Latent TuberculosisPhase 1NCT01967134
Safety and Immunogenicity Study of AERAS-456 Vaccine for Tuberculosis
A Phase 1 study testing H56:IC31 in people with Latent Tuberculosis and Latent Tuberculosis Bacteriology and Histology Unknown, run by Aeras at 1 site in South Africa.
Trial summary
This is a Phase I, open-label, dose-escalation study with three study groups. This study will be conducted in 25 HIV negative subjects, 17 of whom will have Latent Tuberculosis Infection (LTBI) and 8 of whom will not have LTBI at study enrollment. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Latent Tuberculosis, Latent Tuberculosis Bacteriology and Histology Unknown
- What is being tested?
- H56:IC31
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteSouth Africa
- Study dates
- Nov 2011to Jun 2013
- Phase
- Phase 1
- 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 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Has completed the written informed consent process
- Is male or female
- Is aged 18 through 50 years on Study Day 0
- Females: Ability to avoid pregnancy during the trial: Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses if menopausal) in sexual relationships with men must avoid pregnancy with an acceptable method of avoiding pregnancy from 28 days prior to administration of the study vaccine through the end of the study.
- Has general good health, confirmed by medical history and physical examination
- Is able and willing to complete the full follow-up period of 210 days as required by the protocol
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- Is able and willing to commit to avoiding elective surgery for the duration of the study
- Is able and willing to stay in contact with the study site for the duration of the study
- [Groups 2 \& 3] Has latent tuberculosis infection (LTBI), diagnosed by a positive Quantiferon (QFT)
- Has completed simultaneous enrollment in the Registry Protocol
Who cannot join
- Axillary temperature 37.5 C
- Abnormal laboratory values from blood collected within 7 days prior to Study Day 0 vaccination as follows:
- hemoglobin, hematocrit, platelet count, absolute neutrophil count, or absolute lymphocyte count below lower limit of normal (LLN).
- white blood cell count above upper limit of normal (ULN) or below LLN
- alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase (ALP), or creatinine above ULN.
- Abnormal urinalysis that, in the opinion of the investigator, indicates systemic or local disease.
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- History or evidence of tuberculosis disease, including but not limited to pulmonary tuberculosis, pleural tuberculosis, lymph node tuberculosis or tuberculosis meningitis.
- [Group 1] Evidence of latent tuberculosis infection (LTBI), defined as a positive screening QFT or a history of a positive TST or QFT.
- Received a tuberculin skin test (TST) or bacillus Calmette-Guerin (BCG) within 45 days prior to Study Day 0.
- Received investigational Mtb vaccine at any time prior to Study Day 0.
- History or evidence of autoimmune disease.
- History or laboratory evidence of HIV infection.
- History or laboratory evidence of Hepatitis B or C.
- Used immunosuppressive medication (other than inhaled or topical immunosuppressants) within 45 days prior to Study Day 0.
- Received immunoglobulin or blood products within 45 days prior to Study Day 0
- Received any investigational product within 45 days prior to Study Day 0, or plans to participate in any other study involving administration of investigational product during the study period.
- Inability to discontinue daily medications, except contraceptives, inhaled or topical immunosuppressants, or nutritional supplements, during the study period.
- Documented history of allergic reaction or hypersensitivity to any component of the study vaccine.
- Female subjects: currently pregnant or lactating/nursing; or positive serum pregnancy test during screening; or positive urine pregnancy test on the day of Study Day 0, Study Day 56, or Study Day 112 vaccination.
- History or evidence of any systemic disease or any acute or chronic illness that, in the opinion of the investigator, may compromise the safety of the subject in the study or interfere with the evaluation of the safety or immunogenicity of the vaccine.
- History of dermatologic disease or skin features that, in the opinion of the investigator, may interfere with the assessment of injection site reactions.
- History or evidence of any medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the investigator, will make it unlikely that the subject will comply with the protocol.
Trial locations and contacts
1 site in 1 country.
South Africa1 site
SATVI Project Office, Brewelskloof Hospital
Worcester, 6850
About this study
Official title: Phase I Open Label Dose-Escalation Study to Evaluate the Safety and Immunogenicity of H56:IC31 (AERAS-456) in HIV-negative Adults With and Without Latent Tuberculosis Infection
This is a Phase I, open-label, dose-escalation study with three study groups. This study will be conducted in 25 HIV negative subjects, 17 of whom will have Latent Tuberculosis Infection (LTBI) and 8 of whom will not have LTBI at study enrollment. The investigational product is AERAS-456 at a dose of 15 ug of H56 antigen with IC31 500 nmol KLK (15/500), and a dose of 50 ug of H56 antigen with IC31 500 nmol KLK (50/500). The vaccine is administered by intramuscular injection.
Read the detailed description
This is a Phase I, open-label, dose-escalation study with three study groups. This study will be conducted in 25 HIV negative subjects, 17 of whom will have Latent Tuberculosis Infection (LTBI) and 8 of whom will not have LTBI at study enrollment. The investigational product is H56:IC31 (AERAS-456) at a dose of 15 ug of H56 antigen with IC31 500 nmol KLK (15/500), and a dose of 50 ug of H56 antigen with IC31 500 nmol KLK (50/500). The vaccine is administered by intramuscular (IM) injection.
Subjects will be assigned to a study group based on LTBI status at enrollment and time of completion of screening. Subjects without LTBI will be assigned to Group 1. Subjects with LTBI will be sequentially assigned to Groups 2 and 3 based on the order in which they complete screening. All subjects will receive a first dose of study vaccine on Study Day 0, a second dose of study vaccine on Study Day 56, and a third dose of study vaccine on Study Day 112. Enrollment of subjects into Group 2 will begin only after a review of safety data from the 14-day period after initial vaccination of all subjects in Group 1. Likewise, enrollment of subjects into Group 3 will begin only after the corresponding review of safety data from Group 2.
The total duration of study follow-up for all subjects is 210 days. Study groups 1-2 will enroll 8 subjects each and study group 3 will enroll 9 subjects. This study is planned at a single clinical site in South Africa. The sizes specified for each study group were selected because they are judged to be adequate for preliminary safety and immunogenicity evaluations for a Phase I study rather than for statistical reasons.
- Being tested
- H56:IC31
- Keywords
- HIV Negative
- Medical subject headings
- Latent Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
H56:IC31Biological
Also called AERAS 456
H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.
| Study group | Role | What they receive |
|---|---|---|
| H56:IC31 (50 ug H56) LTBI Neg | Experimental | LTBI Negative 3 Doses Receives: Biological: H56:IC31 |
| H56:IC31 (15 ug H56) LTBI Pos | Experimental | LTBI Positive 3 Doses Receives: Biological: H56:IC31 |
| H56:IC31 (50 ug H56) LTBI Pos | Experimental | LTBI Positive 3 Doses Receives: Biological: H56:IC31 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With at Least One Adverse Event (AE) Through Day 210
Solicited AEs: through 14 days after each vaccination Unsolicited AEs: post-vaccination on Study Days 0, 56, and 112 through 28 days after vaccination Injection site reactions and axillary lymphadenopathy: post-injection on the day of each vaccination, and Study Days 2 , 7, 14, and 28 days after each vaccination Serious adverse events (SAE): through Study Day 210
Measured: Through Study Day 210
Secondary outcomes (4)
Median % Change in Response to Peptides From Vaccine Antigen Ag85B From Pre-vaccination to Day 70 in Participants Who Received Two Vaccinations
Whole blood ICS Percent Antigen-Specific T Cell UNS-subtracted Cytokine Response Antigen: Ag85B Cytokine(s): G+2+17+T+
%CD4+ T Cell Response
Measured: Study Day 70
Median % Change in Response to Peptides From Vaccine Antigen ESAT-6 From Pre-vaccination to Day 70 in Participants Who Received Two Vaccinations
Percent Antigen-Specific T Cell UNS-subtracted Cytokine Response 12-Hour Whole Blood Intracellular Cytokine Staining (ICS) Assay Antigen: ESAT6 Cytokine(s): G+2+17+T+
%CD4+ T Cell Response
Measured: Study Day 70
Number of Participants Who Received at Least Two Vaccinations and Tested Positive for Mtb Infection on Day 210
Measure of Mtb positivity by QuantiFERON-TB Gold In-Tube Number of Positive Responses and Shift from Screening to Study Day 210 Post-Vaccination Responses
Measured: Study Day 210
Median % Change in Response to Peptides From Vaccine Antigen Ag85AB From Pre-vacc to Day 210
Responses to vaccine antigen Ag85B measure by Interferon gamma (IFN-γ) ELISpot assay Unstimulated-subtracted IFN-γ ELISpot Response (Spot forming units/10^6 PBMC) Antigen: Ag85B
Measured: Study Day 210
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2013 (estimated)
- Study startNov 2011
- Primary completionDec 2012
- Study completionJun 2013
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 Latent 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
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aeras
- Sponsor type
- University, hospital or other
- Collaborators
- Statens Serum Institut
- Responsible party
- Sponsor
- Investigators
- Angelique Luabeya, MD, Principal investigator, University of Cape Town South African Tuberculosis Vaccine Initiative
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01967134
- Sponsor's protocol ID
- C-032-456
- Status last verified
- Jun 2019
- First submitted
- 18 Oct 2013
- Last updated
- 21 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Luabeya AK, Kagina BM, Tameris MD, Geldenhuys H, Hoff ST, Shi Z, Kromann I, Hatherill M, Mahomed H, Hanekom WA, Andersen P, Scriba TJ; H56-032 Trial Study Group; Schoeman E, Krohn C, Day CL, Africa H, Makhethe L, Smit E, Brown Y, Suliman S, Hughes EJ, Bang P, Snowden MA, McClain B, Hussey GD. First-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults. Vaccine. 2015 Aug 7;33(33):4130-40. doi: 10.1016/j.vaccine.2015.06.051. Epub 2015 Jun 19.
PubMed 26095509
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Open Label Dose-Escalation Study to Evaluate the Safety and Immunogenicity of H56:IC31 (AERAS-456) in HIV-negative Adults With and Without Latent Tuberculosis Infection
- ClinicalTrials.gov ID
- NCT01967134
- Acronym / sponsor ID
- C-032-456
- Keywords
- HIV Negative
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- AerasUniversity, hospital or other
- Collaborators
- Statens Serum Institut
- Study start
- Nov 2011
- Primary completion
- Dec 2012 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 22 Oct 2013 (estimated)
- Results
- Posted 21 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase I, open-label, dose-escalation study with three study groups. This study will be conducted in 25 HIV negative subjects, 17 of whom will have Latent Tuberculosis Infection (LTBI) and 8 of whom will not have LTBI at study enrollment. The investigational product is AERAS-456 at a dose of 15 ug of H56 antigen with IC31 500 nmol KLK (15/500), and a dose of 50 ug of H56 antigen with IC31 500 nmol KLK (50/500). The vaccine is administered by intramuscular injection.
Detailed description
This is a Phase I, open-label, dose-escalation study with three study groups. This study will be conducted in 25 HIV negative subjects, 17 of whom will have Latent Tuberculosis Infection (LTBI) and 8 of whom will not have LTBI at study enrollment. The investigational product is H56:IC31 (AERAS-456) at a dose of 15 ug of H56 antigen with IC31 500 nmol KLK (15/500), and a dose of 50 ug of H56 antigen with IC31 500 nmol KLK (50/500). The vaccine is administered by intramuscular (IM) injection.
Subjects will be assigned to a study group based on LTBI status at enrollment and time of completion of screening. Subjects without LTBI will be assigned to Group 1. Subjects with LTBI will be sequentially assigned to Groups 2 and 3 based on the order in which they complete screening. All subjects will receive a first dose of study vaccine on Study Day 0, a second dose of study vaccine on Study Day 56, and a third dose of study vaccine on Study Day 112. Enrollment of subjects into Group 2 will begin only after a review of safety data from the 14-day period after initial vaccination of all subjects in Group 1. Likewise, enrollment of subjects into Group 3 will begin only after the corresponding review of safety data from Group 2.
The total duration of study follow-up for all subjects is 210 days. Study groups 1-2 will enroll 8 subjects each and study group 3 will enroll 9 subjects. This study is planned at a single clinical site in South Africa. The sizes specified for each study group were selected because they are judged to be adequate for preliminary safety and immunogenicity evaluations for a Phase I study rather than for statistical reasons.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| H56:IC31 (50 ug H56) LTBI Neg | Experimental | Biological: H56:IC31LTBI Negative 3 Doses |
| H56:IC31 (15 ug H56) LTBI Pos | Experimental | Biological: H56:IC31LTBI Positive 3 Doses |
| H56:IC31 (50 ug H56) LTBI Pos | Experimental | Biological: H56:IC31LTBI Positive 3 Doses |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Has completed the written informed consent process
- Is male or female
- Is aged 18 through 50 years on Study Day 0
- Females: Ability to avoid pregnancy during the trial: Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses if menopausal) in sexual relationships with men must avoid pregnancy with an acceptable method of avoiding pregnancy from 28 days prior to administration of the study vaccine through the end of the study.
- Has general good health, confirmed by medical history and physical examination
Key exclusion criteria (22 listed)
- Axillary temperature 37.5 C
- Abnormal laboratory values from blood collected within 7 days prior to Study Day 0 vaccination as follows:
- Abnormal urinalysis that, in the opinion of the investigator, indicates systemic or local disease.
- History or evidence of tuberculosis disease, including but not limited to pulmonary tuberculosis, pleural tuberculosis, lymph node tuberculosis or tuberculosis meningitis.
- [Group 1] Evidence of latent tuberculosis infection (LTBI), defined as a positive screening QFT or a history of a positive TST or QFT.
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 |
|---|---|---|
| H56:IC31Also: AERAS 456H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant. | Biological | H56:IC31 (15 ug H56) LTBI Pos, H56:IC31 (50 ug H56) LTBI Neg, H56:IC31 (50 ug H56) LTBI Pos |
Primary outcome
Number of Participants With at Least One Adverse Event (AE) Through Day 210
Time frame: Through Study Day 210
Solicited AEs: through 14 days after each vaccination Unsolicited AEs: post-vaccination on Study Days 0, 56, and 112 through 28 days after vaccination Injection site reactions and axillary lymphadenopathy: post-injection on the day of each vaccination, and Study Days 2 , 7, 14, and 28 days after each vaccination Serious adverse events (SAE): through Study Day 210
4 secondary outcomes
Median % Change in Response to Peptides From Vaccine Antigen Ag85B From Pre-vaccination to Day 70 in Participants Who Received Two Vaccinations
Time frame: Study Day 70
Median % Change in Response to Peptides From Vaccine Antigen ESAT-6 From Pre-vaccination to Day 70 in Participants Who Received Two Vaccinations
Time frame: Study Day 70
Number of Participants Who Received at Least Two Vaccinations and Tested Positive for Mtb Infection on Day 210
Time frame: Study Day 210
Median % Change in Response to Peptides From Vaccine Antigen Ag85AB From Pre-vacc to Day 210
Time frame: Study Day 210
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26095509Luabeya AK, Kagina BM, Tameris MD, Geldenhuys H, Hoff ST, Shi Z, Kromann I, Hatherill M, Mahomed H, Hanekom WA, Andersen P, Scriba TJ; H56-032 Trial Study Group; Schoeman E, Krohn C, Day CL, Africa H, Makhethe L, Smit E, Brown Y, Suliman S, Hughes EJ, Bang P, Snowden MA, McClain B, Hussey GD. First-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults. Vaccine. 2015 Aug 7;33(33):4130-40. doi: 10.1016/j.vaccine.2015.06.051. Epub 2015 Jun 19.
- Individual participant dataSharing planned: No
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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.
Angelique Luabeya, MD principal investigator
University of Cape Town South African Tuberculosis Vaccine Initiative
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing H56:IC31 in people with Latent Tuberculosis and Latent Tuberculosis Bacteriology and Histology Unknown, 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 10 inclusion and 22 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 21 Aug 2019. 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. 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 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.
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 21 Aug 2019). 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?
Number of Participants With at Least One Adverse Event (AE) Through Day 210 (time frame: Through Study Day 210). 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 NCT01967134, 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 21 Aug 2019.