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| Name | Class |
|---|---|
| Statens Serum Institut | OTHER |
| University of Cape Town Lung Institute | OTHER |
| TASK Applied Science | OTHER |
| The Aurum Institute NPC |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Placebo | Placebo Comparator | Sterile saline for injection |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| H56:IC31 | Biological | 5ug H56/500 nmol IC31 |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marissa Russell | IAVI (previously Aeras) | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Task Clinical Research Centre | Bellville | Cape Town | 7530 | South Africa | ||
| University of Cape Town Lung Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40056922 | Result | 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. |
| Label | URL |
|---|---|
| H56:IC31 POR manuscript | View source |
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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."
01-Oct-2024 until 01-Oct-2034
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.
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Various methods of recruitment were used i.e., advertising, referrals, or proposition. All recruitment materials were approved by IRB and/or IEC. Interested TB patients from local TB clinics were invited to participate in the informed consent process. Recruitment commenced on 31 Jan 2019 and ended on 03 Sep 2021.
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| ID | Title | Description |
|---|---|---|
| FG000 | H56:IC31 | 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. H56:IC31: 5ug H56/500 nmol IC31 |
| FG001 | Placebo | Sterile saline for injection Placebo: Sterile saline for injection |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All randomized participants were included in the intention to treat (ITT) analysis set.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | H56:IC31 | 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. H56:IC31: 5ug H56/500 nmol IC31 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | The primary analysis set for efficacy was the modified Intention to treat (mITT) analysis set. The mITT analysis set included all randomized participants except for those with TB disease recurrence before V6=Day 70 (or 14 days after the second injection for those who received both injections). Participants were evaluated as randomized. | Posted | Count of Participants | Participants | During the period starting 14 days after the 2nd vaccination (V6= Day 70) and ending 12 months after the 2nd vaccination |
|
Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | H56:IC31 | 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. H56:IC31: 5ug H56/500 nmol IC31 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gun shot wound | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection site pain | General disorders | MedDRA 21.1 | Systematic Assessment |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Marisa Russell, Senior Director of Clinical Operations, Clinical Development | IAVI | +27 21 344 1204 | mrussell@iavi.org |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 19, 2021 | Apr 8, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 15, 2023 | Apr 8, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D014397 | Tuberculosis, Pulmonary |
| D014376 | Tuberculosis |
| D012008 | Recurrence |
| D000084063 | Reinfection |
| ID | Term |
|---|---|
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
Not provided
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| OTHER |
| National Institute for Medical Research, Tanzania | OTHER_GOV |
| Ospedale San Raffaele | OTHER |
| European and Developing Countries Clinical Trials Partnership (EDCTP) | OTHER_GOV |
| South African Tuberculosis Vaccine Initiative | OTHER |
2 Cohorts - H56:IC31 and Placebo. First 150 participants will be in a safety group with additional scheduled evaluations.
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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.
| Placebo | Biological | Sterile saline for injection |
|
| 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 | 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. | 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 | 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. | Day 0 through Day 421 |
| 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 | Day 70 through Day 421 |
| 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. | Day 70 through Day 421 |
| 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) | Day 0 through Day 70 |
| 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. | Day 0 through Day 70 |
| 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) | Day 0 through Day 70 |
| 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. | Day 0 through Day 70 |
| Mowbray |
| Cape Town |
| South Africa |
| The Aurum Institute: Tembisa Clinical Research Centre | Tembisa | Gauteng | 1632 | South Africa |
| The Aurum Institute | Klerksdorp | North West | 2570 | South Africa |
| South African Tuberculosis Vaccine Initiative , Project Office, Brewelskloof Hospital , Harlem Street, Worcester | Cape Town | Western Cape | 6850 | South Africa |
| NIMR Mbeya Medical Research Centre | Mbeya | Tanzania |
| Withdrawal by Subject |
|
| Recurrent TB |
|
| Other |
|
| BG001 | Placebo | Sterile saline for injection Placebo: Sterile saline for injection |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Age, Customized | Age, categorical | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Height | Mean | Standard Deviation | cm |
|
| Weight | Mean | Standard Deviation | kg |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
|
| BMI group | Number of participants with low BMI (13 to 25 kg/m^2) and number of participants with high BMI (25 kg/m^2 and above). | Count of Participants | Participants |
|
| Smoking status | Count of Participants | Participants |
|
| Enrollment per trial site | Number of participants enrolled per study site. | Count of Participants | Participants |
|
| Anaemia | Number of participants with and without. Anemia is defined as follows: women: hemoglobin < 12 g/dL men: hemoglobin < 13 g/dL | Count of Participants | Participants |
|
| Diabetes mellitus | Number of participants with and without diabetes mellitus at baseline. Participants with medical history high level term Diabetes mellitus (incl subtypes) which includes non-insulin dependent types. | Count of Participants | Participants |
|
| Comorbidity | Number of participants with comorbidity versus no comorbidity at baseline. Comorbidity defined as history of chronic or intermittent diseases, medical conditions or symptoms judged to influence the primary endpoint as assessed by the medical expert of the trial. | Count of Participants | Participants |
|
| OG000 | H56:IC31 | 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. H56:IC31: 5ug H56/500 nmol IC31 |
| OG001 | Placebo | Sterile saline for injection Placebo: Sterile saline for injection |
|
|
|
| Secondary | 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. | Safety analysis set | Posted | Number | participants | Day 0 through Day 70 |
|
|
|
| Secondary | 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. | Safety analysis set | Posted | Number | participants | Day 0 through Day 70 |
|
|
|
| Secondary | 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. | Safety analysis set | Posted | Number | participants | Day 0 through Day 421 |
|
|
|
| Secondary | 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 | mITT analysis set. The mITT analysis set included all randomized participants except for those with TB disease recurrence before V6 = Day70 (or 14 days after the second injection for those who received both injections). Participants were evaluated as randomized. | Posted | Count of Participants | Participants | Day 70 through Day 421 |
|
|
|
|
| Secondary | 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. | mITT analysis set: The mITT analysis set included all randomized participants except for those with TB disease recurrence before V6 = Day70 (or 14 days after the second injection for those who received both injections). Participants were evaluated as randomized. | Posted | Count of Participants | Participants | Day 70 through Day 421 |
|
|
|
|
| Secondary | 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) | Immunogenicity analysis set: The immunogenicity analysis set consisted of all participants from the mITT population who received both doses of H56:IC31 or placebo and who were included in the immunogenicity cohort (= the first 100 randomized participants at 2 specific sites). | Posted | Median | Inter-Quartile Range | percentage of cells | Day 0 through Day 70 |
|
|
|
| Secondary | 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. | Immunogenicity analysis set: The immunogenicity analysis set consisted of all participants from the mITT population who received both doses of H56:IC31 or placebo and who were included in the immunogenicity cohort (= the first 100 randomized participants at 2 specific sites). | Posted | Median | Inter-Quartile Range | EU/mL | Day 0 through Day 70 |
|
|
|
| Secondary | 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) | Immunogenicity analysis set: The immunogenicity analysis set consisted of all participants from the mITT population who received both doses of H56:IC31 or placebo and who were included in the immunogenicity cohort (= the first 100 randomized participants at 2 specific sites). | Posted | Median | Inter-Quartile Range | Fold increase | Day 0 through Day 70 |
|
|
|
| Secondary | 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. | Immunogenicity analysis set: The immunogenicity analysis set consisted of all participants from the mITT population who received both doses of H56:IC31 or placebo and who were included in the immunogenicity cohort (= the first 100 randomized participants at 2 specific sites). | Posted | Median | Inter-Quartile Range | Fold increase | Day 0 through Day 70 |
|
|
|
| 2 |
| 415 |
| 14 |
| 415 |
| 300 |
| 415 |
| EG001 | Placebo | Sterile saline for injection Placebo: Sterile saline for injection | 6 | 416 | 12 | 416 | 267 | 416 |
| Chest injury | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
|
| Craniocerebral injury | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
|
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
|
| Stab wound | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
|
| Toxicity to various agents | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
|
| Traumatic haemothorax | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Abscess neck | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Abortion incomplete | Pregnancy, puerperium and perinatal conditions | MedDRA 21.1 | Systematic Assessment |
|
| Ectopic pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA 21.1 | Systematic Assessment |
|
| Polyhydramnios | Pregnancy, puerperium and perinatal conditions | MedDRA 21.1 | Systematic Assessment |
|
| Stillbirth | Pregnancy, puerperium and perinatal conditions | MedDRA 21.1 | Systematic Assessment |
|
| Cor Pulmonale | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
|
| Supraventricular tachycardia | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Epilepsy | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Death | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Haemangioma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
|
| Substance-induced psychotic disorder | Psychiatric disorders | MedDRA 21.1 | Systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hospitalization | Surgical and medical procedures | MedDRA 21.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Injection site erythema | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Injection site swelling | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
Not provided
Not provided
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D012141 | Respiratory Tract Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Fatigue |
|
| Injection site pain |
|
| Injection site erythema |
|
| Injection site swelling |
|
| Pyrexia |
|
| Chills |
|
| Chest pain |
|
| Hypothermia |
|
| Asthenia |
|
| Malaise |
|
| Influenza like illness |
|
| Pain |
|
| Injection site pruritus |
|
| Injection site rash |
|
| Peripheral swelling |
|
| Injection site discoloration |
|
| Oedema peripheral |
|
| Suprapubic pain |
|
| Vessel puncture site erythema |
|
| Vessel puncture site pain |
|
| Vessel puncture site swelling |
|
| Musculoskeleta and connective tissue disorders |
|
| Myalgia |
|
| Arthralgia |
|
| Back pain |
|
| Musculoskeletal pain |
|
| Neck pain |
|
| Muscle spasms |
|
| Pain in extremity |
|
| Musculoskeletal chest pain |
|
| Muscle fatigue |
|
| Musculoskeletal stiffness |
|
| Nervous system disorders |
|
| Headache |
|
| Dizziness |
|
| Paraesthesia |
|
| Gastrointestinal disorders |
|
| Nausea |
|
| Abdominal pain |
|
| Diarrhoea |
|
| Toothache |
|
| Abdominal pain upper |
|
| Vomiting |
|
| Dyspepsia |
|
| Abdominal discomfort |
|
| Abdominal pain lower |
|
| Anal fissure |
|
| Constipation |
|
| Gastritis |
|
| Tongue eruption |
|
| Tongue ulceration |
|
| Skin and subcutaneous tissue disorders |
|
| Rash |
|
| Rash papular |
|
| Pruritus generalised |
|
| Dermatitis |
|
| Hyperhidrosis |
|
| Pruritus |
|
| Angioedema |
|
| Dermatitis allergic |
|
| Night sweats |
|
| Papule |
|
| Rash erythematous |
|
| Infections and infestations |
|
| Upper respiratory tract infection |
|
| Gastroenteritis |
|
| Influenza |
|
| Lower respiratory tract infection |
|
| Rhinitis |
|
| Urethritis |
|
| Urinary tract infection |
|
| Abscess |
|
| Anal abscess |
|
| Bronchitis |
|
| Corona virus infection |
|
| Injection site pustule |
|
| Nasopharyngitis |
|
| Otitis externa |
|
| Rash pustular |
|
| Respiratory tract infection |
|
| Sinusitis |
|
| Tinea pedis |
|
| Tinea versicolour |
|
| Tonsillitis |
|
| Tracheobronchitis viral |
|
| Viral upper respiratory tract infection |
|
| Respiratory, thoracic and mediastinal disorders |
|
| Cough |
|
| Rhinorrhoea |
|
| Oropharyngeal pain |
|
| Bronchospasm |
|
| Dyspnoea |
|
| Epistaxis |
|
| Productive cough |
|
| Throat irritation |
|
| Injury, poisoning and procedural complications |
|
| Joint injury |
|
| Ligament sprain |
|
| Limb injury |
|
| Gun shot wound |
|
| Lip injury |
|
| Muscle strain |
|
| Repetitive strain injury |
|
| Soft tissue injury |
|
| Stab wound |
|
| Wound |
|
| Wrist fracture |
|
| Investigations |
|
| Alanine aminotransferase increased |
|
| Aspartate aminotransferase increased |
|
| Gamma-glutamyltransferase increased |
|
| Blood creatinine increased |
|
| Blood pressure systolic increased |
|
| Glucose urine |
|
| Hepatic enzyme increased |
|
| Neutrophil count increased |
|
| Platelet count decreased |
|
| White blood cell count decreased |
|
| Vascular disorders |
|
| Hypertension |
|
| Hypotension |
|
| Reproductive system and breast disorders |
|
| Dysmenorrhoea |
|
| Breast pain |
|
| Genital rash |
|
| Blood and lymphatic system disorders |
|
| Neutropenia |
|
| Neutrophilia |
|
| Eye disorders |
|
| Asthenopia |
|
| Eye pain |
|
| Eye pruritus |
|
| Pinguecula |
|
| Metabolism and nutrition disorders |
|
| Decreased appetite |
|
| Diabetes mellitus |
|
| Hyperglycaemia |
|
| Cardiac disorders |
|
| Palpitations |
|
| Tachycardia |
|
| Ear and labyrinth disorders |
|
| Ear pain |
|
| Immune system disorders |
|
| Seasonal allergy |
|
| Psychiatric disorders |
|
| Insomnia |
|
| Post-traumatic stress disorder |
|
| Renal and urinary disorders |
|
| Dysuria |
|
| Proteinuria |
|
| Adverse event of special interest |
|
| Serious adverse event (SAE) |
|
| Fatal AE |
|
| Related AE |
|
| Related SAE |
|
| SUSAR |
|
| AE leading to discontinuation of IMP |
|
| AE leading to discontinuation of trial |
|
| Severe AE |
|
| Moderate AE |
|
| Mild AE |
|
| AE not recovered/not resolved |
|
| AE recovered/resolved with sequelae |
|
| AE recovered/resolved |
|
| AE outcome unknown |
|
| Related SAE |
|
| SUSAR |
|
| SAE leading to discontinuation of IMP |
|
| SAE leading to discontinuation of trial |
|
| Intensity: Severe |
|
| Intensity: Moderate |
|
| Recovered/resolved with sequelae |
|
| Recovered/resolved |
|
| CD8+ T cells expressing any combination of IL-2, IFN-gamma, TNF-α, or IL-17 Visit 3(Day 0) Baseline |
|
| CD8+ T cells expressing any combination of IL-2, IFN-gamma, TNF-α, or IL-17 Visit 6 (Day 70) |
|