TuberculosisPhase 1/2NCT01198366
Study of AERAS-402 in Healthy Infants
A Phase 1/2 study testing AERAS-402 1.5 x 10^10 vp, AERAS-402 3.0 x 10^10 vp and AERAS-402 1.0 x 10^11 vp in people with Tuberculosis, run by Aeras at 7 sites in 3 countries.
Trial summary
AERAS-402 will be given to infants of at least 16 weeks of age who have already been vaccinated with BCG to determine if AERAS-402 will increase protection of infants to tuberculosis. Read more about this study
- Who is it for?
- Ages 112 to 182 daysHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- AERAS-402 1.5 x 10^10 vp, AERAS-402 3.0 x 10^10 vp and AERAS-402 1.0 x 10^11 vp
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 487 participants
- Where
- 7 sitesin 3 countries
- Study dates
- Sep 2010to Apr 2014
- Phase
- Phase 1/2
- 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 112 to 182 days
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Parent/legal guardian has completed the written informed consent process
- Is age greater than or equal to 112 days (16 weeks) and less than or equal 182 days (26 weeks) on Study Day 0
- Has general good health, confirmed by medical history and physical examination
- Is up to date on all Expanded Program of Immunization (EPI) immunizations for his/her age with a minimum of 14 days between the last EPI vaccination and administration of study vaccine on Study Day 0
- Has ability to complete follow-up period of 728 days as required by the protocol
- Parent/legal guardian is able and willing to stay in contact with the study site for the duration of the study and to provide updated contact information as necessary, and has no current plans to move from the study area for the duration of the study
- Has completed simultaneous enrollment in Aeras Vaccine Development Registry protocol
- Had BCG vaccination ≥ 3 months prior to randomization documented by medical card
Who cannot join
- Acute illness, evidence of any significant active infection or temperature >=37.5°C on the day of randomization
- Used immunosuppressive medication within 45 days before entry into the study (inhaled and topical corticosteroids are permitted)
- Received immunoglobulin or blood products within 45 days before entry into the study
- Ever received any investigational drug therapy or investigational vaccine
- History or laboratory evidence of individual immunodeficiency virus (HIV-1) infection
- History of allergic disease or reactions to any component of the study vaccine
Show all 13Show fewer
- Previous medical history that may compromise the safety of the participant in the study
- Evidence of a new acute illness that may compromise the safety of the participant in the study
- Inability to discontinue daily medications during the study
- History or evidence of any systemic disease on physical examination or any acute or chronic illness that may interfere with the evaluation of the safety or immunogenicity of the vaccine, e.g., including masses between the leg and abdomen (e.g., inguinal hernia or lymphadenopathy)
- History or evidence of active tuberculosis
- A positive QuantiFERON®-TB Gold In-Tube test
- A household contact with active TB disease
Trial locations and contacts
7 sites in 3 countries.
7 sites in 3 countries
Kenya3 sites
Boro Heath Center
Boro
KEMRI/CDC Research and Public Heath Collaboration
Kisumu, 40100
Siaya District Hospital
Siaya
South Africa3 sites
Univeristy of Cape Town
Cape Town, 7925
Perinatal HIV Research Unit (PHRU) Chris Hani Baragwanath Hospital
Soweto, 1864
SATVI: Worcester
Worcester, 6850
Mozambique1 site
CISM: Centro de Investigacao em Saude de Manhica
Manhiça, 1929
About this study
Official title: A Phase II, Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Safety and Immunogenicity of AERAS-402 in BCG-vaccinated, HIV-uninfected Infants Without Evidence of Tuberculosis
AERAS-402 will be given to infants of at least 16 weeks of age who have already been vaccinated with BCG to determine if AERAS-402 will increase protection of infants to tuberculosis.
Read the detailed description
The only currently available tuberculosis vaccine, bacillus Calmette-Guérin (BCG), is estimated to reduce the risk of tuberculosis (TB) in children by up to 70-80%, but protection is incomplete. Efforts to increase TB protection in children include new vaccines for primary immunizations as well as combinations of vaccines given as primary and boosting vaccinations.
AERAS 402 is a live recombinant serotype 35 replication deficient adenovirus vector expressing a fusion protein of three Mycobacterium tuberculosis (Mtb) antigens (Ag85A, Ag85B and TB10.4). It presents Mtb antigens in the setting of a new, live, replication-deficient adenovirus vaccine that may increase T cell-mediated immunity and thus protection from tuberculosis. AERAS-402 appears safe and immunogenic in adults. Since BCG-vaccinated infants are the population for which AERAS-402 might be indicated, AERAS-402 will be administered to infants of at least 16 weeks of age who have already been vaccinated with BCG. This is the first Phase II study of AERAS-402 in infants.
- Conditions
- Tuberculosis
- Being tested
- AERAS-402 1.5 x 10^10 vp, AERAS-402 3.0 x 10^10 vp, AERAS-402 1.0 x 10^11 vp, Placebo
- Keywords
- Tuberculosis, Vaccine, Immunogenicity, Prevention of Tuberculosis
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AERAS-402 1.5 x 10^10 vpBiological
AERAS-402 3.0 x 10^10 vpBiological
AERAS-402 1.0 x 10^11 vpBiological
PlaceboBiological
| Study group | Role | What they receive |
|---|---|---|
| Dose Finding Gr 1 placebo x 2 | Placebo comparator | Subjects received two doses (x2) of placebo (sterile buffer) on study days 0 and 28. Receives: Biological: Placebo |
| Dose Finding Gr 2 AERAS-402 (1.5 x 10^10 vp) x2 | Experimental | Subjects received two doses (x2) of AERAS-402 (1.5 x 10^10 vp) on study days 0 and 28. Receives: Biological: AERAS-402 1.5 x 10^10 vp |
| Dose Finding Gr 3 AERAS-402 (3.0 x 10^10 vp) x 2 | Experimental | Subjects received two doses (x2) of AERAS-402 (3.0 x 10^10 vp) on study days 0 and 28. Receives: Biological: AERAS-402 3.0 x 10^10 vp |
| Dose Finding Gr 4 AERAS-402 (1.0 x 10^11 vp) x 2 | Experimental | Subjects received two doses (x2) of AERAS-402 (1.0 x 10^11 vp) on study days 0 and 28. Receives: Biological: AERAS-402 1.0 x 10^11 vp |
| Expanded Safety Phase Gr 5 AERAS-402 (1.0 X 10^11 vp) x 3 | Experimental | Subjects received 3 doses (x3) of AERAS-402 (1.0 X 10^11 vp) on days 0, 28 and 280. Receives: Biological: AERAS-402 1.5 x 10^10 vp |
| Expanded Safety Phase Gr 5 Placebo x3 | Placebo comparator | Subjects received 3 doses (x3) of placebo (sterile buffer) on days 0, 28 and 280. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events Collected Per Subject
Adverse Events (AEs) are recorded for 28 days post vaccination Serious Adverse Events (SAEs) are recorded for the entire study period to assess the safety profile
Measured: Up to 24 months post vaccination
Secondary outcomes (4)
Percentage of Cells Expressing Various Cytokines Will be Measured by Intracellular Cytokine Staining (ICS) in All Subjects
To evaluate the immunogenicity of AERAS-402 compared to controls, flow cytometric ICS of CD4 and CD8 T cells producing any of three cytokines (IFN-γ, TNF-α, and/or IL-2) alone or in combination after stimulation with a peptide pool of mycobacterial peptides. Dimethylsulfoxide (DMSO) subtracted responses are presented.
Measured: 28 days post last vaccination
Interferon-gamma (IFN-gamma) Enzyme-linked Immunospot (ELISpot) Response: Spot Forming Units/10^6 PBMC According to ELISpot Assay
To evaluate the immunogenicity of AERAS-402 compared to controls. ELISpot assay of specific T cell responses after stimulation with a peptide pool of mycobacterial peptides. Values presented have been corrected for background readings.
Measured: 28 days post last vaccination
Antigen-specific Antibody Response - Mean Optical Density (Mean OD)
To evaluate the immunogenicity of AERAS-402 compared to controls by ELISA Assay for Antigen-specific Antibody Response. Median responses of individual Mean OD (absorbance at 450nm) by study group is presented. Higher OD values suggests the presence of antibody to each of the Mtb antigens (Ag85A, Ag85B and TB10.4).
Measured: 28 day post last vaccination
Percentage of Subjects Converting From a Negative QuantiFERON Test (QFT) to Positive QFT After Vaccination
To evaluate the proportion of on-study QuantiFERON conversions from negative to positive in infants that received AERAS-402 compared to controls. A QFT value of on >= 0.35IU/mL was considered positive for this study.
Measured: up to 24 months post vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2010 (estimated)
- Study startSep 2010
- Primary completionJan 2014
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 487 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aeras
- Sponsor type
- University, hospital or other
- Collaborators
- European and Developing Countries Clinical Trials Partnership (EDCTP)
- Responsible party
- Sponsor
- Investigators
- Robert Walker, Study director, Aeras
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01198366
- Sponsor's protocol ID
- C-029-402
- Status last verified
- Mar 2017
- First submitted
- 7 Sep 2010
- Last updated
- 8 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Tameris M, Hokey DA, Nduba V, Sacarlal J, Laher F, Kiringa G, Gondo K, Lazarus EM, Gray GE, Nachman S, Mahomed H, Downing K, Abel B, Scriba TJ, McClain JB, Pau MG, Hendriks J, Dheenadhayalan V, Ishmukhamedov S, Luabeya AK, Geldenhuys H, Shepherd B, Blatner G, Cardenas V, Walker R, Hanekom WA, Sadoff J, Douoguih M, Barker L, Hatherill M. A double-blind, randomised, placebo-controlled, dose-finding trial of the novel tuberculosis vaccine AERAS-402, an adenovirus-vectored fusion protein, in healthy, BCG-vaccinated infants. Vaccine. 2015 Jun 9;33(25):2944-54. doi: 10.1016/j.vaccine.2015.03.070. Epub 2015 Apr 28.
PubMed 25936724
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Safety and Immunogenicity of AERAS-402 in BCG-vaccinated, HIV-uninfected Infants Without Evidence of Tuberculosis
- ClinicalTrials.gov ID
- NCT01198366
- Acronym / sponsor ID
- C-029-402
- Conditions
- Tuberculosis
- Keywords
- Tuberculosis, Vaccine, Immunogenicity, Prevention of Tuberculosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 487 participants (actual)
- Lead sponsor
- AerasUniversity, hospital or other
- Collaborators
- European and Developing Countries Clinical Trials Partnership (EDCTP)
- Study start
- Sep 2010
- Primary completion
- Jan 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 10 Sep 2010 (estimated)
- Results
- Posted 4 Aug 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
AERAS-402 will be given to infants of at least 16 weeks of age who have already been vaccinated with BCG to determine if AERAS-402 will increase protection of infants to tuberculosis.
Detailed description
The only currently available tuberculosis vaccine, bacillus Calmette-Guérin (BCG), is estimated to reduce the risk of tuberculosis (TB) in children by up to 70-80%, but protection is incomplete. Efforts to increase TB protection in children include new vaccines for primary immunizations as well as combinations of vaccines given as primary and boosting vaccinations.
AERAS 402 is a live recombinant serotype 35 replication deficient adenovirus vector expressing a fusion protein of three Mycobacterium tuberculosis (Mtb) antigens (Ag85A, Ag85B and TB10.4). It presents Mtb antigens in the setting of a new, live, replication-deficient adenovirus vaccine that may increase T cell-mediated immunity and thus protection from tuberculosis. AERAS-402 appears safe and immunogenic in adults. Since BCG-vaccinated infants are the population for which AERAS-402 might be indicated, AERAS-402 will be administered to infants of at least 16 weeks of age who have already been vaccinated with BCG. This is the first Phase II study of AERAS-402 in infants.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Dose Finding Gr 1 placebo x 2 | Placebo comparator | Biological: PlaceboSubjects received two doses (x2) of placebo (sterile buffer) on study days 0 and 28. |
| Dose Finding Gr 2 AERAS-402 (1.5 x 10^10 vp) x2 | Experimental | Biological: AERAS-402 1.5 x 10^10 vpSubjects received two doses (x2) of AERAS-402 (1.5 x 10^10 vp) on study days 0 and 28. |
| Dose Finding Gr 3 AERAS-402 (3.0 x 10^10 vp) x 2 | Experimental | Biological: AERAS-402 3.0 x 10^10 vpSubjects received two doses (x2) of AERAS-402 (3.0 x 10^10 vp) on study days 0 and 28. |
| Dose Finding Gr 4 AERAS-402 (1.0 x 10^11 vp) x 2 | Experimental | Biological: AERAS-402 1.0 x 10^11 vpSubjects received two doses (x2) of AERAS-402 (1.0 x 10^11 vp) on study days 0 and 28. |
| Expanded Safety Phase Gr 5 AERAS-402 (1.0 X 10^11 vp) x 3 | Experimental | Biological: AERAS-402 1.5 x 10^10 vpSubjects received 3 doses (x3) of AERAS-402 (1.0 X 10^11 vp) on days 0, 28 and 280. |
| Expanded Safety Phase Gr 5 Placebo x3 | Placebo comparator | Biological: PlaceboSubjects received 3 doses (x3) of placebo (sterile buffer) on days 0, 28 and 280. |
Who may qualify
- Ages
- 112 to 182 days
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Parent/legal guardian has completed the written informed consent process
- Is age greater than or equal to 112 days (16 weeks) and less than or equal 182 days (26 weeks) on Study Day 0
- Has general good health, confirmed by medical history and physical examination
- Is up to date on all Expanded Program of Immunization (EPI) immunizations for his/her age with a minimum of 14 days between the last EPI vaccination and administration of study vaccine on Study Day 0
- Has ability to complete follow-up period of 728 days as required by the protocol
Key exclusion criteria (13 listed)
- Acute illness, evidence of any significant active infection or temperature >=37.5°C on the day of randomization
- Used immunosuppressive medication within 45 days before entry into the study (inhaled and topical corticosteroids are permitted)
- Received immunoglobulin or blood products within 45 days before entry into the study
- Ever received any investigational drug therapy or investigational vaccine
- History or laboratory evidence of individual immunodeficiency virus (HIV-1) infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AERAS-402 1.5 x 10^10 vp | Biological | Dose Finding Gr 2 AERAS-402 (1.5 x 10^10 vp) x2, Expanded Safety Phase Gr 5 AERAS-402 (1.0 X 10^11 vp) x 3 |
| AERAS-402 3.0 x 10^10 vp | Biological | Dose Finding Gr 3 AERAS-402 (3.0 x 10^10 vp) x 2 |
| AERAS-402 1.0 x 10^11 vp | Biological | Dose Finding Gr 4 AERAS-402 (1.0 x 10^11 vp) x 2 |
| Placebo | Biological | Dose Finding Gr 1 placebo x 2, Expanded Safety Phase Gr 5 Placebo x3 |
Primary outcome
Adverse Events Collected Per Subject
Time frame: Up to 24 months post vaccination
Adverse Events (AEs) are recorded for 28 days post vaccination Serious Adverse Events (SAEs) are recorded for the entire study period to assess the safety profile
4 secondary outcomes
Percentage of Cells Expressing Various Cytokines Will be Measured by Intracellular Cytokine Staining (ICS) in All Subjects
Time frame: 28 days post last vaccination
Interferon-gamma (IFN-gamma) Enzyme-linked Immunospot (ELISpot) Response: Spot Forming Units/10^6 PBMC According to ELISpot Assay
Time frame: 28 days post last vaccination
Antigen-specific Antibody Response - Mean Optical Density (Mean OD)
Time frame: 28 day post last vaccination
Percentage of Subjects Converting From a Negative QuantiFERON Test (QFT) to Positive QFT After Vaccination
Time frame: up to 24 months post vaccination
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25936724Tameris M, Hokey DA, Nduba V, Sacarlal J, Laher F, Kiringa G, Gondo K, Lazarus EM, Gray GE, Nachman S, Mahomed H, Downing K, Abel B, Scriba TJ, McClain JB, Pau MG, Hendriks J, Dheenadhayalan V, Ishmukhamedov S, Luabeya AK, Geldenhuys H, Shepherd B, Blatner G, Cardenas V, Walker R, Hanekom WA, Sadoff J, Douoguih M, Barker L, Hatherill M. A double-blind, randomised, placebo-controlled, dose-finding trial of the novel tuberculosis vaccine AERAS-402, an adenovirus-vectored fusion protein, in healthy, BCG-vaccinated infants. Vaccine. 2015 Jun 9;33(25):2944-54. doi: 10.1016/j.vaccine.2015.03.070. Epub 2015 Apr 28.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Walker study director
Aeras
7 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AERAS-402 1.5 x 10^10 vp, AERAS-402 3.0 x 10^10 vp and AERAS-402 1.0 x 10^11 vp in people with Tuberculosis, run by Aeras at 7 sites in 3 countries.
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 13 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 8 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Kenya, South Africa, Mozambique. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 4 Aug 2015). 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?
Adverse Events Collected Per Subject (time frame: Up to 24 months post vaccination). 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 NCT01198366, which also lists 1 linked publication.
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 8 May 2017.