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Tuberculosis, PulmonaryPhase 2NCT03512249

Study to Evaluate H56:IC31 in Preventing Rate of TB Recurrence

A Phase 2 study testing H56:IC31 in people with Tuberculosis, Pulmonary, run by International AIDS Vaccine Initiative at 6 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a phase 2, double-blind, randomized (1:1), placebo-controlled trial with two parallel groups. H56:IC31 (investigational vaccine) Placebo 900 HIV-negative adults with a diagnosis of drug susceptible pulmonary TB are planned to be included, recruited from TB clinics with established relationships to the trial… Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Tuberculosis, Pulmonary
What is being tested?
H56:IC31
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
831 participants
Where
6 sitesin 2 countries
Study dates
31 Jan 2019to 20 Mar 2023
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 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Completed the written informed consent process.
  • Agrees to give access to medical records for trial related purposes.
  • Was HIV-negative (self-reported) with a diagnosis of drug susceptible pulmonary TB at the start of the TB treatment.
  • Able to provide 2 separate sputum samples within ≤ 7 days of starting TB treatment. Participants are not expected to provide sputum samples prior to starting TB treatment if their 1st screening visit (V1) is performed on the same day as their 2nd screening visit (V2).
  • Confirmed Mtb negative by smear AFB microscopy of 2 separate sputum samples taken at V2. Participants unable to produce sputum, but considered asymptomatic by the investigator, may be considered Mtb negative and eligible for inclusion.
  • Confirmed HIV negative at V2.
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  • Completed ≥ 5 months (22 weeks) of TB treatment with treatment still ongoing at the time of the 1st vaccination and total treatment time not extended beyond 28 weeks.
  • Aged ≥ 18 years on the date of V1 and ≤ 60 years on the date of V3= Day 0.
  • Agrees to stay in contact with the clinical trial site for the duration of the trial, provide updated contact information as necessary, and has no current plans to move from the area for the duration of the trial.

Who cannot join

  • Diagnosis or co-diagnosis of extra pulmonary TB.
  • Hospitalized for the current episode of drug susceptible pulmonary TB disease.
  • History of or ongoing severe disease that in the opinion of the investigator might affect the safety of the participant or the immunogenicity of the investigational product.
  • Insulin dependent diabetes.
  • History of allergic disease or reactions likely to be exacerbated by any component of the investigational product.
  • History or laboratory evidence of immunodeficiency, autoimmune disease or immunosuppression.
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  • History of chronic hepatitis.
  • Severe anemia, defined as hemoglobin less than 10 g/dL or a hematocrit less than 30% based on most recent hematology obtained before randomization.
  • History of receipt of treatment against active TB, prior to the current treatment episode, within the last 5 years
  • Receipt of any investigational TB vaccine previously.
  • Receipt or planned receipt of any investigational drug or investigational vaccine from V1 through V8= Day 421.
  • Receipt or planned receipt of any licensed vaccine from V1 through V6= Day 70, except for SARS-Cov-2 vaccines recommended by national vaccination programs which will be allowed if given > 28 days before and from the time of administration of clinical trial product.
  • Receipt of treatment likely to modify the immune response (e.g. blood products, immunoglobulins, immunosuppressive treatment) within 42 days before V3= Day 0 through V6= Day 70. Inhaled and topical corticosteroids are permitted.
  • Has a body mass index (BMI) < 13 (weight, kg / height, m2) on the date of V1.
  • Female participants of childbearing potential (not sterilized, menstruating or within 1 year of last menses, if post-menopausal): if not willing to use an acceptable method to avoid pregnancy (sterile sexual partner, sexual abstinence, hormonal contraceptives (oral, injection, transdermal patch, or implant) or intrauterine device from 28 days before V3= Day 0 until 2 months after the 2nd vaccination.
  • Female participants: if lactating / nursing, or pregnant as per positive pregnancy test on V2.
  • Not suitable for inclusion in the opinion of the investigator.

Trial locations and contacts

6 sites in 2 countries.

6 sites in 2 countries

South Africa5 sites

  • Task Clinical Research Centre

    Bellville, Cape Town, 7530

  • South African Tuberculosis Vaccine Initiative , Project Office, Brewelskloof Hospital , Harlem Street, Worcester

    Cape Town, Western Cape, 6850

  • The Aurum Institute

    Klerksdorp, North West, 2570

  • University of Cape Town Lung Institute

    Mowbray, Cape Town

  • The Aurum Institute: Tembisa Clinical Research Centre

    Tembisa, Gauteng, 1632

Other trials in South Africa

Tanzania1 site

  • NIMR Mbeya Medical Research Centre

    Mbeya

Other trials in Tanzania

About this study

Official title: Phase 2, Double-blind, Randomized, Placebo-Controlled Study to Evaluate Safety and Efficacy of H56:IC31 in Reducing the Rate of TB Disease Recurrence in HIV Negative Adults Successfully Treated for Drug-Susceptible Pulmonary Tuberculosis

This is a phase 2, double-blind, randomized (1:1), placebo-controlled trial with two parallel groups.

  • H56:IC31 (investigational vaccine)
  • Placebo 900 HIV-negative adults with a diagnosis of drug susceptible pulmonary TB are planned to be included, recruited from TB clinics with established relationships to the trial sites at the start of their TB treatment. 5 study sites in South Africa: 2 sites from the AURUM institute (Klerksdorp and Tembisa) and 3 in Cape Town at TASK Applied Science (TASK), the University of Cape Town Lung Institute (UCTLI) and South African Tuberculosis Vaccine Initiative (SATVI) under UCT, respectively. 1 study site in Tanzania (TZ): 1 site at Mbeya Medical Research Centre (MMRC) under the National Institute for Medical Research (NIMR).
Read the detailed description

This is a phase 2, double-blind, randomized (1:1), placebo-controlled trial with two parallel groups.

  • H56:IC31 (investigational vaccine)
  • Placebo 900 HIV-negative adults with a diagnosis of drug susceptible pulmonary TB are planned to be included, recruited from TB clinics with established relationships to the trial sites at the start of their TB treatment. 5 study sites in South Africa: 2 sites from the AURUM institute (Klerksdorp and Tembisa) and 3 in Cape Town at TASK Applied Science (TASK), the University of Cape Town Lung Institute (UCTLI)) and South African Tuberculosis Vaccine Initiative (SATVI) under UCT, respectively. 1 study site in Tanzania (TZ): 1 site at Mbeya Medical Research Centre (MMRC) under the National Institute for Medical Research (NIMR).

Preclinical data suggest H56:IC31 may be more efficacious if administered while patients are still on treatment. Following the national guidelines for TB treatment in South Africa and Tanzania, we will obtain sputum samples from patients towards the end of treatment at about the same time they are obtained within the national TB control programmes, and if the sputum is smear negative, the criterion for successful treatment within TB programmes, the individual will be eligible for randomization and vaccination towards the end of their six-month treatment period.

As this is a proof of concept TB vaccine study, HIV positive individuals have been excluded as it is not yet known what effect HIV infection may have on the immune response to the vaccine. However, HIV positive individuals are an important population to include in future studies should efficacy be demonstrated in this study.

Being tested
H56:IC31, Placebo
Keywords
tuberculosis, prevention of recurrence, relapse, reinfection, subunit vaccine, whole-genome sequencing
Medical subject headings
Tuberculosis, Pulmonary, Tuberculosis, Recurrence, Reinfection

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • H56:IC31Biological

    Also called H56

    5ug H56/500 nmol IC31

  • PlaceboBiological

    Sterile saline for injection

Study groups in NCT03512249
Study groupRoleWhat they receive
H56:IC31ExperimentalThe H56 fusion protein is formulated with IC31 in a GMP-compliant environment in a ready to use final formulated vaccine. H56:IC31 is administered twice with a 56 days (+/-10) interval, as 5 μg H56 adjuvanted with IC31 consisting of 500 nmol KLK and 20 nmol ODN1a, in a total volume of 0.5mL by the intramuscular route in the deltoid area using standard aseptic technique.
Receives: Biological: H56:IC31
PlaceboPlacebo comparatorSterile saline for injection
Receives: Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of TB Disease Recurrence (Relapse or Reinfection), Defined as TB Diagnosed by Confirmation of Mtb by Culture of Sputum.

    To evaluate the following in HIV-negative participants who have completed at least 5 months (22 weeks) treatment for drug-susceptible pulmonary TB and who test negative for acid fast bacilli (AFB) on sputum smear microscopy prior to vaccination (participants unable to produce sputum, and considered asymptomatic by the investigator, may be considered Mtb negative): Efficacy of H56:IC31 compared to placebo in reducing the rate of recurrent TB disease (relapse or reinfection).

    Measured: During the period starting 14 days after the 2nd vaccination (V6= Day 70) and ending 12 months after the 2nd vaccination

Secondary outcomes (9)

  1. Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term

    Solicited adverse events were infection site reactions (redness, swelling and tenderness/pain) and systemic adverse events (AEs) (fever, arthralgia, myalgia, fatigue, headache, rash, chills, and nausea). All participants were provided with a diary, a thermometer to record axillary temperature, a ruler to measure injection site redness and swelling, and instructions on using the diary for the first 7 days after each vaccination. In the period from 8 days after the vaccinations until the diary review at 14 days after each vaccination, the participants were instructed to fill in the diary only in case of an AE.

    Measured: Day 0 through Day 70

  2. Summary of the Number of Participants Reporting All Adverse Events Within the 14 Days After Each of the 1st and 2nd Vaccinations

    Treatment emergent AEs, AEs within 14 days after vaccination, solicited AEs and solicited SAEs occurring within the 7 days after each vaccination, and unsolicited AEs and SAEs occurring within the first 14 days after each vaccination are summarized.

    Measured: Day 0 through Day 70

  3. Number of Participants With Serious Adverse Events Including Medically Important Events Occurring After the 1st Vaccination Through the End of the Trial

    Number of participants with serious adverse events including medically important events occurring after the 1st vaccination through the end of the trial, comparing H56:IC31 to placebo.

    Measured: Day 0 through Day 421

  4. Efficacy of H56:IC31 Compared to Placebo in Reducing the Rate of TB Disease Relapse

    Rate of TB relapse defined as subjects meeting the primary endpoint of TB disease recurrence, AND determined by whole genome sequencing (WGS) of the Mtb isolate to be the same strain of Mtb as in the subject's original isolate from the time of diagnosis

    Measured: Day 70 through Day 421

  5. Efficacy of H56:IC31 Compared to Placebo in Reducing the Rate of TB Disease Reinfection

    Rate of TB disease reinfection defined as subjects meeting the primary endpoint of TB disease recurrence, AND determined by WGS of the Mtb isolate to be a different strain than in the subject's original isolate from the time of diagnosis.

    Measured: Day 70 through Day 421

  6. Antigen-specific Cell-mediated Immune Responses to H56:IC31 by Whole Blood (Absolute Values)

    Antigen-specific cell-mediated immune responses by whole blood intracellular cytokine staining (WB ICS) at baseline (V3= Day 0) and 14 days after the 2nd vaccination (V6= Day 70) in the immunogenicity cohort. Variables of interest for assessment of antigen specific cell mediated immune response to vaccination were the percentage of CD4+ and CD8+ cells that express IL-2, IFN-gamma, TNF, and IL-17 in the following combinations:

    H56 protein-specific CD4+ T cells expressing the total cytokine response, i.e., any combination of IL-2, IFN-gamma, TNF, and/or IL-17 H56 protein-specific CD4+ T cells co-expressing IL-2 and TNF H56 protein-specific CD4+ T cells co-expressing IL-2, IFN-gamma and TNF H56 protein-specific CD8+ T cells expressing any combination of IL-2, IFN-gamma, TNF, and/or IL-17 (total response)

    Measured: Day 0 through Day 70

  7. Humoral Immune Responses to H56:IC31 by Immunoglobulin G ELISA (Absolute Values)

    Antigen-specific antibody responses (anti-H56 IgG) assessed by IgG ELISA of plasma samples at baseline (V3= Day 0) and 14 days after the 2nd vaccination (V6= Day 70). Summary of immune response at Visit 3 (Day 0/Baseline) and Visit 6 (Day 70) as well as fold increase from Baseline to Day 70.

    Measured: Day 0 through Day 70

  8. Antigen-specific Cell-mediated Immune Responses to H56:IC31 by Whole Blood (Fold Increase)

    Antigen-specific cell-mediated immune responses by whole blood intracellular cytokine staining (WB ICS) at baseline (V3= Day 0) and 14 days after the 2nd vaccination (V6= Day 70) in the immunogenicity cohort. Variables of interest for assessment of antigen specific cell mediated immune response to vaccination were the percentage of CD4+ and CD8+ cells that express IL-2, IFN-gamma, TNF, and IL-17 in the following combinations:

    H56 protein-specific CD4+ T cells expressing the total cytokine response, i.e., any combination of IL-2, IFN-gamma, TNF, and/or IL-17 H56 protein-specific CD4+ T cells co-expressing IL-2 and TNF H56 protein-specific CD4+ T cells co-expressing IL-2, IFN-gamma and TNF H56 protein-specific CD8+ T cells expressing any combination of IL-2, IFN-gamma, TNF, and/or IL-17 (total response)

    Measured: Day 0 through Day 70

  9. Humoral Immune Responses to H56:IC31 by Immunoglobulin G ELISA (Fold Increase From Baseline to Visit 6 [Day 70])

    Antigen-specific antibody responses (anti-H56 IgG) assessed by IgG ELISA of plasma samples at baseline (V3= Day 0) and 14 days after the 2nd vaccination (V6= Day 70). Summary of immune response at Visit 3 (Day 0/Baseline) and Visit 6 (Day 70) as well as fold increase from Baseline to Day 70.

    Measured: Day 0 through Day 70

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Apr 2018
  2. Study start31 Jan 2019
  3. Primary completion20 Mar 2023
  4. Study completion20 Mar 2023

Resources

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
2 Cohorts - H56:IC31 and Placebo. First 150 participants will be in a safety group with additional scheduled evaluations.
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
831 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03512249
Sponsor's protocol ID
A-055
Status last verified
Feb 2026
First submitted
19 Apr 2018
Last updated
24 Feb 2026
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: De-identified participant safety and immunogenicity data have been uploaded to a central repository (https://zenodo.org/records/11610286) and may be shared upon request. WGS and tNGS data are available in the Sequence Read Archive of the National Center for Biotechnology Information as FASTQ files, under study accession number PRJNA1171160."

Publications

  • Borges AH, Russell M, Tait D, Scriba TJ, Nemes E, Skallerup P, van Brakel E, Cabibbe AM, Cirillo DM, Leuvennink-Steyn M, Rutkowski KT, Wood GK, Thierry-Carstensen B, Tingskov PN, Meldgaard EC, Kristiansen MP, Sondergaard RE, Hansen CH, Follmann F, Jensen CG, Gela A, Ntinginya NE, Ruhwald M, Shenje J, White L, Innes C, Selepe P, Ngaraguza B, Holmgren C, Collings T, Andersen P, Dawson R, Churchyard G, Sabi I, Diacon AH, Mortensen R, Hatherill M; POR TB study group. Immunogenicity, safety, and efficacy of the vaccine H56:IC31 in reducing the rate of tuberculosis disease recurrence in HIV-negative adults successfully treated for drug-susceptible pulmonary tuberculosis: a double-blind, randomised, placebo-controlled, phase 2b trial. Lancet Infect Dis. 2025 Jul;25(7):751-763. doi: 10.1016/S1473-3099(24)00814-4. Epub 2025 Mar 5.

    PubMed 40056922

  • Iannucci I, Di Marco F, Moghaddasi K, Miotto P; POR TB study group; Cabibbe AM, Cirillo DM. Towards culture-free sequencing of Mycobacterium tuberculosis: evaluating new targeted and whole-genome approaches for genotyping and drug resistance profiling. Genome Med. 2026 Jul 21. doi: 10.1186/s13073-026-01726-7. Online ahead of print.

    PubMed 42482138

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing H56:IC31 in people with Tuberculosis, Pulmonary, run by International AIDS Vaccine Initiative at 6 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 9 inclusion and 17 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 24 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 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?

Yes. Results are posted in the registry (first posted 24 Feb 2026). 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?

Rate of TB Disease Recurrence (Relapse or Reinfection), Defined as TB Diagnosed by Confirmation of Mtb by Culture of Sputum. (time frame: During the period starting 14 days after the 2nd vaccination (V6= Day 70) and ending 12 months after the 2nd 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 NCT03512249, which also lists 2 linked publications.

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 24 Feb 2026.

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