Tuberculosis InfectionPhase 2A-043NCT03265977
A Phase II Study of H56:IC31 in Healthy Adolescents
A Phase 2 study testing H56:IC31 in people with Tuberculosis Infection, run by Aeras at 4 sites in 2 countries.
Trial summary
This clinical trial will evaluate safety, immunogenicity, and efficacy (prevention of Mtb infection as measured by IGRA conversions) of H56:IC31 in remotely BCG vaccinated adolescents. Read more about this study
- Who is it for?
- Ages 12 to 17 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis Infection
- What is being tested?
- H56:IC31
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Jun 2018to 30 Jun 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 12 to 17 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Has completed the written informed consent and assent process
- Is age ≥12 years and ≤17 years on Study Day 0
- Agrees to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and has no current plans to move from the study area for the duration of the study
- For female participants: agrees to avoid pregnancy from 21 days prior to Study Day 0 through 6 months after the last study vaccination. Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses) in sexual relationships with men must use an acceptable method of avoiding pregnancy during this period. 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)
- Has general good health, confirmed by medical history and physical examination
- Had BCG vaccination at least 5 years ago documented by confirmation of parent/guardian that the participant received all childhood vaccines or by presence of healed BCG scar
- Tests ESAT-6 free IGRA and QFT-Plus negative at screening, using a pre-determined threshold for ESAT-6 free IGRA and the manufacturer's recommended threshold for QFT-Plus of 0.35 IU/mL in either of the TB antigen tubes after nil-subtraction
Who cannot join
- Acute illness on Study Day 0
- Axillary temperature ≥37.5 °C on Study Day 0
- Abnormal laboratory values from the most recent blood collected prior to randomization as follows (abnormal results may be repeated once and if found to be resolved the participant will not be excluded):
- Laboratory evidence of hematologic disease (white blood cell count <3000/mm^3 or >11,500/mm^3; hemoglobin <0.9 times the lower limit of normal of the testing laboratory, by age and gender; absolute neutrophil count <1300/mm^3; absolute lymphocyte count <1000/mm^3).
- ALT, AST, alkaline phosphatase, total bilirubin, creatinine, blood urea nitrogen (BUN) >1.25 times the ULN
- Urinalysis abnormality greater than Grade 1 on the Toxicity Scale (with the exception of hematuria in a menstruating female), or urinalysis abnormality judged clinically significant by the investigator
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- History or evidence of any clinically significant systemic disease, or any acute or chronic illness that might affect the safety, immunogenicity, or efficacy of investigational product in the opinion of the investigator
- History of treatment for active TB disease or latent Mtb infection
- History or evidence, including chest X-ray, of active TB disease
- Shared household with an individual receiving anti-TB treatment, or known to have incompletely treated culture or smear positive TB, at screening
- 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 or investigational vaccine within 180 days before Study Day 0, or planned participation in any other clinical trial during the study period
- Received investigational TB vaccine at any time prior to Study Day 0
- Planned administration/administration of a licensed vaccine in the period starting 28 days before and ending 28 days after each dose of investigational product
- History or laboratory evidence of any past or present possible immunodeficiency state including, but not limited to, any laboratory indication of HIV 1 infection
- History of allergic disease or reactions, including eczema, likely to be exacerbated by any component of the investigational product
- History of alcohol or drug abuse
- Any female currently pregnant or lactating/nursing, or positive urine pregnancy test during screening or Study Day 0
- Received a tuberculin skin test (TST) within 3 months (90 days) prior to Study Day 0.
- Any current medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the investigator, will make it unlikely that the participant will comply with the protocol.
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
South Africa3 sites
Aurum Institute - Klerksdorp
Klerksdorp, 2571
Aurum Institute - Rustenburg
Rustenburg, 0300
Aurum Institute - Tembisa
Tembisa, 1632
About this study
Official title: A Randomized, Placebo Controlled, Double-Blind Phase II Study to Evaluate Safety, Immunogenicity, and Prevention of Infection With Mycobacterium Tuberculosis (Mtb) of H56:IC31 in Healthy Adolescents
This clinical trial will evaluate safety, immunogenicity, and efficacy (prevention of Mtb infection as measured by IGRA conversions) of H56:IC31 in remotely BCG vaccinated adolescents.
Read the detailed description
This clinical trial will evaluate safety, immunogenicity, and prevention of Mtb infection, (measured by IGRA conversion) of H56:IC31 in remotely BCG vaccinated adolescents. A TB vaccination strategy incorporating H56:IC31 in adolescents or young adults, if found to prevent Mtb infection, would likely have a major impact on TB disease, TB transmission, and control of the epidemic. If vaccination with H56:IC31 is shown to prevent infection with Mtb in this proof of concept study in adolescents, additional larger scale studies examining the impact on TB disease in more diverse populations would be warranted.
Primary objectives
- To evaluate the safety profile of H56:IC31 compared to placebo in HIV-uninfected, remotely BCG vaccinated adolescents.
- To evaluate prevention of Mtb infection by H56:IC31 compared to placebo, as measured by rates of conversion using an ESAT-6 free IGRA.
Secondary objectives
- To evaluate prevention of Mtb infection by H56:IC31 compared to placebo, as measured by rates of sustained conversion using an ESAT-6 free IGRA.
- To evaluate trends in ESAT-6 free IGRA prolonged/sustained conversions and late reversions (i.e., through more than 6 months post initial conversion) in ESAT-6 free IGRA converters.
- To investigate the immunogenicity of H56:IC31 in HIV-uninfected, remotely BCG vaccinated adolescents.
- Conditions
- Tuberculosis Infection
- Being tested
- H56:IC31, Placebo
- 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
The H56 antigen is a fusion protein created from 3 Mtb antigens: antigen 85B (Ag85B), ESAT-6, and Rv2660c.
PlaceboOther
Normal saline
| Study group | Role | What they receive |
|---|---|---|
| H56:IC31 | Experimental | 5 ug H56/500 nmol IC31, 0.5 mL Intramuscular (IM), Days 0 and 56 Receives: Biological: H56:IC31 |
| Placebo | Placebo comparator | Normal saline, 0.5 mL IM, Days 0 and 56 Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency and severity of adverse events
To evaluate the safety profile of H56:IC31 compared to placebo in HIV-uninfected, previously BCG vaccinated adolescents.
Measured: Day 0 through month 24
ESAT-6 free IGRA conversion from a negative to positive test at any time point after Day 84 and through end of follow-up for the primary endpoint.
To evaluate prevention of Mtb infection by H56:IC31 compared to placebo, as measured by rates of conversion using an ESAT-6 free IGRA.
Measured: Day 84 through month 24
Secondary outcomes (4)
Primary ESAT-6 free IGRA conversion from a negative to a positive test
Primary ESAT-6 free IGRA conversion from a negative to a positive test at any time point after Day 84 and through end of follow up for the primary endpoint, AND persisting without ESAT-6 free IGRA reversion from a positive to a negative test through 6 months after ESAT-6 free IGRA conversion.
Measured: Day 84 through month 24
Primary ESAT-6 free IGRA conversion from a negative to a positive test
Primary ESAT-6 free IGRA conversion from a negative to a positive test at any time point after randomization and through end of follow up for the primary endpoint, AND persisting without ESAT-6 free IGRA reversion from a positive to a negative test through 6 months after ESAT-6 free IGRA conversion.
Measured: Day 84 through end of study (approximately 24 months)
Initial ESAT-6 free IGRA reversion from a positive to a negative test at any time point after primary ESAT-6 free IGRA conversion through the end of follow up.
To evaluate trends in ESAT-6 free IGRA prolonged/sustained conversions and late reversions (i.e., through more than 6 months post initial conversion) in ESAT-6 free IGRA converters.
Measured: Day 84 through month 24
Percentage of CD4+ and CD8+ T cells that express IFN-γ, TNF, and/or IL-2 alone or in combination in response to stimulation with peptide pools representing the entire amino acid sequence of the vaccine antigens.
Immunogenicity of H56:IC31 in HIV-uninfected, previously BCG vaccinated adolescents.
Measured: Day 0 through month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2017
- Study startJun 2018 (estimated)
- Primary completion30 Apr 2021 (estimated)
- Study completion30 Jun 2021 (estimated)
Why it stopped: Design, sponsorship changed prior to initiation. No study procedures done.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tuberculosis InfectionStudies 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
- Model description
- Participants will be enrolled in two cohorts. Within each cohort participants will be randomized in a 1:1 ratio to receive either H56:IC31 (5 ug H56/500 nmol IC31) or placebo intramuscularly (IM) on Days 0 and 56.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aeras
- Sponsor type
- University, hospital or other
- Collaborators
- Statens Serum Institut, Aurum Institute, South African Tuberculosis Vaccine Initiative, Oslo University Hospital, University of Copenhagen, University of Bergen, National Institute for Medical Research, Tanzania
- Responsible party
- Sponsor
- Investigators
- Dereck Tait, MD, Study director, Aeras
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03265977
- Sponsor's protocol ID
- A-043
- Acronym
- A-043
- Status last verified
- Apr 2018
- First submitted
- 24 Aug 2017
- Last updated
- 10 Apr 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo Controlled, Double-Blind Phase II Study to Evaluate Safety, Immunogenicity, and Prevention of Infection With Mycobacterium Tuberculosis (Mtb) of H56:IC31 in Healthy Adolescents
- ClinicalTrials.gov ID
- NCT03265977
- Acronym / sponsor ID
- A-043 / A-043
- Conditions
- Tuberculosis Infection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Design, sponsorship changed prior to initiation. No study procedures done.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- AerasUniversity, hospital or other
- Collaborators
- Statens Serum Institut, Aurum Institute, South African Tuberculosis Vaccine Initiative, Oslo University Hospital, University of Copenhagen, University of Bergen, National Institute for Medical Research, Tanzania
- Study start
- Jun 2018 (estimated)
- Primary completion
- 30 Apr 2021 (estimated)
- Study completion
- 30 Jun 2021 (estimated)
- First posted
- 29 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical trial will evaluate safety, immunogenicity, and efficacy (prevention of Mtb infection as measured by IGRA conversions) of H56:IC31 in remotely BCG vaccinated adolescents.
Detailed description
This clinical trial will evaluate safety, immunogenicity, and prevention of Mtb infection, (measured by IGRA conversion) of H56:IC31 in remotely BCG vaccinated adolescents. A TB vaccination strategy incorporating H56:IC31 in adolescents or young adults, if found to prevent Mtb infection, would likely have a major impact on TB disease, TB transmission, and control of the epidemic. If vaccination with H56:IC31 is shown to prevent infection with Mtb in this proof of concept study in adolescents, additional larger scale studies examining the impact on TB disease in more diverse populations would be warranted.
Primary objectives
- To evaluate the safety profile of H56:IC31 compared to placebo in HIV-uninfected, remotely BCG vaccinated adolescents.
- To evaluate prevention of Mtb infection by H56:IC31 compared to placebo, as measured by rates of conversion using an ESAT-6 free IGRA.
Secondary objectives
- To evaluate prevention of Mtb infection by H56:IC31 compared to placebo, as measured by rates of sustained conversion using an ESAT-6 free IGRA.
- To evaluate trends in ESAT-6 free IGRA prolonged/sustained conversions and late reversions (i.e., through more than 6 months post initial conversion) in ESAT-6 free IGRA converters.
- To investigate the immunogenicity of H56:IC31 in HIV-uninfected, remotely BCG vaccinated adolescents.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Participants will be enrolled in two cohorts. Within each cohort participants will be randomized in a 1:1 ratio to receive either H56:IC31 (5 ug H56/500 nmol IC31) or placebo intramuscularly (IM) on Days 0 and 56.
| Arm | Type | Receives |
|---|---|---|
| H56:IC31 | Experimental | Biological: H56:IC315 ug H56/500 nmol IC31, 0.5 mL Intramuscular (IM), Days 0 and 56 |
| Placebo | Placebo comparator | Other: PlaceboNormal saline, 0.5 mL IM, Days 0 and 56 |
Who may qualify
- Ages
- 12 to 17 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Has completed the written informed consent and assent process
- Is age ≥12 years and ≤17 years on Study Day 0
- Agrees to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and has no current plans to move from the study area for the duration of the study
- For female participants: agrees to avoid pregnancy from 21 days prior to Study Day 0 through 6 months after the last study vaccination. Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses) in sexual relationships with men must use an acceptable method of avoiding pregnancy during this period. 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)
- Has general good health, confirmed by medical history and physical examination
Key exclusion criteria (22 listed)
- Acute illness on Study Day 0
- Axillary temperature ≥37.5 °C on Study Day 0
- Abnormal laboratory values from the most recent blood collected prior to randomization as follows (abnormal results may be repeated once and if found to be resolved the participant will not be excluded):
- Urinalysis abnormality greater than Grade 1 on the Toxicity Scale (with the exception of hematuria in a menstruating female), or urinalysis abnormality judged clinically significant by the investigator
- History or evidence of any clinically significant systemic disease, or any acute or chronic illness that might affect the safety, immunogenicity, or efficacy of investigational product in the opinion of the investigator
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:IC31The H56 antigen is a fusion protein created from 3 Mtb antigens: antigen 85B (Ag85B), ESAT-6, and Rv2660c. | Biological | H56:IC31 |
| PlaceboNormal saline | Other | Placebo |
Primary outcome
Frequency and severity of adverse events
Time frame: Day 0 through month 24
To evaluate the safety profile of H56:IC31 compared to placebo in HIV-uninfected, previously BCG vaccinated adolescents.
ESAT-6 free IGRA conversion from a negative to positive test at any time point after Day 84 and through end of follow-up for the primary endpoint.
Time frame: Day 84 through month 24
To evaluate prevention of Mtb infection by H56:IC31 compared to placebo, as measured by rates of conversion using an ESAT-6 free IGRA.
4 secondary outcomes
Primary ESAT-6 free IGRA conversion from a negative to a positive test
Time frame: Day 84 through month 24
Primary ESAT-6 free IGRA conversion from a negative to a positive test
Time frame: Day 84 through end of study (approximately 24 months)
Initial ESAT-6 free IGRA reversion from a positive to a negative test at any time point after primary ESAT-6 free IGRA conversion through the end of follow up.
Time frame: Day 84 through month 24
Percentage of CD4+ and CD8+ T cells that express IFN-γ, TNF, and/or IL-2 alone or in combination in response to stimulation with peptide pools representing the entire amino acid sequence of the vaccine antigens.
Time frame: Day 0 through month 24
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2018.
- 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.
Dereck Tait, MD study director
Aeras
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing H56:IC31 in people with Tuberculosis Infection, run by Aeras at 4 sites in 2 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 7 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: withdrawn, as of the sponsor's last update on 10 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in South Africa, Tanzania. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Frequency and severity of adverse events (time frame: Day 0 through month 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Apr 2018.