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Signed Informed Consent Form for participation in the study |
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Men and women aged 18 to 65 years inclusive at the time of signing the Informed Consent Form |
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An established diagnosis of ankylosing spondylitis according to the modified New York classification criteria (van der Linden et al. 1984) |
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Sacroiliitis (bilateral ≥ grade 2 or unilateral grade 3-4) based on central review of radiographs |
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Positive ASAS criteria for axial spondyloarthritis (Rudwaleit et al. 2009) |
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Duration of back pain ≥3 months and age of onset of back pain <45 years |
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Positive HLA-B27 test |
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Active disease at screening and at the Randomization Visit, based on both of the following criteria |
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BASDAI ≥4 |
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back pain NRS score ≥4 (BASDAI question 2) |
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CRP level ≥5 mg/mL at screening |
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At least one of the following criteria, as assessed by the investigator |
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Inadequate response to NSAID therapy defined as an insufficient response to NSAID therapy at a therapeutic dose for at least 4 weeks, or an insufficient response to therapy with two NSAIDs at the maximum allowed dose with a total duration of therapy of at least 4 weeks |
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Contraindications for NSAID therapy |
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Intolerance to more than one NSAID |
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For subjects continuing to receive NSAIDs or COX-2 inhibitors: the dose of the drug |
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should be stable for at least 14 days prior to Visit 1/Week 0 |
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For women: a negative pregnancy test at screening (the test is not performed in women who have been postmenopausal for at least 2 years or are surgically sterile) |
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The ability of the subject, in the opinion of the investigator, to follow the protocol procedures |
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Willingness of subjects and their sexual partners of childbearing potential to use reliable methods of contraception from the date of signing the ICF, throughout the study, and for 8 weeks after the last administration of the test drug/placebo. This requirement does not apply to subjects who have had operative sterilization and women who have been postmenopausal for more than 2 years. Reliable methods of contraception include the use of one barrier method in combination with one of the following in the female partner: spermicides, intrauterine device, oral contraceptives |
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For subjects of childbearing potential (from the ICF signing, throughout the study, and for 8 weeks after the last infusion of the test drug/placebo) |
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no egg donation for female subjects |
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no sperm donation for male subjects |
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Total ankylosis of the spine defined by the presence of syndesmophytes in ≥3 adjacent vertebral segments based on central review of radiographs
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Age less than 18 years at disease onset
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Refusal to take NSAIDs for the treatment of AS for any subjective reasons that do not have a clinical justification
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Use of the following medicines/procedures
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at any time before signing the ICF: use of any monoclonal antibodies or their fragments for any indication
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at any time before signing the ICF: total irradiation of the lymphatic system
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at any time before signing the ICF: bone marrow transplantation, including transplantation of stem and hematopoietic cells for any indication
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at any time before signing the ICF: splenectomy
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within 8 weeks before signing the ICF: treatment with immunoglobulins
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within 12 months before signing the ICF: use of immunosuppressants. Exception: glucocorticoids. A subject receiving glucocorticoids may be included in the study provided that the daily dose of glucocorticoids is ≤10 mg/day (calculated with reference to prednisolone) and was stable for at least 4 weeks prior to the Randomization Visit
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within 4 weeks before signing the ICF and during the screening period: use of synthetic DMARDs and thiopurines, including, but not limited to: 6-mercaptopurine, azathioprine, and others
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Exception: the medicinal products listed below if their dose was stable for 4 weeks
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before signing the ICF and during the screening period
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methotrexate orally or parenterally at a dose not exceeding 25 mg/week, provided
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that therapy was started at least 8 weeks before signing the ICF
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-aminosalicylic acid and its derivatives, including sulfasalazine, at a dose not
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exceeding 3 g/day, provided that therapy was started at least 8 weeks before
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signing the ICF. Subjects with inflammatory bowel disease (IBD) may be treated
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with topical 5-aminosalicylic acid at therapeutic doses
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intra-articular and paraspinal glucocorticoids within 4 weeks prior to the
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Randomization Visit, intramuscular glucocorticoids within 2 weeks prior to
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the Randomization Visit
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use of alkylating agents at any time within 12 months prior to signing the
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ICF
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use of targeted synthetic disease-modifying antirheumatic drugs (kinase
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inhibitors) at any time before signing the ICF
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Vaccination with any vaccines within 12 weeks prior to signing the ICF
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Documented presence of one or more of the following conditions within 8 weeks before
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signing the ICF and during the screening period: acute anterior uveitis, exacerbated
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IBD (attack of Crohn's disease or exacerbation (relapse, attack) of ulcerative
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colitis), exacerbated psoriasis
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Clarification: for subjects with IBD: IBD therapy must be stable for 8 weeks prior to
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signing the ICF. For subjects with psoriasis: topical products may be used
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A current diagnosis or a history of a severe immunodeficiency of any origin
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A diagnosis of HIV infection, hepatitis B, hepatitis C, syphilis
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The following laboratory test results at screening
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Transaminase (ALT and/or AST) activity >1.5 ULN
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ALP activity >1.5 ULN
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WBC count <3.0 cells×109/L
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Neutrophil count <1.5 cells× 109/L
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Lymphocyte count <0.8 cell×109/L
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Platelet count <100 cells×109/L
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Hemoglobin level <100 g/L
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Serum creatinine level >ULN
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A history of hypothyroidism/hyperthyroidism/autoimmune thyroiditis and/or abnormal TSH
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level at screening
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Active or latent tuberculosis, including a history thereof
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Major surgery within 4 weeks prior to signing the ICF or major surgery planned for the
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period of participation in the study
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Documented diagnosis of infectious mononucleosis within 8 weeks prior to signing the
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ICF and during the screening period, any active infection or recurrent infection
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within 4 weeks prior to signing the ICF and during the screening period, including
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fever ≥38 °C at the Randomization Visit; Clarification: if a subject presents with an
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acute infection during the screening, the screening can be extended if agreed with the
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Sponsor. In this case, the Sponsor's representative will decide whether the subject
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can be randomized. Subjects with body temperature ≥38 °C may be rescreened once 4
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weeks after resolution of the condition
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A history of coronavirus infection (positive PCR test for SARC-CoV2-RNA) less than 14
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weeks before signing the ICF
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Clarification: including according to the subject
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A documented diagnosis of any other chronic infection that, in the opinion of the
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investigator, can increase the risk of infectious complications
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Severe infectious diseases (requiring hospitalization, parenteral use of
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antibacterial, antimycotic or antiprotozoal drugs) within 8 weeks prior to signing the
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ICF and during the screening period
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Systemic antibacterial, antimycotic or antiprotozoal therapy within 8 weeks prior to
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signing the ICF and during the screening period
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Epileptic seizures, a history of seizures
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A history of or current (at the time of signing the ICF and during the screening
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period) significant uncontrolled neuropsychiatric disorders, severe depression and/or
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suicide attempts, a risk of suicide and/or any psychiatric illness that, in the
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opinion of the investigator, may pose an excessive risk to the subject or have an
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impact on the subject's ability to follow the protocol
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Known (including from historical data) alcohol or drug dependence, psychoactive
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substance or drug abuse, evidence of alcohol/drug dependence or current abuse that, in
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the investigator's opinion, is a contraindication to AS therapy or limits treatment
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adherence
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The following diseases
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at screening and/or in the past and at the Randomization Visit: non-axSpA
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inflammatory joint disease (including rheumatoid arthritis, gout, psoriatic
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arthritis, Lyme disease, etc.)
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at screening and/or at the Randomization Visit: reactive arthritis
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at screening and/or in the past and at the Randomization Visit: systemic
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autoimmune diseases (including systemic lupus erythematosus, systemic
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scleroderma, inflammatory myopathy, mixed forms of inflammatory connective tissue
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diseases, overlap syndrome, etc.)
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Exception: subjects with psoriasis who have not previously received and do not
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currently need systemic therapy, as well as patients with IBD regarded as an
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extraskeletal manifestation of axSpA, may be included in the study if all other
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eligibility criteria are met
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Comorbidities (including, but not limited to, metabolic, hematological, renal
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hepatic, pulmonary, neurological, endocrine, cardiac, infectious, gastrointestinal
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disorders), including disorders ongoing at the time of screening, which, in the
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opinion of the investigator, may affect the course of radiographic axSpA, the results
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of assessment of its symptoms, or create an unacceptable risk to the subject from
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study therapy
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Grade 3 or 4 obesity
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Known allergy or intolerance to any component of the test drug, premedication drugs
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used in this clinical study
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A history of angioedema
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Fibromyalgia, or other conditions associated with chronic pain
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Lymphoproliferative diseases or malignancies with a remission duration of less than 5
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years, with the exception of cured basal cell carcinoma and cervical cancer in situ
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Pregnancy, pregnancy planning (including pregnancy of female sexual partners of male
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study subjects) less than 8 weeks after the last administration of the test
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drug/placebo, breastfeeding
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Contraindications to MRI
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Simultaneous participation in other clinical studies, as well as previous
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participation in other clinical studies less than 3 months before signing the ICF
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prior participation in this study
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Exception: subjects who dropped out of this study at screening
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