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

NCT05107934 | Suspended Phase 2 DMC FDA Drug

• 1 other identifier: CL04018106
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is the evaluation of the efficacy and safety of RPH-104 treatment in patients with recurrent pericarditis. Pharmacokinetic and pharmacodynamic parameters of RPH-104 multiple doses in this patient population will be assessed as well.

Conditions

Recurrent Pericarditis

Keywords

RPH-104; subcutaneous

Outcome Measures

Primary Outcomes (1)

• Time (days) to the pericarditis recurrence within 24 weeks after randomization in patients with recurrent pericarditis treated with RPH-104 compared to placebo.

  Pericarditis recurrence is defined as the occurrence of at least two of the following signs: * at least 1 day of pericarditis pain ≥ 4 (on the 11 point numerical rating scale (NRS)) (without any other potential causes for the increase in the pain intensity); * at least one CRP value ≥ 1 mg/dL (without any other potential causes for the C-reactive protein (CRP elevation)); * new or progression of existing pericardial effusion during the diastole as demonstrated by echocardiography; * evidence of new widespread ST-elevation (ST segment / T wave ratio in lead v6 \> 0.25) or PR depression on electrocardiogram (ECG). Each sign can occur either on the same day or separated by no more than 7 days from another sign.

  up to Week 24 (of the RW period)

Secondary Outcomes (2)

• Proportion of subjects who maintained Clinical Response at Week 16 of the RW period in RPH-104 group compared to placebo.

  up to Week 16 (of the RW period)

• Percentage of days with no or minimal pain in the first 16 weeks of the RW period in RPH-104 group compared to placebo.

  up to Week 16 (of the RW period)

Study Arms (2)

RPH-104 80 mg

EXPERIMENTAL

Patients will receive RPH-104 dose 160 mg subcutaneously on Day 0, and 80 mg on Day 7, Day 14 and thereafter once in two weeks.

Biological: RPH-104

Placebo

PLACEBO COMPARATOR

Patients (who achieved clinical response defined above by the randomized withdrawal baseline) will receive placebo subcutaneously once every 2 weeks.

Drug: Placebo

Interventions

RPH-104 BIOLOGICAL

solution for subcutaneous injection, 40 mg/mL

RPH-104 80 mg

Placebo DRUG

0.9% Sodium Chloride solution for Injection

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily signed and dated Informed Consent Form for participation in the study.
• Recurrent pericarditis diagnosis.
• ≥ 1 pericarditis episodes experienced prior to screening has met ≥ 2 of the following 4 criteria, in the Investigator's opinion and based on the documented available data, according to 2015 European Society of Cardiology (ESC) Guidelines for the Diagnosis and Management of Pericardial Diseases:
• Pericarditic chest pain
• Pericardial rub
• New widespread ST-segment elevation/PR-segment depression according to ECG findings
• Pericardial effusion (new or worsening)
• Presents with at least the third episode of pericarditis during screening (i.e., at least the second pericarditis recurrence following the first pericarditis episode), and within ≤ 7 days prior to and including RI baseline (first administration of study drug) has at least two of the following signs: 1) ≥ 1 day with NRS pain score ≥ 4 (without any other potential causes for the increase in the pain intensity); 2) CRP ≥ 1 mg/dL, (without any other potential causes for the CRP elevation); 3) new or progression of existing pericardial effusion during the diastole as demonstrated by echocardiography; 4) evidence of new widespread ST-elevation (ST segment or T wave ratio in lead v6 \> 0.25) or PR depression on ECG. Each sign must be presented either on the same day or separated by no more than 7 days from the other sign.
• NSAIDs and/or colchicine and/or CS (in any combination), if used, at stable dose levels for at least 3 days prior to and including RI baseline before RPH-104 administration.
• If using NSAIDs and/ or colchicine and/or CS at RI baseline, is willing and able, in the opinion of the investigator, to taper and discontinue these drugs no later than Week 12 of the RI period.
• 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 physiologically able 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 a negative pregnancy test result (serum test for chorionic gonadotropin).
• 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:
• complete abstinence (if it agrees with the preferable and usual lifestyle of the patient). \[Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\];

You may not qualify if:

• 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;

Sponsors & Collaborators

• R-Pharm Overseas, Inc.: lead
• Data Management 365: collaborator
• Keystat, LLC: collaborator

Study Sites (1)

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Pericarditis

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Yan Lavrovsky

  R-Pharm Overseas, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2021
• First Posted: November 4, 2021
• Study Start: December 1, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: November 15, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)