Study to Assess Efficacy and Safety of M72/AS01E-4 Mycobacterium Tuberculosis (Mtb) Vaccine in Adolescents and Adults

Tuberculosis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06062238
• Other study ID #: Gates MRI-TBV02-301
• Status: Recruiting
• Phase: Phase 3
• Start date: March 5, 2024
• Est. completion date: April 2028

Study information

• Verified date: March 2024
• Source: Bill & Melinda Gates Medical Research Institute
• Contact: Gates MRI
• Phone: +1 857 702 2108
• Email: clinical.trials[@]gatesmri.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20000
• Est. completion date: April 2028
• Est. primary completion date: April 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 15 Years to 44 Years

Eligibility

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.

Related Conditions & MeSH terms

• Mycobacterium Infections
• Tuberculosis

Intervention

Biological:
• M72/AS01E-4 Mycobacterium tuberculosis investigational vaccine
Participants will receive an intramuscular dose of M72 (recombinant fusion protein) reconstituted with AS01E-4 (an adjuvant system), on Day 1 and Day 29.
• Placebo
Participants will receive an intramuscular dose of normal saline (0.9 percent [%] sodium chloride [NaCl]), on Day 1 and Day 29.

Locations

Country	Name	City	State
Indonesia	Gates MRI Investigational Site	Bandung
Indonesia	Gates MRI Investigational Site	Depok
Indonesia	Gates MRI Investigational Site	Jakarta
Indonesia	Gates MRI Investigational Site	Jakarta
Indonesia	Gates MRI Investigational Site	Jakarta
Kenya	Gates MRI Investigational Site	Ahero
Kenya	Gates MRI Investigational Site	Eldoret
Kenya	Gates MRI Investigational Site	Kericho
Kenya	Gates MRI Investigational Site	Kilifi
Kenya	Gates MRI Investigational Site	Kisumu
Kenya	Gates MRI Investigational Site	Machakos
Kenya	Gates MRI Investigational Site	Mombasa
Kenya	Gates MRI Investigational Site	Nairobi
Kenya	Gates MRI Investigational Site	Nairobi
Malawi	Gates MRI Investigational Site	Chichiri
Malawi	Gates MRI Investigational Site	Lilongwe
Mozambique	Gates MRI Investigational Site	Manhica
Mozambique	Gates MRI Investigational Site	Maputo
South Africa	Gates MRI Investigational Site	Bloemfontein
South Africa	Gates MRI Investigational Site	Brits
South Africa	Gates MRI Investigational Site	Cape Town
South Africa	Gates MRI Investigational Site	Cape Town
South Africa	Gates MRI Investigational Site	Cape Town
South Africa	Gates MRI Investigational Site	Cape Town
South Africa	Gates MRI Investigational Site	Cape Town
South Africa	Gates MRI Investigational Site	Cape Town
South Africa	Gates MRI Investigational Site	Cape Town
South Africa	Gates MRI Investigational Site	Durban
South Africa	Gates MRI Investigational Site	Durban
South Africa	Gates MRI Investigational Site	Durban
South Africa	Gates MRI Investigational Site	East London
South Africa	Wits RHI - Shandukani Research	Hillbrow	Gauteng
South Africa	Gates MRI Investigational Site	Johannesburg
South Africa	Gates MRI Investigational Site	Johannesburg
South Africa	Gates MRI Investigational Site	Johannesburg
South Africa	Gates MRI Investigational Site	Johannesburg
South Africa	Gates MRI Investigational Site	Jouberton
South Africa	Gates MRI Investigational Site	Kimberley
South Africa	Gates MRI Investigational Site	Klerksdorp
South Africa	Gates MRI Investigational Site	Ladysmith
South Africa	Gates MRI Investigational Site	Middelburg
South Africa	Gates MRI Investigational Site	Mtubatuba
South Africa	Gates MRI Investigational Site	Paarl
South Africa	Gates MRI Investigational Site	Port Elizabeth
South Africa	Gates MRI Investigational Site	Pretoria
South Africa	Gates MRI Investigational Site	Rustenburg
South Africa	Gates MRI Investigational Site	Soweto
South Africa	Gates MRI Investigational Site	Soweto
South Africa	Gates MRI Investigational Site	Soweto
South Africa	Gates MRI Investigational Site	Tembisa
South Africa	Gates MRI Investigational Site #1	Tembisa
South Africa	Gates MRI Investigational Site	Vereeniging
South Africa	Gates MRI Investigational Site	Worcester
Vietnam	Gates MRI Investigational Site	Hanoi
Vietnam	Gates MRI Investigational Site	Ho Chi Minh city
Vietnam	Gates MRI Investigational Site #1	Ho Chi Minh City
Vietnam	Gates MRI Investigational Site #2	Ho Chi Minh city
Zambia	Gates MRI Investigational Site	Lusaka
Zambia	Gates MRI Investigational Site #1	Lusaka
Zambia	Gates MRI Investigational Site #2	Lusaka
Zambia	Gates MRI Investigational Site	Ndola

Sponsors (3)

Lead Sponsor	Collaborator
Bill & Melinda Gates Medical Research Institute	Bill and Melinda Gates Foundation, Wellcome Trust

Countries where clinical trial is conducted

Indonesia,  Kenya,  Malawi,  Mozambique,  South Africa,  Vietnam,  Zambia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	IGRA-Positive Cohort: Number of participants with laboratory-confirmed pulmonary tuberculosis (TB)	Laboratory-confirmed pulmonary TB case is defined as a participant with suspected pulmonary TB presenting with one or more of the following signs or symptoms: unexplained cough, unintentional weight loss, hemoptysis, unexplained fever, night sweats, pleuritic chest pain; who has least 2 positive Mtb test results (positive Mtb culture and/or positive test result from Xpert Ultra or similar assay, excluding "trace positive"), from the same or from different sputum samples collected during the 3 suspected TB visits, preferably within a 7-day time frame, before initiation of TB treatment.	Up to Month 49
Secondary	IGRA-Negative Cohort: Number of participants with sustained QuantiFERON®-TB Gold Plus assay conversion		Up to Month 49
Secondary	IGRA-Negative Cohort: Number of participants with laboratory-confirmed pulmonary TB		Up to Month 49
Secondary	HIV Cohort: Number of participants with laboratory-confirmed pulmonary TB		Up to Month 49
Secondary	IGRA-Positive Cohort: Number of participants with laboratory-confirmed pulmonary TB (Less stringent laboratory-confirmed pulmonary TB case definition)	Laboratory-confirmed pulmonary TB case is defined as a participant with suspected pulmonary TB presenting with one or more of the following signs or symptoms: unexplained cough, unintentional weight loss, hemoptysis, unexplained fever, night sweats, pleuritic chest pain; who has at least 1 positive Mtb culture or at least 1 positive result from Xpert Ultra or similar assay (excluding "trace positive"), from the same or from different sputum samples collected during the 3 suspected TB visits, preferably within a 7-day time frame, before initiation of TB treatment.; Compose	Up to Month 49
Secondary	All Cohorts: Number of participants with solicited adverse events (AEs)		Up to 7 days
Secondary	All Cohorts: Number of participants with unsolicited AEs		Up to 28 days
Secondary	All Cohorts: Number of participants with serious adverse events (SAEs)		Up to Month 13
Secondary	All Cohorts: Number of participants with potential immunemediated diseases (pIMDs)		Up to Month 13
Secondary	All Cohorts: Number of participants with SAEs related to trial participation		Up to Month 49
Secondary	All cohorts: Number of participants with geometric mean concentration (GMC) of M72-specific antibodies		At Day 1, Month 1, Month 2, Month 7, Month 13, Month 37, and Month 49
Secondary	All cohorts: Number of participants with seropositivity of M72-specific antibodies		At Day 1, Month 1, Month 2, Month 7, Month 13, Month 37, and Month 49