Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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: April 25, 2016
Last verified: April 2016
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
  Hide Participant Flow

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
  Hide Baseline Characteristics

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
  Show All Outcome Measures

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. ]

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
  Hide Serious Adverse Events

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

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.

Serious Adverse Events
    Investigational Vaccine   Control Group
Total, serious adverse events     
# participants affected / at risk   257/1399 (18.37%)   258/1396 (18.48%) 
Congenital, familial and genetic disorders     
Cryptorchism     
# participants affected / at risk   0/1399 (0.00%)   1/1396 (0.07%) 
# events   0   1 
Phimosis     
# participants affected / at risk   1/1399 (0.07%)   2/1396 (0.14%) 
# events   1   2 
Gastrointestinal disorders     
Abnormal faeces     
# participants affected / at risk   0/1399 (0.00%)   1/1396 (0.07%) 
# events   0   1 
Aphthous stomatitis     
# participants affected / at risk   1/1399 (0.07%)   0/1396 (0.00%) 
# events   1   0 
Constipation     
# participants affected / at risk   1/1399 (0.07%)   1/1396 (0.07%) 
# events   1   1 
Diarrhoea     
# participants affected / at risk   1/1399 (0.07%)   0/1396 (0.00%) 
# events   1   0 
Enteritis     
# participants affected / at risk   1/1399 (0.07%)   0/1396 (0.00%) 
# events   1   0 
Gastrooesophageal reflux disease     
# participants affected / at risk   0/1399 (0.00%)   1/1396 (0.07%) 
# events   0   1 
Intestinal functional disorder     
# participants affected / at risk   0/1399 (0.00%)   1/1396 (0.07%) 
# events   0   1 
Intussusception     
# participants affected / at risk   0/1399 (0.00%)   2/1396 (0.14%) 
# events   0   2 
Stomatitis     
# participants affected / at risk   1/1399 (0.07%)   1/1396 (0.07%) 
# events   1   1 
Vomiting     
# participants affected / at risk   3/1399 (0.21%)   0/1396 (0.00%) 
# events   3   0 
General disorders     
Pyrexia     
# participants affected / at risk   1/1399 (0.07%)   3/1396 (0.21%) 
# events   1   3 
Sudden death     
# participants affected / at risk   1/1399 (0.07%)   0/1396 (0.00%) 
# events   1   0 
Hepatobiliary disorders     
Hepatosplenomegaly     
# participants affected / at risk   0/1399 (0.00%)   1/1396 (0.07%) 
# events   0   1 
Infections and infestations     
Abscess     
# participants affected / at risk   1/1399 (0.07%)   3/1396 (0.21%) 
# events   1   3 
Bronchiolitis     
# participants affected / at risk   10/1399 (0.71%)   8/1396 (0.57%) 
# events   11   8 
Bronchitis     
# participants affected / at risk   0/1399 (0.00%)   2/1396 (0.14%) 
# events   0   2 
Bronchopneumonia     
# participants affected / at risk   27/1399 (1.93%)   28/1396 (2.01%) 
# events   29   30 
Burn infection     
# participants affected / at risk   0/1399 (0.00%)   1/1396 (0.07%) 
# events   0   1 
Cellulitis     
# participants affected / at risk   2/1399 (0.14%)   2/1396 (0.14%) 
# events   2   2 
Croup infectious     
# participants affected / at risk   8/1399 (0.57%)   11/1396 (0.79%) 
# events   8   12 
Dysentery     
# participants affected / at risk   1/1399 (0.07%)   1/1396 (0.07%) 
# events   1   1 
Empyema     
# participants affected / at risk   1/1399 (0.07%)   0/1396 (0.00%) 
# events   1   0 
Escherichia urinary tract infection     
# participants affected / at risk   3/1399 (0.21%)   0/1396 (0.00%) 
# events   3   0 
Gastroenteritis     
# participants affected / at risk   91/1399 (6.50%)   88/1396 (6.30%) 
# events   101   94 
Hepatitis A     
# participants affected / at risk   0/1399 (0.00%)   1/1396 (0.07%) 
# events   0   1 
Impetigo     
# participants affected / at risk   2/1399 (0.14%)   2/1396 (0.14%) 
# events   2   2 
Liver abscess     
# participants affected / at risk   0/1399 (0.00%)   1/1396 (0.07%) 
# events   0   1 
Lobar pneumonia     
# participants affected / at risk   0/1399 (0.00%)   2/1396 (0.14%) 
# events   0   2 
Lower respiratory tract infection     
# participants affected / at risk   25/1399 (1.79%)   29/1396 (2.08%) 
# events   26   30 
Lower respiratory tract infection viral     
# participants affected / at risk   0/1399 (0.00%)   1/1396 (0.07%) 
# events   0   1 
Measles     
# participants affected / at risk   2/1399 (0.14%)   0/1396 (0.00%) 
# events   2   0 
Meningitis     
# participants affected / at risk   3/1399 (0.21%)   2/1396 (0.14%) 
# events   3   2 
Meningitis bacterial     
# participants affected / at risk   1/1399 (0.07%)   0/1396 (0.00%) 
# events   1   0 
Meningitis tuberculous     
# participants affected / at risk   0/1399 (0.00%)   1/1396 (0.07%) 
# events   0   1 
Meningitis viral     
# participants affected / at risk   1/1399 (0.07%)   0/1396 (0.00%) 
# events   1   0 
Oral herpes     
# participants affected / at risk   3/1399 (0.21%)   2/1396 (0.14%) 
# events   3   2 
Pneumonia     
# participants affected / at risk   31/1399 (2.22%)   25/1396 (1.79%) 
# events   35   27 
Pneumonia measles     
# participants affected / at risk   2/1399 (0.14%)   0/1396 (0.00%) 
# events   2   0 
Pneumonia respiratory syncytial viral     
# participants affected / at risk   0/1399 (0.00%)   1/1396 (0.07%) 
# events   0   1 
Pneumonia viral     
# participants affected / at risk   1/1399 (0.07%)   2/1396 (0.14%) 
# events   1   2 
Pulmonary tuberculosis     
# participants affected / at risk   6/1399 (0.43%)   5/1396 (0.36%) 
# events   6   5 
Respiratory tract infection     
# participants affected / at risk   6/1399 (0.43%)   10/1396 (0.72%) 
# events   6   10 
Sepsis     
# participants affected / at risk   3/1399 (0.21%)   0/1396 (0.00%) 
# events   3   0 
Subcutaneous abscess     
# participants affected / at risk   1/1399 (0.07%)   0/1396 (0.00%) 
# events   1   0 
Tonsillitis     
# participants affected / at risk   2/1399 (0.14%)   3/1396 (0.21%) 
# events   2   3 
Tuberculosis     
# participants affected / at risk   5/1399 (0.36%)   5/1396 (0.36%) 
# events   5   5 
Upper respiratory tract infection     
# participants affected / at risk   5/1399 (0.36%)   3/1396 (0.21%) 
# events   5   3 
Urinary tract infection     
# participants affected / at risk   8/1399 (0.57%)   4/1396 (0.29%) 
# events   8   4 
Varicella     
# participants affected / at risk   1/1399 (0.07%)   1/1396 (0.07%) 
# events   1   1 
Injury, poisoning and procedural complications     
Accidental drug intake by child     
# participants affected / at risk   1/1399 (0.07%)   0/1396 (0.00%) 
# events   1   0 
Accidental exposure     
# participants affected / at risk   0/1399 (0.00%)   3/1396 (0.21%) 
# events   0   4 
Burns third degree     
# participants affected / at risk   0/1399 (0.00%)   1/1396 (0.07%) 
# events   0   1 
Concussion     
# participants affected / at risk   1/1399 (0.07%)   1/1396 (0.07%) 
# events   1   1 
Excoriation     
# participants affected / at risk   0/1399 (0.00%)   1/1396 (0.07%) 
# events   0   1 
Eye injury     
# participants affected / at risk   0/1399 (0.00%)   1/1396 (0.07%) 
# events   0   1 
Femur fracture     
# participants affected / at risk   2/1399 (0.14%)   4/1396 (0.29%) 
# events   2   4 
Head injury     
# participants affected / at risk   0/1399 (0.00%)   1/1396 (0.07%) 
# events   0   1 
Injury     
# participants affected / at risk   0/1399 (0.00%)   2/1396 (0.14%) 
# events   0   2 
Near drowning     
# participants affected / at risk   1/1399 (0.07%)   0/1396 (0.00%) 
# events   1   0 
Pneumonitis chemical     
# participants affected / at risk   1/1399 (0.07%)   0/1396 (0.00%) 
# events   1   0 
Skin laceration     
# participants affected / at risk   1/1399 (0.07%)   0/1396 (0.00%) 
# events   1   0 
Thermal burn     
# participants affected / at risk   7/1399 (0.50%)   10/1396 (0.72%) 
# events   7   10 
Tibia fracture     
# participants affected / at risk   1/1399 (0.07%)   0/1396 (0.00%) 
# events   1   0 
Investigations     
HIV test positive     
# participants affected / at risk   0/1399 (0.00%)   1/1396 (0.07%) 
# events   0   1 
Metabolism and nutrition disorders     
Kwashiorkor     
# participants affected / at risk   4/1399 (0.29%)   1/1396 (0.07%) 
# events   4   1 
Malnutrition     
# participants affected / at risk   2/1399 (0.14%)   0/1396 (0.00%) 
# events   2   0 
Nervous system disorders     
Altered state of consciousness     
# participants affected / at risk   1/1399 (0.07%)   1/1396 (0.07%) 
# events   1   1 
Cerebral infarction     
# participants affected / at risk   1/1399 (0.07%)   0/1396 (0.00%) 
# events   1   0 
Convulsion     
# participants affected / at risk   2/1399 (0.14%)   1/1396 (0.07%) 
# events   2   1 
Encephalitis     
# participants affected / at risk   0/1399 (0.00%)   1/1396 (0.07%) 
# events   0   1 
Febrile convulsion     
# participants affected / at risk   7/1399 (0.50%)   12/1396 (0.86%) 
# events   7   12 
Guillain-Barre syndrome     
# participants affected / at risk   1/1399 (0.07%)   0/1396 (0.00%) 
# events   1   0 
Reproductive system and breast disorders     
Balanitis     
# participants affected / at risk   1/1399 (0.07%)   0/1396 (0.00%) 
# events   1   0 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome     
# participants affected / at risk   0/1399 (0.00%)   1/1396 (0.07%) 
# events   0   1 
Apnoeic attack     
# participants affected / at risk   0/1399 (0.00%)   1/1396 (0.07%) 
# events   0   1 
Asphyxia     
# participants affected / at risk   1/1399 (0.07%)   0/1396 (0.00%) 
# events   1   0 
Asthma     
# participants affected / at risk   3/1399 (0.21%)   3/1396 (0.21%) 
# events   4   3 
Bronchospasm     
# participants affected / at risk   1/1399 (0.07%)   2/1396 (0.14%) 
# events   1   2 
Obstructive airways disorder     
# participants affected / at risk   1/1399 (0.07%)   0/1396 (0.00%) 
# events   1   0 
Pneumonitis     
# participants affected / at risk   0/1399 (0.00%)   1/1396 (0.07%) 
# events   0   1 
Sleep apnoea syndrome     
# participants affected / at risk   1/1399 (0.07%)   0/1396 (0.00%) 
# events   1   0 
Status asthmaticus     
# participants affected / at risk   1/1399 (0.07%)   0/1396 (0.00%) 
# events   1   0 
Skin and subcutaneous tissue disorders     
Dermatitis     
# participants affected / at risk   0/1399 (0.00%)   1/1396 (0.07%) 
# events   0   1 
Eczema     
# participants affected / at risk   1/1399 (0.07%)   1/1396 (0.07%) 
# events   1   1 
Surgical and medical procedures     
Finger amputation     
# participants affected / at risk   1/1399 (0.07%)   0/1396 (0.00%) 
# events   1   0 




  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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
No text entered.


  More Information