RHAPSODY TRIAL DESIGN

RHAPSODY Clinical Trial Design1,2

Trial design: A Phase 3, multicenter, double-blind, event-driven, RW trial of ARCALYST in recurrent pericarditis patients with acute symptoms of at least a second recurrence despite treatment with traditional therapies (NSAIDs, colchicine, or corticosteroids, alone or in combination).

 

Trial began with a 4-week screening period to establish trial eligibility and was followed by 3 periods:

12-week RI
Initiation of ARCALYST and transition to monotherapy

  • 1-week stabilization
  • 9 weeks weaning from background therapies
  • 2 weeks ARCALYST monotherapy

 Event-driven,
double-blind RW
Treatment with ARCALYST or placebo*

  • 1:1 randomization to weekly ARCALYST or placebo
  • Continued until the prespecified number of primary efficacy end point events 

LTE
Eligible patients were offered open-label ARCALYST for up to 24 additional months 

  • 18 months after the most recent pericarditis event (qualifying or RW period), a decision was made for each patient to:
    • Continue open-label ARCALYST
    • Suspend treatment for observation (ARCALYST rescue for recurrence allowed)
    • Exit the study

*For patients who met the prespecified clinical response criteria for ARCALYST. Based on clinical status and at investigator discretion.

Inclusion and Exclusion Criteria at Screening1‡

Key inclusion criteria

  • Male or female 12 years of age or older
  • Diagnosed with recurrent pericarditis
  • Presenting with at least a second recurrence of pericarditis
  • If using NSAIDs, colchicine, corticosteroids, or any combination thereof, doses remained stable for 3 days prior to first drug administration

This list is not all-inclusive.

Key exclusion criteria

  • Diagnosis of pericarditis secondary to specific prohibited etiologies:
    • Tuberculosis
    • Neoplastic, purulent, or radiation etiologies
    • Post-thoracic blunt trauma (eg, motor vehicle accident)
    • Myocarditis
    • Systemic autoimmune diseases (with exception of Still’s disease)
  • Pregnant, breastfeeding, planning a pregnancy, or planning on fathering a child
  • History of immunosuppression

RHAPSODY Trial Population

Select characteristics of clinical trial participants1,3

  • Total population: 86 
  • Mean patient age: 45 years (range 13-78)
    • 57% female
  • Diagnosis of “idiopathic” pericarditis: 85% (n=73) 
    • Remainder: post-pericardiotomy syndrome and Dressler syndrome
  • Medications used at baseline (alone or in combination)§:
    • NSAIDs: n=58
    • Colchicine: n=69
    • Corticosteroids: n=41
  • Mean duration of disease: 2.4 years
  • Mean pericarditis events per year: 4.4
    • Including the qualifying pericarditis event§
  • Mean qualifying NRS pain score: 6.2
  • Mean qualifying CRP level: 6.2 mg/dL 

§Qualifying pericarditis event: 0-10 point NRS ≥4 and CRP ≥1 mg/dL.

Patient Disposition2

12-week RI

Initiation of ARCALYST and transition to monotherapy (N=86)

 Event-driven,
double-blind RW

Treatment with ARCALYST or placebo (N=61)

LTE

Eligible patients were  offered open-label ARCALYST for up to 24 additional months

99% (74 of 75) chose to enter the LTE

  • 59 directly from  the RW period and 15 from the RI period after enrollment in the RW period closed

52 patients reached the 18-month decision milestone

  • 33 continued open-label ARCALYST
  • 8 suspended treatment for observation
  • 11 exited the study

22  patients discontinued the LTE  prior to reaching the 18-month decision milestone. 

  • 18 US participants transitioning to commercial ARCALYST at the time of US approval
  • 4 (US/ex-US) participants due to lost to follow-up (1), AE (2), and withdrawal of consent (1)

References: 1. Klein AL, Imazio M, Cremer P, et al. Phase 3 trial of interleukin-1 trap rilonacept in recurrent pericarditis. N Engl J Med. 2021;384(1):31-41. 2. Imazio M, Klein AL, Brucato A, et al. Sustained Pericarditis Recurrence Risk Reduction With Long-Term Rilonacept. J Am Heart Assoc. 2024;13(6):e032516. doi:10.1161/JAHA.123.032516. 3. ARCALYST. Package insert. Kiniksa Pharmaceuticals.

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Indication

ARCALYST® (rilonacept) is an interleukin-1 blocker indicated for:

  • Treatment of recurrent pericarditis (RP) and reduction in risk of recurrence in adults and pediatric patients 12 years and older.
  • Treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Auto-inflammatory Syndrome (FCAS), and Muckle-Wells Syndrome (MWS) in adults and children 12 years and older. 
  • Maintenance of remission of Deficiency of Interleukin-1 Receptor Antagonist (DIRA) in adults and pediatric patients weighing 10 kg or more.

Important Safety Information

Warnings and Precautions

  • Interleukin-1 (IL-1) blockade may interfere with the immune response to infections. Treatment with another medication that works through inhibition of IL-1 or inhibition of tumor necrosis factor (TNF) is not recommended as this may increase the risk of serious infection. Serious, life-threatening infections have been reported in patients taking ARCALYST. Do not initiate treatment with ARCALYST in patients with an active or chronic infection.
  • Discontinue ARCALYST if a patient develops a serious infection.
  • It is possible that taking drugs such as ARCALYST that block IL-1 may increase the risk of tuberculosis (TB) or other atypical or opportunistic infections.
  • Although the impact of ARCALYST on infections and the development of malignancies is not known, treatment with immunosuppressants, including ARCALYST, may result in an increase in the risk of malignancies.
  • Hypersensitivity reactions associated with ARCALYST occurred in clinical trials. Discontinue ARCALYST and initiate appropriate therapy if a hypersensitivity reaction occurs. 
  • Increases in non-fasting lipid profile parameters occurred in patients treated with ARCALYST in clinical trials. Patients should be monitored for changes in their lipid profiles.
  • Since no data are available, avoid administration of live vaccines while patients are receiving ARCALYST. ARCALYST may interfere with the normal immune response to new antigens, so vaccines may not be effective in patients receiving ARCALYST. It is recommended that, prior to initiation of therapy with ARCALYST, patients receive all recommended vaccinations, as appropriate.

Adverse Reactions

  • In patients with CAPS or RP, the most common adverse reactions (≥10%) include injection-site reactions and upper respiratory tract infections.
  • In patients with DIRA, the most common adverse reactions (>10%) include upper respiratory tract infections, rash, otitis media, pharyngitis, and rhinorrhea.

Drug Interactions

  • In patients being treated with CYP450 substrates with narrow therapeutic indices, therapeutic monitoring of the effect or drug concentration should /pi.pdfbe performed, and the individual dose of the medicinal product may need to be adjusted.

For more information about ARCALYST, see full Prescribing Information.