Clinical trial NCT03806686: Phase 2a Clinical Trial of ID93+GLA-SE Vaccine in BCG-vaccinated Healthy Healthcare Workers
Official title: A Phase 2a, Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Safety and Explore the Immunogenicity and Efficacy of ID93+GLA-SE Vaccine in BCG-Vaccinated Healthy Healthcare Workers
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Tuberculosis
Keywords: Tuberculosis, TB, vaccine, adjuvant
Lead sponsor: Quratis Inc.
Sponsor class: INDUSTRY
Collaborators: name: Access to Advanced Health Institute (AAHI)
First posted: 2019-01-16
Enrollment: 107
Sex: ALL
Minimum age (years): 19
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be assigned to one of three groups: Low dose ID93+GLA-SE, High dose ID93+GLA-SE, or Control Group.
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate the experimental tuberculosis (TB) vaccine called ID93+GLA-SE. The safety, immunogenicity, and efficacy of ID93+GLA-SE will be compared to placebo, after three intramuscular (IM) injections one month apart in healthy healthcare workers. The healthcare workers will all have had the childhood TB vaccine called BCG, and all of them must have a negative result for a blood test for exposure to the bacteria that cause TB (QuantiFERON-TB Gold Plus, or "QFT"). Study participants will be followed for 12 months after the last injection for safety reasons. Blood will be drawn for laboratory tests for safety, immunogenicity, and efficacy tests. Efficacy will be evaluated by further QFT testing. The study hypothesis is that the vaccine is safe, immunogenic, and effective in this study population.

Detailed description: After signing a written informed consent to participate in the study, subjects will be screened by required assessments per protocol. Eligible subjects who meet the inclusion/exclusion criteria will be randomized in a 1:1:1 ratio to Group 1, Group 2, or Control Group, receiving either ID93+GLA-SE or saline placebo on Days 0, 28, and 56. The investigator will evaluate the safety, immunogenicity, and efficacy of the Investigational Product in the subjects throughout the study.

For safety assessment, subjects will be instructed to record any adverse events in the subject diary after each vaccination. Subject's safety will be reported to the investigators after 7 days from each vaccination (Days 7, 35, 63) via site visit or a phone call. Solicited AEs will be collected up to 7 days after the final vaccination with the Investigational Product and un-solicited AEs will be collected up to 28 days after the final vaccination with the Investigational Product. For long-term safety assessment of the Investigational Product, serious adverse events and adverse events of special interest will be monitored up to 12 months after the final vaccination with the Investigational Product.

For immunogenicity assessment, blood samples for immunology assays will be collected and analyzed before and after each vaccination. For efficacy assessment, QFT-Gold Plus testing will be performed after 3 months and 14months from the first vaccination with the Investigational Product.

Eligibility criteria: Inclusion Criteria:

1. Male or female who is ≥19 and \<65 years of age.
2. Healthcare workers who are QuantiFERON®-TB Gold Plus negative (not latently infected with Mtb) at screening.
3. Able to comply with the scheduled visits, and are expected to continue working in the current medical institution and be available for a continuous follow-up by the investigator via provided contact information.
4. Only for female subjects of childbearing potential:

   * Must be HCG-negative from serum or urine pregnancy test, at screening;

     * Agreed to use one of the following acceptable birth control methods to avoid pregnancy until the end of study (Visit 9): hormonal contraceptives, intrauterine device (IUD) or intrauterine system (IUS), tubal ligation, or combination of barrier methods (combined use of barrier methods such as male condoms, female condoms, cervical cap, diaphragm, sponge, or implant).
5. History of BCG vaccination that is confirmed through medical examination (i.e., asking a subject about his/her condition) or presence of a scar.
6. Body mass index (BMI) ≥19 and ≤33 (kg/m\^2) at screening
7. Subjects who understand the study procedures, and voluntarily decide to participate in the study and sign the informed consent form..

Exclusion Criteria:

1. History of positive tuberculin skin test or positive QuantiFERON®-TB results.
2. History of severe chronic disease that may compromise the safety of the subject during the study (e.g., impairment of pulmonary function from tuberculosis infection or other pulmonary disease; chronic illness with signs of cardiac or renal failure; suspected progressive neurological disease or uncontrolled epilepsy).
3. Body temperature ≥ 38℃ at the time of randomization or within 24 hours before randomization, from acute fever, acute respiratory diseases, or active infection.
4. Malignant tumors or a history of malignant tumors.
5. Plans to have surgery during the study period.
6. Impaired immune functions including autoimmune disease or immunodeficiency disease.
7. History of Guillain-Barre syndrome.
8. Subjects with a history of anaphylaxis or severe allergic reaction to vaccines, eggs, or other allergens.
9. Subjects living with a household member who has active TB or infectious TB.
10. Clinically significant abnormal laboratory values for any of the following tests conducted in the study center, prior to randomization:

    * Hemoglobin, hematocrit, absolute neutrophil count, absolute lymphocyte count, or platelet count: \< LLN (lower limit of normal)
    * White blood cell count: \>ULN (upper limit of normal) or \<LLN (lower limit of normal) (i.e., must be within normal limits)
    * ALT, AST, total bilirubin, alkaline phosphatase, creatinine, or blood urea nitrogen (BUN): \>ULN (upper limit of normal)
11. Received an immunosuppressant, immunity-modifying drug, or other treatment that may affect the immune system including cytotoxic anti-cancer agents or radiotherapy, within 3 months before the randomization.
12. Use of systemic steroids (equivalent to daily prednisone ≥ 15mg/day for more than 14 days), inhaled or intranasal steroids, within 3 months before randomization; however, use of topical corticosteroids are acceptable, regardless of dose.
13. Use of immunoglobulin or blood products within 3 months before randomization or plans to use them during the study period.
14. Human Immunodeficiency Virus (HIV) positive at screening.
15. Subjects with chronic hepatitis (e.g., hepatitis B core antibody or hepatitis C antibody positive) at screening.
16. Unable to discontinue current chronic drug therapy such as thyroxin, insulin, or other medications with hepatotoxicity or myelotoxicity; however, estrogen and progesterone replacement therapy or contraceptives, and topical medications are acceptable.
17. Pregnant or lactating.
18. Received other vaccines within 4 weeks before screening or plans to receive them from the day of screening to 4 weeks after the last vaccination with the Investigational Product or within 4 weeks before the End Visit.
19. Received other investigational drugs within 4 weeks before screening.
20. Subjects deemed ineligible by investigator based on other reasons.

Primary outcomes:
measure: Adverse events
timeFrame: Solicited AEs for 7 days following each injection, unsolicited AEs for 28 days after each injection, SAEs and AESIs for 12 months after the last injection.
Secondary outcomes:
measure: Humoral and cellular immunogenicity assays
timeFrame: Days 0, 28, 56, 84, and 12 months after last injection.
measure: Efficacy at prevention of latent Mtb infection (QFT conversion)
timeFrame: 3 months and 14 months after the first injection.
Other outcomes:
Locations:
city: Gyeonggi-do
country: Korea, Republic of
facility: Ajou University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Chung-Ang University Hospital
Study officials:
affiliation: Quratis Inc.
name: Yu Hwa Choi
role: STUDY_DIRECTOR
References: