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

NCT04556981 | Completed Phase 2 Results DMC

• 2 other identifiers: Gates MRI-TBV02-202221698/Z/20/Z
• Study Type: interventional
• Target: 402
• Locations: 1 country
• Sites: 6

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).

Conditions

Human Immunodeficiency Virus

Keywords

Mycobacterium tuberculosis; M72/AS01E Vaccine; Antiretroviral therapy; Mtb; HIV; TB vaccine

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Solicited Adverse Events (AEs) Through 7 Days Post Dose 1 of Study Intervention

  An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE does not necessarily have a causal relationship with the intervention. Solicited AEs were defined events that participants were specifically asked about and which were noted by participants in the diary card. Solicited local AEs included pain, redness and swelling and general body symptoms such as fever, headache, fatigue, gastrointestinal symptoms, and myalgia.

  Day 1 through Day 7 (after first vaccination)

• Number of Participants With Solicited AEs Through 7 Days Post Dose 2 of Study Intervention

  An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE does not necessarily have a causal relationship with the intervention. Solicited AEs were defined events that participants were specifically asked about and which were noted by participants in the diary card. Solicited local AEs included pain, redness and swelling and general body symptoms such as fever, headache, fatigue, gastrointestinal symptoms, and myalgia.

  Day 29 through Day 35 (after second vaccination)

• Number of Participants With Unsolicited AEs Through 28 Days Post Dose 1 of Study Intervention

  An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE does not necessarily have a causal relationship with the intervention. Unsolicited AEs were all AEs for which the participant was not specifically questioned in the participant diary card. Number of Participants With Unsolicited AEs Through 28 Days after first vaccination has been presented.

  Day 1 through Day 28

• Number of Participants With Unsolicited AEs Through 28 Days Post Dose 2 of Study Intervention

  An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE does not necessarily have a causal relationship with the intervention. Unsolicited AEs were all AEs for which the participant was not specifically questioned in the participant diary card. Number of Participants With Unsolicited AEs Through 28 Days after second vaccination has been presented.

  Day 29 through Day 57

• Number of Participants Reporting Serious AEs (SAEs)

  An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Number of Participants reporting SAEs has been presented.

  Up to Day 390

Secondary Outcomes (6)

• Number of Participants With Potential Immune-mediated Diseases (pIMDs)

  Up to Day 390

• Number of Participants With Clinically Significant Hematology Assessments of Grade 3 or Above After Baseline

  Up to Day 390

• Number of Participants With Clinically Significant Chemistry Assessments of Grade 3 or Above After Baseline

  Up to Day 390

• M72-specific Antibody Titers

  Day 1, Day 29, Day 57, Day 210 and Day 390

• Number of M72 Specific CD4+ and CD8+ T Cell Responders Based on Cytokine Response

  Day 57 and Day 390

Study Arms (2)

M72/AS01E vaccine

EXPERIMENTAL

Biological: M72/AS01E Mycobacterium tuberculosis vaccine

Placebo

PLACEBO COMPARATOR

Biological: Placebo

Interventions

M72/AS01E Mycobacterium tuberculosis vaccine BIOLOGICAL

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

M72/AS01E vaccine

Placebo BIOLOGICAL

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

Placebo

Eligibility Criteria

• Age: 16 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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
• Receipt of any vaccine in the period starting 7 days before, and ending 7 days after, each dose of the study vaccine
• History of previous administration of experimental Mycobacterium tuberculosis vaccine
• 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

Sponsors & Collaborators

• Gates Medical Research Institute: lead
• Wellcome Trust: collaborator

Study Sites (6)

Wits RHI

Johannesburg, Gauteng, 2001, South Africa

Location

Ekhaya VAC

Cape Town, Khayelitsha, 7782, South Africa

Location

CAPRISA

Durban, KwaZulu-Natal, 4001, South Africa

Location

The Aurum Institute

Klerksdorp, North West, 2570, South Africa

Location

Desmond Tutu HIV Foundation

Cape Town, Western Cape, 6850, South Africa

Location

SATVI

Worcester, Western Cape, 6850, South Africa

Location

Related Publications (1)

• Dagnew AF, Han LL, Naidoo K, Fairlie L, Innes JC, Middelkoop K, Tameris M, Wilkinson RJ, Ananworanich J, Bower D, Schlehuber L, Frahm N, Cinar A, Dunne M, Schmidt AC. Safety and immunogenicity of investigational tuberculosis vaccine M72/AS01E-4 in people living with HIV in South Africa: an observer-blinded, randomised, controlled, phase 2 trial. Lancet HIV. 2025 Aug;12(8):e546-e555. doi: 10.1016/S2352-3018(25)00124-9. Epub 2025 Jul 1.

  PMID: 40614747 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Gates MRI

clinical.trials@gatesmri.org

+1 857 702 2108

Study Officials

• Gates MRI

  Gates Medical Research Institute

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2020
• First Posted: September 21, 2020
• Study Start: November 17, 2020
• Primary Completion: August 12, 2022
• Study Completion: August 12, 2022
• Last Updated: July 17, 2025
• Results First Posted: July 17, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

ZA (6)