Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Effects of Multiple Rising Subcutaneous Doses of BI 655064 in Healthy Volunteers and in Rheumatoid Arthritis Patients With Prior Inadequate Response to Methotrexate Therapy

Inclusion criteria

Part 1 (phase Ib) (HVs):

• Healthy males and females according to the investigators assessment, as based on the following criteria: a complete medical history including a physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests
• Age >= 18 and = 18.5 and = 18 and =15mg. For patients who do not tolerate the minimum weekly dose of at least 15 mg due to side effects, a stable weekly dose as low as 7.5 mg is also permitted.
• DAS28 4v-CRP >= 3.5 with >= 6 tender and >= 6 swollen joints out of 68/66 joint count at screening and confirmed by >= 6 tender and >= 6 swollen joints out of 68/66 joint count only at randomisation visit (Visit 2)
• Serum CRP level >= 0.8 mg/dL or ESR >= 28 mm/1h at screening
• Anti-CCP2 or Rheumatoid Factor positivity as per the limits of used assay at screening
• Female patients who meet any of the following criteria from at least 30 days before the first study drug administration and until at least 6 months after last dose of MTX taken in the current trial:

using adequate contraception, e.g. any of the following methods plus condom: implants, injectables, combined oral contraceptives, intrauterine device (IUD)

• sexually abstinent
• have a vasectomised sexual partner (vasectomy at least 1 year prior to enrolment)
• surgically sterilised (including hysterectomy)
• postmenopausal defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous levels of follicle stimulating hormone (FSH) above 40 U/L and estradiol below 30 ng/L is confirmatory)

OR

Male patients who:

• are documented to be sterile or consistently and correctly use a condom while their female partners (if of childbearing potential) agree to use any of the following adequate contraception methods: implants, injectables, combined oral contraceptives, intrauterine device (IUD) from the date of screening until at least 6 months after the last dose of MTX taken in the current trial
• don¿t donate any sperm sample for procreation purposes, from the date of screening until at least 6 months after last dose of MTX taken in the current trial.
• Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation

Exclusion criteria

Part 1 (phase Ib in HVs):

• Any finding in the medical examination (including BP, PR or ECG) deviating from normal and judged clinically relevant by the investigator
• Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
• Any evidence of a concomitant disease judged clinically relevant by the investigator
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Diseases of the central nervous system (such as epilepsy), other neurological disorders or psychiatric disorders
• History of relevant orthostatic hypotension, fainting spells, or blackouts
• History of relevant allergy/hypersensitivity (including allergy to the trial medication or its excipients)
• Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial 12. Alcohol abuse (consumption of more than 140 g/week in females and 210 g/week in males) 13. Drug abuse or positive drug screen 17. Chronic or relevant acute infections, including but not limited to HIV, Hepatitis B and C and tuberculosis (including a history of clinical TB and/or a positive QuantiFERON TB-Gold test) 18. Subject is assessed by the investigator as unsuitable for inclusion e.g. considered not able to understand and comply with study requirements or has a condition that would not allow safe participation in the study 19. Positive pregnancy test, pregnancy or plans to become pregnant within 30 days after study completion 20. Lactation

Further exclusion criteria applicable for part 1 only are given in the CTP.

Part 2 (phase IIa in RA patients):

Part 1