ID93+GLA-SE Vaccine Against Tuberculosis in Older Adults Aged 55-74

A Phase 1, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety and Explore the Immunogenicity of the Tuberculosis (TB) Vaccine Candidate QTP101 (ID93+GLA-SE) in Older Adults (Aged 55~74 Years)

The purpose of this study is to evaluate the safety and explore the immunogenicity of ID93+GLA-SE compared to placebo following three intramuscular (IM) injections on Days 0, 28 and 56 in the Bacillus Calmette-Guérin (BCG)-vaccinated older adults aged 55 to 74 with negative or positive result on the QuantiFERON-TB (QFT) test. Eligible participants will be randomly assigned based on age group and the QFT test results to receive either QTP101 (Dose 1 and Dose 2) or placebo.

Safety and immunogenicity will be monitored from the first dose until 12 months after the final dose of the investigational product. Blood samples for immunogenicity analysis will be collected at five-time points: before the first dose (Day 0), 4 weeks after the first dose (Day 28), 4 weeks after the second dose (Day 56), 4 weeks after the third dose (Day 84), and 48 weeks after the third dose (Day 392). Once the safety and immunogenicity follow-up is completed 48 weeks after the third dose (Day 392) for the last enrolled participant, a final report will be compiled based on the collected data.

This Phase 1 randomized, double-blind, placebo-controlled clinical trial aims to evaluate the safety and explore the immunogenicity of the investigational tuberculosis (TB) vaccine candidate QTP101 (ID93+GLA-SE) in healthy and medically stable older adults aged 55-74 years. The study targets two specific age groups-55-64 years (middle-aged) and 65-74 years (elderly)-to address the unmet need for effective TB prevention in populations with high disease prevalence and risk, particularly in countries with an aging population.

The trial involves three treatment arms:

Low-dose vaccine group: 2 μg ID93 + 5 μg GLA-SE High-dose vaccine group: 10 μg ID93 + 5 μg GLA-SE Placebo group: Normal saline (0.9%)

Participants will receive three intramuscular (IM) injections of their assigned treatment at baseline (Day 0), Day 28, and Day 56. They will be monitored for safety and immunogenicity over 12 months, with regular follow-up visits scheduled at 1, 6, and 12 months post-final injection.

Key Study Elements:

Eligibility Criteria: Participants must be BCG-vaccinated, HIV-negative, and have QuantiFERON-TB Gold (QFT) test results positive or negative. Chronic conditions are permissible if well-controlled. Women of childbearing potential and men must use approved contraception methods during the study.

Safety Monitoring: Adverse events (AEs) will be closely monitored, categorized as immediate AEs (within 30 minutes of vaccination), solicited local/systemic AEs (within 7 days), unsolicited AEs (up to 28 days), and serious AEs (SAEs) monitored until 12 months post-final dose.

Immunogenicity Assessments: Blood samples will be collected pre-vaccination and at multiple intervals (Day 28, 56, 84, and 392) to measure ID93-specific antibody titers (ELISA) and Th1 cytokine responses (ICS).

Sentinel Design for Older Adults: To ensure participant safety, a sentinel group design is employed for cohorts aged 65-74. Initial vaccination will proceed sequentially within smaller sentinel subgroups, with further cohort enrollment contingent on DSMB approval after reviewing safety data.

Study Objective:

This trial aims to establish the safety profile and preliminary immunogenicity of QTP101 as a step toward addressing the persistent global burden of TB, particularly in vulnerable older populations. The results will inform subsequent clinical development phases to optimize the vaccine's dosing and application.

The study's results will provide critical insights into TB vaccine strategies for aging populations, ensuring a foundation for broader preventative interventions.

Inclusion Criteria:

1. Participants who can comply with all scheduled assessment visits during the clinical trial period and who can be continuously monitored by the investigator through the provided contact information

2. Males or females aged 55 to 74 years at the time of consent

3. Participants and/or legally authorized representatives who are capable of providing written informed consent (signed in person in the presence of a witness)

4. Participants with either positive or negative QFT test results at the time of screening; QFT testing can be omitted in the following case: If participants have a documented history of a positive QFT test result, evidenced by submitted records or recorded in the EMR

5. Participants with negative HIV test results at the time of screening

6. Participants with a record of BCG vaccination or BCG scar directly

7. Participants who fall within the following range in physical measurements at the time of screening: 19 ≤ Body Mass Index (BMI) ≤ 33 (kg/m^2) BMI and weight results are rounded to the nearest whole number.

8. Healthy participants or those with well-managed chronic diseases through medical history and clinical examination

9. Female participants must provide evidence at the screening visit (Visit 1) that they meet one of the following criteria to be considered non-fertile:

   • Non-fertile: Defined as post-menopausal or other infertility conditions. Post-menopausal women: No menstrual periods for at least 12 months after stopping all external hormone treatments and over 55 years old. Documented irreversible surgical infertility such as hysterectomy, bilateral oophorectomy, or bilateral salpingectomy. However, tubal ligation is not permitted.
   • Fertile: Women of childbearing potential who have not undergone sterilization must agree to use appropriate contraception during the investigational product administration period and for 6 months after the end of the investigational product administration. They must undergo a serum pregnancy test (β-hCG test) at the screening visit (Visit 1) and urine pregnancy tests (Urine-hCG test) at subsequent visits, with negative HCG results required.

10. Male participants can be enrolled under the following conditions: Men who have not undergone vasectomy must agree to use barrier contraception (e.g., condoms) and agree that both they and their partner will use appropriate contraception during the investigational product administration period and for 6 months after the end of the investigational product administration.

11. Participants who understand the clinical trial procedures, voluntarily decide to participate and sign the informed consent form

12. Participants recommended for tuberculosis prevention treatment who have been adequately informed about and understand latent tuberculosis chemoprophylaxis, and voluntarily agree to participate in the clinical trial while expressing non-consent to the chemoprophylaxis

Exclusion Criteria:

Participants who meet any of the following criteria must be excluded from enrollment.

1. Participants who are suspected of having tuberculosis, have a history of tuberculosis, are currently undergoing treatment for tuberculosis, are being treated for latent tuberculosis infection, or have a history of medication treatment for latent tuberculosis infection at the time of the Screening (Visit 1) or the first administration (Visit 2)

2. Participants who have received other investigational products or used unapproved drugs within 6 months prior to participating in the clinical trial or who plan to use them during the trial period

3. Participants who have previously received an investigational tuberculosis vaccine

4. Participants who test positive for HIV at the screening visit

5. Participants who test positive for HCV or who test positive for HBsAg and negative for HBsAb in HBV tests at the screening visit

6. Participants who are exposed to or will be exposed to investigational or non-investigational products during the clinical trial period or who participate in another clinical trial simultaneously

7. Participants who have received immunoglobulins and/or any blood products within 90 days before the first administration of the investigational product or plan to receive them during the clinical trial period

8. Pregnant or breastfeeding female

9. Participants with the following medical or psychiatric conditions that make it impossible to conduct the clinical trial as judged by the principal investigator:

   • Participants with acute fever (an arbitrary body temperature of 38°C or higher at the time of randomization or within 24 hours before randomization), acute respiratory disease, or active infection.
   • Participants with malignancies or a history of malignancies within the past 5 years.
   • Participants with respiratory diseases: who have received treatment for acute exacerbation or moderate exacerbation of a respiratory condition within 2 years prior to the first administration of the investigational product. (Participants with a history of high-risk pulmonary diseases, such as silicosis, may be excluded at the investigator's discretion, regardless of the treatment period or even if the history is beyond the past 2 years. However, participants with controlled asthma or COPD stage 0 (at-risk) may participate with judgment of the principal investigator.)
   • Participants with serious cardiovascular diseases: congestive heart failure, coronary artery disease, myocardial infarction, uncontrolled hypertension, etc.
   • Participants with neurological diseases: epilepsy, seizures within 3 years before the first administration of the investigational products, migraines, strokes, encephalopathy, Guillain-Barre syndrome, etc.
   • Participants with a history of COVID-19 infection within 90 days before the screening visit (confirmed positive by NAAT or rapid antigen test) or who have not recovered from COVID-19-related symptoms after being diagnosed with COVID-19 more than 90 days before the screening visit.
   • Participants with autoimmune hypothyroidism, autoimmune diseases, immunodeficiency diseases.
   • Participants with other clinically significant medical histories related to the hepatobiliary system, kidneys, endocrine system, urinary system, musculoskeletal system, etc., as judged by the principal investigator.
   • Participants with a history of hereditary or idiopathic angioedema.
   • Participants with a history of organ or bone marrow transplantation.
   • Participants with a history of platelet-related or bleeding disorders, a history of significant bleeding or bruising following intramuscular injection or venipuncture, or who are receiving anticoagulants.

10. Participants who have received radiation therapy within 12 months before the first administration of the investigational product. However, those who have received radiation therapy to the lungs are excluded regardless of the time frame.

11. Participants who have surgery planned during the clinical trial period

12. Participants with a history of severe allergic reactions or anaphylaxis to vaccines or other allergens

13. Participants with clinically significant abnormal findings in laboratory tests, ECG, or chest X-ray at the screening visit as judged by the principal investigator to be unsuitable for participation. Participants with fibrotic nodular lesions on chest X-ray (indicative of spontaneously healed tuberculosis lesions without a history of tuberculosis treatment)

14. Participants who have chronically received immunosuppressants or other immunomodulatory drugs within 6 months before the first administration of the investigational product

    • High-dose corticosteroids (continuous use of doses exceeding 15 mg/day of prednisolone for more than 14 days)
    • However, topical steroids, nasal sprays, inhalers, and eye drops are allowed regardless of the dose

15. Participants who are deemed unsuitable for this clinical trial by the principal investigator for any other reasons

16. Participants with cognitive impairment.

17. Household contacts and close contacts who have been in an indoor environment with an active tuberculosis patient

    • Household Contact: Family members and cohabitants who have been living in the same space or regularly interacting for at least 3 months.
    • Close Contact: Individuals other than household contacts who have had direct contact in an enclosed indoor environment (e.g., classroom, office) for an extended period, defined as continuous or daily contact for at least 8 hours per day, or cumulative contact of 40 hours or more.