Treatment of Idiopathic Recurrent Pericarditis With Goflikicept: Phase II/III Study Results

Valentina Yu Myachikova; Alexey L Maslyanskiy; Olga M Moiseeva; Oksana V Vinogradova; Ekaterina V Gleykina; Yan Lavrovsky; Antonio Abbate; Sergey A Grishin; Alina N Egorova; Margarita L Schedrova; Mikhail Yu Samsonov

doi:10.1016/j.jacc.2023.04.046

Treatment of Idiopathic Recurrent Pericarditis With Goflikicept: Phase II/III Study Results

J Am Coll Cardiol. 2023 Jul 4;82(1):30-40. doi: 10.1016/j.jacc.2023.04.046.

Affiliations

¹ World-Class Research Center for Personalized Medicine, Rare and Genetically Determined Diseases, Research Laboratory of Autoimmune and Autoinflammatory Diseases, St Petersburg, Russia; Almazov National Medical Research Center, Rheumatology and Immunopathology Research Laboratory, St Petersburg, Russia. Electronic address: v.myachikova@gmail.com.
² Almazov National Medical Research Center, Rheumatology and Immunopathology Research Laboratory, St Petersburg, Russia; Saint Petersburg State University, Scientific, Clinical and Educational Center of Gastroenterology and Hepatology, St Petersburg, Russia.
³ Almazov National Medical Research Center, Noncoronary Heart Disease Research Department, St Petersburg, Russia.
⁴ State Autonomous Healthcare Institution "Orenburg Regional Clinical Hospital," Regional Vascular Center, Orenburg, Russia.
⁵ State Autonomous Healthcare Institution "Orenburg Regional Clinical Hospital," Cardiology Department No. 2, Orenburg, Russia.
⁶ R-Pharm Overseas Inc, La Jolla, California, USA.
⁷ Berne Cardiovascular Research Center and Division of Cardiology, School of Medicine, University of Virginia, Charlottesville, Virginia, USA.
⁸ R-Pharm JSC, Medical Department, Moscow, Russia.

PMID: 37380301
DOI: 10.1016/j.jacc.2023.04.046

Abstract

Background: Idiopathic recurrent pericarditis (IRP) is a rare autoinflammatory disease. Interleukin (IL)-1α and IL-1β are the pivotal cytokines in the pathophysiology of acute pericarditis and its recurrence. We created a phase II/III study with a new IL-1 inhibitor-goflikicept in IRP.

Objectives: This study sought to evaluate the efficacy and safety of goflikicept treatment in patients with IRP.

Methods: We conducted a 2-center open-label study of goflikicept in patients with IRP with and without recurrence at time of enrollment. The study consisted of 4 periods: screening, run-in (open-label treatment period), randomized withdrawal, and follow-up. Patients with clinical response to goflikicept in the run-in period were randomized (1:1) to a placebo-controlled withdrawal period, where the time to first pericarditis recurrence (primary endpoint) was evaluated.

Results: We enrolled 22 patients, and 20 of these patients were randomized. Reduction of C-reactive protein level accompanied by reduction of chest pain and pericardial effusion compared to baseline was demonstrated during the run-in period. Recurrence of pericarditis occurred in 9 of 10 patients in the placebo group, and there were no recurrence events in goflikicept group within 24 weeks after randomization (P < 0.001). A total of 122 adverse events were reported in 21 patients (95.5%), with no deaths and no new safety signals identified for goflikicept.

Conclusions: Treatment with goflikicept prevented recurrences and maintained IRP remission with a favorable risk-benefit ratio. Goflikicept reduced the risk of recurrence compared with placebo. (Study to Evaluate the Efficacy and Safety of RPH-104 Treatment in Patients With Idiopathic Recurrent Pericarditis; NCT04692766).

Keywords: autoinflammatory diseases; biologics; inflammation; interleukin-1 inhibitor.

Publication types

Clinical Trial, Phase II
Clinical Trial, Phase III
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Chest Pain
Chronic Disease
Humans
Odds Ratio
Pericardial Effusion*
Pericarditis* / drug therapy
Rare Diseases

Associated data

ClinicalTrials.gov/NCT04692766