A Study of MVA85A in Healthy Infants

This study has been completed.
Sponsor:
Collaborators:
University of Oxford
University of Cape Town
Information provided by (Responsible Party):
Aeras
ClinicalTrials.gov Identifier:
NCT00953927
First received: July 31, 2009
Last updated: February 4, 2014
Last verified: February 2014
Results First Received: October 23, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, 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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

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  
Number of Participants  
[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.  
Safety Issue Yes  

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  
Number of 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 ]

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 ]

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 ]

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 ]

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

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 ]


  Serious Adverse Events


  Other Adverse Events
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Time Frame No text entered.
Additional Description Two subjects within the control group were randomized but did not receive control vaccination.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

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.

Other Adverse Events
    Investigational Vaccine     Control Group  
Total, other (not including serious) adverse events      
# participants affected / at risk     1319/1399     1064/1396  
Gastrointestinal disorders      
Diarrhoea      
# participants affected / at risk     259/1399 (18.51%)     216/1396 (15.47%)  
# events     308     245  
Vomiting      
# participants affected / at risk     191/1399 (13.65%)     157/1396 (11.25%)  
# events     240     199  
General disorders      
Injection site erythema      
# participants affected / at risk     1121/1399 (80.13%)     446/1396 (31.95%)  
# events     1183     459  
Injection site exfoliation      
# participants affected / at risk     143/1399 (10.22%)     13/1396 (0.93%)  
# events     143     13  
Injection site pain      
# participants affected / at risk     363/1399 (25.95%)     154/1396 (11.03%)  
# events     421     175  
Injection site swelling      
# participants affected / at risk     1050/1399 (75.05%)     267/1396 (19.13%)  
# events     1146     273  
Injection site warmth      
# participants affected / at risk     473/1399 (33.81%)     222/1396 (15.90%)  
# events     561     279  
Irritability      
# participants affected / at risk     523/1399 (37.38%)     431/1396 (30.87%)  
# events     659     553  
Pyrexia      
# participants affected / at risk     372/1399 (26.59%)     271/1396 (19.41%)  
# events     449     323  
Infections and infestations      
Rhinitis      
# participants affected / at risk     65/1399 (4.65%)     79/1396 (5.66%)  
# events     67     79  
Upper respiratory tract infection      
# participants affected / at risk     183/1399 (13.08%)     172/1396 (12.32%)  
# events     192     180  
Metabolism and nutrition disorders      
Hypophagia      
# participants affected / at risk     321/1399 (22.94%)     285/1396 (20.42%)  
# events     389     357  
Nervous system disorders      
Hypersomnia      
# participants affected / at risk     376/1399 (26.88%)     324/1396 (23.21%)  
# events     478     419  
Somnolence      
# participants affected / at risk     295/1399 (21.09%)     237/1396 (16.98%)  
# events     368     296  
Psychiatric disorders      
Insomnia      
# participants affected / at risk     398/1399 (28.45%)     359/1396 (25.72%)  
# events     513     447  



  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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