A Study of MVA85A in Healthy Infants

• Sponsor: Aeras (Other)
• Overall Status: Completed
• CT.gov ID: NCT00953927
• Collaborator: University of Oxford (Other), University of Cape Town (Other)
• Enrollment: 2,797
• Locations: 3
• Arms: 2
• Patients Per Site: 932.3

Study Details

Study Description

Brief Summary

This was a Phase II double-blinded randomized controlled evaluation of safety, immunogenicity and efficacy of MVA85A/AERAS-485 in Bacillus Calmette-Guérin (BCG) vaccinated infants without tuberculosis or HIV infection. This study planned to enroll 2784 infants (126 to 182 days of age) who received study vaccine or control and were followed for 15 - 36 months. The study was conducted at a single site in South Africa.

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis	Biological: MVA85A/AERAS-485; Biological: Candida Skin Test Antigen	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2797 participants
• 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
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Investigational Vaccine MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests.	Biological: MVA85A/AERAS-485; Attenuated virus MVA vector with insertion. Single dose vaccine, 1 x 10^8 pfu.; Other Names: 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.; Other Names: Candin(R) Manufactured by Allermed Laboratories of USA.

Outcome Measures

Primary Outcome Measures

1. To Evaluate the Safety Profile of MVA85A/AERAS-485 in Bacillus Calmette-Guerin (BCG) -Vaccinated, HIV-negative Infants. [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.

Secondary Outcome Measures

1. 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. [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.

2. 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. [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.

3. 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. [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.

4. 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. [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.

5. To Discover Correlates of Protection From Tuberculosis in Infants Vaccinated With MVA85A/AERAS-485. [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.

6. 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. [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 126 Days to 182 Days
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Age of 126 through 182 days on the day of randomization (Study Day 0)

2. Written informed consent obtained from the parents/guardian

3. Weight: by chart >3rd percentile on Study Day 0 or, if < 3rd percentile, infant has shown a stable growth pattern

4. BCG vaccination within 7 days of birth

5. Generally good health confirmed by medical history and physical examination within 35 days prior to Study Day 0

6. Must have received age-appropriate doses of pneumococcal vaccine as recommended by the South African Department of Health but no injection within 14 day prior to Study Day 0

7. Ability to complete follow-up period as required by the protocol

8. Completed simultaneous enrollment in the Aeras Vaccine Development Registry protocol

Exclusion Criteria:

1. Acute illness on Study Day 0

2. Fever >=37.5 degrees Celsius on Study Day 0

3. Evidence of significant active infection on Study Day 0

4. Received a Expanded Program of Immunization (EPI) within 14 days prior to Study Day 0

5. Historical or virological evidence of individual or maternal human immunodeficiency virus (HIV-1) infection

6. History of allergic disease or reactions likely to be exacerbated by any component of the study vaccine

7. Previous medical history, or evidence, of an intercurrent illness that may compromise the safety of the infant in the study

8. Evidence of chronic hepatitis from any cause

9. History or evidence of any systemic disease on physical examination or any acute, chronic or intercurrent illness that, in the opinion of the investigator, may interfere with the evaluation of the safety or immunogenicity of the vaccine

10. History of or known tuberculosis or treatment for tuberculosis

11. Shared residence since birth with an individual with active tuberculosis or on anti-tuberculosis treatment for less than 2 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	South African Tuberculosis Vaccine Initiative (Satellite)	Ceres		South Africa	6835
2	South African Tuberculosis Vaccine Initiative (Satellite)	Robertson		South Africa	6705
3	South African Tuberculosis Vaccine Initiative (Headquarters)	Worcester		South Africa	6850

Sponsors and Collaborators

• Aeras
• University of Oxford
• University of Cape Town

Investigators

• 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

Study Documents (Full-Text)

None provided.

More Information

Publications

• Luabeya KK, Tameris MD, Geldenhuys HD, Mulenga H, Van Schalkwyk A, Hughes EJ, Toefey A, Scriba TJ, Hussey G, Mahomed H, McShane H, Landry B, Hanekom WA, Hatherill M. Risk of Disease After Isoniazid Preventive Therapy for Mycobacterium tuberculosis Exposure in Young HIV-uninfected Children. Pediatr Infect Dis J. 2015 Nov;34(11):1218-22. doi: 10.1097/INF.0000000000000874.
• Mulenga H, Tameris MD, Luabeya KK, Geldenhuys H, Scriba TJ, Hussey GD, Mahomed H, Landry BS, Hanekom WA, McShane H, Hatherill M. The Role of Clinical Symptoms in the Diagnosis of Intrathoracic Tuberculosis in Young Children. Pediatr Infect Dis J. 2015 Nov;34(11):1157-62. doi: 10.1097/INF.0000000000000847.
• Tameris M, McShane H, McClain JB, Landry B, Lockhart S, Luabeya AK, Geldenhuys H, Shea J, Hussey G, van der Merwe L, de Kock M, Scriba T, Walker R, Hanekom W, Hatherill M, Mahomed H. Lessons learnt from the first efficacy trial of a new infant tuberculosis vaccine since BCG. Tuberculosis (Edinb). 2013 Mar;93(2):143-9. doi: 10.1016/j.tube.2013.01.003. Epub 2013 Feb 12.
• Tameris MD, Hatherill M, Landry BS, Scriba TJ, Snowden MA, Lockhart S, Shea JE, McClain JB, Hussey GD, Hanekom WA, Mahomed H, McShane H; MVA85A 020 Trial Study Team. Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial. Lancet. 2013 Mar 23;381(9871):1021-8.

• Responsible Party: Aeras
• ClinicalTrials.gov Identifier: NCT00953927
• Other Study ID Numbers: C-020-485; Oxford TB020
• First Posted: Aug 6, 2009
• Last Update Posted: May 24, 2016
• Last Verified: Apr 1, 2016

• Additional relevant MeSH terms: Tuberculosis

Study Results

Participant Flow

Arm/Group Title	Investigational Vaccine	Control Group
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

Baseline Characteristics

Arm/Group Title	Investigational Vaccine	Control Group	Total
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 Participants	1399	1398	2797
Age (Count of Participants)
<=18 years	1399 100%	1398 100%	2797 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	.401 (.039)	.399 (.037)	.400 (.038)
Sex: Female, Male (Count of Participants)
Female	691 49.4%	682 48.8%	1373 49.1%
Male	708 50.6%	716 51.2%	1424 50.9%
Region of Enrollment (participants) [Number]
South Africa	1399 100%	1398 100%	2797 100%

Outcome Measures

1. Primary Outcome

Title	To Evaluate the Safety Profile of MVA85A/AERAS-485 in Bacillus Calmette-Guerin (BCG) -Vaccinated, HIV-negative Infants.
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.

Outcome Measure Data

Analysis Population Description

All subjects vaccinated.

Arm/Group Title	Investigational Vaccine	Control Group
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.
Measure Participants	1399	1396
Number (95% Confidence Interval) [percentage of all subjects vaccinated]	95.9	83.7

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.
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

Outcome Measure Data

Analysis Population Description

Per protocol population

Arm/Group Title	Investigational Vaccine	Control Group
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.
Measure Participants	1399	1395
Number [participants with a diagnosis of TB]	32 2.3%	39 2.8%

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.
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

Outcome Measure Data

Analysis Population Description

Pre-specified population subset

Arm/Group Title	Investigational Vaccine	Control Group
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.
Measure Participants	27	27
Percent cytokine expressing CD4 cells	0.012	0.003
Percent cytokine expressing CD8 cells	0.007	0.000

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.
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

Outcome Measure Data

Analysis Population Description

Pre-specified population subset

Arm/Group Title	Investigational Vaccine	Control Group
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.
Measure Participants	27	27
Median (95% Confidence Interval) [SFC per million PBMCs]	143.000	1.000

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.
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

Outcome Measure Data

Analysis Population Description

Pre-specified population subset

Arm/Group Title	Investigational Vaccine	Control Group
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.
Measure Participants	17	19
Percent IL2/IFN-gamma/TNF expressing CD4 cells	0.030	0.001
Percent IL2/IFN-gamma/ TNF expressing CD8 cells	0.000	0.000

6. Secondary Outcome

Title	To Discover Correlates of Protection From Tuberculosis in Infants Vaccinated With MVA85A/AERAS-485.
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Investigational Vaccine	Control Group
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.
Measure Participants	0	0

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.
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

Outcome Measure Data

Analysis Population Description

Per protocol population who were quantiferon negative at baseline.

Arm/Group Title	Investigational Vaccine	Control Group
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.
Measure Participants	1398	1394
Number [participants]	178 12.7%	171 12.2%

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Investigational Vaccine		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	257/1399 (18.4%)		258/1396 (18.5%)
Congenital, familial and genetic disorders
Cryptorchism	0/1399 (0%)	0	1/1396 (0.1%)	1
Phimosis	1/1399 (0.1%)	1	2/1396 (0.1%)	2
Gastrointestinal disorders
Abnormal faeces	0/1399 (0%)	0	1/1396 (0.1%)	1
Aphthous stomatitis	1/1399 (0.1%)	1	0/1396 (0%)	0
Constipation	1/1399 (0.1%)	1	1/1396 (0.1%)	1
Diarrhoea	1/1399 (0.1%)	1	0/1396 (0%)	0
Enteritis	1/1399 (0.1%)	1	0/1396 (0%)	0
Gastrooesophageal reflux disease	0/1399 (0%)	0	1/1396 (0.1%)	1
Intestinal functional disorder	0/1399 (0%)	0	1/1396 (0.1%)	1
Intussusception	0/1399 (0%)	0	2/1396 (0.1%)	2
Stomatitis	1/1399 (0.1%)	1	1/1396 (0.1%)	1
Vomiting	3/1399 (0.2%)	3	0/1396 (0%)	0
General disorders
Pyrexia	1/1399 (0.1%)	1	3/1396 (0.2%)	3
Sudden death	1/1399 (0.1%)	1	0/1396 (0%)	0
Hepatobiliary disorders
Hepatosplenomegaly	0/1399 (0%)	0	1/1396 (0.1%)	1
Infections and infestations
Abscess	1/1399 (0.1%)	1	3/1396 (0.2%)	3
Bronchiolitis	10/1399 (0.7%)	11	8/1396 (0.6%)	8
Bronchitis	0/1399 (0%)	0	2/1396 (0.1%)	2
Bronchopneumonia	27/1399 (1.9%)	29	28/1396 (2%)	30
Burn infection	0/1399 (0%)	0	1/1396 (0.1%)	1
Cellulitis	2/1399 (0.1%)	2	2/1396 (0.1%)	2
Croup infectious	8/1399 (0.6%)	8	11/1396 (0.8%)	12
Dysentery	1/1399 (0.1%)	1	1/1396 (0.1%)	1
Empyema	1/1399 (0.1%)	1	0/1396 (0%)	0
Escherichia urinary tract infection	3/1399 (0.2%)	3	0/1396 (0%)	0
Gastroenteritis	91/1399 (6.5%)	101	88/1396 (6.3%)	94
Hepatitis A	0/1399 (0%)	0	1/1396 (0.1%)	1
Impetigo	2/1399 (0.1%)	2	2/1396 (0.1%)	2
Liver abscess	0/1399 (0%)	0	1/1396 (0.1%)	1
Lobar pneumonia	0/1399 (0%)	0	2/1396 (0.1%)	2
Lower respiratory tract infection	25/1399 (1.8%)	26	29/1396 (2.1%)	30
Lower respiratory tract infection viral	0/1399 (0%)	0	1/1396 (0.1%)	1
Measles	2/1399 (0.1%)	2	0/1396 (0%)	0
Meningitis	3/1399 (0.2%)	3	2/1396 (0.1%)	2
Meningitis bacterial	1/1399 (0.1%)	1	0/1396 (0%)	0
Meningitis tuberculous	0/1399 (0%)	0	1/1396 (0.1%)	1
Meningitis viral	1/1399 (0.1%)	1	0/1396 (0%)	0
Oral herpes	3/1399 (0.2%)	3	2/1396 (0.1%)	2
Pneumonia	31/1399 (2.2%)	35	25/1396 (1.8%)	27
Pneumonia measles	2/1399 (0.1%)	2	0/1396 (0%)	0
Pneumonia respiratory syncytial viral	0/1399 (0%)	0	1/1396 (0.1%)	1
Pneumonia viral	1/1399 (0.1%)	1	2/1396 (0.1%)	2
Pulmonary tuberculosis	6/1399 (0.4%)	6	5/1396 (0.4%)	5
Respiratory tract infection	6/1399 (0.4%)	6	10/1396 (0.7%)	10
Sepsis	3/1399 (0.2%)	3	0/1396 (0%)	0
Subcutaneous abscess	1/1399 (0.1%)	1	0/1396 (0%)	0
Tonsillitis	2/1399 (0.1%)	2	3/1396 (0.2%)	3
Tuberculosis	5/1399 (0.4%)	5	5/1396 (0.4%)	5
Upper respiratory tract infection	5/1399 (0.4%)	5	3/1396 (0.2%)	3
Urinary tract infection	8/1399 (0.6%)	8	4/1396 (0.3%)	4
Varicella	1/1399 (0.1%)	1	1/1396 (0.1%)	1
Injury, poisoning and procedural complications
Accidental drug intake by child	1/1399 (0.1%)	1	0/1396 (0%)	0
Accidental exposure	0/1399 (0%)	0	3/1396 (0.2%)	4
Burns third degree	0/1399 (0%)	0	1/1396 (0.1%)	1
Concussion	1/1399 (0.1%)	1	1/1396 (0.1%)	1
Excoriation	0/1399 (0%)	0	1/1396 (0.1%)	1
Eye injury	0/1399 (0%)	0	1/1396 (0.1%)	1
Femur fracture	2/1399 (0.1%)	2	4/1396 (0.3%)	4
Head injury	0/1399 (0%)	0	1/1396 (0.1%)	1
Injury	0/1399 (0%)	0	2/1396 (0.1%)	2
Near drowning	1/1399 (0.1%)	1	0/1396 (0%)	0
Pneumonitis chemical	1/1399 (0.1%)	1	0/1396 (0%)	0
Skin laceration	1/1399 (0.1%)	1	0/1396 (0%)	0
Thermal burn	7/1399 (0.5%)	7	10/1396 (0.7%)	10
Tibia fracture	1/1399 (0.1%)	1	0/1396 (0%)	0
Investigations
HIV test positive	0/1399 (0%)	0	1/1396 (0.1%)	1
Metabolism and nutrition disorders
Kwashiorkor	4/1399 (0.3%)	4	1/1396 (0.1%)	1
Malnutrition	2/1399 (0.1%)	2	0/1396 (0%)	0
Nervous system disorders
Altered state of consciousness	1/1399 (0.1%)	1	1/1396 (0.1%)	1
Cerebral infarction	1/1399 (0.1%)	1	0/1396 (0%)	0
Convulsion	2/1399 (0.1%)	2	1/1396 (0.1%)	1
Encephalitis	0/1399 (0%)	0	1/1396 (0.1%)	1
Febrile convulsion	7/1399 (0.5%)	7	12/1396 (0.9%)	12
Guillain-Barre syndrome	1/1399 (0.1%)	1	0/1396 (0%)	0
Reproductive system and breast disorders
Balanitis	1/1399 (0.1%)	1	0/1396 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/1399 (0%)	0	1/1396 (0.1%)	1
Apnoeic attack	0/1399 (0%)	0	1/1396 (0.1%)	1
Asphyxia	1/1399 (0.1%)	1	0/1396 (0%)	0
Asthma	3/1399 (0.2%)	4	3/1396 (0.2%)	3
Bronchospasm	1/1399 (0.1%)	1	2/1396 (0.1%)	2
Obstructive airways disorder	1/1399 (0.1%)	1	0/1396 (0%)	0
Pneumonitis	0/1399 (0%)	0	1/1396 (0.1%)	1
Sleep apnoea syndrome	1/1399 (0.1%)	1	0/1396 (0%)	0
Status asthmaticus	1/1399 (0.1%)	1	0/1396 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis	0/1399 (0%)	0	1/1396 (0.1%)	1
Eczema	1/1399 (0.1%)	1	1/1396 (0.1%)	1
Surgical and medical procedures
Finger amputation	1/1399 (0.1%)	1	0/1396 (0%)	0
Other (Not Including Serious) Adverse Events
	Investigational Vaccine		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1319/1399 (94.3%)		1064/1396 (76.2%)
Gastrointestinal disorders
Diarrhoea	259/1399 (18.5%)	308	216/1396 (15.5%)	245
Vomiting	191/1399 (13.7%)	240	157/1396 (11.2%)	199
General disorders
Injection site erythema	1121/1399 (80.1%)	1183	446/1396 (31.9%)	459
Injection site exfoliation	143/1399 (10.2%)	143	13/1396 (0.9%)	13
Injection site pain	363/1399 (25.9%)	421	154/1396 (11%)	175
Injection site swelling	1050/1399 (75.1%)	1146	267/1396 (19.1%)	273
Injection site warmth	473/1399 (33.8%)	561	222/1396 (15.9%)	279
Irritability	523/1399 (37.4%)	659	431/1396 (30.9%)	553
Pyrexia	372/1399 (26.6%)	449	271/1396 (19.4%)	323
Infections and infestations
Rhinitis	65/1399 (4.6%)	67	79/1396 (5.7%)	79
Upper respiratory tract infection	183/1399 (13.1%)	192	172/1396 (12.3%)	180
Metabolism and nutrition disorders
Hypophagia	321/1399 (22.9%)	389	285/1396 (20.4%)	357
Nervous system disorders
Hypersomnia	376/1399 (26.9%)	478	324/1396 (23.2%)	419
Somnolence	295/1399 (21.1%)	368	237/1396 (17%)	296
Psychiatric disorders
Insomnia	398/1399 (28.4%)	513	359/1396 (25.7%)	447

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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).