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

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ClinicalTrials.gov Identifier: NCT03737110
Recruitment Status : Active, not recruiting
First Posted : November 9, 2018
Results First Posted : July 13, 2021
Last Update Posted : July 13, 2021
Sponsor:
Information provided by (Responsible Party):
Kiniksa Pharmaceuticals, Ltd. ( 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.

Condition or disease Intervention/treatment Phase
Recurrent Pericarditis Drug: Rilonacept Drug: Placebo Phase 3

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 86 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 3, Double-Blind, Placebo-Controlled, Randomized Withdrawal Study With Open-label Extension, to Assess the Efficacy and Safety of Rilonacept Treatment in Subjects With Recurrent Pericarditis
Actual Study Start Date : January 7, 2019
Actual Primary Completion Date : May 29, 2020
Estimated Study Completion Date : May 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Rilonacept

Arm Intervention/treatment
Experimental: 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.

Drug: Rilonacept
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
Other Names:
  • KPL-914
  • Arcalyst® for Cryopyrin-Associated Periodic Syndromes (CAPS)

Placebo Comparator: 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.

Drug: Rilonacept
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
Other Names:
  • KPL-914
  • Arcalyst® for Cryopyrin-Associated Periodic Syndromes (CAPS)

Drug: Placebo
Placebo SC injections once weekly




Primary Outcome Measures :
  1. Time to Pericarditis Recurrence in the RW Period [ Time Frame: 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 :
  1. Major Secondary Efficacy Endpoint: Percentage of Participants Who Maintained Clinical Response at Week 16 of the RW Period [ Time Frame: 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.

  2. Major Secondary Efficacy Endpoint: Percentage of Days With No or Minimal Pericarditis Pain at Week 16 of the RW Period [ Time Frame: 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.


  3. 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 [ Time Frame: 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.


  4. Percentage of Participants Who Maintained Clinical Response at Week 24 of the RW Period [ Time Frame: 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.

  5. Percentage of Participants Who Maintained Clinical Response at Week 8 of the RW Period [ Time Frame: 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.

  6. Percentage of Days With No or Minimal Pericarditis Pain at Week 24 of the RW Period [ Time Frame: 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.


  7. Percentage of Days With No or Minimal Pericarditis Pain at Week 8 of the RW Period [ Time Frame: 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.


  8. Percentage of Participants With Absent or Minimal Pericarditis Symptoms at Week 24 of the RW Period Based on the PGIPS [ Time Frame: 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.


  9. Percentage of Participants With Absent or Minimal Pericarditis Symptoms at Week 8 of the RW Period Based on the PGIPS [ Time Frame: 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.


  10. Percentage of Participants Without Pericarditis Recurrence in the First 24 Weeks of the RW Period [ Time Frame: 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.

  11. Time to Pericarditis Pain ≥ 4 on the NRS in the RW Period [ Time Frame: 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'.

  12. Time to CRP Level ≥ 1 mg/dL in the RW Period [ Time Frame: RW Period (mean 24.8 weeks) ]
    Kaplan-Meier estimate.

  13. Time to Pericardial Rub in the RW Period [ Time Frame: 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.

  14. Time to Widespread ST-segment Elevation or PR-segment Depression on Electrocardiogram (ECG) in the RW Period [ Time Frame: 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.

  15. Time to New or Worsening Pericardial Effusion on Echocardiography (ECHO) in the RW Period [ Time Frame: RW Period (mean 24.8 weeks) ]
    Pericardial effusion based on ECHO was evaluated by the central laboratory during the RW period. Kaplan-Meier estimate.

  16. Number of Participants in ECHO Pericardial Effusion Size Categories at RW Period Baseline, RW Week 24 and Worst Post-baseline in the RW Period [ Time Frame: 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).

  17. Change From RW Period Baseline Over Time in CRP Levels in RW Period [ Time Frame: 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.

  18. Change From RW Period Baseline Over Time in Weekly Average of Pericarditis Pain in the RW Period [ Time Frame: 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.

  19. Percentage of Participants With Absent or Minimal Pericarditis Symptoms Over Time After RW Period Week 24 Based on the PGIPS [ Time Frame: 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.


  20. 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) [ Time Frame: 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.

  21. Change From RW Period Baseline in Short Form-36 (SF-36) Physical and Mental Component Scores at RW Period Week 24 [ Time Frame: 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.

  22. Change From RW Baseline in SF-36 Individual Scores at RW Period Week 24 [ Time Frame: 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.

  23. Change From RW Period Baseline in the Short Form Health Survey-6 Domains (SF-6D) Utility Index Score at RW Period Week 24 [ Time Frame: 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).

  24. Change From RW Period Baseline in 5-level EuroQoL-5 Dimensions (EQ-5D-5L) Individual Scores and Index Value to RW Period Week 24 [ Time Frame: 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.

  25. Change From RW Period Baseline in Insomnia Severity Index (ISI) Total Score at RW Period Week 24 [ Time Frame: 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).


  26. Change in ISI Categories From RW Period Baseline to RW Period Week 24 [ Time Frame: 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).


  27. Percentage of Participants Using Oral Rescue Therapy (ORT), Corticosteroid, or Bailout Rilonacept for Pericarditis Every 4 Weeks Cumulatively in the RW Period [ Time Frame: 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.

  28. Percentage of Participants Using ORT for Pericarditis in the First 24 Weeks of RW Period [ Time Frame: RW Period (up to Week 24) ]
    ORT included analgesics, NSAIDs, and/or colchicine.

  29. Percentage of Participants With Pericardial Delayed Hyperenhancement, Myocardial Delayed Hyperenhancement or Pericardial Effusion on Magnetic Resonance Imaging (MRI) at RW Week 24 [ Time Frame: 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

  30. Time From First Dose to Pain Response in the RI Period [ Time Frame: 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.

  31. Time From First Dose to CRP Normalization in the RI Period [ Time Frame: 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.

  32. Time From First Dose to Rilonacept Monotherapy in RI Period [ Time Frame: 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.

  33. Time From First Dose to Treatment Response in RI Period [ Time Frame: 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.

  34. Percentage of Participants Achieving Clinical Response at RI Period Week 12 [ Time Frame: 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.

  35. Percentage of Participants With CRP Normalization at RI Period Week 12 [ Time Frame: RI Period Week 12 ]
    CRP normalization was defined as CRP ≤ 0.5 mg/dL.

  36. Change From Baseline Over Time in Weekly Average of Pericarditis Pain NRS Score in RI Period [ Time Frame: 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'.

  37. Change From Baseline Over Time in CRP Levels in RI Period [ Time Frame: RI Period Baseline, RI Period Day 4, Weeks 1, 2, 4, 6, 12 ]
  38. Percentage of Participants With Resolution of Pericarditis-Related ECHO and ECG Abnormalities at Week 12 of the RI Period [ Time Frame: RI Period Baseline, RI Period Week 12 ]
  39. Percentage of Days With No or Minimal Pain in the RI Period While on Treatment [ Time Frame: 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'.

  40. Percentage of Participants With No or Minimal Pericarditis Symptoms Over Time in the RI Period, Based on the PGIPS [ Time Frame: 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.


  41. Percentage of Participants With No or Minimal Pericarditis Activity Over Time in the RI Period, Based on the PGA-PA [ Time Frame: 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.


  42. Change From RI Period Baseline in the SF-36 Domain Scores and Physical and Mental Scores to RI Period Week 12 [ Time Frame: 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.

  43. Change From RI Period Baseline in SF-6D Scores at RI Period Week 12 [ Time Frame: 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).

  44. Change From RI Period Baseline in 5-level EuroQoL-5 Dimensions (EQ-5D-5L) Individual Scores and Index Value at RI Period Week 12 [ Time Frame: 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.

  45. Change From RI Period Baseline in ISI Total Score at RI Period Week 12 [ Time Frame: 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).


  46. Change in ISI Categories From RI Period Baseline to RI Period Week 12 [ Time Frame: 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).


  47. Number of Participants Who Were Off Background Pericarditis Medication on or Before RI Period Weeks 4, 8, 10, and 12 [ Time Frame: RI Period Baseline, RI Period Weeks 4, 8, 10, 12 ]
  48. Number of Participants With Pericarditis Recurrences (Based on Investigators' Judgement) in the Long-Term Extension (LTE) Period [ Time Frame: LTE Period (up to 24 months) ]
    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.

  49. Percentage of Participants With Clinical Response at Each CRP Assessment (Weeks 12 and 24) of the LTE Period [ Time Frame: LTE Period Weeks 12 and 24 ]
    Clinical response is defined as rilonacept monotherapy + CRP ≤ 0.5 mg/dL + NRS ≤ 2. 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 NRS, where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. The pain NRS at the visit when CRP was assessed was used.

  50. Change From LTE Baseline Over Time in CRP Levels [ Time Frame: LTE Baseline, up to 24 months ]
  51. Change From LTE Baseline Over Time in Pericarditis Pain NRS [ Time Frame: LTE Baseline, up to 24 months ]
    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 NRS, where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'.

  52. Percentage of Participants With Absent or Minimal Pericarditis Activity In the LTE Period Based on the PGIPS [ Time Frame: LTE Period (up to 24 months) ]
    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).

  53. Percentage of Participants With Absent or Minimal Pericarditis Activity Over Time in the LTE Period Based on the PGA-PA [ Time Frame: LTE Period (up to 24 months) ]
    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.

  54. Change From RI Baseline in the SF-36 Domain Scores and Physical and Mental Scores in the LTE Period [ Time Frame: LTE Baseline, up to 24 months ]
    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.

  55. Change From LTE Baseline in SF-6D Scores in LTE Period [ Time Frame: LTE Baseline, up to 24 months ]
    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).

  56. Change From LTE Baseline in EQ-5D-5L Individual Scores and Index Value in the LTE Period [ Time Frame: LTE Baseline, up to 24 months ]
    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.

  57. Change From LTE Baseline in ISI Total Score in the LTE Period [ Time Frame: LTE Baseline, up to 24 months ]

    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).


  58. Change From LTE Baseline in ISI Categories in the LTE Period [ Time Frame: LTE Baseline, up to 24 months ]

    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).


  59. Percentage of Participants Requiring Addition of Standard of Care (SOC) Pericarditis Therapy Every 4 Weeks Cumulatively in the LTE Period [ Time Frame: LTE Period (up to 24 months) ]
  60. Change From LTE Baseline in Pericardial Signs in ECHO in the LTE Period [ Time Frame: LTE Baseline, up to 24 months ]
  61. Change From LTE Baseline in Pericardial Signs in ECG in LTE Period [ Time Frame: LTE Baseline, up to 24 months ]
  62. Change From LTE Baseline in Pericardial Signs in MRI in the LTE Period [ Time Frame: LTE Baseline, up to 24 months ]
  63. Number of Participants With Corticosteroid Use Over Time in the LTE Period [ Time Frame: LTE Period (up to 24 months) ]
  64. Percentage of Participants With Pericardial Delayed Hyperenhancement, Myocardial Delayed Hyperenhancement or Pericardial Effusion at LTE Period Week 24 [ Time Frame: LTE Period, Week 24 ]
  65. Annualized Recurrent Rate [ Time Frame: RW and LTE Periods ]

    Annualized recurrent rate was calculated for participants randomized to rilonacept utilizing pooled data in RW and LTE periods.

    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.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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/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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03737110


Locations
Show Show 20 study locations
Sponsors and Collaborators
Kiniksa Pharmaceuticals (UK), Ltd.
Investigators
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Study Director: Clinical Operations Study Director Kiniksa Pharmaceuticals (UK), Ltd.
  Study Documents (Full-Text)

Documents provided by Kiniksa Pharmaceuticals, Ltd. ( Kiniksa Pharmaceuticals (UK), Ltd. ):
Study Protocol  [PDF] March 10, 2020
Statistical Analysis Plan  [PDF] June 16, 2020

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Kiniksa Pharmaceuticals (UK), Ltd.
ClinicalTrials.gov Identifier: NCT03737110    
Other Study ID Numbers: KPL-914-C002
2018-002719-87 ( EudraCT Number )
First Posted: November 9, 2018    Key Record Dates
Results First Posted: July 13, 2021
Last Update Posted: July 13, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pericarditis
Heart Diseases
Cardiovascular Diseases
Rilonacept
Anti-Inflammatory Agents