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

Study Overview
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Brief Summary
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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).

Official Title
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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)

Conditions
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Human Immunodeficiency Virus

Intervention / Treatment
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* Biological: M72/AS01E Mycobacterium tuberculosis vaccine
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: M72/AS01E vaccine<br> | Biological: M72/AS01E Mycobacterium tuberculosis vaccine<br>* 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<br>|
| Placebo Comparator: Placebo<br> | Biological: Placebo<br>* Participants will receive an intramuscular dose of saline (0.9% NaCl), on Day 1 and Day 29<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mtb, HIV, Mycobacterium tuberculosis, M72/AS01E Vaccine, Antiretroviral therapy, TB vaccine