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

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ClinicalTrials.gov Identifier: NCT03512249
Recruitment Status : Not yet recruiting
First Posted : April 30, 2018
Last Update Posted : August 31, 2018
Sponsor:
Collaborator:
Statens Serum Institut
Information provided by (Responsible Party):
Aeras

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.

    4 trial sites are planned in South Africa (ZA): 1 site in Klerksdorp at the Aurum Institute and 3 sites in Cape Town at TASK, UCT Lung Institute and SATVI. 1 trial site is planned in Tanzania (TZ): 1 site in Mbeya at NIMR.


Condition or disease Intervention/treatment Phase
Tuberculosis, Pulmonary Biological: H56:IC31 Biological: Placebo Phase 2

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. 4 trial sites are planned in South Africa (ZA): 1 site in Klerksdorp at the Aurum Institute and 3 sites in Cape Town at TASK, UCT Lung Institute and SATVI. 1 trial site is planned in Tanzania (TZ): Mbeya at 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 900 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 2 Cohorts - H56:IC31 and Placebo. First 100 participants will be in a safety group with additional scheduled evaluations.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:

The unblinded persons in the study are the study vaccine manager (and designee) who manages the subject 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 subject treatment assignments to any blinded member of the study team. There will be 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.

Primary Purpose: Prevention
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
Estimated Study Start Date : September 30, 2018
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : December 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Arm Intervention/treatment
Experimental: 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.

Biological: H56:IC31
5ug H56/500 nmol IC31
Other Name: H56

Placebo Comparator: Placebo
Sterile saline for injection
Biological: Placebo
Sterile saline for injection




Primary Outcome Measures :
  1. • 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 ]
    Efficacy of H56:IC31 compared to placebo in reducing the rate of recurrent TB disease (relapse or reinfection)


Secondary Outcome Measures :
  1. Solicited adverse events and all adverse events occurring the first 14 days after each of the 1st and 2nd vaccinations [ Time Frame: Day 0 thru Day 70 ]
    Safety of H56:IC31 compared to placebo

  2. Serious adverse events including medically important events occurring after the 1st vaccination through the end of the trial [ Time Frame: Day 0 thru Day 421 ]
    Safety of H56:IC31 compared to placebo

  3. Efficacy of H56:IC31 compared to placebo in reducing the rate of TB disease relapse [ Time Frame: Day 0 thru Day 421 ]
    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

  4. • Efficacy of H56:IC31 compared to placebo in reducing the rate of TB disease reinfection [ Time Frame: Day 0 thru Day 421 ]
    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.

  5. Antigen-specific cell-mediated immune responses to H56:IC31 [ Time Frame: Day 0 thru Day 70 ]
    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)

  6. Humoral immune responses to H56:IC31 [ Time Frame: Day 0 thru Day 70 ]
    • Humoral immune responses by IgG ELISA of plasma samples taken at baseline (V3= Day 0) and 14 days after the 2nd vaccination (V6= Day 70)



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Completed the written informed consent process.
  2. Agrees to give access to medical records for trial related purposes.
  3. Was HIV-negative (self-reported) with a diagnosis of drug susceptible pulmonary TB at the start of the TB treatment.
  4. Able to provide 2 separate sputum samples within ≤ 7 days of starting TB treatment.
  5. Confirmed Mtb negative by smear AFB microscopy of 2 separate sputum samples taken at V2. Subjects unable to produce sputum, but considered asymptomatic by the investigator, may be considered Mtb negative and eligible for inclusion.
  6. Confirmed HIV negative at V2.
  7. 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.
  8. Aged ≥ 18 years and ≤ 60 years on the date of V3= Day 0.
  9. 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.

Exclusion Criteria:

  1. Diagnosis or co-diagnosis of extra pulmonary TB.
  2. Hospitalized for the current episode of drug susceptible pulmonary TB disease.
  3. History of or ongoing severe disease that in the opinion of the investigator might affect the safety of the subject or the immunogenicity of the investigational product.
  4. Insulin dependent diabetes.
  5. History of allergic disease or reactions likely to be exacerbated by any component of the investigational product.
  6. History or laboratory evidence of immunodeficiency, autoimmune disease or immunosuppression.
  7. History of chronic hepatitis.
  8. Severe anemia, defined as hemoglobin less than 10 g/dL or a hematocrit less than 30% based on most recent hematology obtained before randomization.
  9. History of receipt of treatment against active TB, prior to the current treatment episode, within the last 5 years
  10. Receipt of any investigational TB vaccine previously.
  11. Receipt or planned receipt of any investigational drug or investigational vaccine from V1 through V8= Day 421.
  12. Receipt or planned receipt of any licensed vaccine from V1 through V6= Day 70.
  13. 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.
  14. Has a body mass index (BMI) < 13 (weight, kg / height, m^2)
  15. Female subjects 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.
  16. Female subjects: if lactating / nursing, or pregnant as per positive pregnancy test.
  17. Not suitable for inclusion in the opinion of the investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03512249


Contacts
Contact: Dereck Tait, MD 27 21 442 4991 dtait@aeras.org
Contact: Hanlie Bester 27 21 442 4980 ext 5001 hbester@aeras.org

Locations
South Africa
Task Clinical Research Centre
Bellville 7530, Cape Town, South Africa
University of Cape Town Lung Institute
Mowbray, Cape Town, South Africa
Aurum Institute Not yet recruiting
Klerksdorp, North-West, South Africa, 2570
South African Tuberculosis Vaccine Initiative , Project Office, Brewelskloof Hospital , Harlem Street, Worcester Not yet recruiting
Cape Town, Western Cape, South Africa, 6850
Contact: Mark Hatherill    +27(0)846718280    Mark.Hatherill@uct.ac.za   
Principal Investigator: Justin Shenje         
Tanzania
National Institute for Medical Research Not yet recruiting
Mbeya, Tanzania
Sponsors and Collaborators
Aeras
Statens Serum Institut
Investigators
Study Director: Dereck Tait, MD Aeras
Study Director: Morten Ruhwald, MD, PhD Statens Serum Institut

Responsible Party: Aeras
ClinicalTrials.gov Identifier: NCT03512249     History of Changes
Other Study ID Numbers: A-055
First Posted: April 30, 2018    Key Record Dates
Last Update Posted: August 31, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Tuberculosis
Recurrence
Tuberculosis, Pulmonary
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Disease Attributes
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections