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

NCT ID: NCT04556981

Last Updated: 2025-07-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 402 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-17
• Study Completion Date: 2022-08-12

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

M72/AS01E vaccine

Group Type: EXPERIMENTAL

M72/AS01E Mycobacterium tuberculosis vaccine

Intervention Type: 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

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

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

Interventions

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

Intervention Type: BIOLOGICAL

Placebo

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

Intervention Type: BIOLOGICAL

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
• 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
• 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
• Indeterminate QFT result
• 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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Wellcome Trust

OTHER

Sponsor Role: collaborator

Gates Medical Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gates MRI

Role: STUDY_DIRECTOR

Gates Medical Research Institute

Locations

Wits RHI

Johannesburg, Gauteng, South Africa

Ekhaya VAC

Cape Town, Khayelitsha, South Africa

CAPRISA

Durban, KwaZulu-Natal, South Africa

The Aurum Institute

Klerksdorp, North West, South Africa

Desmond Tutu HIV Foundation

Cape Town, Western Cape, South Africa

SATVI

Worcester, Western Cape, South Africa

Countries

South Africa

References

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.

Reference Type: DERIVED

PMID: 40614747 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

221698/Z/20/Z

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

Gates MRI-TBV02-202

Identifier Type: -

Identifier Source: org_study_id