Clinical trial NCT02800811 (phase 1, status: completed)
Conditions: rheumatoid arthritis, complication of transplant
ICD codes: M06.9, M05.9, M06.08, M06.00, M06.011, M06.012, M06.019
Drugs: fr104, placebo
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

        Subjects meeting all of the following criteria are eligible to participate in this study:

          1. Male or female, aged 18 to 60 years, extremes includes;

          2. In good health condition [medically stable] as determined on the basis of medical
             history, vital signs, clinical laboratory testing, and general physical examination
             performed at screening; Note: a retest can be done in case of an out of range clinical
             laboratory test value that will determine a subject's eligibility. This retest is
             preferably to be done at an unscheduled visit. The result of the retest are considered
             for subject eligibility. If the retest is outside normal reference ranges, the subject
             are eligible for inclusion only if the investigator judges the abnormalities to be not
             clinically significant.

          3. Electrocardiogram (ECG) within normal range, or showing no clinically relevant
             deviations, as judged by the investigator; Note: a retest can be done in case of an
             out of range ECG value that can determine a subject's eligibility.

          4. Weighs at least 50 kg and no more than 100 kg and has a Body Mass Index (BMI) within
             normal range: 18.0≤BMI<30.0 kg/m2;

          5. Negative urine test for selected drugs of abuse at screening;

          6. Negative alcohol breath test at screening;

          7. Female subject is postmenopausal or surgically sterile (having had a hysterectomy,
             bilateral oophorectomy, or tubal ligation);

          8. Female subject has a negative pregnancy test at screening;

          9. Non-vasectomized male subjects having a female partner of childbearing potential must
             agree to the use of an effective method of contraception until 90 days after the last
             administration of study drug ;

         10. Male subject has to agree not to donate sperm until 90 days after the last
             administration of study drug;

         11. Willing to adhere to the prohibitions and restrictions specified in this protocol;

         12. Informed Consent Form (ICF) signed voluntarily before any study-related procedure is
             performed, indicating that the subject understands the purpose of and procedures
             required for the study and is willing to participate in the study;

         13. Subjects were to be EBV-positive as per positive IgG Epstein-Barr nuclear antigen
             (EBNA) test;

         14. Nonsmoker or light smoker, i.e., smokes maximal 5 cigarettes (or 3 cigars or 3
             pipe-full) per day, and ability and willingness to refrain from smoking during
             confinement and ambulant visits in the clinical research center.

             For Part 1, Cohort B only:

         15. The subject did not undergo a KLH challenge.

        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.