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

• ClinicalTrials.gov Identifier: NCT04556981
• Recruitment Status: Completed
• First Posted: September 21, 2020
• Last Update Posted: June 13, 2023
• Sponsor: Bill & Melinda Gates Medical Research Institute
• Collaborator: Wellcome Trust
• Information provided by (Responsible Party): Bill & Melinda Gates Medical Research Institute

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).

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 402 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)
• Actual Study Start Date: November 17, 2020
• Actual Primary Completion Date: August 12, 2022
• Actual Study Completion Date: August 12, 2022

Arms and Interventions

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

Outcome Measures

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 ]

Eligibility Criteria

• 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

Contacts and Locations

Locations

South Africa

Wits RHI

Johannesburg, Gauteng, South Africa, 2001

Ekhaya VAC

Cape Town, Khayelitsha, South Africa, 7782

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

SATVI

Worcester, Western Cape, South Africa, 6850

Sponsors and Collaborators

Bill & Melinda Gates Medical Research Institute

Wellcome Trust

Investigators

• Study Director: Gates MRI; Bill & Melinda Gates Medical Research Institute

  Study Documents (Full-Text)

Documents provided by Bill & Melinda Gates Medical Research Institute:

Study Protocol  [PDF] February 26, 2021

Statistical Analysis Plan  [PDF] February 20, 2022

More Information

• Responsible Party: Bill & Melinda Gates Medical Research Institute
• ClinicalTrials.gov Identifier: NCT04556981
• Other Study ID Numbers: Gates MRI-TBV02-202; 221698/Z/20/Z ( Other Grant/Funding Number: Wellcome Trust )
• First Posted: September 21, 2020
• Last Update Posted: June 13, 2023
• Last Verified: June 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

• 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:

Tuberculosis; Acquired Immunodeficiency Syndrome; HIV Infections; Mycobacterium Infections; Immunologic Deficiency Syndromes; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Immune System Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases