Clinical trial NCT06062238: Study to Assess Efficacy and Safety of M72/AS01E-4 Mycobacterium Tuberculosis (Mtb) Vaccine in Adolescents and Adults
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter, Clinical Trial to Assess the Prophylactic Efficacy, Safety, and Immunogenicity of the Investigational M72/AS01E-4 Mycobacterium Tuberculosis (Mtb) Vaccine When Administered Intramuscularly on a 0,1-month Schedule to Adolescents and Adults
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Tuberculosis
Keywords: Mycobacterium tuberculosis
M72/AS01E-4 vaccine
Safety
Immunogenicity
Efficacy
Mtb
HIV
TB vaccine
Lead sponsor: Bill & Melinda Gates Medical Research Institute
Sponsor class: OTHER
Collaborators: name: Wellcome Trust
name: Bill and Melinda Gates Foundation
First posted: 2023-10-02
Enrollment: 20081
Sex: ALL
Minimum age (years): 15
Maximum age (years): 44
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is a randomized, double-blind, placebo-controlled, multicenter, clinical trial to assess the prophylactic efficacy, safety, and immunogenicity of the investigational M72/AS01E-4 Mtb vaccine when administered intramuscularly (IM) on a 0,1-month schedule to adolescents and adults. This trial will be conducted in 3 cohorts: Interferon gamma release assay (IGRA)-positive Cohort, IGRA-Negative Cohort and Human Immunodeficiency virus (HIV) Cohort.


Eligibility criteria: Inclusion criteria:

* Capable of giving informed consent or informed assent (as appropriate). For participants below the age of consent, the participant's parent, or legally authorized representative (LAR) will be required to sign a statement of informed consent, in addition to the minor's signed statement of assent.
* In the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of diary cards as applicable, and return for follow-up visits).
* Agree to actively stay in contact with the trial site for the duration of the trial for the participants own safety.
* Agree to provide updated contact information as necessary, and have no current plans to relocate from the trial area for the duration of the trial.
* Healthy, or with preexisting stable disease, as established by medical history and physical examination and as determined by the investigator.
* Negative sputum Xpert Ultra or similar assay result at screening.
* Both males and females are included. Females are included with restrictions. Females must either be of non-childbearing potential, defined as pre-menarche, have a history of either current tubal ligation, hysterectomy, or ovariectomy, or post-menopause, or, if she is of childbearing potential, she has practiced abstinence from penile-vaginal intercourse or adequate contraception for 28 days prior to vaccination, has a negative pregnancy test on the day of screening and the day of first vaccination, and agrees to continue abstinence or adequate contraception until 2 months after the second dose of trial intervention.
* HIV-negative test result at screening (IGRA-Positive Cohort and IGRA-Negative Cohort only).
* HIV Cohort only: Participants with documented HIV infection who fulfill all of the following criteria:

  1. Have reactive anti-HIV antibody at screening.
  2. Have been on antiretroviral therapy (ART) for at least 3 consecutive months at screening and agree to remain on ART throughout the trial.
  3. Have documented HIV Ribonucleic acid (RNA) \<200 copies per milliliter (/mL) at screening.
  4. Have Cluster of differentiation (CD)4+ cell count ≥200 cells/microliter (μL) at screening.
  5. Have had Tuberculosis preventive therapy (TPT) in the past and are not receiving TPT at the time of screening, according to the judgment of the investigators.
  6. Have an IGRA-positive or negative result at screening.

Exclusion criteria:

* Current TB, or history of TB or treatment for TB disease.
* Clinical suspicion of pulmonary TB at screening, defined as a participant presenting with one or more of the following signs or symptoms: unexplained cough, unexplained fever, night sweats, unintentional weight loss, hemoptysis, pleuritic chest pain.
* 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, or that will interfere with the assessments or the safety of the participant.
* Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., invasive, or malignant cancers), other than HIV infection in the HIV Cohort.
* Known bleeding disorder that is considered a contraindication to intramuscular injection or phlebotomy.
* Any cytotoxic drugs or administration of medications known to have a major impact on the immune system, as determined by the investigator, within 90 days prior to Day 1. These include immune globulin, blood, or blood products, potent immunosuppressants and immunomodulators, and systemic corticosteroids (exceeding 20 mg/day prednisone equivalent). Inhaled, topical, and intra-articular corticosteroids are allowed.
* Planned receipt of blood, or blood products during the trial period.
* Receipt or planned receipt of any vaccine in the period starting 28 days before, and ending 28 days after, each dose of the trial vaccine.
* History of previous administration of an experimental Mtb vaccine including M72/AS01E in a previous trial.
* History of allergy or hypersensitivity to the trial intervention, excipients, or related Substances.
* An indeterminate IGRA test result at screening
* Female participants with any one of the following conditions: currently pregnant or lactating; having positive serum pregnancy test during the screening window, positive urine pregnancy test on Day 1, planning a pregnancy within 2 months after completion of the vaccination series.
* Only in the HIV Cohort: Safety laboratory values at screening that are of concern, based on investigator's judgment. Note that preexisting stable chronic disease will not necessarily lead to exclusion, especially if laboratory values are graded as mild.
* Participation in an interventional clinical trial in which the participant has been or will be exposed to an investigational product (pharmaceutical product or device), within 28 days prior to signing consent or assent, or during the trial period.
* Individuals who are acting as personnel for this trial, or who have immediate family members (brother, sister, child, parent, or the spouse/partner) who are acting as personnel for this trial.
* Child in Care, defined as a child who is under the care (control or protection) of an agency, organization, institution or entity by the courts, the government body, acting in accordance with powers conferred in them by law or regulations. The definition of a child in care can include a child who is cared for by foster parents or living in a care home or institution, provided that the arrangements fall within the definition above. The definition of a child in care does not include a child who is adopted or has an appointed LAR.
* Participants who had a Tuberculin Skin Test (TST) within 6 months prior to Day 1.

Primary outcomes:
measure: IGRA-Positive Cohort: Number of participants with laboratory-confirmed pulmonary tuberculosis (TB)
timeFrame: Up to Month 49
Secondary outcomes:
measure: IGRA-Negative Cohort: Number of participants with sustained QuantiFERON®-TB Gold Plus assay conversion
timeFrame: Up to Month 49
measure: IGRA-Negative Cohort: Number of participants with laboratory-confirmed pulmonary TB
timeFrame: Up to Month 49
measure: HIV Cohort: Number of participants with laboratory-confirmed pulmonary TB
timeFrame: Up to Month 49
measure: IGRA-Positive Cohort: Number of participants with laboratory-confirmed pulmonary TB (Less stringent laboratory-confirmed pulmonary TB case definition)
timeFrame: Up to Month 49
measure: All Cohorts: Number of participants with solicited adverse events (AEs)
timeFrame: Up to 7 days
measure: All Cohorts: Number of participants with unsolicited AEs
timeFrame: Up to 28 days
measure: All Cohorts: Number of participants with serious adverse events (SAEs)
timeFrame: Up to Month 13
measure: All Cohorts: Number of participants with potential immunemediated diseases (pIMDs)
timeFrame: Up to Month 13
measure: All Cohorts: Number of participants with SAEs related to trial participation
timeFrame: Up to Month 49
measure: All cohorts: Number of participants with geometric mean concentration (GMC) of M72-specific antibodies
timeFrame: At Day 1, Month 1, Month 2, Month 7, Month 13, Month 37, and Month 49
measure: All cohorts: Number of participants with seropositivity of M72-specific antibodies
timeFrame: At Day 1, Month 1, Month 2, Month 7, Month 13, Month 37, and Month 49
Other outcomes:
Locations:
city: Bandung
country: Indonesia
facility: 2201-Gates MRI Investigational Site
city: Depok
country: Indonesia
facility: 2204-Gates MRI Investigational Site
city: Jakarta
country: Indonesia
facility: 2202-Gates MRI Investigational Site
city: Jakarta
country: Indonesia
facility: 2205-Gates MRI Investigational Site
city: Jakarta
country: Indonesia
facility: 2203-Gates MRI Investigational Site
city: Eldoret
country: Kenya
facility: 1205-Gates MRI Investigational Site
city: Homa Bay
country: Kenya
facility: 1203-Gates MRI Investigational Site
city: Kericho
country: Kenya
facility: 1206-Gates MRI Investigational Site
city: Kilifi
country: Kenya
facility: 1207-Gates MRI Investigational Site
city: Kisumu
country: Kenya
facility: 1202-Gates MRI Investigational Site
city: Machakos
country: Kenya
facility: 1208-Gates MRI Investigational Site
city: Mombasa
country: Kenya
facility: 1204-Gates MRI Investigational Site
city: Nairobi
country: Kenya
facility: 1209-Gates MRI Investigational Site
city: Nairobi
country: Kenya
facility: 1201-Gates MRI Investigational Site
city: Chichiri
country: Malawi
facility: 2402-Gates MRI Investigational Site
city: Lilongwe
country: Malawi
facility: 2401-Gates MRI Investigational Site
city: Bloemfontein
country: South Africa
facility: 1033-Gates MRI Investigational Site
city: Brits
country: South Africa
facility: 1016-Gates MRI Investigational Site
city: Cape Town
country: South Africa
facility: 1021-Gates MRI Investigational Site
city: Cape Town
country: South Africa
facility: 1024-Gates MRI Investigational Site
city: Cape Town
country: South Africa
facility: 1006-Gates MRI Investigational Site
city: Cape Town
country: South Africa
facility: 1003-Gates MRI Investigational Site
city: Cape Town
country: South Africa
facility: 1034-Gates MRI Investigational Site
city: Cape Town
country: South Africa
facility: 1022-Gates MRI Investigational Site
city: Cape Town
country: South Africa
facility: 1008-Gates MRI Investigational Site
city: Durban
country: South Africa
facility: 1009-Gates MRI Investigational Site
city: Durban
country: South Africa
facility: 1026-Gates MRI Investigational Site
city: Durban
country: South Africa
facility: 1029-Gates MRI Investigational Site
city: East London
country: South Africa
facility: 1010-Gates MRI Investigational Site
city: Johannesburg
country: South Africa
facility: 1028-Gates MRI Investigational Site
city: Johannesburg
country: South Africa
facility: 1031-Gates MRI Investigational Site
city: Johannesburg
country: South Africa
facility: 1018-Gates MRI Investigational Site
city: Johannesburg
country: South Africa
facility: 1020-Gates MRI Investigational Site
city: Johannesburg
country: South Africa
facility: 1007-Gates MRI Investigational Site
city: Jouberton
country: South Africa
facility: 1014-Gates MRI Investigational Site
city: Kimberley
country: South Africa
facility: 1027-Gates MRI Investigational Site
city: Klerksdorp
country: South Africa
facility: 1017-Gates MRI Investigational Site
city: Ladysmith
country: South Africa
facility: 1012-Gates MRI Investigational Site
city: Middelburg
country: South Africa
facility: 1004-Gates MRI Investigational Site
city: Mtubatuba
country: South Africa
facility: 1002-Gates MRI Investigational Site
city: Paarl
country: South Africa
facility: 1001-Gates MRI Investigational Site
city: Port Elizabeth
country: South Africa
facility: 1013-Gates MRI Investigational Site
city: Pretoria
country: South Africa
facility: 1005-Gates MRI Investigational Site
city: Rustenburg
country: South Africa
facility: 1019-Gates MRI Investigational Site
city: Soweto
country: South Africa
facility: 1011-Gates MRI Investigational Site
city: Soweto
country: South Africa
facility: 1015-Gates MRI Investigational Site
city: Tembisa
country: South Africa
facility: 1025-Gates MRI Investigational Site
city: Tembisa
country: South Africa
facility: 1032-Gates MRI Investigational Site #1
city: Vereeniging
country: South Africa
facility: 1030-Gates MRI Investigational Site
city: Worcester
country: South Africa
facility: 1023-Gates MRI Investigational Site
city: Lusaka
country: Zambia
facility: 1302-Gates MRI Investigational Site
city: Lusaka
country: Zambia
facility: 1303-Gates MRI Investigational Site
city: Lusaka
country: Zambia
facility: 1301-Gates MRI Investigational Site
city: Ndola
country: Zambia
facility: 1304-Gates MRI Investigational Site
Study officials:
affiliation: Bill & Melinda Gates Medical Research Institute
name: Gates MRI
role: STUDY_DIRECTOR
References: