RHAPSODY: Rationale for and design of a pivotal Phase 3 trial to assess efficacy and safety of rilonacept, an interleukin-1α and interleukin-1β trap, in patients with recurrent pericarditis.

Abstract

Recurrent pericarditis (RP) occurs in 15% to 30% of patients following a first episode, despite standard treatment with nonsteroidal anti-inflammatory drugs, colchicine, and corticosteroids; many patients become dependent on corticosteroids. Rilonacept (KPL-914), an interleukin-1α and β inhibitor, is in development for the treatment of RP. RHAPSODY, a double-blind, placebo-controlled, randomized-withdrawal (RW) pivotal Phase 3 trial (NCT03737110), enrolls patients 12 years or older presenting with at least a third pericarditis episode, pericarditis pain score ≥4 (11-point numeric rating scale [NRS]), and C-reactive protein ≥1 mg/dL at screening. After a subcutaneous loading dose (adults, 320 mg; children, 4.4 mg/kg), all patients receive blinded weekly subcutaneous rilonacept (adults, 160 mg; children, 2.2 mg/kg) during the run-in period. Patients must taper and discontinue concomitant pericarditis medications during the blinded run-in period and achieve clinical response (C-reactive protein ≤0.5 mg/dL and weekly average NRS ≤2.0 during the 7 days prior to and including the day of randomization) by end of the run-in (while on rilonacept monotherapy) to be randomized to either continued rilonacept or placebo in the RW period. Primary efficacy end point was time to adjudicated pericarditis recurrence during the RW period; secondary efficacy end points were proportion of patients maintaining clinical response, percentage of days with NRS ≤2, and percentage of patients with no-to-minimal pericarditis symptoms at week 16 of the RW period. Safety evaluations include adverse event monitoring, physical examinations, and laboratory tests. The RHAPSODY trial will evaluate the efficacy and safety of rilonacept in the treatment of RP to improve outcomes and patient health-related quality of life.

• Authors: Allan L Klein, Massimo Imazio, Antonio Brucato, Paul Cremer, Martin LeWinter, Antonio Abbate, David Lin, Alberto Martini, Anna Beutler, Steven Chang, Fang Fang, Anais Gervais, Randy Perrin, John F Paolini
• Journal: American heart journal (Am Heart J) Vol. 228 Pg. 81-90 (10 2020) ISSN: 1097-6744 [Electronic] United States
• PMID: 32866928 (Publication Type: Clinical Trial, Journal Article)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Interleukin-1alpha
• Interleukin-1beta
• Recombinant Fusion Proteins
• rilonacept

Topics

• Adolescent
• Adult
• Anti-Inflammatory Agents (administration & dosage, adverse effects)
• Clinical Trials, Phase III as Topic
• Double-Blind Method
• Drug Administration Schedule
• Drug Monitoring (methods)
• Female
• Humans
• Injections, Subcutaneous
• Interleukin-1alpha (antagonists & inhibitors)
• Interleukin-1beta (antagonists & inhibitors)
• Male
• Pericarditis (diagnosis, drug therapy, physiopathology, psychology)
• Quality of Life
• Randomized Controlled Trials as Topic
• Recombinant Fusion Proteins (administration & dosage, adverse effects)
• Secondary Prevention (methods)