TuberculosisPhase 1C-037-456NCT02375698
A Phase I Study of Safety & Immunogenicity of AERAS-456 in HIV-Neg. Adults Treated for Drug-susceptible Pulmonary TB
A Phase 1 study testing H56:IC31 in people with Tuberculosis, run by Aeras at 3 sites in South Africa.
Trial summary
This is a Phase I, double-blind, randomized, placebo-controlled safety and immunogenicity study in adults who have recently been successfully treated for drug-susceptible pulmonary Tuberculosis (TB). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Tuberculosis
- What is being tested?
- H56:IC31
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 3 sitesSouth Africa
- Study dates
- 21 Nov 2014to 24 Oct 2016
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Is HIV-negative.
- Is male or female aged 18 through 60 years on Study Day 0.
- Has completed the written informed consent process.
- Has a diagnosis of confirmed pulmonary tuberculosis and is on standard TB treatment.
- Is confirmed to be Mtb negative by either 2 GeneXpert tests or 2 cultures from sputum samples taken on 2 different days at least 1 week apart, the first after at least 4 calendar months of TB treatment and the second day not later than after 5 calendar months (with a window of plus 1 week) of treatment.
- Agrees to complete the prescribed course of TB treatment (completion of TB treatment can occur after vaccination on Study Day 0; subject must have completed at least 5 calendar months of TB treatment on Study Day 0; if TB treatment is completed before randomization/vaccination then the time from completion of TB treatment to randomization/vaccination should not exceed 28 days).
- For female subjects: agrees to avoid pregnancy between screening and up until two months after last vaccination. 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 use an acceptable method of avoiding pregnancy from 28 days prior to administration of study vaccine up until two months after the last vaccination. Acceptable methods of avoiding pregnancy include a sterile sexual partner, sexual abstinence (not engaging in sexual intercourse), hormonal contraceptives (oral, injection, transdermal patch, or implant), vaginal ring, or intrauterine device (IUD).
- Agrees to stay in contact with the study site for the full duration of the study, providing updated contact information as necessary, and has no current plans to move from the study area during the duration of the study.
Who cannot join
- Evidence of a new acute illness that may compromise the safety of the subject in the study on Study Day 0.
- History of TB prior to current episode.
- TB meningitis or other forms of severe TB with high risk of a poor outcome.
- Previous medical history that may compromise the safety of the subject in the study, including but not limited to severe impairment of pulmonary function from tuberculosis infection or other pulmonary disease; chronic illness with signs of cardiac or renal failure; suspected progressive neurological disease; or uncontrolled epilepsy.
- Evidence of any systemic disease or any acute or chronic illness that may interfere with the evaluation of the safety of the vaccine.
- History or laboratory evidence of any possible immunodeficiency state.
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- History of allergic disease or reactions likely to be exacerbated by any component of the study vaccine.
- Received any non-BCG TB vaccine previously.
- For female subjects: Currently pregnant, lactating/nursing, or a positive urine HCG.
- Severe anemia, defined as hemoglobin less than 10 g/dL or a hematocrit less than 30 percent based on screening hematology obtained within 7 days before randomization on Study Day 0.
- History of autoimmune disease or immunosuppression.
- Used immunosuppressive medication within 42 days before Study Day 0 (inhaled and topical corticosteroids are permitted).
- Received immunoglobulin or blood products within 42 days before Study Day 0.
- Received any investigational drug therapy or investigational vaccine within 6 months before Study Day 0, or planned participation in any other investigational study during the study period.
- Received any licensed vaccine within 28 days before Study Day 0, or receipt of any vaccine or immunomodulating agent through Study Day 63.
- Is, in the judgment of the principal investigator, not suitable to participate in this clinical study.
Trial locations and contacts
3 sites in 1 country.
South Africa3 sites
Task Clinical Research Centre
Bellville, Cape Town
The Aurum Institue
Johannesburg
University of Cape Town Lung Institute
Mowbray, Cape Town
About this study
Official title: A Phase I, Double-blind, Randomized, Placebo-controlled, Study to Evaluate the Safety and Immunogenicity of AERAS-456 in HIV Negative Adults Successfully Treated for Drug-susceptible Pulmonary Tuberculosis
This is a Phase I, double-blind, randomized, placebo-controlled safety and immunogenicity study in adults who have recently been successfully treated for drug-susceptible pulmonary Tuberculosis (TB). The safety and immunogenicity profile of escalating doses of AERAS-456 in HIV-negative subjects recently treated for drug-susceptible pulmonary TB will be investigated. The study will be conducted at three sites in South Africa.
Read the detailed description
This study will be the first evaluation of AERAS-456 in subjects who have completed a full course of treatment prescribed for pulmonary TB. Subjects will begin screening for study participation when they have completed 4 calendar months of TB treatment. Subjects meeting the inclusion/exclusion criteria will be randomized within a study group in a 3:1 ratio (N=18 AERAS-456; N=6 placebo) to receive two 0.5 mL intramuscular injections of AERAS-456 or placebo eight weeks apart, on Study Day 0 and Study Day 56.
- Conditions
- Tuberculosis
- Being tested
- H56:IC31, Placebo
- Medical subject headings
- 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).
PlaceboBiological
The placebo consists of 10mM Tris and 169 mM NaCl pH 7.4.
| Study group | Role | What they receive |
|---|---|---|
| Gr 1 H56:IC31 5/500 | Experimental | 5ug H56 + 500 ug IC31 Receives: Biological: H56:IC31 |
| Placebo | Placebo comparator | The placebo consists of 10mM Tris and 169 mM NaCl pH 7.4. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Unsolicited AEs: 28 days after each vaccination Solicited AEs: 7 days after each vaccination SAEs: through Day 420 Adverse events of special interest: through Day 420
Measured: Day 0 to Day 420
Secondary outcomes (1)
Mean Percent Change From Baseline of Participants' Responses to TB Antigens Ag85A and ESAT-6
13-Color PBMC Intracellular Cytokine Staining (ICS) Assay using PBMCs Percent Antigen-specific T Cell DMSO-subtracted, ANY Cytokine Response - Change from Baseline T Cell: CD4
Measured: Day 224
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2015 (estimated)
- Study start21 Nov 2014
- Primary completion24 Jun 2016
- Study completion24 Oct 2016
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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aeras
- Sponsor type
- University, hospital or other
- Collaborators
- Statens Serum Institut
- Responsible party
- Sponsor
- Investigators
- Dereck Tait, MBChB, Study director, Aeras
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02375698
- Sponsor's protocol ID
- C-037-456
- Acronym
- C-037-456
- Status last verified
- Aug 2017
- First submitted
- 20 Feb 2015
- Last updated
- 30 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Tait D, Diacon A, Borges AH, van Brakel E, Hokey D, Rutkowski KT, Hunt DJ, Russell M, Andersen PL, Kromann I, Ruhwald M, Churchyard G, Dawson R. Safety and Immunogenicity of the H56:IC31 Tuberculosis Vaccine Candidate in Adults Successfully Treated for Drug-Susceptible Pulmonary Tuberculosis: A Phase 1 Randomized Trial. J Infect Dis. 2024 Nov 15;230(5):1262-1270. doi: 10.1093/infdis/jiae170.
PubMed 38557639
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Double-blind, Randomized, Placebo-controlled, Study to Evaluate the Safety and Immunogenicity of AERAS-456 in HIV Negative Adults Successfully Treated for Drug-susceptible Pulmonary Tuberculosis
- ClinicalTrials.gov ID
- NCT02375698
- Acronym / sponsor ID
- C-037-456 / C-037-456
- Conditions
- Tuberculosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- AerasUniversity, hospital or other
- Collaborators
- Statens Serum Institut
- Study start
- 21 Nov 2014 (actual)
- Primary completion
- 24 Jun 2016 (actual)
- Study completion
- 24 Oct 2016 (actual)
- First posted
- 3 Mar 2015 (estimated)
- Results
- Posted 18 Nov 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, double-blind, randomized, placebo-controlled safety and immunogenicity study in adults who have recently been successfully treated for drug-susceptible pulmonary Tuberculosis (TB). The safety and immunogenicity profile of escalating doses of AERAS-456 in HIV-negative subjects recently treated for drug-susceptible pulmonary TB will be investigated. The study will be conducted at three sites in South Africa.
Detailed description
This study will be the first evaluation of AERAS-456 in subjects who have completed a full course of treatment prescribed for pulmonary TB. Subjects will begin screening for study participation when they have completed 4 calendar months of TB treatment. Subjects meeting the inclusion/exclusion criteria will be randomized within a study group in a 3:1 ratio (N=18 AERAS-456; N=6 placebo) to receive two 0.5 mL intramuscular injections of AERAS-456 or placebo eight weeks apart, on Study Day 0 and Study Day 56.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gr 1 H56:IC31 5/500 | Experimental | Biological: H56:IC315ug H56 + 500 ug IC31 |
| Placebo | Placebo comparator | Biological: PlaceboThe placebo consists of 10mM Tris and 169 mM NaCl pH 7.4. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Is HIV-negative.
- Is male or female aged 18 through 60 years on Study Day 0.
- Has completed the written informed consent process.
- Has a diagnosis of confirmed pulmonary tuberculosis and is on standard TB treatment.
- Is confirmed to be Mtb negative by either 2 GeneXpert tests or 2 cultures from sputum samples taken on 2 different days at least 1 week apart, the first after at least 4 calendar months of TB treatment and the second day not later than after 5 calendar months (with a window of plus 1 week) of treatment.
Key exclusion criteria (16 listed)
- Evidence of a new acute illness that may compromise the safety of the subject in the study on Study Day 0.
- History of TB prior to current episode.
- TB meningitis or other forms of severe TB with high risk of a poor outcome.
- Previous medical history that may compromise the safety of the subject in the study, including but not limited to severe impairment of pulmonary function from tuberculosis infection or other pulmonary disease; chronic illness with signs of cardiac or renal failure; suspected progressive neurological disease; or uncontrolled epilepsy.
- Evidence of any systemic disease or any acute or chronic illness that may interfere with the evaluation of the safety of the vaccine.
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). | Biological | Gr 1 H56:IC31 5/500 |
| PlaceboThe placebo consists of 10mM Tris and 169 mM NaCl pH 7.4. | Biological | Placebo |
Primary outcome
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Day 0 to Day 420
Unsolicited AEs: 28 days after each vaccination Solicited AEs: 7 days after each vaccination SAEs: through Day 420 Adverse events of special interest: through Day 420
1 secondary outcome
Mean Percent Change From Baseline of Participants' Responses to TB Antigens Ag85A and ESAT-6
Time frame: Day 224
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 38557639Tait D, Diacon A, Borges AH, van Brakel E, Hokey D, Rutkowski KT, Hunt DJ, Russell M, Andersen PL, Kromann I, Ruhwald M, Churchyard G, Dawson R. Safety and Immunogenicity of the H56:IC31 Tuberculosis Vaccine Candidate in Adults Successfully Treated for Drug-Susceptible Pulmonary Tuberculosis: A Phase 1 Randomized Trial. J Infect Dis. 2024 Nov 15;230(5):1262-1270. doi: 10.1093/infdis/jiae170.
- 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.
Dereck Tait, MBChB study director
Aeras
3 sites 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 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 16 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 30 Jul 2024. 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 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 18 Nov 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 Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: Day 0 to Day 420). 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 NCT02375698, 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 30 Jul 2024.