Study to Assess the Efficacy and Safety of Rilonacept Treatment in Participants With Recurrent Pericarditis

Phase 3

Completed

• Conditions: Recurrent Pericarditis
• Interventions: Drug: Rilonacept; Drug: Placebo

• Registration Number: NCT03737110
• Lead Sponsor: Kiniksa Pharmaceuticals (UK), Ltd.

Brief Summary

The primary objective of this study was to assess the efficacy of rilonacept treatment in participants with recurrent pericarditis.

Detailed Description

In the single-blind run-in (RI) period, rilonacept 320 mg (or 4.4 mg/kg in pediatric participants ≥12 and \<18 years old) subcutaneous (SC), followed by 160 mg (or 2.2 mg/kg in pediatric participants ≥12 and \<18 years old) injections once weekly.

During the Randomized-Withdrawal (RW) period, eligible participants are randomized 1:1 to double-blinded administration of study drug:

* Rilonacept 160 mg (or 2.2 mg/kg in pediatric participants ≥12 and \<18 years old) SC injections once weekly

* Matching 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 numerical rating scale (NRS) and have 1 C-reactive protein (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 \[or 4.4 mg/kg for pediatric subjects\]) irrespective of randomized treatment assignment and as soon as at least 5 days have passed since the last study drug injection.

Upon completion of the RW period (i.e., when the prespecified number of primary efficacy endpoints \[clinical events committee-confirmed pericarditis recurrence\] events have occurred), all participants who did not discontinue study drug have an option to continue treatment with open-label rilonacept in the Long-Term Extension (LTE) or to withdraw from the study. Participants still in the RI period at the time that the RW period has ended and the LTE is opened will have the option to enter the LTE directly when they have completed the RI period and have met the definition of clinical response or to withdraw from the study.

Study Timeline

• Study First Submitted: 2018-10-30
• Study First Submitted QC: 2018-11-08
• Study First Posted: 2018-11-09
• Study Start: 2019-01-07
• Primary Completion: 2020-05-29
• Results First Submitted: 2021-05-25
• Results First Submitted QC: 2021-06-21
• Results First Posted: 2021-07-13
• Study Completion: 2022-06-30
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-14
• Last Update Posted: 2023-09-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 86

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/or corticosteroids (in any combination), if used, at stable dose levels (or at least not increased) for at least 3 days prior to first study drug administration
6. Female subjects must be postmenopausal, or incapable of pregnancy or permanently sterile, or if of childbearing potential must agree to use highly-effective method of contraception.
7. Must be up-to-date with all immunizations, in agreement with current local immunization guidelines for immunosuppressed subjects, before first study drug administration.
8. Is able to adequately maintain a daily subject diary according to protocol.
9. Agrees to refrain from making any new, major lifestyle changes that may affect pericarditis symptoms (e.g., changing exercise pattern) from the time that the informed consent form (ICF) is signed through the end of the double-blind randomized withdrawal period.

Key

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Exclusion Criteria

1. Has a diagnosis of pericarditis that is secondary to specific prohibited etiologies.
2. Has a history of immunosuppression, including positive human immunodeficiency virus (HIV) test results.
3. Has a history of myeloproliferative disorder.
4. Has a history of demyelinating disease or symptoms suggestive of multiple sclerosis.
5. Has a history of active or latent tuberculosis (TB) prior to screening
6. Has chest x-ray at screening or within 12 weeks before receiving first administration of study drug, with evidence of malignancy or abnormality consistent with prior or active TB infection.
7. Has a history of positive or intermediate results for hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C virus antibody at screening.
8. Has a history of malignancy of any organ system within the past 5 years before screening (other than a successfully treated non metastatic cutaneous squamous cell carcinoma or basal cell carcinoma and/or localized carcinoma in situ of the cervix).
9. Has a known or suspected current active infection or a history of chronic or recurrent infectious disease, including, but not limited to, chronic renal infection, chronic chest infection, sinusitis, recurrent urinary tract infection, or an open, draining infected skin wound.
10. Has had an organ transplant.
11. In the Investigator's opinion, has a history of alcoholism or drug/chemical abuse within 2 years before screening.
12. Has a known hypersensitivity to rilonacept or to any of its excipients.
13. Has received an investigational drug during the 30 days before screening or is planning to receive an investigational drug (other than that administered during this study) or use an investigational device at any time during the study.
14. In the Investigator's opinion, has any other medical condition that could adversely affect the subject's participation or interfere with study evaluations.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	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.
Placebo	Rilonacept	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.
Rilonacept	Rilonacept	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.

Primary Outcome Measures

Name	Time	Method
Time to Pericarditis Recurrence in the RW Period	RW Period (mean 24.8 weeks)	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).

Secondary Outcome Measures

Name	Time	Method
Change From LTE Baseline in Pericardial Signs in ECG	LTE Baseline, LTE Week 24
Major Secondary Efficacy Endpoint: Percentage of Participants Who Maintained Clinical Response at Week 16 of the RW Period	RW Period Week 16	Participants were asked to select the score that best describes their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. Clinical response was defined as a weekly average of daily pericarditis pain on the NRS ≤ 2.0 and C-reactive protein (CRP) level ≤ 0.5 mg/dL, and on monotherapy of randomized study drug at Week 16.
Major Secondary Efficacy Endpoint: Percentage of Participants With Absent or Minimal Pericarditis Symptoms Based on the Patient Global Impression of Pericarditis Severity (PGIPS) at Week 16 of the RW Period	RW Period Week 16	Percentage of participants with no or minimal pericarditis symptoms at Week 16, based on the PGIPS, a single-item measure of the participant's impression of the overall severity of pericarditis symptoms at the time the questionnaire is administered using a 7-point rating scale ranging from absent (0=no recurrent pericarditis symptoms) to very severe (6=recurrent pericarditis symptoms that cannot be ignored and markedly limits daily activities).; The exact 95% CI is calculated with randomization strata pooled. Participants who had received bailout rilonacept or rescue medication before the time point were considered nonresponders.
Major Secondary Efficacy Endpoint: Percentage of Days With No or Minimal Pericarditis Pain at Week 16 of the RW Period	RW Period Week 16	Participants were asked to select the score that best describes their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. No or minimal pain was defined as non-missing NRS ≤ 2.; The percentage of days with no or minimal pericarditis pain in the first 16 weeks was calculated for each participant using 16×7 as the denominator. Missing values in pain diary were counted as 0 day with no or minimal pain. Days of using oral rescue therapy or corticosteroid count as 0 day with no or minimal pain. If bailout rilonacept was used, each administration (loading dose or not) was counted as 7 days without qualifying no or minimal pain.
Percentage of Participants Who Maintained Clinical Response at Week 24 of the RW Period	RW Period Week 24	Participants were asked to select the score that best describes their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. Clinical response was defined as a weekly average of daily pericarditis pain on the NRS ≤ 2.0 and C-reactive protein (CRP) level ≤ 0.5 mg/dL, and on monotherapy of randomized study drug at Week 24.
Percentage of Participants Who Maintained Clinical Response at Week 8 of the RW Period	RW Period Week 8	Participants were asked to select the score that best describes their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. Clinical response was defined as a weekly average of daily pericarditis pain on the NRS ≤ 2.0 and C-reactive protein (CRP) level ≤ 0.5 mg/dL, and on monotherapy of randomized study drug at Week 8.
Percentage of Days With No or Minimal Pericarditis Pain at Week 24 of the RW Period	RW Period Week 24	Participants were asked to select the score that best describes their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. No or minimal pain was defined as non-missing NRS ≤ 2.; The percentage of days with no or minimal pericarditis pain in the first 24 weeks was calculated for each participant using 24×7 as the denominator. Missing values in pain diary were counted as 0 day with no or minimal pain. Days of using oral rescue therapy or corticosteroid count as 0 day with no or minimal pain. If bailout rilonacept was used, each administration (loading dose or not) was counted as 7 days without qualifying no or minimal pain.
Percentage of Participants With Absent or Minimal Pericarditis Symptoms at Week 24 of the RW Period Based on the PGIPS	RW Period Week 24	Percentage of participants with no or minimal pericarditis symptoms at Week 24, based on the PGIPS, a single-item measure of the participant's impression of the overall severity of pericarditis symptoms at the time the questionnaire is administered using a 7-point rating scale ranging from absent (0=no recurrent pericarditis symptoms) to very severe (6=recurrent pericarditis symptoms cannot be ignored and markedly limits daily activities).; The exact 95% CI is calculated with randomization strata pooled. Participants who had received bailout rilonacept or rescue medication before the time point were considered nonresponders.
Percentage of Days With No or Minimal Pericarditis Pain at Week 8 of the RW Period	RW Period Week 8	Participants were asked to select the score that best describes their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. No or minimal pain was defined as non-missing NRS ≤ 2.; The percentage of days with no or minimal pericarditis pain in the first 24 weeks was calculated for each participant using 8×7 as the denominator. Missing values in pain diary were counted as 0 day with no or minimal pain. Days of using oral rescue therapy or corticosteroid count as 0 day with no or minimal pain. If bailout rilonacept was used, each administration (loading dose or not) was counted as 7 days without qualifying no or minimal pain.
Percentage of Participants Without Pericarditis Recurrence in the First 24 Weeks of the RW Period	up to 24 weeks in the RW Period	Pericarditis recurrence is defined as the recurrence of typical pericarditis pain associated with supportive objective evidence of pericarditis. At any time during the RW period, participants who experienced a suspected recurrence of pericarditis symptoms reported to the study site/clinic for a scheduled or unscheduled visit, during which clinical assessments were performed to gather all the necessary diagnostic data to confirm or rule out the presence of pericarditis recurrence. A pericarditis recurrence event adjudication package was then prepared for adjudication by CEC. Kaplan-Meier estimate.
Time to Pericarditis Pain ≥ 4 on the NRS in the RW Period	RW Period (mean 24.8 weeks)	Participants were asked to select the score that best described their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'.
Time to New or Worsening Pericardial Effusion on Echocardiography (ECHO) in the RW Period	RW Period (mean 24.8 weeks)	Pericardial effusion based on ECHO was evaluated by the central laboratory during the RW period. Kaplan-Meier estimate.
Percentage of Participants With Absent or Minimal Pericarditis Symptoms at Week 8 of the RW Period Based on the PGIPS	RW Period Week 8	Percentage of participants with no or minimal pericarditis symptoms at Week 16, based on the Patient Global Impression of Pericarditis Severity (PGI-PS). The PGI-PS is a single-item measure of the participant's impression of the overall severity of pericarditis symptoms at the time the questionnaire is administered, using a 7-point rating scale ranging from absent (no recurrent pericarditis symptoms) to very severe (recurrent pericarditis symptoms cannot be ignored).; The exact 95% CI is calculated with randomization strata pooled. Participants who had received bailout rilonacept or rescue medication before the time point were considered nonresponders.
Time to CRP Level ≥ 1 mg/dL in the RW Period	RW Period (mean 24.8 weeks)	Kaplan-Meier estimate.
Time to Pericardial Rub in the RW Period	RW Period (mean 24.8 weeks)	Kaplan-Meier estimate. A pericardial rub (also called a pericardial friction rub) is an audible medical sign used in the diagnosis of pericarditis.
Time to Widespread ST-segment Elevation or PR-segment Depression on Electrocardiogram (ECG) in the RW Period	RW Period (mean 24.8 weeks)	Kaplan-Meier estimate. ST-segment elevation and PR-segment depression are ECG changes in the evolution of acute pericarditis.
Number of Participants in ECHO Pericardial Effusion Size Categories at RW Period Baseline, RW Week 24 and Worst Post-baseline in the RW Period	RW Period Baseline, RW Period Week 24, RW Period (mean 24.8 weeks)	Pericardial effusion based on ECHO was evaluated by the central laboratory during the RW period. "None or trivial/physiologic" is considered to be normal. The "RW Worst Post-baseline" category denotes the largest size of pericardial effusion category in which a participant was reported at any time during the RW period (post-baseline).
Change From RW Period Baseline Over Time in CRP Levels in RW Period	RW Period Baseline, RW Period Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, 56	Estimated from ANCOVA models including treatment arm as fix effect, baseline value, baseline value by treatment interaction, randomization strata as covariates.
Change From RW Period Baseline Over Time in Weekly Average of Pericarditis Pain in the RW Period	RW Period Baseline, RW Period Weeks 1-50, 54	Participants were asked to select the score that best described their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. Estimated from ANCOVA models including treatment arm as fix effect, baseline value, baseline value by treatment interaction, randomization strata as covariates.
Percentage of Participants With Absent or Minimal Pericarditis Symptoms Over Time After RW Period Week 24 Based on the PGIPS	RW Period Weeks 32, 40, 48, 56	The PGIPS, a single-item measure of the participant's impression of the overall severity of pericarditis symptoms at the time the questionnaire is administered using a 7-point rating scale ranging from absent (0=no recurrent pericarditis symptoms) to very severe (6=recurrent pericarditis symptoms cannot be ignored and markedly limits daily activities).; The exact 95% CI is calculated with randomization strata pooled. Participants who had received bailout rilonacept or rescue medication before the time point were considered nonresponders.
Percentage of Participants With Absent or Minimal Pericarditis Activity Over Time in the RW Period Based on the Physician Global Assessment of Pericarditis Activity (PGA-PA)	RW Period Baseline, RW Period Weeks 8, 16, 24, 32, 40, 48, 56	The PGA-PA is a single-item, clinician-reported outcome measure that Investigators use to rate their impression of the patient's overall pericarditis disease activity at the time the assessment is completed, using a rating scale ranging from absent to very severe. The Investigator selected the box that best described a participant's pericarditis activity at the time of occurrence of the assessment: Absent, Minimal, Mild, Moderate, Moderately Severe, Severe, Very Severe.
Change From RW Period Baseline in Short Form-36 (SF-36) Physical and Mental Component Scores at RW Period Week 24	RW Period Baseline, RW Period Week 24	The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the physical component summary (PCS) score of the SF-36. Items 5-8 primarily contribute to the mental component summary (MCS) score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best) with higher scores indicating better health. Increases from baseline indicate improvement.
Change From RW Baseline in SF-36 Individual Scores at RW Period Week 24	RW Period Baseline, RW Period Week 24	The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Scores on each item are summed and averaged (range: 0=worst to 100=best) with higher scores indicating better health. Increases from baseline indicate improvement.
Change From RW Period Baseline in the Short Form Health Survey-6 Domains (SF-6D) Utility Index Score at RW Period Week 24	RW Period Baseline, RW Period Week 24	The SF-6D is calculated based on responses to 11 items on the SF-36, that correspond to 6 domains: physical functioning, role participation (combined role-physical and role-emotional), social functioning, bodily pain, mental health, and vitality. Individual respondents can be classified on any of 4 to 6 levels of functioning or limitations for each of 6 domains, thus allowing a respondent to be classified into any of 18,000 possible unique health states. Using a standard gamble technique, each of these health states were mapped onto the SF-6D index score, which ranges from 0.00 (worst possible health state/death) to 1.00 (best possible health state/perfect health).
Change From RW Period Baseline in 5-level EuroQoL-5 Dimensions (EQ-5D-5L) Individual Scores and Index Value to RW Period Week 24	RW Period Baseline, RW Period Week 24	The EQ-5D-5L is a self-reported health status questionnaire that consists of 6 questions used to calculate a health utility score for use in health economic analysis. There are 2 components to the EQ-5D-5L: a 5-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Individual and index scores range from 0 to 1, with low scores representing a higher level of dysfunction. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.
Change From RW Period Baseline in Insomnia Severity Index (ISI) Total Score at RW Period Week 24	RW Period Baseline, RW Period Week 24	Participant's sleep quality was assessed with the ISI survey questionnaire. The ISI is a 7-item survey, with each question having 5 possible answers (none, mild, moderate, severe, or very severe), scored as 0, 1, 2, 3, or 4, respectively. Scores are summed for a total score, which ranges from 0 to 28. Lower scores are considered good, better, or healthy, and increasingly higher scores are considered to indicate greater insomnia.; Clinical interpretation of the total score is as follows: 0 to 7 = no clinically significant insomnia; 8 to 14 = subthreshold insomnia; 15 to 21 = clinical insomnia (moderate severity); 22 to 28 = clinical insomnia (severe).
Change in ISI Categories From RW Period Baseline to RW Period Week 24	RW Period Baseline (BL), RW Period Week (Wk) 24	Participant's sleep quality was assessed with the ISI survey questionnaire. The ISI is a 7-item survey, with each question having 5 possible answers (none, mild, moderate, severe, or very severe), scored as 0, 1, 2, 3, or 4, respectively. Scores are summed for a total score, which ranges from 0 to 28. Lower scores are considered good, better, or healthy, and increasingly higher scores are considered to indicate greater insomnia.; Clinical interpretation of the total score is as follows: 0 to 7 = no clinically significant insomnia; 8 to 14 = subthreshold insomnia; 15 to 21 = clinical insomnia (moderate severity); 22 to 28 = clinical insomnia (severe).
Percentage of Participants With Pericardial Delayed Hyperenhancement, Myocardial Delayed Hyperenhancement or Pericardial Effusion on Magnetic Resonance Imaging (MRI) at RW Week 24	RW Period Week 24	MRI assessments were performed in a subgroup of participants (MRI substudy) to assess the percentage of participants with: * Pericardial delayed hyperenhancement; * Myocardial delayed hyperenhancement; * Pericardial effusion
Percentage of Participants Using Oral Rescue Therapy (ORT), Corticosteroid, or Bailout Rilonacept for Pericarditis Every 4 Weeks Cumulatively in the RW Period	RW Period (mean 24.8 weeks)	ORT included analgesics, NSAIDs, and/or colchicine. ORT use while waiting for at least 5 days since previous administration of study drug before receiving bailout, or within 5 days before the assessment of pericarditis recurrence, was excluded.
Percentage of Participants Using ORT for Pericarditis in the First 24 Weeks of RW Period	RW Period (up to Week 24)	ORT included analgesics, NSAIDs, and/or colchicine.
Time From First Dose to Rilonacept Monotherapy in RI Period	RI Period (up to 12 weeks)	Time to rilonacept monotherapy was defined as the number of weeks from first dose to the first day of achieving monotherapy.
Time From First Dose to Pain Response in the RI Period	RI Period (up to 12 weeks)	Participants were asked to select the score that best described their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. Time to pain response was defined as number of days from first dose to the first day a participant's daily pain NRS was ≤ 2 of the 3 days over which the rolling average daily pain NRS was ≤ 2.
Time From First Dose to CRP Normalization in the RI Period	RI Period (up to 12 weeks)	Time to CRP normalization, defined as CRP ≤ 0.5 mg/dL, was censored at treatment discontinuation, taking prohibited medication, or Week 12, whichever occurred first.
Time From First Dose to Treatment Response in RI Period	RI Period (up to 12 weeks)	Time to treatment response is defined as time from first dose to the first day of pain response, and CRP ≤ 0.5 mg/dL within 7 days before or after pain response. Treatment response day will be the first day that the above criterion is met. If pain response occurs before CRP ≤ 0.5 mg/dL, each 3-day rolling average of NRS should be ≤ 2.0 from the day of pain response to the day of CRP ≤ 0.5 mg/dL. The response day will be the day of pain response. If CRP ≤0.5 mg/dL occurs before pain response, the response day will also be the day of pain response.
Percentage of Participants Achieving Clinical Response at RI Period Week 12	RI Period Week 12	Participants were asked to select the score that best described their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. Clinical Response was defined as a weekly average of daily pericarditis pain of ≤ 2.0 on the 11-point NRS and CRP level ≤ 0.5 mg/dL and participants must have been able to stop background SOC pericarditis therapy by Week 10.
Percentage of Participants With CRP Normalization at RI Period Week 12	RI Period Week 12	CRP normalization was defined as CRP ≤ 0.5 mg/dL.
Change From Baseline Over Time in Weekly Average of Pericarditis Pain NRS Score in RI Period	RI Period Baseline, RI Period Weeks 1-12	Participants were asked to select the score that best described their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'.
Change From Baseline Over Time in CRP Levels in RI Period	RI Period Baseline, RI Period Day 4, Weeks 1, 2, 4, 6, 12
Percentage of Participants With Resolution of Pericarditis-Related ECHO and ECG Abnormalities at Week 12 of the RI Period	RI Period Baseline, RI Period Week 12
Percentage of Days With No or Minimal Pain in the RI Period While on Treatment	RI Period (up to Week 12)	No or minimal pain is defined as non-missing daily NRS ≤ 2, where participants were asked to select the score that best describes their average level of pericarditis pain over the previous 24 hours using an 11-point NRS, where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'.
Percentage of Participants With No or Minimal Pericarditis Symptoms Over Time in the RI Period, Based on the PGIPS	RI Period Baseline, RI Period Weeks 6 and 12	The PGIPS, a single-item measure of the participant's impression of the overall severity of pericarditis symptoms at the time the questionnaire is administered using a 7-point rating scale ranging from absent (0=no recurrent pericarditis symptoms) to very severe (6=recurrent pericarditis symptoms cannot be ignored and markedly limits daily activities).; The exact 95% CI is calculated with randomization strata pooled. Participants who had received bailout rilonacept or rescue medication before the time point were considered nonresponders.
Percentage of Participants With No or Minimal Pericarditis Activity Over Time in the RI Period, Based on the PGA-PA	RI Period Baseline, RI Period Weeks 6 and 12	The PGA-PA is a single-item, clinician-reported outcome measure that Investigators use to rate their impression of the patient's overall pericarditis disease activity at the time the assessment is completed, using a rating scale ranging from absent to very severe. The Investigator selected the box that best described a participant's pericarditis activity at the time of occurrence of the assessment: Absent, Minimal, Mild, Moderate, Moderately Severe, Severe, Very Severe.; The exact 95% CI is calculated with randomization strata pooled. Participants who had received bailout rilonacept or rescue medication before the time point were considered nonresponders.
Annualized Rate of Pericarditis Recurrence in the Long-Term Extension (LTE) Period Based on Investigator's Assessment (Based on Investigators' Judgement)	LTE Period, through LTE Follow up (up to Week 48)	Annualized Recurrence Rate is defined as the number of recurrences in LTE periods for all participants/Sum of participant years in LTE periods for all participants. Participant years in LTE period is defined as the time from 1st dose date of LTE period to the date of End of Study, or data cutoff date, whichever is earlier. The 95% CI was calculated using an exact method with Poisson distribution. Pericarditis recurrence is defined as the recurrence of typical pericarditis pain associated with supportive objective evidence of pericarditis.
Percentage of Participants With Absent or Minimal Pericarditis Activity In the LTE Period Based on the PGIPS	LTE Baseline, LTE Month 12, LTE Month 24	Percentage of participants with no or minimal pericarditis symptoms in the LTE Period, based on the PGIPS, a single-item measure of the participant's impression of the overall severity of pericarditis symptoms at the time the questionnaire is administered using a 7-point rating scale ranging from absent (0=no recurrent pericarditis symptoms) to very severe (6=recurrent pericarditis symptoms that cannot be ignored and markedly limits daily activities).
Change From LTE Baseline in ISI Total Score	LTE Baseline, LTE Week 24	Participant's sleep quality was assessed with the ISI survey questionnaire. The ISI is a 7-item survey, with each question having 5 possible answers (none, mild, moderate, severe, or very severe), scored as 0, 1, 2, 3, or 4, respectively. Scores are summed for a total score, which ranges from 0 to 28. Lower scores are considered good, better, or healthy, and increasingly higher scores are considered to indicate greater insomnia.; Clinical interpretation of the total score is as follows: 0 to 7 = no clinically significant insomnia; 8 to 14 = subthreshold insomnia; 15 to 21 = clinical insomnia (moderate severity); 22 to 28 = clinical insomnia (severe).
Change From RI Period Baseline in the SF-36 Domain Scores and Physical and Mental Scores to RI Period Week 12	RI Period Baseline, RI Period Week 12	The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Scores on each item are summed and averaged (range: 0=worst to 100=best) with higher scores indicating better health. Increases from baseline indicate improvement.
Change From RI Period Baseline in SF-6D Scores at RI Period Week 12	RI Period Baseline, RI Period Week 12	The SF-6D is calculated based on responses to 11 items on the SF-36, that correspond to 6 domains: physical functioning, role participation (combined role-physical and role-emotional), social functioning, bodily pain, mental health, and vitality. Individual respondents can be classified on any of 4 to 6 levels of functioning or limitations for each of 6 domains, thus allowing a respondent to be classified into any of 18,000 possible unique health states. Using a standard gamble technique, each of these health states were mapped onto the SF-6D index score, which ranges from 0.00 (worst possible health state/death) to 1.00 (best possible health state/perfect health).
Change From RI Period Baseline in ISI Total Score at RI Period Week 12	RI Period Baseline, RI Period Week 12	Participant's sleep quality was assessed with the ISI survey questionnaire. The ISI is a 7-item survey, with each question having 5 possible answers (none, mild, moderate, severe, or very severe), scored as 0, 1, 2, 3, or 4, respectively. Scores are summed for a total score, which ranges from 0 to 28. Lower scores are considered good, better, or healthy, and increasingly higher scores are considered to indicate greater insomnia.; Clinical interpretation of the total score is as follows: 0 to 7 = no clinically significant insomnia; 8 to 14 = subthreshold insomnia; 15 to 21 = clinical insomnia (moderate severity); 22 to 28 = clinical insomnia (severe).
Change From RI Period Baseline in 5-level EuroQoL-5 Dimensions (EQ-5D-5L) Individual Scores and Index Value at RI Period Week 12	RI Period Baseline, RI Period Week 12	The EQ-5D-5L is a self-reported health status questionnaire that consists of 6 questions used to calculate a health utility score for use in health economic analysis. There are 2 components to the EQ-5D-5L: a 5-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Individual and index scores range from 0 to 1, with low scores representing a higher level of dysfunction. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.
Change in ISI Categories From RI Period Baseline to RI Period Week 12	RI Period Baseline (BL), RI Period Week (Wk) 12	Participant's sleep quality was assessed with the ISI survey questionnaire. The ISI is a 7-item survey, with each question having 5 possible answers (none, mild, moderate, severe, or very severe), scored as 0, 1, 2, 3, or 4, respectively. Scores are summed for a total score, which ranges from 0 to 28. Lower scores are considered good, better, or healthy, and increasingly higher scores are considered to indicate greater insomnia.; Clinical interpretation of the total score is as follows: 0 to 7 = no clinically significant insomnia; 8 to 14 = subthreshold insomnia; 15 to 21 = clinical insomnia (moderate severity); 22 to 28 = clinical insomnia (severe).
Number of Participants Who Were Off Background Pericarditis Medication on or Before RI Period Weeks 4, 8, 10, and 12	RI Period Baseline, RI Period Weeks 4, 8, 10, 12
Change From LTE Baseline Over Time in CRP Levels	LTE Baseline, LTE Week 12, LTE Week 24
Percentage of Participants With Absent or Minimal Pericarditis Activity Over Time in the LTE Period Based on the PGA-PA	LTE Baseline, LTE Week 12, LTE Week 24	The PGA-PA is a single-item, clinician-reported outcome measure that Investigators use to rate their impression of the patient's overall pericarditis disease activity at the time the assessment is completed, using a rating scale ranging from absent to very severe. The Investigator selected the box that best described a participant's pericarditis activity at the time of occurrence of the assessment: Absent, Minimal, Mild, Moderate, Moderately Severe, Severe, Very Severe.
Change From LTE Baseline in the SF-36 Domain Scores and Physical and Mental Scores	LTE Baseline, LTE Week 24	The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Scores on each item are summed and averaged (range: 0=worst to 100=best) with higher scores indicating better health. Increases from baseline indicate improvement.
Change From LTE Baseline in Pericardial Signs in MRI	LTE Baseline, LTE Week 24
Change From LTE Baseline in SF-6D Health Utility Index Score	LTE Baseline, LTE Week 24	The SF-6D is calculated based on responses to 11 items on the SF-36, that correspond to 6 domains: physical functioning, role participation (combined role-physical and role-emotional), social functioning, bodily pain, mental health, and vitality. Individual respondents can be classified on any of 4 to 6 levels of functioning or limitations for each of six domains, thus allowing a respondent to be classified into any of 18,000 possible unique health states. Using a standard gamble technique, each of these health states were mapped onto the SF-6D index score, which ranges from 0.00 (worst possible health state/death) to 1.00 (best possible health state/perfect health).
Change From LTE Baseline in EQ-5D-5L Individual Scores and Index Value	LTE Baseline, LTE Week 24	The EQ-5D-5L is a self-reported health status questionnaire that consists of 6 questions used to calculate a health utility score for use in health economic analysis. There are 2 components to the EQ-5D-5L: a 5-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Individual and index scores range from 0 to 1, with low scores representing a higher level of dysfunction. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.
Change From LTE Baseline in ISI Categories	LTE Baseline (BL), LTE Week 24	Participant's sleep quality was assessed with the ISI survey questionnaire. The ISI is a 7-item survey, with each question having 5 possible answers (none, mild, moderate, severe, or very severe), scored as 0, 1, 2, 3, or 4, respectively. Scores are summed for a total score, which ranges from 0 to 28. Lower scores are considered good, better, or healthy, and increasingly higher scores are considered to indicate greater insomnia.; Clinical interpretation of the total score is as follows: 0 to 7 = no clinically significant insomnia; 8 to 14 = subthreshold insomnia; 15 to 21 = clinical insomnia (moderate severity); 22 to 28 = clinical insomnia (severe).
Number of Participants With Pericardial Delayed Hyperenhancement, Myocardial Delayed Hyperenhancement or Pericardial Effusion at LTE Period Week 24	LTE Week 24
Percentage of Participants Requiring Addition of Standard of Care (SOC) Pericarditis Therapy Every 4 Weeks Cumulatively in the LTE Period	LTE Period, through LTE Follow up (up to Week 24)
Change From LTE Baseline in Pericardial Signs in ECHO	LTE Baseline, LTE Week 24
Annualized Rate of Pericarditis Recurrence in LTE Periods Based on Investigator's Assessment	LTE Period, through LTE Follow up (up to Week 48)	Annualized Recurrence Rate is defined as number of recurrences in LTE periods for all participants/Sum of participant years in LTE period for all participants. Participant years in LTE period is defined as the time from 1st dose date of LTE period to the date of End of Study, or data cutoff date, whichever is earlier. The 95% CI was calculated using an exact method with Poisson distribution.; Pericarditis recurrence was defined as the recurrence of typical pericarditis pain associated with supportive objective evidence of pericarditis. At any time during the RW period, participants who experienced a suspected recurrence of pericarditis symptoms reported to the study site/clinic for a scheduled or unscheduled visit, during which clinical assessments were performed to gather all the necessary diagnostic data to confirm or rule out the presence of pericarditis recurrence.
Annualized Rate of Pericarditis Recurrence in RW Period Based on CEC Adjudication	RW Period (mean 24.8 weeks)	Annualized Recurrence Rate is defined as the number of recurrences in RW period for all participants/Sum of participant years in RW period for all participants. Participant years in RW period is defined as the time from randomization date to the date of EORW or last dose date + 6 weeks, whichever is earlier. The 95% CI was calculated using an exact method with Poisson distribution.; Pericarditis recurrence was defined as the recurrence of typical pericarditis pain associated with supportive objective evidence of pericarditis. At any time during the RW period, participants who experienced a suspected recurrence of pericarditis symptoms reported to the study site/clinic for a scheduled or unscheduled visit, during which clinical assessments were performed to gather all the necessary diagnostic data to confirm or rule out the presence of pericarditis recurrence.

Trial Locations

Locations (21)

Arthritis and Rheumatology of Georgia; 🇺🇸 Atlanta, Georgia, United States

The Loretto Hospital; 🇺🇸 Chicago, Illinois, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Swedish Medical Center; 🇺🇸 Seattle, Washington, United States

Minneapolis Heart Institute Foundation; 🇺🇸 Minneapolis, Minnesota, United States

Cedars-Sinai Medical Institute; 🇺🇸 Los Angeles, California, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Cardiology Consultants of Philadelphia; 🇺🇸 Yardley, Pennsylvania, United States

Intermountain Healthcare; 🇺🇸 Murray, Utah, United States

HeartCare Partners Clinical Research Unit; 🇦🇺 Milton, Queensland, Australia

Galilee Medical Center; 🇮🇱 Nahariya, Israel

Sheba Medical Center at Tel-Hashomer; 🇮🇱 Ramat Gan, Israel

Azienda Ospedaliera Città della Salute e della Scienza di Torino; 🇮🇹 Turin, Piedmont, Italy

Ospedale Pediatrico Bambino Gesù; 🇮🇹 Roma, Lazio, Italy

University Of Vermont Medical Center; 🇺🇸 Burlington, Vermont, United States

GenesisCare - Cardiology Research; 🇦🇺 Doncaster East, Victoria, Australia

ASST Fatebenefratelli Sacco - Ospedale Fatebenefratelli e Oftalmico; 🇮🇹 Milan, Lombardy, Italy

Bnai Zion Medical Center; 🇮🇱 Haifa, Israel

Shaare Zedek Medical Center; 🇮🇱 Jerusalem, Israel

Mayo Clinic - PPDS; 🇺🇸 Rochester, Minnesota, United States

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States