Trial Outcomes & Findings for A Study of MVA85A in Healthy Infants (NCT NCT00953927)

Last Updated: 2016-05-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

2797 participants

Primary outcome timeframe

AEs recorded 28 days post-vaccination; SAEs recorded for entire study period.

Results posted on

2016-05-24

Participant Flow

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	1399	1398
Overall Study COMPLETED	1294	1303
Overall Study NOT COMPLETED	105	95

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Lost to Follow-up	61	65
Overall Study Withdrawal by Subject	36	25
Overall Study Death	7	4
Overall Study Other study discontinuation	1	1

Baseline Characteristics

A Study of MVA85A in Healthy Infants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Investigational Vaccine n=1399 Participants MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests.	Control Group n=1398 Participants Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.	Total n=2797 Participants Total of all reporting groups
Age, Categorical <=18 years	1399 Participants n=5 Participants	1398 Participants n=7 Participants	2797 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	.401 years STANDARD_DEVIATION .039 • n=5 Participants	.399 years STANDARD_DEVIATION .037 • n=7 Participants	.400 years STANDARD_DEVIATION .038 • n=5 Participants
Sex: Female, Male Female	691 Participants n=5 Participants	682 Participants n=7 Participants	1373 Participants n=5 Participants
Sex: Female, Male Male	708 Participants n=5 Participants	716 Participants n=7 Participants	1424 Participants n=5 Participants
Region of Enrollment South Africa	1399 participants n=5 Participants	1398 participants n=7 Participants	2797 participants n=5 Participants

PRIMARY outcome

Timeframe: AEs recorded 28 days post-vaccination; SAEs recorded for entire study period.

Population: All subjects vaccinated.

Outcome measures

Outcome measures
Measure	Investigational Vaccine n=1399 Participants MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests.	Control Group n=1396 Participants Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.
To Evaluate the Safety Profile of MVA85A/AERAS-485 in Bacillus Calmette-Guerin (BCG) -Vaccinated, HIV-negative Infants.	95.9 percentage of all subjects vaccinated Interval 94.7 to 96.8	83.7 percentage of all subjects vaccinated Interval 81.7 to 85.6

SECONDARY outcome

Timeframe: 15 to 36 months post-vaccination

Population: Per protocol population

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.

Outcome measures

Outcome measures
Measure	Investigational Vaccine n=1399 Participants MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests.	Control Group n=1395 Participants Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.
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.	32 participants with a diagnosis of TB	39 participants with a diagnosis of TB

SECONDARY outcome

Timeframe: 28 days post-vaccination

Population: Pre-specified population subset

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.

Outcome measures

Outcome measures
Measure	Investigational Vaccine n=27 Participants MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests.	Control Group n=27 Participants Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.
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. Percent cytokine expressing CD4 cells	0.012 percentage of cytokine expressing cells Interval 0.003 to 0.038	0.003 percentage of cytokine expressing cells Interval 0.0 to 0.011
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. Percent cytokine expressing CD8 cells	0.007 percentage of cytokine expressing cells Interval 0.0 to 0.011	0.000 percentage of cytokine expressing cells Interval 0.0 to 0.01

SECONDARY outcome

Timeframe: 7 days post-vaccination

Population: Pre-specified population subset

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.

Outcome measures

Outcome measures
Measure	Investigational Vaccine n=27 Participants MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests.	Control Group n=27 Participants Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.
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.	143.000 SFC per million PBMCs Interval 107.0 to 295.35	1.000 SFC per million PBMCs Interval 0.0 to 2.0

SECONDARY outcome

Timeframe: 28 days post-vaccination

Population: Pre-specified population subset

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.

Outcome measures

Outcome measures
Measure	Investigational Vaccine n=17 Participants MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests.	Control Group n=19 Participants Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.
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. Percent IL2/IFN-gamma/TNF expressing CD4 cells	0.030 percentage of cytokine expressing cells Interval 0.022 to 0.079	0.001 percentage of cytokine expressing cells Interval 0.0 to 0.001
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. Percent IL2/IFN-gamma/ TNF expressing CD8 cells	0.000 percentage of cytokine expressing cells Interval 0.0 to 0.0	0.000 percentage of cytokine expressing cells Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 15 to 36 months post-vaccination

Population: Per protocol population who were quantiferon negative at baseline.

The number (percentage) of infants with QuantiFERON conversions at any time on the study were summarized by treatment group.

Outcome measures

Outcome measures
Measure	Investigational Vaccine n=1398 Participants MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests.	Control Group n=1394 Participants Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.
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.	178 participants	171 participants

Adverse Events

Investigational Vaccine

Serious events: 257 serious events

Other events: 1319 other events

Deaths: 0 deaths

Control Group

Serious events: 258 serious events

Other events: 1064 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Bernard Landry

Aeras

Phone: 301-547-2919

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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).
Publication restrictions are in place

Restriction type: OTHER

Measure	Investigational Vaccine n=1399 participants at risk MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests.	Control Group n=1396 participants at risk Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.
Infections and infestations Rhinitis	4.6% 65/1399 • Number of events 67 Two subjects within the control group were randomized but did not receive control vaccination.	5.7% 79/1396 • Number of events 79 Two subjects within the control group were randomized but did not receive control vaccination.
Infections and infestations Upper respiratory tract infection	13.1% 183/1399 • Number of events 192 Two subjects within the control group were randomized but did not receive control vaccination.	12.3% 172/1396 • Number of events 180 Two subjects within the control group were randomized but did not receive control vaccination.
Metabolism and nutrition disorders Hypophagia	22.9% 321/1399 • Number of events 389 Two subjects within the control group were randomized but did not receive control vaccination.	20.4% 285/1396 • Number of events 357 Two subjects within the control group were randomized but did not receive control vaccination.
Psychiatric disorders Insomnia	28.4% 398/1399 • Number of events 513 Two subjects within the control group were randomized but did not receive control vaccination.	25.7% 359/1396 • Number of events 447 Two subjects within the control group were randomized but did not receive control vaccination.
Nervous system disorders Hypersomnia	26.9% 376/1399 • Number of events 478 Two subjects within the control group were randomized but did not receive control vaccination.	23.2% 324/1396 • Number of events 419 Two subjects within the control group were randomized but did not receive control vaccination.
Nervous system disorders Somnolence	21.1% 295/1399 • Number of events 368 Two subjects within the control group were randomized but did not receive control vaccination.	17.0% 237/1396 • Number of events 296 Two subjects within the control group were randomized but did not receive control vaccination.
Gastrointestinal disorders Diarrhoea	18.5% 259/1399 • Number of events 308 Two subjects within the control group were randomized but did not receive control vaccination.	15.5% 216/1396 • Number of events 245 Two subjects within the control group were randomized but did not receive control vaccination.
Gastrointestinal disorders Vomiting	13.7% 191/1399 • Number of events 240 Two subjects within the control group were randomized but did not receive control vaccination.	11.2% 157/1396 • Number of events 199 Two subjects within the control group were randomized but did not receive control vaccination.
General disorders Injection site erythema	80.1% 1121/1399 • Number of events 1183 Two subjects within the control group were randomized but did not receive control vaccination.	31.9% 446/1396 • Number of events 459 Two subjects within the control group were randomized but did not receive control vaccination.
General disorders Injection site exfoliation	10.2% 143/1399 • Number of events 143 Two subjects within the control group were randomized but did not receive control vaccination.	0.93% 13/1396 • Number of events 13 Two subjects within the control group were randomized but did not receive control vaccination.
General disorders Injection site pain	25.9% 363/1399 • Number of events 421 Two subjects within the control group were randomized but did not receive control vaccination.	11.0% 154/1396 • Number of events 175 Two subjects within the control group were randomized but did not receive control vaccination.
General disorders Injection site swelling	75.1% 1050/1399 • Number of events 1146 Two subjects within the control group were randomized but did not receive control vaccination.	19.1% 267/1396 • Number of events 273 Two subjects within the control group were randomized but did not receive control vaccination.
General disorders Injection site warmth	33.8% 473/1399 • Number of events 561 Two subjects within the control group were randomized but did not receive control vaccination.	15.9% 222/1396 • Number of events 279 Two subjects within the control group were randomized but did not receive control vaccination.
General disorders Irritability	37.4% 523/1399 • Number of events 659 Two subjects within the control group were randomized but did not receive control vaccination.	30.9% 431/1396 • Number of events 553 Two subjects within the control group were randomized but did not receive control vaccination.
General disorders Pyrexia	26.6% 372/1399 • Number of events 449 Two subjects within the control group were randomized but did not receive control vaccination.	19.4% 271/1396 • Number of events 323 Two subjects within the control group were randomized but did not receive control vaccination.