Efficacy and Safety of RPH-104 Treatment in Patients With Recurrent Pericarditis

Exclusion Criteria

• •* Hypersensitivity to the study drug (RPH-104), and/or its components/excipients
• •* History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies or fusion proteins.
• •* Pericarditis secondary to: a) tuberculosis (TB); b) postthoracic blunt trauma; c) myocarditis; d) systemic autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, etc.; Still's disease and familial Mediterranean fever are not considered as autoimmune diseases); e) neoplastic, purulent, or radiation etiologies.
• •* Is currently receiving CS at a dose of \> 60 mg/day prednisone (or equivalent).
• •* Prior therapy with:
• •* rilonacept - less than 6 weeks prior to the baseline assessment (Day 0 of run-in treatment period);
• •* canakinumab - less than 12 weeks prior to the baseline assessment (Day 0 of run-in treatment period);
• •* anakinra - less than 5 days prior to the baseline assessment (Day 0 of run-in treatment period);
• •* Tumor necrosis factor (TNF) inhibitors, Interleukin 6 (IL-6) inhibitors, Janus kinase inhibitors - less than 12 weeks prior to the baseline assessment (Day 0 of run-in treatment period);
• •* immunosuppressive agents (azathioprine, cyclosporine, mycophenolate, mofetil, tacrolimus, sirolimus, mercaptopurine) - within 24 weeks prior to the baseline assessment (Day 0 of run-in treatment period), methotrexate - less than two weeks prior to the baseline assessment (Day 0 of run-in treatment period),
• •* any other biological preparations less than 5 half-lives prior to the treatment initiation (Day 0 of run-in treatment period).
• •* The use of a live (attenuated) vaccine within 3 months prior to Day 0 of the RI treatment period and/or the need to use this type of a vaccine within 3 months after the discontinuation of the study drug. Live attenuated vaccines include vaccines against viral infections such as measles, rubella, mumps, chickenpox, rotavirus, influenza (in the form of a nasal spray), yellow fever, polio (oral polio vaccine); vaccines against tuberculosis (BCG), typhoid (oral typhoid vaccine) and typhus (epidemic typhoid vaccine) vaccines. Patient's immunocompetent family members should refrain from administration of a polio vaccine during the patient's participation in the study.
• •* Conditions or signs that, according to the Investigator, indicate impairment (weakening) of the immune response in the patient and/or significantly increase the risk of the use of immunosuppressive therapy, including, but not limited to, the following conditions at the screening:
• •* active bacterial, fungal, viral (including COVID-19) or protozoal infection;
• •* opportunistic infections and/or Kaposi's sarcoma;
• •* chronic bacterial, fungal or viral infection requiring systemic antimicrobial therapy;
• •* HIV-infection, hepatitis B or C (patients with treated hepatitis C and negative Polymerase chain reaction (PCR) tests after 3 and 6 months are regarded as cured from hepatitis C and can be included in this study); within 6 months prior to the beginning of the screening period:
• •* disseminated herpes zoster infection, herpetic encephalitis, meningitis and other non-self-limiting infections caused by herpes viruses;
• •* A history of active tuberculosis or the presence of risk factors or signs indicating the presence of active or latent infection caused by M. tuberculosis, including but not limited to, the following:
• •* living in specific conditions that increase the risk of contacts with tuberculosis-infected patients, such as prisoners, gathering of homeless people etc. within a year before the beginning of the screening period;
• •* work experience in a healthcare setting with unprotected contacts with patients having high risk of tuberculosis or patients with tuberculosis within a year prior to the beginning of the screening period;
• •* close contact, i.e. being in the same room (at home or in another confined environment) for an extended period of time (days or weeks rather than minutes or hours) with a person with active pulmonary tuberculosis within a year prior to the beginning of the screening period;
• •* test results indicating active tuberculosis or latent infection caused by M. tuberculosis: positive result of QuantiFERON-TB/T-SPOT test.TB during the screening period; findings of chest X-ray exam in two views confirming pulmonary tuberculosis during the screening period.
• •* The presence of any other significant comorbidities (cardiovascular, nervous, endocrine, urinary tract, gastrointestinal tract, liver, blood clotting disorders, autoimmune diseases, etc.) or conditions that may, in the reasonable opinion of the Investigator, adversely affect the participation and well-being of the study subject and/or distort the evaluation of the study results.
• •* Uncontrolled diabetes mellitus.
• •* History of organ transplant, or the need for transplant surgery at the beginning of the screening period, or elective transplant surgery during the study.
• •* The presence of any malignancies during the screening period or within 5 years prior to its initiation, except for non-metastatic basal cell and squamous cell skin cancer after complete resection or carcinoma in situ of any type following complete resection.
• •* Mental disorders that, in the reasonable opinion of the Investigator, may affect the patient's participation in the study or his/her ability to comply with the Protocol procedures.
• •* Pregnancy or breast-feeding.
• •* History of abuse of alcohol or psychoactive substances as assessed by the Investigator.
• •* Severe renal impairment (creatinine clearance by Cockcroft-Gault formula \<30 mL/min at screening.
• •* Presence of any of the following laboratory abnormalities at screening:
• •* Absolute neutrophil count \<1.5 х 10\^9/L,
• •* White blood cells (WBC) count \<3 х 10\^9/L,
• •* Platelet count \<100 х 10\^9/L,
• •* Hemoglobin ≤ 80 g/L,
• •* Glycated hemoglobin (HbA1c) ≥ 8%,
• •* Alanine transaminase (ALT) and/or Aspartate aminotransferase (AST) ≥ 3.0 х Upper limit of normal (ULN),
• •* Total bilirubin \>1.5 х ULN (except for cases of documented Gilbert's syndrome).
• •* Concomitant participation in other clinical studies at the beginning of the screening or the use of any unapproved (investigational) medicinal products within 4 weeks or 5 half-life periods (whichever is longer) up to the baseline assessment (Day 0 of the run-in treatment period).