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Label indication ARCALYST (rilonacept) is an interleukin-1 blocker indicated for: Treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Autoinflammatory Syndrome (FCAS), and Muckle-Wells Syndrome (MWS) in adults and children 12 years and older ( 1.1 , 14.1 ) Maintenance of remission of Deficiency of Interleukin-1 Receptor Antagonist (DIRA) in adults and pediatric patients weighing 10 kg or more ( 1.2 ,… FDA label
Also known as KPL-914, Arcalyst® for Cryopyrin-Associated Periodic Syndromes (CAPS)
Rilonacept · 2 trials · 1 indication
Time to pericarditis recurrence (from randomization to 1st recurrence). Kaplan-Meier. Clinical Events Committee (CEC)-confirmed recurrences used for primary analysis. Recurrence defined as recurrence typical pericarditis pain with supportive objective evidence. CEC-adjudicated recurrences defined as:1) Re-appearance/worsening pericarditis pain (1 NRS ≥ 4) AND elevated CRP (≥1.0 mg/dL) on same day/separated by ≤ 7 days OR 2) Re-appearance/worsening pericarditis pain (1 NRS ≥ 4) AND abnormal CRP (\> 0.5 mg/dL) on same day/separated by ≤ 7 days AND 1 supportive evidence OR 3) Re-appearance/worsening pericarditis pain (no NRS ≥ 4) AND elevated CRP (≥ 1.0 mg/dL) not attributable to other causes AND 1 supportive evidence. Supportive evidence: White blood cell count \> upper limit normal, fever \> 38C, pericardial rub, electrocardiogram changes consistent with pericarditis, new/worsening pericardial effusion (echocardiogram), new/worsening pericardial inflammation (magnetic resonance imaging).
The average level of pericarditis pain over previous 24 hours was assessed by participants at each visit using 11-point pain NRS (where "0" indicates "no pain" and "10" indicates pain "as bad as it could be").
The average level of pericarditis pain over previous 24 hours was assessed by participants at each visit using 11-point pain NRS (where "0" indicates "no pain" and "10" indicates pain "as bad as it could be").
Baseline is defined as the last non-missing assessment prior to the first study drug administration.
The average level of pericarditis pain over previous 24 hours was assessed by participants at each visit using 11-point pain NRS (where "0" indicates "no pain" and "10" indicates pain "as bad as it could be"). Baseline is defined as the last non-missing assessment prior to the first study drug administration.
| Arm | Type | Description |
|---|---|---|
| Rilonacept | EXPERIMENTAL | RI period: single-blind rilonacept 320 mg (or 4.4 mg/kg in pediatric participants) SC, followed by 160 mg (or 2.2 mg/kg in pediatric participants) injections once weekly. RW period: eligible participants randomized to double-blinded administration of rilonacept 160 mg (or 2.2 mg/kg in pediatric participants) SC injections once weekly. Participants with pericarditis recurrence who meet the protocol criteria for bailout rilonacept (report at least 1 day with pericarditis pain ≥4 on the 11-point NRS and have 1 CRP value ≥ 1 mg/dL \[either on the same day or separated by no more than 7 days\]) receive bailout rilonacept (2 open-label injections of 160 mg rilonacept \[or 4.4 mg/kg for pediatric participants\]) irrespective of randomized treatment assignment and as soon as at least 5 days have passed since the last study drug injection. LTE period: open-label administration of rilonacept 160 mg (or 2.2 mg/kg in pediatric participants) SC injections once weekly. |
| Placebo | PLACEBO_COMPARATOR | RI period: single-blind rilonacept 320 mg (or 4.4 mg/kg in pediatric participants) SC, followed by 160 mg (or 2.2 mg/kg in pediatric participants) injections once weekly. RW period: eligible participants randomized to placebo SC injections once weekly. Participants with pericarditis recurrence who meet the protocol criteria for bailout rilonacept (report at least 1 day with pericarditis pain ≥4 on the 11-point NRS and have 1 CRP value ≥ 1 mg/dL \[either on the same day or separated by no more than 7 days\]) receive bailout rilonacept (2 open-label injections of 160 mg rilonacept \[or 4.4 mg/kg for pediatric participants\]) irrespective of randomized treatment assignment and as soon as at least 5 days have passed since the last study drug injection. LTE period: open-label administration of rilonacept 160 mg (or 2.2 mg/kg in pediatric participants) SC injections once weekly. |
| KPL-914: Part 1 Participants | EXPERIMENTAL | Part 1 enrolls symptomatic participants with recurrent idiopathic pericarditis (RIP) with an elevated marker of systemic inflammation (C-reactive protein \[CRP\] \> 1mg/dL). |
| KPL-914: Part 2 Participants | EXPERIMENTAL | Part 2 enrolls symptomatic participants with RIP with CRP ≤1 mg/dL which, in the opinion of the Investigator, can be attributed to concomitant medications (e.g., corticosteroids) and with pericardial inflammation present on cardiac magnetic resonance imaging (MRI) confirmed by the imaging core lab. |
| KPL-914: Part 3 Participants | EXPERIMENTAL | Part 3 enrolls participants with corticosteroid-dependent RIP not experiencing symptoms which would meet the diagnostic criteria for a flare of pericarditis. |
| KPL-914: Part 4 Participants | EXPERIMENTAL | Part 4 enrolls symptomatic participants with recurrent post pericardiotomy syndrome (PPS) with an elevated marker of systemic inflammation (CRP \> 1mg/dL). |
| KPL-914: Part 5 Participants | EXPERIMENTAL | Part 5 enrolls participants with corticosteroid-dependent recurrent PPS not experiencing symptoms which would meet the diagnostic criteria for a flare of pericarditis. |
| Name | Type | Description |
|---|---|---|
| Rilonacept | DRUG | Rilonacept 320 mg (or 4.4 mg/kg in pediatric participants ≥12 and \<18 years old) SC , followed by 160 mg (or 2.2 mg/kg in pediatric participants ≥12 and \<18 years old) injections once weekly |
| Placebo | DRUG | Placebo SC injections once weekly |
| KPL-914 | DRUG | KPL-914 (rilonacept) will be provided in its commercially available formulation as a lyophilized powder to be reconstituted for SC administration. Adult participants (≥ 18 years of age) KPL-914 will be administered as an initial loading dose of 320 mg SC, delivered as 2 subcutaneous injections of 160 mg SC each on Day 0, then 160 mg SC dosed once weekly for 5 subsequent weeks. Pediatric participants (6 to \<18 years of age) KPL-914 will be administered with an initial loading dose of 4.4 mg/kg, up to a maximum of 320 mg, delivered as 2 subcutaneous injections of 2.2 mg/kg each with a maximum single-injection volume of 2 mL. Participants considered to be 'treatment responders' will be offered participation in an optional 18-week extension period (EP) in which KPL-914 can be continued for a total duration of KPL-914 treatment of up to 24 weeks. |
Key Inclusion Criteria: 1. Male or female aged 12 or older 2. Has a diagnosis of recurrent pericarditis 3. Must provide Informed Consent 4. Presents with at least the third episode of pericarditis during screening. 5. Has received nonsteroidal anti-inflammatory drugs (NSAIDs) and/or colchicine and/...
Rilonacept is being developed for the treatment of recurrent pericarditis, a cardiovascular condition characterized by repeated inflammation of the sac surrounding the heart. It is an investigational therapy and has not been approved by the FDA for this indication.
Rilonacept targets interleukin-1 beta (IL1B). It is an IL1B inhibitor, meaning it works by blocking the activity of this inflammatory cytokine. By inhibiting IL1B, rilonacept aims to reduce the inflammation that drives recurrent pericarditis.
Rilonacept is being developed by Kiniksa Pharmaceuticals International, plc, which trades on the Nasdaq under the ticker symbol KNSA. Kiniksa is focused on developing therapies for cardiovascular and other inflammatory diseases.
Rilonacept is in Phase 3 clinical development for recurrent pericarditis. The Phase 3 trial has been completed. It is an investigational drug and has not been approved by the FDA for any indication.
Rilonacept has been studied in a Phase 3 clinical trial, NCT03737110, titled "Study to Assess the Efficacy and Safety of Rilonacept Treatment in Participants With Recurrent Pericarditis." This completed trial enrolled 86 participants across the United States, Australia, Israel, and Italy.
Rilonacept is also known by the brand name Arcalyst. Both names refer to the same investigational drug candidate being developed by Kiniksa Pharmaceuticals for recurrent pericarditis.