TuberculosisPhase 2NCT01017536
Safety and Immunogenicity of AERAS-402 in HIV-infected, Bacillus Calmette-Guerin (BCG)-Vaccinated Adults
A Phase 2 study testing AERAS-402 in people with Tuberculosis and HIV Infections, run by Aeras at 1 site in South Africa.
Trial summary
This was a Phase II, randomized, double-blind, placebo-controlled trial conducted at 1 site in South Africa. A total of 26 subjects were randomized 1:1 to receive 2 doses of either AERAS-402 at 3 x 10^10 vp (N=13) or placebo (N=13) on Study Days 0 and 28. Read more about this study
- Who is it for?
- Ages 21 to 45 years
- Conditions the study is for
- Tuberculosis, HIV Infections
- What is being tested?
- AERAS-402
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteSouth Africa
- Study dates
- Dec 2009to May 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 21 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age 21 years through 45 years (i.e., subject had not yet reached his/her 46th birthday at day of randomization).
- Had completed the written informed consent process prior to undergoing any screening evaluations.
- Had BCG vaccination at least 5 years previously, documented by medical history or presence of scar.
- Females: Ability to avoid pregnancy for at least 6 months after receiving the last study vaccination: Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses if menopausal) must have avoided pregnancy from 28 days prior to administration of the study vaccine and must have agreed to avoid pregnancy through at least 6 months after receiving the last study vaccination. Acceptable methods of avoiding pregnancy included a sterile sexual partner, sexual abstinence (not engaging in sexual intercourse), or use of a combination of at least two forms of acceptable contraception: hormonal contraceptives (oral, injection, transdermal patch, or implant), vaginal ring, intrauterine device (IUD), and the use of a condom or a diaphragm; or the use of a condom or a diaphragm combined with spermicide.
- Was able to carry out activities of daily living independently.
- Had Body Mass Index (BMI) of at least 19 (wt./ht.2) by nomogram.
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- Had ability to complete follow-up period as required by the protocol.
- Was able and willing to commit to avoiding elective surgery for at least 6 months after receiving the last study vaccination.
- Was able and willing to stay in contact with the study site for the duration of the study.
- Had committed to simultaneous enrollment in Aeras Vaccine Development Registry Protocol.
- Had laboratory evidence of human immunodeficiency virus (HIV) infection, defined as a positive HIV-1 ELISA test plus a positive confirmatory test (e.g., a second HIV-1 ELISA, PCR, or rapid ELISA).
- Had four (4) (for Group 1) or three (3) (for Group 2)* CD4+ lymphocyte count tests, each performed at least four days apart within the 42-day screening period, with at least three (for Group 1) or two (for Group 2) CD4+ lymphocyte count results greater than 350 cells / mm3.
- Not currently receiving antiretroviral drugs.
- Committed to not participate in any other clinical trials during the first 12 months of participation in this study.
Who cannot join
- Acute illness.
- Fever ≥37.5°C.
- Significant symptomatic infection.
- Used immunosuppressive medication within 42 days prior to randomization (inhaled and topical corticosteroids were permitted).
- Received immunoglobulin or blood products within 42 days prior to randomization.
- Received any investigational drug therapy or vaccine within 182 days prior to randomization.
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- History of having received any adenovirus-vector-based vaccine.
- Medical history that may have compromised the evaluation of safety of the subject in the study (e.g., diabetes, seizure disorder, sickle cell disease).
- Pregnant or breastfeeding female, or intention to become pregnant during the study within 6 months after receiving the last study vaccination.
- Liver function tests >Grade 2 per the toxicity table.
- Currently receiving treatment for TB, or evidence of active TB disease based on history, physical examination, chest X-ray, or laboratory evaluation (INH prophylaxis was permitted).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Immunogenicity of AERAS-402 in HIV-infected, BCG-vaccinated Adults With CD4+ Lymphocyte Counts Greater Than 350 Cells/mm3
This was a Phase II, randomized, double-blind, placebo-controlled trial conducted at 1 site in South Africa. A total of 26 subjects were randomized 1:1 to receive 2 doses of either AERAS-402 at 3 x 10^10 vp (N=13) or placebo (N=13) on Study Days 0 and 28. Dose-escalation to a second group of 40 subjects was planned, but although no safety concerns were identified, the sponsor decided not to continue the study.
Read the detailed description
Further study details as provided by Aeras.
- Conditions
- Tuberculosis, HIV Infections
- Being tested
- AERAS-402, Placebo
- Keywords
- HIV, Tuberculosis, Vaccine
- Medical subject headings
- Tuberculosis, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AERAS-402Biological
AERAS-402 is a replication-deficient serotype 35 adenovirus containing DNA that expresses a fusion protein of three Mycobacterium tuberculosis (Mtb) antigens: 85A, 85B and TB10.4.
PlaceboBiological
Placebo was the identical buffer solution in which AERAS-402 is formulated.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Thirteen subjects received placebo vaccine that did not contain any AERAS-402. Receives: Biological: Placebo |
| Investigational Vaccine | Experimental | Thirteen subjects received active vaccine 3 x 10^10 vp AERAS-402. Receives: Biological: AERAS-402 |
What is being measured
The primary outcome is the main question the study is designed to answer.
CD4+ Lymphocyte Count
Assess the effect of AERAS-402 on the CD4+ lymphocyte count after 6 months in HIV-infected, BCG-vaccinated adult subjects with no evidence of active tuberculosis (TB disease) Change in cells/mm^3 pre-vaccination to Study Day 182
Measured: CD4+ counts from samples collected on Study days 0 and 182.
Secondary outcomes (2)
Change in HIV Viral Load in HIV-infected, BCG-vaccinated Adult Subjects Before and After Administration of AERAS-402 (From Day 1 to Day 182)
Measured: 6 months (day 182) post Study Day 0 vaccination.
Mtb-specific T Cell Response in HIV-infected BCG-vaccinated Adult Subjects With no Evidence of TB Disease
Intracellular cytokine staining (ICS) assay immune response was expressed as the percentage of CD4+ and 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 Ag85A, Ag85B, and TB10.4 peptide pools.
Measured: Study days 28 and 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2009 (estimated)
- Study startDec 2009
- Primary completionMar 2012
- Study completionMay 2012
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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aeras
- Sponsor type
- University, hospital or other
- Collaborators
- Crucell Holland BV
- Responsible party
- Sponsor
- Investigators
- Gavin Churchyard, MD, PhD, Principal investigator, Aurum InstituteBernard Landry, MPH, Study director, Aeras
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01017536
- Sponsor's protocol ID
- C-017-402
- Status last verified
- Jul 2016
- First submitted
- 18 Nov 2009
- Last updated
- 9 Sep 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Churchyard GJ, Snowden MA, Hokey D, Dheenadhayalan V, McClain JB, Douoguih M, Pau MG, Sadoff J, Landry B. The safety and immunogenicity of an adenovirus type 35-vectored TB vaccine in HIV-infected, BCG-vaccinated adults with CD4(+) T cell counts >350 cells/mm(3). Vaccine. 2015 Apr 8;33(15):1890-6. doi: 10.1016/j.vaccine.2015.02.004. Epub 2015 Feb 17.
PubMed 25698492
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Immunogenicity of AERAS-402 in HIV-infected, BCG-vaccinated Adults With CD4+ Lymphocyte Counts Greater Than 350 Cells/mm3
- ClinicalTrials.gov ID
- NCT01017536
- Acronym / sponsor ID
- C-017-402
- Conditions
- Tuberculosis, HIV Infections
- Keywords
- HIV, Tuberculosis, Vaccine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- AerasUniversity, hospital or other
- Collaborators
- Crucell Holland BV
- Study start
- Dec 2009
- Primary completion
- Mar 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 20 Nov 2009 (estimated)
- Results
- Posted 13 Oct 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a Phase II, randomized, double-blind, placebo-controlled trial conducted at 1 site in South Africa. A total of 26 subjects were randomized 1:1 to receive 2 doses of either AERAS-402 at 3 x 10^10 vp (N=13) or placebo (N=13) on Study Days 0 and 28. Dose-escalation to a second group of 40 subjects was planned, but although no safety concerns were identified, the sponsor decided not to continue the study.
Detailed description
Further study details as provided by Aeras.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Biological: PlaceboThirteen subjects received placebo vaccine that did not contain any AERAS-402. |
| Investigational Vaccine | Experimental | Biological: AERAS-402Thirteen subjects received active vaccine 3 x 10^10 vp AERAS-402. |
Who may qualify
- Ages
- 21 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- Age 21 years through 45 years (i.e., subject had not yet reached his/her 46th birthday at day of randomization).
- Had completed the written informed consent process prior to undergoing any screening evaluations.
- Had BCG vaccination at least 5 years previously, documented by medical history or presence of scar.
- Females: Ability to avoid pregnancy for at least 6 months after receiving the last study vaccination: Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses if menopausal) must have avoided pregnancy from 28 days prior to administration of the study vaccine and must have agreed to avoid pregnancy through at least 6 months after receiving the last study vaccination. Acceptable methods of avoiding pregnancy included a sterile sexual partner, sexual abstinence (not engaging in sexual intercourse), or use of a combination of at least two forms of acceptable contraception: hormonal contraceptives (oral, injection, transdermal patch, or implant), vaginal ring, intrauterine device (IUD), and the use of a condom or a diaphragm; or the use of a condom or a diaphragm combined with spermicide.
- Was able to carry out activities of daily living independently.
Key exclusion criteria (11 listed)
- Acute illness.
- Fever ≥37.5°C.
- Significant symptomatic infection.
- Used immunosuppressive medication within 42 days prior to randomization (inhaled and topical corticosteroids were permitted).
- Received immunoglobulin or blood products within 42 days prior to randomization.
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-402AERAS-402 is a replication-deficient serotype 35 adenovirus containing DNA that expresses a fusion protein of three Mycobacterium tuberculosis (Mtb) antigens: 85A, 85B and TB10.4. | Biological | Investigational Vaccine |
| PlaceboPlacebo was the identical buffer solution in which AERAS-402 is formulated. | Biological | Placebo |
Primary outcome
CD4+ Lymphocyte Count
Time frame: CD4+ counts from samples collected on Study days 0 and 182.
Assess the effect of AERAS-402 on the CD4+ lymphocyte count after 6 months in HIV-infected, BCG-vaccinated adult subjects with no evidence of active tuberculosis (TB disease) Change in cells/mm^3 pre-vaccination to Study Day 182
2 secondary outcomes
Change in HIV Viral Load in HIV-infected, BCG-vaccinated Adult Subjects Before and After Administration of AERAS-402 (From Day 1 to Day 182)
Time frame: 6 months (day 182) post Study Day 0 vaccination.
Mtb-specific T Cell Response in HIV-infected BCG-vaccinated Adult Subjects With no Evidence of TB Disease
Time frame: Study days 28 and 56
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25698492Churchyard GJ, Snowden MA, Hokey D, Dheenadhayalan V, McClain JB, Douoguih M, Pau MG, Sadoff J, Landry B. The safety and immunogenicity of an adenovirus type 35-vectored TB vaccine in HIV-infected, BCG-vaccinated adults with CD4(+) T cell counts >350 cells/mm(3). Vaccine. 2015 Apr 8;33(15):1890-6. doi: 10.1016/j.vaccine.2015.02.004. Epub 2015 Feb 17.
- Aurum InstituteLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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.
Gavin Churchyard, MD, PhD principal investigator
Aurum Institute
Bernard Landry, MPH study director
Aeras
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AERAS-402 in people with Tuberculosis and HIV Infections, run by Aeras at 1 site 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 14 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 9 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 13 Oct 2014). 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?
CD4+ Lymphocyte Count (time frame: CD4+ counts from samples collected on Study days 0 and 182.). 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 NCT01017536, 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 9 Sep 2016.