Inhibition of JAK Enzymes in early stage Joint inflammation

INTERVENTION: Trade Name: Olumiant 2 mg/4 mg Filmtabletten Product Name: Baricitinib blinded Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: Baricitinib CAS Number: 1187594‐09‐7 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 4‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use CONDITION: Preclinical Phase of rheumatoid arthritis ; MedDRA version: 23.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 ‐ Musculoskeletal and connective tissue disorders Therapeutic area: Diseases [C] ‐ Musculoskeletal Diseases [C05] PRIMARY OUTCOME: Main Objective: To evaluate the effect of JAK Inhibition with baricitinib in preclinical stage of arthritis Primary end point(s): Number of patients with development of arthritis Secondary Objective: • To evaluate the effect of serological biomarkers such as pro‐inflammatory cytokines, interferon signatures, bone biomarkers in preclinical arthritis; • To evaluate safety of baricitinib in preclinical stage of arthritis; • To identify (imaging and serological) biomarkers which may predict the course of disease in preclinical stage of arthritis ; • To evaluate the effect of baricitinib on physical (hand) function in preclinical stage of disease; Timepoint(s) of evaluation of this end point: week 48 SECONDARY OUTCOME: Secondary end point(s): • Number of patients with development of arthritis at week 24 ; • Fulfillment of the ACR/EULAR 2010 RA classification criteria; • Imaging:; o Ultrasound: Number of participants without signs of PD Synovitis or PD Tenosynovitis at week 24 and 48 compared to baseline and compared within both groups; • Explorative serological biomarkers: (week 24 and week 48 compared to baseline); o Change in anti CCP2 antibody levels (RE/ml) ; o Change in anti CCP2 antibodies in HLA‐defined subgroups; o Glycosylation profile of total IgG, and CCP2 antibodies; o Number and frequency of total and CCP2‐specific B cells; o MS‐based unbiased metabolic profiling of plasma metabolites; o Changes in GBP1 levels; • Clinical outcomes, physical function and PROs:; o Patients without tender joints at week 48 compared to baseline; o Joint count 76/78; HAQ; SDAI/CDAI/DAS28‐CRP; o Pain: VAS global, VAS pain, VAS physician; o Subjective (SACRAH, sMHQ) and objective (moberg‐pick up test (MPUT)) hand function; o Safety; Timepoint(s) of evaluation of this end point: week 24 / week 48 compared to baseline INCLUSION CRITERIA: • Clinical: no arthritis in 76/78 joint count • Imaging: = 1 B‐Mode or PD (Power Doppler) signal with ultrasound at one of the 76/78 joints or flexor/extensor tendons of hand or feet • Autoantibodies: (2 different Autoantibodies are compulsory, one of them anti‐CCP antibodies) o Anti‐CCP antibody positivity at Screening o Anti‐modified antibodies: (citrullinated vimentin, citVIM; citrullinated a‐enolase, citENO; citrullinated fibrinogen alpha, citFIBa; citrullinated fibrinogen beta, citFIBb) (carbamylated vimentin, carVIM; ornithine acetylated vimentin (ac‐orn VIM) and lysine acetylated Vimentin, ac‐lys VIM)or RF • Genetics: HLA Status with positive risk allel for RA such as HLA DRB1*01,*02,*03,…*015 • female or male patients, at least 18 and at most 64 years of age Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.