexia  372/1399 (26.59%)  449 271/1396 (19.41%)  323
Infections and infestations     
Rhinitis  65/1399 (4.65%)  67 79/1396 (5.66%)  79
Upper respiratory tract infection  183/1399 (13.08%)  192 172/1396 (12.32%)  180
Metabolism and nutrition disorders     
Hypophagia  321/1399 (22.94%)  389 285/1396 (20.42%)  357
Nervous system disorders     
Hypersomnia  376/1399 (26.88%)  478 324/1396 (23.21%)  419
Somnolence  295/1399 (21.09%)  368 237/1396 (16.98%)  296
Psychiatric disorders     
Insomnia  398/1399 (28.45%)  513 359/1396 (25.72%)  447
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The disclosure restrictions on the PI include submission of study data as an Investigator’s Brochure prior to publication, sponsor’s review (for a period of 60-180 days from the time submission to the sponsor for review), correction of factual errors, accommodation of reasonable comments of sponsor relating to regulatory submissions/interpretation of the Study Data (including assertion of safety and efficacy).
Results Point of Contact
Name/Title: Bernard Landry
Organization: Aeras
Phone: 301-547-2919
Responsible Party: Aeras
ClinicalTrials.gov Identifier: NCT00953927     History of Changes
Other Study ID Numbers: C-020-485
Oxford TB020 ( Other Identifier: The University of Oxford )
First Submitted: July 31, 2009
First Posted: August 6, 2009
Results First Submitted: October 23, 2013
Results First Posted: December 12, 2013
Last Update Posted: May 24, 2016