A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multi-center, Phase III Study to Evaluate the Efficacy and Safety of Baricitinib as a Remission-Induction and Glucocorticoid-Sparing Regimen in Subjects with New-Onset Polymyalgia Rheumatica (JAK-SPARE 1)

Who can take part

• Diagnosis of PMR as confirmed by the investigator at screening and at baseline, fulfilment (also in retrospect) of the provisional 2012 ACR-EULAR classification criteria
• Diagnosis of PMR of maximum 3 weeks at screening visit
• GC naïve or on GC treatment for a maximum of 3 weeks at screening with an initial dose of maximum 25 mg/day
• Willing and able to receive oral prednisone/prednisolone 20 mg/day at randomization and to follow a pre-specified tapering regimen
• Willing to receive treatment for prevention of GC-induced bone loss
• Willing and being able to understand and follow the study procedures
• Male and female subjects agreeing to conduct efficient contraception (unless they have no childbearing potential, means a. Women who are infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation b. Women aged 55 years or older who are not on hormone therapy and who have had at least 6 months of spontaneous amenorrhea c. Women aged 55 years or older who have a diagnosis of menopause
• Written informed consent
• Female and Male subjects from ≥ 50 years old and higher

Who cannot take part

• Previous treatment with baricitinib, tofacitinib, upadacitinib, filgotinib or tocilizumab (an exception to this criterion may be granted for single dose exposure upon application to the sponsor on a case-by-case basis)
• Have received plasmapheresis within 12 weeks of screening
• Have a current or recent (< 4 weeks prior to randomization) clinically serious viral, bacterial, fungal or parasitic infection or any other active or recent infection, that in the opinion of the investigator would pose an unacceptable risk to the patient if participating in the study
• Have had symptomatic herpes zoster infection within 12 weeks prior to randomizatio
• Conditions other than PMR requiring continuous or intermittent treatment with oral or parenteral GCs or parenteral administration of GCs, unless the last exposure to GCs was >1 months before screening
• Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
• History of any malignancy prior to screening and patients with an increased risk of malignancy, which, according to the investigator, would pose an unacceptable risk to the patient if participating in the study; in Czech Republic this would also include active smoking patients or patients with a history of long-term smoking
• Have a history of intravenous drug abuse, other illicit drug abuse, or chronic alcohol abuse within the 2 years prior to screening or are concurrently using, or expected to use during the study, illicit drugs (including marijuana
• Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization. Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening
• Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that in the opinion of the investigator could constitute an unacceptable risk when taking investigational product or interfere with the interpretation of data
• Immunization with a live/attenuated vaccine within 12 weeks prior to baseline or are expected to need/receive a live vaccine during the course of the study (with the exception of herpes zoster vaccination at the discretion of the investigator)
• Have a history of disseminated/complicated herpes zoster (for example, multidermatomal involvement, ophthalmic zoster, CNS involvement, or post-herpetic neuralgia)
• Have serologic evidence of current or past Hepatitis B, or Hepatitis C
• Have evidence of HIV infection and/or positive HIV antibodies
• Positive QuantiFERON TB test, history of Tuberculosis, or active Tuberculosis-infection (without at least 4 weeks of adequate therapy for Tuberculosis and no history of re-exposure since their treatment was completed); patients must have no clinical features of active TB and have a screening chest x-ray with no evidence of active TB
• Primary or secondary immunodeficiency (history of or currently active) unless related to primary disease under investigation
• Any medical or psychological condition that in the opinion of the Principal Investigator would interfere with safe completion of the trial
• Neuropathies or other conditions that might interfere with pain evaluation unless related to primary disease under investigation
• Other inflammatory rheumatic diseases (e.g. rheumatoid arthritis)
• Patients with known allergy or intolerance to the study drug or its’ excipients
• Have experienced any of the following VTE (DVT/pulmonary embolism, myocardial infarction, unstable ischemic heart disease stroke, or New York Heart Association Stage III/IV heart failure within 12 weeks of screening. For Centres within Czech Republic and Italy patients with any history of it must not be included
• Have a history of recurrent (≥ 2) VTE (DVT/PE)
• Have screening laboratory test values, including thyroid-stimulating hormone (TSH), outside the reference range for the population that, in the opinion of the investigator, pose an unacceptable risk for the patient´s participation in the study. Patients who are receiving thyroxine as replacement therapy may participate in the study, provided stable therapy has been administered for ≥ 12 weeks and TSH is within the laboratory´s range. Patients who have TSH marginally outside the laboratory´s normal reference range and are receiving stable thyroxine replacement therapy may participate if the treating physician has documented that the thyroxine replacement therapy is adequate for the patient
• Have any of the following specific abnormalities on screening laboratory tests: a. ALT or AST >2 x ULN b. Alkaline phosphatase (ALP) ≥2 x ULN c. Total bilirubin ≥ 1.5 x ULN d. Hemoglobin <9 g/dL (90.0 g/L) e. Total white blood cell count <2500 cells/µL (<2.50 x 103 / µL or <2.50 GI/L) f. Neutropenia (absolute neutrophil count [ANC] <1200 cells/ µL (<1.20 x 103/ µL or <1.20 GI/L) g. Lymphopenia (lymphocyte count <500 cells/µL) (<50 x 103/ µL or <50GI/L) h. Thrombocytopenia (platelets <100,000 cells/µL) (<100 x 103/µL or <100 GI/L) i. eGFR <60 mL/min/1.73 m2 (Bedside Schwartz formula 2009) In the case of any of the aforementioned laboratory abnormalities, the test may be repeated once by the central laboratory during screening and values resulting from repeat testing may be accepted for enrolment eligibility if they meet the eligibility criterion
• For Centers in Czech Republic only: Patients above 65 years of age at screening visit
• Evidence of GCA (cranial or large vessel) as indicated by unequivocal clinical symptoms (except PMR), imaging and/or biopsy results. Routine screening of eligible PMR patients for GCA with imaging methods or temporal artery biopsy is not recommended
• Have a symptomatic herpes simplex at the time of randomization
• Are largely or wholly incapacitated permitting little or no self-care, such as being bedridden or confined to wheelchair
• Pregnant women or nursing (breast feeding) mothers
• Patients with reproductive potential not willing to use an effective method of contraception
• Patients with lack of peripheral venous access
• Have screening electrocardiogram (ECG) abnormalities that, in the opinion of the investigator, are clinically significant and indicate an unacceptable risk for the patient´s participation in the study