Study to Evaluate the Efficacy and Safety of RPH-104 Treatment in Patients With Idiopathic Recurrent Pericarditis

• Status: Recruiting
• Trial end date: 2022-06-21
• Target enrollment: 0
• Participant gender: All

Summary

The goal of this study is to evaluate the Efficacy and Safety of RPH-104 Treatment in patients in comparison to placebo with Idiopathic Recurrent Pericarditis

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: R-Pharm International, LLC
• Collaborators: Covance; Data Management 365 LLC; Unimed Laboratories CJSC

Criteria

Inclusion Criteria:

• Voluntarily signed and dated Informed Consent Form for participation in the study.

• Confirmed diagnosis of idiopathic recurrent pericarditis, established on the basis of the European Society of Cardiology (ESC) diagnostic criteria (2015):

• The patients may be enrolled in the study with signs of disease recurrence or without them (while on therapy with NSAIDs/CS/colchicine: any of these drugs or their combinations), but they have to have at least two documented episodes of pericarditis at least 4-6 weeks in between (the second episode can be verified at the moment of the study site visit).

• For patients demonstrating signs of disease recurrence - stable therapy(i.e. constant doses and dosing regimen) with NSAIDs/CSs for at least 3 days and/or colchicine for at least 7 days prior to the screening

• For patients without signs of disease recurrence - continuous therapy with NSAIDs/CSs/colchicine (any of these drugs or their combinations)

• The patient's ability and willingness (in the reasonable opinion of the Investigator) to come to the study site for all scheduled visits, to undergo all study procedures and comply with the protocol requirements, including consent to subcutaneous injections by qualified personnel of the study site.

• Consent of women of childbearing potential (defined as all women with a physiological ability to become pregnant)) to use highly effective contraceptive methods throughout the study, starting from the beginning of the screening (signing of the Informed Consent Form) and for at least 8 weeks after discontinuation of the study drug; and the negative pregnancy test result (serum test for chorionic gonadotropin).

OR Consent of sexually active male subjects to use highly effective contraceptive methods throughout the study, starting from the beginning of the screening and for at least 8 weeks after discontinuation of the study drug.

Highly effective methods of contraception include the following:

1. complete abstinence (if it agrees with the preferable and usual lifestyle of the patient). [Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception];

2. sterilization: bilateral removal of the ovaries (with or without removal of the uterus) or tubal ligation at least 6 weeks before the start of the study therapy. If only the ovaries have been removed, the reproductive status of the woman should be confirmed by subsequent hormone tests;

3. use of a combination of any two of the following (a+b or a+c, or b+c):

(a) the use of oral, injectable or implanted hormonal contraceptives; in the case of oral contraceptives, women should consistently use the same drug for a minimum of 3 months prior to the initiation of the study treatment; b) placement of an intrauterine device (IUD) or intrauterine system (IUS); c) barrier methods of contraception: a condom or occlusive cap (diaphragm or cervical/vault caps) and spermicidal foam/gel/film/cream/vaginal suppository

4. sterilization of male partner 6 weeks before the study therapy (at least) with proper documentation of the absence of sperm cells in the ejaculate

Exclusion Criteria:

• Hypersensitivity to the study drug (RPH-104), and/or its components/excipients and/or drugs of the same chemical class

• History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies.

• Diagnosis of pericarditis of known etiology (tuberculosis-related, tumor-induced,bacterial), rheumatic diseases

• Previously diagnosed auto-inflammatory diseases

• Prior therapy with:

• rilonacept - less than 6 weeks prior to the baseline assessment (Day 0 of the run-in treatment period);

• canakinumab - less than 12 weeks prior to the baseline assessment (Day 0 of the runin treatment period);

• anakinra - less than 5 weeks prior to the baseline assessment (Day 0 of the run-in treatment period);

• TNF inhibitors, IL-6 inhibitors, Janus kinase inhibitors - less than 12 weeks prior to the baseline assessment (Day 0 of the run-in treatment period);

• immunosuppressive agents (azathioprine, cyclosporine, mycophenolate, mofetil, tacrolimus, sirolimus, mercaptopurine) - less than 24 weeks prior to the baseline assessment (Day 0), methotrexate - less than two weeks prior to the baseline assessment (Day 0),

• any other biological preparations less than 5 half-lives prior to the treatment initiation.

• The use of live (attenuated) vaccine within 3 months prior to Day 0 (of the run-in 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 immunomodulatory therapy, including, but not limited to, the following:

• active bacterial, fungal, viral or protozoal infection revealed at the beginning of the screening period;

• opportunistic infections and/or Kaposi's sarcoma at the beginning of the screening period;

• chronic bacterial, fungal or viral infection requiring systemic therapy at the beginning of the screening period;

• HIV-infection, hepatitis B or C (patients with treated hepatitis C and negative PCR tests after 3 and 6 months are regarded as cured from hepatitis C and can be included in this study);

• 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 tuberculosisinfected patients, such as prisons, gathering of homeless people etc. over the past year until the beginning of the main treatment period;

• work experience in a healthcare setting with unprotected contacts with patients having high risk of tuberculosis or patients with tuberculosis within the past year prior to the beginning of the main treatment 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 the past year prior to the beginning of the treatment 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, other 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

• 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 main 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 the screening

• Concomitant participation in other clinical studies at the moment of the beginning of the screening or the use of any not approved (investigational) medicinal products within 4 weeks of 5 half-life periods (depending on what is longer) up to the baseline assessment (Day 0 of the run-in treatment period).

• Presence of any of the following at the screening:

• Absolute neutrophil count <1.5 х 10^9/L,

• WBC count <3.5 х 10^9/L,

• platelet count <100 х 10^9/L,

• hemoglobin ≤ 80 g/L,

• glycated hemoglobin (HbA1c) ≥ 8%

• ALT and/or AST ≥ 3.0 х ULN,

• Total bilirubin >1.5 х ULN (except for cases of documented Gilbert's syndrome)

• Prior participation in this clinical study.