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

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)

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).

Study Overview

• Status: Completed
• Conditions: Human Immunodeficiency Virus
• Intervention / Treatment: Biological: M72/AS01E Mycobacterium tuberculosis vaccine; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 402
• Phase: Phase 2

Contacts and Locations

Study Locations

• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2001
      • Wits RHI
  • Khayelitsha
    • Cape Town, Khayelitsha, South Africa, 7782
      • Ekhaya VAC
  • Kwazulu-Natal
    • Durban, Kwazulu-Natal, South Africa, 4001
      • CAPRISA
  • North West
    • Klerksdorp, North West, South Africa, 2570
      • The Aurum Institute
  • Western Cape
    • Cape Town, Western Cape, South Africa, 6850
      • Desmond Tutu HIV Foundation
    • Worcester, Western Cape, South Africa, 6850
      • SATVI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 35 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Biological: Placebo; Participants will receive an intramuscular dose of saline (0.9% NaCl), on Day 1 and Day 29
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Solicited Adverse Events (AEs) Through 7 Days Post Each Dose of Study Intervention	Day 1 through Day 36
Number of Participants With Unsolicited AEs Through 28 Days Post Each Dose of Study Intervention	Day 1 through Day 57
Number of Participants With Serious AEs (SAEs) through end of study	Up to Day 390

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Bill & Melinda Gates Medical Research Institute
• Collaborators: Wellcome Trust
• Investigators: Study Director: Gates MRI, Bill & Melinda Gates Medical Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2020
• Primary Completion (Actual): August 12, 2022
• Study Completion (Actual): August 12, 2022

Study Registration Dates

• First Submitted: September 10, 2020
• First Submitted That Met QC Criteria: September 17, 2020
• First Posted (Actual): September 21, 2020

Study Record Updates

• Last Update Posted (Estimated): June 13, 2023
• Last Update Submitted That Met QC Criteria: June 12, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: HIV; Antiretroviral therapy; Mycobacterium tuberculosis; Mtb; M72/AS01E Vaccine; TB vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Slow Virus Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Mycobacterium Infections; Tuberculosis; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes
• Other Study ID Numbers: Gates MRI-TBV02-202; 221698/Z/20/Z (Other Grant/Funding Number: Wellcome Trust)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• 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