Safety and Immunogenicity of a Mycobacterium Tuberculosis Vaccine M72/AS01E in Participants With Well-controlled HIV (MESA-TB)
Primary Purpose
Human Immunodeficiency Virus
Status
Completed
Phase
Phase 2
Locations
South Africa
Study Type
Interventional
Intervention
M72/AS01E Mycobacterium tuberculosis vaccine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Human Immunodeficiency Virus focused on measuring Mycobacterium tuberculosis, M72/AS01E Vaccine, Antiretroviral therapy, Mtb, HIV, TB vaccine
Eligibility 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
Sites / Locations
- Wits RHI
- Ekhaya VAC
- CAPRISA
- The Aurum Institute
- Desmond Tutu HIV Foundation
- SATVI
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
M72/AS01E vaccine
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Number of Participants With Solicited Adverse Events (AEs) Through 7 Days Post Each Dose of Study Intervention
Number of Participants With Unsolicited AEs Through 28 Days Post Each Dose of Study Intervention
Number of Participants With Serious AEs (SAEs) through end of study
Secondary Outcome Measures
Number of Participants With Potential Immune-mediated Diseases (pIMDs)
Number of Participants With Clinically Significant Safety Laboratory Assessments Grade 3 or Above
M72-specific Antibody Concentrations Pre- and Post-vaccination Through the End of the Study
Frequency of M72-specific CD4+ T Cells and CD8+ T Cells Response Pre- and Post-vaccination Through the End of the Study
Magnitude of M72-specific CD4+ T Cells and CD8+ T Cells Response Pre- and Post-vaccination Through the End of the Study
Polyfunctionality of M72-specific CD4+ T cells and CD8+ T cells Response pre- and Post-vaccination Through the End of the Study
Full Information
NCT ID
NCT04556981
First Posted
September 10, 2020
Last Updated
June 12, 2023
Sponsor
Bill & Melinda Gates Medical Research Institute
Collaborators
Wellcome Trust
1. Study Identification
Unique Protocol Identification Number
NCT04556981
Brief Title
Safety and Immunogenicity of a Mycobacterium Tuberculosis Vaccine M72/AS01E in Participants With Well-controlled HIV
Acronym
MESA-TB
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)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
November 17, 2020 (Actual)
Primary Completion Date
August 12, 2022 (Actual)
Study Completion Date
August 12, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bill & Melinda Gates Medical Research Institute
Collaborators
Wellcome Trust
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Immunodeficiency Virus
Keywords
Mycobacterium tuberculosis, M72/AS01E Vaccine, Antiretroviral therapy, Mtb, HIV, TB vaccine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
402 (Actual)
8. Arms, Groups, and Interventions
Arm Title
M72/AS01E vaccine
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Biological
Intervention Name(s)
M72/AS01E Mycobacterium tuberculosis vaccine
Intervention Description
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
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Participants will receive an intramuscular dose of saline (0.9% NaCl), on Day 1 and Day 29
Primary Outcome Measure Information:
Title
Number of Participants With Solicited Adverse Events (AEs) Through 7 Days Post Each Dose of Study Intervention
Time Frame
Day 1 through Day 36
Title
Number of Participants With Unsolicited AEs Through 28 Days Post Each Dose of Study Intervention
Time Frame
Day 1 through Day 57
Title
Number of Participants With Serious AEs (SAEs) through end of study
Time Frame
Up to Day 390
Secondary Outcome Measure Information:
Title
Number of Participants With Potential Immune-mediated Diseases (pIMDs)
Time Frame
Up to Day 390
Title
Number of Participants With Clinically Significant Safety Laboratory Assessments Grade 3 or Above
Time Frame
Up to Day 390
Title
M72-specific Antibody Concentrations Pre- and Post-vaccination Through the End of the Study
Time Frame
Day 1 through Day 390
Title
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
Title
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
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gates MRI
Organizational Affiliation
Bill & Melinda Gates Medical Research Institute
Official's Role
Study Director
Facility Information:
Facility Name
Wits RHI
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
2001
Country
South Africa
Facility Name
Ekhaya VAC
City
Cape Town
State/Province
Khayelitsha
ZIP/Postal Code
7782
Country
South Africa
Facility Name
CAPRISA
City
Durban
State/Province
Kwazulu-Natal
ZIP/Postal Code
4001
Country
South Africa
Facility Name
The Aurum Institute
City
Klerksdorp
State/Province
North West
ZIP/Postal Code
2570
Country
South Africa
Facility Name
Desmond Tutu HIV Foundation
City
Cape Town
State/Province
Western Cape
ZIP/Postal Code
6850
Country
South Africa
Facility Name
SATVI
City
Worcester
State/Province
Western Cape
ZIP/Postal Code
6850
Country
South Africa
12. IPD Sharing Statement
Plan to Share IPD
Yes
Learn more about this trial
Safety and Immunogenicity of a Mycobacterium Tuberculosis Vaccine M72/AS01E in Participants With Well-controlled HIV
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