A Study to Target the Type I IFN Receptor by Administrating Anifrolumab in RA Patients With a High IFN Signature (TarIFNiRA)

Inclusion Criteria: * Aged 18 through 70 years at the time of screening * Written informed consent * Weigh ≥50.0 kg and ≤100.0 kg at screening * Diagnosis of RA according to the 2010 ACR/EULAR classification criteria for RA * At study entry, patients must take at least one conventional synthetic (cs)DMARD (methotrexate (MTX), leflunomide, sulfasalazine (SSZ)) regularly for at least the preceding 12 weeks, with stable doses for at least the preceding 8 weeks. * moderately to severely active RA: ≥4 tender joints of 28 joints examined, ≥4 swollen joints of 28 joints examined and an elevated serum C-reactive protein level (CRP). * Received at least one TNF-inhibitor (TNFi) but not more than 3 biological (b)DMARDs and discontinued treatment because of an insufficient response after at least 3 months. * Oral Glucocorticoids (OCS) are allowed at stable doses of ≤10 mg/day prednisone or equivalent, if already used before the screening visit, dose must be stable for at least 2 weeks, and will be kept stable throughout the course of the study * High type I IFN gene signature test * Seronegative for human immunodeficiency virus (HIV) and negative test for hepatitis B surface antigen and hepatitis C - antibodies * Negative serum β-human chorionic gonadotropin (β-hCG) test at screening (females of childbearing potential only). * Females of childbearing potential must use 2 effective methods of avoiding pregnancy, only one of which is a barrier method, from screening until 12 weeks after the final dose of the investigational product unless the subject is surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy), has a sterile male partner, is 1 year post-menopausal, or practices sustained abstinence.Cessation of birth control after the specified period for investigational product should be discussed with a responsible physician. Post-menopausal is defined as at least 1 year since last menses and the subject having an elevated follicle- stimulating hormone (FSH) level greater than the central laboratory value of post-menopausal at screening * All males (sterilised or non-sterilised) who are sexually active must use condom (with spermicide where commercially available for contraception if sexually active with a woman of child bearing potential) from Day 0 until at least 12 weeks after receipt of the final dose of the investigational product. It is strongly recommended that female partners of child bearing potential of male subjects also use a highly effective method of contraception (other than a barrier method) throughout this period. * Male subjects must not donate sperm during the course of the study and for 12 weeks after the last dose of the investigational product. * Females with an intact cervix must have documentation of a normal Pap smear with no documented malignancy (e.g., cervical intraepithelial neoplasia grade III \[CIN III\], carcinoma in situ \[CIS\], or adenocarcinoma in situ \[AIS\]) within 2 years prior to randomization. Any abnormal Pap smear result documented within 2 years prior to randomization must be repeated to confirm patient eligibility. * Meets all of the following tuberculosis (TB) criteria: * No history of latent or active TB prior to screening, with the exception of latent TB with documented completion of appropriate treatment * No signs or symptoms suggestive of active TB from medical history or physical examination * No recent contact with a person with active TB OR if there has been such contact, referral to a physician specialising in TB to undergo additional evaluation prior to randomisation (documented appropriately in source), and, if warranted, receipt of appropriate treatment for latent TB at or before the first administration of investigational product * Negative QuantiFERON-tuberculosis Gold \[QFT-G\] test for tuberculosis within 3 months prior to randomisation * A chest radiograph with no evidence of current active infection (eg, tuberculosis) or old active TB, malignancy, or clinically significant abnormalities obtained during the screening period or anytime within 12 weeks prior to signing of the informed consent General Exclusion criteria: * Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of patient safety or study results * Concurrent enrolment in another clinical study with an investigational product * Individuals involved with the conduct of the study, their employees, or immediate family members of such individuals * Lactating or pregnant females or females who intend to become pregnant anytime from initiation of screening until the 12-week safety follow-up period following last dose of investigational product * Current alcohol, drug or chemical abuse, or a history of such abuse within 1 year before Week 0 (Day 0) * Major surgery within 8 weeks before signing informed consent form (ICF) or elective major surgery planned during the study period * Spontaneous or induced abortion, still or live birth, or pregnancy ≤4 weeks prior to signing the ICF * Low type I IFN transcript scores in peripheral whole blood (type I Interferon Gene signature test) * At screening (within 4 weeks before Week 0 \[Day 0\]), any of the following: * Aspartate aminotransferase (AST) \>2.0 × upper limit of normal (ULN) * Alanine aminotransferase (ALT) \>2.0 × ULN * Total bilirubin \>ULN (unless due to Gilbert's syndrome) * Serum creatinine \>2.0 mg/dL (or \>181 μmol/L) * Urine protein/creatinine ratio \>2.0 mg/mg (or \>226.30 mg/mmol) * Neutrophil count \<1000/μL (or \<1.0 × 109/L) * Platelet count \<150.000/μL (or \<150 × 109/L) * Haemoglobin \<8 g/dL (or \<80 g/L) * Glycosylated haemoglobin (HbA1c) \>8% (or \>0.08) at screening (diabetic patients only) Exclusion criteria related to concomitant medications: * Receipt of any investigational product (small molecule or biologic agent) within 4 weeks or 5 half-lives prior to signing of the ICF. * Prior receipt of Anifrolumab * Prior receipt of a JAK-inhibitor * A known history of allergy or reaction to any component of the investigational product formulation or history of anaphylaxis to any human gamma globulin therapy * Regular use of \>1 nonsteroidal anti-inflammatory drug (NSAID) within 2 weeks prior to week 0 (Day 0); OR receipt of fluctuating doses of a NSAID within 2 weeks prior to Week 0 (Day 0) * Receipt of any of the following: Intra-articular, intramuscular or intravenous glucocorticosteroids within 6 weeks prior to Day 0 * Any live or attenuated vaccine within 8 weeks prior to signing the ICF (administration of killed vaccines is acceptable); Patients should be up to date on required vaccinations, including influenza \[inactivated/recombinant\] vaccine prior to study entry * Bacillus Calmette-Guerin (BCG) vaccine within 1 year of signing the informed consent form * Blood transfusion within 4 weeks prior to signing the ICF Exclusion criteria related to other diseases: * History of any non-RA disease that has required treatment with oral or parenteral corticosteroids for more than a total of 2 weeks within the last 24 weeks prior to signing the ICF Exclusion criteria related to infection and malignancy risk factors: * Splenectomy * Any severe herpes infection at any time prior to Week 0 (Day 0), including, but not limited to, disseminated herpes (ever), herpes encephalitis (ever), recurrent herpes zoster (defined as 2 episodes within 2 years) or ophthalmic herpes (ever) * Any herpes zoster infection that has not completely resolved within 12 weeks prior to signing the ICF * Opportunistic infection requiring hospitalisation or parenteral antimicrobial treatment within 3 years of randomisation * Any of the following: * Clinically significant chronic infection (ie, osteomyelitis, bronchiectasis, etc) within 8 weeks prior to signing the ICF (chronic nail infections are allowed) * Any infection requiring hospitalisation or treatment with intravenous anti-infectives not completed at least 4 weeks prior to signing the ICF * Any infection requiring oral anti-infectives (including antivirals) within 2 weeks prior to Day 0 * History of cancer, apart from: * Squamous or basal cell carcinoma of the skin treated with documented success of curative therapy ≥3 months prior to Week 0 (Day 0) * Cervical cancer in situ treated with apparent success with curative therapy ≥1 year prior to Week 0 (Day 0)