phase 1 clinical trial of single-vial id93 + gla-se in healthy adults

Conditions: Pulmonary TB

Summary: this is a phase 1, double-blind, randomized clinical trial to evaluate the safety, tolerability, and immunogenicity of single-vial lyophilized id93 + gla-se compared to the two-vial presentation consisting of lyophilized id93 and liquid gla-se administered as two im injections in healthy adult subjects (aged 18 - 55).

subjects will receive a total of two doses administered im on days 0 and 56. subjects will be monitored for approximately 421 days (one year following the last study injection), including safety laboratory analyses done just prior to and 7 days following each study injection. tears and nasal swabs will be obtained for exploratory antibody analysis at days 0, 70, and 224. blood samples will be obtained for immunological assays (secondary and exploratory) at days 0, 7, 14, 56, 63, 70, 84, and 224).

Eligibility criteria:
inclusion criteria: 1. males and females 18 to 55 years of age. 2. in good general health as confirmed by a medical history and physical exam, vital signs\*, and screening laboratories conducted no more than 30 days prior to study injection administration. \*temperature \ 54 bpm, systolic blood pressure ≤140 mmhg and \>89 mmhg, diastolic blood pressure ≤90 mmhg and ≥60 mmhg. note: athletically trained subjects with a pulse ≥40 may be enrolled at the discretion of the principal investigator or designated licensed clinical investigator. 3. screening laboratory values within normal limits: sodium, potassium, alt, ast, total bilirubin, alkaline phosphatase, creatinine, random glucose, total wbc count, hemoglobin, and platelet count. 4. negative hiv 1/2 antibody, hepatitis b surface antigen (hbsag), and hepatitis c virus (hcv) antibody. 5. urine dipstick for protein and glucose (negative to trace protein are acceptable). 6. women of childbearing potential\* in sexual relationships with men must agree to practice acceptable contraception\*\* for the 30-day period before day 0 through 90 days after the last study injection. \*not sterilized via tubal ligation, bilateral oophorectomy, hysterectomy or successful essure® placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or \ 40 miu/ml. \*\*includes, but is not limited to, sexual abstinence, monogamous relationship with vasectomized partner who has been vasectomized for 6 months or more prior to the subject receiving study product, barrier methods such as condoms or diaphragms with spermicide or foam, effective intrauterine devices, nuvaring ®, and licensed hormonal methods such as implants, injectables or oral contraceptives ("the pill"). 7. able to understand and comply with planned study procedures and willing to be available for all study-required procedures, visits and calls for the duration of the study. 8. provide written informed consent before initiation of any study procedures. 9. willing to abstain from donating whole blood or blood derivatives until 90 days after the final study injection. exclusion criteria: 1. previous exposure to id93 vaccines or experimental products containing gla-se. 2. history of treatment for active or latent tuberculosis infection. 3. history or evidence of active or documented latent tuberculosis, or positive quantiferon®-tb gold test. 4. shared a residence within the last year prior to randomization with an individual on anti-tuberculosis treatment or with culture or smear positive tuberculosis. 5. received a tuberculin skin test within 3 months (90 days) prior to randomization. 6. history of autoimmune disease or immunosuppression. 7. used immunosuppressive medication (e.g., oral or injected steroids) within 3 months prior to randomization (inhaled and topical corticosteroids are permitted). 8. received any investigational drug therapy or investigational vaccine within past 6 months prior to randomization, or planned participation in any other investigational study during the study period. 9. received investigational tb vaccine at any time prior to randomization. 10. received any vaccine within 30 days prior to the first study vaccination and no planned immunizations between day 0-84 or day 210-224 due to the washout period prior to immunology blood draws. 11. history or laboratory evidence of immunodeficiency state including but not limited to laboratory indication of hiv-1 infection at screening. 12. history of allergic disease or reactions, likely to be exacerbated by any component of the study vaccine. 13. history of allergic reaction to kanamycin-related antibiotics. 14. subjects with a history of previous anaphylaxis or severe allergic reaction to vaccines or unknown allergens. 15. previous medical history that may compromise the safety of the subject in the study, including but not limited to: severe 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 or infantile spasms. 16. known or suspected alcohol or drug abuse within the past 5 years. 17. smokes 1 pack or more of cigarettes per day. 18. history of keloid formation or excessive scarring. 19. history or evidence on physical examination of any systemic disease or any acute or chronic illness that, in the opinion of the investigator, may interfere with the evaluation of the safety or immunogenicity of the vaccine, including axillary lymphadenopathy. 20. received a blood transfusion or immunoglobulin within the past 3 months prior to randomization. 21. donated blood products (platelets, whole blood, plasma, etc.) within past 1 month prior to randomization. 22. presence of any febrile illness, oral temperature of \>100.4 °f/38.0 °c within 24 hours of study injection administration. such subjects may be re-evaluated for enrolment after resolution of illness. 23. positive serum (at screening visit only) or urine pregnancy test at screening or within 24 hours prior to study injection for women of childbearing potential. 24. breastfeeding at any time throughout the study. 25. rash, tattoos, or any other dermatological condition on the upper anterolateral arm that could adversely affect the vaccine injection site or interfere with its evaluation. 26. bmi \ 35 kg/m2. 27. any medical or neuropsychiatric condition which, in the investigator's opinion, would render the subject incompetent to provide informed consent or unable to provide valid safety observations and reporting. 28. cancer or treatment for cancer within 3 years of study injection administration. persons with a history of cancer who are disease-free without treatment for 3 years or more are eligible. persons with treated and uncomplicated basal cell carcinoma of the skin are eligible. 29. subjects unlikely to cooperate with the requirements of the study protocol.

Keywords: vaccine, recombinant, adjuvant, gla-se, id93