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

NCT03512249 | Completed Phase 2 Results DMC

• 1 other identifier: A-055
• Study Type: interventional
• Target: 831
• Locations: 2 countries
• Sites: 6

Brief 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 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).

Conditions

Tuberculosis, Pulmonary

Keywords

tuberculosis; prevention of recurrence; relapse; reinfection; subunit vaccine; whole-genome sequencing

Outcome Measures

Primary Outcomes (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).

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

Secondary Outcomes (9)

• 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

  Day 0 through Day 70

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

  Day 0 through Day 70

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

  Day 0 through Day 421

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

  Day 70 through Day 421

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

  Day 70 through Day 421

Study Arms (2)

H56:IC31

EXPERIMENTAL

The 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.

Biological: H56:IC31

Placebo

PLACEBO COMPARATOR

Sterile saline for injection

Biological: Placebo

Interventions

H56:IC31 BIOLOGICAL

5ug H56/500 nmol IC31

Also known as: H56

H56:IC31

Placebo BIOLOGICAL

Sterile saline for injection

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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 HIV negative at V2.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• International AIDS Vaccine Initiative: lead
• Statens Serum Institut: collaborator
• University of Cape Town Lung Institute: collaborator
• TASK Applied Science: collaborator
• The Aurum Institute NPC: collaborator
• National Institute for Medical Research, Tanzania: collaborator
• Ospedale San Raffaele: collaborator
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator
• South African Tuberculosis Vaccine Initiative: collaborator

Study Sites (6)

Task Clinical Research Centre

Bellville, Cape Town, 7530, South Africa

Location

University of Cape Town Lung Institute

Mowbray, Cape Town, South Africa

Location

The Aurum Institute: Tembisa Clinical Research Centre

Tembisa, Gauteng, 1632, South Africa

Location

The Aurum Institute

Klerksdorp, North West, 2570, South Africa

Location

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

Cape Town, Western Cape, 6850, South Africa

Location

NIMR Mbeya Medical Research Centre

Mbeya, Tanzania

Location

Related Publications (1)

• 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.

  PMID: 40056922 RESULT

Related Links

• H56:IC31 POR manuscript

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Tuberculosis; Recurrence; Reinfection

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The Covid-19 pandemic had implications on the trial conduct. The main impacts were delays in recruitment and visit windows being exceeded during the periods where the sites had to close for trial visits and activities. The two protocol amendments, FV 4.0 dated 03 Feb 2021 and FV 5.0 dated 19 May 2021, were implemented, as mitigation measures. Recruitment had to be stopped before enrolment of the planned 900 participants due to expiry of IP.

Results Point of Contact

• Title: Marisa Russell, Senior Director of Clinical Operations, Clinical Development
• Organization: IAVI

mrussell@iavi.org

+27 21 344 1204

Study Officials

• Marissa Russell

  IAVI (previously Aeras)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The unblinded persons in the study are the study vaccine manager (and designee) who manages the participant inventory log(s) at the trial site, the unblinded site staff, and the unblinded clinical trial site monitor(s) responsible for monitoring the investigational product at the trial site. All unblinded persons must take care to not reveal individual participant treatment assignments to any blinded member of the study team. There is an unblinded contact person at the sponsor's site in order to manage queries from the unblinded site staff or the unblinded monitors in the trial. The study vaccine manager (and designee) should be a designated site team member, such as the study pharmacist. Unblinded site staff must not participate in the evaluation of adverse events. The randomization list will be provided by the unblinded statistician and will be implemented as a module in the eCRF.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: 2 Cohorts - H56:IC31 and Placebo. First 150 participants will be in a safety group with additional scheduled evaluations.

Study Record Dates

• First Submitted: April 19, 2018
• First Posted: April 30, 2018
• Study Start: January 31, 2019
• Primary Completion: March 20, 2023
• Study Completion: March 20, 2023
• Last Updated: February 24, 2026
• Results First Posted: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 01-Oct-2024 until 01-Oct-2034
• Access Criteria: 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. Research proposals should be submitted to the corresponding author (albs@ssi.dk). The proposal will be discussed for methodologically soundness by the POR TB study group. The research proposal's scientific relevance, design, statistical power, feasibility, and overlap with already published data will be assessed. Upon completion of the review, feedback will be provided to the proposer or proposers. In some circumstances, a revision of the concept might be requested. If the concept is approved for implementation, a writing group will be established consisting of the proposers and representatives from the POR TB study group. Study documents such as the trial protocol and informed consent forms may also be shared upon written request to the corresponding author, per the same process.

Locations

TA (1); ZA (5)