Safety, Tolerability, PK, PD, and Immunogenicity of Single and Multiple Ascending Intravenous Doses of FR104

Exclusion Criteria

• •Subjects meeting one or more of the following criteria are excluded from participation in this study:
• •1. A history of any clinically significant (as determined by the investigator) cardiac, endocrinology, hematology, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy excluding non-melanoma skin cancer;
• •2. A known allergy, hypersensitivity, or intolerance to the study drug, or to any of its compounds;
• •3. The subject has a history of severe allergic or anaphylactic reactions;
• •4. The subject has a history of consuming more than 21 (14 for females) units of alcoholic beverages per week or has a history of alcoholism or drug/chemical/substance abuse within past 2 years prior to screening (Note: one unit = 330 mL of beer, 110 mL of wine or 28 mL of spirits);
• •5. Evidence or history of any clinically significant infections within the past 3 months;
• •6. History of or evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB) diagnosed by a positive QuantiFERON® TB-Gold In Tube test or a positive tuberculin skin test ("Mantoux") in case of a weak positive QuantiFERON® TB-Gold In Tube test;
• •7. Subjects with known clinically relevant immunological disorders, or auto-immune disorders, (e.g., rheumatoid arthritis, lupus erythematosus, scleroderma, etc...);
• •8. Subjects with a recent infection of EBV diagnosed by a positive IgM VCA;
• •9. A positive hepatitis panel (including hepatitis B surface antigen \[HBsAg\] and anti-hepatitis C virus \[HCV\] antibodies \[Abs\]) or positive human immunodeficiency virus (HIV) antibody screens;
• •10. The subject has a supine systolic blood pressure (SBP) \<90 or \>160 mmHg and a diastolic blood pressure (DBP) \<50 or \>90 mmHg, or pulse rate higher than 100 bpm, either at screening (blood pressure measurements taken after subject has been resting in a supine position for a minimum of 5 minutes); Note: a retest can be done in case of an out of range vital signs value that will determine a subject's eligibility. The result of the retest are considered for subject eligibility.
• •11. The subject is pregnant or breastfeeding;
• •12. The subject has received a vaccine within 60 days prior to study drug administration;
• •13. The subject has received any systemic immunosuppressant agent within 6 months prior to study drug administration;
• •14. The subject has received any antibody or biologic medicinal product within 6 months prior to study drug administration;
• •15. The subject has received any systemic steroid within 2 months prior to study drug administration;
• •16. Use of a prohibited therapy within 14 days prior to study drug administration;
• •17. Receipt of any investigational drug within 30 days or ten half-lives, whichever is longer, prior to the initial study drug administration;
• •18. The subject is participating in another clinical trial or has participated in another dose group of the current trial;
• •19. Had a significant blood loss (including blood donation \[\>500 mL\]) or having had a transfusion of any blood product within the 60 days or donated plasma within 7 days prior to the initial study drug administration;
• •20. A condition that, in the opinion of the investigator, could compromise the well-being of the subject or course of the study, or prevent the subject from meeting or performing any study requirements.
• •21. Intent to visit regions where tuberculosis and mycosis are endemic during the period of 3 months after dosing (4 months after dosing for subjects in Cohort C) , i.e., deserts areas, Eastern Europe, Central and South America, Africa except Egypt, Russia, Asia, Indonesia.