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TuberculosisPhase 2NCT00953927

A Study of MVA85A in Healthy Infants

A Phase 2 study testing MVA85A/AERAS-485 and Candida Skin Test Antigen in people with Tuberculosis, run by Aeras at 3 sites in South Africa.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 126 to 182 daysHealthy volunteers can take part
Conditions the study is for
Tuberculosis
What is being tested?
MVA85A/AERAS-485 and Candida Skin Test Antigen
Type of treatment
Vaccines
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
2,797 participants
Where
3 sitesSouth Africa
Study dates
Jul 2009to Oct 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 126 to 182 days
  • All sexes
  • Healthy volunteers accepted
  • Child

Who may be able to join

  • Age of 126 through 182 days on the day of randomization (Study Day 0)
  • Written informed consent obtained from the parents/guardian
  • Weight: by chart >3rd percentile on Study Day 0 or, if < 3rd percentile, infant has shown a stable growth pattern
  • BCG vaccination within 7 days of birth
  • Generally good health confirmed by medical history and physical examination within 35 days prior to Study Day 0
  • 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
  • Ability to complete follow-up period as required by the protocol
  • Completed simultaneous enrollment in the Aeras Vaccine Development Registry protocol

Who cannot join

  • Acute illness on Study Day 0
  • Fever >=37.5 degrees Celsius on Study Day 0
  • Evidence of significant active infection on Study Day 0
  • Received a Expanded Program of Immunization (EPI) within 14 days prior to Study Day 0
  • Historical or virological evidence of individual or maternal human immunodeficiency virus (HIV-1) infection
  • History of allergic disease or reactions likely to be exacerbated by any component of the study vaccine
Show all 11Show fewer
  • Previous medical history, or evidence, of an intercurrent illness that may compromise the safety of the infant in the study
  • Evidence of chronic hepatitis from any cause
  • 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
  • History of or known tuberculosis or treatment for tuberculosis
  • Shared residence since birth with an individual with active tuberculosis or on anti-tuberculosis treatment for less than 2 months

Trial locations and contacts

3 sites in 1 country.

South Africa3 sites

  • South African Tuberculosis Vaccine Initiative (Satellite)

    Ceres, 6835

  • South African Tuberculosis Vaccine Initiative (Satellite)

    Robertson, 6705

  • South African Tuberculosis Vaccine Initiative (Headquarters)

    Worcester, 6850

Other trials in South Africa

About this study

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

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.

Read the 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.

Conditions
Tuberculosis
Being tested
MVA85A/AERAS-485, Candida Skin Test Antigen
Medical subject headings
Tuberculosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MVA85A/AERAS-485Biological

    Also called Manufactured by IDT of Germany.

    Attenuated virus MVA vector with insertion. Single dose vaccine, 1 x 10^8 pfu.

  • Candida Skin Test AntigenBiological

    Also called Candin(R), Manufactured by Allermed Laboratories of USA.

    1 test, administered once as a placebo control.

Study groups in NCT00953927
Study groupRoleWhat they receive
Investigational VaccineExperimentalMVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests.
Receives: Biological: MVA85A/AERAS-485
Control GroupPlacebo comparatorCandida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.
Receives: Biological: Candida Skin Test Antigen

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    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.

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

Secondary outcomes (6)

  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.

    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.

    Measured: 15 to 36 months post-vaccination

  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.

    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.

    Measured: 28 days post-vaccination

  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.

    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.

    Measured: 7 days post-vaccination

  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.

    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.

    Measured: 28 days post-vaccination

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

    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.

    Measured: 15 to 36 months post-vaccination

  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.

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

    Measured: 15 to 36 months post-vaccination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Aug 2009 (estimated)
  2. Study startJul 2009
  3. Primary completionOct 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
2,797 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00953927
Sponsor's protocol ID
C-020-485
Other IDs
Oxford TB020
Status last verified
Apr 2016
First submitted
31 Jul 2009
Last updated
24 May 2016
Data monitoring committee
Yes

Publications

  • 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. doi: 10.1016/S0140-6736(13)60177-4.

    PubMed 23391465

  • 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.

    PubMed 23410889

  • 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.

    PubMed 26226446

  • 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.

    PubMed 26252568

  • Muller J, Tanner R, Matsumiya M, Snowden MA, Landry B, Satti I, Harris SA, O'Shea MK, Stockdale L, Marsay L, Chomka A, Harrington-Kandt R, Thomas ZM, Naranbhai V, Stylianou E, Mbandi SK, Hatherill M, Hussey G, Mahomed H, Tameris M, McClain JB, Evans TG, Hanekom WA, Scriba TJ, McShane H, Fletcher HA. Cytomegalovirus infection is a risk factor for tuberculosis disease in infants. JCI Insight. 2019 Dec 5;4(23):e130090. doi: 10.1172/jci.insight.130090.

    PubMed 31697647

  • Bunyasi EW, Tameris M, Geldenhuys H, Schmidt BM, Luabeya AK, Mulenga H, Scriba TJ, Hanekom WA, Mahomed H, McShane H, Hatherill M. Evaluation of Xpert(R) MTB/RIF Assay in Induced Sputum and Gastric Lavage Samples from Young Children with Suspected Tuberculosis from the MVA85A TB Vaccine Trial. PLoS One. 2015 Nov 10;10(11):e0141623. doi: 10.1371/journal.pone.0141623. eCollection 2015.

    PubMed 26554383

  • Matsumiya M, Harris SA, Satti I, Stockdale L, Tanner R, O'Shea MK, Tameris M, Mahomed H, Hatherill M, Scriba TJ, Hanekom WA, McShane H, Fletcher HA. Inflammatory and myeloid-associated gene expression before and one day after infant vaccination with MVA85A correlates with induction of a T cell response. BMC Infect Dis. 2014 Jun 9;14:314. doi: 10.1186/1471-2334-14-314.

    PubMed 24912498

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MVA85A/AERAS-485 and Candida Skin Test Antigen in people with Tuberculosis, run by Aeras at 3 sites in South Africa.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 May 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Dec 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00953927, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2016.

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