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