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Safety and Immunogenicity of a Mycobacterium Tuberculosis Vaccine M72/AS01E in Participants With Well-controlled HIV (MESA-TB)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04556981
Recruitment Status : Not yet recruiting
First Posted : September 21, 2020
Last Update Posted : September 21, 2020
Sponsor:
Information provided by (Responsible Party):
Bill & Melinda Gates Medical Research Institute

Brief Summary:
The purpose of this study is to assess the safety and immunogenicity of M72/AS01E vaccination in virally suppressed, antiretroviral-treated participants with human immunodeficiency virus infection (HIV).

Condition or disease Intervention/treatment Phase
Human Immunodeficiency Virus Biological: M72/AS01E Mycobacterium tuberculosis vaccine Biological: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Placebo-controlled, Observer-blind, Phase 2 Study to Evaluate Safety and Immunogenicity of the Investigational M72/AS01E Mycobacterium Tuberculosis (Mtb) Vaccine in Virally Suppressed, Antiretroviral-treated Participants With Human Immunodeficiency Virus (HIV)
Estimated Study Start Date : October 2020
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: M72/AS01E vaccine Biological: M72/AS01E Mycobacterium tuberculosis vaccine
Participants will receive an intramuscular dose of M72 (10 micrograms of recombinant fusion protein) reconstituted with AS01E (an adjuvant system), on Day 1 and Day 29

Placebo Comparator: Placebo Biological: Placebo
Participants will receive an intramuscular dose of saline (0.9% NaCl), on Day 1 and Day 29




Primary Outcome Measures :
  1. Number of Participants With Solicited Adverse Events (AEs) Through 7 Days Post Each Dose of Study Intervention [ Time Frame: Day 1 through Day 36 ]
  2. Number of Participants With Unsolicited AEs Through 28 Days Post Each Dose of Study Intervention [ Time Frame: Day 1 through Day 57 ]
  3. Number of Participants With Serious AEs (SAEs) through end of study [ Time Frame: Up to Day 390 ]

Secondary Outcome Measures :
  1. Number of Participants With Potential Immune-mediated Diseases (pIMDs) [ Time Frame: Up to Day 390 ]
  2. Number of Participants With Clinically Significant Safety Laboratory Assessments Grade 3 or Above [ Time Frame: Up to Day 390 ]
  3. M72-specific Antibody Concentrations Pre- and Post-vaccination Through the End of the Study [ Time Frame: Day 1 through Day 390 ]
  4. Frequency of M72-specific CD4+ T Cells and CD8+ T Cells Response Pre- and Post-vaccination Through the End of the Study [ Time Frame: Day 1 through Day 390 ]
  5. Magnitude of M72-specific CD4+ T Cells and CD8+ T Cells Response Pre- and Post-vaccination Through the End of the Study [ Time Frame: Day 1 through Day 390 ]
  6. Polyfunctionality of M72-specific CD4+ T cells and CD8+ T cells Response pre- and Post-vaccination Through the End of the Study [ Time Frame: Day 1 through Day 390 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   16 Years to 35 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant with documented human immunodeficiency virus (HIV) infection who fulfill all of the following:

    • Has reactive anti-HIV antibody at screening
    • On antiretroviral therapy (ART) for at least 3 consecutive months at screening
    • Has documented HIV RNA <200 copies/mL at screening
    • Participants with CD4+ cell counts ≥200 cells/μL at screening
  • Participants have had tuberculosis (TB) preventive therapy (TPT) in the past and are not receiving TPT at the time of screening, according to the judgment of the investigators
  • Participants who are healthy as determined by medical evaluation including medical history, physical examination and laboratory tests
  • Capable of giving signed informed consent and informed assent (if appropriate), which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) or informed assent form, and in the protocol.
  • Female participants of childbearing potential must agree not to become pregnant from the time of study enrollment for one year after study intervention. Women physically capable of pregnancy, sexually active and having no history of hysterectomy or tubal ligation or menopause must agree to use an effective method of avoiding pregnancy during this period.
  • Participants who agree to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and have no current plans to relocate from the study area for the duration of the study.

Exclusion Criteria:

  • Acute illness or fever ≥99.5°F (or ≥37.5˚C) on Day 1
  • History of active TB disease
  • Evidence of active TB disease with any of the following:

    • Have symptoms or signs of TB disease
    • Have a positive sputum Xpert MTB/RIF assay (only in participants with sputum sample at screening)
    • Are on treatment for active TB disease
  • Evidence and/or history of clinically significant medical conditions (other than HIV infection) as judged by the investigator, including malignancies
  • 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
  • Any medications or other therapies that may impact the immune system such as immune globulin, interferon, immunomodulators, cytotoxic drugs or other drugs known to be frequently associated with major organ toxicity as determined by the investigator, within 90 days prior to Day 1
  • Immunosuppressive agents including systemic steroids - prior corticosteroid therapy within 90 days prior to Day 1 (permitted: 5 mg/day prednisone equivalent, inhaled, topical, and intra-articular corticosteroids)
  • Receipt or donation of blood or blood products within 90 days prior to Day 1 or planned receipt or donation during the study period
  • Participation in an interventional clinical trial and/or receipt of any investigational drug within 180 days prior to signing informed consent or assent
  • History of previous administration of experimental Mycobacterium tuberculosis vaccine
  • Safety laboratory values outside of normal range, for age and sex that are suggestive of a disease state (Grade 1 abnormalities, as per Division of AIDS [DAIDS] toxicity table version 2.1, will not lead to exclusion if the investigator considers them not clinically significant.)
  • 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
  • Current hepatitis B and/or hepatitis C infection
  • History of allergy or hypersensitivity to the study drug, excipients or related substances
  • Shared residence with an individual who is receiving TB treatment or with someone who is known to have incompletely treated TB, e.g., Xpert MTB/RIF assay-positive, polymerase chain reaction (PCR)-positive, culture-positive, smear-positive TB, or clinically diagnosed unconfirmed TB
  • Female participants with any one of the following conditions: currently pregnant or lactating/nursing; having positive serum pregnancy test during the screening window, planning a pregnancy within 1 year after first dose of study product
  • Individuals who are acting as study personnel or immediate family members (brother, sister, child, parent) or the spouse/partner of study personnel.
  • Child in Care

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): NCT04556981


Contacts
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Contact: Gates MRI +1 857 702 2108 clinical.trials@gatesmri.org

Locations
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South Africa
Wits RHI
Johannesburg, Gauteng, South Africa, 2001
CAPRISA
Durban, Kwazulu-Natal, South Africa, 4001
The Aurum Institute
Klerksdorp, North West, South Africa, 2570
Desmond Tutu HIV Foundation
Cape Town, Western Cape, South Africa, 6850
CIDRI-Africa
Cape Town, Western Cape, South Africa, 7784
SATVI
Worcester, Western Cape, South Africa, 6850
Sponsors and Collaborators
Bill & Melinda Gates Medical Research Institute
Investigators
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Study Director: Gates MRI Bill & Melinda Gates Medical Research Institute
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Responsible Party: Bill & Melinda Gates Medical Research Institute
ClinicalTrials.gov Identifier: NCT04556981    
Other Study ID Numbers: Gates MRI-TBV02-202
First Posted: September 21, 2020    Key Record Dates
Last Update Posted: September 21, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Bill & Melinda Gates Medical Research Institute:
Mycobacterium tuberculosis
M72/AS01E Vaccine
Antiretroviral therapy
Mtb
HIV
TB vaccine
Additional relevant MeSH terms:
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Tuberculosis
Mycobacterium Infections
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases